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Hello, and welcome back to another CEO Corner segment. I'm Abizer Gaslightwala, Chief Executive Officer of Akari Therapeutics.

ASCO remains one of the most important scientific and strategic events in oncology each year. This year's meeting did not disappoint by any means, featured more than 5,000 abstracts spanning virtually every area of cancer research and drug development. What stood out to me this year was not only the accelerating pace of innovation across oncology, but also the continued industry focus on the most difficult-to-treat genetically defined cancers, in particular, KRAS-driven tumors like pancreatic cancer, where significant unmet need still exists today.

We also continue to see significant momentum surrounding the ADC landscape and accelerating investment by pharma and biotech in this category. Importantly, based on many of the talks, I believe we are now at the cusp of ADC 2.0 to transform this category. This was aptly stated by a key leader in the field, Dr. Anthony Tolcher during his presentation when he called it on his slide.

Now it's all about ADC payloads and maturity of Top1 and MMAE. This talk drove continued emerging data that highlights the limited efficacy of ADCs that follow other ADCs of the same payload class. One data set highlighting this point was in breast cancer. When patients who took an ADC with a Top1 inhibitor relapse and then tried a different ADC with the same type of payload, the efficacy seen was minimal and not deemed successful. This is really important, given that there is now a growing number of patients who have relapsed after their first ADC therapy and currently have no other ADC options for them to take due to payload homogeneity.

This further emphasizes the urgent need for novel payloads like Akari is developing that can serve all these first-line ADC refractory patients with new hope. We believe our PH1 payload platform may be uniquely positioned within this evolving ADC landscape, given its novel and first-in-class mechanism of spliceosome modulation to attack cancer tumors through multiple methods and avoid the potential resistance mechanisms that current ADCs with traditional payloads experience.

We are now very proud of our first accepted ASCO abstract with what we believe more to come in the future. This abstract highlighted preclinical data demonstrating unique combination synergy between the PH1 ADC payload and a KRAS inhibitor in KRAS-mutated pancreatic cancer models. Given ASCO's strong focus on precision medicine and the extreme excitement regarding KRAS therapies at this conference, we believe this data could open up a new potential dimension of opportunity for Akari's novel ADC payload in the rapidly evolving multibillion-dollar potential KRAS therapy category.

Looking ahead, we remain focused on continuing to advance AKTX-101 through our targeted initiation of a Phase I first-in-human clinical trial by mid-2027 while further scientifically validating our PH1 spliceosome-modulating payload platform. We also look forward to continuing to provide updates and evolving data as we progress along the path to IND and clinical development. Thank you for your continued support, and I look forward to sharing additional updates with you in the CEO quarter.

We've always said we believe our payload can be attached to many different types of antigen targets and molecules and create a library or pipeline of ADC molecules. And so this is the power of the payload coming to fruition.

Welcome back, and thank you for joining us for another virtual investor What This Means segment. My name is Jenene Thomas. I am CEO of JTC IR, and I will be the moderator for today's segment. I am very excited to welcome back Akari Therapeutics to our virtual investor platform. And I am very pleased to be joined by Abizer Gaslightwala. He is Director, President and CEO of Akari Therapeutics. Welcome back, Abizer.

Thanks, Jenene. Thanks for having me here today.

Always happy to have you. And before we get started, I just want to inform our audience that Akari Therapeutics is listed on NASDAQ and trades under the ticker AKTX. And during today's discussion, the company will be making forward-looking statements, and I encourage everyone to view the company's website at akaritx.com or the SEC's website for their latest filings and information.

Okay, Abizer. So just to set the stage for why we're here today, Akari recently announced the filing of a key new patent and unveiled its second ADC pipeline candidate, which you're calling AKTX-102, targeting CEACAM5 expressing solid tumors. So today, we'll discuss what this announcement means for Akari's expanding ADC pipeline, its rapidly growing patent estate and the company's path towards the clinic with its lead program, AKTX-101. So that was a mouthful there. I first want to congratulate you. Lots of progress, Abizer. And so I'm just going to dive right in, if that's okay?

Sure. Happy to dive in.

To start, your recent patent filing introduced AKTX-102 as a second ADC program. What does this milestone say about the scalability of Akari's PH1-powered ADC platform and its ability to generate multiple differentiated pipeline assets?

Yes. Well, thanks for the question, Jenene, and the time here to give some context and perspective. It's a really exciting development for us on AKTX-102, the second product candidate we want to move forward, second antigen target for the ADC. In particular, this shows the power of the payload. We are a novel payload company. We've always said we believe our payload can be attached to many different types of antigen targets and molecules and create a library or pipeline of ADC molecules. And so this is the power of the payload coming to fruition.

Obviously, our lead ADC, AKTX-101, a TROP2 ADC is moving well along its way to potentially get to the clinic soon. This shows that our biology, our research continues across other novel antigen targets. In particular, we'll speak to in a minute, we think the CEACAM5 target is very unique, very differentiated and very difficult for some interesting biological reasons. And so when we take our novel biological insights and then are able to kind of create a next-generation best-in-class antibody, and then couple that with what we believe is the best-in-class payload, that's going to be really a transformational kind of molecule opportunity we have to attack certain types of cancers.

So Abizer, my next question is CEACAM5 has been a long-standing but challenging oncology target. So how does Akari's novel antibody construct combined with PH1 spliceosome modulating payload enable a differentiated approach compared to prior CEACAM5-directed therapies?

Yes, great question. So this is where we're really excited about the novel biological insights we have around this target. So you mentioned CEACAM5. It's not new new, but it's been a very difficult target, very relevant, in particular in some of these cancers like stomach cancer, colon cancer, pancreatic cancer, super high unmet need in those cancers. And this target is a really relevant way to attack those cancers with an ADC.

The problem is CEACAM5 is what we call a target that sheds. It means is it expressed in the tumor, but it often sheds into the blood. And so when you try to make a molecule targeting it, it's a little confusing. It's like is it targeting the blood or the tumor? And the way the target antigen set up, just the complexity of the biology, where you actually target to be most effective?

So knowing that, that's some of the problems that we encounter that are there with this target, even though it's a really good target. So we figured out certain ways to circumvent that. I can't speak to all the details, and that's covered in the patent about how we're doing this. So essentially, we have found a way to kind of engineer around those constructs and those problems in a new novel antibody that we believe will address those problems that others have not been able to address, and that gives us a competitive advantage as we move this high-value target into an ADC.

So you take the antibody design, that's half of it, and you combine it with what we believe is the best payload moving forward potentially, and we have a really unique ADC construct, not only on the payload side, but in this case, also on the antibody side that is differentiated to any CEACAM5 ADC that's put into the clinic today.

Excellent. It sounds like this could be an important breakthrough in the space. So we'll definitely keep an eye on your progress there, Abizer. So next, as Akari expands its pipeline with AKTX-102, how are you prioritizing execution on your lead program, AKTX-101, as it advances towards IND or CTA submission and first-in-human clinical studies?

Sure. Great question in terms of where we're spending our effort, where do we spend our resources. And so first and foremost, AKTX-101, our lead TROP2 ADC is our primary focus and our key area of attention and highest priority this year. As we mentioned in our press release last year, we started IND-enabling activities with our high-quality partner, WuXi. That is work underway. We're targeting a very tight time line to get to an IND CTA filing by the end of this year to hopefully start a clinical trial soon after that, our first in-human study. That is the focus and attention of our team.

That being said, we're able to move along a product in a program like AGTX-102 on -- in a very limited budget way and limited resource way because it's still earlier in discovery. So it doesn't require the heavy lifting of big scale manufacturing, nonclinical GLP tox. Those are things that 101 is going through. The 102 asset, we can move along at a much lower kind of investment and resource base because it's a little earlier. So it's a way of kind of walking and chewing your gum, but we can do both as long as we make sure we're walking and walking pretty fast and paying attention to where we're going.

Excellent. And so you're so talented to be able to do both.

I try everyday.

Absolutely. That's great Abizer. Thanks for that background there. Another question I have, and I think this is going to be top of mind for investors. So this latest patent filing further expands Akari's IP estate across payloads, antibody design and ADC architecture. How should investors think about the role of this growing IP portfolio supporting long-term value creation and potential partnering opportunities?

Sure. Great. So what I would say is this patent portfolio continues to grow. The ADC patent we just filed on the CEACAM5 is a unique extension of our novel biology and our ability to build really high-quality unique antibodies, that falls on top of our novel payload IP estate that we're building. And so as a reference, we filed 3 patents last year. In particular, we already have patent protection on the composition of matter for the payload, which is very unique, our RNA splice targeting payload PH1.

But what we did last year to supplement that is really patenting around the modes of action and how the payload works. Those are more general that are outside the actual composition of matter because we've seen unique modes of action of this payload. We are filing intellectual property to protect that so that others can infringe on that. And so this is where we think our payload has a lot of legs, not just on the actual structure of the molecule, but how it actually works and it works in many different ways.

It has a cytotoxic ability. It affects what we call splice-driven variant cancers, that's the RNA splicing. It has unique immuno-oncology properties, either as a single agent or with checkpoint inhibitors, the most successful class of immunotherapies. So that's the bedrock of our IP and the CEACAM5 IP is just adding on top of that around a great antibody that can be coupled with this novel payload.

Excellent. So Abizer, I know you love this question, why Akari, why now? I feel like you answered that throughout this entire discussion that we've had so far. But let's go more directly and kind of have a succinct response here. What key milestones should investors be watching across both AKTX-101 and Akari's broader ADC platform over the next 12 to 18 months?

Sure. So I'll kind of highlight there are big milestones and there are going to be milestones along the way. Some of them I can't speak to because they're a little bit confidential under embargo. So we -- in terms of what we outlined and it's in our corporate deck and materials, what we speak to is that we would like to have an IND or CTA filing by the end of 2026. That is our target. That would enable us to actually open up a clinical trial in a region of the world to initiate our first-in-human Phase I study.

So we think within 12 months, that's a big target for us. It's a corporate goal. It's a big area of focus, high priority, as I mentioned. And then subsequently after that, we hope within the 6-month time frame, so a total of 18 months out, we hope to get our first read of initial clinical data in our Phase I data. That would be safety, the dosing and potential activity -- clinical activity of efficacy if we can get some reads in certain tumor types. So think about that 12- to 18-month time line of getting all the filings ready and starting a clinical trial and getting some initial safety, potential efficacy activity data, that's what's going to happen in this next 12 to 18 months.

Now there are going to be milestones along the way. We are continuing to develop a robust package to file the IND that encompasses new preclinical data that will read out. We will talk about that throughout the year. We're going to present other really compelling preclinical data on our TROP2 ADC that we believe establishes as a best-in-class ADC. So keep an eye out for our press releases when we say we're going to present data at either research conferences throughout the year.

And then we also will be continuing to talk to regulators around our strategy. We might make some public announcements of what those outcomes are as we continue to get data for the filing to get to the clinical trial, we might release more aspects of that. So those could be these interim kind of milestones throughout the year as we get to those 2 big milestones, both in end of '26 and '27.

Excellent. Well, Abizer, 2025 certainly was an important year for the company, a lot of activity, really setting the stage for what seems to be an action-packed 2026. So congratulations. I cannot wait to have you back, and thanks for your time today.

And with that, this does conclude the Virtual Investor Meet segment featuring Akari Therapeutics. I'd like to thank Abizer for joining us today. And as a reminder, Akari Therapeutics trades on NASDAQ under the ticker AKTX. And if you like what you saw today, I encourage you to visit akaritx.com for more information on the company and to sign up, to follow the company, to receive their alerts, as well as follow their social channels to stay current on the latest information.

And you can also visit virtualinvestorco.com for our latest segments and events calendar. I would like to thank everybody for joining and like to wish you a great rest of your day.

