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Good morning. I will be your conference operator for today. At this time, I would like to welcome everyone to the Immunon Second Quarter 2026 Financial Results and Business Update Conference Call. I will now turn the call over to Vother Pinto, Managing Director of Investor Relations at KCSA Strategic Communications for introductions. Please go ahead.

Thank you, operator, and good morning. Welcome to the MUNON second quarter 2026 financial results and business update conference call. Joining us today are Stacey Limborg, President and Chief Executive Officer, Dr. Douglas Fowler, Chief Medical Officer, and Josh Blanchard, Chief Financial Officer. Michael Tudargo, the company's Executive Chairman, is also on the line for the Q&A portion of today's call. Before we begin, I'd like to remind everyone that our remarks today include forward-looking statements. These statements are made pursuant to the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, and include, but are not limited to, statements regarding the timing and enrollment of the company's clinical trials, the potential of the company's therapies to address unmet medical needs, the market potential for its product candidates if approved, and the company's plans and expectations for its development programs, words such as may, will, expect, plan, anticipate, estimate, and intend identify these forward-looking statements and actual results may differ materially from those projected.

Additional information on the factors that could cause actual results to differ is detailed in the new announced filings in the series and the change commission, which are available at sec.gov and on the company's website. looking statements made on the call speak only as of today's date and the company undertakes no obligation to update them except as required by law with that. And now let's turn the call over to Dr. Stacy Lindbergh. Stacy, please go ahead.

Thank you, Valter, and good morning, everyone. Thank you for joining us today and for your continued support of Immunon. The second quarter marked another period of focused execution and key validation of both Immunon-001, our lead asset, and our TheraPlas platform. Across our clinical programs, we continue to demonstrate the strength of our data, which is earning growing recognition within the scientific community while remaining disciplined in our execution. Our North Star remains unchanged. Bring a much needed new treatment option to women with advanced ovarian cancer. that affects approximately 300,000 women worldwide each year, has a five-year survival rate of roughly 40 percent, and has seen little meaningful advancement in the standard of care for nearly three decades. Before we dive into this quarter's progress, I want to invite our investors and members of the media to join us for our R&D Day on September 23rd in New York City. We look forward to providing a deeper look at the science behind Immunon 001, the progress we've made, and the opportunities that lie ahead.

Now onto the second quarter, I'll begin by highlighting three themes that have shaped this quarter. First, the continued validation of our technology and platform. Second, the strong pace of enrollment in our pivotal Phase 3 Ovation 3 study. And third, the disciplined financial and operational execution across our company as we maintain focus and remain focused on advancing. our phase three clinical trial. So first up, continued validation of our technology and platform, turning to the clinical foundation that underpins everything we are doing, the final data from our completed phase two Ovation 2 study, which continues to strengthen our conviction in Immunon OO1. In successive analyses, we have observed a consistent and clinically meaningful improvement in median overall survival. recently 14.7 months in the intention to treat an all-comers population of newly diagnosed patients. This alongside a highly favorable safety and tolerability profile that successfully addresses the historic barriers associated with systemic IL-12. complementary translational findings including lower rates of minimal residual disease, higher circulating tumor DNA clearance, and encouraging rates of no evidence of disease following frontline therapy. further reinforce the biological activity of localized, durable IL-12 expression at the tumor site.

These consistent clinical and translational signals give us high confidence as we advance the pivotal phase three program. Staying with the first theme and really focusing more on the additional validation that comes through our phase two MRD or minimal residual disease trial as a reminder in July we reported encouraging preliminary data from this trial. The study is being conducted in collaboration with Breakthrough Cancer and is led by investigators at MD Anderson Cancer Center. The study is designed not only to evaluate clinical activity, but also to better understand how Immunon 001 remodels the tumor immune microenvironment following frontline treatment. Among patients who had reached the study's primary assessment and endpoint of second-look laparoscopy, treatment with immunon-001 was associated with a lower rate of MRD positivity compared to the control arm, 44% versus 67%. It was associated with a higher circulating tumor DNA clearance with immunon arm 87.5% versus 62% in the control arm and a higher proportion of patients achieving no evidence of disease following frontline therapy, which was 100% in the immunon treatment arm versus percent in the control arm. While these are preliminary findings from a small cohort, they provide encouraging evidence of deeper anti-tumor activity for immunon 001.

The translational analyses continue to support Immunonta 01's proposed mechanism of action. We observed robust IL-12 expression within macrophages, activation of downstream cytokines, including the FDA-endorsed potency assay interferon gamma. We observed evidence of both macrophage and T cell activation consistent with remodeling the tumor microenvironment from an immunologically cold state to one that is immunologically active or hot. Finally, these encouraging biological and clinical findings continue to be accompanied by a highly favorable safety profile. Across the MRD study, which is also true more broadly, we have observed no cytokine release syndrome, no systemic toxicities, and no serious immune-related adverse events. reinforcing our belief that ME-9001 has successfully overcome the historic safety challenges associated with IL-12 based therapies. Enrollment momentum in Phase 3 and turning to our lead Phase 3 asset, we remain very encouraged by the continued pace of enrollment in our pivotal Ovation 3 study. The trial continues to generate strong engagement from investigators and patients, reflecting the strength of the data generated in Ovation 2. include the well-established safety profile and compelling overall survival and efficacy results that we believe are unlike anything previously reported in the setting.

Operationally, the team has executed with discipline and speed. From protocol finalization through site activation and first patient enrollment, we have moved at a pace meaningfully faster than industry benchmarks for phase three study startups. Enrollment rates are exceeding our internal assumptions with the majority of activated sites performing at or above plan This momentum reflects the strength of our data and the enthusiasm of investigators at leading cancer centers that are involved in our trial. Combined with the efficiencies gained from our sharpened organizational focus in in-house manufacturing, we are demonstrating the operational excellence required to advance a late-stage program of this importance. With that, I'll turn the call over to Dr. Douglas Fowler, our Chief Medical Officer, who can expand on these data and offer perspective on the Phase 3 progress in more detail. Douglas?.

Thank you, Stacey. As Stacey mentioned, Ovation 3 is our pivotal Phase 3 trial evaluating Immunon 001 in combination with standard-of-care neoadjuvant and adjuvant chemotherapy in patients with newly diagnosed advanced epithelial ovarian cancer. We continue to be very encouraged by the trial's execution and momentum. Site activation has proceeded efficiently, and enrollment continues to exceed our planned assumptions. We are currently enrolling approximately 0.5 patients per site per month, compared with the 0.3 patients per site per month assumed in our trial plan, and compared with historical ovarian cancer study rates of about 0.2 patients per site per month. From a clinical perspective, we believe this enrollment trend reflects several factors. encouraging survival and biomarker data generated in the OPCMATION-2 study, Growing familiarity with Ibn al-Zahra among investigators. a high conversion rate from prescreening to randomization, and operational efficiencies that simplify study participation without delaying initiation of standard of care treatment. Equally important, the quality of the study remains very strong. Patient compliance with scheduled study visits and treatments have been excellent.

Electronic case report forms continue to be completed in a timely manner. and the resulting data are supporting the ongoing maturity of the trial database. Finally, and very importantly, the safety profile remains highly favorable and completely consistent with our prior experience. To date, we have observed no cytokine release syndrome, no systemic toxicities, and no serious immune-related adverse events. Safety, therefore, remains comparable across both treatment arms, and a recent scheduled independent IDMC, Independent Data Monitoring Committee, review identified no new safety concerns. These enrollment and safety findings build on the foundation established by Ovation 2, which demonstrated a 14.7-month increase in median overall survival. 45.1 months versus 30.4 months, and a 24.2 month increase among patients who received PARP inhibitor maintenance, 65.6 months versus 41.4 months, with zero serious immune-related adverse events observed. The interim data, survival data, have been published in Gynecologic Oncology and were presented at the ASCO annual meeting in 2025. And we plan to submit the final overall survival data, which I just specified, to a major medical conference and expect to present those findings in early 2027.

In addition, because of the unique technology of the TheraPlas platform, which enables the safe and efficacious delivery of IL-12 to tumors and thereby solves a decade-long barrier, were invited to present at the inaugural AACR Drug Discovery and Development Congress, the D3 Congress, in July. Additional emerging translational data fully documenting the ability of Immunon 001 in our clinical studies to effectively reprogram the immunologically cold tumor microenvironment of advanced ovarian cancers into a hot anti-tumor environment was just accepted for presentation at the Annual Society for the Immunotherapy of Cancer, CITSE, conference in November 2026.

I'll now hand the call back to Stacey. Thank you, Douglas. I'd like to turn briefly to how we're managing the business because our actions speak to the confidence that we have in Immunon O-01 and the opportunity ahead. Every decision we make is guided by a single priority, advancing our pivotal phase three Ovation 3 study as efficiently and thoughtfully as possible. That commitment is also reflected in how the leadership team and employees have chosen to be compensated. leaders across the organization as well as members of their teams have voluntarily elected to receive a meaningful portion of their compensation in equity rather than cash. This This is a tangible demonstration of the confidence we have in the program. belief in the long-term opportunity and our alignment with shareholders. At the same time, we remain disciplined stewards of capital, carefully allocating resources to maximize the value of our clinical programs while maintaining strong alignment with our investors. On the financing front, in June we completed a financing of up to $10 million to support the Ovation 3 clinical program.

The structure was designed with our shareholders in mind, preferred stock, which is both non-redeemable and non-convertible, along with secured promissory notes. In this financing, there were no warrants, thus minimizing shareholder dilution and reducing financing overhang. Looking ahead, we will need to continue to strengthen our balance sheet with additional capital to support the full execution of the phase three trial as well as our GNA needs. We are actively exploring options that maintain the same discipline that I just spoke of. With that, let me turn the call over to Josh Blasher, who recently joined us as interim CFO to review our financial results. Josh?.

Thank you, Stacy, and good morning, everyone. Details of Immunon's second quarter 2026 financial results are included in the press release we issued this morning and are a form 10-Q, which we filed before the market opened this morning. Research and development expenses for the second quarter were $1.5 million compared with $1.5 million. 1.2 million for the same period last year, primarily reflecting higher clinical and manufacturing costs related to the Ovation 3 study. General and administrative expenses for 1.3 million for the second quarter, down approximately 20% when compared with the 1.6 million in the prior year period. to the ongoing cost containment initiative to which Stacy referred earlier. This remains one of the highest priorities for management. Net cash used for operating activities for the second quarter was 3.0 million down from 4.0 million used in the first quarter of 2026. As of June 30, in 2026, we had cash and cash equivalents of 6.9 million.

Together with the financing we completed in June and our ongoing cost discipline initiatives, we believe this supports an operating runway through the end of the year. With that, I'd like to turn the call back to Stacey for closing remarks.

Thank you, Josh. I'd like to start with Operator to open the line for questions first before my closing remarks.

Thank you, and we will now begin the question and answer session. If you would like to ask a question, please press star followed by the number 1 on your telephone keypad to join the queue. If you would like to redraw your question, simply press star 1 again. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. And your first question comes from Emily Bodner from HC Wainwright. Please go ahead.

Hi, good morning. This is Joey on for Emily. Congratulations on all the progress and thank you for taking our questions. To start off on the Phase 2 MRD trial, do you believe that the MRD improvement rates that you've been seeing with immunon-001 would be sufficient to show a statistically significant improvement versus control? And how is this And how important is this numerically higher rate of no evidence versus disease versus control? And on top of that, also, when you discuss the September R&D day coming up, do you plan to disclose any data from the ongoing trials, including the MRD trial and the Ovation 3? And lastly, for the rapid site activation that you've been discussing, is this sustainable? What's increasing your confidence in this going forward? And is there potential for any adjustments to enrollment timelines that might be quicker than the first half of the 2029 timeline?.

Great. Thank you. Thanks, Jory, for the questions. Douglas, you want to start with the MRD trial, the question about how the trial was set up and is it likely to reach statistical significance?.

I'd be happy to. The MRD trial is a small trial, and we certainly may reach statistical significance. The trial is still ongoing. We're still enrolling patients and still assessing MRD by multiple means. the time when the patients have finished their adjuvant chemotherapy but because it's a small numerically small trial whether we reach statistical significance or not we will have to see as the trial progresses. We think that we will. The importance of this trial, I think that was also part of your question, is that this is another way of showing the increased depth of response that we get by adding Immunon to standard of care therapy. We've been able to see quite clearly that many of the patients, after having neoadjuvant interval debulking surgery and adjuvant therapy, still have disease either macroscopically or microscopically. And we've been able to substantially... decrease that by adding immunon. Clearly the emerging field of MRD, as you well know, is a way of determining, for example, whether additional therapy might be used, using it as a prognostic factor. But clearly when you've completed therapy, having residual disease is is not a good thing to have.

So the fact that we can decrease, clearly decrease molecularly and microscopically and macroscopically the amount of any disease remaining is quite important, I think, prognostically for the patients and completely consistent with the improvements in survival the very impressive improvements in survival that we saw in the Ovation 2 study. There was one other part of your question, I think you were asking, are we going to be talking about MRD in Ovation 3? We are. are assessing things like circulating tumor DNA in the phase three study, but we do not have that data available at this time to discuss at R&D day.

Stacey? Thank you. Thanks. I'll offer a few other comments. So in terms of the statistical significance of the MRD trial, it's always important to understand how a trial was planned. So that trial was the sample size was not determined because of statistical powers. So at the end of the day, we know that's one influence of the likelihood of a statistically significant finding. This really is an important trial that ultimately is designed to answer some critical questions. We will hear Dr. Amir Jazari, who's the national PI, reflecting on that trial. at the R&D day, and if the effect continues to be large, then one might see statistical significance, but that was not the goal, as Douglas pointed out. We will be putting out an agenda for the R&D day and look forward to releasing that in the near future and you'll get some greater insight into what we plan to cover.

We do think it will be a very, very compelling set of presentations and will allow for interaction with some key experts and clinicians. who have been treating patients with immunonone-01 for a couple of decades. Number three, your question about enrollment, is it sustainable? I would say yes, and a large part of that is the knowledge and experience that we have from Ovation 2 and the planning that we have done, including using clinical trial simulations to look at what we would expect in terms of enrollment over time and looking at trial sites. We are very, very carefully activating sites to make sure that we stay ahead and that we're able to complete the enrollment on our target timeline. And we're tracking extremely well to that. So, you know, the plan and bringing on new sites really brings new reinforcements and the excitement level that we're continuing to see from the sites that were early in the trial. So we're feeling extremely confident, and we'll be working closely with the partners to ensure that we're delivering this trial as we've promised.

Great. Thank you for taking our questions and congratulations again.

Your next question comes from Jason McCarthy from Maxim Group, LLC.

Please go ahead. Hi, good morning. Thank you for taking the questions. It's kind of a multi-part question, all related to the MRD study, if you'd bear with me. So what is the expected timing? to be published. Is the gynecologic oncology group of the GOG involved in any way or were they potentially becoming involved given that there's currently no MRD standard for ovarian cancer? And following that up, can you discuss a bit about how, the way I see it, is that that study is kind of breaking new ground in how ovarian cancer could ultimately be managed.

Thank you, Jason. Those are great questions. So let me start and then Douglas, I'll turn it over to you. I know you have spent a lot of time thinking about how the innovative approaches and really the translational data that we have will help advance the process. advance the treatment paradigm and really understanding how we can assess and measure the disease. But the expected timing, you know, the trial, this is an emerging endpoint. The second look laparoscopy is something that the FDA has has expressed interest in, but does require a second procedure with patients. And the trial itself is growing and increasing, and we have continued to have discussions with breakthrough cancer and the lead PI around the progress of the trial and we're delighted that we've already accomplished a couple of goals. Number one, that we know now that immunon can be safely treated, administered concomitantly with Bevacizumab.

That was one internal goal that we had and wanted knowledge of. has already been accomplished. Number two is focused on the ability to treat women with immunon in the maintenance setting, and we have women that are receiving treatment in the maintenance setting. So outside of the questions that you've asked relative to this this landscape, we are very pleased with those learnings. And we would expect, I would say, As we go through the end of the year, we're expecting and hoping that the trial will reach full enrollment, and then there's a timeframe that is required to observe patients through second look laparoscopy. But that's the general landscape. The GOG is not involved in any formal way. in the MRD trial. We have involved them in our thoughts and plans, strategic input specifically to the phase three trial. We had an advisory board with them.

And we have GOG sites that are involved in our phase three trial. But right now, they have not been integral to the plans around the MRD trial. Douglas, would you like to pick up and comment on any of the three questions that you'd like to add to? Sure.

Certainly. There's a... I'm sorry. Did you have... Were you speaking, Jason? No, no, I didn't say the same. Okay, I heard something, sorry. With respect to the question, will the MRD data be published? Absolutely. We're in discussions with the principal investigator as to when he and we will start presenting data from this trial in national forums. Excuse me. Stacey's comments about GOG, I'd like to expand them a little bit because part of the question, GOG, like everybody taking care of patients with advanced ovarian cancer, is very interested in having a set of guidelines with respect to measurable residual disease. disease, this would be very helpful, most helpful if we had additional therapies to give to patients. the hard parts about determining the prognostic abilities of measurable residual diseases, best way to do that is to have a therapy which actually impacts on the outcomes of the patients. And we believe that we did this quite impressively in Ovation 2. We improved overall survival. We believe that we can do this.

We certainly hope that we can do this, repeat this in Ovation 2. And therefore, we'd have a population of patients in which we use studies like circulating tumor DNA in a population in which we advanced and improved on overall survival. It's those kind of studies that can validate and make the FDA look at something like circulating tumor DNA as an important prognostic marker. So we hope in Ovation 3 to be able to contribute to the ongoing work to develop a good MRD assay for ovarian cancer.

Thank you. Great. Thanks. And I thought that this question might have been asked and answered about the continued or potential continuation of the 0.5 patients per site per month rate. Is there any seasonality to enrollment for ovarian cancer? Is summer historically a little bit more challenging versus winter?.

fluctuations that can change that number. Douglas, what's your observation over the years you've been doing trials?.

Yes, for reasons I still don't quite understand, Jason. There is a lower rate of diagnoses and certainly enrollment onto clinical trials for many, many malignancies in the summer, including very acute malignancies like acute myeloid leukemia. But particularly with diseases like ovarian cancer, many patients in the summer Try to ignore their symptoms for a longer period. That's not a great way of saying it. But try to suppress their concern over the summer and don't get as many diagnoses over the summer as we would expect to see in the fall.

Yes, Jason, with the continued, I was just going to add, with the continued enrollment that we're seeing, we fully expected that, and it gives us even more confidence in the timeline because we're still seeing very strong numbers manifesting.

Yes. Okay. And just lastly, going back to the MRD trial, is getting that second look laparoscopy commitment from patients challenging, just given that it's a second procedure?.

Or does everybody kind of commit to doing that? Well, to enroll in the trial, they would have to be, you know, all trials require for there to be a review of the protocol and the procedures that they will go through, that all patients will go through. So to enroll in the trial, it's something you would have to align with. I do think that it's an innovative, very innovative protocol, and it's ultimately establishing a relationship ultimately with endpoints that we would hope in the future, in the future would be easier to access, right? This is part of how we advance science. We start out with, if it's imaging, it could be other diseases, more comprehensive explorations. And then what you hope is to be able to get it down into something that's a blood test. And I do think that there are some really powerful translational assays that are being explored and in this trial ultimately should have a really compelling set of insights that are brought not only from doing the second look laparoscopy, this is a very compelling, you know, in point that ultimately gives confidence, you know, that in fact, which women are truly not seeing. seeing advancement of the cancer and seeing minimal residual disease versus those that aren't, but then ultimately being able to connect that to other measures that we have, which should advance the field. So I do think it's going to be very, very exciting to see what we gain at the back end.

Thank you.

Great. Thanks for taking the questions. Looking forward to the next updates. And when do you plan on putting the.

putting out registration for the R&D date? It'll be coming soon. It'll be coming soon. Okay. We'll issue a press release and we'll share details of the agenda and look forward to those that come in person and also we'll have a webcast. So it will be an exciting day. Well worth coming in. For those in the city, coming to be with us in person and being able to interact with the esteemed faculty in person.

Great, thank you. Thank you. And your next question comes from David Boats from Zach's Small Cap Research. Please go ahead.

Hey, good morning, everyone. I appreciate you taking the questions. I've got a couple on enrollments.

Kind of as a follow up to Jason's question, but do you see a site productivity increase.

kind of the longer the site is open. So I know you talked a little bit about seasonality, but just... you see any increase in kind of that average 0.5 patients per month per site increase the longer the site is open? And then I'm also wondering if you're seeing any meaningful differences in screening or enrollment rates for HRD positive versus HRD negative patients.

Douglas, do you want to start? Douglas R. I'd be happy to.

David, your point about enrollment increasing as the site becomes more comfortable with it, I would say that's a generally something that we have seen, although the exception to that rule is the very first site that we opened, which in rolled amazingly from day one. But certainly in sites that, for example, sites that were not part of Ovation 2, there is a learning curve. The pharmacy... learns how to prepare the drug, administer the drug, et cetera. But it's a very fast learning curve. Once one patient has been in, I think everybody becomes comfortable, as they would with any new technology, and more patients are identified. And I forgot the second part of the question, which I thought I had written down. What was the second aspect?.

