Addex Therapeutics Ltd

for standing by. Welcome to the ADEX Therapeutics Third Quarter 2025 Financial Results and Corporate Update Conference Call and Webcast. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be the question and answer session. To ask a question during the session, you need to press star, one, one on your telephone keypad. You will then hear an automatic message advising your hand is raised. To withdraw a question, please press star, one, and one again. If you wish to ask a question via the webcast, please use the Q&A box available on the webcast link anytime during the live event. Please be advised that this conference is being recorded. I would now like to hand the conference over to our third 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 conference call. I'm here with Misha Kalinchev, our Head of Translational Science, who will be providing an update on our R&D program. 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 post-stroke recovery program and gather the PAM preclinical program for cost. 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 program because 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 in Divior successfully completed IND enabling studies with their selected drug candidate for substance use disorders. Under the terms of the agreement, Addix is eligible for payments of up to US$330 million on successful achievement of pre-specified 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 pre-defined list of reserved indications. As mentioned, we have selected a compound under advancing its development for chronic cost. We have repositioned diproglurons, our mGluR5 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 mGluR5 inhibitors in this interesting therapeutic indication. Included in this agreement is a research collaboration in which we are working with Syntaxis and the University of Lund to complete preclinical prototypes and prepare the clinical studies. Our spin-out company NeuroSterics is making excellent progress in advancing its portfolio of preclinical programs, including a potentially best-in-class M4PAM schizophrenia. In June, we invested in Stalicla, a private clinical stage neurodevelopmental disorders-focused company. Stalicla has developed proprietary precision medicine patient stratification technology platform, which allows the company to select patients based on their biological dysregulation rather than behavioural phenotype. Proof of concept, the platform has been demonstrated by applying the technologies to identify and develop drugs in subpopulations of patients suffering from autism spectrum disorder. Spelicula 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 2.2 million Swiss francs 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 neurosteric spin-out 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 Dick Proclorent and are executing our plans to reposition the development recovery. As mentioned, our partner Indovio has selected a GABBV-PAM drug candidate for development in substance use disorders and has successfully completed IMD enabling studies. We are advancing an independent GABBV-PAM program for CONICOP and are ready to start IMD enabling studies such as securing financing. NearestX has made excellent progress in advancing its pipeline, including completing IMD and aging studies for their M4PAM program. The program is on track to those 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 the program and our plans for development in brain injury recovery. Depravidorant is an orally available, highly selective mGluR5 negative ulcering modulator, which we believe could improve the outcome of rehabilitation for patients suffering from traumatic brain injury or stroke. The mechanism of action of Depravidorant targets neuroplasticity early in rehabilitation to promote rebuilding of neuronal connections and sensory motor recovery. There is large unmet medical needs 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 therapies. mGOR5 receptor is a suitable target to address post-stroke recovery as it is densely expressed in the brain. involved in neural plasticity and modulates excitatory-inhibitory equilibrium. In fact, activation of AMGULAR5 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 AMGULAR5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neuroplasticity and creating of new functional pathways, moving the neural network toward the pre-lesion state. Exciting new evidence, recently published in the journal Brain, suggests that the negative ulcerative modulator of MGR5, MPET, 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 sensorimotor function was observed in animals treated with our ANGLA-5 NAM depredulant. MRI imaging of the resting state functional connectivity in post-stroke rodents shows that daily administration of MPEP also stimulates intra- and inter-hemispheric 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. Depravirant 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 depravulant can become a first-in-class drug to facilitate post-stroke recovery. We can also speculate that depravulant-mediated adaptive rewiring as facilitation of recovery following brain damage would also be seen in traumatic brain injury patients. Let's now turn to GABA-B program and the exciting opportunity that it offers to the chronic cough patients. There is a strong rationale for developing GABA-B 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 by a cough hypersensitivity syndrome. There is a large unmet medical need in novel antitrust 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 GABA-B positive ulcerative modulators in treatment of chronic cough comes from the clinical evidence that baclofen, a GABA-B agonist, is used off-label in cough patients and from the anatomical evidence that GABA-B receptors are strongly expressed in airways and in the neuronal pathway regulating cough. Therefore, we believe that GABA-BPAMs could offer superior efficacy in cough patients. The pre-IND activities, including in vivo proof-of-concept studies, non-GLT talks, 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 cold in vivo. No signs of tolerance were seen after subchronic dosing, and more than 60-fold safety margin was demonstrated based on respiratory depression as sedation biomarker. The IND-enabling studies are planned and ready to start, subject to securing finance. In the model of citric acid-induced cough in guinea pigs, acutely administered compound A delivered a robust antitrusive efficacy, reducing the cough number dose-dependently and achieving 70% reductions at the maximal doses. The antitrusive profile of compound A was similar to that of nalbufin or repitam, baclofen, and coge. Compound A increased the latency to first cough dose-dependently, thus delaying the onset of cough. The antigenic 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 mcg. In contrast, nalbufin or repetant baclofen and codeine resulted in robust reductions in respiratory rate at their highest doses, indicative of sedative-like effects. When evaluation of the attitudinal efficacy across compounds was done at their respective highest doses free from respiratory effects, compound A was shown to be superior to nalbufin or repetant baclofen and codeine in both cough number and cough latency measures. In the model of ATP-potentiated citric acid COF in GDPs in a head-to-head comparison experiment, a futilely 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 COF with a robust reproducible attitudes of efficacy and good PKPD. The compound has the potential to have the best in class efficacy and tolerability profile and broad application in core patients. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs, and non-human primates subject to raising financing we are ready to start the R&D enabling studies. This concludes our prepared remarks on the progress of our R&D.

