Addex Therapeutics Ltd - ADR Stock

Good day, and thank you for standing by. Welcome to the Addex Therapeutics First Quarter 2026 Financial Results and Corporate Update Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Tim Dyer, CEO. Please go ahead.

Hello, everyone. I would like to thank you all for attending our Q1 2026 Financial Results Conference Call. I am here with Mikhail Kalinichev, our Head of Translational Science, who will provide an update on our R&D programs. I draw your attention to the press release and the financial statements issued earlier today, which are available on our website.

I also draw your attention to our disclaimer. We will be making certain forward-looking statements that are based on the knowledge we have today. I will start this conference call by giving a quick overview of our recent activities and achievements before reviewing our pipeline. I will then hand over to Misha, who will review in more detail our mGluR5 negative allosteric modulator program for brain injury recovery and the GABAB positive modulator program for cough. I will then review our 2026 Q1 financial results. Following that, we will open the call for Q&A.

So starting with the highlights. Q1 has seen several important achievements across our pipeline. We have made excellent progress in our GABAB positive modulator cough program as we continue to complete preclinical characterization of our selective compound. We recently announced robust antitussive activity in a nonhuman primate cough model as well as solid antitussive activity in an idiopathic pulmonary fibrosis model in Guinea pigs.

These data further demonstrate the potential of our selective compound in this important unmet medical need. In parallel to completing the preclinical profiling, we are working to secure funding to advance the program into the IND-enabling studies. Mikhail will be sharing some of the data with you later in our presentation.

We have repositioned dipraglurant, our mGluR5 negative allosteric modulator for brain injury recovery and have made good progress in preparing the program for clinical studies in post-stroke recovery patients. In 2025, we entered into an option agreement, giving us access to an exclusive license to intellectual property covering the use of mGluR5 in brain injury recovery, including stroke and TBI.

Included in the agreement is a research collaboration under which we are working with Sinntaxis and the University of Lund in Sweden to complete preclinical profiling of dipraglurant and prepare for clinical studies. Again, Misha will talk more about this exciting program later in the presentation.

As a reminder, we spun out our portfolio of preclinical neuropsychiatric assets in 2024 to create Neurosterix and raised $65 million from a syndicate of investors led by Perceptive Advisors. We retained a 20% equity interest in Neurosterix, the value of which is unfortunately not being properly reflected in our current share price. Neurosterix has made excellent progress in advancing its pipeline, including its M4 PAM and mGluR7 NAM programs. The lead drug candidate in the M4 PAM program, NTX-253, is in Phase I, and we expect data in Q3 this year.

On the financial side, we completed the quarter with CHF 0.9 million of cash and have successfully raised CHF 0.3 million in Q2. Given that our cash burn is extremely low following the Neurosterix spin-out, this provides us with cash runway through into Q4 of 2026 on a going concern basis. However, current cash does not fund the progression of our unpartnered programs into the clinic.

So now for a quick review of our pipeline. As mentioned, we continue to believe in dipraglurant and we are executing our plans to reposition the development for brain injury recovery. As a reminder, we have regained the rights to ADX-71149 from our partner, J&J, with a high-value data set and significant GMP materials. We're currently evaluating a number of therapeutic indications for future development. And in parallel, we are discussing with potential partners for the asset.

For our GABAB PAM collaboration with Indivior, Indivior has selected a compound for development in substance use disorders and has successfully completed IND-enabling studies. As a reminder, under the terms of the agreement, Addex is eligible for payment of up to $330 million on successful achievement of prespecified regulatory clinical and commercial milestones as well as tiered royalties on the level of net sales from high single digit up to low double digits.

As mentioned earlier, we are advancing an independent GABAB program for cough and expect to start IND-enabling studies this year, subject to securing financing. Also presented on this slide is the portfolio of our spin-out company, Neurosterix. We are expecting Phase I data from NTX-253 program in Q3. Backup M4 PAM compound, NTX-529 has been selected for IND-enabling studies, which should start shortly. The mGluR7 NAM program has selected NTX-819, a highly selective first-in-class compound, which has demonstrated robust preclinical anxiolytic and antidepressant-like activity, which supports its development as a potential next-generation therapy. We expect NTX-819 to complete IND-enabling studies in the coming months.

Now I will hand over to Misha, who will give you some more details about our exciting portfolio.

Thanks, Tim. Hello, everyone. I will start by speaking about dipraglurant and our plans for development in brain injury recovery. Dipraglurant is an orally available, highly selective mGLu5 negative allosteric modulator, which we believe could improve the outcome of rehabilitation for patients suffering from traumatic brain injury or stroke. The mechanism of action of dipraglurant targets neuroplasticity early in rehabilitation to promote rebuilding of neuronal connections and sensory motor recovery.

The unmet medical need and commercial opportunity in post-stroke and TBI recovery is undisputed. Stroke is among the leading causes of chronic, often lifelong, disability as it leads to motor sensory cognitive impairment and multiple comorbidities. There are over 100 million stroke survivors worldwide, and the number is growing at the annual rate of 12 million. A variety of rehabilitation therapies are used with post-stroke patients, but the recovery is slow and often inadequate. There is an urgent need for pharmacological agents that can facilitate the recovery stimulated by rehabilitation therapies.

Now to why mGLu5 NAM is such a great target for this indication. mGLu5 receptor is a suitable target to address post-stroke recovery as it is densely expressed in the brain involved in neuroplasticity and modulates excitatory/inhibitory equilibrium. In fact, activation of mGluR5 has been observed in a large range of neurological disorders, including stroke, where it plays a role in so-called maladaptive rewiring of the brain following stroke. Inhibition of mGluR5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neuroplasticity and creation of new functional pathways moving the neural network towards the pre-lesion state.

Now to the data. I would like to refer you to the left-hand figure, which shows exciting new evidence recently published in the journal, Brain. These data show the negative rats modulator of mGLu5 MTEP administered daily in rats following stroke results in a sustained and growing improvement in sensory motor function in comparison to vehicle treatment.

In the right-hand figure, we can see a similar improvement in sensory motor function that was observed in animals treated with our mGLu5 NAM dipraglurant. We are currently working with our collaboration partner, Sinntaxis, to complete the preclinical profile of dipraglurant in this animal model. In addition to the compelling in vivo data, MRI imaging of the resting state functional connectivity in post-stroke rodents show that daily administration of MTEP also stimulates intra and interhemispheric connectivity in the brain disrupted by stroke. It is important to note that improvement in brain connectivity after stroke is known to correlate with functional recovery and is observed across species.

Dipraglurant is ideally suited to be used in conjunction with rehabilitation therapies in post-stroke patients as it has a fast onset of action and short half-life. It has shown good tolerability in healthy subjects and in Parkinsonian patients showing only mild-to-moderate CNS-related adverse effects. We have a drug product ready and a strong patent position and believe dipraglurant can become a first-in-class drug to facilitate post-stroke recovery.

We can also speculate that dipraglurant-mediated adaptive rewiring and facilitation of recovery following brain damage would also be seen in traumatic brain injury patients. The next step in clinical development is to perform an imaging study in stroke patients to show the intra- and interhemispheric connectivity in the brain disrupted by stroke.

Now I would like to update you on our GABAB positive allosteric modulator cough program. As a part of our agreement with Indivior, Addex has exercised its right to select a compound to advance its own independent GABAB PAM program for the treatment of chronic cough. I will now present this exciting opportunity.

There is a strong rationale for developing GABAB PAMs for chronic cough. Chronic cough is a persistent cough that lasts more than 8 weeks and can be caused by a variety of factors, including respiratory infections, asthma, allergies and acid reflux, but also possibly by a cough hypersensitivity syndrome. There is a large unmet medical need in novel antitussive drugs as current standards of care are ineffective in 30% of patients or only moderately effective in up to 60% of patients. In addition, the current treatments carry risks of serious side effects.

Support for using GABAB PAMs in treatment of chronic cough comes from the clinical evidence that baclofen, a GABAB agonist is used off-label in cough patients and from the anatomical evidence that GABAB receptors are strongly expressed in airways and in the neuronal pathway regulating cough. Therefore, we believe that GABAB PAMs could offer superior efficacy in cough patients.

The pre-IND activities, including in vivo proof-of-concept, non-GLP tox and CMC have been completed, and our clinical candidate has shown favorable efficacy, tolerability and developability profiles. Our clinical candidate has demonstrated a consistent minimum effective dose on 1 mg per kg and ED50 of 6 mg per kg in cough frequency in a Guinea pig model of cough. No signs of tolerance were seen after subchronic dosing and more than 60-fold safety margin was demonstrated based on respiratory depression sedation biomarker.

Recently, we confirmed the antitussive efficacy in the nonhuman primates and our currently -- and now currently evaluating the compound in rabbits. IND-enabling studies are planned and ready to start subject to securing financing.