Is there any meaningful difference that you're seeing in the screening around HRA for HRA positive versus HRA negative? Thank you. No, absolutely not. patients have been enrolled essentially equally. Okay. And lastly, I don't know if it's going to be too early to start thinking about this, but about the timing of the two interim analyses. Mostly I'm thinking about if you can comment on when those might be occurring in relation to the current overall enrollment timeline.

Yes, I'll take that. David, it's a great question. It is early, but it's always great to be looking down the path. You know, one of the things that is important when we think about the timing of interims, which is, as you'll know, from our protocol and our plans agreed upon in advance with the FDA, so they're event-driven time points, and we will start that process. process once we have fully enrolled trials, the trial is fully enrolled. So this is something that we could actually talk about in greater detail in a later call and maybe go further into the trial design, but was arrived at not only with extensive simulations and understanding what the timeline is likely to be and when you might expect the events, which are deaths, until the end of the year. unfortunately, but are critical to have in the standard of care arm so that you can ascertain and see the treatment effect that exists. So there's very careful thought given to confidence in decisions and ultimately for the FDA to see these characteristics and align that if we meet the criteria that's set, that it would be worthy of a BLA filing for full approval. And we will certainly be able to talk more about that in the future.

Okay, great. I appreciate you taking the questions. Thank you, David. Thank you, everyone. Thank you.

And your next question comes from Camp Dolliver from Brookline Capital Markets. Please go ahead.

Great, thanks, and good morning. Just one topic, which is plans for site activations over the next few months.

Thanks, Ken. I will just offer comments on that. We have been extremely focused on activating sites to stay on track with our target timeline. We are tracking very well with that against our plan as we described. To give a brief overview of the plan, we have been working with broad sense of that. We have 35% of the planned sites that are already active or are in the process of being activated. So that's currently. And we have for the sites that remain to fill out the number of sites which we've planned, we have close to double the number of sites identified that are required to fill this. So we're tracking extremely well and feel very good about really about the engagements we're having.

We still continue to have some incoming calls in addition to the calls that we're making and look like we'll be able to put together the full plan really in the timeframe that aligns with our plan.

Great, thank you. Thank you, Kemp. There are no further questions at this time. now like to turn the call back over to Stacey Lindborg, President and CEO, for the closing remarks.

go ahead. Thank you, Frans. And thank you to everyone who joined us today and for all the thoughtful questions. You guys always ask very meaningful questions that allow us to talk more about our plans and how we're executing. So thank you for that. As you've heard today, we continue to make meaningful progress against every area that matters the most for our company and for the patients we serve. Our clinical data continue to strengthen enrollment in Ovation 3 is progressing ahead of expectations. External validation of Aminata 01 continues to grow, and we have remained disciplined in how we're deploying capital and execute the business. We recognize there's still work that's important ahead of us, and we believe the foundation we've built leaves us well-positioned for the next stage of development. Our priorities remain clear, execute on the Phase 3 study, generate high-quality data, and ultimately deliver a much-needed treatment option for women with advanced ovarian cancer.

With a clear clinical path, a differentiated product profile, and a capital strategy designed to support our path forward efficiently. We believe Immunon is well positioned to deliver meaningful value creating milestones in the periods ahead. We also look forward to seeing you at R&D Day in New York on September 23rd. Please mark it down. You'll have an invitation to register soon. And we look forward to keeping you updated on our progress and appreciate your continued interest and support. Have a great day, everybody.

Ladies and gentlemen, thank you all for joining and that concludes today's conference call. All participants may now disconnect.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Good morning. My name is Tina, and I will be your operator today. At this time, I would like to welcome everyone to the IMUNON First Quarter 2026 Final Results Conference Call. [Operator Instructions]

I would now like to turn the call over to Brandon Weiner of ICR Healthcare Investor Relations, representative of IMUNON. Please go ahead.

Thank you. Good morning, everyone, and welcome to IMUNON's First Quarter 2026 Financial Results and Business Update Conference Call.

During today's call, management will be making forward-looking statements regarding IMUNON's expectations and projections about future events. In general, forward-looking statements can be identified by words such as expects, anticipates, believes or other similar expressions. These statements are based on current expectations and are subject to a number of risks and uncertainties, including those set forth in the company's periodic filings with the Securities and Exchange Commission. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements.

I also caution that the content of this conference call is accurately is accurate only as of the date of the live broadcast, May 12, 2026. IMUNON undertakes no obligation to revise or update comments made during this call, except as required by law.

With that said, I would like to turn the call over to Dr. Stacy Lindborg, IMUNON's President and Chief Executive Officer. Stacy?

Thank you, Brandon, and good morning to everyone joining us on the call this morning. Joining me on the call is Dr. Douglas Faller, our Chief Medical Officer; and Mr. Jeffrey Church, our Interim Chief Financial Officer, who will review our financial results for the first quarter of 2026. Mr. Michael Tardugno, the Executive Chairman of our Board, is also on the line and will be available for Q&A.

We've entered the second quarter of 2026 with continued momentum following what was truly a transformative year in 2025, and we've made strong progress since our last conference call. We recently announced the final clinical data from our completed Phase II study OVATION 2, and IMNN-001, our proprietary IL-12 immunotherapy continues to demonstrate its potential to redefine frontline treatment for women with newly diagnosed advanced ovarian cancer. The pivotal Phase III study, OVATION 3, is advancing well, and we remain on track to randomize approximately 80 patients by the end of the first quarter of 2027.

The capital funding environment has been challenging, not only for IMUNON, but also for the biotech sector generally. We continue to take steps to sharpen our focus on enrolling this important OVATION 3 study as rapidly as possible and to conserve cash. The reaction from the investment community to our progress and the data we have presented to date, including the results from our OVATION 2 Phase II clinical study has been very positive.

Focusing now on our Phase III study, we do understand that the primary challenge is the time it will take to fully enroll this 500-patient trial and to generate sufficient data for a future BLA filing. Given the significant improvement in overall survival that we've seen in Phase II and we expect to see in Phase III, our primary endpoint, overall survival is both a major strength and a practical time consideration. On one hand, overall survival remains the gold and definitive standard for demonstrating efficacy in oncology and would support a BLA filing based on a single pivotal trial. On the other hand, it requires some time for the data to mature and reach a formal readout, in fact, longer than some investors might prefer.

We're solving this dilemma in 2 ways. First, through a disciplined bridge financing strategy that raises targeted capital to advance OVATION 3 and bring us closer to trial readout, positioning the company to attract new fundamental investors. Second, by structuring these financings in a creative manner designed to minimize dilution and limit pressure on IMUNON's share price. This could include the upside of a deal utilizing preferred shares, which are not immediately tradable, have no warrants with redemption at the market and would also increase shareholder equity. This kind of a deal could compare favorably to registered direct deals that are typically dilutive and often include investors with little long-term interest in the company. We'll have more to say on this in the near future and provide -- we will provide updates as they become available.

As always, our goal is to finance the company while not forgetting our shareholders and to keep a sharp focus on our North Star, which is bringing an innovative and much needed new treatment option to women with advanced ovarian cancer. Our approach has always intended to be as investor-friendly as the options available to us permit.

Based on our unprecedented IMNN-001 clinical data thus far, we are confident that our program will attract investments from one or more strategic partners that is minimally dilutive or nondilutive. Looking ahead, we are planning an R&D Day event in Q3 of 2026, and I look forward to inviting you to hear from our IMUNON team, trial investigators and oncology experts on the value of our IMNN-001 program to clinicians and patients. The strong response from our current trial investigators, patients and the broader medical community supports our belief in the significant potential of IMNN-001 to make a meaningful difference in women's lives. I know your attendance will be rewarded with the inspiring attitude of the physicians and scientists who are intimately involved with our unique proprietary DNA-mediated recruitment of the entirety of the body's defense against rogue malignancies, something that we have the pleasure of experiencing on a regular basis.

I'll now turn it over to Dr. Douglas Faller for clinical commentary. Douglas?

Thank you, Stacy. Building on your comments, the enthusiasm within the gynecologic oncology community continues to grow. Our Phase II OVATION 2 clinical data showing a clinically meaningful 14.7 month median overall survival benefit with IMNN-001 treatment plus standard of care chemotherapy and the ability of IMNN-001 to activate both innate and adaptive immunity remains highly compelling to investigators. Our scientific presentations have reinforced IMNN-001's unique profile, localized IL-12 delivery with negligible systemic exposure, favorable safety and clear signals of immune activation predictive of superior outcomes. In addition, we look forward to presenting the final OS results from OVATION 2 at an upcoming national conference.

As Stacy also mentioned, we are thrilled to share that our next R&D Day will be scheduled in Q3 2026. This event will showcase the final efficacy analysis from OVATION 2, along with additional promising safety, efficacy and translational data from our MRD study and a new highly supportive translational data from OVATION 2.

Building on the transformative clinical and translational results we have already reported in the public domain, these presentations will further highlight the significant potential of IMNN-001. I'm happy to say that investigators continue to proactively approach us about joining our Phase III OVATION study. Study enrollment is progressing nicely and remains on track with current sites performing well. Safety data remains clean and consistent with prior clinical results, including data from the ongoing Phase II MRD study, which further support the favorable tolerability and unique mechanism of action of IMNN-001. These consistent findings give us high confidence as we advance the pivotal Phase III trial.

Back to you, Stacy.

Thank you, Douglas. Before turning to our financial update, I want to highlight that we remain focused on disciplined execution and strategic focus as we advance the most important development program in our company's history, IMNN-001, and of course, with our initial sites on ovarian cancer.

Our multipronged financing strategy continues to balance the need to extend our cash runway while minimizing dilution and moving IMNN-001 forward as quickly as possible. Shareholder value remains paramount and every decision is stress test against our commitment to fully fund the OVATION 3 study.

Now over to Jeff Church for a review of our first quarter 2026 financial results. Jeff?

Thank you, Stacy. Details of IMUNON's first quarter 2026 financial results are included in the press release we issued this morning and in our Form 10-Q, which we filed before the market opened this morning. We continue to manage our cash position prudently through targeted financing activities, cost-saving initiatives and operational efficiencies. Our disciplined approach, including the strategic reorganization announced earlier this year and the completion of the OVATION 2 study supports our ability to advance the OVATION 3 study while extending our operating runway.

Research and development expenses increased to $2.3 million in the first quarter of 2026. from $2.2 million in the same period last year. During 2025, the company initiated enrollment of the OVATION 3 study. And also in 2026, we've closed the OVATION 2 study.

General and administrative expenses remain unchanged at $2 million in each of the first quarters of 2026 and 2025.

Net cash used for operating activities was $4 million in the first quarter of 2026. This compares to $2.8 million in the comparable prior year period. This increase was largely due to the trial-related expenses associated with starting up the OVATION 3 study.

With that financial review, I'll turn the call back to Stacy.

Thank you, Jeff. Tina, that concludes our prepared remarks. If you could open the call for questions?

[Operator Instructions] And our first question comes from the line of Emily Bodnar with H.C. Wainwright.

I noticed you gave initial guidance on enrollment completion for the first time. So maybe just kind of walk through what gives you confidence in this timing and how demand for OVATION 3 enrollment has kind of played into those assumptions?

Douglas, can you apprise us of our goals of fully enrolled? When we expect all the trial to be fully enrolled and other reflections on the interest in the trial?

I'm happy to. Emily, thanks for your question. We're enrolling 500 patients total, as you know, in our study, and we expect the last patient to be enrolled in Q1 2029. We are increasing the number of sites that we have activated, and that's been a push this year. And we are expecting to have 80 patients enrolled approximately a year from now, as I think you know, which would be [indiscernible] of the total that we will enroll for the trial.

Your next question comes from the line of David Bautz with Zacks Small-Cap Research.

So another question about enrollment. So you've been indicating for a while now that enrollment has been, I guess, remaining ahead of schedule. I was wondering if you could just quantify that a little bit. Is this due to site efficiencies or investigator enthusiasm, patient demand? What's kind of driving that?

Yes. Maybe I'll start, and Douglas, you can add. Trials always have an assumption of patients per site per month. And when we look at early in the trial, when you are starting with your early sites, we always have internal targets for -- by month, right, that we're hoping to accomplish. And when we say we're ahead of target, it really reflects that by month, we've consistently had more patients enrolled than we were -- than our forecast.

I think that as we ultimately set goals, and it is very critical that we're completing the enrollment of this trial very expeditiously. You heard me reflect on our last earnings call that we were targeting this to be complete in the first quarter of 2029. That then becomes our true target, and it becomes critical that we're enrolling sites up to the number that we believe we need to be successful in doing this. And I would say we're tracking very well with the process of now a brand-new set of cohort of sites that are coming on board.

And I'm really delighted by the early sites. These are obviously -- we're strong partners from OVATION 2. They know our product. They comment when we're with them in their centers of how visible it is to them when they're doing surgery on their patients, how different women who have been treated with IMUNON look relative to the control. And therefore, it's not surprising that some of these are substantially above the assumptions that we've made for the number of patients per site across the whole study. But it's been quite remarkable from that viewpoint.

But Douglas, why don't you offer some additional perspective?

Well, I will echo what Stacy said and also just mention that we've been very gratified at the excitement and the number of patients some of the sites have enrolled upon just starting up. It's really, I think, a testimony to the belief of our investigators in the potential benefit of IMNN-001 that they are very aggressively identifying patients who should benefit and talking with the patients and putting these patients on study.

So, again, just as Stacy has been pleased, our whole team, clinical team has been very happy with the strong engagement of the investigators. And as I said, in some cases, a flurry of activity as soon as their site is activated.

Okay. Great. And do you think this rate of enrollment has had any -- led to any increased collaborator interest at all?

Collaborator, meaning partners, BD partners?

Yes.

I don't think that's necessarily interacting in terms of those 2 streams. But I do think that the counter would be true. If we are not successfully enrolling the trial, then you can expect that, that would have a negative impact on BD and I'd say even investor interactions. But I think that this really ultimately being able to describe which of us have spoken of in the past, I think could elaborate on if you'd like. But we continue to have sites that were not part of OVATION 2 that reach out that are seeing our data presented in the scientific community when our paper came out with the full publication from OVATION 2. We had outreach from centers, not just in the U.S. but in other parts of the world. And that enthusiasm tied with the other aspect of the visibility that we've gotten in the medical community really speaks volumes. And I do think all of those positively impact all of our endeavors, partnerships, investors, et cetera.

Your next question comes from the line of Jason McCarthy with Maxim Group.

Could you -- it's more of an abstract question. Can you just review us -- sorry, review with us the powering assumptions around OVATION 3 and how many months OS you need to see? And I know it's far off, but that interim data sometime in, call it, 2030 or so, is that expected to be blinded or unblinded in terms of sacrificing some of the power?

And more broadly, there's been an uptick in clinical trial activity around WEE1 inhibitors. There's new ADCs that have come after Enhertu. There's been a lot of activity around the PI3Ks in different categories. So how do you see the treatment landscape potentially shifting in ovarian cancer over the duration of the OVATION 3 trial potentially having an impact positive or negative?

So these are great questions, Jason. Let me try to take them one at a time. And I think that I'll start with the first 2. Number one, it's an unblinded trial in the sense of the patients and the treating clinicians are unblinded. As you know, the reason for that is the insertion of a catheter really makes it unethical to run a blinded trial, which the FDA agrees with us on that front, we would not want to have to insert an unneeded catheter in the standard of care patients who are randomized to standard of care.

So we -- that's separate from saying, is there a structure and appropriate protection of the trial and integrity of the data that's occurring in the trial. And so there are components of what we do that will really -- we will be operating in a manner in terms of access to data unless it's truly needed for the job and would fit practices. We'll be acting in a manner as if it's blinded internally.

And in terms of the assumptions, we have continued to see the treatment effect grow across the number of times that we refreshed the OVATION 2 data. And then finally, of course, the final readout as we prepared and now have closed out the trial site. So we saw the trial go from initially an 11-month improvement over the standard of care and overall survival, median overall survival upwards to close to 15 months, which is really, really quite remarkable. And you'll hear more from us in the future. We're really looking at how we can harness the final set of the data and how we can bring that to bear in terms of the Phase III trial and if, in fact, it would permit us to pull forward the final analysis. So I would say it's early for us to talk about that, but it is something that we're carefully thinking through as any company would. When you have new information, you always want to make sure that you're your trial is really operating in the best information possible.

So the trial that we have described in the past, and this will continue, we'll have interim analyses. We have 2 planned. And right now, they're designed to allow for an early stopping for efficacy that would occur about a year or 1.5 years after the fully enrolled patients. The second would occur about a year later. And I think that we'll be offering more guidance on this front.

So -- and the last piece that in terms of the blinded and unblinded aspect, as we're ultimately talking to investors and thinking about how we can align the financing with long-minded investors that are really thinking about the course of this trial, we will have the ability to spread the amount that we will need to run the full trial really over the course of this trial. And one of the exciting aspects of the fact that it is an unblinded trial does permit us to allow for consideration of gaining and giving insight publicly into the secondary endpoint. So to really build some confidence that we're observing, we're observing secondary endpoints, which are all hard endpoints, pathological scoring and other such endpoints that were part of our OVATION 2 and really building a confidence that could derisk financings and tranches, especially over time. So those are things that we're working through and have resonated well with our discussions with investors.

On the front of the changes happening in the competitive landscape, Douglas, can you offer some perspective?

I'd be happy to, Jason. So as a clinician, I'm very excited that there are second-line plus therapies being developed, including the ADCs you mentioned and also actually Ber antibodies. The community is excited by this because we've been so limited in what we could provide patients second and third line and fourth line.

While these are advances, I think one has to say that they are small advances. The benefits in terms of PFS, the benefits in terms of survival are poor or let's say, not terribly strong. We're talking months, and they're certainly not curative, as you know. Yet they are going to be available for our patients, second and third line, both the treatment arm and the control arm. And so the implications on our study are really modest, I think.

In addition, just to further emphasize the importance of frontline care, which is what we're delivering, even PARP inhibitors, which as maintenance have improved PFS in patients with frontline ovarian cancer. These are now being restricted more and more. The actual benefit of the PARP inhibitors, some of them have led to the FDA walking back some of the approvals. This doesn't affect our study. We're using PARP inhibitors as the FDA has suggested. But it just, to me, further highlights the need for new and effective treatments upfront, which is what we're delivering.

So the landscape for patients, second and third line has improved somewhat, maintenance, perhaps less so. But we are in front of all of these things, and we are expecting -- we are hoping to reproduce the results we saw in OVATION 2, which are not a few months benefit in survival, but over a year in survival. That's our ambition.

[Operator Instructions] And our next question comes from the line of James Molloy with AGP.

Matt on for Jim today. Congrats on the progress this quarter. Just a few from us. How should we expect the SG&A spend to look going forward given the recent reorganization? And I have a follow-up on clinical.

Matt, it's a great question. And Jeff, do you want to cover just high level what we expect by quarter?

Right. Based on our current projections after the reorganization that we implemented in the first quarter, we're looking at spend over the next coming quarters in the $4.5 million to $5 million. We expect our G&A level to remain fairly consistent with where we were in the first quarter, but we would see an increase as we bring on more sites and enrollment starts to step up as it relates to the OVATION 3 study.

And Matt, just a follow-up point to what Jeff just provided, what we shared in terms of the strategic restructuring, there were positions eliminated, but there also were jobs that were redefined. And so a huge part of this is ensuring that, not only our resources are being well served, clearly, we don't want to carry resources that are not directly contributing to our top priorities, but it also is really about making sure we can go as quickly as possible and that we're all focused on the launch of the Phase III trial directly towards the completion and preparation for the commercial landscape, both on the manufacturing side and as we begin to prepare for the BLA.

Great. And then in terms of just the kind of reorganization broadly at the FDA, have there been any discussions about utilizing some of these pathways like CNPD later down the line, accelerated approval as you guys get to the interim reads? And how have those gone with this new kind of administration there?

Yes. I think that we've designed a really well-thought-out trial, which has always received very positive and professional engagement with the FDA. So we've described over time, but it's -- I never get tired of reflecting on the point that we got in writing from FDA that they had no safety concerns about the trial right around the time that we were finalizing the protocol in the end of Phase II meeting. So we clearly understand that we've designed a trial that sets us up for filing if we're successful, if the trial meets the statistical thresholds. And it's also under the agreement with the FDA.

The interim analyses were a core part of the trial design and the analysis plan. They are designed to allow for full approval of the group that's being analyzed in that interim analysis if we meet the threshold. So as with all Phase III trials, you clearly outlined what that threshold will be. We've used a very efficient alpha spending for the interim analysis. Probably that goes beyond what you're wanting to talk about, but that's something we care a lot about is being very efficient and ensuring that we're getting enough an opportunity to the interims, but then ultimately allowing the final analysis to really be set up very effectively.

