Addex Therapeutics Ltd

Good day and thank you for standing by. Welcome to the ADEX Therapeutics full year 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 today's conference has been recorded. I would now like to hand the conference over to our 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 MBLR5 negative allosteric modulator program for brain injury recovery and the GABA-B positive allosteric modulator preclinical program for COTS. 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 GABA-B PAM chronic cough program as we continue to complete preclinical characterization of our selected compound. We recently announced robust anti-tusive activity in a non-human primate chronic cough model, as well as solid anti-tusive activity in an IPF model in guinea pigs. These data further demonstrate the potential of our selected 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 IMD-enabling studies. Misha will be sharing some of the data with you later in our presentation. We've also repositioned dipregluerant, our mGluR5 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 Mglo5 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 Syntaxis and the University of Lund to complete preclinical profiling and 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 ADX 71149, we have regained the rights to this phase two 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 IMD-enabling studies. As a reminder, under the terms of the agreement, Alex is eligible for payment 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. In June of 2025, we invested in Stelikla, a private clinical stage neurodevelopmental disorder-focused company. Stelikla has developed a proprietary precision medicine patient stratification technology platform, which allows companies to select patients based on their biological dysregulation rather than behavioral phenotype. Proof of concept of the platform has been demonstrated by applying the technologies to identify and develop drugs in sub-populations of patients suffering from autism spectrum disorder. SELICLA has made excellent progress in advancing its patient stratification study in autism and preparing its lead asset for a phase three study in cocaine use disorders. We completed the year with 1.6 million Swiss francs 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 nearest DERIC 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 DIP Proglorant and are executing our plans to reposition the development of brain injury recovery, and in particular, post-stroke recovery. As mentioned, our partner individual has selected a GABA-B PAM drug candidate for development in substance use disorders and completed IND enabling studies. We're advancing an independent GABA-B 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 NeurAsterix and raise 65 million from a syndicate of investors led by perceptive advisors. We retained a 20% equity interest in NeurAsterix. NeurAsterix has made excellent progress in advancing its pipeline in 2025 including starting phase one studies with Ntx253, its M4 positive allocent modulator program and we are expecting phase one 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 Deprav-Lurant and our plans for development in brain injury recovery. Deprav-Lurant 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 Depragurant 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 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-inhibitor equilibrium. In fact, activation of mGlu5 has been observed 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 angle 5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neural plasticity and creating of new functional pathways, moving the neural network towards a pre-lesion state. Exciting new evidence recently published in the journal Brain suggests that the negative ulcerative 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 MQL5 NAMP depraglurant. MRI imaging of the resting state functional connectivity in post-stroke rodents shows that daily administration of ANTEP 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. Depraglurant 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 Dipramulon can become a first-in-class drug to facilitate post-stroke recovery. We can also speculate that depravulone-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, ADEX has exercised its rights 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 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 possibly by a cough hypersensitivity syndrome. There is a large unmet medical need in novel antitrusive 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 treatment carry risks of serious side effects. Support for using GABA-B PAMs in treatment of chronic cough comes from the clinical evidence that Buclofen, 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, non-GLP talks, and CMC have been completed. And our clinical candidate has shown favorable efficacy, tolerability, and developability profile. Our clinical candidate has demonstrated a consistent minimum effective dose of 1 mcg per kick and ED50 of 6 mcg per kick in call 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 antitrusive efficacy of Compound 1 in the non-human primates. The IID-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 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 vetitant, baclofen, and codeine. Compound A increased the latency to first cough dose-dependently, thus delaying the onset of cough. The antidepressant 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 mgs per kick. In contrast, nalbufin or reputant baclofen and codeine resulted in robust reductions in respiratory rate at their highest doses, indicative of sedative-like effects. When evaluation of the antitrusive efficacy across compounds was done at the respective highest doses, free from respiratory effects, compound A was shown to be superior to nalbufin or repitant 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 profile. In the citric acid-induced cough model, subchronic administration of compound A for seven 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 gross hormone release in animals treated subchronically with compound A. In the model of IPF-related exacerbated chronic cough in guinea pigs, on days zero, animals received a single oropharyngeal administration of bleomycin or were left intact. Bleomycin-exposed animals were then treated with compound A, 10x per kg, or VEGO orally once daily for 28 days. Intact animals received only legal. On days 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. The difference between the groups grew progressively larger over time, indicative of exacerbated cough in IPF-like conditions. 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 controls starting day 14. Chronic treatment with compound A reversed the effect of leomycin 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 non-human 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 mSq. In summary, we have selected a clinical candidate for chronic cough with a robust reproducible anti-juice efficacy of one nick per kick and good PKPD. The compound showed a favorable developability profile in non-GLP TOC studies performed in rats, dogs, and non-human primates. the compound has a potential to have the best in disease efficacy and tolerability profile and broad application in COV patients. The compound showed a favorable developability profile in non-GLP tox studies performed in rats, dogs, and notional 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.