Now to the data. In the model of citric acid-induced cough in Guinea pigs, acutely administered compound A delivered a robust antitussive efficacy, reducing the cough number dose dependently and achieving 70% reductions at the maximum doses. The antitussive profile of compound A was similar to that of nalbuphine, orvepitant, baclofen and codeine.

Now to cough latency. Compound A increased the latency to first cough dose dependently, thus delaying the onset of cough. The antitussive profile of compound A in delaying cough onset was similar or better than that of reference drugs. As a reminder, our objective in the program is to design a GABAB PAM with the efficacy of reference compounds, but without the CNS side effects such as sedation.

In the same experiment where the compound A showed efficacy, we monitored respiratory rate, a biomarker of sedation. As you can see from the slide, compound A was well tolerated as there were no marked changes in respiratory rate at up to 60 mg per kg. In contrast, nalbuphine, orvepitant, baclofen and codeine resulted in robust reductions of respiratory rate at doses required to achieve maximal efficacy, indicative of sedative-like effects.

When we evaluated the antitussive efficacy across compounds at the respective highest doses free from respiratory effects, compound A was shown to be superior to nalbuphine, orvepitant, baclofen and codeine in both cough number and cough latency measures. In the model of ATP-potentiated citric acid cough in Guinea pigs in a head-to-head comparison experiment, acutely administered compound A and the P2X3 inhibitor had similar efficacy and tolerability profiles.

As a reminder, P2X3 inhibitor activities peripherally mediated, which explains the lack of sedative effects, but also the reason for more than 30% of cough patients do not respond to treatment. In the citric acid-induced cough model, subchronic administration of compound A for 7 days showed no signs of tolerance, neither in cough frequency nor in latency to first cough. Also, there were no changes in the respiratory rate, body temperature and growth hormone release in animals treated subchronically with compound A.

Compound A was also assessed in the IPF-related exacerbated chronic cough model in Guinea pigs. Here is the study design. On day 0, animals received a single oropharyngeal administration of bleomycin or were left intact. Bleomycin-exposed animals were then treated with compound A or vehicle orally once daily for 28 days. Intact animals received vehicle.

On day 7, 14, 21 and 28, animals were exposed to low concentrations of citric acid to stimulate cough. On day 28, at the end of the experiment, the lung tissue was collected for histopathological analysis. The total number of coughs was significantly higher in bleomycin-exposed vehicle-treated animals than in healthy controls. This difference between the groups grew progressively larger over time, indicative of exacerbated cough in IPF-like condition.

Chronic treatment with compound A resulted in robust and enduring reductions in the number of coughs with 40% to 60% reduction magnitude. The latency to first cough showed significant reductions in bleomycin-exposed vehicle-treated animals versus intact control starting day 14. Chronic treatment with compound A reversed the effects of bleomycin throughout the testing period, returning the latencies to the levels of intact control animals.

A histological analysis of the lung tissue collected on day 28 revealed that chronic administration of compound A was associated with markedly lower Ashcroft scores and lower percentage of affected lung in comparison to bleomycin-exposed vehicle-treated animals. This suggests that compound A administered over 28 days reduced lung fibrosis.

Now to the nonhuman primate cough data. Similar to what we saw in Guinea pigs, in the model of citric acid induced cough in nonhuman primates, compound A demonstrated a more than 60% reductions in number of coughs at 2 mg per kg. In summary, we have selected a clinical candidate for chronic cough with a robust reproducible antitussive efficacy at 1 mg per kg and good PK/PD. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs and nonhuman primates.

The compound has the potential to have the best-in-disease efficacy and tolerability profile and broad application in chronic cough patients. Subject to raising financing, we are ready to start the IND-enabling studies.

This concludes our prepared remarks on the progress of our R&D programs. Now I hand it back to Tim.

Thanks, Misha. Now for a review of our Q1 2026 financials. Starting with the income statement. The operating loss amounts to CHF 0.5 million in Q1 2026 compared to CHF 0.6 million in Q1 2025. The decrease of CHF 0.1 million between both periods is primarily due to reduced outsourced R&D.

As a reminder, on April 2, 2024, we received an equity interest of 20% in Neurosterix as part of our Neurosterix spin-out transaction. Under IFRS, we are required to account for the investment using the equity method of accounting and recognize our share of their results in our income statement. For the 3-month period ended 31st of March 2026, our share of the net loss of Neurosterix amounted to CHF 1.3 million compared to CHF 0.8 million for the 3-month period ended March 31, 2025. This increase is primarily driven by the move of NTX253 into clinical development by Neurosterix.

The net loss amounted to CHF 1.7 million during the first quarter compared to CHF 1.5 million during the same period ended March 31, '25. Again, strongly driven by the increase in our share of the Neurosterix net loss, compensated by a reduction in our own internal net loss, which reduced by 23%.

Now to the balance sheet. We completed Q1 with CHF 0.9 million of cash held in Swiss francs and to a lesser extent, U.S. dollars compared to the CHF 1.6 million held at the end of 2025. The decrease of CHF 0.8 million is primarily due to our operating loss of CHF 0.5 million and an increased net working capital of CHF 0.3 million, driven by one-off annual payments made at the beginning of the year, such as retirement benefit contributions and insurance premiums.

Our current assets amounted to CHF 25,000, primarily related to increased prepaid retirement benefits. Our noncurrent assets of CHF 3.5 million at the end of March primarily relate to our investment in Neurosterix accounted for using the equity method and to a lesser extent, our investment in Stalicla.

Current liabilities remained steady at CHF 1.2 million at the end of March compared to December and primarily relate to accruals and payables from outsourced R&D and professional service activities. Noncurrent liabilities primarily relate to the retirement benefit obligations calculated in accordance with IAS 19 and amounted to CHF 0.3 million at the end of Q1 compared to CHF 0.4 million at the end of December.

Now to the cash flow statement. We started the quarter with CHF 1.6 million. We used CHF 766,000 for operations, primarily related to R&D and G&A activities. We received CHF 65,000 from the sale of treasury shares and completed the year with CHF 935,000 -- sorry, completed the quarter with CHF 935,000.

As mentioned in the highlights, we have been active with our ATM facilities, both on the NASDAQ and the SIX Exchange and have raised small amounts of capital in Q2 to strengthen the balance sheet while we await good news from our [indiscernible] Neurosterix.

Now to summarize, we have made excellent progress advancing our GABAB PAM program for cough and our dipraglurant post-stroke recovery program. Our spin-out company, Neurosterix, continues to advance its portfolio with their M4 PAM program on track to complete Phase I in Q3. We are very pleased by the progress Stalicla is making in advancing on its business strategy and pipeline. We are looking forward to completing our evaluation of potential indications for our mGluR2 PAM program and securing the financial resources to advance our portfolio into clinical studies.

This concludes the presentation, and we will now open the call for questions.

[Operator Instructions]

And now we're going to take our first question. And it comes from the line of Raghuram Selvaraju from H.C. Wainwright & Co.

We have 4 of them. Two of these relate to the chronic cough program. Firstly, I was wondering if you could provide us with some assessment of the relative positioning of your lead candidate, the GABAB PAM against nalbuphine extended release. And also, I was wondering if you are thinking about potential dosing formulations that may reduce dosing frequency and therefore, improve patient convenience as you look towards advancing this into the clinic.

And then the second question on that front is related specifically to the Guinea pig model. I was just wondering how you typically measure the cough intensity in that context? And to what extent you rely on those measurements relative to the assessment of the lung tissue?

Yes, happy to answer the question. Let me start with the first, which is comparison of nalbuphine with our candidate, compound A. As you saw on the slide that I shared, the overall profile is very, very similar. Compound A appears to be more potent. We see a minimum effective dose at 1, whereas with nalbuphine, one needs to administer 3, exactly in the same model in Guinea pigs where cough is stimulated by sulfuric acid inhalation. And in terms of maximal efficacy, both deliver approximately 70% reduction.

The difference comes from the tolerability aspect of nalbuphine versus GABAB PAM. Here, at the top dose, 30 mg per kg, we see significant reductions in respiratory rate and it nicely aligns with what we know on the tolerability profile of nalbuphine in clinical trials where it showed CNS-related side effects even at the dose which was lower to the one -- corresponding dose to the one we tested in animals, even at the efficacious dose, which roughly aligns to 3 to 5 mg per kg in a guinea pig if we use 75 kilo calculation for a human body weight. So based on that, we expect similar efficacy to nalbuphine, but markedly wider therapeutic margin.

And regarding your second question on the formulation, our current formulation is expected to deliver once-daily compound. So there will be no need for extended release unless we will aim for something that is once weekly or once monthly. But once-daily formulation is believed to be achieved with the current simple formulation that we have. And that contrasts with nalbuphine very well as with nalbuphine, even extended release formulation, requires twice daily administration. So that shows another advantage of GABAB PAM clinical candidate over nalbuphine.