Okay. We are ready to get started, and welcome, everyone, to the Akari Therapeutics Corporate Update Webcast. [Operator Instructions] Note that this webcast is being recorded at the company's request, and a replay will be made available on the company's website following the end of the event.

At this time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations or future projections. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the safe harbor provisions of the federal securities laws and are based on Akari Therapeutics current expectations, and actual results could differ materially.

As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports Akari Therapeutics files with the Securities and Exchange Commission. These documents are available in the Investors section of the company's website and on the Securities and Exchange Commission's website, and we encourage you to review these documents carefully.

So joining on today's call from the Akari Therapeutics leadership team are Abizer Gaslightwala, he is President and Chief Executive Officer; and Dr. Satyajit Mitra, he is Head of Oncology.

I would now like to turn the call over to Abizer. Please proceed.

Great. Well, thank you, Jenene, and welcome, everyone. We thank you for joining us today.

Go to the next slide, please. So I'm just going to give you a brief overview of what we're going to talk about today. I'll just give some opening remarks and a corporate overview for Akari. Then we'll also get into the payload overview for ADCs, kind of what the landscape looks like, and how we are a little bit different, but then we're going to kind of roll that out a little bit more with Dr. Mitra. He's going to walk through some of the really interesting data that was presented at SITC, The Society for Immunotherapy of Cancer about 1.5 weeks ago in Washington, D.C., where he'll do a deep dive into our novel payload and talk about what's unique about it and interest to focus on our splicing targeting payload and the ADC data that we presented.

And then I'll conclude with some follow-up steps on our lead asset, AKTX-101 and where we're going in terms of development plans and next steps, and we'll do some Q&A. And again, as a reminder, for Q&A, you'll be able to submit your questions through the webcast and our IR team will be able to field those to us.

Go to the next slide, please. So I just want to give a high-level overview. Many of you might be familiar with this already, but just as a brief orientation within oncology, which continues to be the #1 therapeutic area in the pharma biotech sector, antibody drug conjugates, or ADCs, continue to be the most popular and exciting modality to treat cancer patients. These have continued to be prominent in this news, as you probably heard and seen.

And as an example, there are over six, $1 billion, what we call blockbuster product, already that are ADCs across a number of different cancer indications, whether they're solid tumors or blood cancers, and this class is rapidly growing and accelerating as well with new products entering every day. And this market is expected to surpass over $30 billion shortly. And as we look at these ADCs, you hear some of these -- you see some of these at the bottom, some of the names you might be familiar with, you can see the different types of tumors to go after. You can see the respective sales just in 2024, cumulative sales worldwide, and these are continuing to accelerate.

What's interesting when you look at the payload that's used on all these blockbuster ADCs and importantly, on the right, which is all the ADCs and early to mid-stage development, you see two payload classes dominating, DNA damaging agents and microtubule inhibitors. And those are two kind of biological mechanisms how these payloads were, which are very similar to how -- exactly how chemotherapy, traditional chemotherapy works.

So yes, some of these ADCs use targeted chemotherapy, maybe different versions of the older ones. But these are the two payload classes that over 95% of all ADCs are using. And so although there's been tremendous success with these two payload classes, which again are versions of chemotherapy, and they've done a great job with the current ADC set, we want to walk you through why it's important to diversify this payload approach because as good as these ADCs have become, there's more opportunity to go beyond the current efficacy and safety profiles we see.

So let me walk you through why that is. Can we go to the next slide. So in terms of Akari, we're advancing ADCs beyond today's efficacy safety limitations you see today with urgency and efficiency. So getting to that first point, payload innovation for ADCs. Why do we need that? Well, as good as those ADCs have been, that we just walked through, there are limitations. Let's take, for example, an ADC class called TROP2, it's a target on many different solid tumors. And when you look at some of the current ADCs approved in the U.S. market for TROP2, what you see is some interesting stats, you see the median progression-free survival, which basically is the amount of time someone as a cancer patient goes about their tumor progressing. That means 50% of patients get less of response. And this response on average for these current approved ADCs is only about 5.5 to 7 months. So imagine roughly about 6 months a benefit you get with these ADCs.

Now it's better than where these patients are before. But 6 months doesn't seem to really move the needle for many patients and their families. We also see tremendous side effects still with these ADCs. As I mentioned, many of these ADCs use chemotherapy-like payloads, so you're going to expect chemotherapy like toxicities. And one of the more important things we look at both for a patient and a physician is dosing interruptions when a patient actually has to stop their dosing of a product because their toxicity is too bad. Well, that's bad because that means you're not treating the cancer. So when you look at the, again, current TROP2, ADCs, anywhere from 22% to 66% of these ADCs have to be dose interrupted in the clinical trials, where they were dosing patients. And that's a best-class scenario because clinical trials are just an objective experiment.

So imagine, again, the tolerability and safety issues. So when you look across efficacy and safety, there's clearly despite progress by these current ADCs, there's clearly opportunity to improve on both. And that's what makes us excited about Akari's PH1 splicing modulating payload. It is totally different than those chemotherapies we've heard about and talk about. It is -- it has a 1, 2 punch, and we'll speak more about that in a second.

It is cytotoxic, which means it kills the cancer cell that's targeted. But more importantly, it has a strong immuno-oncology action, dual action for the payload. And we know that immuno-oncology, the immune system is the best way to actually attack cancer, and we have a payload that does that in full totality. And we're going to talk about that data that was presented at SITC. So what you anticipate that very soon.

We also know from our preclinical data, this payload PH1 is superior when we've seen in preclinical testing to some of the current ADC payloads, and we have a number of data, and we'll walk through some of that as well in terms of some of that data that gives us conviction and confidence in this payload performance.

We've also seen in our initial safety testing that the payload for our ADC, this PH1 as a differentiated safety profile. We don't see some of the safety events and issues that we see with the current ADCs. And that gives us a lot of encouragement that hopefully we can improve that statistic around dose interruptions, and we can see better dose continuation, which means you're treating the cancer more readily. So this is the reason why we think payload innovation is needed in the ADC market to fully unlock the potential. And we have a great solution with our PH1 splicing modulating payload, which you'll hear more about.

Well, what does that payload mean? Now that Akari has a first-in-class leading best-in-class payload, we can actually start applying that, and we have our lead asset, AKTX-101, it's actually going after TROP2 as well as a target, and we're going to speak more about that at the end of the presentation. We believe this payload can be leveraged not just for AKTX-101, but across many other ADCs to create a pipeline of ADC. So we think there is a pipeline in this payload opportunity.

And we've already demonstrated preclinical experiments, and you'll see some of this shortly. We think this payload is super active in many areas. We actually filed some patents early this year because of that. We believe we're active in certain cancer mutations or oncogenic drivers of what they're called. They are pretty bad in certain cancer types. We actually find our payload is very effective against those, and we filed a patent around that. We also know our payload is very active in immune activation. We filed some patents around that in the fourth quarter, and you'll be seeing that data that was presented and part of that patent filing as well shortly.

And the last piece I want to kind of differentiate Akari maybe from other biotechs. How do we think about ourselves in terms of not only this innovation, but how we're bringing this innovation to market, and we're doing it with urgency of speed and efficiency of capital. And how are we doing that? Well, we're going to be using a lot of partnerships to incentivize speed to get to the clinic. And you'll hear more about that on the 101 program shortly because we think that partnerships risk shares and opportunities to get people with the same incentives and alignment to deliver results is more important than just paying vendors to do work. That also allows us to defer capital outlays until we get to value inflection points.

As we progress our pipeline, not only do we benefit but our partners benefit, and that's how it allows us to be more efficient with our capital. It allows us to advance our preclinical assets like AKTX-101 to the clinic at much lower cost than a traditionally seen from ADC development and really allows value inflection for Akari. If we can get these assets quicker into the clinic, we did get a valuation for Akari that could approach what clinical stage ADC companies are today, pending we generate positive Phase I data into the clinic soon, so that's the Akari story. We're really excited about the payload innovation, but how we're actually executing against that payload innovation to bring this new type of ADC to patients hopefully in the future.

We go to the next slide. And with that, I want to transition to Satyajit, Dr. Mitra is our Head of Oncology, and he will walk you through the exciting data around the payload, set up some background as well as walk you through the SITC data that we just presented with great anticipation and excitement. Thank you.

Thanks, Abizer. Next slide, please. So Abizer talked about how exciting the ADC field is. And my first slide is about the limitations of ADC. So don't get me wrong. It's the fastest-growing plus of modality, which is upended traditional chemotherapy and appended many targeted chemotherapies on the way to success. So -- but as is often the case with something a modality that leapfrogs very quickly, it creates a vacuum in its space. So since 2013, HER2-positive breast cancer and gastric cancer patients were receiving the drug, Kadcyla.

And many years later, this was replaced by a drug that performed better and HER2. Then the question immediately arises, what do you do in a post -- and HER2 setting? Is the target still relevant? Do the cancer patients still express HER2? Do we give HER2 ADCs with different payloads? Well, early studies seem to suggest that the resistance is due to the payload. So you can follow a HER2 ADC with another HER2 ADC of a different payload class and you can still expect activity.

But if you follow the same -- different target, ADC against a different target, you have -- with the same payload or the same payload class, you may not capture that activity. So this immediately posed an important question, where do resistance -- where does resistance come from? Where are the mutations that give rise to resistance. And you can see in various patient pools, there are mutations in topoisomerase that make it refractory not only to the payload -- ADC with the same payload that it has been treated with, but also potentially to the payload class.

So anyone who's been treated with an irinotecan version, the mutation makes it refractory to deruxtecan and reduces the binding affinity to something like exatecan. And this about 60 such topoisomerase is coming through the ranks in clinical studies. So this poses a big challenge in oncology, how do you sequence ADC after ADC?

The other problem is when you look at the resistance per se, and you look at the toxicity profile. One of the toxicity problems is that there is toxicity with a payload class. So irrespective of whether you treat with them any version of irinotecan. You have nausea, vomiting, diarrhea. You have gut toxicity associated with that payload plus. You're not going to walk away from them. There is -- you get less or more of that toxicity. As you -- engineer incremental changes around the payload. You tweak a linker here or there or you make more changes about the payload, you are still stuck with the toxicity of the payload class.

So how does one deal with that? You have to change the game. You can't play by the same rules and expect to win. So this screams out for the field to generate different payloads. And payloads of a different class altogether, different mechanism of action altogether. So what we did is we started working on a novel payload class. And we asked ourselves the question, what are some of these hallmarks that we should capture. One important hallmark is cytotoxicity itself.

We should have the ability to kill cancer cells. In addition to that, we thought that there was no better modality than activation of the immune system. And looking at the success of checkpoint inhibitors across the spectrum in multiple indications where it brought out efficacy, unlocked efficacy of 30% of all patients, we decided to -- this is our Godzilla. We need to get this in our payloads. So we engineered and look for biologies that were compatible with this philosophy, and we discovered splicing at the heart of intersection of both these two, cytotoxicity as well as activation of the immune system.

Then the problem with trailblazing and being first in class is you don't know what problems do you expect. And all the patients that are developing resistance to either microtubule inhibitor class or topoisomerase inhibitors class. They have a common problem, and that is overexpression of efflux transporters, you do your best to dose the patients get the drug levels to the extent that it causes tumor regression, but then the cancer cells adapt by overexpressing these drug Efflux Pump and pumps these payloads out of the cancer cell.

By being second, what we can do is engineer our payloads and look for payloads that are refractory to drug efflux pumps. So we tackle this problem by basically stepping outside the box and going into splicing biology.

Next slide, please. So what is splicing? You've heard the Central Dogma DNA to RNA to protein and -- but in that, a very key step is that of splicing. Splicing impacts about 80% of all human genes that have non-coding regions in them. And these are precisely spliced out before functional proteins are made. If these proteins are not excised properly. Then there's a gate check mechanism called nonsense mediated DK, which takes care of the proteins that are going to be misfolded or misspliced. And as a result of that, these never want to make functional protein. What we do with the splicing modulator payload, ADC, is that we throw a wrench in these works.