And so we're really not right now with this Phase III trial focused on the idea of accelerated approval. We're focused on full approval. But I do think we'll keep line of sight to ways and opportunities that maybe will allow additional interactions with FDA, maybe more accelerated and higher priority or if we reach a point in time where we want to formally engage FDA around programs that they're speaking about.

Douglas, do you have anything you want to add to that?

I just wanted to add one thing. As you know, Matt, accelerated approvals are usually based on early surrogate endpoints. And the upheaval of the FDA and some of the decisions that they've made really don't affect us. We are looking at OS. And the FDA actually just recently issued a guidance saying for oncology trials, we want to see OS as the primary endpoint. That's always been our intention, that is how our trial is written. And we would not expect any surprises in taking an OS benefit to the FDA.

It would be in oncology in all my years of experience, an OS benefit is never questioned. So we're not having to deal with -- we won't have to deal with potential changes in what's expected by the FDA. We have the gold standard and what they call the gold standard as our primary endpoint.

This concludes the Q&A portion of the call. I'll now turn the call back to IMUNON's President and CEO, for concluding remarks. Stacy?

Thank you all for joining the call. With our Phase III trial OVATION 3 patient enrollment on track, the enduring strength of our Phase II overall survival data and the compelling translational evidence, and our sharpened financial discipline, IMUNON is well positioned for value inflecting milestones in 2026 and beyond.

I want to assure you we remain steadfast stewards of the resources you have entrusted to us and are fully committed to delivering a potential paradigm shift in ovarian cancer treatment while creating lasting shareholder value. Thank you for your continued support.

And this concludes today's conference call. You may now disconnect.

Good morning. My name is Desire, and I will be your operator today. At this time, I would like to welcome you to Imunon's Fourth Quarter and Full Year 2025 Financial Results Conference Call. [Operator Instructions]

I would now like to turn the call over to Peter Vozzo of ICR Healthcare Investor Relations representative for Imunon. Please go ahead.

Thank you, Desire.

Good morning, everyone, and welcome to Imunon Fourth Quarter and Full Year 2025 Financial Results and Business Update Conference Call. During today's call, management will be making forward-looking statements regarding immuno expectations and projections about future events. In general, forward-looking statements can be identified by the words such as expects, anticipates, believes or other similar expressions. These statements are based on current expectations and are subject to a number of risks and uncertainties, including those set forth in the company's periodic filings with the Securities and Exchange Commission. No forward-looking statements can be guaranteed, and actual results may differ materially from those such statements. I also caution that the content of this conference call is accurate only as of the date of the live broadcast, March 31, 2026. Immuno undertakes no obligation to revise or update comments made during this call, except as required by law. .

With that said, I would like to turn the call over to Dr. Stacy Lindborg, Imunon's President and Chief Executive Officer. Stacy?

Thank you, Peter, and good morning, everyone. Joining me on the call this morning is Dr. Douglas Fowler, our Chief Medical Officer; and Mr. Jeff Church, our Interim Chief Financial Officer, who likely needs no introduction, given his tenure with immuno. He'll be walking through and reviewing our financial results for the fourth quarter and full year of 2025. Mr. Michael Tardugno, the Executive Chairman of our Board is also on the line and will be available for Q&A. We entered 2026 with strong momentum following a truly transformational year in 2025.

Our proprietary IL-12 immunotherapy immunon-001, and continues to demonstrate its potential to redefine frontline treatment for women with newly diagnosed advanced ovarian cancer based on all available data thus far, both translational and clinical and immuno 001 is rapidly advancing in the OVATION II pivotal Phase III study. The urgency of this program remains front and center for our efforts. -- to create value for our shareholders and to address the unmet need in ovarian cancer, which continues to claim far too many lives as the standard of care traditional chemotherapy in the frontline setting has not advanced in over 30 years.

In our OVATION 2 study, IMMUNON-0-01 demonstrated the first ever overall survival benefit in a randomized frontline clinical trial for this patient population with a final overall survival readout showing continued improvement in median overall survival across the trial through 3 different analyses that were conducted. Starting first with the original Phase II clinical trial data readout in July of 2024, which was across all endpoints. The median overall survival benefit was reported as 11.1 months.

The median overall survival improvement observed in the subsequent clinical data readout in December 2024 was 13 months. And as we disclosed this week, has now expanded to 14.7 months in the final review of the trial results. Moreover, patients treated with PARP inhibitors as maintenance therapy. In addition to ImmUNN-01 and standard of care chemotherapy demonstrated a median increase of an overall survival of more than 2 years.

The timing of this final analysis was defined in the protocol to occur when the last patient enrolled in the trial had reached 3 years post treatment, and these truly unprecedented Phase II results have given our laser-focused execution of the ongoing rigorous Phase III trial, which was as agreed to with FDA, is designed to confirm the Phase II results and support full regulatory approval. Throughout 2025, we showcased the strength of these Phase II clinical data and the compelling translational insights at major scientific forums highlighted by the platform presentation at the 2025 ASCO Annual Meeting and the simultaneous publication of the AVATION2I study results in the peer-reviewed journal gynecological oncology.

We capped off the year with a highly successful R&D Day we hosted in November and New York City, and the investment community and leading clinicians heard directly from key opinion leaders about Immunon's ability to turn immunologically cold tumors hot to remodel the tumor microenvironment and deliver meaningful clinical survival benefits to women with newly diagnosed advanced ovarian cancer where none had existed before. This momentum carried into 2026 with OVATION II trial enrollment well ahead of plan.

In a protocol that is virtually identical to the Phase II study, OVATION III is a 1:1 randomized trial to evaluate IMMUNI-001 and plus standard of care, neoadjuvant and adjuvant chemotherapy, which includes interval debulking surgery versus the standard of care alone in women with treatment-naive advanced ovarian cancer. The adaptive trial design with interim analysis for early efficacy stopping rules provides 95% power on the primary endpoint of overall survival, while offering the potential for accelerated time lines of a BLA for full approval.

Key updates since our Q3 2025 results conference call underscore the strength of our Phase II foundation and the accelerating progress in Phase III based on the strong response from patients, our clinical trial investigators and the broader medical community. And I'll just highlight a few areas, starting with site activation status. Phase III trial enrollment remains strong with 7 clinical sites actively enrolling patients. and up to 43 additional high-quality centers under evaluation or in start-up mode.

Returning investigators from the OVATION 2 study have been joined by new top-tier centers. many proactively reaching out following our data presentations and publications. We have contracted a global CRO to support rapid advancement of Phase III trial site activation and study overall. Turning to enrollment velocity. Building on the strong progress we reported in late 2025, patient randomization and treatment in the Phase III trial have continued at an impressive pace and enrollment remains ahead of plan.

The early sites have delivered higher than the assumed rate of 0.3 patients per month with some sites delivering as high as 1 patient per month. This early momentum driven by the compelling Phase II study overall survival benefit positions us well for continued acceleration of site activation and patient enrollment. Our goal is to have approximately 80 patients enrolled in the trial within the next 12 months and enrollment completed in 2029.

Turning to regulatory and design validation. Based on the FDA's endorsement of overall survival is the primary endpoint of the Phase III trial combined with the robust statistical framework and precedent in oncology clinical drug development, Ovation 3 continues to derisk the path to a potential regulatory approval in both the U.S. and Europe. On translational data and the MRD trial data, we have data from the ongoing Phase II minimal residual disease or MRD studyin collaboration with breakthrough Cancer Foundation. This trial further reinforces Immuno 001 novel mechanism of action with demonstration of preferential uptake of peritoneal macrophages, profound tumor microenvironment remodeling, complete pathological responses and durable IL-12 and interferon gamma expression with excellent tolerability, even in combination with bevacizumab.

We've successfully capped our enrollment in the MRD study at 30 patients, allowing the trial to meet all core objectives and upon completion, channel resources and highly productive sites fully into the Phase II OVATION II trial. Preliminary data from the Phase II MRD study continue to align with the overall survival benefit shown in the Phase II OVATION II study and support potential label extensions in the future.

I'll now turn over the call to Dr. Douglas Fowler for clinical commentary.

Thank you, Stacy. The enthusiasm within the gynecologic community that we saw at our R&D Day in November and throughout 2025 has only grown. The Phase II OVATION 2 clinical data showing a clinically meaningful 14.7 month median overall survival benefit and the ability of Immonon to activate both innate and adaptive immunity continue to resonate strongly with our investigators. Our multiple presentations at leading congresses in 2025 highlighted Immunon's unique profile localized IL-12 delivery with negligible systemic exposure, favorable safety and clear signals of immune activation predictive of superior outcomes. Interestingly, after seeing our data presentations, many investigators have been approaching us, asking us to join our Phase II OVATION study rather than vice versa.

I find this kind of initiative to be most unusual in my long experience conducting clinical trials and also very gratifying. It further supports the consensus of the significant potential of immUnON-001 to address the unmet medical needs in newly diagnosed ovarian cancer. Ovation 3 has leveraged this interest from day 1. As Stacy said, study startup was completed in record time and early sites have exceeded enrollment forecasts. Safety data remains clean, mirroring the excellent tolerability seen across our immuno 001 clinical programs. The Phase II MRD study has provided real-time confirmation of the favorable safety profile with no dose-limiting toxicities, no discontinuations due to immuno 001 and very encouraging trends in progression-free survival and MRD negativity.

These consistent findings across our studies give us high confidence as we scale the Phase III pivotal trial. Back to you, Stacy.

Thank you, Douglas. Before turning to our financial update, I want to highlight that 2025 was defined by disciplined execution and strategic focus. We advanced the most important development program in our history while navigating a challenging capital markets environment with prudent and foresight. Our multipronged financing strategy combining targeted equity raises, opportunistic ATM usage and ongoing partnership discussions. -- has allowed us to extend our cash runway while minimizing dilution and advanced immuno on 001 as quickly as possible. Shareholder equity remains paramount. Every decision a stress test against our commitment to fully fund the Avation 3 study with long-minded investors. We're making solid progress on this front and believe that once we secure a lead investor, we will be able to assemble a syndicate quickly. .

While the markets are improving and our ongoing calls with strong investors remain highly encouraging, we recognize that this time -- this process inherently takes time. We will continue to balance the ultimate goal of financing the trial with long-term-oriented investors against the need to prudently extend our cash runway. We firmly believe that successfully completing this full financing is in the best interest of all of our constituents, including patients who are at the center of everything we do and all shareholders as we believe -- this will enable our investors to realize significant value.

We are encouraged by continued interest and potential nondilutive partnerships for our TheraPlas technology platform and immunon01. On the financing side, prudence of our prudent use of our ATM facility and warrant exercises supplemented our cash position in 2025. Monthly cash usage has been further optimized, and we announced a strategic reorganization in February 2026 to reduce nonessential costs and to sharpen our operational focus exclusively on Ovation iii. Streamlining operations and focusing scientific leadership while preserving all critical expertise in the interest of all immunon stakeholders. These actions, combined with our continued manufacturing efficiencies, which are great, are designed to deliver on our milestone with maximum efficiency.

Now over to Church for a review of our fourth quarter and full year 2025 financial results. Jeff?

Thank you, Stacy. Details of Immunon's fourth quarter and full year 2025 financial results were included in the press release we issued this morning and in our annual report on Form 10-K, which we filed before the market opened this morning. As of December 31, 2025, cash and cash equivalents were $8.8 million, reflecting disciplined cash management and net proceeds from warrant exercises and targeted ATM uses during the year. We project that this cash balance, together with our ongoing financial activities and cost-saving initiatives extends our operating runway into the second half of 2026.

Research and development expenses for 2025 were $7.8 million, which was significantly lower than 2024, primarily due to the completion of the OVATION 2 study. optimization of the MRD study and focused spend on the OVATION III study, manufacturing and start-up activities. General and administrative expenses were down 8% year-over-year through streamlined operations and renegotiated commitments. Net loss for 2025 was $14.5 million or $6.83 per share compared to $18.6 million or [indiscernible] per share, reflecting meaningful improvement driven by our cost discipline.

I just would like to remind everyone that all share and per share amounts reflect the 15 for 1 reverse stock split effective in July 2025. And and the 15% stock dividend declared in the third quarter of 2025. With that financial review, I'll turn the call back to Stacy.

Thank you, Jeff. And Deserewith that, we'll open the call for questions. .

[Operator Instructions] And our first question comes from the line of Emily Bodnar with H.C. Wainwright.

First one, have you presented the final data from Ovation to the FDA, particularly on the PARP inhibitor patient population. And have you received any feedback from the FDA on focusing on this patient population first in your OVATION II study? And then maybe if you could just kind of outline how you're thinking about upcoming milestones and catalysts for 2026? And any Ovation 3 updates that you're considering for this year? .

Thanks, Emilia. -- very well formulated and comprehensive question. So let me take it in steps. So first, we have not presented the OS data to the FDA. We are incredibly excited by the fact that it continued to improve. But really, this last analysis reinforces exactly the plans that we have in place. I think you specifically asked about the PARP-treated patients. And while this is even a larger effect than what we see in the intent-to-treat population, we know that this is a relatively small group in the trial and it becomes important that we're replicating the finding.

So we will be presenting the data to the investor community and will also be presenting it to the clinical community. In fact, we got an abstract submitted over the weekend to a meeting that will really afford us to have some great discussions with potential new principal investigators. So our focus right now is really around the Phase III trial ensuring that we're continuing to build the amazing momentum and excitement in the medical community around this data and then ultimately delivering on the trial. So -- maybe I'll stop there really quickly and see if there's anything else, Douglas, do you want to add to the latest data.

Just that -- although we're very excited about the results in the patients treated with PARP inhibitors, -- we're equally excited about the results that we see in the entire population. And this greater than a year increase in survival is, as you know, unprecedented in ovarian cancer. No 1 has seen anything like this in the entire time I've been practicing medicine. So the ability as we replicate this in the Phase III, this will be incredibly meaningful for patients. And the whole population of patients is what I'm getting at not just the patients who receive parities. If they continue to benefit as much as they did in the Phase II, that's wonderful, but we're focused on benefiting -- providing benefit to the entire population of newly diagnosed women with advanced ovarian cancer. .

Emily, if I remember correctly, the other questions were focused around upcoming catalysts and our plan for this year and beyond. And I would say that we have catalysts that we're going to be very excited to report back 1 of them being around the momentum of the trial. And so you heard in my prepared remarks, that we are -- our goal is to have 80 patients enrolled by this time next year. and reporting our momentum will be a very critical component of ultimately the overall time line that we've been committed to -- so that will be 1 catalyst. We will continue to have presentations at medical and scientific congresses.

We have samples -- tissue samples still from evasion 2 that we intend to analyze and have, in the near term, a comprehensive analysis and publication around translational data that we think will really be very compelling for the scientific and medical community that we'll be able to go beyond what we've presented to date. And I think that will be a very meaningful contribution. We have the potential for partnership progress that may provide opportunities to extend runway further. And of course, we are continuing with our strategic goal of financing the trial with long-minded investors. And those are all things that we're very, very actively involved with.

So our plans for 2026 really are going to be focused on our funding for the company, making sure we have the cash runway and that we are really increasing our institutional base in the -- in parallel. And then second, enrolling the trial and ensuring that we're spending a lot of time with our partners that are involved in this trial and the broader medical community as we're really helping translate the value for women newly diagnosed and bringing forward a product that really should revolutionize the standard of care.

Our next question comes from the line of James Molloy with Alliance Global Partners.

Could you walk us through -- I know you gave excellent guidance or very clear guidance about 80 patients by this time next year and 2029 to complete enrollment of the trial. Could you walk us through what potential cut points for interim looks we might be able to anticipate going forward over the next 12 months? .

Yes. Great question, James. Thank you. So the interim analyses, which have been laid out are all very carefully designed through comprehensive simulations, which are always looking at the time frame in which you might expect to be able to see a successful hit, if you will, so a p-value that would allow you to file your BLA. And as you know, we've described this in the past, and we've had reviews of our protocol, we've designed these debt for the 2. So the important component, given what we know very well from the literature and other immuno agents.

We need to observe patients long enough to be able to see events in the control arm for there to be really the ability to have success. So we've designed these interims to occur after the point that we would have fully enrolled trial. And we expect, based on the simulations that we've done in the past that the first interim would occur about a year after that. So that is what we're actively working towards and it's, as always, designed to allow for if we see a bigger effect then we have assumed in the protocol. This interim, in fact, the first interim may provide and will -- would provide an opportunity for us to act more quickly than weighting. But it also is important that we're being very careful with these entrants?

And of course, because you're using type 1 error rate as you're ultimately doing these formal analyses. So that's kind of a bit of an insight into how we balance the various dimensions and what we can expect going forward.

And then maybe a follow-up question on the final data on the Ovation Q showing the excellent survival data. How did that change the potential partnership environment, if at all you can share with us?

So it's obviously very early. We just released the data last week. We are participating tomorrow in the Med instead investor conference, and we are getting new inquiries that are occurring even as of this week. But I expect that to continue to develop these kinds of partnerships, whether they're geographic in nature or -- they're more fundamental with big pharma really ultimately have to fit with a strategy and an interest and an intent from a timing standpoint. So -- but we're very pleased to see renewed and new inquiries. .

Next question comes from the line of Jason McCarthy with Maxim Group.

Stacy. Going back to Ovation -- is there going to be an opportunity when you continue to mine that data? Will you have anything related to minimal residual disease or any [indiscernible] looks for MRD or any more immune data that might be suggestive of T cell memory or something that's keeping these patients' disease kind of in check and that could be driving these longer-term survivors?

Yes. Maybe I'll start and then I'd like Douglas to pick up. So we won't have anything from Ovation II that relates to the minimal residual disease or second look laparoscopy because it's an additional procedure that is not part of standard of care, and therefore, it wasn't implemented in Ovation 2 nor will it be implemented in Ovation 3. So that is an exploratory and it's an endpoint that I think has gotten a lot of interest as a potential predictor of overall survival that was incorporated into what we call the MRD study. So the Ovation I won't give insights into that, but we will continue to contribute not only to our own learnings but also the literature from the trial that we're doing in combination with breakthrough cancer. But we do have other data that we'll be able to get from Ovation 2.

And I'll let Douglas go into some of that.

Yes. Yes, we've been over the last 9 months or so, as you know, and alluded to, we've been releasing more and more translational data, and we have additional translational data to present, and we will -- we're planning on publishing that also. This may include looking at peripheral responses in addition to the responses that we've shown so dramatically in the tumor and the tumor micro environment. So we're very excited about the translational data. Just to expand on what Stacy said, even though we call 1 of our trials, MRD is not really officially established for ovarian cancer. There's no -- there are no criteria that have been shown to be predictive of patients outcome.

The MRD study is an approach to start working on that. But that data has yet to evolve and we will try to determine over time what the best approach to MRD might be for it to be predictive in ovarian cancer. It's something of great interest. This is in part why breakthrough cancer got involved in the MRD study because they also would like to be able to generate a test like MRD, which could be predictive of patient outcomes. And in addition, in our Phase III, we will be looking at circulating tumor DNA. This may end up being a marker for MRD. It's not established yet in ovarian cancer, but our trial might be 1 of the ones that could establish circulating tumor DNA as a predictive marker. So that's yet to come.

Great. Are there going to be updates from the MRD study in 2026 that we could look towards as potential catalysts?

It's possible. I think that it will ultimately depend really on -- the -- our interactions with the study PI, Dr. Mir Dasari, we know that he presented data that was very exciting to see the analytical data, and he decided to really take a cohort of patients and analyze them together rather than continuing to analyze patients over time, individual patients over time, and the clinical data, of course, will be continuing to evolve. So we're in early discussions with him around where we may present that in the medical community, and we'll be thinking very much about bringing Ford insights. It will be an exciting other arena for information.

I don't know last question. I don't know if I'm overlapping what James had asked previously about enrollment timing. But when you get to the 80, are you going to release any details on the HRD status of the patients, just so you can get a sense of the percentages that are in the trial or maybe in the trial?

An interesting question. I think right now -- and if I just step back and I look at what we've learned with this final analysis, our the overall effect that we've observed in the all-comers population has continued to grow so substantially that while the underlying genetics, which right now plays a critical role in the maintenance therapy and and become central to how the trading community is taking care of patients. What's interesting is that our principal investigators are probably as excited about the effect in the HR proficient patients as they are in the HRD positive. And so it will continue to be a very interesting and important part of our Phase III trial. But I think that we will really be looking holistically at the full trial and be very excited because we're able to influence and extend the life of an all-comers population.

So it's -- that's my thinking of this. And I think that we'll have to think very carefully about the exposure that we give to an ongoing Phase III trial. It's a -- it's an open-label trial, and we'll have the ability where we find it important from an investor standpoint to think about maybe secondary endpoints and provide updates. But those will be taken with great caution just to preserve the integrity of the trial. That was the anything there.

Yes. The only thing I wanted to add is although this is an open-label study because to preserve data integrity we and the company are blinded in terms of efficacy, not safety but efficacy. So we will not even ourselves be seeing the efficacy data as the trial progresses in terms of primary.

