Addex Therapeutics Ltd. Q2 FY2025 Earnings Call

Good day, and thank you for standing by. Welcome to the Addex Therapeutics Half Year 2025 Financial Results, Corporate Update Conference Call and Webcast. 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 the 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 the 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 a 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 a 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 to 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% 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 in a solid position to deliver on our strategic objectives. This concludes the presentation, and we will now open the call for questions.

We are now going to proceed with our first question, which comes from 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.

Thank you, Ram, for your question. It's very encouraging to see continued excitement in the neuropsychiatry CNS space. This started at the end of 2023 and has continued through 2024, with renewed interest shown in several recent transactions. We strongly believe in CNS. We spun out Neurosterix with CHF 65 million in financing through a Series A last April, which was intended to advance our portfolio of neuropsych assets, and they are progressing very well. I cannot speculate on the future of Neurosterix as we are now a passive investor holding 20%. Regarding Stalicla, they are exploring various strategies for financing like many private biotech companies seeking funding. They are actively in discussions with potential pharmaceutical partners at both the pipeline and platform levels. Stalicla has pioneered the ability to stratify patients based on biological dysregulation rather than just phenotypes, focusing their platform on autism spectrum disorders and developing an in-house portfolio. We are excited about what they are doing. They are currently pursuing discussions for Series C financing, and we will continue to support their efforts. I hope this 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. There are two questions here. I'll let Misha address the question regarding chronic cough. As for the muscarinic M4 space, we are all aware that Karuna has launched Cobenfy, which is gaining significant traction. There are several competitors in the fixed dose combination area, but we at Neurosterix are focused on developing a highly selective M4 positive allosteric modulator. AbbVie has shifted their M4 PAM, emraclidine, back into clinical development, which is exciting news despite some setbacks earlier this year. Additionally, Neumora has moved two compounds into Phase I. We and others are confident in the M4 PAM space. We are advancing a once-daily small molecule that addresses compliance issues in schizophrenia. Although our current focus at Neurosterix is progressing through Phase I and into Phase II studies, I believe longer-acting formulations of M4 PAM will eventually be developed, primarily for compliance reasons. That's my input on the M4 PAM program at Neurosterix. Now I'll turn it 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.

There are no further questions showing. Thank you, ladies and gentlemen. This brings the main part of our conference to a close. 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.