Now I hand it back to Tim. Thanks, Misha. Now for a view of the Q3 2025 financials. Starting with the income statements, income in Q3 2025 remains similar to our income in Q3 2024 and amounted to $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 Eurostarix Group at zero cost. R&D expenses of £0.2 million in Q3 2025 are primarily related to our Gather the Pound programme, and remain similar to Q3 2024. G&A expenses of 0.5 million in Q3 2025 remain stable compared to Q3 2024. As a reminder, we are accounting for our investment in Eurospherics using the equity method of accounting and therefore recognize our share of net loss of 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 2.2 million Swiss francs of cash held in Swiss francs and U.S. dollars. Other current assets amounted to 0.2 million, primarily related to prepaid R&D and G&A costs. Our long current assets of 5 million as of September 30th, 2025, primarily related to our 20% equity interest in U.S. tax group. on the balance sheet and the equity method of counting for associates. And also to a lesser extent, our investment in Spelicla. Current liabilities, 1.2 million at the end of September, increased by 0.4 million compared to December 31, 2024. This is primarily due to increased payables related to professional services. Non-current liabilities of 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 off-lake obligations. Now to summarise, we've made excellent progress in advancing our GABBV PAN programme for COF and our ViproGluon post-stroke recovery programme. Our spin-out company, Eurosterex, continues to advance our portfolio with the M4 PAN programme set to start Phase 1 this year. We're very pleased to be to buy the progress the LICRA is making in advancing its business strategy and pipeline. We're looking forward to completing our evaluation of potential indications for our NGLAR2PAM program, which we received back from J&J and continue to advance our portfolio into or towards clinical studies. This concludes the presentation, and we will now open the call for questions.

Thank you, dear participants.

As a reminder, if you wish to ask a question over the phone, please press star, one, one, on your telephone keypad, and wait for a name to be announced. To withdraw a question, please press star, one, and one again. Alternatively, you can submit your questions via the webcast. Please stand by, we'll compile the Q&A and all studies. We'll take a few moments. And now we're going to take our first question. Just give us a moment. And it comes from the line of Ram Sargaraju from HC Wainwright. Your line is open. Please ask your question.

Thank you so much for taking my questions. 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 defepixent 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 Stalikla to be and what the outlook might be for Stalikla 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 Miradaroc, which was originally approved as an anti-HIV medication. And if you could perhaps give us a sense of how those trials, particularly the CAMARIS trial, might provide important learnings for future development of a candidate in post-stroke recovery like Dipakurant. And lastly, maybe you can give us a sense of what Indivior is looking for next in your ongoing collaboration and what capitalists you expect over the course of 2026. Thank you.

Okay. Yeah, so the first question regarding the commercial outlook in COF. You're absolutely right. Jaffa Pixent seems not to be doing particularly well. I think, you know, 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 Camley Pixent was acquired by GSK when GSK acquired Bellis for $2 billion was because It seems to not have the same taste disturbance issues that getlipixent had. And we understand that, you know, data from the phase three with canlipixent is coming out in the coming months. We have, you know, we have done some commercial assessments on cough. We haven't actually disclosed, you know, our position. on how we see the commercial opportunity. You know, we still see it as a significant unmet medical need. We know from our discussions with KOL that, you know, Baclofen is efficacious in cough patients. The only reason it's not being used more widely is it's a drug that have to be dosed about five times a day. And, you know, the efficacious dose is sedative. So, you know, 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, you know, up to 50% of patients of COFF patients who take P2X3 inhibitors or Getopixin are discontinuing treatment or non-responding. We haven't got any breakout of, you know, the non-responders versus the ones that discontinued due to the case disturbance. So that's question one.

Misha, would you like to add anything to that? Yeah, I just wanted to mention that The recent evaluation of responders to jefapixant 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 a 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 GABA-BPAM will be able to address needs of all these patients.

So on to the question two about Stelicla.

Yeah, so we're very happy with the progress that Stelicla is making. I mean, they are, they're continuing to execute on their warehousing studies. So they're recruiting, it's a non pharmacological intervention study that they're recruiting patients in order to stratify them into the different phenotypes that they've identified. And these patients have sort of been warehoused ready for the pharmacological intervention study. 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 two clinical program, phase two clinical studies for two subpopulations within autism spectrum disorder. They're also in parallel working on outlicensing an asset that they in-license from Novartis. This is a Mavaglurant, an MGR5. the most advanced femoral 5-megaballosteric 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 outlicensing of that. And so I think, you know, one of these activities or both we're hoping will occur. Now, the question regarding IPO, I mean, Private companies are always, you know, staying close to the idea of IPOs, especially, you know, if there's a strong need for capital. Given the current warming up of the market, I'm aware that Stelikler 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 CAMERAS trial with Mara Siroc. Two weeks ago, we were actually in Sweden discussing with our partners in Texas, the Lund University, and we had the pleasure of meeting the lead investigator, Sean Ducklow. 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 . Misha, would you like to?

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 a 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 MWR5. 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 MGR5, CCR5, is upregulated after stroke. Its inhibition in the animal, either genetically or pharmacologically, facilitates recovery exactly like what happens with MGR5. Both receptors are GPCRs, and both receptors are upregulated after a 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 Camaro study is heavily leaning towards more motor, and in our discussion with clinical experts, we will put as much emphasis on sensory readouts as in 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

Thanks.

So on to the fourth question regarding Indivior. I mean, Indivior, as I said, they successfully completed the IMD 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.

Thank you very much. Are there any other questions?

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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 disconnect.