Good day and thank you for standing by. Welcome to the Addex Therapeutics Third Quarter 2023 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be the question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Tim Dyer. Please go ahead.

Thank you. Hello everyone. I would like to thank you all for attending our Q3 2023 financial results conference call. I'm here with Robert Lutjens, our Head of Discovery-Biology and Mikhail Kalinichev, our Head of Translational Science. 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 achievements before handing over to Robert and Mikhail, who will review our clinical and preclinical pipeline. I will then review our Q3 2023 financial results. Following that, we will open the call for Q&A. So starting with the highlights, our partner Janssen completed recruitment of the ADX71149 Phase 2 epilepsy study earlier this month and we've confirmed that data is expected in Q2 2024. I'd like to remind you that an independent interim review committee established by Janssen to review the unblinded data from Part 1 of Cohort 1 made its recommendation to continue the study. This recommendation and the decision of Janssen to continue the study is very encouraging and suggests that 149 is safe and well-tolerated and may be having a positive impact on this patient population. We have made substantial progress in our collaboration with our partner Indivior and advancing several novel GABAB compounds coming through your candidate selection. As a reminder, Indivior primary interest is in substance use disorder and under the agreement, we have retained the right to select drug candidates for development in certain exclusive preserved indications. We are focusing our independent program on cough. During Q3, we have continued to advance compounds through clinical candidate selection, multiple…

Thanks, Tim. Hello everyone. I will start by speaking about our Phase 2 epilepsy study with ADX71149 which is being executed by Janssen. Janssen is making excellent progress and has recently completed recruitment of 110 patients across two cohorts. Epilepsy is a large multi-billion dollar market opportunity where despite several available treatments [Ph], many patients are still in need of improved therapies to treat the disease. As a reminder, ADX71149 is a metabotropic glutamate receptor subtype 2 or mGluR2 positive allosteric modulator discovered in partnership with Janssen using ADX's proprietary allosteric modulation platform. ADX71149 has demonstrated both thermal and efficacy and a strong synergistic effect in combination with inhibitors of SV2A such as Keppra and Briviact. 149 has also been thoroughly profiled in preclinical and clinical studies by Janssen demonstrating its good safety and tolerability profile in healthy volunteers and patients. Janssen is responsible for development and are currently operationally executing both the Phase 2 study and an open label extension study in epilepsy patients. We have significant economics in our deal with Janssen with prelaunch milestones of €109 million, low double digit royalties on net sales and Janssen is responsible for all development costs. To illustrate the synergistic effect seen with the combination of 149 and levetiracetam, the active molecule in Keppra, here is the data obtained in the six hertz psychomotor seizure model widely recognized as having high translational value to characterize the efficacy of anti-epileptic drugs. As a reminder, ADX71149 given alone in this model produces a robust protection against six hertz indecencies with an ED50 determined to be approximately 20 milligrams per kilo. In combination studies with varying doses of levetiracetam, a fixed dose of 149 increased the potency of levetiracetam leading to an approximate 35 fold shift in ED50. Conversely, using a fixed dose of…

Thank you, Robert. Following termination of the development of Dipraglurant in PD-LID, we embarked on the detailed evaluation of a number of potential indications of interest for future development, including substance use disorder, migraine and the other forms of pay. We have completed this exercise and have identified post strong recovery as an interesting indication for the fuel development of dipraglurant. We believe the differentiated profile of Dipraglurant makes it particularly suitable for post-stroke 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 impairments 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 inadequate. There is an urgent need for pharmacological agents that can facilitate the recovery stimulated by rehabilitation therapies. 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-inhibitory equilibrium. In fact, activation of mGlu5 receptor 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 mGlu5, on the other hand, can facilitate adaptive rewiring of the brain, promoting neuroplasticity 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 negative allosteric modulator of mGlu5 receptor, MTEP, addressed 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…

Thanks, Mikhail. Let me start with an update on our M4 PAM program as a potential novel treatment of schizophrenia and other psychosis. Schizophrenia affects approximately 1% of the world population, and patients have been treated with the same mechanism of action for the last 50 years with limited efficacy and significant tolerability issues often leading to treatment discontinuation and relapse. This space is seeing a major breakthrough with the advent of a completely novel approach based on activation of muscarinic M4 acetylcholine receptors. The recent filing of an NDA and acceptance by FDA to a drug-type xenominine, a nonselective M1/M4 agonist, and a peripherally restricted pan-muscarinic antagonist strongly validates the M4 receptor activation approach. In addition, a Phase 1b testing of emraclidine an M4 PAM positive allosteric modulator developed by Cerevel and schizophrenia patients showed an antipsychotic effect paving the way for our M4 positive allosteric modulator program. Without going into too much detail, the mechanism of action of muscarinic M4 acetylcholine receptors allow us to reduce striatal dopamine tone without directly blocking the dopamine receptors. The strategy used by current antipsychotic agents. This allows to retain a therapeutic effect without the side effects of typical and atypical antipsychotics. Standard of care antipsychotics as well as non-selective muscarinic agents suffer from significant side effects, leading to high treatment discontinuation rate. CAR XT represents a significant step in providing a new treatment of schizophrenia patients, before selectivity issues may still result in suboptimal tolerability. Our allosteric modulation approach is providing many advantages over an agonist approach, in particular with absolute receptor subtype selectivity, and without the potential side effects linked to constant receptor activation, such as receptor desensitization and reduced efficacy due to tolerance. The aim of our M4-positive modulation program is to identify highly selective and brain-penetrant molecules, offering…

