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.