Okay. So just also -- sorry, 1 more, just a hypothetical. I'm not sure if you'd have the answer for this or not. There is a trial that's going to read out in the second half of this year for an oncolytic virus. -- in the relapsed refractory setting for poor ovarian cancer that the expectations is that they can resensitize to platinum. So for chemotherapy, it suggests that if they're successful, that it could change the standard of care potentially even in the neoadjuvant setting. And I'm bringing it up because this trial is going to take a long time ovation 3.

And if you thought about how some potentially new therapies that could be on the market could influence how patients are managed by the time you get to the Ovation 3 full top line data?

Thank you for that question. we're certainly very aware of the drugs that are being developed in the relapsed/refractory space, both platinum-sensitive and platinum-resistant -- the most patients, interestingly, their tumors are sensitive to platinum. The idea that you have to sensitize patients in the neoadjuvant setting or the adjuvant saying, really is not something that is at all mainstream. Most patients do respond to chemotherapy. Unfortunately, durable responses are rare earth, and then you get into second and third-line treatments.

As you know, there have been at least 1 and soon 2 drugs approved in different settings in second, third, fourth line patients who are not being treated with platinum again. and that's wonderful. We're very happy that there are drugs that provide a bit of a survival benefit in second or third line. But as we all know on the phone, and in this call, putting the best therapy upfront and making the biggest impact on the tumor is critical if you're going to treat ovarian cancer successfully. So we're very happy to be in front line. Very proud of the fact that we're in front line, and we believe that we will be providing advantage over time in terms of increases in survival to the patients that we're treating.

Next question comes from the line of Kam Dolliver with Brookline Capital Markets.

Right. First, are the savings from the restructuring of any significance that we would see them, the impact of them in the first half of this year?

So Ken, really, what we reported as a strategic restructuring really is around ensuring that we are using all of our resources to the best of our ability and focused on Phase III. So we're ensuring that we have the ability to hire and bring in needed expertise for the future as we're thinking about the commercial setting, and we're looking to the upcoming year and beyond. So it really is not about a pure number, but it is about just an ongoing evolution of making sure that we're taking the talent we have in-house that we're focusing our attention for each person to ensure that we're bringing the most value possible and that we're really removing anything that is off target from the OVATION III, which is our sole focus right now.

Okay. And with regard to your commentary regarding the pace of enrollment at the site level, I'm going to split a hair, if I can, because it may be informative. Is that pace increasing, say, month to month? Or is it just -- has it just been consistently above your forecast? .

So I'll give you -- we only have, of course, the time frame from the very first patient to now. But we see that for the entire trial, we are above the assumption of 0.3 points per month per site. So the -- if you look across all the sites, the average is above that. And when we -- the numbers that I was reporting of these sites that actually are delivering 1 patient per month or even just slightly below, that is across the whole time period that they're delivering. So I do think you tend to see kind of episodic enrollment that can happen but the numbers that we're reporting are not singular months, they're summarizing the entire time thus far.

I do think we're hearing phenomenal feedback. We're spending time in the site in our sites that are actively enrolling patients. We're having calls regularly as well. These conversations in terms of the data, we get to see a broader set of the community, for example, with the abstract we were putting in over the weekend. You have quite a few PIs that were part of Innovation 2. They are about to be on this abstract and to see the excitement and their responses. gratitude for being included and really just pure excitement with the data.

Douglas, why don't you comment more?

No, that's exactly right. The -- this is the first time that they had seen the final data in terms of survival, and there was a great deal of enthusiasm as you might expect. They were very happy that their patients have seen this much benefit.

So we really think this will be a difference maker for Vision II compared to Evasion going into Vision 2, we had a lot of promise. We had a mechanism of action that made a lot of sense was very clearly established in the literature Phase III now, we have evidence of a clinical effect that's never been seen. And we continue to really hear that, that becomes very critical. We can actually see the numbers that are entering prescreening, and we see a very high rates ultimately coming through to randomization was really the exceptions being things like inclusion criteria, unmet, that will always be the case or inability, perhaps somebody that's traveled a very long way and doesn't feel like they can make the schedule, but really, the rate of being exposed to this potential the way that our -- 1 of our PIs who's been involved with our program for a long time, talks about this with patients is you're going to get the standard of care, which you'll get in this trial.

If you do not have interest in research and in this protocol, if you want to consider it protocol and if you're randomized to the experimental aarm, then you have a chance at a product that may extend your survival. So it's been a very straightforward discussion as they're describing it to us, and we're getting -- as we might expect a positive response from patients and from the sites.

And our last question comes from the line of David Bautz with Wall cap Research.

Thanks for the overview this morning. So I just have a couple of financial questions. So as resources become available, is the company get a look to open additional sites in the U.S. or you'd be looking at ex U.S. to get any international sites open. And then as far as payments for the Phase III trial, I guess I'm just kind of where how is it being played for either -- did you have a bubble paid upfront? Is it pay as you go? Like how is it structured?

So David, great question. I was having a little hearing you. So let me respond to your questions. And if I don't hit on them, we'll have you further -- so we are actively enrolling and accelerating the enrollment of trials. And right now, those are focused in the U.S., although we have sites in Canada that we know are very interested, and we have had conversations as we're looking to consider the strategy of, if we want to accelerate further adding a European country as well.

So we've already had some discussions with leading sites in Central Europe. So that's a conversation that we expect to advance over the next year. But right now, we believe that we will be able to meet our enrollment accelerations, and we have a lot of confidence with the sites that we're going after, and we're starting with in the U.S. So we think that's actually the best way to start. In terms of payments for the trial, these trials are structured, the trial is structured pretty traditionally, you have contracts with individual sites. There are start-up fees and then fees as patients are being treated as part of the protocol. We have an ability to take advantage of what is standard of care and to have that be paid through the traditional routes and some of the procedures not be due to be paid by immunon, and we've taken full advantage of that to really structure the contracts accordingly.

David. This concludes the Q&A. I'll turn the call back to Dr. Limburg for closing remarks.

Thank you, Dara, and thank you all for joining this call. with the Phase III study enrolling ahead of plan, as we've just been talking about, the enduring strength of our Phase II overall survival data and the compelling translational evidence that Douglas spoke about and our sharpened financial discipline, we really know that immunon is well positioned for milestones that will create value inflection in 2026 and beyond. We remain steadfast stewards of the resources you have entrusted to us and are fully committed to delivering a potential paradigm shift for ovarian cancer treatment while creating lasting shareholder value.

We thank you for your continued support and look forward to future calls.

Ladies and gentlemen, that concludes today's call. Thank you all for joining in. You may now disconnect.

Good morning. My name is [ Myron Fernandes ], and I will be your operator today.

At this time, I would like to welcome you all to Imunon Third Quarter Financial Results Conference Call.

[Operator Instructions].

I would now like to turn the call over to [ Peter Vozzo ] from ICR Healthcare Investor Relations representative for Immune. Please go ahead.

Thank you, [ Myron ]. Good morning, everyone, and welcome to Imunon's Third Quarter 2025 Financial Results and Business Update Conference Call. During today's call, management will be making forward-looking statements regarding Imunon's expectations and projections about future events. In general, forward-looking statements can be identified by the words such as expects, anticipates, believes or other similar expressions.

These statements are based on current expectations and are subject to a number of risks and uncertainties, including those set forth in the company's periodic filings with the Securities and Exchange Commission. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements.

I also caution that the content of this conference call is accurate only as of the date of this live broadcast, November 13, 2025.

Imunon undertakes no obligation to revise or update comments made during this call, except as required by law.

With that said, I would like to turn the call over to Dr. Stacy Lindborg, Imunon's President and Chief Executive Officer. Stacy?

Thank you, [ Peter ], and good morning, everyone. Joining me on the call this morning is Dr. Douglas Faller, our Chief Medical Officer; and Ms. Kim Graper, our Interim Chief Financial Officer, who will be reviewing our financial results for the third quarter of 2025. Mr. Michael Tardugno, the Executive Chairman of our Board; and Dr. Khursheed Anwer, our Chief Scientific Officer, are also on the line and will be available for Q&A.

We continue to make meaningful progress with our proprietary IL-12 immunotherapy, IMNN-001 through the OVATION 3 pivotal Phase III trial for newly diagnosed advanced ovarian cancer. The urgency of this program remains front and center to our efforts to create value for shareholders and to address the unmet need of ovarian cancer, which continues to claim far too many lives as the standard of care in the frontline setting has not advanced in over 30 years.

Our OVATION 2 study demonstrated the first ever overall survival benefit in a critical FDA endpoint in our randomized frontline trial. We are now laser-focused on confirming those unprecedented results in a well-regarded rigorous Phase II trial. Three days ago, we hosted a highly successful R&D Day in New York City at the Harvard Club, featuring renowned ovarian cancer opinion leaders, clinicians, statistical experts alongside members of our leadership team.

The event underscored the transformative potential of IMNN-001 for women with newly diagnosed advanced ovarian cancer. The investment community and those interested in advances in ovarian cancer treatment and women's health more broadly heard directly from investigators about the unmet need in this disease affecting globally 300,000 new cases each year and claiming the lives of 13,000 women each year in the U.S. alone. This is why IMNN-001's potential to deliver a 13-month median overall survival benefit in Phase II with a hazard ratio as low as 0.42 in PARP maintained patients represents a potential paradigm shift.

We've just come off a powerful series of presentations at the world's leading oncology and scientific forums, including ASCO, SITC, ESMO, the AACR Ovarian Cancer Special Conference focused on advancements in ovarian cancer and finally, IGCS. And the momentum is undeniable. OVATION 3 enrollment is surging ahead of plan, and this 1:1 randomized trial is evaluating IMNN-001 plus the standard of care, neoadjuvant and adjuvant chemotherapy with interval debulking surgery versus standard of care alone in women who have treatment-naive advanced ovarian cancer.

In July, we initiated a 500-patient all-comers trial of women with advanced ovarian cancer, which has the flexibility to prioritize a 250-patient HRD-positive subgroup. This would enable us to realize a 40% cost savings with this prioritized group. The study design employs interim analyses for early efficacy stopping rules demonstrating trial success with power above 95% on the clinically meaningful primary endpoint of overall survival.

And as was discussed at R&D Day, this analysis is accelerated over a traditional trial, which would only read out the overall survival at the end of the study and success with these interim analyses is expected to deliver full approval, not accelerated approval.

Key updates since our last call that I'll just quickly tick through. First, the site activation status of OVATION 3. We have been deliberate and consistent with our cash management responsibilities, which applies to our decisions around site activation. our sites were initially activated in the U.S., and we expect this to double before year's end with 4 additional sites well progressed in start-up activities.

Returning investigators from OVATION 2 are being joined by additional top-tier centers, many of which are proactively reaching out to Imunon following the recent publication of the OVATION 2 study results in the Journal of Gynecologic Oncology, which was published on the same day as the 2025 ASCO platform presentation.

We also have inquiries about the trial from interested sites at other recent conferences.

Furthermore, while we have moderated the activation of sites in 2025 to reflect our current cash position, we are preparing for a site activation surge.

To this end, we have accelerated the engagement of a global CRO to identify new study centers for start-up in the new year, and we estimate we will have all sites in the new trial activated before the end of 2026.

Next, I'll comment on enrollment velocity. The first patient in OVATION 3 was randomized and treated in July of this year, and we have seen strong investigator enthusiasm for the trial, which has surpassed our internal enrollment target set for the end of 2025 with 9 patients randomized by the end of October. I think you can all appreciate how important it is to have strong momentum at the start of the trial, and we have started this trial with an impressive pace.

Moving to regulatory and design validation. The FDA has endorsed overall survival as a single study registration endpoint. And based on precedent and European regulations, we expect OVATION 3 to meet regulatory expectations for approval in Europe.

During our R&D Day, [ Dr. Giorgio Paulon ], PhD in statistics with the Company B Consultants, a highly regarded statistical consulting firm, highlighted this adaptive event-driven study design, a technique that is well aligned with precedented FDA approvals in oncology via interim analysis of overall survival. And he also highlighted the robust statistical foundation of our Phase III trial with conservative power estimates, yielding high estimates of probability of success of this trial.

Let me just pause. And if you didn't have the opportunity to join our symposia live, I would encourage you to look on our website, the Imunon.com website in the Investor tab and under Scientific Presentations to watch it. We provide details of the power assumptions, and it is remarkable to hear directly from these experts that were on the faculty that day.

Lastly, new translational data in our MRD study. We had [ Dr. Amir Jazaeri ] from MD Anderson Cancer Center presenting at our R&D Day. He's the lead PI for the ongoing Phase II minimal residual disease or MRD study being conducted in collaboration with the Breakthrough Cancer Foundation. Dr. Jazaeri spoke to data collected so far in the trial, demonstrating IMNN-001's preferential uptake by peritoneal macrophages, including profound tumor microenvironment remodeling.

Patients achieved complete pathological responses with durable intratumoral IL-12 and interferon gamma expression. All with negligible systemic exposure and excellent tolerability, even as IMNN-001 in this trial is being administered with bevacizumab and treatment has continued in maintenance settings.

Additional biomarker data, which was presented at SITC last week by Dr. Falller, further confirmed T cell and macrophage infiltration and immune activation that are predictive of superior prognosis.

[ Dr. Premal H. Thaker ] from Washington University emphasized during the R&D Day that IMMUN-001 is able to turn what are immunologically cold ovarian tumors hot by engaging both innate and adaptive immunity, renewing the promise of immunotherapy in this devastating disease. These mechanistic insights, paired with unprecedented survival signals, have fueled investigators' commitments to accelerate enrollment.

We estimate full enrollment in OVATION 3 will occur by late 2028, and I'll note that this can be accelerated with financing.

I'll now turn over the call to Dr. Douglas Faller for some clinical commentary and comments. Douglas?

Thank you, Stacy. As Stacy noted, our R&D Day on Monday in New York really crystallized the excitement we are seeing within the gynecologic oncology community regarding IMNN-001 and OVATION 3. [ Dr. Thaker ] and [ Dr. Jazaeri's ] presentations, followed by the rich discussion during the Q&A portion of the events, underscore the clinical importance of the data collected and reported in both OVATION 2 and the MRD study in women treated with IMNN-001.

As Stacy mentioned, over the last 3 months, we've been invited to present our OVATION 3 trial and the emerging translational data from OVATION 2 at 4 prestigious international scientific and clinical congresses. These include the ESMO 2025 in Berlin, the International Gynecologic Cancer Society meeting in Cape Town, the AACR Special Conference on Ovarian Cancer in Denver, and the Society for Immunological Therapy of Cancer, SITC International Meeting in 2025 in Washington, D.C.

These global forums gave us the opportunity to interact with both scientists and clinicians. After our presentations, a number of clinical investigators impressed by our novel therapy and the patient benefit realized in OVATION 2 approached me asking if their hospital could participate in the OVATION 3 trial.

Similarly, scientists intrigued by the demonstration in patients that IMNN-001 turns immunologically cold tumors into hot tumors with antitumor activity, asked about the possibility of collaborating with us. Interestingly, at the SITC meeting several days ago, several participants noted the renewed interest in harnessing the powerful antitumor effects of interleukin-12 as evidenced by at least 15 interleukin-12-related presentations.

However, they also noted that with the exception of ours, these presentations were focused on their early attempts to formulate or deliver interleukin-12 so as to avoid the well-known systemic toxicities. These attempts include intratumoral injection, which is not a long-term strategy.

All of these efforts were preclinical or early Phase I. In contrast, Imunon, as you know, has a pivotal Phase III registrational trial, OVATION 3, actively recruiting. This OVATION 3 trial has been fully leveraging the excitement of IL-12 as a cancer therapeutic and the remarkable OVATION 2 clinical outcomes.

As Stacy mentioned, the study start-up, as defined by protocol approval to patient enrollment, was achieved in 15 weeks, nearly half of what is typically seen as the industry standard for Phase III trials.

As we engage with our first set of study centers, we continue to see great interest and enthusiasm from our investigators, with the early sites so far activated, far exceeding monthly estimates of the number of patients enrolled per site per month.

OVATION 3 is still in its early stages, but we're observing clean safety run-in data from the first patients. Meanwhile, the ongoing Phase II MRD study, as Stacy mentioned, continues to reinforce IMNN-001's favorable profile, giving us real-time confidence as we scale the pivotal trial.

Following a recent MRD study in the DSMB meeting, we're pleased to share that the benefit-risk profile of IMNN-001 has been further strengthened in this MRD study and mirrors what we have seen in OVATION 2. No dose-limiting toxicities, no discontinuations due to IMNN-001, and no elevations in immune-related adverse events.

Furthermore, preliminary clinical data presented by [ Dr. Jazaeri ] at R&D Day highlights the high probability of progression-free survival on the IMUNON arm a lower MRD positivity rate and a lower percentage of biopsies positive during second look in the MRD patients.

Lastly, the MRD study's demonstration of the feasibility and safety of combining IMUNON with bevacizumab and the preliminary view into the idea of IMNN-001 as maintenance positions IMNN-001 uniquely for future trials and possible label extensions that could contribute even further to the fight against this terrible cancer.

Back to you, Stacy.

Thanks, Douglas. Before turning to our financial update, I'd like to offer and really further highlight progress in advancing our MRD trial and share an update.

First, notably, the Break Through Cancer Foundation selected this trial for funding from hundreds of competing proposals, which is a very strong endorsement that echoes [ Dr. Jazaeri's ] remarks at our R&D Day on the importance of frontline therapy as the best opportunity to achieve a cure for ovarian cancer.

And based on the preliminary clinical data from the trial that Douglas just reviewed, we are thrilled with the consistency of IMNN-001's effect compared to our OVATION 2 clinical results. We've made great progress in the enrollment of the MRD trial, with 3 patients being randomized and treated in the month of October, resulting in a total of 25 patients randomized to date.

Based on this progress, in September, we reviewed the MRD study and confirmed that its core objectives, which include those that we have internally for the IMNN-001 development plan and breakthrough cancer goals as well, these core objectives can be fully met with a smaller cohort of patients.

Accordingly, we decided to cap enrollment at 30 patients in the intent-to-treat population, a milestone that we expect to reach in the first half of 2026. We will be thrilled to close out this trial and capture its full learnings, enabling us to channel our resources into the pivotal OVATION 3 Phase III trial.

In fact, I'll mention that we've already begun conversations with this success in mind. We've started conversations with MRD investigators about transitioning their sites to OVATION 3 at that time, a move that would further accelerate enrollment in our registration trial. And I'll note that we've received positive reactions to these inquiries.

Turning to our financial strategy. We continue to navigate a challenging biotech capital markets environment with discipline and foresight. Our multipronged approach, combining the potential for nondilutive partnerships with prudent equity raises, opportunistic use of our ATM facility remains on plan, and we've made significant progress.

Shareholder dilution is a valid concern, and we share it. That's why every financing decision is a stress test against our commitment to preserve value while actively working to fully fund this pivotal program. We have ongoing reviews for potential partnerships with TheraPlas and interest expressed by pharmaceutical companies in PlaCCine from a recent scientific meeting, but nothing that is imminent. These kinds of partnerships take time to build, and I look forward to providing more detail if we advance these discussions to terms.

On the equity side, we've raised $4.5 million during the third quarter through warrant exercises and targeted ATM usage. Monthly cash burn is now approximately $1.25 million to $1.5 million, reflecting streamlined G&A expenses, renegotiated facility leases and a laser focus on advancing IMNN-001 milestones.

Furthermore, operating expenses for 9 months ended September 30 between 2025 compared to 2024 is 31% lower, which includes 44% decrease in R&D expenses and a 52% decrease in CMC expenses. And mind you, this is all while manufacturing product for Phase III, conducting CMC development work in preparation for reduced cost of products sold in the commercial landscape and accelerating site patient activation.

With cash through mid-Q1 2026 and multiple near-term catalysts, such as enrollment momentum, regular presentations at medical and scientific congresses and the potential for partnership progress, we are well poised to extend our runway further, ideally through value-enhancing non-dilutive transactions.

A few other updates of note. The NASDAQ compliance matter is closed. We achieved the dollar minimum bid price requirement on August 9. We sustained shareholder equity above the $2.5 million confirmed on August 22. In fact, we're far above this. This matter was also formally closed by NASDAQ on September 3, 2025, and I'm delighted to report that as reported in the current 10-Q, we are at 4.1% in the shareholder equity threshold.

Now I'll turn over to Kimberly Graper for our review of the third quarter 2025 results.

Thank you, Stacy. Details of Imunon's third quarter 2025 financial results are included in the press release we issued this morning and in our Form 10-Q, which we filed before the market opened this morning.

As of September 30, 2025, cash and cash equivalents were $5.3 million.

During the third quarter, the company received approximately $4.5 million of net proceeds from the exercise of warrants and sales under our ATM equity facility.

The ATM facility carries a nominal 3% fee with no warrants. We project that this cash balance extends our operating runway into mid-quarter, first quarter of 2026.

