Addex Therapeutics - Earnings Call - Q3 2025

Transcript

Speaker 0

Thank you for standing by. Welcome to the ADX Therapeutics Third Quarter twenty twenty five Financial Results and Corporate Update Conference Call and Webcast. At this time, all participants are in listen only mode. After the speakers' presentation, there will be the question and answer session. 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.

Speaker 1

Thank you. Hello, everyone. I'd like to thank you all for attending our third quarter twenty twenty five financial results conference call. I'm here with Misha Kalinichev, our Head of Translational Science, who will be providing an update on our R and 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 dipaglutide post stroke recovery program and gabapam preclinical program for cough. I will then review our Q3 twenty twenty five financial results.

Following that, we will open the call for Q and A. The 2025 has seen several important achievements across our pipeline. We've made excellent progress in our GABA B PAM program. With us, 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, ADX is eligible for payments of up to $330,000,000 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 select compounds for development in a predefined list of reserved indications. As mentioned, we have selected a compound on advancing its development of chronic cough. We have repositioned diproglurant, 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 Mgra5 inhibitors in this interesting therapeutic indication. Included in this agreement is a research collaboration with which we are working with Syntaxis and the University of Lund to complete preclinical profiling of different programs and prepare the clinical studies. Our spinout 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 Stellicla, a private clinical stage neurodevelopmental disorders focused company. Stellicla 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 disorders. Stellicola has made excellent progress 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 2,200,000.0 of cash, which provides us with a cash runway through mid-twenty twenty six. I'd like to highlight that the cash burn has been significantly reduced following the NeuroStarix 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 diproglant and are executing our plans to reposition this development brain injury recovery. As mentioned, our partner Indivior has selected the GABA B PAM drug candidate for development in substance use disorders and successfully completed IND enabling studies. We are advancing an independent gabapam program for chronic cough and are ready to start IND enabling studies subject to securing financing. NeuroStex made excellent progress 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.

Speaker 2

Thanks, Tim. Hello, everyone. I will start by speaking about dipragorant and our plans for development in brain injury recovery. Dipragorant is an orally available, highly selective mGluR5 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 dipraggluran targets neuroplasticity early in rehabilitation to promote rebuilding of neuronal connections and sensorimotor 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 one hundred million stroke survivors worldwide, and the number is growing at the annual rate of twelve 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.

MGluR5 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 MgLAR5 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 MgLR5, 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 states. Exciting new evidence recently published in the journal Brain suggests that the negative allosteric modulator of mGOR5, MpEp, administered daily in rats following stroke results in a sustained and growing improvement in sensorimotor function in comparison to vehicle treatment. Similar improvement in sensorimotor function was observed in animals treated with our m Guafive NAM dipraglutide.

MRI imaging of the resting state functional connectivity in post stroke autos shows that daily administration of NTAP 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. Cupraglirond 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 dipraglione can become a first in class drug to facilitate for stroke recovery.

We can also speculate that dipraglutide mediated adaptive rewiring and facilitation of recovery following brain damage would also be seen in traumatic brain injury patients. Let me 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 GABAB PAMs for chronic cough. Chronic cough is a persistent cough that lasts for more than eight 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 anti juicy drugs as current standards of care are ineffective in thirty percent of patients, and only moderately effective in up to sixty percent of patients.

In addition, the current treatments carry risks of serious side effects. Support for using GABA B positive ulceric 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 B 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 one mg per kg and ED fifty of six mg per kg in models of cough in vivo. No signs of tolerance was 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 financing. In the model of citric acid induced coughing guinea pigs, acutely administered compound a delivered a robust anti juicy efficacy, reducing the cough number dose dependently, and achieving 70% reductions at the maximal doses. The anti juicy profile of compound A was similar to that of nalbuphine or repitam, baclofen, codeine.

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 sixty mgskg. In contrast, nalbuphine or repitrant baclofenacudine resulted in robust reductions in respiratory rate at their highest doses indicative of sedative like effects. When evaluation of the attitudes of efficacy across compounds was done at the respective highest doses free from respiratory effects, compound A was shown to be superior to Norbuffin or Repetant, Bakufin, codeine in both COF number and COF latency measures.

In the model of ATP potentiated citric acid COF 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 p two x three inhibitor while showing signs of similar tolerability. In summary, we have selected a clinical candidate for chronic cough with a robust reproducible attitudes of efficacy of one mg per kg and good PKPD. The compound has a 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 raising financing, we are ready to start the IND enabling studies. This concludes our prepared remarks on the progress of our IND. Now I hand it back to Tim.

Speaker 1

Thanks, Misha. Now for a review of the Q3 twenty twenty five financials. Starting with the income statement. Income in Q3 twenty twenty five remained similar to our income 2024 and amounted to $100,000 It is mainly related to the maintenance of patents licensed to Indivior, which they are funding and to the fair value of services received from NeuroStarix Group, zero cost. R and D expenses of $200,000 in Q3 twenty twenty five are primarily related to our GAVAGRID PAM program and remain similar to Q3 twenty twenty four.