By throwing this wrench, you are impacting hundreds of proteins that are vital to the cancer cell and therein is your cytotoxic mechanism. Some of these proteins will misfold and come up the endoplasmic reticulum and the protein factories. And that results in death by unfolded protein response or ER stress.

Finally, if by some miracle, you do -- the cancer cell does survive this onslaught, then these misfolded proteins, these unnatural proteins called neopeptides, they are presented on the cancer cell surface. And these look like foreign proteins to the immune system. So they light up the cancer cell, like Christmas lights, and this activates the immune system and kicks it into high gear.

Next slide, please. So we've heard the story of every chemotherapy or every ADC payload, basically saying we kill cancer cells and increase the level of immunogenicity, or it releases neoepitopes and activates the immune system. But the question is how much? How much do you -- purchase do you get when you tweak the biology towards production of these foreign proteins called neopeptides.

So in this comparison, on the left, we want to look at a payload, which targets microtubule and this is called DM4, and it's found in the folate receptor ADC, ELAHERE. So we're able to look at how much new epitopes that ADC, that payload mix and compare it to ours, which is on the right. So this is a transcriptomic study. You're looking at all RNA species across the board in an unbiased manner. All the strike through the middle in black reflect genes that are unchanged, and anything above that is increased, anything below that has decreased. So in the blue, we appreciate all the genes that are going to be depleted from the system and cause cytotoxicity. And you can find that there's a three-fold increase in the number of depleted genes by our payable. So 199 versus 660. So what we see here is a more potent cytotoxic mechanism with respect to the DM4 payload from the splicing perspective.

Now if you look above and look at our focus on the red dots, here, we are asking a question, where are the proteins that are not found in the human proteome, so these are like foreign proteins. These are like neoepitopes. And when you look at these sequences, you find that there is almost a tenfold increase in the payload induced neoepitopes. What that means for us is that while our payload is also cytotoxic and will create neoepitopes by all the classic mechanisms that other chemotherapies and ADC payloads do, we will produce a different class of neoepitopes of the frame shift category.

So now let me talk you through how these two are different. Neoepitopes from cancer cells are generally something a carbohydrate residue that is higher in cancer cells versus normal cells, or it is a property of two sequences coming together. And you have a two amino acid difference at the junction. But a splicing modulator causes a frame shift for all the amino acids downstream of that where you throw the wrench in the works. So it has the impact of creating hundreds of amino acids that are different. So what I'm telling you is that all neoepitopes are not created equal, and this class of neoepitopes or frameshift neoepitopes, which are induced via payload increase the antigenicity and these basically kick the immune cells into high gear.

Next slide, please. So this is one of the slides that we presented at SITC. And here, you can appreciate what this payload, how it changes the characteristics of the same antibody. So this is -- we have now -- we spoke about Kadcyla, right? Now we're going to go head-to-head against Kadcyla, plus/minus anti-PD-1.

In a colon cancer model, which has HER2, so what we have done is we've treated these mice bearing tumors for a period of only 14 days with the ADCs, and we followed it for a period of 5 months to see tumor regression. And when you get tumor regression, you want to know the mechanisms behind it. If there's an immune mechanism. You want to know what that is. If you see different rates of complete regression, we want to understand why that is.

So over to the right, you see all the individual tumor growth curves in our mice experiment. What we see is that our ADC called Tras PH1 gives you nearly the same efficacy, captures the same efficacy of that of Kadcyla and slows down tumor growth. But in addition to that, it causes a small rate of complete regression, about 11% of the mice. And this results in the tumors going away completely. That's what we call complete regression.

Now in this experiment, the checkpoint inhibitor, anti-PD1 worked really well and cured 33%, 1/3 of the mice of their tumors. And even in that backdrop, our ADC combined very well with checkpoint inhibitors unlock further efficacy. So if you look at our combination, Tras PH1 plus anti-PD1 and compared that to Kadcyla, we find that there is a near doubling of complete regressions, 14 out of 19, 74% versus 42%. This was behind some of the efficacy that we observed. So now let us find out why we saw this efficacy. By doing something called immuno profiling, looking at the immune cells, when the cancer aggressions were happening. And we find that each arm was associated with a different immune mechanism.

Next slide, please. So our single-agent ADC did something, which was really unexpected. As expected, we reduced the frameshift neopeptides. That's the mechanism of the payload. But as a result of increased neoepitopes we found all the antigen presenting cells, the macrophages responding and getting activated. These then presented these antigens to B cells and B cells made anti-neoepitope antibodies that was the primary mechanism in the Tras PH1 alone arm. We saw some changes, and these were anti-neoepitope based changes. There were no surprises in the anti-PD-1 arm. The anti-PD-1 arm had an effect on T cells. It unlocked and unleash their activity. And that is pretty much expected from anti-PD.

But when we put anti-PD-1 and Tras PH1 together, we not only saw both the individual activities of anti-PD-1 and Tras PH1. We saw something in addition to that. And that is in our jargon is what we call true synergy. We saw activation of a kind of lymphocyte called gamma delta T cells. And gamma delta T cells are the 1 of 2 lymphocytes, other than natural killer cells that are capable of finding tumors and killing them without the need for antigen-presenting cells. So they are epitope-independent. These -- there is an entire industry of people who make gamma delta T cells, train them and reintroduce them back into cancers to unlock efficacy.

And we are getting those gamma delta T cells activated downstream payload. So basically, I want to summarize this section by telling you. In terms of getting differentiated efficacy and differentiated safety, one has to venture out of the box, to get outside the safety zone of the conventional payloads. You have to try something different. You cannot get the same activity. You cannot expect different things by doing the same kind of sequence. Incremental changes are not going to bring about unleash a totally different spectrum of efficacy or a different spectrum of safety.

And by working on this payload over the years, we have found that this payload irrespective of which target, we hook this payload onto. We captured the immune phenotype as well as the cytotoxicity. So we are very, really excited to try this in multiple cases. So we presented this data at SITC, and it was received very well. I mean in the -- at the talk, there was the first person of the mic said just spontaneously this is ingenious. And then followed with a tough question. You would expect that.

We got an overwhelming response at our poster session. All the usual suspects from pharma, came to a poster looked at it, something new and novel on the horizon. We excited academics as well as MDs alike. We had people from academia offering ideas and suggestions by the minute. And they just couldn't help themselves. They're going on and on with these suggestions and making mental notes. And KOLs, very reputed KOLs who done 50-plus clinical trials. When are we going to get our hands on this ADC, on this payload to try this for our patients. And all I could say is soon, soon, soon. So anyway, luckily, I didn't have -- I mean, I don't have -- I didn't have an answer for them then, but Abizer has an answer for you now.

So I'll hand it back to you, Abizer.

Great. Thank you, Satya. That's a good segue of where I'm going to go through. Let's just stay here on this slide for a second. I just want to recap, Satya, thank you for that really comprehensive overview of the history of ADC payloads, the limitations and the whole design principles of you and the R&D team of why you came up with something to go after RNA splicing biology and the payload that's been developed through years of testing and these fantastic results. I think if I were to take a step back, I would say these results are unprecedented for any ADC payload because in any of the literature you look at, no payload has demonstrated this type of immuno-oncology effect is very unique.

This is charting new ground, which is why the SITC organizers wanted us to have a main oral presentation and a poster. And what I think is really interesting just to kind of -- I'm not an immunology expert, but when I look at it, I think of these as two puzzle pieces. When you think about our ADC payload and what it does versus the checkpoint inhibitors, which are the most successful class of agents in oncology at $50 billion plus and growing.

Our agent activates this innate kind of immune system, which is one type and the antibodies, the humoral B-cell antibodies as well. And then the checkpoint inhibitor are the T cell. So when we marry them all together, we're getting this really unique response of innate adaptive, which are T cells, innate the macrophages and neutrophils, the adaptives of T cells and the humoral of B cells.

I don't think any payload with any immunotherapy has ever demonstrated that kind of pleiotropic broad-based effect, which gives us continued excitement around we have something novel, and how we want to progress it. So thank you for putting that in really simple terms for us to understand. Now the question is how are we going to take this in? As Satya said into clinic and start demonstrating these results as Satya said this payload dynamics can be generalized to any antigen target. Hence, why we're really excited. The data that Satya just presented was an HER2 antibody that we put our payload on. That was a test prototype.

Let's go to the next step and talk about AKTX-101. This is our TROP2 directed ADC. We have a lot of good translational data preclinically that gives us good insights into where we want to go, and what we want to do is we actually want to take this product now and do the final stages of manufacturing -- final manufacturing scale-up, and what we call our toxicology final safety studies. We've done preliminary studies. And that is at the last step before you enter human clinical trials. These are the big steps. These means that you have a really good molecule and you're ready to go prime time in a sense. So that's what we're starting. We call them clinical trial enabling activities or what your IND enabling that's a filing with the FDA to kind of start clinical trials. These are the activities you see on the top, the CMC and nonclinical based, manufacturing and final safety studies.

And then that will lead into us hopefully starting this Phase I initial first in human, that's FIH study in late '26, early '27. And our target area where we want to go into, in particular -- sorry, we would do this first in human and then potentially expand this into a really specific tumor type. In that specific tumor type is urothelial or bladder cancer in the second-line setting.

So what I want to kind of emphasize there's a couple of points. If you remember at the beginning about what Akari is, we're not only about payload innovation, we're also in a sense, trying to rework the biotech model innovation on ADCs. We want to get there in a very accelerated time line. If you were to just ask other ADC companies, this is a pretty accelerated time line to get to where we are now from a lead product candidate to actually starting a clinical trial within a year.

But we're also doing it in a way where we're bringing partners in to help us defer capital outlays and does it in a very efficient way relative to the traditional model of our products are brought into the clinic. So we're excited that we're not only bringing innovation on the ADC side. We're also just trying to innovate how we actually -- on the business side, how we progress things in different ways with risk sharing with partnerships, with shared incentives and capital efficient ways as well. And so we're really excited about this kind of process to get to the first-in-human trial specifically.

So with that, let's go to the next slide. I'll just kind of summarize. So I think as you heard, we'll tell you again, why they need for novel payloads. Well, as you heard, as I mentioned and Satya really talked in detail, when you look at the current ADCs as good as they are, there are limitations, both on the efficacy and safety side, and we use the TROP2 ADCs as an example in terms of the efficacy limitations and safety tolerability. This is true of other antigen targets, other antibodies and those payloads, which are only 2 classes.

And that leads us to why we have a splicing modulating payload and what we put on to AKTX-101, our lead molecule directed against TROP2. We think there's continued unmet need in this TROP2 expressing cancers. And as I mentioned, maybe early in the slide, we talked about the urothelial second line. Well, the reason we're thinking of second line is exactly the reason Satya mentioned because many of the patients in the front line have developed resistance or lost efficacy to the first-line ADC, which uses a microtubule inhibitor.

So exactly the reason we're seeing Satya talk about that theoretically is playing out in the market, and we see a growing pool of these refractory bladder cancer patients. We think that's a unique opportunity for us to go after. But we're not done there. We think TROP2 has a lot of lives. We know we could potentially go in gastric cancer. We have some really compelling data. And lung and breast are also known as potential strong areas that we could take our ADC into as well. And that's based on the robust efficacy we've had.

So a lot of broad potential for our lead ADC. And that time line, I talked about to get to the first-in-human clinical trial data. We'd like to hopefully get more in the 12 versus 15, but we think that's the window and that's on a very accelerated time frame in a capital-efficient way.

And I think the take-home is ultimately, we get into the clinic. We prove some of this preclinical data in a human clinical trial setting. We think that is a really attractive value inflection for Akari that gets us into a different space, comparable to other early-stage clinical ADC companies.

So with that, I really want to thank you for your time today. And we're going to open it up for questions and Q&A. And Jenene from JTC will help us navigate that.

