Addex Therapeutics - Earnings Call - H1 2025

Transcript

Tim Dyer (Founder and CEO)

Thank you. Hello, everyone. I'd 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 GABA-B 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 have made excellent progress in our GABA-B 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 $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 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 GABA-B 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 mGluR2 positive allosteric modulator program, including the phase 2 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 mGluR5 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 mGluR5 inhibitors in this interesting therapeutic indication. In June, 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 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 development of the drug for brain injury recovery.

As mentioned, our partner Indivior has selected a GABA-B PAM drug candidate for development in substance use disorders and has successfully completed IND-enabling studies. We are advancing our independent GABA-B 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.

Mikhail Kalinichev (Head of Translational Science)

Thank you, Tim. Let me start with GABA-B positive 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, GABA-B receptor activation has been clinically validated in a number of disease areas using baclofen, a GABA-B orthosteric 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 GABA-B 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 GABA-B PAM program for the treatment of chronic cough. I will now present this exciting opportunity. There is a strong rationale for developing GABA-B PAM 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 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 GABA-B 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 GABA-B PAMs in the treatment of chronic cough comes from the clinical evidence that baclofen, the 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 minimal effective dose of 1 mg/kg and ED50 of 6 mg/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 and sedation as biomarkers. 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% reductions at the maximal doses. The antitussive profile of Compound A was similar to that of naltrexone, aprepitant, 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 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/kg. In contrast, naltrexone, aprepitant, 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 highest doses free from respiratory effects, Compound A was shown to be superior to naltrexone, aprepitant, baclofen and codeine in both cough number and cough latency measures. Reductions in body temperature, rodent-specific biomarker of GABA-B receptor occupancy in the brain suggest that at 60 mg/kg of Addex compound, there are less than 50% GABA-B receptors occupied in contrast to near 100% receptor occupancy at 3 mg/kg of baclofen.

Increases in growth hormone release in plasma, a translational biomarker of GABA-B receptor occupancy in the brain, confirmed less than 50% receptor occupancy at up to 60 mg/kg of Compound A. Following subchronic administration for seven 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 hormone were seen in subchronic 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/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 known GLP tox studies performed in rats, dogs, and non-human primates. Subject to raising financing, we are ready to start the IND-enabling study. This concludes our prepared remarks on the summary of our R&D program. Now, I hand it back to Tim.

Tim Dyer (Founder and CEO)

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 GABA-B 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 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 US dollars. Other current assets amounted to CHF 0.4 million, primarily related to prepaid R&D and G&A costs. Our non-current assets of CHF 5.8 million as of June 30, primarily related to the 20% equity interest in Neurosterix 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.

Non-current liabilities of CHF 0.1 million at the end of June decreased by 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 GABA-B 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 and our mGluR5 NAM program, and dipraglurant is ready to restart clinical development for brain injury recovery. Our GABA-B PAM cough program has demonstrated excellent preclinical efficacy and tolerability with IND-enabling studies ready to start. We are validating partnerships with industry, supportive investors, and a reasonably strong balance sheet, which puts us in a solid position to deliver on our strategic objectives.

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

Operator (participant)

Thank you. As a reminder to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Once again, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. To ask a question via the webcast, please access the Ask a Question tab. Thank you. 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. Please ask your question.

Raghuram Selvaraju (Managing Director of Health Equity Research)

Thank you so much for taking my questions, and 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. Thank you.

Tim Dyer (Founder and CEO)

Okay. Thank you very much, Ram, for that question. I mean, it's very encouraging to see that there is continued renewed excitement within the neuropsychiatry CNS space. I mean, 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. We are strong believers in CNS. And again, we've spun out Neurosterix with CHF 65 million in financing in the 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 our 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 selecting based on phenotypes. And they very much focus the platform on autism spectrum disorders. They've developed a portfolio in-house. We're very excited about what they'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.

Raghuram Selvaraju (Managing Director of Health Equity Research)

Yep. Now, 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's 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? Thank you.

Tim Dyer (Founder and CEO)

Okay. So yeah, there's two questions there. I'll leave Misha to answer the question on chronic cough. I mean, with regard to the muscarinic M4 space, I mean, we are all fully aware that Karuna has launched Cobenfy. This new class of antipsychotic is getting a lot of traction. I mean, there's a number of competitors out there, both in the fixed-dose combination area, but we are very focused. Well, we, Neurosterix is very focused on an absolutely selective M4 PAM. As you know, AbbVie have now moved 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 one. So 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 one and then into a phase 2 study, I'm sure M4 PAMs will be developed into longer-acting formulations. Not because they need to be, but just from a compliance point of view. So 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 GABA-B.

Mikhail Kalinichev (Head of Translational Science)

Yeah. From the range of GABA-B PAMs that we had, we intentionally selected a centrally acting compound in order to broaden and maximize the range of chronic cough 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 GABA-B agonist and other P2X3 inhibitors. We saw very robust effects of nalbuphine in IPF cough patients. And also, in the 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 the chronic cough domain.

Raghuram Selvaraju (Managing Director of Health Equity Research)

Thank you very much for that clarification. Very helpful.

Operator (participant)

Thank you. As a reminder to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. To ask a question via the webcast, please access the Ask a Question tab. Please stand by while we compile the Q&A roster. This will take a few moments. Thank you. There are no further questions showing. Thank you, ladies and gentlemen. This brings the main part of our conference to a close. And I would like to hand back to Mr. Tim Dyer for the closing remarks.

Tim Dyer (Founder and CEO)

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.