Addex Therapeutics Ltd

Good day and thank you for standing by. Welcome to the ADEX Therapeutics First Quarter 2024 Financial Results and Corporate Update Conference Call. 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 11 on your telephone keypad. You will then hear an automated message advising your hand is raised. To withdraw a question, please press star 11 again. Alternatively, you can submit your questions via the webcasts. Please be advised that today's conference has been recorded. I would now like to hand the conference over to your first speaker today, Tim Dyer. Please go ahead.

Hello, everyone. I'd like to thank you all for attending our Q1 2024 Financial Results Conference Call. I am 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 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 some of our clinical and preclinical programs. I will then speak about the recent launch of NeuroSterics before reviewing the Q1 2024 full-year financial results. Following that, we will open the call for Q&A. We've made great progress in our GABA B positive allosteric modulator program, which is funded by our partner, Indivior, and are on track for Indivior to select a drug candidate for advancing into IND-enabling studies at the end of this month. As a reminder, under the agreement with Indivior, we have the right to select our own drug candidate after they have selected their candidate and to develop it in eight reserved disease areas where Indivior is precluded from developing their candidate. We have selected chronic cough and expect to complete preclinical characterization in the second half of 2024. We launched Neurosterix with a Series A financing round of 63 million led by perceptive advisors This is an innovative financing transaction that provides us with the resources needed to advance our preclinical portfolio without diluting our shareholders' interest in our clinical stage assets and partner programs. As part of the transaction, we received 5 million Swiss francs and a 20% equity interest in NeuroSterix, securing the balance sheet and retaining significant upside in the programs for our shareholders. I will speak more about this innovative financing transaction later in the presentation. Our partner, Janssen, completed the phase two epilepsy study evaluating adjunctive ADX71149 administration in patients with focal onset seizures with suboptimal response to levotiracetam or grivotiracetam. We reported top line data in May and unfortunately the study did not achieve statistical significance for the primary endpoint of time for patients to reach baseline seizure count when ADX71149 was added to standard of care We expect the full data set from the study in the second half of this year, and we'll work with our partners to determine next steps for the program. Now, for a quick review of our pipeline, as mentioned, 71149 has reported top-line data, and we are expecting full data set in the second half of this year. We continue to believe in Dipaklarant, and it's executing our plans to commence development in both dyskinesia, so you were Parkinson's disease, as well as preparing for a phase two group concept study in post-stroke recovery. As mentioned, our GABA-B-PAM collaboration is coming to the end of the discovery phase with drug candidates on track to start IND enabling studies later this year. And DVO is executing the substance use disorder program. And we are preparing our candidate for development in chronic cough. 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 Depravilurant and our plans for development in brain injury recovery. Following termination of the development of Depravilurant in PD-LEAD, we embarked on a detailed evaluation of a number of potential indications of interest for future development, including substance use disorder, migraine, and other forms of pain. We have completed this exercise and have identified brain injury recovery as an interesting indication for the future development of Depragnolab. We believe the differentiated profile of Depragnolab makes it particularly suitable for enhancing the impact of rehabilitation in traumatic brain injury and stroke patients. 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 simulated by rehabilitation therapies. AMGUL5 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 MGOR5 has been observed in a range of neurological disorders, including stroke, where it plays a role in so-called maladaptive rewiring of the brain following stroke. Inhibition of MGOR5, 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 state. Exciting new evidence recently published in the journal Brain suggests that the negative allosteric modulator of mGluR5, 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 daily with our mGluR5 numb depregnation. MRI imaging of the resting state functional connectivity in post-stroke rodents shows that daily administration of M-TAP also stimulates intra- and inter-hemispheric connectivity in the brain disrupted by stroke. It's important to note that improvement in brain connectivity after stroke is known to correlate with functional recovery and is observed across species. The Progleron 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 dipragluron can become a first-in-class drug to facilitate post-stroke recovery. We can also speculate that dipragluron-mediated adaptive rewiring and facilitation of recovery following brain damage can also be seen in traumatic brain injury patients. Let me now switch to GABA-B positive ulcering modulator preclinical program, which is partners with Indivior. The aim of this collaboration is to deliver a new treatment for substance use disorders. Indivior is supporting the research at ADEX and have recently committed an additional 2.7 million Swiss francs funding for us to complete clinical candidate selection activities. In addition to 13.8 million Swiss francs, total funding so far. As a reminder, GABA-B receptor activation has been clinically validated in a number of disease areas, including using Buclofen, a GABA-B orthosteric agonist. Buclofen 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 of baclofen but longer half-life and improved side effect profile. We are well on our way to meeting this objective with multiple novel drug candidates, rapidly advancing through candidate selection phase, with the aim to nominate drug candidates ready to enter IND enabling studies in H2 2024. As part of our agreement with Indivio, we have the right to select drug candidates from the funded research activities for our own independent GABA-B PAM program. we have selected to focus our independent program on cough, and therefore, I will 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 an overactive cough reflex. There is a large unmet medical need in novel anti-juice 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 treatments carry risks of serious side effects. On the next slide, we showed 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, Gihapixant. Support for using GABA-B PAMs 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 anatomical evidence, the GABA-B receptors are strongly expressed in airways and in the neuronal pathway regulating calls. Therefore, we believe that GABA-B PAMs could offer superior efficacy in call patients. Thus, we believe that GABA-B PAMS could be an innovative new treatment of chronic cough administered once daily via oral dosing and offering improved efficacy and tolerability with fewer non-responder patients suitable for chronic dosing, therefore significantly improving patients' quality of life. We are working with multiple compounds progressing in late clinical candidate selection phase, and we expect to move into IND-enabling studies in H22024 in parallel to delivering compounds for our partner in Divio. This concludes our prepared remarks on the progress of our R&D programs. Now I hand it back to Tim.