[Operator Instructions] So our first question is from James Molloy. He's a research analyst with AGP.

So these are -- there's three questions here or three parts to it. I'm going to read all of it and then we can break it down because I think it's important to put it all together. So the question comes in, how would you characterize the current partnership environment? Are there any partners currently in the data room or under NDA. And there's been some recent high-profile M&A in the oncology space, J&J and Halda and for $3 billion, Genmab and MRUS for $8 billion and has this activity increase interest around AKTX's portfolio.

Sure. So I think I remember the second and third. Can you remind me the first -- sorry, the first one was...

Sure. How would you characterize the current partnership environment?

Yes. So I think the partnership environment continues to evolve. I think you're seeing a variety of different partnerships you're seeing outright licensing and acquisition molecules. You're seeing company acquisitions, the Genmab one was mentioned as well. So we think there's actually increasing deal flow and activity, maybe it gets to the third part of the question. I think in particular, you see ADCs in oncology is still bright spot in the biotech sector, which gives us a lot of excitement and excitement in our plan to move forward.

You saw a lot of ADC deals in the first half of the year, just recently in the last 4 to 6 weeks, if not broader, you've seen a number of deals on the ADC, whether they're financing, whether they're acquisitions or licensing by big pharma or not. I think it continues to show the excitement around targeted therapies, ADCs, in particular. So we're pretty encouraged. I think the second part, obviously, you cannot disclose confidential information around partnership discussions we have. What I can say is we enter a lot of both nonconfidential, and we do have a number of confidential discussions we're having with potential pharma partners. Obviously, I can't give any more details than that, but we are active.

And I would say the reason we're active, and you can imagine how many inbound some of these pharma companies get. It's a splicing modulating payload. What Satya just talked about, that is stopping power that gets people to look at it again, and that's why people talk to us both on a non-con and confidential basis to explore more about what does Akari have and why does it look different? And wow, this does feel different. And these aren't companies that are new to ADCs. These are companies that have experience with ADC. So the fact that we're getting our foot in the door and having these conversations, again, speaks to the uniqueness and novelty and innovation on this payload.

And I think [indiscernible] commented on some of the deals, I mean, I think you look at the Genmab deal, obviously, but that was a Merus was a bispecific, I believe, a little bit different technology begin around targeted therapies in oncology. But I'll just mention Genmab in general, some of the bets they made may not be playing out. And I'm not saying they made a wrong bet, but just the ProfoundBio acquisition they did a couple of years ago, they've discontinued 2 out of 3 of those ADCs.

So I think even the thesis on how some of these traditional ADCs have played out, either due to the limitations Satya mentioned or competitive dynamics of competing against the same types of ADCs. Some companies are finding they need to change the playbook a little. And we think that's exactly a good segue for why our novel payload is changing the playbook for ADCs and gives us excitement.

I think I got them all. Did I get all?

I think you did. Yes. Great job. Okay. Our next question is, can you speak to the unmet need of bladder cancer and the market opportunity?

Yes, sure. I think it's a great question. And one might ask and if you're familiar with the bladder cancer metastatic, so there are many different types of bladder cancer. There's muscle invasive, non-muscle invasive. We're going to focus on the metastatic, which is the most severe unmet need, which essentially means the bladder cancer is spread, metastasis, other parts of the body, that's where the prognosis is the worst for patients due to the overall tumor burden.

In that setting, there has been significant advancements. So let me just kind of characterize. And after I give this, I'll have Satya to add any things I might miss on this. But when you think about this metastatic bladder cancer patient therapies like cisplatin, which is a platinum-based therapy, effective, but super toxic and limited efficacy, subject to resistance mechanisms as Satya mentioned for chemotherapy. That's been the frontline setting forever using cisplatin, maybe combinations of cisplatin. And then there's a bit of a revolution or change that happened in the bladder -- metastatic cancer and bladder cancer market.

In ADC product called Padcev, enfortumab vedotin uses a microtubule inhibitor actually change the landscape. And this is, again, I think, a success of ADCs that you had a targeted agent like enfortumab vedotin that went into metastatic bladder cancer showed some great data, both as a single agent in combination with a checkpoint inhibitor. And that is approved in the frontline setting and Padcev, enfortumab vedotin is more than a $1 billion drug, and it's on its path to do even more. It's moving into earlier lines, what we call a neo-adjuvant setting, which is when the cancer is a little less spread.

And so it's a great success story. That being said, as great as the data is, and what Padcev, enfortumab vedotin has done, it targets an antigen called Nectin-4, which is different than the target we're going after, both targets are highly expressed Nectin-4, and TROP2 are very highly expressed in bladder cancer. As good as that data is when you look at what we call, again, the median progression-free survival from their pivotal trial data on combination therapy, it's about 12 months. And that is a big advancement from where cisplatin was, which is about under 6 months. So it has made significant inroads, but think about 12 months for a cancer patient.

When we say median, that means 50% of patients relapse less than 12 months and 50% relapse later than 12 months, that's median. So if you're a cancer patient, yes, that's an advancement, but you're only talking about maybe less than a year for half -- you're 1 out of 2 that may be less than a year before your tumor is going to continue to progress. And that's not a great long-term prognosis. So we want to change that. So there is now a growing pool of patients that have taken Padcev and Padcev have another combination agents and are probably relapsing. And we know this pool is growing. And so that's exactly that target population. And it's similar to what other companies have done and strategies that you go after refractory populations with super high unmet need that are not refractory to an ADC, refractory to chemotherapy.

And again, as Satya mentioned, going after those same patients with the same payload like a microtubule inhibitor, probably not going to work because they become resistant. So that's exactly the perfect setting for us to take a splicing modulating payload like ours into and we have a tremendous amount of preclinical data that's probably our strongest potentially in this setting for bladder cancer. So hopefully, I gave some perspective of the unmet need, and why we're excited, Satya, I just want to turn it over to you to add additional thoughts and ideas on that.

I think you captured most of it. The only thing I would add there is in -- the mechanism of resistance there, the reports are basically not you have some amount of nectin-4 loss, you have MDR overexpression. So it's a good thing that this payload has been optimized for nonbinding to MDR. And it's against a different target, which overlaps in expression in about 80% of all urothelial cancers that express nectin-4, so that being the case, you have now an opportunity to treat patients where there is inflamed setting, which responded to PD-1 and increase the neoepitopes in that setting, so to unlock further efficacy. So it's a good place to be in, in terms of frequency of high-expressing target. And it's a good place to be in with respect to the -- how hot the cancer setting is.

Yes. That's a great additional point, Satya, although we might look initially as a single agent in this population, it gives us optionality to actually bring forward the combination data with an anti-PD-1 or checkpoint to get the kind of results we saw preclinically, we'd love to replicate because that could be the long enduring efficacy we could see and the unique kind of profile of our payload really comes to fashion. So again, that's exactly the vision we want to go. We want to go into these hot tumors, which are more immunoactive and bladder cancer is one of these. So thank you for adding additional perspective that builds on the SITC data.

Next question comes from Aydin Huseynov, he is a research analyst with Ladenburg Thalmann. His question is, can you help us better understand the differentiation of AKTX-101 from Trodelvy and given both our TROP2 target, where do you think AKTX-101 presents the best opportunity?

Yes. I'm going to give maybe a high level, and I'll ask Satya to walk through the more details. So Trodelvy is a TROP2 directed ADC. It was the first approved. It's actually a pretty successful drug. But if you look at it's over $1 billion in sales, it's approved in the breast cancer setting, two major areas, triple-negative breast cancer and then another subset of breast cancer called hormone receptor-positive, HER2 negative. What Trodelvy is, it is an antibody against TROP2, it uses the payload called the -- it's a topoisomerase I inhibitor. It's a cousin of irinotecan, which I think Satya mentioned has its own toxicity. So by definition, that payload will have very similar toxicities. When you look at its package insert, it's got Grade 3. So to get to the differentiation point, it's got great box warnings for neutropenia, which means low white blood cell count high infection rates, potentially, it has high rates of diarrhea, and some other GI issues, those are Reno-TCAM-like side effects, if you're familiar with that chemotherapy. It's a similar set of side effects for this payload. And there's also a linker that they use that I'll let Satya explain that's different than the way we're using. So it's around the payload is very different, has some of those historical legacies of topoisomerase I and the linker strategy they're using, we would probably say and others would agree is maybe not optimal that creates other side effects, but I'll let Satya maybe describe in more detail.

So there are a number of differences and in our approach to Trodelvy. Trodelvy is basically the active moiety of irinotecan. SN-38 booked onto an hRS7 antibody via a CL2A linker, so this linker is acid-labile. And by the nature of the release of the payload is in the extracellular million. So whenever you go into a tumor, the environment is generally more static than the rest of the body. So it deploys there.

But no matter how good you are at deploying the payload at the decided location, there is always leaching of payloads from the tumor and exposure to organ. So you get organ tox and some of the gut tox is what Abizer rightly pointed out. Our ADCs are non-cleavable. And they only deploy in context of the target that is expressed only on the cancer cells. So we are trying to partition the payload specifically to the cancer cell. And we've taken a lot of precaution to prevent this payload from causing systemic issues.

And this is because of, obviously, of the immune phenotype. We want to make sure that there is no off-target effects. So you get a lot of off-target effects in Trodelvy, which is in tune with the bystander killing, but we have reduced that in order to get less immune flare-up. We do get bystander activity separately from immune system when we bring immune cells into the tumor, they take care of the heterogeneity problem. They target the tumor -- the target non-expressing cells as well as the target expressing cells, both equally. So in that way, we countered bystander problem in a different way through an immune bystander approach. So very differentiated.

So I'd maybe add a couple of points. Thank you, Satya, for giving it a little bit more technical scientific explanation. So essentially, we avoid collateral damage, the way we've engineered our linkers and payloads. We try to avoid that collateral damage. And we also -- because of our payload, we actually cause immune activation in a different way, hence, the kind of responses we get.

And just to kind of bring that home, when you see we've done some head-to-head work against Trodelvy and in the gastric cancer model, just looking at the pure side of toxicity. We have superiority to Trodelvy, in a gastric cancer preclinical model. So that gives us a lot of conviction that yes, this payload is super active, and it's capable of being the lead TROP2 agent at least in this preclinical model of gastric cancer.

Our next question is from Viju Gupta. He's a translational scientist. I just lost my screen, there we go. At WashU, Viju says great information, there are two questions. Number one, is your mouse model, a subcu model or orthotopic? And number two, PH1 being related to statins, do you anticipate effects of cholesterol pathway?

I'll defer these to Satya. Why don't you go ahead take them, Satya?

Sure. The first part of the question, we typically test our ADCs against tumors that have grown subcu, although we are not opposed to doing the old orthotopic experiment. But in this case, whether we're doing urothelial models or gastric cancer models, these are typically subcu. The second question, whether PH1 being related to statins. So I don't see a lot of similarity in the molecules per se. The cholesterol molecules will have that perhydrocyclopentanophenanthrene link system. This is very different from that. And even when we have done our nonhuman primate studies, we haven't seen any changes per se in cholesterol level, that seems to suggest that the cholesterol pathway may be important.

Our next question is how does PH1 perform if it's used alone without PD-1? And in a clinical setting with the sequencing of therapies affect its efficacy.

I'm going to let Satya maybe take that on, and I might add some following comments.

Sorry, I lost audio for there for a bit, Jenene, can you repeat that?

No problem. I'm happy to repeat it. So how does PH1 perform if it's used alone without PD-1. And in a clinical setting with the sequencing of therapies affect its efficacy?

That is actually a brilliant question, and that's front and center on everybody's mind, right? So the first part of the question, I'll try to break it up is, when you use this as a single agent, you do capture the cytotoxic efficacies. And you also see the effects on the innate immune system because that's their in mice in humans at baseline. So you see the effects on macrophages, you'll see the effects of neutrophils. So there will be some baseline killing and some baseline immune activation.