R&D expenses were $1.9 million for Q3 2025, down from $3.3 million in the same period last year, primarily due to completion of the OVATION 2 study and lower costs associated with the Phase I Plaque in DNA vaccine trial and development costs for the Plaque in DNA vaccine technology platform.

G&A expenses were $1.6 million in Q3 2025, down from $1.7 million in the same period last year due to lower employee-related legal and travel expenses.

Net loss for Q3 2025 was $3.4 million or $1.16 per share compared to $4.8 million or $3.76 per share in the third quarter of 2024. Please note that all shares and per share amounts have been adjusted to reflect a 15-for-1 reverse stock split of our common stock, which we effected on July 25, 2025, and a 15% stock dividend we declared in the quarter.

With that, the financial review, I'll turn the call back to Stacy.

Thank you, Kim. Before we open the line for questions, I want to reflect on the questions we received through the webcast, the live webcast at Monday's symposia. I was able to work the majority of these questions into my prepared remarks with the exception of one question that

I'd like to address as we kick off our Q&A. And this question came from David Bautz through to, and I'll read the question. It looks like macrophages are the primary cell type that takes up IMNN-001 that how long do these cells continue to produce IL-12 based on the presence of IMNN-001?

Is there some type of feedback mechanism that IMNN-001 produces to prolong the production of IL-12 in these cells after IMNN-001 is metabolized? Or is there an IMNN-001 plasmid that encodes IL-12 long lasting? It's a very great question. I apologize, David, we didn't see it and weren't able to address it day of the meeting. But I'd like Khursheed offer comments to this question.

Sure, Stacy. Yes, it's a good question, of course. The unformulated plasmid, which is administered into the peritoneal cavity, typically clears, I would say, within 24 hours and may last a little longer if it is formulated with a delivery system such as that in IMNN-01, where the nanocomplexes have a protective effect on the DNA. However, once the plasmid is taken up by the cells of the peritoneal cavity such as macrophages or other immune cells or epithelial cells, it is internalized into the cell nucleus and can stay much longer, giving rise to long-lasting up to several days, the levels of gene product, which is IL-12 in the case of IMNN-001.

So yes, it is indeed the plasmid inside the cell that lasts longer, giving rise to the pharmacokinetic that we have seen with IMNN-001 of IL-12 and interferon gamma production.

Thanks, Khursheed. I appreciate that. So operator, with that, please open the call for questions.

[Operator Instructions]

[Audio Gap]

We have the first question from the line of David Baultz from Zacks. Please go ahead.

Yes good morning everyone, I appreciate you answering that question that I had the other day. Sorry, I wasn't able to ask it in person there. But thank you for that response there. I wanted to start actually clear something I have to make sure I understood. So you had mentioned that positive results in one of the interim efficacy and looking at the interim analysis would lead to a full approval, you think? And is that a full approval for all ovarian cancer patients? Or would it be just for the HRD population?

Yes. clarifying that. And I think that when we were talking about the ability to accelerate the analysis through the use of an internal interim analysis, I wanted to make sure that people understood that, that was the acceleration of getting to results. And if we are successful and we meet the statistical thresholds that are outlined and agreed to by the FDA, we would expect full approval in the group that we're testing. The trial is continuing in an all-comers population, then at the end of the trial, that would allow a broader label indication.

So, but I think it is really important to understand we're really reflecting the devastation of this disease and the need as we saw, we know that we're also making rather conservative assumptions, power assumptions, so it's very possible. In fact, [ Giorgio ] spoke to the likelihood of being successful at 1 of the 2 interim analyses. We want that urgency to be very clear. We want to be able to move forward rapidly with a BLA filing based on that data and then to be able to allow for the product to be approved in that indication and accessible to patients. But it would allow the trial to continue to the end and to have -- to then potentially expand to the all-comers population.

Okay. That makes sense. Kind of keeping along the same theme, what p-value or can you say what p-value needs to be hit at either the first or second interim analysis in order to be able to stop the trial if it's efficacious?

Yes. It's, unfortunately, it's a little more complicated than just a raw p-value because, and this is where [ Giorgio ] did a really great job of really highlighting the simulation results. They set complex operating characteristics that ultimately are needed to take into account kind of an information fraction of where you are in the trial and therefore, appropriately control type 1 error rate.

The logistics of it are very well documented, and there was a very large report that was submitted to the FDA that these simulations really documented proper control of type 1 error and then all of the operating characteristics that the FDA would be keen to understand. It's not just a fixed p-value. If you are interested in more, we can have perhaps another conversation on it. But it's very well laid out based on where this would occur. When in the point of the trial when the 50th HRD event, which is the trigger for the first interim would occur, that's not a fixed point in time. It's an unknown that will evolve and then that will affect these thresholds.

Okay. Yes. Understood. Then lastly, I believe it was [ Dr. Thaker ] had talked about pain management for when IM and then 001 is administered and kind of how that pain management has evolved basically with her experience of the drug. I'm just curious, is there a set protocol for that pain management at all the different clinical sites? Or is it kind of up to the clinicians' discretion?

That is a really great question. Douglas, do you want to take that?

I'd be happy to. Thank you for asking the question because, obviously, patient comfort and is critical for us and for the ability of patients to get the drug.

In patients who have ovarian cancer in the peritoneal space, they are often quite tender because of the inflammation that's there before the drugs start to work and infusing anything into the space can cause discomfort for patients. This happened in some patients in OVATION 2 and the physicians, in combination with Imunon, decided that rather than waiting for this to occur that we could prophylactically treat patients, give them some analgesia prior to the infusions, prior to even the first infusion. If there were going to be any discomfort, this would alleviate it. If it turns out it's not necessary later on, that could be stopped for individual patients. It's been quite useful, quite successful. To answer your question more fully, this is part of the protocol. This is mandated for all patients.

This was also incorporated into the MRD study, and we have data from [ Dr. Jazaeri's ] sites that he's managing, that this has been very successful. They've not had problems with any sort of abdominal discomfort in patients. So far in OVATION 3, we've not seen that either. The prophylaxis for potential discomfort with the infusion seems to be working very well.

We have the next question from the line of James Molloy from Alliance Global Partners.

I had a question for Dr. Faller. One of the things you talked about on the R&D Day was about the durability of response in sort of speaking to the mechanism of action of triggering the immune system and some of the IL-12 expression in the fluid and tissues. Can you walk us through that a little bit, please?

Very happy to. Please stop me if I'm telling you something you already know and it's not appropriate to your question.

The problem with IL-12 delivered systemically, as you know, has been it's simply not tolerable. It's too potent. Like IL-2, you can't give it at high enough doses systemically, let's say, intravenously because of -- it's hard to call it toxicity, let's call it adverse events. I don't call it toxicity because it is actually the intended activity of the cytokine. But patients have -- just like IL-2, patients with third space, a lot of fluid into outside of the vascular system, low blood pressures, fevers, et cetera. That's prevented IL-12, excuse me, and IL-2 from being used effectively.

Here, we're delivering the drug where the tumor is into the intraperitoneal space. That's where the ovarian cancer has spread in all the patients that we're treating. As Khursheed mentioned earlier, this is a gene therapy. The plasmid gets taken up by the tumor cells and also by the tumor microenvironment cells, the stromal cells and express IL-12. IL-12 then induces interferon gamma and TNF alpha to incredibly potent immune effectors that stimulate both the adaptive and the innate immune systems.

The IL-12 levels in the peritoneal fluid, we've reported in OVATION 1 and in OVATION 2, go up by several logs. There's a tremendous amount of IL-12 and its downstream effector cytokines expressed in the intraperitoneal fluid and in the tissues, as you would expect, in the peritoneum. However, in OVATION 1 and in OVATION 2, we've monitored IL-12 levels systemically, and we don't see increases in IL-12 systemically, no more than twofold. This is the basis for the remarkable safety we have. We're not seeing the kind of immune adverse events that everyone else who tries to deliver the drug systemically have seen.

We're not seeing any cytokine release syndrome kind of events, which completely goes along with the fact that we're not elevating cytokines, IL-12 or its effectors systemically. It's just where the tumor is in the intraperitoneal space.

The durability, Khursheed already addressed the amount of time that the plasmid is expressed. We can see IL-12 levels in the peritoneal fluid for at least a week after a single injection, and we give the drug weekly, at least during the time that the patient is getting chemotherapy. The durability of responses when I was pointing to the slides was just showing that we give the drug during the chemotherapy, which is 6 cycles essentially plus interval debulking surgery at the beginning of treatment for the patients. Yet we're seeing effects years later. We're seeing the curve separate. We're seeing a benefit for survival in patients. This is long after we stop giving the drug. This is consistent with what you would like to see, what you'd expect to see from an effective immune therapy.

Once you've educated the immune system to kill the tumor, it should persist. You should not necessarily have to keep stimulating. Although in the MRD study, we are exploring maintenance therapy to see if that would add additional benefit.

One of the things that Stacy had mentioned I think as well as talking about the OVATION 3 meeting the regulatory approval for the EU. Any details on that process? Maybe also, I know you mentioned, Stacy, that obviously, you're constrained by the amount of cash you have to run the trial. If you have more cash, you run it quicker. If you had unlimited funds, how quickly could you run this trial?

Stacy, maybe I could address if you don't mind, the regulatory issues, and then you could talk about the financial ones.

Go ahead.

Okay. The issues in Europe are twofold, as I'm sure you know. One is getting the drug approved by the EMA. But equally important is getting payers to actually agree to support use of the drug in Europe. What payers want to see in cancer is survival. PFS is not something that traditionally, in my experience, payers are willing to pay for. Our endpoint is overall survival. We've already ticked the box that the payers would want to see. The study is designed in a way that should be completely acceptable to the EMA. I've had a lot of experience in dealing with the EMA and many other regulatory agencies outside of the U.S. We could open studies in Europe. It's not necessary for European approval, but let me turn it over to Stacy now with respect to what we'd like to do with adequate funding.

Yes. It's an interesting question. I can tell you that when you think about some of the remarks that Douglas provided that really characterize how quickly we're moving. I can promise you we're going to be very focused on advancing this trial and taking advantage of every opportunity that we can.

We've done a number of different kind of internal forecasts. As I shared before, right now, our estimate is that we'll be able to fully enroll this trial in about 3 years. We have done a forecast that is as quick as 2 years. I think that is something that we put plans behind to consider how we would achieve it, and we believe that it is possible.

Beyond that, I really wouldn't want to go too much further. There are ways that you could actually pull it in even further. But I think it gives you an idea of the way that we're looking at this and ensuring that we will be ready and able to accelerate very quickly some of these proactive approaches with our -- the CRO that we're working with that interestingly enough and importantly, don't change the overall price that we expect to pay, including even pay the CRO. We're just advancing activities so that we'll be poised and we can actually see the site activations when we want them rather than waiting to engage them at that time. So those are some of the operational strategies.

We have the next question from the line of Emily Bodnar from H.C. Wainwright.

First one, I'm curious if you're planning to share an update from the OVATION 2 trial, particularly the PARP inhibitor treated patients in terms of median OS since in the last update, it was not reached yet. And if so, when you might expect to do that?

And then second question, how many sites for the OVATION 3 trial are you expecting to be sites that were part of OVATION 2? And are those sites that you're kind of targeting initially?

Yes. Emily, thanks for both of those questions. Let me take a stab at both. And then if there are other points, Douglas she could maybe add on.

In terms of OVATION 2, so in our protocol, we stated that we would monitor overall survival. We designated the period of time that we would continue to monitor it. And it really puts us in a place where we're starting to wind down sites. We expect by the end of the year that we'll have the data fully refreshed and the sites that we'll be closing. And I think at the end of the day, when you look at this trial, we know that the data that we've collected, even going to the very first interim across the all-comers, the median was observed in both treatment arms. We know the data was mature for very robust conclusions. And so I think I would say we shouldn't expect nor would the medical community expect to see significant changes to these results. But we will likely have this process really finalizing towards the end of the year and early next year.

Douglas, I don't know if you have any kind of -- you already commented on the reflection of how long we're seeing this effect past the treatment period. But when we ultimately look at the size of separation and at R&D Day, we looked at some of the graphs that have come out of these recent immune checkpoint inhibitors where you see really no separation.

Tell me your reflection as a clinician on the time periods when we were observing and did these 2 readouts really, were these appropriate in terms of when you would be expecting the separation, the phase of the curve to really be well estimated?

Certainly. And you've actually already spoken to it, Stacy, that OVATION 2, the primary endpoint is median -- well, a secondary endpoint was median survival in the entire population. And that's when we -- our initial readout, we achieved that information.

In trials in cancer, once you've gotten median survival in your primary population, longer observations yield less and less information. I think it's curves with fewer patients on them start to become less informative. So we're very pleased to be seeing the effects over time that we've seen. I think that the concept of using this drug in the neoadjuvant setting is really was a remarkably smart choice early on in its development so that the -- and this became a big -- of great interest at ASCO.

Using immunologically active drugs in the neoadjuvant setting where there's still tumor there allows the immune system to be educated in the setting of the tumor. Using it later in an adjuvant setting when there's little or no tumor there, drugs like -- even like checkpoint inhibitors as was being realized at ASCO are much less effective.

So I don't have anything beyond that to say, Stacy.

Emily, your second question was about the sites from OVATION 2 and maybe even -- I don't know if you were getting at the overlap or the total number in OVATION 3, but we will have great overlap in OnovAION 2 and OVATION 3. Not surprisingly, we started with sites that were very strong enrollers, very enthusiastic about the trial. We see that certainly extending to many other sites from OVATION 2. But we will have new sites simply because we are planning to have up to 50 sites. And we'll ultimately look at the number of sites that we need to really stay with our forecast and keep enrollment going. And then we'll plan accordingly. We have flexibility in the way the protocol is written that we can go higher if we decide we want to do so.

But you have to carefully manage not bringing in too many sites, really keeping your sites that are performing extremely well. And the enthusiasm of these early sites, and I would say really the sites from OVATION 2, not only from their knowledge of the product, you heard Dr. Thacker at R&D Day actually comment on the fact that she's been working on IMNN-001 for almost a decade. So she was involved in OVATION 1, OVATION 2 now is, again, the study PI for OVATION 3, their confidence and conviction in what's happening in these women, which, of course, they see when they're doing surgery, they observe as they're meeting with them for years after enrollment in the trial, it's palpable, right? It's incredibly clear. They believe very much that the potential for this product to be transformative to care is great.

So it's really wonderful to see these clinicians that are offering up to meet with new sites. They're very willing to offer perspective on the ways that they've managed. Every trial has new aspects that sites have to really get comfortable with, and they're very willing to share operational updates as well as really talk about data and what they've observed in patients over time. So it really is kind of the best of both worlds.

Ladies and gentlemen, that concludes the question-and-answer session for today. I will now turn the call back over to Dr. Lindborg for closing remarks.

Thank you, and thanks to everybody for joining the call.

With OVATION 3 enrolling ahead of plan, we've talked about the compelling clinical and translational data from R&D Day and also recent conferences, including SITC just last week and active partnership discussions, Imunon is poised for multiple value-inflecting milestones. We remain diligent in stewarding the resources you provided, as I hope you're able to see very clearly in the queue and are steadfast in our mission to redefine ovarian cancer treatment and deliver lasting shareholder value. So thank you all for your support and look forward to meeting again at the next quarterly earnings.

Thank you. Ladies and gentlemen, that concludes today's conference. Thank you for participating, and you may now disconnect your lines.

All right. Good morning, everyone. I'm Stacy Lindborg. I'm the CEO of Imunon, and it is my true honor to get to welcome you to the 2025 Imunon R&D Day. As I look across the people in the room and certainly have reviewed the -- those that registered online for the live webcast, we have esteemed guests here and investors and partners, which we're delighted by. So we'll be showcasing IMNN-001's progress with our novel immunotherapy, IMNN-001. But what really matters is our goal. And we are in pursuit of the first immunotherapy that will be approved for frontline advanced ovarian cancer.

The enthusiasm that I feel and experience as I interact with many of you is also reflected by the registration that we saw for this event, which we're delighted by. And it continues to underscore really the shared urgency that we have and the hope that we have for women that are fighting advanced ovarian cancer. It's a really devastating disease. So thank you for your unwavering support for IMNN-001, our mission and the desire to transform outcomes for ovarian cancer.

Today, we'll give an update on our program, our IMNN-001 program, sharing compelling data and the significant potential that this data underlies for IMNN-001 to be a breakthrough treatment for women newly diagnosed with ovarian cancer. Along with the latest milestones and progress on our ongoing Phase III trial, OVATION III, that brings us closer to delivering this transformative therapy to patients. To frame our discussion, it's important to reflect on 2 foundational truths that continue to drive our work. Number one, the standard of care for newly diagnosed ovarian cancer has remained essentially unchanged for 25 years. And no frontline therapy, I'm hearing whispers of longer. They can add that when they come up our esteemed panel. No frontline therapy has ever demonstrated an overall survival benefit in improving this setting, so frontline setting until IMNN-001 until our OVATION 2 data, which will be reminded of today.

IMNN-001 in combination with standard chemotherapy represents a potential breakthrough in newly diagnosed ovarian cancer. Our Phase II data showed a remarkable 13-month extension over the standard of care and overall survival with a highly favorable benefit to risk profile. And as I stated before, no other frontline ovarian cancer treatment has achieved an overall survival improvement, making IMNN-001 uniquely positioned to make a meaningful difference in the lives of women facing this disease. We approach this program with great urgency because the unmet need is profound and the opportunity to change the treatment paradigm is within reach.

One quick note of housekeeping. We'll hold questions until we finish all of the talks, and then we'll have time for questions. And of course, for those that came to the symposia, we'll have time following with coffee and pastries. But we encourage everyone on the webcast to participate. Please submit questions online. We'll be monitoring the Q&A log. And any questions we don't get to, we'll collect them and we'll make sure that we share them. We find ways to answer questions and follow up after the event. So one last comment before we dive in. I really want to pause and just thank our speakers for making the effort to come here. You all have busy calendars. And I know that even without the government shutdown and the risk of missing surgery tomorrow in clinic, that taking time away from very important and pressing work is a priority that you have to think very carefully about, and we're grateful for you being here and offering the perspective that will be very important to be reflected on today. So thank you for pushing that work aside and joining.

Okay. So with that, I'm thrilled to turn to the program and introduce our first speaker, Dr. Premal Thaker. She'll be speaking today on advancing ovarian cancer care, Imunon's potential to transform the microtumor environment from cold to hot. And Dr. Thaker is the David & Lynn Mutch Distinguished Endowed Professor and is Chief of the Gynecologic Oncology Department at Washington University in St. Louis. She's a research member of the Siteman Cancer Center, and she specializes in gynecologic oncology with a background in cancer biology from MD Anderson, focusing in angiogenesis, invasion and the impact of biobehavioral factors like stress on ovarian and endometrial cancers.

Dr. Thaker leads clinical trials and novel therapeutics for gynecologic cancers, having served as national PI for several trials, including our OVATION 2 and our ongoing now OVATION 3 trial, in addition to other ongoing trials in platinum-resistant ovarian cancer. She directs clinical research for Washington University's Endometrial Cancer SPORE, and I'm delighted to invite her to the platform.

Thank you, and good morning. Everyone made it. Hopefully, you didn't have as much of a challenging time as myself and Dr. Jazaeri, but here we are. So thank you for the kind introduction. It gives me great pleasure because I've actually been part of this program for quite some time. So I feel very passionate because I've actually seen the science evolve and also making sure that we continue to evolve that. So I hope you'll get as passionate once you see the data as we talk about the unmet need. So as Stacy mentioned, there is such a high unmet need because we really haven't changed the paradigm. We've changed the maintenance strategies in ovarian cancer, but we really have not changed the treatment strategy in terms of chemotherapy and what we can offer our patients.

And over 21,000 women actually will be diagnosed closely in the United States this year alone, and we will lose 13,000 women. And really, the reason this happens is because the cancer is so insidious and we actually find most of our patients, over 80% of them at an advanced stage, Stage 3 or 4. So the cancer is widely metastatic at that point. Patients are highly symptomatic and they come and they finally present because we don't have the holy grail of a screening test like we do for some other cancers. And because of that, most patients will have a response, but 70% of our patients will actually recur in the first 2 to 5 years, which makes it quite challenging when someone recurs, as we all know, that's -- we lose our opportunity to cure patients and hopefully give them substantial life.

And over 60,000 -- I'm sorry, 60% of our patients will die within 5 years of the diagnosis. So we really do need breakthrough therapies for these women because we haven't really changed the paradigm. And this actually is the first immunotherapy to hopefully give us that opportunity, as you'll hopefully appreciate today. So why do we have so much hope in immunotherapy is mainly because of the cytokine we're really targeting, IL-12. So if you actually have been following the IL-12 story even in the 1990s, early 2000s, there's been over 37 trials that have looked at how to give IL-12 because everyone understands the potential of IL-12 being such a key cytokine for really changing both the innate and the adaptive immune system, which is a really rare thing to actually modulate both sides of the immune system and hopefully give a lasting effect.

