Good day and thank you for standing by. Welcome to the Addex Therapeutics Full Year 2023 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. Please be advised that today’s conference has been recorded. I would now like to hand the conference over to our speaker today, Tim Dyer. Please go ahead.

Hello, everyone. I’d like to thank you all for attending our 2023 financial results conference call. I’m here with Mikhail Kalinichev, our Head of Translational Science, who will provide 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 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 the 2023 activities and recent achievements before reviewing our pipeline. I will then hand over to Mikhail, who will review in more detail some of the clinical and preclinical programs. I will then speak about the recent launch of Neurosterix before reviewing our 2023 full year financial results. Following that, we will open the call for Q&A. So to start with the highlights, our partner Janssen has completed the Phase 2 epilepsy clinical study and we are now expecting to report data from the study by mid-May this year. I’d like to remind you that an Independent Interim Review Committee established by Janssen to review the unbiased 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 ADX71149 is safe and well tolerated and may be having a positive impact on this patient population. We continue to believe there is value in Dipraglurant and have substantially completed our evaluations of future development for dyskinesia and Parkinson’s disease. We have worked with experts on a new trial design, which we believe will overcome the recruitment challenges we encountered in the past. However, our preferred strategy for this indication is to secure a partner prior to restarting development. We’ve also identified post-stroke recovery as an interesting area for future development of Dipraglurant and are currently profiling Dipraglurant in preclinical models of post-stroke recovery. Furthermore, preclinical data was recently published in the Journal Brain, which strongly supports the rationale for inhibition of mGlu5 receptor as a treatment for post-stroke recovery. We are pursuing discussions with potential funding sources including industry partners for this interesting potential future development path for Dipraglurant. In 2023 we announced the extension of our GABAB PAM Indivior collaboration through until June 2024 with CHF2.7 million of additional research funding. With this additional R&D funding we have made excellent progress and advanced multiple drug candidates through the clinical candidate selection phase. As a reminder, Indivior’s 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 reserved indications. We are focusing our independent program on cough. During 2023 we demonstrated robust efficacy with multiple drug candidates in preclinical models of substance use disorder and cough and are therefore well on track to delivering drug candidates for Indivior and for our own independent cough program. We expect Indivior and ourselves to select compounds to advance into R&D enabling studies in the second half of 2024. We led a consortium that was awarded a €4 million grant from the Eurostar grant program to advance our mGluR2 negative allosteric modulator program through to delivery of clinical candidates. This is a program for mild neurocognitive disorders that is currently in lead optimization. Last but by no means least, we very recently announced the launch of 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 asset and partner program. I will speak more about this innovative financing transaction later in the presentation. Now for a quick review of our pipeline. As mentioned, we are excited to see the Phase 2 data from our epilepsy program which is being executed by Janssen. We continue to believe in Dipraglurant and are executing our plans to recommence development in both dyskinesia-associated Parkinson’s disease, as well as preparing Dipraglurant for a Phase 2 proof-of-concept study in post-stroke recovery. Our GABAB PAM collaboration is coming to the end of the discovery phase with candidates on track to start IND enabling studies later this year. Indivior is executing the substance use disorder program and we are preparing for candidates for development in cough. Now I will hand over to Mikhail who will give you more details about our exciting portfolio.