You won't get the purchase of T and B cells, most likely you won't get the activation of T cells without the anti-PD-1, but you do get activation of T-cells and anti-neoepitope antibodies, even in the absence of PD-1. So that was behind the mechanism, if you remember, in the Tras PH1 story. So we do get some activity. We do get long-term activity that we have seen in our HER2 models, which are xenograft. So by xenograft means they don't -- we use new mice there to allow the human tumors to grow out, and they don't have an immune system. So in those experiments, we do see very good killing, and it is in one of these experiments that we performed equally or slightly better than Trodelvy in the gastric setting, as Abizer pointed out.

So the second part of the question is about ADC sequencing and why that matters. Typically, when you administered anti-PD-1 and you give ADC, you're performing concomitant dosing and concomitant dosing means you're giving both these agents so that there is maximum overlap between the exposures of anti-PD-1 and the ADC. And this is to make sure that there is -- it unlocks each other's efficacy.

We have done experiments in urothelial bladder setting, where we have given a dose dense regiment of anti-PD-1 following the ADC treatment to see if the effect of neoepitopes translates to activation. So in these experiments, anti-PD1 did not give any efficacy on its own. The tumor growth curves were similar to control, but you get about 50% TGI where you treat with the ADC alone.

But when you add anti-PD-1, following the ADC treatment, you see the curve dip. And basically, you get -- you're unleashing more activity from T cells in this setting, even though the anti-PD-1 arm by itself did nothing. So I think there is an opportunity with this payload to sequence anti-PD-1 after ADC treatment to get some kind of activity. And we have seen that in preclinical experiments.

Yes. And I'll just add a couple of points. I think that's a great explanation on the sequencing because that data was pretty unique when we did before and after kind of regimens, and you saw a unique difference. I think the other thing I'll just add on the single agent what also impresses me like, obviously, the B cells, and we activate the B cells, that's very unique to our single-agent activity.

The macrophages, which are those immune system cells in the tumor microenvironment. What's interesting around cancer is that cancer is very smart. It finds a way to take those macrophages, which are typically the first responders in a sense to any kind of things different. And it subdues them into becoming tumors impressive. So they actually don't do their job. If cancer kind of signals to them not to do their job.

And what we found is that we actually were able what we call repolarized those macrophages to do their job. So we got them to wake up from their trans and the cancer cells put them in, and we found as a single agent, they got repolarized to do their job, which then starts again create activity of the immune system. That was as a single agent, again synergized, when we add a checkpoint inhibitor. So again, we have potent single-agent activity, whether it's cytotoxicity or immune activation, it just gets to really see the full light of day with the checkpoint inhibitor, Satya mentioned.

Great. Okay. These are -- we have about 2 minutes left. So I wanted to give you the opportunity for some closing remarks before we end the webcast.

Sure. First, I'd like to thank everyone for joining the call today. Hopefully, you walk away with more information around why we're excited around this novel payload, the need for novel payload. ADCs are hot, and how we can continue to build on that and take ADCs to the next chapter and change outcomes for cancer patients. And hopefully, you walk away with a clear conviction of the plan we have to get there. This is not great science for the sake of science. It's science that we're going to apply to get to the clinic and make a difference for patients that we have an accelerated plan to get there as soon as we can in a capital-efficient way. So I want to thank all the participants for joining us. Thank you, Satya, for a great presentation. Thank you, JTC, for organizing and helping us today.

Great. Absolutely. So this does conclude the webcast. As a reminder, the replay will be available on the company's website. We did have some additional questions, doesn't have time for them, so we will get back to everyone that submitted questions following the call.

All right. Thanks, everyone, and have a great day.

Okay. We are ready to get started. Good afternoon, everyone, and thank you for joining us today for another virtual investor closing bell segment. My name is Jenene Thomas. I am CEO of JTC IR, and I will be the moderator for today's event. I am very pleased to be joined by Abizer Gaslightwala. He is President and Chief Executive Officer of Akari Therapeutics. Welcome, Abizer.

Thanks, Jenene. Thanks for having me here today.

We are so excited to showcase Akari on our platform today and share your story with our audience. And before we get started, I do want to remind our audience that Akari Therapeutics is publicly listed on NASDAQ and trades under the ticker AKTX. So we're not going to wait any longer, Abizer. We've been looking forward to having you on. So let's dive right in. I'm going to turn it over to you for an overview of Akari.

Great. Well, thank you, Jenene, and welcome to everyone who's joining live and those of you watching the recorded, thank you for taking the time to watch. So I would like to just maybe go through the disclosures, but let's get to the first page. We are Akari Therapeutics, and let me reemphasize our new vision and focus based on being an oncology company.

We're focused on innovating antibody drug conjugates or ADCs, as you hear the term. And I'm going to focus on 2 terms as immuno-oncology therapies and for patients to be cancer free. And I want you to remember those 2 terms because we're going to reference those as we go through what the opportunities are and what our special approach is around addressing those with our unique platform and payload that we put on our ADCs.

You'll learn more about that, but immuno-oncology and the opportunity for patients to be cancer free. So with that, let me just give a corporate overview. As I just mentioned, antibody drug conjugates, ADCs. We are developing ADCs with what we call novel immuno-oncology payloads. Just as a reference, when we say ADCs, there's an antibody and think about that as a super smart guided missile. It knows exactly it's GPS, it knows exactly where to go in a very targeted way.

But what's the actual payload that's in that antibody or that missile, that's what's unique about what we're doing at Akari. We are developing very good missiles and those guidance systems, our own unique one. But more importantly, we're attaching what we think is the most innovative payload out there today.

We think it has the potential to redefine ADCs in the way that these current ADCs on market are not, and we'll speak to that in a minute. But that's the idea. It's what we -- our payload is called a spliceosome modulator. We call it PH1 and it's designed to both kill cancer cells and activate the immune system, which is why we call it immuno-oncology.

So then what does that mean? That sounds some fancy science and high level, what are we actually going to do with this guided missile with is really novel innovative platform, a payload called a spliceosome modulator. What we've already put it into specific programs. Our lead program, AKTX-101, it's directed against a cancer target called Trop2 that's expressed differentially or higher on cancer tumors. And we've attached the PH1 onto it. So it's a Trop2 target, PH1 payload ADC.

And we'll go into more detail when we go through the Trop2 program, but this is some of the specifics of that we're focusing on a number of solid tumors and have a clear plan on how to potentially get to a filing to start clinical trials in the second half of 2026. More to come on that. And then we have a second program where we've been able to take the same payload, PH1, and we're developing a novel antibody or that guided missile that we think is unique and potentially best-in-class and first-in-class from what anyone else is doing out there.

So we're going to create this really cool new guided missile, and we're going to put our PH1 spliceosome modulator payload. We don't want to disclose the target yet. It's still a little early, but we hope to -- we'll talk more about this a little later in the presentation as well. But you can see here we're focusing on a number of solid tumors, including colon, gastric and lung.

So before I move over and now you have a sense of the corporate overview and where we're going to go with these 2 programs and our spliceosome payload, I want to take a step back and make this more personal because cancer is personal for all of us. When you see these terms on here, you see bladder cancer, lung cancer, colon cancer, gastric cancer.

Many of you either know people in your family or friend circle that have had these tumors or if not these tumors, other types of cancers because there are many other solid tumors and blood cancers like lymphomas and leukemias. And that's exactly what we're trying to do. We're really trying to go after these tumors that have significant unmet needs.

So despite the advances in therapy across these, think about those patients in your family, and your friend network or people you've heard about through colleagues who've been affected by these and think about the outcomes that they have and think about their treatment paradigm and the difficulty it is. And we want to change that. And we think we have a great platform here to go after some of these tumors, maybe even more with more molecules or these molecules, and that's our opportunity.

So if you think about, again, as you go through this presentation and listen me present, think about that patient, that picture of that patient that you know through your network and think about what we're trying to do for that patient, and that's the opportunity and promise of what we're trying to do when we think our advanced ADC platform.

That's something I think about every day. That's something our team thinks about at Akari and keeps us motivated around ultimately what our mission is to help patients be cancer free. So as I just give an overview, again, we're going to talk about 2 programs a little later. AKTX-101 is our lead. It's pretty advanced. It has significant work done behind it. We'll actually share some really compelling, what we call preclinical data before we get into clinical trials or humans.

And we are doing what we call IND-enabling, which are studies that were at the big scale where you need to do things so you can make the product and it's safe -- very safe to support going into clinical trials. That's on target to get into the second half of '26 to enable us to start clinical trials potentially.

And then the AKTX-102, which we'll talk about a little bit more, we're still advancing that. Again, really novel science there where we think we can couple the advanced antibody or missile with our payload as well, and we'll speak a little bit more to that later. So I just want to give some background on the ADC class in totality.

So you may have heard about ADCs. Maybe you know some background. If you don't, here's the kind of net summary of it. ADCs are the fastest-growing and one of the most prevalent now cancer modalities of therapies that are being used to treat cancer patients. And you can see on this chart here, there are 7, what we call -- sorry, 6 products here that have achieved what we call in our industry blockbuster status, which is more than $1 billion in annual sales, which is no easy feat.

So ADCs have been on a long journey, and now they've reached this prime time and you see these products across many different solid tumors and what we call liquid tumors or blood cancers, you see ADCs now penetrating these markets because of their compelling design in the way they're constructed around the smart missile with the payload. So yes, there's success. And this class is expected to grow over $30 billion by 2032.

We think the potential could be even bigger given how many ADCs in development and what the opportunities are. We're just scratching the surface. However, if you look at ADCs, despite the success, which has been significant, what you see is that it's been in a pretty narrow way, and it's been limited because all the ADCs today and the ones in development, over 90% of them are using -- remember that payload I mentioned are using the same 2 types of payloads.

Those 2 types of payloads, one is called the microtubule inhibitor, you see on the chart on the right, about 23%, almost 1/4. And you see this big red called Topoisomerase I inhibitors about over 60%. It's cousin or DNA damaging agent, the 10%. So if you sum all those up, you're talking over 90%, 95% of all ADCs use 2 classes of payloads, DNA damaging agents, which include the Topo-1s or microtubules.

Well, if you go back to anything in life, if everyone is doing the same thing, would you expect a different outcome? Probably not. And so that's the kind of take home from this, that what Akari is trying to do is go outside that window, not follow what everyone else is doing. Because when you do that, you usually get incremental innovation. And I'm going to speak why incremental innovation is not what cancer patients need. They need what we call step function or revolutionary advancement.

And if you're going to focus on the same payloads that are already out there today, these 6 products in the left use 1 of these 2 payload classes, all the ones we talked about over 90%, 95% use these 2 payloads, you're probably not going to get a different outcome or it's going to be incrementally better.

So that's where we think we have a unique competitive advantage because we're approaching this with a different payload, a better payload and importantly, a payload that we think activates the immune system, which is the best way to potentially get patients to be cancer free. So as I mentioned on the slide before, I wanted to kind of give a sense of where that opportunity is.

So despite the success of ADC therapies in those lung cancer -- well, not even lung cancer because ADCs are not penetrated lung as much, but in gastric or if you think about breast cancer or you think about other areas in bladder cancer today, you look at those 2 payload classes, the Topo-1 inhibitors I mentioned and the microtubule.

And you see in general across some of these ADCs that are approved today, when they use a single agent, in general, you see a couple of interesting kind of generalizations that come about. Irrespective of the antibody, the tumor, the payload, you see a little less -- about 50% of all patients get a response. And a response is measured by something called in cancer objective response rates as the clinical trial term.

So when you define response by that term, it's about 50%, a little less than 50% of patients actually get a response. And when they do, that response, again, as measured by defined endpoint, is about 6 months. So imagine irrespective of the antibodies out there today and the payloads they're using these 2 classes, about 50% of patients don't respond, if you see on the red. And even when they do respond, they only get about a 6-month benefit. Think about 6 months. Think about that in terms of a patient. That's 2 seasons. Maybe that's fall and winter or maybe that's summer and fall.