There was also a question on intensity. We use plethysmography chambers that deliver cough frequency and cough latency. There is no way of measuring cough intensity with that setup. The cough intensity is even challenging to measure in human patients. But there are some technical advances that may deliver intensity measures, but it's still in development.

Okay. And then with respect to the Neurosterix equity holding, I was just wondering, maybe, Tim, you can comment on this, what strategically your outlook is for long-term management of this equity position? And if you have any thoughts around how Addex might ultimately assess the disposition of this or potential monetization of it? And how you're thinking about this specifically in the context of the possible future public listing of Neurosterix.

I was also wondering if from a scientific perspective, you could comment on the complex interplay between muscarinic receptor signaling pathways. And in particular, if you could talk a little bit about -- this doesn't necessarily have to be solely in the context of what Neurosterix is doing, although I presume that is probably the most relevant aspect. But if you could talk specifically about M1, M4 receptor modulation relative to M4 and M7 receptor modulation and how these aspects might potentially have differing therapeutic applicabilities within the context of schizophrenia versus depression?

Okay. So let me take the first one about the equity holding, and thank you very much for the questions. So -- yes, let's just rewind. I mean, look, we founded Neurosterix really as a financing vehicle for some of our preclinical programs. And if you remember back and you dig into the press releases back in 2024, Neurosterix raised $65 million. Addex received a 20% equity holding. And if you run the numbers, the 20% equity interest that Addex received was valued based on the post-money valuation of Neurosterix at about $20 million. Now clearly, with a market cap of $8 million today, there seems to be a little bit of a disconnect.

Now what we know about Neurosterix is that Neurosterix has advanced in the last 2 years an M4 PAM from clinical candidate selection substantially through Phase I, and we're expecting Phase I to complete very soon with data coming out in Q3. It's also identified a backup compound in the M4 PAM program called NTX529, which is ready to go into IND-enabling studies. It's advanced the mGluR7, which is a first-in-class compound with a battery of preclinical data showing its potential in neuropsychiatry, in particular, the anxiolytic effects and antidepressant effects. So we believe that our equity holding is not being correctly reflected.

Now the question is really do we try and monetize it today? We have had some inbound interest. And one strategy could be to monetize the Neurosterix interest and sell it and to then use the proceeds to invest in our cough program. Alternatively, Neurosterix at some point will be executing a Series B, whether that's in the private arena or whether it's part of a public offering. I'm not in a position on this call in the context of Addex to comment on that. However, we are evaluating all opportunities regarding building value for our shareholders with that equity position.

Now what I would like to do is hand over to Misha who will talk at length because he is very knowledgeable about the muscarinic space.

Thank you, Tim. So we believe that the contribution of M1 into the antipsychotic efficacy of Cobenfy, which is a co-administration of xanomeline and trospium, is speculative. There is still -- this is being discussed, but there is no robust data that support that M1 component is necessary or is contributing significantly into its efficacy, either in cognition or in psychosis reduction.

As you know, there were multiple companies that were developing M1 -- muscarinic M1 selective compounds for cognitive improvement and all those clinical trials show lack of activity. Some also showed a range of muscarinic cholinergic side effects, which also brought additional aspects to consider.

If we look at animal studies that evaluated antipsychotic-like profile of xanomeline, in rodents, it was very clear that the main bulk of activity, if not exclusively, in amphetamine-induced hyperactivity model is driven by muscarinic M4 receptor with virtually no contribution from M1. So -- and then, of course, we have positive Ib clinical trial with emraclidine. So putting all together, we believe that having a selective M4 positive modulator will be able to deliver clinical efficacy, which we see with xanomeline. That was the main question. Then you mentioned receptor 7. I believe you had in mind mGluR7. Am I correct?

Yes, mGluR7. The interplay between that and M1 and M4 systems, yes.

Well, there is no direct evidence of interaction between muscarinic M4 and mGluR7. There is some evidence of interaction between mGluR7 and mGluR8. They may create heterodimers and their co-administration can have an impact on the outcome, but I'm not aware of any functional interaction between these 2 receptors.

[Operator Instructions]

Dear speakers, there are no further questions for today. Thank you, ladies and gentlemen. This brings the main part of our conference to a close. And I would like to hand back to Tim Dyer for closing remarks.

Thank you. And thank you, everyone, for attending this call. We look forward to speaking to you again soon, and we wish you a very nice end of your day, end of your week. Thank you. Bye, bye.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

Good day, and thank you for standing by. Welcome to the Addex Therapeutics Full Year 2025 Financial Results and Corporate Update Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your first speaker today, Tim Dyer. Please go ahead.

Thank you. Hello, everyone. I would like to thank you all for attending our 2025 full year financial results conference call. I'm here with Misha Kalinichev, our Head of Translational Science, who will provide an update on our R&D programs.

I draw your attention to the press release and the financial statements issued earlier today, which are available on our website. I also draw your attention to our disclaimer. We will be making certain forward-looking statements that are based on the knowledge we have today.

I will start this conference call by giving a quick overview of our recent activities and achievements before reviewing our pipeline. I will then hand over to Misha, who will review in more detail our mGlu5 negative allosteric modulator program for brain injury recovery and the GABAB positive allosteric modulator preclinical program for cough. I will then review our 2025 full year financial results. Following that, we will open the call for Q&A.

So 2025 has seen several important achievements across our pipeline. We made excellent progress in our GABAB PAM chronic cough program as we continue to complete preclinical characterization of our selective compound. We recently announced robust antitussive activity in a nonhuman primate chronic cough model as well as solid antitussive activity in an IPF model in Guinea pigs.

These data further demonstrate the potential of our selective compound in this important unmet medical need. In parallel to completing the preclinical profiling, we are working to secure funding to advance the program into the IND-enabling studies. Misha will be sharing some of the data with you later in our presentation.

We've also repositioned dipraglurant, our mGlu5 NAM for brain injury recovery and have made good progress in preparing the program for clinical studies in post-stroke recovery patients. In 2025, we entered into an option agreement, giving us access to an exclusive license to intellectual property covering the use of mGlu5 5 inhibitors in the brain injury recovery, including stroke and traumatic brain injury.

Included in the agreement is a research collaboration under which we are working with Sinntaxis and the University of Lund to complete preclinical profiling dipraglurant and are preparing for clinical studies. Misha will also talk more about this program later in the presentation.

So following the decision by our partner, J&J, to terminate development of ADX71149, we have regained the rights to this Phase II asset with a high-value data set and significant materials. We're currently evaluating a number of therapeutic indications for future development. And in parallel, we are discussing with potential partners for the asset. Our partner, Indivior, has selected a compound for development in substance use disorders and has completed IND-enabling studies.

As a reminder, under the terms of the agreement, Addex is eligible for payment of up to USD 330 million on successful achievement of prespecified regulatory clinical and commercial milestones as well as tiered royalties on the level of net sales from high single digits up to low double digits.

In June of 2025, we invested in Stalicla, a private clinical stage neurodevelopmental disorder focused company. Stalicla has developed a proprietary precision medicine patient stratification technology platform, which allows the company to select patients based on their biological dysregulation rather than behavioral phenotype. Proof-of-concept platform has been demonstrated by applying the technologies to identify and develop drugs in subpopulations of patients suffering from autism spectrum disorder.

Stalicla has made excellent progress in advancing its patient stratification study in autism and preparing its lead asset for a Phase III study in cocaine use disorders. We completed the year with CHF 1.6 million of cash, which provides us with cash runway through mid-2026. I'd like to highlight that the cash burn has been significantly reduced following the Neurosterix spin-out transaction, however, the current cash does not fund the progression of our unpartnered programs into the clinic.

Now for a quick review of our pipeline. We continue to believe in dipraglurant and are executing our plans to reposition the development of brain injury recovery and in particular, post-stroke recovery. As mentioned, our partner, Indivior has selected a GABAB PAM drug candidate for development in substance use disorders and completed IND-enabling studies. We are advancing an independent GABAB PAM program for chronic cough and expect to start IND-enabling studies this year, subject to securing financial backing for the program.

As a reminder, we spun out our portfolio of neuropsychiatric assets in 2024 to create Neurosterix and raised $65 million from a syndicate of investors led by Perceptive Advisors. We retained a 20% equity interest in Neurosterix. Neurosterix has made excellent progress in advancing its pipeline in 2025, including starting Phase I studies with NTX-253, its M4 positive allosteric modulator program, and we are expecting Phase I to be completed this quarter.

Now I will hand over to Misha, who will give you some more details about our exciting portfolio.

Thanks, Tim. Hello, everyone. I will start by speaking about dipraglurant and our plans for development in brain injury recovery. Dipraglurant is an orally available, highly selective mGlu5 negative allosteric modulator, which we believe could improve the outcome of rehabilitation for patients suffering from traumatic brain injury or stroke.