Thanks Tim. Hello everyone. I will start by speaking about our Phase 2 epilepsy study with ADX71149, which has been completed recently by Janssen. Epilepsy is a large multi-billion-dollar market opportunity where despite several available treatment options, many patients are still in need of improved therapies to treat their seizures. As a reminder, ADX71149 is a metabotropic glutamate receptor subtype 2 or mGluR2 positive allosteric modulator discovered in partnership with Janssen using Addex’s proprietary allosteric modulation platform. ADX71149 has demonstrated both standalone efficacy and a strong synergistic effect in combination with inhibitors of SV2A such as Keppra and Briviact. ADX71149 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, responsible for development, has just completed both the Phase 2 study and an open label extension study in epilepsy patients. Results are expected by mid-May this year. We have significant economics in our deal with Janssen with pre-launch milestones of €109 million, low double-digit royalties on net sales and Janssen is responsible for all development costs. To illustrate the synergistic effect, same with the combination of ADX71149 and levetiracetam, the active molecule in Keppra, here are the data obtained in the 6 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 robust protection against 6 hertz induced seizures with an ED50 of approximately 20 mg per kg. In combination studies with varying doses of levetiracetam, a fixed dose of ADX71149 increased the potency of levetiracetam leading to approximately a 35-fold shift in its ED50 values. Conversely, using a fixed dose of levetiracetam with varying doses of ADX71149 increased the potency of ADX71149 leading to approximately a 14-fold shift in its ED50, suggesting a positive pharmacodynamic relationship or strong synergistic effect for the two molecules when given in combination. This extraordinary effect of a combination of an mGlu2-PAM with an SV2A antagonist has been patented, offering strong protection for this program until 2035 without additional extension. This is the Phase 2 study design. The study is a double-blind placebo-controlled proof-of-concept study enrolling patients with focal onset seizures who have suboptimal response to treatment with levetiracetam, Keppra, or brivaracetam, Briviact. In this Phase 2 study design, patients establish a 28-day seizure count over a 56-day baseline period prior to being randomized to receive either ADX71149 or matching placebo, the primary endpoint in this time taken to return to their monthly baseline seizure count. The study has two parts, Part 1 being the four-week acute efficacy phase and Part 2 being an eight-week maintenance phase of efficacy. Part 2 includes patients who did not reach their baseline seizure count during Part 1 of the study and continue on their randomized drug or placebo. An open-label extension study was ongoing in parallel, offering all patients the opportunity to get treated with ADX71149 in combination with levetiracetam or brivaracetam. As previously announced last year, an Independent Interim Review Committee convened by our collaboration partner recommended to continue the study following review of unblinded data from Part 1 of Patient Cohort 1. This was encouraging news, suggesting that ADX71149 is safe and well-tolerated and potentially offering benefit to epilepsy patients. We look forward to sharing the topline data of Cohorts 1 and 2 in mid-May this year. Following termination of the development of Dipraglurant in PD-LID, we embarked on a detailed evaluation of a number of potential indications of interest for future development, including substance abuse disorder, migraine, and other forms of pain. We have completed this exercise and have identified post-stroke recovery as an interesting indication for future 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 the leading causes of chronic often lifelong disabilities, 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 an 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 therapies. The mGlu5 receptor is a suitable target to address post-stroke recovery, as it is densely expressed in the brain, involving neuroplasticity and modulates excitatory-inhibitory equilibrium. In fact, activation of mGlu5 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 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 modulation of mGlu5, MPEP, administered daily in rats following a stroke, results in 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 mGlu5 non-Dipraglurant. MRI imaging of the resting-state functional connectivity in post-stroke rodents shows that daily administration of MPEP also stimulated intra- and interpenetratory 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. Dipraglurant 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 Dipraglurant can become a first-in-class drug to facilitate post-stroke recovery. We can also speculate that Dipraglurant-mediated adaptive rewiring and facilitation of recovery following brain damage can also be seen in traumatic brain injury patients. Let me now switch to the GABAB positive allosteric modulator preclinical program, which is partnered with Indivior. The aim of this collaboration is to deliver a new treatment for substance use disorders. Indivior is supporting the research at Addex and has recently committed an additional CHF2.7 million funding for us to complete clinical candidate selection activities, in addition to CHF13.8 million total funding so far. 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 the 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-lives and improved side effects profile. We are well on our way to meeting this objective, with multiple novel drug candidates rapidly advancing through the clinical 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 Indivior, we have the right to select drug candidates from the funded research activities for our own independent GABAB 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 GABAB 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-tumor 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 standards of care and show no taste-related side effects, as seen with a newly approved P2X3 inhibitor, GABAB PAM. Support for using GABAB PAMs in treatment of chronic cough comes from the clinical evidence that baclofen, a GABAB agonist, is used off-label in cough patients and from 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. Therefore, we believe that GABAB PAMs could be an innovative new treatment for 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 the late clinical candidate selection phase and we expect to move into IND enabling studies in H2 2024 in parallel to delivering compounds for our partner, Indivior. Now I hand it over back to Tim.