Don't cancer patients want more than just 2 seasons, don't they want a year, don't they want 2 years, don't they want 5 years? Don't they want to see children graduate? Don't they want to see grandchildren born? Don't they want to see moment changing event -- life-changing things in their lives -- moment -- sorry, moment event in their lives. And so when you think about that patient need, it's not being met.

So despite the success of ADCs today, we're not getting the level of responses and the durability we want. So we call that duration, durability and the deep responses we want. And that's where we think we have the opportunity with Akari with our novel payload, the spliceosome modulator to drive these more durable and deeper responses.

So this is the opportunity that we can do better than the 50%, and we can do better than the 6 months. And let me show you some data why that gives us conviction about why we think our payload approach can do that. So again, as we think about our spliceosome modulator, this unique payload, PH1, as I mentioned, we kill cancer cells, but importantly, activate the immune system.

And we think this is the most important part. Our mechanism of action, which is called a spliceosome modulator affects splicing. I mean you think about splicing, think about a film, that's the best analogy. No one watches an uncut unedited film. They actually just spice it together because if you don't, the sound doesn't match with the video, the video is out of frame, none of it's in sequence and no one wants to watch a movie that hasn't been edited.

That's what we actually do. We actually prevent the splicing machine from doing its job. So our modulator actually interrupts that splicing machine from splicing and editing the RNA, which then helps kill the cell, but importantly, makes the cell foreign to the immune system in a really profound way, and that activates the immune system in a powerful way.

And it's so powerful. We actually see it synergizes with other immunotherapies, the most important class being called checkpoint inhibitors. So you've never heard of a big product called KEYTRUDA or maybe it's cousin OPDIVO. KEYTRUDA is the most successful oncology product ever. It's premised, it's based on immunotherapy, and it's based on activating the immune system.

It's a $25 billion product and the entire class that KEYTRUDA created is probably about a $50 billion product across 7 other similar products. So think about the opportunity, and they have not found a good partner to synergize with these checkpoint inhibitors. There's been a lot of work in our industry and biotech to figure out to make some bets, but none of those have played out.

And what we've seen in our preclinical data is not only do we activate the immune system, but we do it in a complementary way in a synergistic way with checkpoint inhibitors. So synergy is 1 plus 1, it doesn't equal 2, it equals 4. And that's where I'm going to show you some data shortly that says this is why we believe in the power of our approach in that it kills cancer cells while activating the immune system and amplifying the immune system when we put it with the most successful oncology class that we've seen in the history of our cancer therapies.

We've also engineered our payload to be next generation in terms of some of the payloads today. We want to make sure the cancer cell can figure out how to go after it and circumvent it. So we've engineered some resistance mechanisms. We've tried to reduce the off-target toxicity and improve the safety and tolerability profile. So I just want to give you that sense of this payload is designed with a lot of deliberate intentionality in terms of how do we maximize its efficacy while also improving its safety tolerability perspective.

So now we have some background on our special secret sauce, the spliceosome modulator. Let's actually talk about Trop2, our lead program, AKTX-101. As we mentioned, it's -- a Trop2 is the guided missile that focuses on that target, which is expressed on cancer cells, a number of different cancer cells. And we've advanced this pretty far in terms of we have a really good molecule.

We've characterized the molecule. We've seen really good efficacy and safety in initial preclinical studies. So that leads us to give confidence that we are going to try to start some additional activities later this year, moving into 2026 that would help us actually get to what we call a regulatory filing to start clinical trials. That is a big deal in cancer space because if you actually look at cancer R&D, many products never make it out of this phase.

They don't even make it to the phase we're in with AKTX-101, which is what we call a final product candidate because most of them failed the safety or efficacy or combination. So the fact we've advanced this far and now we're ready to take some steps to kind of make it even more formal is a tribute to the work that's already been going before on this AKTX-101 and years of work that have helped us not only advance the payload, but this molecule.

And where we're going to go with that? Well, if you go back to that slide I mentioned around the unmet need, we think bladder cancer is still a particular space with unmet need. And there is a product called PADCEV that's very successful there. It's a multibillion-dollar product, and it works well in the first line.

But unfortunately, people get that -- they lose their response. As you said earlier, about almost 50% of people don't get a response when they take single-agent PADCEV. And when they do get a response, they may only last for 6 months, and we think that's a perfect opportunity based on the data I'm about to show you that gives us a lot of conviction that bladder cancer could be a big opportunity for AKTX-101.

But it doesn't stop there. We think we have the bigger, bigger opportunities even in gastric, which is a horrible disease. If you think about a gastric cancer patient, if you know any, they often have their stomach resected. They lose the ability to eat food, which is a horrible situation for a patient that's trying to maintain the nutrition while fighting their cancer. So we think there's an opportunity to go in gastric.

And then in cancer, lung cancer is still the largest solid tumor, the largest tumor of any in terms of its incidence and its mortality, and we think there's a tremendous opportunity in lung cancer. And by the way, that's where KEYTRUDA made its mark in lung cancer immunotherapy, that is still its biggest source of business. And we think we can complement that and add on to that.

So why do we believe? Well, let me start with this bladder cancer preclinical data set. So this is an experiment on the left where we looked in bladder cancer cells, and we tested what we call a placebo vehicle. We tested an IO drug, which is a checkpoint inhibitor. And we tested our AKTX-101, which in this graph is labeled as Trop2 P.

And then we did something else. We actually took our AKTX-101, which is Trop2 PH1 and we added it to the checkpoint inhibitor. You see the respective lines, you see on the left this axis is called tumor volume or how fast the tumor grows in the mouse when it's implanted. You can see in the black, unfortunately, you can expect that the tumor grows unchecked and usually, these mice cannot survive once they're 3,000, they usually die or are sacrificed.

You can see that on placebo or vehicle, the mice progress pretty fast. You see some effect, whether they're treated with our AKTX-101 in the initial part up to 15 days or IO drug, the checkpoint inhibitor, but you see after while that effect stops and the tumor takes over and continues to grow.

So we do have an effect that's important. We have an effect in 15 days. And by the way, these models are not 100% predictive of human bladder cancer, but they're meant to be a surrogate. So we see some effect. We see a flattening of the tumor growth curve, which is a good sign that we can actually impact the tumor growth. But unfortunately, it escapes these drugs and it continues to grow.

What's really exciting is that you see the combo arm. You take our AKTX-101 and you drive it with a checkpoint inhibitor and you not only see the tumor flat line, but you actually see it regress. You actually see it get close to 0 within 3 weeks of initiation. Now often, these tumors grow unchecked after a certain period of time. But for 3 weeks, for us to maintain this tumor to 21 speaks to the synergistic effect we're having with the checkpoint inhibitor.

It speaks to the mechanism that I just mentioned around killing cancer cells, activating the immune system. That's what's really exciting. And when you've got to go to the right and you play out, these are called survival curves. You take those same groups and you put them on survival and you look at the survival, you can see that the black, as I mentioned, they usually die out when the tumor gets that big.

You see they have the shortest amount of survival in days. You see the single agent AKTX-101 and the IO are about comparable when you look at that. But you see a dramatic difference in the combination regimen in terms of overall survival. 60 for a cancer mouse is pretty long when you look at these models. So we're really excited about this data, which we think is super unique.

But this is not the only data, you can say, well, okay, I've heard there's other Trop2s out there, and you're not the first to market to compare against those other Trop2s. Well, this is an experiment to answer that. So we actually took an approved -- the first Trop2 approved product called Trodelvy. It's a Trop2 ADC. It uses one of those payloads I mentioned earlier, the topoisomerase I inhibitor. It was approved in 2019, I believe.

And you see -- this is not an indication where it's approved, this is a gastric cancer model. And you see when we -- when Trodelvy is given, the vehicle on the very left in this chart is, again, when you don't treat with anything, you see 0 out of 10, which are tumor responses, basically no response. That's what you expect.

When you dose Trodelvy at its approved dose, you actually see only about 20% of the mice get a total remission in this gastric cancer model. But when you take our Trop2 AKTX-101 as a single agent, you see 50% of the mice actually get a total response. And we see that statistically significantly when you go to the table at the bottom, when there are 2 different kind of molecules we tested on our AKTX-101.

I won't get into the nuances, but you see what we call PH1 DAR4, you can see even the DAR4, the DAR2, the 2 different versions, we are statistically superior to Trodelvy in this model, in this preclinical model. So this gives us more conviction that, yes, we may be not the first Trop2 ADC in the market, but we think we're much better and we're better than the first Trop2 that got approved if you believe this experiment.

So this is due to the payload, not the antibody. Our antibody is a high-quality antibody. It's different than Trodelvy, but it does what an antibody does. It targets, it's a smart missile. It hones in on the actual cancer tumor. The reason we see this difference is the payload. Our payload, our spliceosome modulator works in such a fundamentally different way than the topoisomerase I inhibitor on Trodelvy, and this is where we think we're seeing the benefit in an experiment like this.

I'll show you the last piece of data. This is actually done not with our Trop2, but with another proof-of-concept antibody drug conjugate we built called hHer2. This is not something we're taking forward, but this proves again the technology. This is probably one of the most exciting experiments because if you go back to what we said around it, stimulating the immune system, and the immune system is key to getting patients to be cancer-free and how you combine with checkpoint inhibitors, the most successful class in oncology today.

However, checkpoint inhibitors only work in 20% of patients. So how can we improve their ability to work in a broader set? Well, this is an experiment that gives us reasons to believe around all those 3. So again, if you believe -- if you look at this mouse, it was injected with colon cancer cells. And you can see the black line, which is basically placebo, there was basically no responses. And even on the checkpoint inhibitor, the blue line, this is a pretty tough cancer model. None of the mice responded.

When you look at our single agent, trastuzumab PH1, this antibody drug conjugate with our payload, you see almost 40% of the mice survived. And what's really impressive, when you combine the checkpoint inhibitor with our ADC with the payload, almost 90% of the mice survived up to 150 days. And this is after we stopped injecting them after 3 weeks because that was the way that this experiment was designed for this model.

Imagine, we got a 90% survival cure remission rate after only 3 weeks of dosing out to 150 days. So that's the synergy I talked about with combined with checkpoint inhibitors. And even as a single agent, we see that almost 40% of these mice survive. What's really compelling is if you take these mice, these naive mice and you actually rechallenge them. And you're not redosing with our product, but you're just rechallenging them with cancer cells comparing to mice that were never treated in this first experiment.

That's the black line, the mice that were never treated. But you see that this orange line is the ones that were rechallenged. You see none of them actually develop the cancer tumor. That's really profound because what that means is that these mice have what we call immunological memory. They have learned how to attack the cancer so that when they see it again, they can actually defeat it. And this is without us dosing any more drug.

So this is a proof of concept that helps to validate our idea of stimulating and activating the immune system in a profound way and doing it in synergy with a checkpoint inhibitor that we trained the mouse's immune system to like essentially beat the cancer, not just once but on an ongoing enduring way. And if we can demonstrate that moving forward in humans, this is a unique value prop for our payload that has not been demonstrated elsewhere in other antibody drug conjugates.

So this is, again, some of the reasons we have a lot of conviction and belief in the science of our payload the spliceosome modulator. So I'm going to move on because as every good antibody drug conjugate, any therapy, efficacy is important, but so is safety. So we have to make sure that this product is safe enough to take into clinical trials testing and establish further. And many products fail because they don't. So essentially, -- when we look at this, we've actually done some safety work in rats, but importantly, what we call nonhuman primates, which are large animal species similar to humans.

And that is a standard that we do in our industry before we test in humans. And what we found is that we found that we have a dose that's tolerated at what we think is an effective dose to go into humans and that we feel confident then we can actually dose in the humans at a place that will be therapeutically effective. That's one of the most important things out of this study.