The mechanism of action of dipraglurant targets neuroplasticity early in rehabilitation to promote building of neuronal connections and sensory motor recovery. There is a large unmet medical need in post-stroke recovery and rehabilitation. Stroke is among leading causes of chronic often lifelong disability as it leads to motor sensory, cognitive impairment and multiple comorbidities. There are over 100 million stroke survivors worldwide, and the number is growing at the annual rate of 12 million.

A variety of rehabilitation therapies are used with post-stroke patients, but the recovery is slow and often inadequate. There is an urgent need for pharmacological agents that can facilitate the recovery stimulated by rehabilitation therapies. mGlu5 receptor is a suitable target to address post-stroke recovery as it is densely expressed in the brain, involved in neuroplasticity and modulates excitatory/inhibitory equilibrium.

In fact, activation of mGlu5 has been observed in a large -- in a range of neurological disorders, including stroke, where it plays a role of so-called maladaptive rewiring of the brain following stroke. Inhibition of mGLu5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neuroplasticity and creating of new functional pathways moving the neural network towards a pre-lesion state.

Exciting new evidence recently published in the Journal of Brain suggests that the negative allosteric modulator of mGLu5 MTEP administered daily in rats following stroke results in a sustained and growing improvement in sensory motor function in comparison to vehicle treatment. Similar improvement in sensory motor function was observed in animals treated with our mGlu5 NAM, dipraglurant.

MRI imaging of the resting state functional connectivity in post-stroke rodents shows that daily administration of MTEP also stimulates intra and interhemispheric connectivity in the brain disrupted by stroke. It is important to note that improvement in brain connectivity after stroke is known to correlate with functional recovery and is observed across species.

Dipraglurant is ideally suited to be used in tandem with rehabilitation therapies in post-stroke patients as it has a fast onset of action and short half-life. It has shown good tolerability in healthy subjects and in Parkinsonian patients showing only mild-to-moderate CNS-related adverse effects. We have a drug product ready and a strong patent position and believe dipraglurant can become a first-in-class drug to facilitate post-stroke recovery.

We can also speculate that dipraglurant-mediated adaptive rewiring and facilitation of recovery following brain damage would also be seen in traumatic brain injury patients. As part of our agreement with Indivior, Addex has exercised its rights to select a compound to advance its own independent GABAB PAM program for the treatment of chronic cough.

I will now present this exciting opportunity. There is a strong rationale for developing GABAB PAMs for chronic cough. Chronic cough is a persistent cough that lasts for more than 8 weeks and can be caused by a variety of factors, including respiratory infections, asthma, allergies and acid reflux, but also possibly by a cough hypersensitivity syndrome. There is a large unmet medical need in novel antitussive drugs as current standards of care are ineffective in 30% of patients or only moderately effective in up to 60% of patients.

In addition, the current treatments carry risks of serious side effects. Support for using GABAB PAMs in treatment of chronic cough comes from the clinical evidence that baclofen, a GABAB agonist, is used off-label in cough patients and from the anatomical evidence that GABAB receptors are strongly expressed in airways and in the neuronal pathway regulating cough. Therefore, we believe that GABAB PAMs could offer superior efficacy in cough patients.

The pre-IND activities, including in vivo proof-of-concept, non-GLP tox and CMC have been completed, and our clinical candidate has shown favorable efficacy, tolerability and developability profiles. Our clinical candidate has demonstrated a consistent minimum effective dose of 1 mg per kg and ED50 of 6 mg per kg in cough frequency in Guinea pigs. No signs of tolerance were seen after subchronic dosing and more than 60-fold safety margin was demonstrated based on respiratory depression and sedation biomarker.

Recently, we also confirmed the antitussive efficacy of Compound 1 in the nonhuman primates. The IND-enabling studies are planned and ready to start subject to receiving funding. In the model of citric acid-induced cough in Guinea pigs, acutely administered Compound A delivered a robust antitussive efficacy, reducing the cough number dose dependently and achieving 70% reductions at the maximal doses. The antitussive profile of compound A was similar to that of Nalbuphine, Orvepitant, Baclofen, and Codeine.

Compound A increased the latency to first cough dose dependently, thus delaying the onset of cough. The antitussive profile of Compound A in delaying cough onset was similar or better than that of reference drugs. In the same experiment, Compound A appeared well tolerated as there were no marked changes in respiratory rate at up to 6 mg per kg. In contrast, Nalbuphine, Orvepitant, Baclofen and Codeine resulted in robust reductions in respiratory rate at their highest doses, indicative of sedative-like effects.

When evaluation of the antitussive efficacy across compounds was done at the respective highest doses free from respiratory effects, Compound A was shown to be superior to Nalbuphine, Orvepitant, Baclofen and Codeine in both cough number and cough latency measures. In the model of ATP potentiated citric acid cough in Guinea pigs in a head-to-head comparison experiment, acutely administered Compound A and the P2X3 inhibitor had similar efficacy and tolerability profiles.

In the citric acid-induced cough model, subchronic administration of Compound A for 7 days showed no signs of tolerance, neither in cough frequency nor in latency to first cough. Also, there were no changes in the respiratory rate, body temperature and growth hormone release in animals treated subchronically with Compound A.

In the model of IPF-related exacerbated chronic cough in Guinea pigs, on day 0, animals received a single oropharyngeal administration of bleomycin or were left intact. Bleomycin-exposed animals were then treated with Compound A 10 mg per kg or vehicle orally once daily for 28 days. Intact animals received only vehicle. On day 7, 14, 21 and 28, animals were exposed to low concentration of citric acid to stimulate cough.

On day 28, at the end of the experiment, the lung tissue was collected for histopathological analysis. The total number of coughs was significantly higher in bleomycin-exposed vehicle-treated animals than in healthy controls. The difference between the groups grew progressively larger over time, indicative of exacerbated cough in IPF-like condition. Chronic treatment with Compound A resulted in robust and enduring reductions in the number of coughs with 40% to 60% efficacy.

The latency to first cough showed significant reductions in bleomycin-exposed vehicle-treated animals versus intact control starting day 14. Chronic treatment with Compound A reversed the effect of bleomycin throughout the testing period, returning the latencies to the levels of intact control animals. Histopathological analysis of the lung tissue collected on day 28 revealed that chronic administration of Compound A was associated with markedly lower Ashcroft scores and lower percentage of affected lung in comparison to bleomycin-exposed vehicle-treated animals.

In the model of citric acid-induced cough in nonhuman primates, Compound A had no effect on the number of coughs at 0.6 and 1 while producing significant and more than 60% reductions at 2 mg per kg.

In summary, we have selected a clinical candidate for chronic cough with a robust reproducible antitussive efficacy of 1 mg per kg and good PK/PD. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs and nonhuman primates. The compound has a potential to have the best-in-disease efficacy and tolerability profile and broad application in cough patients. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs and nonhuman primates. Subject to raising financing, we are ready to start the IND-enabling studies. This concludes our prepared remarks on the progress of our R&D programs.

Now I hand it back to Tim.

We recognized CHF 0.2 million of income in 2025 compared to CHF 0.4 million in 2024. The decrease is primarily due to the completion of the funded research phase of our collaboration with Indivior in June of 2024. This has been partially offset by the fair value of the services received from Neurosterix Group at 0 cost.

R&D expenses -- sorry, R&D expenses of CHF 0.7 million primarily related to our GABAB PAM program and decreased by CHF 0.2 million in 2025 compared to 2024, mainly due to the completion of the research phase of our collaboration with Indivior. G&A expenses remained stable at CHF 2.3 million in 2024 and 2025 and primarily relate to professional service fees linked to corporate development activities. As a reminder, on April 02, 2024, we received an equity interest of 20% in Neurosterix U.S. Holdings LLC as part of the Neurosterix spin-out transaction.

Under IFRS accounting standards, we are required to account for the investment using the equity method of accounting and recognize our share of Neurosterix results in our income statement. For the 12-month period ended December 31, 2025, our share of these net -- of the net loss of Neurosterix amounted to CHF 4 million compared to CHF 2.2 million for the period April '24 through December '24. The finance net result is close to 0 in both '25 and 2024 and is primarily related to foreign exchange differences on our U.S. cash deposits.

Now moving on to the balance sheet. Our assets are primarily held in cash, and we completed 2025 with CHF 1.6 million in cash held in Swiss francs and U.S. dollars. Our current assets amounted to [ CHF 41,000 ] primarily related to decreased prepaid [ patent ] costs and retirement benefits. Our noncurrent assets of CHF 4.6 million as of December primarily relate to our investment in Neurosterix, which has been accounted using the equity method and the investment in Stalicla of CHF 0.8 million. Current liabilities of CHF 1.2 million at the end of the year 2025 increased by CHF 0.4 million compared to December of the previous year 2024 and primarily relate to R&D-related accruals and payables.