Thanks, Mikhail. Now, before I move on to the financials, I would like to spend a few moments to speak about the Neurosterix transaction. Due to the excellent progress made by our R&D team in advancing our unpartnered preclinical portfolio, our M4 PAM, mGlu7 NAM, and mGlu2 NAM programs reached a stage of development where they now need significant amounts of financing to progress into the clinics. Unfortunately, given the low market capitalization of Addex, raising the amount of capital needed would have been extremely challenging and highly dilutive for our shareholders, so we decided to spin out these programs and our platform into a new private company and raise the necessary capital into the new private entity. We believe this is an excellent transaction for Addex shareholders, as it has secured CHF5 million for Addex and removed the financing overhang on the Addex stock. We have retained a 20% interest in Neurosterix, so we can benefit from the upside from advancing the programs into the clinic, which is now secured by the $63 million capital from a high-quality investor syndicate led by Perceptive Advisors. As part of the transaction, we have divested our allosteric modulation technology platform, including the majority of our staff and significantly reduced our cash burn going forward. However, we have entered into a service agreement with Neurosterix to ensure that we can access the skills needed to execute on our business strategy. Now, for a review of our 2023 financial results. Starting with the income statement, we recognize CHF1.6 million of income in 2023, compared to CHF1.4 million in 2022. The primary source of revenue is research funding from our collaboration with Indivior, which is recognized as the associated research costs are incurred. In terms of expenses, R&D expenses were CHF7 million in 2023, compared to CHF14.7 million in 2022. The decrease of CHF7.7 million is primarily due to the termination of Dipraglurant development in dyskinesia with Parkinson’s disease and the disbanding of our U.S. clinical team in 2022. G&A expenses were CHF5 million in 2023, compared to CHF7.3 million in 2022. The decrease of CHF2.3 million is primarily due to reduced share-based service costs and decreased D&O insurance costs. The finance results are primarily related to foreign exchange losses on cash held in U.S. dollars, partially offset by interest income on U.S. cash deposits, which we hold as a hedge against near-term U.S. dollar denominated costs. Now to the balance sheets, our assets are primarily held in cash and we completed 2023 with CHF3.9 million cash held in Swiss francs and U.S. dollars. Other current assets amount to CHF0.4 million, primarily related to R&D prepayment and trade receivables that mainly relate to our agreement with Indivior. Current liabilities of CHF2.9 million as at the end of December 2023 decreased by CHF0.4 million compared to the same time in 2022 and primarily relate to R&D payables and accrued expenses. Non-current liabilities of CHF0.6 million increased by CHF0.5 million compared to December 31, 2022, and primarily related to retirement benefit obligations. Now to the cash flow statements, we started the year with CHF7 million. We raised net proceeds of CHF4.5 million in an equity offering executed in April 2023. We received CHF1.2 million from the sale of treasury shares and received CHF1.9 million research funding from Indivior. We spent CHF9.9 million on our operations. We have an unrealized gain of CHF0.4 million on forex and U.S. dollar cash balances are converted to Swiss francs, resulting in CHF3.9 million of cash at the end of the year. Now to summarize, I hope you have understood how transformative the Neurosterix deal is for Addex. We’ve strengthened the balance sheet and secured the financing to execute on the development of our preclinical portfolio, including advancing the very exciting M4 PAM program for schizophrenia into the clinic. Our Janssen partnership is poised to deliver Phase 2 data in epilepsy by mid-May this year, which will be an important value inflection point for the program and the company. And our partnership with Indivior is on track to deliver clinical candidates ready for IND enabling studies by the end of June of this year. Dipraglurant is ready to restart clinical development on the subject of a number of partnering discussions. Our independent GABAB PAM cough program is on track to start IND enabling studies. Also, we are validating partnerships with industry, supportive investors, and a 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.

Thank you. And now we’re going to take our first question and it comes from the line of Joanne Lee from Maxim Group. Your line is open. Please ask a question.

Hi. This is Joanne speaking. Thanks for taking the question, and firstly, congratulations on the Neurosterix deal. So now that you know you’ve secured some funding through that deal, what are the upcoming actions, specifically which program are you prioritizing for advancement?