The other thing is that we did see some side effects as with any therapy, but we found that many of them were mild, reversible or transient and that they can be managed. And oncologists are very good at managing toxicities of therapies given the armament that they have today. So this is important that we found that we can mitigate the side effects and then the transient and they reset after a while.

We also found that our toxicity profile could be compatible with checkpoint inhibitors. Again, we mentioned we want to combine. It would be bad if you actually had cumulative toxicities that actually make it worse, that would be a bad thing because that would prohibit you from combining with a checkpoint inhibitor. We find that our toxicity profile is compatible and there's no evidence of similar toxicities that you see with checkpoint inhibitors, which is good.

And I think finally, the last thing, what we think is really compelling is that this is a very differentiated safety profile than the other Trop2s, like I mentioned, Trodelvy or others that are approved. We see what we call myelo or bone marrow toxicities, things like neutropenia, which are white blood cells, diarrhea, Trodelvy actually has warnings in its label around these. Or what we see is lung disease or lung scarring with some other Trop2 ADCs that use the Topo-1 inhibitor.

We don't see any of those because our payload is different. It works in a very different way, and it targets cancer cells in a different way. And so again, the theory and the design and the intent of our ADC is being played out even in our safety studies. So that's the Trop2. Hopefully, you walk away with more knowledge and excitement around it as much knowledge and excitement as we have and how we continue to advance the science.

I do want to transition to AKTX-102 before I kind of wrap up. This is what we think potentially a best-in-class, first-in-class ADC with our payload. We don't want to disclose the target yet. We're developing some really novel proprietary ways to develop this antibody to guide missile that we want to kind of link up with our payload. Once we do that, we will disclose more, and we want to advance this rapidly into preclinical development to get to the same stage as AKTX-101.

Importantly, what we think is really unique opportunities, colon cancer, we think, is a huge opportunity for this target that we haven't disclosed yet as well as gastric and again, going back to lung. And I want to call out colon because this is the -- probably the fourth largest, most common tumor type. It's actually increasing in incidence, unfortunately. It's one of the few that's actually growing today versus declining.

Think about anyone that has been affected by colon cancer. It's -- outcomes are devastating for patients. And to be honest, there hasn't been as much advancement here. We think this is a big opportunity in addition to gastric cancer and then, of course, lung cancer, where we think there's continued unmet need given how large the market size is for AKTX-102. So very novel science, more to come on this later in the year, but I just want to kind of leave you with the market opportunity is significant given the unmet need and our ability to go in these spaces where some of the ADCs are not playing as well.

So I want to kind of give a perspective of -- I want to talk about partnerships as well a little bit. So how are partnerships looking? That is a core part of our strategy. We want to bring in partners early. We want to continue to bring them along. And how is that? Well, this is like a reflection of the ADC space, and this is why we believe ADCs as a modality will continue to grow, continue to be successful, as I talked about earlier.

And this is just the deal flow in the last 12 months of early stage, and the majority of all these are even preclinical discovery stage. And you can see the list of these from December of last year to this year. You see upfront payments. You see some of the terms that are publicly disclosed that they are. And I think this shows that there's still a robust set of deal activity happening, and there's opportunities to partner with players around these ADCs.

And we believe we offer a unique opportunity because all these others are doing the same thing. As I mentioned, they're all using the same classes of payloads, and they're not really changing the approach. This is where we think we have a unique opportunity. We're actively talking to many of these companies, whether they're on here or the general pharma biotech sector around partnership opportunities.

So I want to leave you with what some of the value drivers are and what to continue to -- as you follow Akari, what to be on the lookout for. We are continuing to advance the science on AKTX-101. We expect to hopefully have some new preclinical study data in lung and some other areas in the fourth quarter. And as I said, we're going to continue to advance the development of this to get to human trials.

We're going to start what we call large-scale high-quality manufacturing, which is called good manufacturing practice, GMP. We're going to start some of that work and hope to have some of the initial work done in the first half of next year. And then that will lead to potentially us finalizing all the work needed to get to a potential clinical trial application in the second half of next year.

So we're rapidly trying to advance AKTX-101 to the clinic, and we will be looking for partners along the way as they see that progress. These are the things that partners like to look for. Have you left the product nomination stage to actually manufacturing and what we call advanced safety testing. And these are the things we're going to do that make us more attractive for partners either at that stage or even beyond.

And then AKTX-102, we're going to continue to disclose more about that by the end of the year. So stay tuned on that. And I also want to just highlight, just continue to stay abreast of our corporate overviews, our news updates, our website. We will have some data that we're going to present at upcoming scientific conferences later this year, really compelling data. I won't speak too much to it. I just want to set it up for your anticipation, get you excited about it, but there's a lot of stuff happening in terms of data generation and marching the science in new directions.

So with that, if I would just close, if you look at our investment summary as we talked about, basically, on our antibody drug conjugate, we have a novel immuno-oncology payload. Immuno-oncology, we think, is a differentiated way to approach the cancer market and in particular for ADCs and our spliceosome modulators of heart. It's different than over 90% of the payloads being used today.

Our lead asset, AKTX-101, is off to the races, has clear time line milestones as we've talked about. And 102, we think can be a best-in-class, first-in-class ADC, as we talked about, more to come on that. We continue to look at high market opportunities across both assets in lung, bladder, colon and gastric and then I want to reemphasize our continued strong focus and momentum on trying to capitalize on the deal flow for early-stage ADCs and how we can create near-term value for Akari and its shareholders.

So with that, I want to turn it back over to Jenene, and thanks for the opportunity.

Great. Abizer thanks. I have to be honest, I did not want that story to end. Very compelling, certainly an exciting time for Akari. Congratulations on all your work so far. I can't wait to hear what's next. So we are going to move to the Q&A portion of this event. [Operator Instructions] Abizer while our audiences are thinking of their questions and typing them in, I have a few that I prepared in anticipation for this discussion.

So our first one, so most ADCs today rely on the Topo-1 or microtubule inhibitors, which limit with limited innovation in payload. Sorry for that tongue twister. How do you see the PH1 spliceosome modulator breaking the cycle of group think and resetting the bar for ADC payload innovation?

Yes. No, great question. And it's a tongue twister as well I have to practice it myself, there's a lot of stuff to keep track of jargon. But no, what I would say is if you go back, and this is in our corporate deck, you look at that one slide that speaks to the unmet need and that 50% or less of patients actually get a response in terms of what's the response rate and then how durable is it? Only about 6 months on average maintain that response.

And that's because not that the payloads are bad today, but those are the limitations of those payloads. So they're doing the work that they've been designed to do, but they're going to reach some ceiling or limit based on the biology of those payloads. So that's exactly the unmet need we're trying to tap into.

And if we find a better payload, like what we believe the spliceosome modulator, we will have a different ceiling. We will have a different ability to change those numbers of 50% in 6 months. So those are the 2 numbers you should think about in terms of unmet need. We want to change that 50% of response rates and the 6 months of response duration, that's our opportunity, and we think the spliceosome modulator can address that over the current payloads that are being used today.

Excellent. Okay. So in your presentation, the preclinical data suggests your PH1 payload kills cancer cells while also activating the immune system. So how do you expect this dual mechanism to translate into better patient outcomes compared with the current single mechanism payloads?

Sure. Yes. And I think it's a great way to kind of connect the presentation with some of the data. And so let me kind of thread it in different ways. Think about that 6-month response rate, that durability. So getting patients to have better durability really means are you going to treat them with more toxic things because at some point, people have to stop taking therapies because they're too toxic and too many side effects or the cancer develops resistance and/or both as it happens.

So we want to extend durability, the best way is actually the immune system. The immune system is the most powerful way to treat cancer. Unfortunately, it gets tricked by cancer initially into getting suppressed. So the idea behind the KEYTRUDA and the OPDIVA was that, and this was a lot of great science innovation creating those great products is that can you reawaken immune system to do a better job killing the cancer, because it's been proven checkpoint inhibitors, although they only work in 20% of the patients that they're treated when they work, they really work because if you get a response, the immune system starts to kick in and have what we call durability response, 1-year remissions, 2-year remissions, potentially complete remissions forever some patients if they're lucky.

And so we want to build on that. And the best way to do that is that experiment I mentioned where we talked about creating immunological memory. So we see that we're creating that long-term duration of effect by combining with a checkpoint inhibitor. That gives us confidence that we can change the outcome to help patients be cancer-free and get back to that aspiration I mentioned earlier. So that's our opportunity to take the immune system, really wrap it up in a controllable way, combine it with a checkpoint inhibitor and really get that longer last duration effect.

So do better than 6 months, do a year, do 2 years, do hopefully forever. And that's the power of the immune system. And that's why we believe in the spliceosome modulation, that's the most powerful aspect of this payload.

Excellent. So we're seeing a real spotlight on the ADC space, definitely a hot area. And with that, we've seen really strong deal flow in this space, even at a very early preclinical stage. I mean, I know you showed that chart in your presentation.

So with AKTX-101 and the payload -- the PH1 payload being so differentiated, what is your partnering strategy? You touched on it a bit, but love to hear and have our audience here what your actual strategy is there.

Sure. No, I think it's a really good question, and I think a key area of interest because we do think that's an area of value creation for our current shareholders. So in the near term and even midterm, long term. So I think when we think about partnerships, if you look at that slide, again, it's in the corporate deck, you'll see that all those partnerships, there are similarities, but there are differences.

And I think that speaks to partnership. We are open to the flexible nature of partnerships. There's going to be some that -- some people might be like, "Hey, we love your technology. We want to collaborate with you. Can we do a partnership where we do joint research". And if a company comes to us and says, "Hey, we have a great antibody, we want to pair with your payload, -- let's do a partnership, let's do that". That's a more in-depth partnership. There could be another partnership where someone says, "Hey, we like your molecule. We don't want to bring it in-house, but we're going to co-fund and develop it with you. So we'll make an investment and you'll get to certain milestones and then we'll revisit along the way if we want to license it or not". We'll be open to that, again, depending on deal terms and constructs.

And I think the third option or bucket I would think about, again, these are general buckets and the flavors in between, is that someone might come and say, we love your molecule, can we license it? And okay, well, if the terms are right, we'll license the whole thing for you and you can take it from us, but then we won't have control or ownership but also responsibility. And we want to be thoughtful around who we do that with and whether they will take care of what we call our baby and our payload.

But I just give you that example of that's probably one example on one side where we totally out-license the full asset and we let someone take it over. On the opposite side, it's, hey, there's going to be maybe a partnership of we're going to co-develop and create new molecules, new ADCs that aren't even on the map that we saw. Maybe a pharma partner has a target or an antibody that's different than the ones we are, and they want to combine it with our payload because our payload is so good, and that's the optionality of our payload, and they want to do a research agreement.

Well, that's a different type of agreement. And then there's stuff in between. So we're open and flexible to all 3 of those. And we don't want to hinder ourselves because as a novel payload, we actually offer all that optionality. And so we want to be open to all those.

Excellent. Okay. And I do have one more question because I just think of you and listen to you and your enthusiasm for the Akari story and the opportunity that exists. And you are fairly new to the seat as CEO of Akari.

You come from Jazz Pharmaceuticals, a well-established, very successful company. I think it's got to be anywhere around $7 billion to $8 billion market cap. What -- tell us, please, what made Akari so attractive for you to leave Jazz?

Yes. I think it's a great question. And if I had more time, I would have touched it earlier in the presentation, so I'm glad you're asking for it, but I'll ask you this now. Ultimately, yes, it was really the science and the opportunity. This spliceosome modulator really caught my eye because at Jazz, we -- as proud of the team what we did there when I joined, we -- in about 4.5, 5 years, we grew a $350 million business, 3 products to 6 products, about $1 billion before I left.