Noncurrent liabilities of CHF 0.4 million as of December 31, '25, increased by CHF 0.2 million compared to December 2024, primarily due to an actuarial experience adjustment in the calculation of the defined benefit obligations. Now to the cash flow statement. On December 31, 2025, the cash balance amounted to CHF 1.6 million and decreased by CHF 1.7 million compared to the beginning of the year. This is primarily due to the cash used in operating -- operations and investing activities for a combined amount of CHF 2.9 million, which has been partly offset by the sale of treasury shares for a total amount of CHF 1.3 million during the year.

Now to summarize, we have made excellent progress advancing the GABAB PAM program for cough and our dipraglurant post-stroke recovery program. Our spin-out company, Neurosterix, continues to advance its portfolio with their M4 positive modulator program on track to complete the Phase I this quarter. We are very pleased by the progress [indiscernible] is making at advancing on its business strategy and pipeline, and we are looking forward to completing our evaluation of potential indications for our mGlu2 PAM program and securing the financial resources to advance our portfolio into clinical studies.

This concludes the presentation, and we will now open the call for questions.

[Operator Instructions] Now we're going to take our first question. And it comes from the line of Raghuram Selvaraju from H.C. Wainwright.

This is [indiscernible] sitting in for Ram. I have two questions. The first is which subsets of patients with chronic cough is the GABAB PAM most likely to be aimed at? Would you say it's IPF, sarcoidosis or something else? And how large could that total market be if the compound had a broad antitussive label?

Yes. So, Misha, would you like to answer?

Yes, of course. Well, considering the profile of this compound, which has balanced central peripheral activity profile, we believe that it will be suitable for a broad range of chronic cough patients, especially due to the fact that it has central component, which we believe is very important in reducing central sensitization seen in certain chronic cough patients. These patients do not respond to peripherally restricted P2X3 inhibitors, but can respond to morphine, which we believe is centrally acting.

So this way, the profile is able to address problems in chronic cough [ circuit ] that are both peripheral and central. Our initial intention is to confirm the efficacy of the compound in chronic cough patients that come from unexplained or refractory chronic cough category. But once this efficacy is confirmed, we intend to broaden our patient population in subsequent studies.

And which psychiatric clinical indications might be best suited to address Addex's portfolio of mGlu7 NAM candidates?

The mGlu7 candidate is not in Addex. It's sitting in the spin-out company, Neurosterix. So we're not at liberty to talk in detail about that. But in general, maybe Misha, you can say what you can.

Absolutely. There are a number of academic studies looking at mGlu7 knockout mice that show quite remarkable and very broad potential for inhibitors as mGlu7 knockout show reduced anxiety and depression-like reactivity. They show reduced expression of conditioned fear. They show reduced aggressivity and agitation and certain signs of reduced responsiveness to psychostimulants.

So even with this data that have been then confirmed in several pharmacological studies, some of those that were published by us show that we can orient the mGlu7 negative modulators towards anxiety and panic, agitation, aggressivity, depression and perhaps psychosis and mania.

[Operator Instructions] Dear speakers, there are no further questions for today. Thank you, ladies and gentlemen. This brings the main part of our conference to a close. And I would like to hand back to Tim Dyer for closing remarks.

Thank you. So I'd just like to thank everyone for attending our 2025 conference call. And I wish you all a very nice day, and we look forward to speaking to you again soon. Thank you.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

Good day, and thank you for standing by. Welcome to the Addex Therapeutics Third Quarter 2025 Financial Results and Corporate Update Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to our first speaker today, Tim Dyer, CEO. Please go ahead.

Thank you. Hello, everyone. I'd like to thank you all for attending our third quarter 2025 financial results conference call. I'm here with Misha Kalinichev, our Head of Translational Science, who will be providing an update on our R&D programs. I draw your attention to the press release and the financial statements issued earlier today, which are available on our website. I also draw your attention to our disclaimers. We will be making certain forward-looking statements that are based on the knowledge we have today. I will start this conference call by giving a quick overview of our recent activities and achievements before reviewing our pipeline. I will then hand over to Misha, who will review in more detail our dipraglurant post-stroke recovery program and GABAB PAM preclinical program for cough.

I will then review our Q3 2025 financial results. Following that, we will open the call for Q&A. The third quarter of 2025 has seen several important achievements across our pipeline. We've made excellent progress in our GABAB PAM program. We continue to complete preclinical characterization of our selected compound. We've also selected a backup compound for this important program. As a reminder, our partner, Indivior, successfully completed IND-enabling studies with their selected drug candidate for substance use disorders. Under the terms of the agreement, Addex is eligible for payments of up to USD 330 million on successful achievement of prespecified regulatory clinical and commercial milestones as well as tiered royalties on the level of net sales from high single digits up to low double digits. Also under the terms of the agreement, we have the right to select compounds for development in a predefined list of reserved indications.

As mentioned, we have selected a compound and are advancing its development for chronic cough. We have repositioned dipraglurant, our mGlu5 negative allosteric modulator for brain injury recovery and have made good progress in preparing the program for clinical studies. As a reminder, earlier this year, we entered into an option agreement, giving us access to an exclusive license to intellectual property covering the use of mGlu5 inhibitors in this interesting therapeutic indication. Included in this agreement is a research collaboration in which we are working with Sinntaxis and the University of Lund to complete preclinical profiling of dipraglurant and prepare the clinical studies. Our spin-out company, Neurosterix is making excellent progress in advancing its portfolio of preclinical programs, including a potentially best-in-class M4 PAM schizophrenia. In June, we invested in Stalicla, a private clinical stage neurodevelopmental disorders focused company.

Stalicla has developed a proprietary precision medicine patient stratification technology platform, which allows the company to select patients based on the biological dysregulation rather than behavioral phenotype. Proof-of-concept platform has been demonstrated by applying the technologies to identify and develop drugs in subpopulations of patients suffering from autism spectrum disorders. Stalicla has made excellent progress in advancing its patient stratification study in autism as well as advancing discussions with pharma to apply its technology more broadly in neuropsychiatric disorders. We completed the third quarter with CHF 2.2 million of cash, which provides us with a cash runway through mid-2026. I'd like to highlight that the cash burn has been significantly reduced following the Neurosterix spinout transaction; however, current cash does not fund progression of our unpartnered programs into the clinic. Now for a quick review of our pipeline. We continue to believe in dipraglurant and are executing our plans to reposition the development of brain injury recovery.

As mentioned, our partner, Indivior has selected the GABAB PAM drug candidate for development in substance use disorders and we successfully completed IND-enabling studies. We are advancing an independent GABAB PAM program for chronic cough and are ready to start IND-enabling studies subject to securing financing. Neurosterix made excellent progress advancing its pipeline, including completing IND-enabling studies for their M4 PAM program. Program is on track to dose patients this year, and we expect to be able to announce further progress in the coming months.

Now I will hand over to Misha, who will give you some more details about our exciting portfolio.

Thanks, Tim. Hello, everyone. I will start by speaking about dipraglurant and our plans for development in brain injury recovery. Dipraglurant is an orally available, highly selective mGlu5 negative allosteric modulator, which we believe could improve the outcome of rehabilitation for patients suffering from traumatic brain injury or stroke. The mechanism of action of dipraglurant targets neuroplasticity early in rehabilitation to promote rebuilding of neuronal connections and sensory motor recovery. There is large unmet medical need in post-stroke recovery and rehabilitation. Stroke is among leading causes of chronic often lifelong disability as it leads to motor, sensory, cognitive impairment and multiple comorbidities. There are over 100 million stroke survivors worldwide, and the number is growing at the annual rate of 12 million. A variety of rehabilitation therapies are used with post-stroke patients, but the recovery is slow and often inadequate.

There is an urgent need for pharmacological agents that can promote the recovery stimulated by rehabilitation therapy. mGlu5 receptor is a suitable target to address post-stroke recovery as it is densely expressed in the brain, involved in neuroplasticity and modulates excitatory-inhibitory equilibrium. In fact, activation of mGlu5 has been observed in a range of neurological disorders, including stroke, where it plays a role in maladaptive rewiring of the brain following stroke. Inhibition of mGlu5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neuroplasticity and creating of new functional pathways moving the neural network towards the pre-lesion state. Exciting new evidence recently published in the Journal Brain suggests that the negative allosteric modulator of mGlu5, MPEP administered daily in rats following stroke results in a sustained and growing improvement in sensory motor function in comparison to vehicle treatment.

Similar improvement in sensory motor function was observed in animals treated with our mGlu5 NAM dipraglurant. MRI imaging of the resting state functional connectivity in post-stroke rodents shows that daily administration of MTEP also stimulates intra and interhemispheric connectivity in the brain disrupted by stroke. It is important to note that improvement in brain connectivity after stroke is known to correlate with functional recovery and is observed across species. Dipraglurant is ideally suited to be used in tandem with rehabilitation therapies in post-stroke patients as it has a fast onset of action and short half-life. It has shown good tolerability in healthy subjects and in Parkinsonian patients showing only mild to moderate CNS-related adverse events. We have a drug product ready and a strong patent position and believe dipraglurant can become a first-in-class drug to facilitate post-stroke recovery.