However, over time, we've not been able to effectively give it because of side effects. So really, what's important is knowing that we give this medication not intravenously, but intraperitoneally into the abdomen itself, which is really where this disease is housed. And so we're changing the tumor microenvironment. And because we're actually giving it into the intraperitoneal cavity, we can give it repetitively, which is the key because we all know that nothing works the first time. If any of you are parents, you know the first time you tell your children something, they don't necessarily do it. It's repetition. I see some smiles. Some people are listening. That's good. Same thing with intraperitoneal chemotherapy. It gives us the opportunity to give it weekly to patients. So really trying to start changing that tumor microenvironment.

And also in gynecologic oncology, in 2006, we actually used to give intraperitoneal chemotherapy. So there was an NCI mandate that said this should be a therapy and an option. So now we're giving intraperitoneal immunotherapy, which is really good because of the fact that there's a lot of us, myself and Dr. Jazaeri, who have given intraperitoneal chemotherapy and understand the benefits for our patients. So we can get durable and local expression of IL-12 with this modulation of IMNN-001. And we know it increases really the benefit in the tumor microenvironment without those systemic toxicities that we had seen within -- I'm sorry, recombinant IL-12 previously that really did not allow for the administration effectively. And that's why a lot of companies had given up on IL-12. Fortunately, Imunon had not.

So how do we realize that we're really targeting and changing the tumor microenvironment as I'm demonstrating and talking with you today. It's really from our earlier work of looking at both the Phase I where we were looking in more translational samples. And even in OVATION II, we did collect translational samples. And what you can really see on the right-hand side because this doesn't project too well, but is that there's an increase in your dendritic and your myeloid -- I'm sorry, your effector memory T cells. So you can see on the panel all the way on the right in the pretreatment, you really don't see a change. But after you've given actually the intraperitoneal IL-12, you can see post treatment that all of these cells increase. And why is that important? It's actually making the immune system activated in order to fight the cancer. You're really changing a change in terms of making more T cells come and be able to fight this cancer. And we know that's very important because a lot of times these cancers can evade the immune system, and you don't see these sort of increases.

Additionally, when we looked at it in patient samples, you can see that we really don't see an increase of IL-12 in the blood. So we really -- that's what helps us limit the toxicities that we see for patients. You see the huge increase in the ascites of these patients because a lot of these patients come not only with a huge disease burden of physical tumor implants, but they're carrying several liters of fluid. And so it's easy for us to aspirate and look at these changes over time. And that's also important. And then what also we know is that interleukin-12 and interferon gamma both collectively work better and help with anti-angiogenesis. So it's not only the immune system that is attacking. And importantly, what you can see is in our higher doses of 100 milligrams per meter square, you can see the sustained improvements of the actual full change of making a difference in the levels.

So demonstrating that this really is our dose that we require to use for our Phase III that's ongoing. So what also is important is that this is not new. Immunotherapy is something that ovarian cancer clinicians, physician scientists have been trying to capture how to use the immune system more effectively because we do feel that it is a cold tumor. And if we can change it, the tumor microenvironment, we will have a better success in terms of actually making a difference for these patients. So there's been countless thousands of patients who have gone to immune checkpoint inhibitors and upfront therapy without really seeing the benefits that we were hoping we would see. So why do we think that IMNN-001 works differently? It's really the fact that the microenvironment contains cells which are known to dampen the immune response. So how do we really reverse that? And really, the way we can do this is by increasing the numbers of favorable immune cells from both the innate as well as the adaptive immune systems.

So once again, what we did in OVATION 1 is looking at can we really decrease those immunosuppressive biomarkers that we know really make it worse for patients. So what you can see is that we decrease many of the critical immunosuppressive biomarkers such as FOXP3, IDO1, PD-1 and PD-L1, resulting in the CA-125, which is a tumor protein to go down as a way that we can measure how our patients doing. Additionally, what we do is we can see that we're changing the milieu. We're giving an improvement in our CD8+ and CD84 T cells in the tumor.

So really changing the dynamic of that tumor microenvironment because we know that, that will make a better sort of immunoresponsive environment for our patients. And so this is how we believe immunologically, we really are changing because we can actually physically measure, and that was by us taking lavages of the patient's abdomen, so we could serially see these improvements, which is really critical because a lot of times, we just say a drug fails without understanding the biology. But here, we really have taken the opportunity to try to understand is our hypothesis working, and it appears to be so.

So this is really important because the fact, as Stacy mentioned, we've really not seen any overall survival benefits. And when I'm pointing out these checkpoint inhibitor trials that we have on the top over here with Rucaparib and Nivolumab and below it, you're looking at the use of first, which is the use of Niraparib with Dostarlimab. I want to point out that these are actually trials in patients after we know that they respond. So this was partly in patients who are using a maintenance therapy that we know have responded. IMNN-001, we take patients who really are sort of at the worst, right? They're getting -- they've just started their disease journey. We don't know if they're going to respond to chemotherapy yet. We don't know what the response is going to be. And we start the treatments concurrently with chemotherapy with the immunotherapy intraperitoneally.

So that also is super important because we are taking patients at the start of their journey. So we're not self-selecting the patients who may have not made it and then go on to these maintenance therapies. And even though this is not powered the Phase II, it really gives a very strong signal about how patients respond and that we were able to change the tumor microenvironment because it's really important when you talk to a patient to talk about overall survival benefit. People want to know how is it going to impact my life. And when you talk about overall survival, that's meaningful and impactful, especially when you give patients over a year and this data is still maturing. So that's another Christmas, another holiday. It's not just giving them 3 months where it's hit or miss, what quarter of the year you've made it. So patients are also excited to take therapies that they know are going to help them.

So then we, of course, looked at our sort of HRD and PARP-treated patients. When the OVATION 2 trial was sort of being developed. I wish we all had like hindsight 2020. We didn't realize that PARP inhibitors were going to become the new standard for patients with a BRCA mutation. So it was not prescribed, but it was definitely considered part of standard of care. So we have patients who did go on to get PARP inhibitors. And what we see is that the response is even more dramatic in patients who are able to get a PARP inhibitor along with IMNN-001. And why do we think it works even better in those patients is that we know that patients who have a homologous recombination deficiency have an impairment in repairing their DNA. And when they do, they're going to have more mutations, more neoantigens, and we know that's how immunotherapy tends to work even better for those patients.

So that's why we feel like it even boosts even further immune activation for those patients in particular. And this data, even though it's not -- as I said, it was not prescribed, it definitely shows that this is what we're continuing to see. So I want to tell you that this really can transform care for patients. The impact in overall survival harnesses the patient's own immune system, which is really what we want. We wanted to locally be giving out the IL-12, and Dr. Jazaeri will show some interesting data of how he can see those differences. So we're not just delivering IL-12, but we're activating the patient's own immune system to overcome the barriers that sometimes we've seen with other molecules. It also activates both the innate and the adaptive immune systems to give you more effective, durable responses and memory. That's what we see in a lot of immunotherapy trials across other disease sites is that you'll see overall survival benefits because you have to teach your immune system.

It's just like when you get the flu. The first time you might be down and out, but the next time you're exposed to it, hopefully, it's not as severe the side effects because your immune system has learned how to sort of deal with that challenge. And so that's also very key for our patients. And then we're turning the tumor microenvironment from cold to hot. That's a very lovely science way of saying we really are trying to make it more ability for patients to have their immune system, help them complete the therapies as well as potentially even augment future therapies if they recur as well. And then lastly, we do see that we see that the cytokines are induced locally and not systemically. So we do not see cytokine release syndromes. We don't see that patients have barriers because they have high fevers, they can't get the treatments. So that really is also important because you want to be able to do this, as I said, repetitively and giving the durability.

So the other part that's really important for OVATION 2, which was presented at ASCO this past year was that the benefit was seen for all of the trial endpoints. And so what you can see is that there was not one endpoint that was not favored for IMNN-001. And so that really is very important because even though some of these were not powered, it does show you that everything is going in the same direction. So this is not like we're just picking out one subset and focusing on them. We really see that it benefits all our patients, whether they've been treated with PARPs, not treated with PARPs, if they're also HRD -- I'm sorry, HR proficient, which is even the hardest group to treat, it's very important. And so it's a highly favorable benefit risk profile that we see for patients.

We do see that also when we go in for our surgeries because interval debulking, we do after we give patients their neoadjuvant chemo, so meaning they get chemotherapy with IMNN-001 for 3 cycles and then they get surgery followed by additional therapy. We do see a real biological response in the operating room by more patients having chemotherapy response scores that are favorable that our pathologists can tell us as well as the fact that we're able to get R0 surgical resections, which means we're able to remove all the tumor we can see. So all of this helps us believe that we're really making a difference for these patients, and we don't see many side effects except for abdominal pain, and that's mainly from the distension of infusing a medication into the abdomen. But we've gotten smarter. We've learned how to premedicate patients so they can tolerate this. We also educate better. So we know patients to how to respond when they have these side effects.

So they're not suffering, but they're also not just not being proactive about it. And then we do see some nausea and vomiting, but we're able to also help with that with antiemetics. And some of the nausea and vomiting is really because of the disease itself. It sort of coats the entirety of your GI system. So these patients have motility issues and they really do have issues with just sort of absorption and digestion. So this leads us to OVATION 3, which is what we're really excited. It's launched, and it is our Phase III trial that is actually going to randomize patients after either a diagnostic laparoscopy or a biopsy to confirm that they actually have ovarian cancer as well as for us to know about their HRD status ultimately so that we can make sure that when we have the prescribed maintenance therapy at the end of trial that they're well balanced. And you can see that it's really the same as OVATION 2 that patients will get neoadjuvant chemotherapy versus neoadjuvant chemotherapy with IMNN-001 weekly, followed by interval debulking surgery, followed by continuation of their arm and then they'll go on to maintenance therapy only for HRD participants.

So this really gives us confidence that we'll be balanced because we now know based on the current state of affairs, where we are in terms of prescribed -- being prescriptive about maintenance therapy. We also will be looking at overall survival because I told you that is the most meaningful. The FDA always wants overall survival and all of us in drug development try to hedge and be like, we'll get you a PFS, and we think it's going to become an OS. But this trial really has benefited and shown an OS benefit in the Phase II, and we're very highly confident that we'll get an OS benefit in the Phase III. Additionally, we hope that because we'll be looking at the HRD subgroup, we might be able to get an accelerated approval because it really does show that it is even extremely more effective in this population. And then we'll be looking at the patient's perspective. So we haven't really done official quality of life measures, but we will in this trial, of course, because we definitely hear from patients, but we will be measuring this at prespecified time points.

And then this is an event-driven statistical methodology with an interim analysis for hopefully an early interim approval for the HRD-positive group, but we have statisticians who will explain that much better than I. And so with that, I really hope that you understand that IMNN-001 is really poised to make a difference for patients. Having done this for now close to 20 years, I hate to say my age, but I really would love to leave an indelible mark on this population of patients who really need to have effective medications and therapies and can we do it together to really drive this forward.

So I hope you join us and follow us because we really are very optimistic with the sort of prophylactic pain medications that we're going to give, the ability to actually get intraperitoneal therapy to patients because it also makes sense to patients that why are you giving these not only systemic medications, but medications that are treating where the cancer is thriving sadly. So patients also understand and they want immunotherapy. And now we finally have something that's effective. So thank you for your attention, and I'll hand it over to our next speaker.

Thank you, Premal. Okay. The next speaker, Dr. Amir Jazaeri, will be speaking on the use of IMNN-001 in combination with chemotherapy to prevent minimal residual disease after frontline therapy. And we'll be really unveiling progress with this trial and safety and tolerability and translational insights. So Dr. Jazaeri is the David Gershenson Distinguished Professor in Ovarian Cancer Research and the Vice Chair for Clinical Research in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center.

He also serves as the Director for the Gynecologic Cancer Immunotherapy Program and has helped establish a broad range of immuno-oncology programs for gynecologic cancers that include adaptive cell therapies, also focused on intraperitoneal immunotherapies and translational immunobiology. His other areas of research include understanding the basis for minimal residual disease, which you'll hear us refer to frequently as MRD in gynecologic cancers and designing clinical trials to intervene during this phase of the disease. He's the study PI for Imunon's ongoing MRD trial, and he'll share new data today in his presentation from that. So Dr. Jazaeri?

Thanks so much. So it's a pleasure to share with you some of our preliminary findings from this trial. I would think of this trial as kind of a forward-looking kind of what's next. And I really credit Imunon for their dedication to improving outcomes for women with ovarian cancer. And when you're truly dedicated to a purpose, you're never satisfied with your current efforts. You're always thinking what could be better, what could be different. And so I'll share with you sort of how we're thinking that maybe there's a shortcut to accelerate all clinical trials in the frontline setting by focusing on minimal residual disease.

I also want to acknowledge funding from Breakthrough Cancer Foundation. So a few years ago, with this trial being the flagship of our ovarian MRD project, we got $15 million in funding and a lot of the clinical and transitional data that I'm going to share with you was directly a result of that. And so if we think about the number of cancer cells in the body, this figure kind of shows that in ovarian cancer, obviously, patients are diagnosed with large number of cancer cells because they have advanced stage disease. Over time, with the standard treatment, this number comes down below this orange line, which is meant to depict limit of clinical detection. But very few patients, as you heard from Dr. Thaker's talk are cured. And what happens is with time, the number of cancer cells rises again. It becomes clinically detectable. And when that happens, what do we do? We still treat them with some of the same chemotherapies.

And by the way, when the cancer becomes detectable, basically, it's incurable. And only then after several additional lines of therapy, do we think about trials of novel therapies. And some years ago, we started to sort of think about, well, what if we could overcome this limit of clinical detection, what if we could do a second operation called a second look laparoscopy, which is a minimally invasive operation that's done at the end of frontline therapy. It's an outpatient procedure. And during this operation, we do multiple biopsies. We do washings of peritoneal areas. We aspirate all that fluid and biopsies, we send it all to pathology. And if any of those biopsies or if the fluid contains cancer cells, then we deem that patient as being MRD positive or surgical MRD positive.

And so by identifying patients that are MRD positive, as you might imagine, these patients have worse outcomes, and I'm going to share some data on that with you. And so what we hope to achieve is to provide the opportunity to do trials of novel therapies or novel maintenance therapies in this setting. But it also -- this is where I think we can have sort of a shortcut. MRD can also be thought of as an endpoint, surrogate endpoint. And so we hope that by looking after patients are done with frontline treatment and not having to wait until the cancer makes a clinical recurrence, we can accelerate treatment in the frontline setting. And this is exactly the sort of the impetus behind the MRD trial that I'm going to share with you.

And that's because currently, frontline trials are hampered by the fact that we have to wait until clinical recurrence, which takes a long time. I think the study rationale is very similar to OVATION 2. So I'm not going to -- Dr. Thaker covered that very well, but I just want to make the point again that frontline treatment is the best opportunity to achieve cures for ovarian cancer. So we think it's the right place to try to have an impactful intervention. You heard that IL-12 promotes inflammation in the tumor microenvironment, making cold tumors hot. And I'll share with you some of our translational data that demonstrates that. You heard again that systemic IL-12 is poorly tolerated. And I think sort of the innovative nanoparticle encapsulated IL-12 that's IMNN-001 has really been an innovation that allows patients to receive this potentially useful cytokine.

And of course, the idea of combining with IL-12 and chemotherapy is very attractive. Again, I won't go into OVATION 2 results. You just heard it reviewed. I just want to make the case that our study very much builds on the very attractive PFS and OS advantages that are seen in OVATION 2. But I also want to point out a couple of differences in our study. So we include bevacizumab in both arms, whereas I think in OVATION 2, that wasn't included. And again, I already mentioned that our endpoint is going to be minimal residual disease, and that's shown here in the schema of the trial.

Again, patients start with -- patients that are suspected to have advanced stage ovarian cancer, undergo diagnostic laparoscopy. This is just to make sure that they should get neoadjuvant chemotherapy, not primary surgery. This also gives us an opportunity to collect tumor tissue at that pretreatment time point. Patients are then randomized to the control arm, which is neoadjuvant chemotherapy plus bevacizumab for 4 to 6 cycles, depending on their response and/or to the experimental arm and the experimental arm, of course, includes IMNN-001 that's administered intraperitoneally through an IP port. All patients will undergo interval cytoreductive surgery and then get additional chemotherapy. And the other sort of interesting thing about our study, as I mentioned, the primary endpoint is detection of surgical minimal residual disease by second look laparoscopy.

But also by the time we initiated our study, we were kind of aware of PARP inhibitors and need for maintenance therapy. And so here, we have a unique sort of maintenance approach where patients that are homologous recombination deficient or HRD positive get bevacizumab plus Olaparib, which is a standard maintenance strategy. And they get that in both arms. So regardless of the arm, if you're HRD-positive, you're going to get PARP inhibitor, and patients that are HR proficient in the control arm get bevacizumab alone, which is, again, the current standard maintenance therapy for these patients. But in the experimental arm, we thought that it would be advantageous to look at extended exposure to IMNN-001. So these patients get bevacizumab plus IMNN-001. The only difference is during the frontline therapy, the frequency of administration is weekly.

During the maintenance phase because it's prolonged, we didn't want to expose patients to the need for weekly therapy. So here, the frequency matches that of bevacizumab, which is once every 3 weeks. And then, of course, this allows us to serially collect biospecimens, including tumor, cell-free DNA, microbiome and IP fluid because, again, they have an IP port placed. I'm going to share with you some of the translational data. But for MRD to be useful, it has to correlate with outcomes that we care about. This is a paper that we just published in clinical cancer research and showing surgical. And also, we looked at cell-free DNA or circulating tumor DNA detection of MRD as well. So for those of you who are interested, this has a lot of details on that and how they correlate with outcomes.

We also showed that with these serial samples from the tumor microenvironment made possible by the second look operations, we can also do very cool translational stuff. And in fact, one of the pictures of the sort of the -- from our -- one of our figures made the cover for clinical cancer research. And this is really the bottom line. Why do we care about MRD -- because it makes a huge difference. So you can see this is a surgical MRD. So patients that were second look negative, shown here in blue versus positive. You can see the huge median progression-free survival differences. And here on the right-hand side, you can see overall survival is not reached in patients that are MRD negative and 32 months in patients that are -- and again, you can see the hazard ratios and large or small p-values.

We saw the same thing with circulating tumor DNA. For time constraints, I'm not going to show that data, but if you're interested, you can see our paper. And this brings me to the MRD study, the current trial. We've assessed 35 patients for eligibility. Some patients did not have high-grade serous ovarian cancer pathology. This trial is limited to patients with that histology. And then you can see some of the other reasons patients did not qualify. 25 patients have been randomized. Of these 25 patients, a few withdrew consent, but 7 of them remain in frontline phase. And about 12 of them have made it to the second look laparoscopy time point. I actually think it might be 11 because one of my patients had count issues, so we had to delay the second look laparoscopy. So a total of 11 evaluable patients. And this is -- this just goes through very granularly in terms of what are the outcomes for these patients.

So this shows how far patients in the control arm have progressed. On the top, again, you can see the main stages of the study, diagnostic laparoscopy, neoadjuvant chemo, interval cytoreductive surgery, more chemo, second look time point and maintenance and follow-up. And here, you also see the chemotherapy response scores that Dr. Thaker alluded to. So -- and you can see that patients in the control arm, 4 out of the 6 of them that have gone through second look laparoscopy have had positive findings. And then the next slide shows basically the same thing for patients on the experimental arm. And here, you can see only 2 out of the 5 patients.

Again, these are small numbers, but you can see sort of the rate. And you see overall better chemotherapy response scores as well in this group. And this information is summarized here where, again, I just want to point out the asterisks. These are only 11 patients. And so this information should be interpreted with caution. But you can see progression-free survival already separation of the curves, which is promising finding. And then here are some of the clinical outcomes. I mentioned the MRD positivity rate. It's 40% in the experimental arm and 2/3 of the patient in the control arm have had MRD positive. Now for positivity rate, we consider anybody who has any biopsy positive. But of course, when we do these operations, we do 10 to 15 biopsies. And one could infer that the number of biopsies that are positive, obviously, if you have more residual cancer, more biopsies are going to be positive.

And so if we look at that in the experimental arm, the patients that were positive, it was 1 out of 10 biopsies, 1 out of 11 biopsies. So only 9.5% of patients that were positive in the experimental arm had biopsies that are positive. consider the control arm, those patients that were MRD positive in the control arm, you can see that they were really positive, so a much higher rate of biopsy positive. And again, in the experimental arm, even though we have very small numbers, there is already some indication that the mean chemotherapy response score is higher so that they're more responding to chemotherapy in the experimental arm.

So we also, again, had an opportunity with the serial biospecimen collections to ask some key translational questions. The first is, how does IL-12 and chemotherapy reshape the tumor microenvironment and impact immune activation. Can surgical MRD function as a reliable surrogate endpoint for survival outcomes? Again, that's a key sort of aspect of the study. And then does circulating tumor DNA assess and correlate with surgical MRD, providing validation for circulating tumor DNA as a further surrogate endpoint. I'm going to mainly talk about the sort of the tumor microenvironment because some of the other transitional questions are awaiting further data.