Yeah. So we continue to execute on the Indivior collaboration. So our primary focus is to deliver the clinical candidates so that Indivior can make their selection by the end of June. Because under the deal, we have the right to then select second choice. They have third choice. We have fourth choice. So that’s really our priority, because once Indivior is able to select, it means we can also select and that will then give us the candidate that we can advance into the IND-enabling studies for the cough program.

Gotcha. So I’m getting that the priority would be the GABAB program and the Indivior. So I’m aware that you guys have been releasing some positive preclinical data and are currently in the candidate selection phase. I wanted to ask what specific criteria are you considering when evaluating potential candidates for this program? And as a follow-up, additionally, regarding the collaboration with Indivior, it’s currently set to continue until the end of June. Are you considering independently moving the asset into the clinic or are there discussions underway to extend that collaboration further? Thank you.

In addition to the GABAB program, we also have Dipraglurant. We’ve worked extensively to design a new study in PD-LID and are currently finishing preclinical work in the stroke recovery area. Addex has been engaging in discussions with potential partners regarding both Dipraglurant in PD-LID and in post-stroke recovery. Additionally, we have started to identify some potential partners for the GABAB cough program. However, we cannot share much information about the GABAB candidates until Indivior has made their selection, as they have the first choice. Though we have a good idea of which candidates they might choose, we cannot disclose any information until that selection is formalized. Regarding how we are characterizing the candidates and what the target product profile would look like, that information is confidential, and we cannot share it. I apologize for that.

Got it. Well, that’s very helpful. Really exciting stuff ahead, and thanks again for taking the questions.

You’re welcome. Thanks.

Thank you. Now we’re going to take our next question. Just give us a moment. And the next question comes to the line of Raghuram Selvaraju from H.C. Wainwright & Co. Your line is open. Please ask your question.

Thanks very much for taking my questions and congratulations on all the progress, the Neurosterix transaction in particular. Just wanted to ask, first of all, with respect to the M4 program, can you give us a sense, Tim, of what some of the recent precedent transactions or comparators might be in this space? And what implications that could have for Neurosterix, as well as Addex’s stake in Neurosterix going forward, especially if you continue to have development success with work regarding that specific target?

Yeah. Hello, Ram. Thank you very much for the question. And yeah, at the back end of last year, Cerevel, which is leading the field in muscarinic M4 positive allosteric modulators with Emraclidine and they’re in Phase 2. They were purchased for a little south of $9 billion by AbbVie, so that’s a very nice comparator. We believe our program is about two and a half years behind theirs, and clearly that M&A activity, I would say, sharpened the interest of Perceptive and the investor syndicate that has put the $63 million behind Neurosterix. And then, coming pretty quickly after the Cerevel M&A, BMS purchased Karuna, which has filed for registration with a product called KarXT. Now, KarXT is an M4, M1 preferring agonist. So, again, much of the efficacy that’s been seen in the phase three program of KarXT is coming from its M4 agonist activity, which is a very strong validation, again, of the M4 PAM approach in schizophrenia. Now, again, we’re some way off from filing for registration. However, we have $60 million on the balance sheet of Neurosterix. We are owning 20% of it. And so you can imagine we’ve got the capital to advance the M4 PAM program through Phase 1 development.

Excellent. Also can you just clarify two other points? The first is, with respect to the other programs that Neurosterix plans to advance, maybe give us a flavor of what the target indications might be beyond schizophrenia or adjunctive therapy in schizophrenia, which probably would be the most appropriate application of the M4 pathway modulator, as well as if there are likely to be any future targets that Addex could conceivably retain the right to pursue using the original Addex technology platform or if these are all going to ultimately be taken forward by Neurosterix? Thank you.

The technology platform and all preclinical programs, except for the GABAB PAM, have now transitioned to Neurosterix. As a result, Addex’s interest in these programs is through our equity stake, which we intend to safeguard in the future. The other targets being funded include the mGluR7, which is the negative allosteric modulator program for stress-related disorders, alongside several intriguing neuropsychiatric indications that we cannot disclose at this time. Additionally, there is the mGluR2 negative modulator program, which has also moved to Neurosterix, in conjunction with the Eurostar grant received last year. This program, supported by some of the $60 million residing in Neurosterix, is being propelled quickly towards clinical candidate selection through the Eurostar consortium, although it is currently in the lead optimization stage. This program targets cognition, an unmet medical need prevalent in various neurodegenerative disorders. Again, we cannot share specifics about the indications we will pursue. Furthermore, there is another program targeting an undisclosed neurological target, and we have concrete plans within Neurosterix to effectively utilize the platform. However, I cannot provide further details about these activities at this moment.