So why would I leave such a growth momentum? It was because really the ADC market has done so well. But I knew I didn't want to just join any ADC company to lead. I wanted to join one that had a novel competitive edge because I see that's what makes the difference in cancer patients and the cancer market. So when I first came across Akari, I quickly saw this pivot to oncology, but it was premised on the spliceosome modulator.

And the idea of novel payloads, that's where the innovation is going to happen. That's where the value creation is going to happen if you have the right set of people and the team and the plan to execute. So I believe coming here, I can bring the right set of leveraging the current team, but also bringing in other additional team members, but the focus and the plan and the strategy to execute.

So we want to take the great scientists there, and I believe we have the opportunity to execute and make a high value for everyone for both patients, providers and importantly, for our shareholders as well. So that was the conviction that I had when I came and I still believe it even more so today.

All right. And thanks for that background. I appreciate that. I think it is important for our audience to understand that.

I think it's a huge component of why the story is so compelling because it's not only attractive potentially to investors, potential partners, but you see the value there. So I appreciate you going through that.

Sure, sure.

All right. So we do have some questions. [Operator Instructions] And if you Okay. So our first question comes in when you're thinking about the Phase I, how do you envision the trial design and target indication? And have you had any interactions with FDA?

Yes. No, great question. I'd say we're early on that side. It's a little premature. I think we shared our initial thinking, we think the post-Enfortumab PADCEV market in bladder cancer is an attractive space. We think there's still continued high unmet need after people fail first-line ADCs or whatever therapy they're on. We think that's a unique opportunity. Our data, as we talked to that preclinical data is pretty compelling to give us confidence we could work in that area.

We have not thought about trial designs yet. I think as we continue to progress the asset towards a first-in-human clinical trial, we will -- I mean listen, there's not probably a lot of permutations are fairly standard designs when you look at single-agent studies in refractory populations, you're probably going to do something that's been done or a flavor of that's been done in the past.

I wouldn't say it's starting from scratch. We're going to leverage what's been done in the past and what other -- some Trop2s have done, in particular, Trodelvy, how they got approved and kind of a similar path. So I wouldn't say it's going to be that groundbreaking, but I would say we haven't finalized that work. We want to do some other things to kind of get us going, and then we'll kind of engage in that probably next -- later this year, next year.

All right. Our next question from a strategic standpoint, is your goal to take AKTX-101 through pivotal studies independently? Or do you see a partnership or acquisition as the most likely end game?

Well, without forecasting with certainty, I would say likely the latter. But again, we have to be open to all options. And one of the things that's interesting is the longer a company keeps an asset and develops it, the more value creation you have. Now that's premised on you have to keep on derisking the asset and you have to continue to invest in the asset to do that.

If you look at late-stage companies or companies that are approved, the value that they get ascribed on their acquisition or licensing is significantly higher, and that starts to decline as you go earlier in the cycle. But again, that's because they derisk and they spent more money. So I think we want to be open to creating value as quickly as possible for our investors and what we're trying to and validate the platform.

Because then if we validate the platform, that will enable us to do more opportunities and build more ADCs and do more partnerships. So I would say, although we're open to all options, our bias is going to be we would like to partner this when we have enough data and it's appropriate earlier versus later. That enables us to return value back to our shareholders quicker versus later. It enables us to reinvest the capital and building a broader pipeline.

However, we just can't be close to all -- we have to be open to all, but I think if we had a choice, we would probably want to partner earlier versus later. But again, we have to be open to all options.

All right. Our next question is, these are great presentation. I found it to be very compelling. There's a huge disconnect between the current stock price valuation and where this opportunity sits. So what is your plan for the stock price and turning this around?

Sure. Great question. And I do want to make a comment, particularly in the last week or 2 and even over the late summer. Listen, we don't want to comment on day-to-day fluctuations in the stock price. However, we're as frustrated as many of our U.S. shareholders as well.

And I think we have to remember that with small cap biotech market cap biotechs, there's often other factors, technical trading and broader sector dynamics that affect our stock as well. So I think that's part of it. But again, we can't get caught in the day-to-day. And so I'll just say we're frustrated as well where we sit because we don't think it reflects the science and the value and the strategy that we -- that I just articulated.

So that being said, let me say what we're doing about it. What we're doing is we're going to continue to develop and execute on this plan. As you just heard this, we feel really confident and compelled on the data that we have to date. our plan moving forward. We want to continue to advance AKTX-101 and the broader pipeline, as I outlined earlier, and keep that going. We want to continue to generate high-quality science and data that's a big part of any oncology company or any successful pharma biotech.

And I spoke to some of those things to look for in terms of data presentations later this year and updates on our pipeline. And we want to continue to execute. We have to be focused on our execution in a laser-like way. This is one of the toughest biotech markets in 20, 20 years plus. That means the operators and companies that are super razor-focused on the right things versus the peripheral things that the right things will stay -- will be successful, and that's what we believe.

And so what I would say is on the stock price, hopefully, you walked away with as much excitement around spliceosome modulation that I have, that our team has, that we continue to do. And we feel we really have an opportunity to drive significant differentiation and address unmet need in the cancer market. And if we do that and we continue to execute and deliver on what we just said with a good strategic plan, as I just outlined, that will reflect in the share price.

Sometimes there's a lag on that, but we do think it will reflect in the share price. And I'm just committed, I'm committing and our team is committing to all the shareholders, we're working extra hard every day, not because the price of the stock is not what we want because we truly believe that this is the plan of success, and we're committed to it.

And so you have our commitment that we're working as hard as we can every day, every month, every year ongoing to execute on what you just saw, and we're going to stay laser-focused on execution, and that will then play out into the stock price.

Appreciate that, Abizer. Those questions are always tough, right? But I think that I go back to one of your first slides and your mission of making patients cancer free. That has to drive you. That has to be a part of it.

And it's unfortunate because I think everything that you shared with us, all of the data that you've gone through your plans, your execution, the space that you're in that and all of the enthusiasm, it has to be frustrating for you. It has to be frustrating for shareholders. I look at it, I see the disconnect. So it's just -- it's down to execution and data, right?

Yes. And Jenene, can I discretely add. I mean, it is frustrating when you see that stock price because it's not reflective of what the team and I have been doing. I can tell you what I see that all of you don't see an insider everything I see these things, I continue to see data that makes me super compelling, like not just from the first time we run on this platform, but the experiments we're doing now, the future experiments we're going to do, I'm excited.

Like I keep on seeing every time -- I won't say every time, but many times we're doing these experiments, we're seeing great results. Science is hard to predict, not every experiment works, but it just continues to add the body of confidence I see. And then we're going to bring some of that data to you in the near future. So you see it as well, and that's the stuff we're talking to partners about so they see it as well. So that's what again, gets me motivated that we are doing -- we have a really novel platform, and we're doing the right work to help it shine to make it attractive and thus advance it.

Excellent. All right. It looks like we have another question here. So Abizer, you showed a table of ADC deals due to the majority of those programs in those transactions using microtubule inhibitors. I don't know what it is with respect to the tongue twister for me, I apologize. Have you reached out to those companies about your technology?

Yes. I would -- yes, we have, and we continue to reach out to a broader spectrum than even on that sheet. We actively talk to a number of the major players that you can imagine, both in large, mid, even small cap biotech pharma around opportunities around partnership. And I think one of the things is we have to show people our data to show them why it's compelling.

So although we're exciting and new, remember, there's also an adoption curve of anything new. And people go with what they know and pharma and biotech kind of rides in momentums and waves and herd. So the herd is around the Topo-1 and microtubule inhibitors since they're so prevalent, it's easy for people to follow what they know.

So does that make it harder for us to have people see why we're doing something different. It doesn't -- it's not hard that people want to say, hey, I want to hear something different because I'm tired of the same story. It's just that they want to see more data to believe it. And so that's just being -- I mean, you can -- the honor of being leading edge and innovative is great because you have the first-mover advantage.

But sometimes you have to prove people a little bit more than others because they want to see more data before they do something. So I think we are actively engaging a lot of these partners to show them the wide body of data that we have, why they should believe, how we continue to derisk this and get them excited. And we are getting traction.

I mean I can't speak to specifics, but we are having the conversations with the right people and the right companies. And when we have enough of them, it's like collision, eventually, they're all going to -- one of them is going to successfully result in something.

Excellent. All right. So those are the questions that have come in from our audience. And before I close, I was just thinking about the question that came in related to valuation and stock price. I have a little bit of a different question.

You shared -- again, you shared a compelling exciting story. We see your enthusiasm and the opportunity, I think you outlined very well for our audience and for potential investors. So if you think about Akari and you think about someone that is taking a look, maybe heard a presentation for the first time today or has been kind of following but really hasn't done more than just follow the story. What would you say to our audience, to those paying attention, why investors should do the work, make a decision and potentially become an investor in Akari Therapeutics right now?

Sure. So I would always go back to if you want to invest in biotech and life sciences, you got to do your homework and make sure you feel good. You also have to be ready to stomach a lot of ups and downs. And like that comes with biotech investing because it's unpredictable because it's biology and it's science, which is unpredictable by itself.

But I think you have to get convicted around two things. One, do you believe in the science, you really fundamentally believe in what's being told you and you have a lot of faith and it's differentiated and you see that it has a compelling vision and value differentiation. But two, do you believe in what I would say, the team and the plan because ultimately, science is only as good as science and it sits on the shelf, but it's the team and the plan that, that team is going to develop and execute that's going to drive that science forward.

And I think as you look at any company, knowing you got to have a little bit of a stronger stuff in the biotech space, particularly now, if you can answer those 2 questions, you feel good about an investment that you should go in. And I'm not saying you need to bet a lot, but bet a little. As an investor, I was buying and I see dips and I still have a conviction I buy more, nothing changes because you think it's a good investment.

And so I think it's more about your overall risk profile and then your belief. And I'll tell you my personal belief, I'll just share an anecdote. -- when I first looked at a company called Seagen probably in 2007 as a personal investor, and I worked in the biotech space back then as well, this antibody drug conjugating sounds pretty interesting because people take systemic chemo and it kills you and no one likes systemic chemo because it's poison.

Well, this seems like a cool way to developed to combine an antibody, which is high tech that Genentech put out there in oncology that has shown so much effect as a single antibody and combine it with these chemos. And maybe these people in Seattle have something interesting, and it's taken a long time. They've been around for a long time, but they seem like they do something interesting.

And next thing you know, Seagen continues to get approvals and deals. And I came in late to the story. I think there were people that were wiser and smarter than me that even knew this 5 or 8 years before that. But I can tell you, I came in and I never looked back. to the point where Pfizer bought them for $43 billion, and I did personally decent on that transaction.

So I think you -- but what happened is despite the dips, there were a lot of dips on Seagen. And I stayed and I doubled down many times because I believe in the science, and I believe in the team on the execution and what they were doing. And I think if you believe in those 2 things, you should buy an investment. And if you don't, you shouldn't invest or you should sell your position. So I tell you that is objective advice.

Excellent. Well, Abizer, I have to say I thoroughly enjoyed this conversation. Your presentation was compelling. I think you did a great job outlining the opportunity for our audience and really appreciate you taking the time and doing that. So with that, everyone, this does conclude the virtual investor closing bell featuring Akari Therapeutics.

And I would like to thank Abizer for joining us today. I'd also like to thank our audience for your participation and as always, great questions. And as a reminder, Akari Therapeutics trades on NASDAQ under the ticker AKTX. If you like what you saw today, I encourage you to visit akaritx.com for more information on the company and to sign up to follow the company to receive their alerts as well as follow their social channels on X and LinkedIn to stay current on the latest information.

And you can also visit virtualinvestorco.com for a replay of today's segment as well as our latest events calendar. Abizer, thanks again. I can't wait to have you back. Congratulations on your progress, and we really look forward to seeing what's to come for Akari.

Well, thank you, Jenene. Thanks for having me, and thanks to the audience for your attention. Appreciate it.

Absolutely. Thanks, everyone, and wishing you a great rest of your day.