Thanks, Robert. I'll now switch to an overview of the financials. Starting with the income statement, we recognized CHF0.3 million of income in Q3 compared to CHF0.4 million in Q3 of 2022. Primary source of revenue is research funding from our collaboration with Indivior. In terms of expenses, R&D expenses were CHF1.8 million in Q3 2023 compared to CHF2.8 million in Q3 2022. The decrease of CHF1 million is primarily due to the determination of Dipraglurant development in PD-LID in June of 2022. G&A expenses were CHF1.2 million in Q3 compared to CHF1.8 million in the same period as 2022. The decrease of CHF0.6 million is primarily due to reduced share-based service costs and decreased D&O insurance. The finance result is primarily related to foreign exchange gains on U.S. dollar cash deposits and to a lesser extent to interest income. Out of the balance sheet, our assets are primarily held in cash and we completed Q3 with CHF4.8 million of cash held in Swiss francs and U.S. dollars. Other current assets amount to CHF1 million and primarily relate to prepaid D&O insurance and retire benefits – related to our agreement with Indivior. Current liabilities CHF1.9 million decreased by CHF1.4 million compared to December 31, 2022 and primarily relate to our R&D payables and accruals. Non-current liabilities of CHF0.3 million decreased by CHF2 million compared to December 31st, 2022 and primarily relate to retirement benefit applications. Now to summarize, the ADX 71149 Phase II Epilepsy Clinical Study completed recruitment of patients and top line results are expected in Q2 of next year. We believe the recommendation of the Independent Review Committee to continue the study is very encouraging and suggests that 149 could be having positive impact on patients. We continue to believe in the value of Dipraglurant and are completing preclinical profiling and post-stroke recovery. In parallel, we are pursuing collaborative arrangements to advance development and look forward to sharing more information in the future. Our preclinical programs continue to make solid progress towards delivering drug candidates for future clinical development and important therapeutic areas in stress-related disorders, chronic cough, cognition, schizophrenia. As a reminder, our portfolio was discovered in-house from our pioneering allosteric modulator drug discovery platform. And currently, we have significant intellectual property in all programs. We have a track record of securing partnerships at the preclinical stage and supported top-tier investors. We recognize the 2023 stock performance and current market capitalization is very disappointing. However, we are having multiple business discussions across our portfolio and strongly believe that if we are successful in executing our near-term partnering strategy, then our stock price should move to recognize the value of our portfolio. This concludes the presentation and we will now open the call for questions.

[Operator Instructions] Now we're going to take our first question over the phone and it comes from Leonel Delgado from [Indiscernible]. Your line is open. Please ask your question.

Hi, thanks for taking my question. So the question is, what can we expect if the epilepsy readout in 2Q 2024 is positive? So the question is basically, what is the immediate implication for Addex in 2024? Thank you.

Yes, so thanks for the question. Well, the immediate implications for Addex, well, as you know, Janssen is operationally executing the study. They're responsible for financing the study. So Addex has very little, well, no control over the future development. And we have very limited visibility. However, we believe that the data that's been generated is received because they've looked at two doses. So should the study be positive, then we would expect the program to be moved forward into a pivotal study. But again, we don't have visibility exactly what the plans of Janssen are with respect to future development.

Thank you.

Thank you. [Operator Instructions] At this moment, there are no further questions over audio lines, and we will proceed to any written questions. And so the first question comes from the line of Peter Alick [Ph]. And the question is, €4 million, Eurostar's grant, when will the money be paid?

Yes, so yes, some of that money comes to Addex, and some of that money goes to consortium partners. And we are expecting that money to be, or a significant part of the money that's allocated to Addex to be received by Addex quite soon. But we are not providing the details of how that money is split at the current time.

Thank you. The next question comes from the land of Jesse Brodkin [Ph]. In the IRB review of unblinded data from 149, were efficacy measures unblinded? Also, were any changes in dosage made between Cohort 1 and Cohort 2?

Yes, so thanks for the question. Yes, so the independent interim review committee had some very clear guidance from Janssen. And they were given clear guidance that they should recommend to stop the study if there is a certain level of split between active dose and placebo. And the fact that they, and also, of course, if they saw any significant safety issues, then they had to recommend stop. Now, the recommendation to continue means that they must have seen at least a signal of efficacy and no safety, significant safety concerns. Now, and that was Cohort 1. Now, what we know is that Cohort 2 is a higher dose than Cohort 1. And this is why we are very encouraged by the combination of the recommendation to Janssen to continue and the fact that Cohort 2 is a higher dose. And now that they have completed recruitment, we are guaranteed of data. I hope that answers your question.

Thank you. [Operator Instructions] The speakers will just give a moment for the last entries. Thank you, ladies and gentlemen. This brings the main part of our conference for a close. And I would now like to hand it back to Tim Dyer for any closing remarks.

Yes, well, thank you everyone for attending the Q3 conference call and the corporate updates. We look forward to speaking to you again soon and just wish you a nice end of your day. Thank you, bye-bye.

That does conclude our conference for today. Thank you for participating. You may now all disconnect. Have a nice day.