We can also speculate that dipraglurant-mediated adaptive rewiring and facilitation of recovery following brain damage would also be seen in traumatic brain injury patients. Let me now turn to GABAB program and the exciting opportunity that it offers to the chronic cough patients. There is a strong rationale for developing GABAB PAM for chronic cough. Chronic cough is a persistent cough that lasts for more than 8 weeks and can be caused by a variety of factors, including respiratory infections, asthma, allergies and acid reflux, but also by cough hypersensitivity syndrome. There is a large unmet medical need in novel antitussive drugs as current standards of care are ineffective in 30% of patients and only moderately effective in up to 60% of patients.

In addition, the current treatments carry risks of serious side effects. Support for using GABAB positive allosteric modulators in treatment of chronic cough comes from the clinical evidence that baclofen GABAB agonist is used off-label in cough patients and from the anatomical evidence that GABAB receptors are strongly expressed in airways and in the neuronal pathway regulating cough.

Therefore, we believe that GABAB PAMs could offer superior efficacy in cough patients. The pre-IND activities, including in vivo proof-of-concept studies, non-GLP tox and CMC have been completed. Our clinical candidate has shown favorable efficacy, tolerability and developability profiles. The compound has demonstrated a consistent minimum effective dose of 1 mg per kg and ED50 of 6 mg per kg in models of cough in vivo. No signs of tolerance were seen after subchronic dosing and more than 60-fold safety margin was demonstrated based on respiratory depression, a sedation biomarker. The IND-enabling studies are planned and ready to start subject to securing financing. In the model of citric acid-induced cough guinea pig, acutely administered compound A delivered a robust antitussive efficacy, reducing the cough number dose dependently and achieving 70% reductions at the maximal doses. The antitussive profile of compound A was similar to that of nalbuphine, Orvepitant, Baclofen, and Codeine.

Compound A increased the latency to first cough dose dependently, thus delaying the onset of cough. The antitussive profile of compound A in delaying cough onset was similar or better than that of reference drugs. In the same experiment, compound A appeared well tolerated as there were no marked changes in respiratory rate at up to 60 mg per kg. In contrast, Nalbuphine, Orvepitant, Baclofen, and Codeine resulted in robust reductions in respiratory rate at their highest doses, indicative of sedative-like effects. When evaluation of the antitussive efficacy across compounds was done at the respective high doses free from respiratory effects, compound A was shown to be superior to Nalbuphine, Orvepitant, Baclofen, and Codeine in both cough number and cough latency measures. In the model of ATP potentiated citric acid cough in guinea pig in a head-to-head comparison experiment, acutely administered compound A exhibited a trend of better efficacy and potency in comparison to that of P2X3 inhibitor while showing signs of similar tolerability.

In summary, we have selected a clinical candidate for chronic cough with a robust reproducible antitussive efficacy of 1 mg per kg and good PK/PD. The compound has the potential to have the best-in-class efficacy and tolerability profile and broad application in cough patients. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs and nonhuman primates. Subject to raising financing, we are ready to start the IND-enabling studies. This concludes our prepared remarks on the progress of our R&D.

Now I'll hand it back to Tim.

Thanks, Misha. Now for a review of the Q3 2025 financials. Starting with the income statement. Income in Q3 2025 remains similar to our income in Q3 of 2024 and amounted to CHF 0.1 million, which is mainly related to the maintenance of patents licensed to Indivior, which they are funding and to the fair value of services received from Neurosterix Group at 0 cost. R&D expenses of CHF 0.2 million in Q3 2025 are primarily related to our GABAB PAM program remain similar to Q3 2024. G&A expenses of CHF 0.5 million in Q3 2025 remained stable compared to Q3 2024. As a reminder, we are accounting for our investment in Neurosterix using the equity method of accounting and therefore, recognized our share of the net loss of CHF 0.9 million for Q3 2025, which is similar to the amount for Q3 2024. Now to the balance sheet. Our assets are primarily held in cash, and we completed Q3 2025 with CHF 2.2 million of cash held in Swiss francs and U.S. dollars. Other current assets amounted to CHF 0.2 million, primarily related to prepaid R&D and G&A costs.

Our noncurrent assets of CHF 5 million as of September 30, 2025, primarily related to our 20% equity interest in Neurosterix Group recorded on the balance sheet under the equity method of accounting for associates and also, to a lesser extent, our investment in Stalicla. Current liabilities of CHF 1.2 million at the end of September increased by CHF 0.4 million compared to December 31, 2024. This is primarily due to increased payables related to professional services. Noncurrent liabilities of CHF 0.2 million at the end of Q3 are consistent with amounts at the end of December of 2024 and primarily attributable to retirement benefit obligations. Now to summarize, we've made excellent progress in advancing our GABAB PAM program for cough and our dipraglurant post-stroke recovery program. Our spin-out company, Neurosterix continues to advance its portfolio with the M4 PAM program set to start Phase I this year.

We are very pleased to be -- by the progress Stalicla is making advancing its business strategy and pipeline. We're looking forward to completing our evaluation of potential indications for our mGlu2 PAM program, which we received back from J&J and continuing to advance our portfolio towards clinical studies. This concludes the presentation, and we will now open the call for questions.

[Operator Instructions] And now we take our first question -- and it comes from the line of Ram Selvaraju from H.C. Wainwright.

Four quick ones. Firstly, I was wondering if you could comment on the commercial outlook for a potential therapeutic intervention in chronic refractory cough, particularly in the context of the fact that gefapixant doesn't appear to now be a factor in the United States market. Secondly, I wanted to ask about ultimately, what you expect the next funding catalyst for Stalicla to be and what the outlook might be for Stalicla to pursue a path to a public listing, if that's something you can comment on at this time.

Thirdly, I wanted to see if you could give us some context around competitive clinical development in the post-stroke recovery space, particularly as this pertains to CCR5 receptor modulators and especially the ongoing clinical programs with maraviroc, which was originally approved as an anti-HIV medication. And if you could perhaps give us a sense of how those trials, particularly the CAMAROS trial might provide important learnings for future development of a candidate in post-stroke recovery like dipraglurant. And lastly, maybe you can give us a sense of what Indivior is looking for next in your ongoing collaboration and what catalysts you expect over the course of 2026?

Okay. Yes. So the first question regarding the commercial outlook in cough. You're absolutely right. Gefapixant seems not to be doing particularly well. I think -- I mean, there are a number -- well, first of all, it's not registered in the U.S. I mean one of the reasons that Camlipixant was acquired by GSK when GSK acquired BELLUS for CHF 2 billion is because it seems to not have the same taste disturbance issues that Gefapixant had. And we understand that data from the Phase III with Camlipixant is coming out in the coming months. We have done some commercial assessments on cough. We haven't actually disclosed our position on how we see the commercial opportunity. However, we still see it as a significant unmet medical need.

We know from our discussions with KOLs that baclofen is efficacious in cough patients. And the only reason it's not being used more widely. It's a drug that has to be dosed about 5 times a day. And the efficacious dose is sedative. So patients can't drive their cars. And therefore, it's really a last resort. What we've also heard from KOLs that we're working with is that up to 50% of cough patients who take P2X3 inhibitors or gefapixant are discontinuing treatment or nonresponding. We haven't got any breakout of the nonresponders versus the ones that discontinue due to the disturbance. So that's question one. Misha, would you like to add anything to that?

Yes. I just wanted to mention that recent evaluation of responders to gefapixant shows that there are up to 50% of patients that have no benefit from this mechanism, which is higher than was initially predicted, which was around 30%. It's not surprising considering that P2X3 inhibitor really captures only single mechanism, peripheral mechanism that is responsible for chronic cough. There are multiple other peripheral mechanisms leading to chronic cough. And importantly, there are central mechanisms that remain to be addressed. And the advantage of the approach that we are taking is that centrally acting GABAB PAM will be able to address needs of all these patients.

So on to the question too about Stalicla. Yes. So we're very happy with the progress that Stalicla is making. I mean they are -- they're continuing to execute on their warehousing study. So they are recruiting nonpharmacological intervention study, but they're recruiting patients in order to stratify them into the different phenotypes that they've identified. And these patients are sort of been warehoused ready for the pharmacological intervention studies. And -- regarding the fundraising, they are currently working on a private company. I think it's well understood that they are working on a Series C financing. This financing is to fund 2 clinical program, Phase II clinical studies for 2 subpopulations within autism spectrum disorders.