And so this is just, again, to kind of demonstrate the opportunity here. So at the time of diagnosis, where patients have more tumor, we have the opportunity to collect fluid, tumor samples and blood samples, then patients undergo neoadjuvant and we collect blood samples there. Again, at the time of interval surgery, we collect fluid and tumor and same with second look laparoscopy. And then we're using these biospecimens to do cutting-edge profiling of the tumor microenvironment. From the peritoneal fluid, we can collect single cells and do single-cell RNA sequencing. And on tissues, we can look at protein expression using CODEX and look at RNA expression using Visium HD. And so I'm going to just talk you through some of the early findings based on 3 patients in each arm that have undergone this type of serial analysis. This is single-cell RNA sequencing from, again, IP fluid. So cells collected from the IP fluid. This UMA just is a clustering algorithm that shows the different cell types based on their RNA expression.

And what we noticed, which was very exciting and kind of truth -- setting the truth was that when we look at IL-12 expression, so IL-12 is a protein that has 2 subunits, IL-12A and B in terms of the genes that encode for it. And what you can see is among the different cell types, IL-12 is mainly expressed in the macrophages. And this is -- again, these are cells within the peritoneal cavity. And in fact, if we look at individual patient samples, so these are patients from the experimental arm, 3 patients from the experimental arm and 3 patients from the control arm, you can see that baseline levels in the experimental arm are very low. And in all 3 patients, but especially in these first 2 patients, you can see the significant upregulation of IL-12 at the interval cytoreductive surgery and second look time points.

So this really shows that the mechanism of action of the treatment is really working, and it's not just random expression of IL-12. This IL-12 nanoparticles are being picked up by macrophages and being controlled. And as you can see in the control arm, you don't see anything like that. And so IL-12 expression is good, but we were interested in does this really impact downstream immunosuppressive aspects of the ovarian cancer tumor microenvironment. And so here, we're showing immunosuppressive gene signature. And you can see in the control arm, if anything, there is an elevation between baseline interval surgery and second look time points, there's elevation, whereas in the experimental arm, there is a decrease in levels of the gene expression.

And we just have more time points from the experimental arm. So that's why there's more data because these patients have an IP port and we can interrogate them more frequently. So this was all in the IP fluid, and this was kind of exciting, and we're like, okay, this is working. But what about what's happening in the tissue environment? And to interrogate the tissue environment, we use Visium HD. For those of you who may not be familiar with this technology, basically, Visium HD looks at gene expression, but by preserving the spatial characteristics of tissue sections. So we start with H&Es, and that gives us kind of where the cells are. That information is then digitally collected. And then we look at gene expression and then there are software that put all of this together, so you can see single cell resolution spatial data that preserves areas of tumor and other cells in the immune environment. And I'll just kind of walk you through an example.

So this is a patient on the experimental arm. These are the H&E sections from baseline interval cytoreductive surgery and second look laparoscopy time points. And if we overlay the Visium HD data, this -- the white here shows tumor cells, okay? The green is fibroblasts, blue macrophages and then the T and B cells are shown in red. And so what you can see in the baseline, this is before any treatment, there's tons of cancer cells and some fibroblasts. What you don't see is any macrophages, you don't see any immune cells. And by the interval cytoreductive time point, you start to see some macrophages.

Again, the blue is macrophages, and you see lymphoid aggregates shown here in red. And then at the second look time point, you see lots of macrophages, immune aggregates and very few cancer cells. And so this is showing in the tumor cells, and again, excitingly, the data that I showed you on macrophages picking up and expressing IL-12 was in the peritoneal fluid. But looking at the tissue, we show that the macrophages that are in the tissue are also expressing IL-12, which is really exciting because that's, of course, where we hope to see the action.

And in fact, if you look at macrophage gene expression profile, so these are differentially expressed genes. And on the right-hand side are genes that are higher expressed at the interval cytoreductive surgery. On the left-hand side, it's pretreatment. You can see that 2 genes that are highest -- and on the Y-axis, you see the statistical significance, the higher, the more statistically significant. On the X axis, you see the level of expression. So you see IL-12 and A and B as being the highest, most statistically significant genes that are overexpressed in tumor resident macrophages. The other cool observation is some immunosuppressive molecules like SPP1 and CSF-1 receptor that are known and established markers of immune suppression are lower expressed or higher expressed in the baseline sample. So their expression goes down in the interval tumor reductive surgery.

And again, we can show this on a patient level. You can see individual patients in the experimental arm and control arm where IL-12a levels go up, whereas they're flat in the control arm. So that's great. But can we say something about T cell activation and T cell function? So we looked at 2 genes, Granzyme B and granulysin. These genes are usually expressed in cytotoxic T cells that have been antigen experienced and are attacking the tumor. And what you can see is, again, in the experimental arm, the level of these transcripts goes up, whereas in the control arm, if anything, it declines between the baseline and interval cytoreductive surgery time point.

And here, you can see cytotoxic T cells are shown in red, and you can see, again, the blue that are IL-12 positive macrophages. You can see them surrounding and activating T cells and supporting their role in killing the cancer cells. So last but not least, one of the first things that happens with T cell activation is that T cells try to turn themselves off by expressing checkpoint molecules. And what we can see is, we see evidence of T cell activation based on checkpoint expression in T cells. Again, that's increasing in the experimental group, but going down in the control arm. This also raises kind of the interesting possibility of in the future, possibly combining IMNN-001 with checkpoint molecules may be an attractive strategy.

And we see basically the same thing in peritoneal fluid cells. So this was in the tissue and BATF is basically a transcription factor for many checkpoints. In the peritoneal fluid, the control arm are shown here in the dotted arm. So you can see reduction in interferon stimulated CD8 positive T cells versus we see activation and markers of immune checkpoint activation in the CD8 cells. So last thing, I just want to kind of talk about some of these technologies that I showed you, the Visium HD and the CODEX are novel and they are very informative, but we get nice information out of them. However, they're expensive, time-consuming and they're not really sort of applicable to day-to-day clinical practice.

And so one of the things that we want to do with some of this data and are starting to look at is to use AI to get the same segmentation information just from regular H&E samples, which are, of course, routine in pathology, see if we can look at different immune cell and other cell populations just by AI modeling and maybe get similar predictors of outcome. And so I hope that I've been able to show you that the clinical value of MRD trial, we've enrolled 19 out of the planned 30 patients.

And notably, there's been no problems with toxicity. No patient has come off due to toxicity due to IMNN-001 and patients have been successfully treated not just during the frontline treatment, but also on the maintenance therapy. I hope that I convinced you of macrophage activation that IMNN-001 induces robust expression of IL-12A and B in both peritoneal tumor and in tissue resident macrophages and that this IL-12 expression is leading to tumor microenvironment remodeling. And so with that, thank you for your attention, and I'll turn it over to the next speaker.

Thank you, Dr. Jazaeri. So it's my pleasure to now introduce Dr. Giorgio Paulon, who is a statistical scientist at Berry Consultants. He focuses from a research perspective in design and implementation of novel Bayesian adaptive designs, including platform trials. And he has experience in simulation, interim and final analyses of critical studies and presenting results to DSMBs of clinicians and statisticians.

His work has really supported high-impact publications, including a pivotal New England Journal of Medicine a trial and a paper published on minimally invasive treatment of intracerebral hemorrhage. Giorgio is passionate about enhancing the reproducibility of clinical research, developing advanced statistical methods and promoting transparent data-driven decisions. His training -- his formal training, he holds a PhD in statistics from University of Texas at Austin, where he developed Bayesian clustering methods for longitudinal data and collaborated on auditory neuroscience projects.

He earned 3 other degrees from prestigious universities in Milan, Italy and Paris, France, a bachelors in mathematical engineering and a masters in statistics and a double degree in a top internal managers and engineering program. Importantly, for Imunon and OVATION 3, he is responsible for the statistical simulations that he'll be speaking to today and really the overall framework, which provides the foundation for this pivotal trial. So Giorgio?

Thank you, and thank you, everyone, for being here. So good morning. I'm proud to represent Berry Consultants here, the company that I work for and to kind of showcase our collaboration with Imunon. Berry Consultants is, I would say, a small consulting firm that was created 25 years ago by Scott and Don Berry. Don Berry, you probably know him, especially those of you that are in the oncology space. He was Head of Quantitative Sciences at MD Anderson. And then he decided to create his own company to bring kind of statistical rigor, but also innovation in a real-life trial and push the envelope, especially with regulators, FDA and EMA for bringing innovation and bringing value to patients faster and to the overall community also faster.

So today, I will be speaking about a couple of things. The first part of the presentation, I really want to kind of emphasize again the Phase II results that we've had. But I will focus mostly on how we've used this data to kind of drive our assumptions for the Phase III portion of the study. So we've already seen this in the first presentation. So we've had a very robust Phase II study that studied IMNN-001 with a very well robust design, design trial that was randomized and controlled where the 2 arms are clearly defined, and that allows us to interpret very clearly the results of that Phase II trial.

It was a very large Phase II trial, I would say, compared to what I'm used to seeing. Obviously, Phase II trials are not necessarily built to be powered to detect statistically significant results. But what we've seen in the previous presentations as well is that we've seen consistent positive results in this Phase II study. So I'm going to focus on a couple of things, the consistency of the effect that we've seen from 2 perspective across the endpoints and also across the subgroup, and that kind of really lays the foundation for our Phase III study. And then I'm going to show you how that data was used to create our assumptions that are very robust for a Phase III study.

So we've seen this slide before. What I really want to emphasize here is that this is pretty uncommon for a Phase II study where you see benefit across subgroups. And to the credit of the company, there is not just a focus on a small subset of patients that are even more promising to bring to Phase III, but we go with kind of the overall population where we see a benefit. So all of these primary and secondary endpoints have hazard ratios in the right direction that are favoring the therapeutic intervention. And that's not always the case. Oftentimes, we find a subgroup and then we do a Phase III study in a specific subgroup. And then the second thing that is very striking is that there's a signal both in PFS and OS.

Obviously, as I mentioned, there's no really need. The goal of a Phase II study is not to be powered for statistical significance. But there are techniques and in particular, this highlights the totality of effect methodology developed by L.J. Wei at Harvard that combine -- can combine endpoint to see how stronger the effect is when you combine this kind of evidence. So here, you see that we have both PFS and OS estimates. They are in the right direction. None of them on their own are statistically significant. Again, that is beyond the goal of the Phase II study. But then there's techniques where you can combine these 2 endpoints and find even more signal in the data and quantify the benefit to patients, in this case, several months between the experimental arm and the control arm for either of these outcomes.

And I will also say these 2 endpoints are very especially OS uncontroversial for FDA. It's actually what is recommended. And so that's what will be brought up to the Phase III portion of the study, the OS endpoint. Okay. So how do we use this, I would consider a large amount of data for the Phase II, larger than usual, at least to build a robust Phase III design. Again, this is the schematic of the trial that was already well described in the first presentation. What I would like to emphasize here, a couple of things are the certification factors, those are very important in this study and the fact that we have a very clinically meaningful primary endpoint that is robust, is very accepted by FDA. It's a so-called hard endpoint. So there's no worry or no notion of biases in assessing the outcomes.

This is all-cause mortality. And this trial will target the most responsive subgroup. It still will focus on all comers by the end of the trial. But initially, we'll target the most responsive subgroup, so the HRD positive subgroup and will enable accelerated readout of the data. And I will describe how in a couple of slides. And then even the methodology is very kind of statistically sound. It's an event-driven trial. So in time-to-event outcomes like time to death for this trial, what defines information is the number of events that you observe in this case deaths. And so this trial will have triggers for interim analysis and final analysis that are based on events, and that's kind of the cleanest source of information that you can have in a Phase III trial like this.

Okay. So how would this work in practice? I've tried to put together a schematic. So -- the key feature -- there's 2 key adaptive features of this trial. One is that it starts prioritizing HRD patients. So the total number -- the total sample size target enrollment is 500. They are split equally between HRD and HRP. And the HRD patients will be primarily targeted initially because the goal is to allow an early readout in the HRD-positive population and then potentially expand to an overall ITT analysis later on when more data comes in. So the HRD analysis is the one that I will mostly focus on here. And you see that after randomizing 250 subjects, there will be 2 interim analysis before the final analysis.

The first one will be targeted by 50% of information. So when 68 events in that HRD cohorts are reached. And then there's a second interim analysis at 101 events in the HRD subgroup and then the final analysis will be at 135 events. So this is a so-called group sequential design. It's, again, very accepted and with precedent by the FDA, especially in oncology. What this means is that if any of these earlier interim looks that are prespecified, there's a signal in the data that is strong enough, then Imunon could file for an accelerated approval or an early BLA in the HRD cohort and then wait and potentially expand once all of the ITT data comes through. And this kind of probability of success that you see here in the middle of the slide, I will describe that further later on, but I just want to emphasize that if our assumptions that I'll show you in a couple of slides are correct, then there is a very substantial chance that this trial will stop early, especially in the HRD population.

Okay. So there's quite a bit of regulatory precedent for FDA full approvals that are based on interim overall survival data. So here, I just picked a few from the field of oncology. So we have a couple of examples from triple-negative breast cancer and also non-small cell lung cancer. These are trials that either allowed, so in the first one or actually did stop early for an early filing based on interim OS data, especially the second one is something that mirrors quite closely what we're doing here with the IMNN-001 and OVATION 3. It's a study that allowed prespecified earlier looks by an independent DSMB.

And again, if the p-value of the study or the signal was strong enough, the study could stop early for early success. And I will try to quantify later on how earlier that can be. So I have a couple of slides on the assumptions that we've made that are one of the most important things that we make when we design clinical trials. So -- and what I would like to emphasize is that our assumptions are quite conservative. This is the scenario that we expect. So we have on the left here, the OVATION through data stratified by HRD and HRP populations. You see it in the Kaplan-Meier. And then overlaid on it, it's what we are assuming in terms of the ground truth.

The ground truth is if we had an infinite amount of data, what would we actually observe. And I think more significantly on the right, I'm showing that in terms of the hazard ratio. So hopefully, you see again, on the x-axis HRD and HRP population separately, you see a 95% credible interval with 2-point estimates. You see one that is denoted by O, that is what was observed in the OVATION 2 study. And then there's an A that is what we are assuming the effect will be in OVATION 3 when we designed the study.

So you see that even under what I'm calling expected scenario, this is just one of the scenarios considered, we are assuming something that is slightly weaker than what was observed in OVATION 2. And we do this to give us ourselves a little buffer because obviously, there's still variability out there in the OVATION 2 study. So even under this expected -- what we're calling expected scenario that in reality is slightly weaker than OVATION 2, we see a very large power of 98%. Now we -- what we do when we simulate clinical trials is that we try to be as -- in a way conservative as possible. We try to simulate a wide variety of scenarios because we never know how things will play out in real life.

So we also have a so-called weaker scenario where the effect that we're assuming is even weaker than what we were seeing in OVATION 2. And that really is to give us this margin of safety between the observed effect and the assumed effect. And even under this case, we still are adequately powered by what FDA considers acceptable, which is 82%. And again, this is not the target scenario. It's just kind of a dial back weaker scenario just to give us confidence that we could still meet in 82% of the cases, statistical significance. Okay. At this point, you should ask yourselves, how do we come up with these numbers, the 82%, the 98% and also how often the trial stops early. The way we do this, there's generally 2 ways. They're both accepted by FDA and there's guidance.

Sometimes we're lucky enough where there's analytical formulas to calculate power for clinical trials. More often, we do simulation, and this is very similar to, I guess, in finances called risk modeling. We have a set of assumptions, simulate the outcomes and then analyze repeatedly across tens of thousands, hundreds of thousands, sometimes virtual trials, what actually happens, and then we characterize the operating characteristics based on that. So this is very much an iterative process that we've been going on with Imunon for about 1.5 years, where we set up the expectations of the trial, where it's accrual rate, dropout rate, hazard rates and the treatment effect profiles.

And then we iterate through the design to optimize it and tailor it to the needs of Imunon. And so we do this thousands of times. And then we see kind of an aggregate picture, which is how many of these trials that we've simulated actually win and meet the primary endpoint. This allows us to, on one hand, characterize power, which is probably the most important operating characteristic of a trial, but it also allows us to look at individual trials, example trials, and we've shown many of these to understand if in this case, Imunon was happy with how the trial was performing. So this is kind of the key -- the evidence-based framework that we use to come up with numbers and check the robustness of our assumptions.

Okay. The last thing that I would like to really focus on here is how kind of the second level of innovation in this trial, which is the early looks, the early prespecified looks. And here, I wanted to quantify based on our assumptions, how earlier Imunon could file for early success and how often that happens again across our simulation. So in the graph that you see here on the left, what I'm reporting is the probability that the trial will stop at the first interim, the second interim and then the third interim is actually the final analysis for the HRD population. And so as an example, you see a light green here in the second graph -- sorry, in the middle part of the graph, which is the default assumption or the expected assumption.

And under this scenario, 93% of the trials will stop either at the first or the second interim. So there's about 50% that stop the first interim and then another 43% that stop at the second interim. So again, this is the expected scenario, which is slightly weaker observed effect than OVATION 2. And those interims, just to give you an idea, occur on average, the first interim about 2 years earlier than the final readout of the data. And then the second interim on average is 1 year earlier than the maximum target of events in the HRD population.

So this really can enhance the clinical development and the early filing that translates into a benefit for patients, clinicians, investors and society at large should the effect be observed. Okay. So to summarize, hopefully, I convinced you that we have a very robust design that has some innovation -- some elements of innovation, but it is also very, in a way, statistically sound and very accepted by FDA with a regulatory precedent. The main adaptive feature is that we can look early for signals in the data based on prespecified rules and file for early BLA. And that FDA, we've already gone through several interactions, but this is all framework that aligns with the regulatory precedent and gives us confidence that this trial can be a success. Thank you.

Thank you, Giorgio. Okay. Our final presentation before we go into Q&A, which is really always fabulous taking the effort to come together as you guys did that are in the room, you have an opportunity to really go deep with a set of phenomenal experts. So Dr. Douglas Faller will be talking about IMNN-001's potential from his perspective and giving an update on the progress of our Phase III trial, OVATION 3. And Dr. Faller is -- I'm delighted to say he's our Chief Medical Officer. He received his MD from Harvard Medical School and has a PhD and a Bachelor’s from the Massachusetts Institute of Technology, so MIT.

He was Professor of Medicine at Harvard Medical School and subsequently, he founded and served as the first Director of Boston University's Comprehensive Cancer Center, where he was at Gruenbaum Professor for Cancer Research and Professor of Medicine, Biochemistry, Pediatrics, Microbiology, Pathology and Laboratory medicine. Dr. Faller is the scientific founder of multiple technology and pharmaceutical companies, and we were delighted to have him join largely based on the strength of our data and potential. As you were joining, Douglas, it was really exciting to hear your viewpoint over your career of observing ovarian cancer and really the potential for IMNN-001. So please come and share your thoughts with us.

Thank you, and thank all of you for joining us today. My job is to try to put together some of the things that you've heard. I'll do it very briefly because I certainly can't match the quality of the presentations you've had so far. I think you'll agree that the data that you've seen is exciting, and some of it is really brand new. The information that Dr. Jazaeri presented, I don't think has been presented outside of breakthrough cancer as far as I know. This is the first time it's been presented publicly.

As Stacy mentioned, it's this kind of exciting data and this kind of promise that form the reasons why I joined Imunon very happily. I'll mention one other thing, one other reason that I joined Imunon. As you know and you've heard, as you know, -- this is a frontline cancer trial, a frontline trial in ovarian cancer. It's very unusual, as your experience will tell you, for a small company to start their first approval in a frontline setting. It's a gutsy move for a small company. Most companies, including large companies start at the relapsed/refractory setting, an easier path to get approval, but one that would take another 10 years to get into a frontline setting.

So Imunon has decided to go where the patient need is the greatest despite the fact it's a bit of a harder path. Although from what you've seen today, I think you -- I hope you will agree that we have great reason for being confident that this is where we'll be successful. So what we've tried to show this morning is a number of things, a number of different parameters that collectively make us confident and optimistic and really enthusiastic about our probability of success and about our probability to provide meaningful benefit to patients over a relatively short term. We have a mechanism of action that's novel and immunotherapy that we can show alters the microenvironment. This is something that people have been trying to do, and I'll get back to this in a later slide.

The drug we're using, IL-12 activates both the innate and the adaptive immune systems as both Dr. Thaker and Dr. Jazaeri mentioned. And this gives us sort of a double way of hitting the tumor from both arms of the immune system. You've seen the impressive clinical responses we've had in OVATION 2, and these are further substantiated with the early data from the MRD study. And finally, we've got emerging translational data from both the MRD study, which you've just heard and the OVATION 2 study, which I've had the privilege of presenting at multiple meetings over the last couple of months that continues to support our mechanism of action.