G and A expenses of $500,000 in Q3 twenty twenty five remained stable compared to Q3 twenty twenty four. As a reminder, we are accounting for our investment in Eurosteryx using the equity method of accounting and therefore recognized our share of net loss of $900,000 for Q3 twenty twenty five, which is similar to the amount for Q3 twenty twenty four. Now to the balance sheet. Our assets are primarily held in cash, and we completed Q3 twenty twenty five with CHF2.2 million of cash held in Swiss francs and U. S.

Dollars. Other current assets amounted to $200,000 primarily related to prepaid R and D and G and A costs. Our non current assets of $5,000,000 as of 09/30/2025, primarily related to our 20% equity interest in Eurosteoix Group recorded on the balance sheet under the equity method of accounting for associates and also to a lesser extent, our investment in Stellickla. Current liabilities, 1,200,000.0 at the September, increased by $400,000 compared to 12/31/2024. This is primarily due to increased payables related to professional services.

Noncurrent liabilities of 200,000.0 at the end of Q3 are consistent with amounts at the December 2024 and primarily attributable to retirement benefit obligations. Now to summarize, we've made excellent progress in advancing our GABA B PAN program for cough and our diproglure post stroke recovery program. Our spin out company, Eurosteryx, continues to advance portfolio with the M4 PAM program set to start Phase I this year. We're very pleased to be by the progress Vellixa is making advancing its business strategy and pipeline. We're looking forward to completing our evaluation of potential indications for our Englod II PAM program, which we received back from J and J and continuing to advance our portfolio into or towards clinical studies.

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

Speaker 0

You, dear participants. You. And now we're going to take our first question. Just give us a moment. And it comes from the line of Ram Selvaraju from H.

C. Wainwright. Your line is open. Please ask your question.

Speaker 3

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 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 Stellixa to be And what the outlook might be for Stellicola to pursue a path to a public listing? If that's something you can comment on at this time.

Thirdly, wanted to see if you could give us some context around contextual competitive clinical development in the post stroke recovery space, particularly as this pertains to CCR5 receptor modulators, and especially the ongoing clinical programs with Mirabarok, which was originally approved as an anti HIV medication. And if you could perhaps give us a sense of how those trials, particularly the CAMARUS trial, might provide important learnings for future development of a candidate in post stroke recovery like deproglurant? 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? Thank you.

Speaker 2

Okay.

Speaker 1

Yes. So the first question regarding the commercial outlook in cough. You're absolutely right. Gefapixon seems not to be doing particularly well. I think, I mean, there are a number well, 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 Bellis for $2,000,000,000 was because it seems to not have the same taste disturbance issues that gefapixant had. And we understand that data from the Phase III with cambipixant 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.

We still see it as a significant unmet medical need. We know from our discussions with KOLs that baclofen is efficacious in cough patients. The only reason it's not being used more widely is it's a drug that has to be dosed about five times a day. 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 fifty percent of 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 discontinued due to the taste disturbance. So that's question one. Misha, would you like to add anything to that?

Speaker 2

Yeah. I just wanted to mention that the recent evaluation of responders to gefapixant shows that there are up to fifty percent of patients that have no benefit from this mechanism, which is higher than was initially predicted, which was around thirty percent. It's not surprising considering that p two x three 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 gabapam will be able to address needs of all these patients.

Speaker 1

So on to the question two about Stellixla. Yes. So we're very happy with the progress that Stellixla is making. I mean they are continuing to execute on their warehousing studies. So they're recruited to 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 are sort of being warehoused ready for the pharmacological intervention studies. And regarding the fundraising, they are currently working on a mean, it's a private company. I think it's well understood that they are working on a Series C financing. This financing is to fund two program, Phase II clinical studies for two subpopulations within autism spectrum disorder. They're also in parallel working on out licensing an asset that they in licensed from Novartis.

This is Mavaglarant, an MGR5, the most advanced MGR5 megadallosteric 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. And given the current warming up of the market, I'm aware that Stellickler 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 CAMRUS trial with mirabiroc. Two weeks ago, we were actually in Sweden discussing with our partners in Texas, the Lind University, and we had the pleasure of meeting the lead investigator, Sean Duplo, 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 dipoleurons.

And, Nisha, would you like to add anything?

Speaker 2

Yes. Happy to follow-up this topic. Of course, we follow this story since it was first shared by the science magazine few years back, and then a series of very elegant experiments published in the sound 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 MOR five.

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 MOR five CCR five is upregulated after stroke. Its inhibition in animal either genetically or pharmacologically facilitates recovery exactly like what happens with mGluR5. 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. 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 the motor ones. So for sure there is a lot to learn, but we are very much in tune with this approach and looking forward to the outcome of this clinical trial.

Speaker 1

Thanks. So on to the fourth question regarding Indivior. 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.

Speaker 3

Thank you very much.

Speaker 1

Are there any other questions?

Speaker 0

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 Dye for closing remarks.

Speaker 1

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.

Speaker 0

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