They are also in parallel working on out-licensing an asset that they in-licensed from Novartis. This is mavoglurant, an mGlu5 -- most advanced mGlu5 negative allosteric modulator, which has shown excellent data in a Phase II study for cocaine use disorder. I know that they are getting some traction from various pharma parties around the out-licensing of that. So I think one of these activities or both, we're hoping will occur. Now the question regarding IPO. I mean, private companies are always staying close to the idea of IPOs, especially if there's a strong need for capital, given the current warming up of the market, I'm aware that Stalicla is certainly looking at this as a potential funding mechanism. So that's number two.

Number three, regarding stroke, thank you very much for raising the topic of the CAMAROS trial with [indiscernible]. Two weeks ago, we were actually in Sweden discussing with our partner, Sinntaxis, Lund University, and we had the pleasure of meeting the lead investigator, Sean Dukelow, who is leading that study, and we are certainly planning to collaborate with him and others that are involved in that study and there's a lot of learnings from that study that we can certainly benefit from when planning the study of dipraglurant. And Misha, would you like to add?

Yes, happy to follow up this topic. Of course, we follow this story since it was first shared by the Science magazine a few years back and then a series of very elegant experiments published in the [ cell ] journal and now a clinical trial. We follow this with interest and excitement. We believe that it shows that there is a potential for improvement in post-stroke recovery via adding a pharmacological agent exactly as we proposed with mGlu5.

We are not surprised as there are multiple overlapping and redundant mechanisms in the brain and identifying yet another mechanism that follows very similar path kind of supports our hypothesis. Very much like mGlu5, CCR5 is upregulated after stroke. Its inhibition in the animal either genetically or pharmacologically facilitates recovery exactly like what happens with mGlu5. Both receptors are GPCRs. And both receptors are upregulated after stroke. So there are multiple parallels, and we are very excited.

For sure, there will be many learnings for us at the end of this CAMAROS clinical trial, in particular, to understand how one can address sensory versus motor recovery readouts and the CAMAROS study is heavily leaning towards more motor. And in our discussion with clinical experts, we will put as much emphasis on sensory readouts as the motor ones. So for sure, there's a lot to learn, but we are very much in tune with this approach and looking forward to the outcome of this clinical trial.

Thanks. So on to the fourth question regarding Indivior. I mean Indivior, as I said, they've successfully completed the IND-enabling studies, and they are currently preparing to move the program forward. Unfortunately, I cannot give any more information on that at this stage. But again, we are still happy with the progress they are making to move the study forward.

Are there any other questions?

[Operator Instructions] Thank you, ladies and gentlemen. This brings the main part of our conference to a close. And I would now like to hand the conference back to Tim Dyer for closing remarks.

So I'd like to thank you all for attending, and we look forward to speaking to you again soon. I wish you all a great day.

This concludes today's conference call. Thank you for participating. You may now all disconnect.

Good day, and thank you for standing by. Welcome to the Addex Therapeutics Half Year 2025 Financial Results, Corporate Update Conference Call and Webcast. [Operator Instructions] Please note that today's conference is being recorded.

I would now like to turn the conference over to your speaker, Tim Dyer, CEO. Please go ahead, sir.

Thank you. Hello, everyone. I would like to thank you all for attending our half year 2025 financial results conference call. I'm here with Mikhail Kalinichev, who will provide an update on our R&D programs. I draw your attention to the press release and the financial statements issued yesterday, which are available on the website.

I also draw your attention to our disclaimer. We will be making certain forward-looking statements that are based on the knowledge we have today.

I will start this conference call by giving a quick overview of our recent activities and achievements before reviewing our pipeline. I will then hand over to Misha, who will review in more detail our GABAB PAM preclinical program for cough. I will then review our financial results. Following that, we will open the call for questions.

The first half of 2025 has seen several important achievements across our pipeline. We've made excellent progress in our GABAB PAM program with our partner, Indivior, successfully completing IND-enabling studies with their selective drug candidate for substance use disorders. As a reminder, under the terms of the agreement, Addex is eligible for payments of up to USD 330 million on successful achievement of prespecified regulatory clinical and commercial milestones as well as tiered royalties on the level of net sales from high single digit up to low double digits.

Also under the terms of the agreement, we have the right to select compounds for development in a predefined list of reserved indications. We have selected a compound to advance our own independent GABAB PAM program for the treatment of chronic cough. We have substantially completed preclinical profiling of our selected drug candidate and recently published robust antitussive data in multiple preclinical models of cough. Misha will speak about this exciting data later in our presentation.

We also regained rights to our mGlu2 positive allosteric modulator program, including the Phase II asset, ADX71149, from our partner, Johnson & Johnson. We are currently evaluating a number of therapeutic indications for the future development of this program. We have repositioned dipraglurant, our mGlu5 negative modulator, for brain injury recovery and recently entered into an option agreement giving us access to an exclusive license to intellectual property covering the use of mGlu5 inhibitors in this interesting therapeutic indication.

In June, we invested in Stalicla, a private clinical-stage neurodevelopmental disorder focused company. Stalicla has developed proprietary precision medicine patient stratification technology platform, which allows the company to select patients based on their underlying biological dysregulation rather than their behavioral phenotype. Proof of concept of the platform has been demonstrated by applying the technologies to identify and develop drugs in subpopulations of patients suffering from autism spectrum disorders.

We believe that Stalicla's technology platform can be broadly applied to other disease areas where patients are defined based on behavioral phenotype or where there is significant heterogeneity within the patient population.

Moving on to the financials. We completed the half year with CHF 2.3 million of cash, which provides us with a cash runway through mid-2026. I'd like to highlight that the cash burn has been significantly reduced following the Neurosterix spin-out transaction. However, current cash does not fund the progression of our unpartnered programs into the clinic.

Now for a quick review of our pipeline. We continue to believe in dipraglurant and are executing our plans to reposition the development of the drug for brain injury recovery. As mentioned, our partner, Indivior, has selected a GABAB PAM drug candidate for development in substance use disorders and successfully completed IND-enabling studies. We are advancing our independent GABAB PAM program for chronic cough and are ready to start IND-enabling studies subject to securing financing.

Neurosterix has made excellent progress in advancing its pipeline, including completing IND-enabling studies for their M4 PAM program. The program is on track to dose patients this year, and we expect to be able to announce further progress in the coming months.

Now I will hand over to Misha, who will give you some more details about our exciting portfolio.

Thank you, Tim. Let me start with GABAB allosteric modulator program which is partnered with Indivior. The aim of this collaboration is to deliver a better baclofen for substance use disorders. As a reminder, GABAB receptor activation has been clinically validated in a number of disease areas using baclofen, a GABAB allosteric agonist. Baclofen is FDA-approved for treatment of spasticity and is widely used off-label to treat numerous diseases, including substance use disorders.

However, baclofen has a short half-life and comes with significant side effects, hampering its wider use. Thus, there is a strong need for a better baclofen. We believe this can be achieved with positive allosteric modulators and their differentiated pharmacology, having the efficacy that is similar or better than that of baclofen but longer half-life and improved side effect profile.

Our partner, Indivior, has selected a GABAB PAM drug candidate for development in substance use disorders and completed IND-enabling studies in H1 2025. As part of our agreement with Indivior, Addex has exercised its right to select a compound to advance its own independent GABAB PAM program for the treatment of chronic cough. I will now present this exciting opportunity.

There is a strong rationale for developing GABAB PAM for chronic cough. Chronic cough is a persistent cough that lasts for more than 8 weeks and can be caused by a variety of factors, including respiratory infection, asthma, allergies and acid reflux but also by cough hypersensitivity syndrome. There is a large unmet medical need in novel antitussive drugs as current standards of care are ineffective in 30% of patients and only moderately effective in up to 60% of patients. In addition, the current treatments carry risks of serious side effects.

On the next slide, we show that GABAB PAMs are likely to have a superior tolerability profile in comparison to the current standard of care and show no taste-related side effects, as seen with a newly approved P2X3 inhibitor, gefapixant. Support for using GABAB PAMs in treatment of chronic cough comes from the clinical evidence that baclofen, a GABAB agonist, is used off-label in cough patients and from the anatomical evidence that GABAB receptors are strongly expressed in airways and in the neuronal pathway regulating cough. Therefore, we believe that GABAB PAMs could offer superior efficacy in cough patients.

With pre-R&D activities including in vivo proof of concept studies, non-GLP tox and CMC have been completed. Our clinical candidate has shown favorable efficacy, tolerability and developability profile. The compound has demonstrated a consistent minimum effective dose of 1 mg per kg and ED50 of 6 mg per kg in models of cough in vivo. No signs of tolerance were seen after sub-chronic dosing and more than sixty-fold safety margin was demonstrated based on respiratory depression and sedation biomarker. The IND-enabling studies are planned to start this year.