You've seen the clinical data. I'm still smiling every time I look at it because of the benefits that we can provide to patients. One of the things that I believe Dr. Thaker mentioned was immunotherapies should have the ability to provide long-term benefit. Chemotherapy, the kind and even targeted therapies, for the most part, provide benefit while you're delivering them. In contrast, Look at the separation of curves and look at the length of time that we're providing benefit to patients. We're only giving our drug over this very short period of time at the beginning, and yet we see long-term benefit, exactly what you hope for if you kickstarted the immune system and the immune system continues to recognize and kill tumor cells.

I won't go through all the things that Premal mentioned. But again, the survival data is really unprecedented, as she stated. In fact, after her talk at ASCO, one of the speakers who came up to a microphone said this is a milestone in ovarian cancer. An improvement in survival she implied is something we've been waiting for, for decades. The consistent benefit across other endpoints has been mentioned several times, something that's very reassuring and unusual in a Phase II trial. The fact our safety has been excellent. We've seen no cytokine release syndrome, no adverse events related to immunity, something that has plagued every other approach trying to use interleukin-12.

And as I said and several speakers have said, we have clear evidence for an altered tumor environment, cold to hot. I'm sure following biological or biopharma and following cancer, you've been hearing cold to hot forever, mostly in the setting of people saying, we think our drug can turn a cold tumor to hot. I've been involved in many, many BD discussions with companies who say they can do that. We can do that. We have shown that, not in the test tube, not in the mouse, in patients. And I'll show you a little bit more of that data in a moment. And I talked about the long-lasting immune response already. And so just a little bit more data, and this is some of the data, just a tiny bit of it that I've been presenting at scientific conferences over the last couple of months.

The data is still emerging. And some of the data Premal showed from OVATION 1, this is some of the data from OVATION 2. We have a whole panel of data. But the idea of turning cold to hot, as I said, has been something of a holy grail and something that everyone has wanted to do. And the inability to do that is, unfortunately, why, as Premal also mentioned, the checkpoint inhibitors have really shown, unfortunately, no benefit in ovarian cancer. You can't get checkpoint inhibitors to work if you don't have T cells in the tumor, activated T cells ready to kill the tumor if you remove the checkpoint.

In this case, we can convert the tumor from cold to hot. So as one example, the ratio of -- sorry, I keep hitting the wrong buttons here. The ratio of CD8 cells to T regulatory cells -- I'm losing the pointer -- is quite low as you would expect in a cold tumor. But when we sample the tumor after just 3 cycles of chemotherapy at Imunon, we can see increases in the ratio of CD8 cells to T regulatory cells, both in the tumor and in [indiscernible]. Similarly, we talked -- so this is the adaptive part of the immune system. The [indiscernible] of the immune system, the monocytes and macrophages, M2 macrophages actually promote tumor growth and development. M1 promote anticancer activity.

The ratio of M1 to M2 is low in both tumor -- in the cold tumor and cold stroma before we get treatment. After we get treatment, we see a substantial increase in the M1 antitumor macrophages and monocytes compared to [indiscernible]. I'm sorry, I'm too far from the microphone? Okay. I'll just point randomly then. If we look at conversely, so the immunostimulation is substantially increased. And conversely, markers of immune suppression, some of which Premal alluded to in the OVATION 1 study are reversed. We can see T regulatory cells, which just won the Nobel Prize this year for their importance in preventing autoimmune diseases are a terrible thing to have in a tumor because it prevents the immune response in the tumor.

We can show decreases in T regulatory cells, both in the tumor and in the stroma, the tumor stroma. And finally, exhausted T cells go down once we stimulate the patient's tumor with the IL-12 with IMNN-001. We have a robust study design, 1:1 randomized treatment control with the endpoint that the FDA wants to see. Very importantly, we have a well-established biomarker, which is driving our study. I suspect you all know, but I'll mention it anyway. It's been well documented, including by a group of my colleagues in the business school at my alma mater that having a biomarker to drive your clinical study increases your chances of success at every phase of clinical development, up to a four fold increase in Phase I, Phase II, Phase III and registration.

So the fact that we're using this biomarker that we've identified as a -- which is predictive of response to IMNN-001, we're using it in our trial and our statistical plan to take advantage of this increased probability of success. We have a limited duration of treatment, which is good for patients. And I've already shown you translates into a long benefit for patients, long after our drug has stopped, just what you'd hope for in an immune therapy. Dr. Thaker talked about the quality of life measurements we're going to be doing, including the ones we've already done in OVATION 2. And you've heard already from Giorgio about our confidence in our statistical design resulting from modeling of the design.

Our OVATION II trial is successfully underway. We have multiple sites activated. And surprisingly, and unusually in my long experience, our enrollment is already exceeding our internal forecasts. So we're very gratified by that. We haven't mentioned it up to this point, but I think many of you know that we have FDA approval for our CMC plan for drug originating in our own GMP facility. And this is a huge significant cost savings and a strategic advantage. We don't have to rely on others for our drug supply. We've been excited about our kickoff of our trial and about the number of patients we've enrolled. We actually are going personally to visit each of our sites as they come online to talk with the investigators and to share best practices and advice from the trials that have already started and are already enrolling.

The favorable benefit to risk ratio that we saw in OVATION 2 with very good safety and really impressive clinical responses and durations of response Have been further strengthened by the data you've heard today from the MRD study. And the other thing that the MRD study has done for us already, it's shown that we can combine safely with bevacizumab, which some gynecologic oncologists like to use in combination with chemotherapy. And as you also heard, we're able to show that we can safely give Imunon in a maintenance setting. So both of these set us up for future studies and future approvals for IMNN-001.

We're well positioned to bring on 50 sites by the second half of 2026. I mentioned we've had multiple very successful engagements that we've been invited to attend, including recently ESMO and International Gynecologic Cancer society. I presented at ACR and most recently at SITC, I just came back from the SITC meeting. And several people mentioned that -- SITC is the Society for Immunotherapy in Cancer, the 25, I believe, year-old society in which -- for which nothing was happening for many years. And now the innovations in immunotherapy for cancer have made this one of the most important meeting, international meetings of the year.

One of the things that was noted by a number of speakers there was the interest in IL-12. There were many more IL-12 presentations than there had been in previous settings. One person came up to me, one clinical scientist and said, I've been going around and looking at all the posters about the presentations for IL-12. And he said, I've been interested in IL-12 for years. It's the most potent cytokine against cancer. All of these posters, all of these companies, all of these investigators are trying to figure out a way of delivering it safely. You've done it. They're trying to figure out whether they can use it to help patients. You've done it. He said, I'm glad this is the last presentation because this is what I'm going to take home.

So in each of these, as I mentioned -- and also, we've had investigator interest. We've had investigators who have come up to me after presentations who have said, can I participate in your Phase III trial? This is something I'd really like to do. So on the basis of what they heard, they were excited enough to want to participate in our trial. So this is the last slide. I'd like to just make the point again, we have really -- our trial -- our Phase III trial is built on unprecedented and clinically compelling overall survival data.

We're continuing to get positive safety and efficacy data from Dr. Jazaeri's trial. We've got new translational data that's still emerging from both his trial and our OVATION 2 trial that confirms we have a potent novel mechanism of action and a mechanism of action that we can document is operative in patients. And finally, the biomarker-driven aspects of our trial, we think will even more greatly enhance our probability of success. So thank you very much for your attention, and I'll turn it back to Stacy.

Thank you, Douglas. So we'll open it up for Q&A, and I'm going to get us started actually, Premal, as I was listening to your presentation and thinking about you're one of the sites that's open. You enrolled in OVATION 2. You've now enrolled multiple patients in OVATION 3. How are you finding the interaction with patients with this data? Is it impacting the ability to really help them understand what this trial could mean for them? Yes, we do need to use this.

Thank you for the question. I'll also say I date back to OVATION 1. So I've been a trooper here and believing in this. So it's actually really encouraging and easy to now talk to patients because now we have published articles so patients can actually see it because, as you know, patients are consumers of their health care. And so they are educated. They want to hear what's front and like leading sort of scientific news. So I think it is much easier actually because we have published data, we continue to have data. I'm actually very excited to like present now the MRD data as well to sort of say, here's another trial that shows the benefit and the change.

And as I mentioned before, patients have been craving for immunotherapy in all cancers and ovarian cancer is no different. If you watch the news or watch TV, you see a million different ads, right, direct consumer about like medications. And this is finally our opportunity to offer that to patients. And as I mentioned, there's nothing else in upfront ovarian cancer. And when I counsel patients about clinical trials, I tell them that if you want what's the past, that's standard of care. If you want what's the future, come join us in a clinical trial because everything we've done in the past was a clinical trial.

And patients really wanted -- they're much more sort of very giving with their time because they know it's going to be a weekly treatment, and they're actually disappointed because they're randomized, right? So I can't guarantee you're going to be on this. However, it's a 1:1 randomization, which is good, too, because sometimes it's not like that. So I definitely do feel that patients are very passionate.

Do you want to add something from the MRD experience? Dr. Jazaeri has been nothing short of a powerhouse with that trial and has enrolled the majority of the patients. So you have a lot of conversations.

Yes. No, our trials open at 3 institutions just recently, a fourth institution is activated. I just want to echo Premal's. We have a patient who comes from Illinois to MD Anderson and she's on the experimental arm. So she comes every week to get this treatment. And I think I'm always -- every time I assume I know what patients are going to do, I've always been kind of humbled that when patients sort of are convinced that something might be in their best interest, they go through extreme lengths to do what they can to advocate for their care. So I just wanted to add that.

Okay. What questions, Tim? You guys want to come up maybe, just come and stand?

Tim Molloy from Alliance Global Partners. I had a couple of questions to Dr Jazaeri. You talked a little about safety [indiscernible].

Okay. I think one of the things that we are learning and getting better of is the administration weekly for these patients because I think also one of the things we didn't touch on as much is that even though not all patients got 17 doses, we are seeing the change in the tumor microenvironment even if patients get lower or less number of doses of the therapy. So it definitely tells you how potent it is.

But with the adding of sort of the prophylactic pain medications, being much more aggressive of educating about antiemetics, we really are not seeing patients discontinue, and we improved the tolerability quite substantially. So we aren't seeing patients coming off because of adverse events from this. So we don't see cytokine release syndrome. We don't see interstitial lung disease, things that you commonly hear with immunotherapy. We don't see high fevers because a lot of times, patients when they get sort of these powerful cytokines can get that as part of a cytokine release syndrome. So we're not having patients in ICUs and they can tolerably come to and from every week to get their treatments.

Yes. I would just say that we had, of course, the benefit of Premal's pioneering work as OVATION 1 and 2. So we knew that premedicating patients really resolves any concerns about IP administration. And of course, IP administration resolves all of the previous lack of success with systemic administration. So we really haven't had any issues with tolerability.

One follow-up, Giorgio. You ran the hundreds of thousands of trials, was there a particular thing that came out [indiscernible] trial mostly or [indiscernible] particular things that we should be watching for going forward?

No, we don't necessarily do those to look for things that could derail the trial. I mean, ultimately, what derails the trial is if you don't observe what you are hoping for and you're expecting, right? So the reason for the simulation is more to calibrate, for example, how aggressive you want to be with the interim looks, for example. So we use kind of a conservative approach, which is -- I can go more in details, but it's an O'Brien-Fleming spending function, meaning you do multiple looks to the data, right, first interim, second interim and then the final. How early do you want to start looking? Those are the things that we looked at. We didn't want to look too early because we're expecting a little bit of a delayed effect.

So those are the things that we try to mitigate. Don't look too early. have enough evidence that is strong enough that gives you a solid foundation, but it also allows you to save time ultimately. So those are the kind of things that we iterate and we optimize for.

[indiscernible].

Yes. No, I mean I think you raised a really good point. That's why the first thing I pointed out is these are based on 11 observations. But I think what we hope to do is to look at when we have the full complement of the data so that there will be 15 patients in each arm. And of course, I should have maybe mentioned specifically, but all of these patients are going to be also followed to progression-free survival and then overall survival as well. I think FDA has been very clear that they support surrogate endpoints so long as they're tied to traditional endpoints, and they're encouraging more trials to do that in order for us to have a better understanding of what might be a useful surrogate endpoint and what may not.

So all of these patients in both arms are going to be followed to traditional endpoints. And I think then we'll see what we'll see. And again, sort of -- that's why I presented the biopsy data because in some ways, MRD positivity as a dichotomous variable may not even fully capture the benefit. But when you look at how many of the biopsies were positive in patients on the experimental arm versus control arm, I think there, again, you're seeing kind of the differences.

I'd just like to add one more other point. And obviously, our sophistication of technology has improved greatly if we look over the last decade. But you can also see this is from OVATION 1, OVATION 2 and then MRD study. We're looking at very similar variables, looking at sort of immunosuppressive signatures that are changed by this. So I would say even though the data is small subsets, you're seeing a consistency, which is, I think, really important. It's not like we're showing you just one trial that demonstrated this benefit. We're showing you a body of work.

Yes, it's an important point. And all 4, this is now OVATION 3 is the fourth trial in the frontline patient population and has consistently shown the effects, which from my perspective, when I look at the underlying biology of what's happening in the micro tumor environment and then you look at the clinical data, that's one thing, Emily, to your question of confidence that adds a lot for me.

What other questions do we have? [Graham]?

[indiscernible]

I might clarify that -- and I'm realizing I'm not sure on the webcast that you can hear the question, so I'll repeat this question. So you commented on that we are enrolling faster than our expectations, which is true. And you want to know if there is a -- if we can understand what the patients are choosing not to do from in terms of other trials that they might consider. That's correct. I can start and then others can add on. So Premal referenced first in her remarks that it was -- it's a rather bold decision to go after the frontline treatment as we know there are women who don't respond to frontline chemotherapy.

And therefore, you're bringing people into the trial that may fail just from the current standard of care. You've been very consistent, I think, in pointing that out. This is one of the things that makes frontline treatment studying the first-line frontline treatment very difficult. But what's -- and then therefore, it's not surprising that when you look at where there's been innovation recently, it's in maintenance or the later lines. And to the best of my knowledge, we don't know any other late-phase trials that are actively -- that are active in this space.

So right now, that would mean that really patients would have the standard of care. That would be what they receive in this trial is that we build on with IMNN-001. But there have been other trials that have read out recently. Premal showed a couple of the survival curves, but those very different mechanisms of action and we're unable to show a prolongation of overall survival. So I think right now, those are basically the choices more to add?

Yes. I would echo those thoughts. I think one of the things we also have in this country an increase in neoadjuvant chemotherapy because the bar of trying to get all the cancer out, it has evolved from being less than 2 centimeters, you can leave some larger implants to now you need no gross residual like nothing you can see. So I can definitely say that's really hard to achieve. So a lot of patients now, at least 50% to maybe up to 60% in this country get neoadjuvant. We do the laparoscopies, like Dr. Jazaeri mentioned, to make sure we give every patient that opportunity.

The only other upfront trial is really looking at heated intraperitoneal chemotherapy for neoadjuvant patients, only in an HRD population and that, too, you have to sort of go through your 3 cycles of chemo, make sure you're fit and then you get randomized. So patients are opting for options sooner because they are feeling the side effects and realizing that if you're giving a medication in the abdomen, and like I said, a lot of patients like that concept because when you talk about chemotherapy, they're like it goes throughout my whole body, right? So that's why I get my hair loss and other systemic effects.

And even though this is causing some systemic effects in the intraperitoneal cavity, it's really changing where the cancer is located. So I think that resonates with patients. And I'd like to say that there's a little less mistrust in science right now, but sadly, there is more based on our current ways of how people are getting information. But I think the patients are really wanting to do the best for themselves, and this is an opportunity. So I think it's easier, as I said, other than when I did OVATION 1, where it's a Phase I and you're sort of hoping that this would work. So it is much easier this time around.

And remind me that the [indiscernible] trial that's ongoing, do you have to actually have partial or complete remission from chemo. Is that right?

We should have a response.

Response, yes, response. Other questions?

It's not an all [indiscernible].

Graham, do you have another question?

There was a reference earlier to use of AI [indiscernible].

Yes. So this, I think, falls under the umbrella of research and investigational aspects. And basically, I showed a lot of sophisticated ways you can interrogate the tumor environment, but these are expensive, time-consuming. And so where we see, hopefully, in the future, AI playing a role is to take the routine H&E section that all pathologists create when they receive tissue from surgeries and be able to see something and say something predictive at that level that doesn't require weeks of analysis and bioinformatics and things like that. So that's kind of a future direction that we have.

Other questions? Okay.

I was just curious about -- so the average numbers of [indiscernible].

I don't know that that's the average, but we shoot for 10 to 15 roughly. Yes.

[indiscernible].

So what we want to do is, we want to do systematic biopsies. So we do several areas in the pelvis, several areas next to the bowel, several areas in the upper abdomen plus anything that looks suspicious, any scar. What we've learned is that when we look with surgery, we can't -- very rarely can we tell obvious areas of cancer. So we have to do biopsies of suspicious areas, biopsies of where ovarian cancer likes to hide, for example, in fatty tissues near the diaphragm. And then because you can only biopsy so many areas, we also do the washings where we put in sterile saline, we swish that around and we aspirate that and the cells that are collected through that washing are also submitted to pathology.

So that's kind of the way we have to -- but surgery is not perfect either. Unfortunately, many patients that have negative surgery, as you saw from the Kaplan-Meier curve, still progress. However, the time to progression is clearly different. And again, we're also sort of thinking that with ctDNA technologies becoming more and more sensitive than, and something that we can check repeatedly unlike surgery that you can only do once. I think that's going to be probably the preferred way to look at MRD. And there's pros and cons to both, but happy to discuss at the break.

Great question. Certainly, all of these markers and advancing technology for any of us that have lived through cancer with loved ones, you're always wanting markers that give you a sign of hope and success and that the treatment is working. So it's very powerful to see what all the work that Dr. Jazaeri that you continue to do. Any other remaining questions? Otherwise, we have coffee. I'm going to make a couple of just closing remarks, if you guys can have a seat if you'd like.

So I hope that you guys enjoy it. I think it definitely, I know for everybody takes time away and to come to the Harvard Club for those of you here in New York ahead of your -- going to your day job and your office. It means a lot to be able just to allow the conversations to go deeper. So enjoyed the conversation before this, we'll enjoy it after. I found it certainly engaging, and I learn every time I hear discussions of really what you're facing on a day-to-day as you treat patients. We heard a lot of really interesting ideas.

I think certainly, it was important, and we've gotten a couple of -- we've gotten questions as we've met with investors in the non-deal capacity about the trial design. Giorgio did a really great job of showing the conservative nature of the assumptions, which is, of course, what you want going in. The value of the grid that he showed with even the more robust efficacy. Obviously, if you have larger efficacy than you expect, you know that the chances of a successful trial increase. But when you look even at a weaker assumption, which we don't expect, based on the data, we still see that we have a trial that we would expect to read out positive.

So very high probability of success estimate. So very great insight. It was certainly wonderful seeing the new data from the MRD study. It's a trial that has been going and really an important partnership with Break Through Cancer Foundation and their commitment to ovarian cancer. And of course, just hearing the viewpoints on our trial and the Phase III trial and really the properties of it. And so we are really -- we believe we have a very clear path going forward. I would hope that even the most skeptical of individuals that might be watching this or really just as a nature of being critical of evidence, I really think that it would be hard to deny that we're knocking on the door of something incredibly powerful and that this really does represent a true potential for a breakthrough.

And I would say as being not only a novel therapeutic, it is a platform therapy. So when we think about IMNN-001, we know from preclinical research and really the literature that this really has potential not just for ovarian cancer, but other solid tumors. And then, of course, the ability to modify with through the platform to different targets. As we learn in science, we have an ability to play to that. So what's next? You've heard OVATION 3, we're actively enrolling. We have great momentum heading towards the end of this year. We've been very careful with spend as we're very carefully navigating our cash runway. And so we started with 4 sites.

They are exceeding our expectations, and we are prepared. We actually should double the number of sites before the end of the year. We have 4 more that are either fully negotiated. We're waiting on IRB to give the final go. So we will be bringing a new wave on board, and then we've pulled forward the identification of the sites you saw reference to up to 50. So you're going to see a real infusion that's going to happen in the new year, which will be very exciting. Our regulatory strategy, we've shared, it's always been a strength. We are continuing to have dialogue.

In fact, we're advancing our CMC as we do development work, and we're preparing for commercialization. It's really important that we're producing product, of course, for the Phase III trial, but ultimately thinking about a bigger scale. And that is all advancing and moving very well. And then for those of you, the investors, in particular, that we're having more and more conversations with that really don't just care about the returns, but care about what we're able to do for patients. I think everybody appreciates that when we look at the U.S. market alone has -- is valued at about $1 billion using conservative estimates from checkpoint inhibitor pricing and looking at the market with a significantly higher potential, obviously, globally.

So we are executing with urgency, women who have ovarian cancer deserve that and really can't thank you enough for coming and for your partnership as we step through these important steps and this registration trial with the goal of bringing forward the first immunotherapy for ovarian cancer. So thank you for your time today.

We should still have coffee and pastry so we can go out and I know all of the speakers are able to be here for a little while, so we can have some dialogue there. Thank you.