In the model of citric acid induced cough in guinea pigs, acutely administered compound A delivered a robust antitussive efficacy, reducing the cough number dose dependently and achieving 70% reduction at the maximal doses. The antitussive profile of compound A was similar to that of nalbuphine, [ olretitant ], baclofen and codeine. Compound A also increased the latency to first cough dose dependently, thus delaying the onset of cough. Its profile in delaying cough onset was similar or better than that of referenced drugs.

In the same experiment, compound A appeared well tolerated as there were no marked changes in respiratory rate at up to 60 mg per kg. In contrast, nalbuphine, [ olretitant ], baclofen and codeine resulted in robust reductions of respiratory rate at their highest doses, indicative of sedative-like effects. When evaluation of the antitussive efficacy across compounds was done at the respective high doses free from respiratory effects, compound A was shown to be superior to nalbuphine, [ olretitant ] baclofen and codeine in both cough number and cough latency measures.

Reductions in body temperature, a rodent-specific biomarker of GABAB receptor occupancy in the brain, suggests that at 60 mg per kg of Addex compound, there are less than 50% GABAB receptors occupied in contrast to near 100% of occupancy at 3 mg per kg of baclofen. Increases in growth hormone release in plasma, a translational biomarker of GABAB receptor occupancy in the brain, confirmed less than 50% receptor occupancy at up to 60 mg per kg of compound A.

Following sub-chronic administration for 7 days, compound A showed signs of improved efficacy and potency and no signs of tolerance in comparison to an acute treatment. No marked changes in respiratory rate, body temperature and growth hormones were seen in sub-chronic versus acute treatment conditions with compound A. In the model of ATP-potentiated citric acid cough in guinea pigs, in a head-to-head comparison experiment, acutely administered compound A exhibited a trend of better efficacy and potency in comparison to that of P2X3 inhibitor while showing signs of similar tolerability.

In summary, we have selected a clinical candidate for chronic cough with a robust reproducible antitussive efficacy of 1 mg per kg and good PK/PD. The compound has the potential to have the best-in-class, best-in-disease efficacy and tolerability profile and broad application in cough patients. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs and nonhuman primates. Subject to raising financing, we are ready to start the IND-enabling study.

This concludes our prepared remarks and the progress of our R&D program. Now I hand it back to Tim.

Thanks, Misha. Now for a review of our Q2 2025 financials. Starting with the income statement. Income decreased by CHF 0.1 million in Q2 2025 compared to 2024 and amounted to CHF 0.1 million. The decrease is primarily due to the completion of the funded research phase of our collaboration with Indivior.

R&D expenses of CHF 0.2 million primarily related to our GABAB PAM program and decreased by CHF 0.1 million in Q2 2025 compared to Q2 2024, and again, mainly due to the completion of the research phase of our collaboration with Indivior. G&A expenses of CHF 0.5 million decreased by CHF 0.1 million in Q2 2025 compared to Q2 2024 primarily due to decreased legal fees.

The share of net loss from the 20% participation in Neurosterix Group, accounted for using the equity method since April 2, 2024, increased by CHF 0.7 million and amounted to CHF 1.2 million for Q2 2025 compared to Q2 2024. Under IFRS, we are required to recognize our share of their results, which is a net loss.

Now to the balance sheet. Our assets are primarily held in cash, and we completed H1 2025 with CHF 2.3 million of cash held in Swiss francs and U.S. dollars. Other current assets amounted to CHF 0.4 million, primarily related to prepaid R&D and G&A costs. Our noncurrent assets of CHF 5.8 million as of June 30 primarily related to the 20% equity interest in Neurosterix Group, recorded on the balance sheet under the equity method of accounting for associates, and our investment in Stalicla.

Current liabilities of CHF 1.1 million at the end of June increased by CHF 0.3 million compared to December 2024, primarily due to increased payables. Noncurrent liabilities of CHF 0.1 million at the end of June decreased by CHF 0.1 million compared to the end of December, primarily due to the reduction in retirement benefit obligations following changes in financial assumptions.

Now to summarize. We have made excellent progress in our GABAB PAM program with our partner, Indivior, successfully completing IND-enabling studies with their selected compound for development in substance use disorders. Neurosterix has made excellent progress with their lead M4 PAM drug candidate successfully completing IND-enabling studies.

We have strengthened the IP in our mGlu5 NAM program and dipraglurant is ready to restart clinical development for brain injury recovery. Our GABAB PAM cough program has demonstrated excellent preclinical efficacy and tolerability with IND-enabled study ready to start. We are validating partnerships with industry supportive investors and a reasonably strong balance sheet, which puts us on a solid position to deliver on our strategic objectives.

This concludes the presentation, and we will now open the call for questions.

[Operator Instructions] We are now going to proceed with our first question, and the questions come from the line of Raghuram Selvaraju from H.C. Wainwright & Co.

Congratulations on all the recent progress. I just wanted to ask if you could comment on recent developments in the neuropsychiatry space, both from a precedent M&A as well as a licensing standpoint, that might conceivably have implications for both Neurosterix and Stalicla. And also, if you could comment on Stalicla's future funding requirements as well as the possibility of public listing for that entity.

Okay. Thank you very much, Ram, for that question. It's very encouraging to see that there is continued renewed excitement within the neuropsychiatry CNS space. As you know very well, this all started at the back end of 2023 and continued through 2024, and now we see renewed interest with a number of recent transactions. So we are strong believers in CNS.

And again, we've spun out Neurosterix with CHF 65 million in financing in a Series A in April last year really as a financing mechanism to get our portfolio of neuropsych assets moving. And they are moving very, very nicely. I really cannot speculate about the future of Neurosterix as we are a passive investor now, only holding 20%.

With respect to Stalicla, Stalicla is currently pursuing a number of strategies around financing, as are most private biotechs that are looking for money. They are discussing actively with potential pharma partners both at the preclinical -- sorry, at the pipeline level but also at the platform level. As you know, one of the things that Stalicla has pioneered and potentially is a world leader in this ability to stratify patients based on their underlying biological dysregulation as opposed to just select them based on phenotypes.

And they very much focused the platform on autism spectrum disorders, and they've developed a portfolio in-house. We're very excited about what we're doing. Now the financing need, they're pursuing a number of discussions with investors to do a Series C financing, and we will continue to be very supportive of what they are doing. So I hope that answers your question.

Yes. No, very helpful. Two other very quick ones, if I may. Notwithstanding the inability to speculate on the future of Neurosterix, I was just wondering if you could give us some insights into whether or not the development of long-acting injectable formulations could conceivably be a part of Neurosterix' long-term strategy in targeting the neuropsych space.

And also, if you could comment on the ideal or optimal target patient population for your chronic cough program, specifically as this pertains to those patients who have chronic cough of specific etiology, to what extent you've already determined what the ideal target patient population would be for future clinical development.

Okay. So there's two questions there. I'll leave Misha to answer the question on chronic cough. With regard to the muscarinic M4 space, we are all fully aware that Karuna has launched Cobenfy, this new class of antipsychotic. It's getting a lot of traction. There's a number of competitors out there both in the fixed dose combination area. But we are very focused -- well, Neurosterix is very focused on an absolutely selective M4 PAM.

As you know, AbbVie have now moved -- moving their M4 PAM, emraclidine, back into clinical development, so this is very exciting news, despite them hitting a little bit of a bump in the road last year -- or earlier this year, I should say. We've also seen Neumora as well moving two compounds into Phase I. I think we and others are strongly believing in the M4 PAM space. We are moving forward a compound, which is a once-daily small molecule.

Now we all know that in schizophrenia, compliance is an issue. So while at the moment, the development within Neurosterix is very focused on moving through Phase I and then into a Phase II study, I'm sure M4 PAM will be developed into longer-acting formulations, not because they need to be but just from a compliance point of view, That's the comments that I can make on the M4 PAM program within Neurosterix. And I'll hand over to Misha for comments on the GABAB.

Yes. From the range of GABAB PAMs that we had, we intentionally selected a centrally acting compound in order to broaden and maximize the range of clinical patients that we can aim at. This has been discussed a number of times with KOLs. And the progress of nalbuphine nicely captures the potential of centrally acting antitussive drugs and their superiority over peripherally restricted antitussive drugs, such as gefapixant and other P2X3 inhibitors.

We saw very robust effect of nalbuphine in IPF cough patients. And also in a recent data, they replicated this effect in refractory chronic cough patients. So that suggests that, indeed, the central approach, the central activity is essential for achieving maximal coverage of a variety of patients within chronic cough domain.

[Operator Instructions] There are no further questions showing. Thank you, ladies and gentlemen. This brings the main part of our conference to be close. And I would like to hand back to Mr. Tim Dyer for the closing remarks.

Well, thank you, everyone, for attending our half year 2025 conference call. We look forward to speaking to you again soon, and wish you all a very pleasant rest of your day.

This concludes today's conference call. Thank you all for participating. You may now disconnect your lines. Thank you.