Thank you very much. And just one quick housekeeping item, if I may. Can you tell us whether the equity stake that Addex has in Neurosterix is in any way preferred and/or if Addex might in the future have the ability or the option, or at least, would not be restricted in any way from investing in Neurosterix and future funding rounds in order to maintain the 20% equity holding? Thank you.

No. Addex has the same rights as the investors and Addex has the right to participate pro rata in all future financing and our intention is to protect our 20% interest in Neurosterix going forward. But as you can imagine…

Thank you very much.

…so as you can imagine, with $60 million on its balance sheet, we don’t expect to have to participate in a future fundraising for quite some time.

Thank you. And now we’re going to take our next question. And the question comes to the line of Michael Okunewitch from Maxim Group. Your line is open. Please ask a question.

Hey there. Good morning or good afternoon everyone. Thank you for taking my questions and congrats on all the progress this past quarter. So, I guess, I’d like to ask just on the epilepsy program, given that that data is approaching, could you remind us of the criteria that the IRC were using to determine whether or not to proceed with that?

We haven't disclosed the specific criteria yet. However, we do know that the Independent Review Committee must have seen at least some positive signals in the first cohort during the initial four-week acute efficacy period, which involved 60 patients. They also must not have observed any safety or tolerability issues. Those are the details we have, but we don't know the exact criteria they were using. That's all we can share at this time.

Thank you for that. I would like to see, are you at liberty to discuss any more granularity on the pre-launch milestone structure for that program? But in particular, if any are attached to that Phase 2 data?

Right. So if you look through the previous disclosure, Addex received a milestone when J&J dosed the first patient in Phase 1. We also received a milestone when J&J dosed the first patient in Phase 2. We’re also at liberty to disclose that the €109 million of milestones are all development and regulatory. So there are no sales milestones included in that amount. So I think you can sort of work out. And if you look at the amounts of the Phase 1 and Phase 2 milestones, you could probably work out when the next milestone is coming and you can probably work out that it’s pretty back-ended. So we’re not relying on any cash inflows from this partnership to finance Addex for some time.

Thank you. That leads to my last question, which is more focused on modeling and financial aspects. I would like to understand the assumptions behind your runway projection and what portion of the previous burn rate was allocated to staff and programs that are now managed by Neurosterix?

We have significantly reduced Addex's operational expenses. Our guidance for 2026 does not account for the cash needed for the basic clinical development of Dipraglurant, nor does it include costs for developing the cough program. What is included are the operational costs of Addex, such as being a public company, investor relations, business development, finance activities, as well as some preclinical work on Dipraglurant for stroke and clinical activities to prepare the development plan for Dipraglurant in stroke and Parkinson’s dyskinesia, along with funds to complete the preparation and the CMC for the GABAB cough program.

All right. Thank you very much for taking my questions today and once again congrats on the fantastic progress.

Thank you.

Thank you. And now we will proceed to any written questions. Just give us a moment. We have a few questions from the webcast. The first question comes from Michael Hofer, and his question is, how high the first milestone payment is to be expected?

Oh! I’m sorry, but we’re not at liberty to disclose that information. As I pointed out in the response to one of the previous questions, there was a publicly disclosed Phase 1 milestone and a publicly disclosed Phase 2 start milestone. But we’re not at liberty to guide on the next milestone, I’m afraid.

Thank you. We have another question from Michael Hofer. What will be the forecasted expenses in 2024? Do they drop significantly and from which month?

Yeah. So we’re not disclosing the details of the forecast. However, I mean, if you look at the expenses of 2023, it will be significantly reduced because all the facilities, all the majority of the staff have moved to Neurosterix and that is effective the 1st of March.

Thank you. We have another question from Michael Hofer. Why no number can be named for these milestone payments? There are for sure contracts, and the amounts are written down. How much is the next milestone payment to be expected? I expect here a clear number?

Well, you’ll need to talk to J&J, because J&J have not authorized us to give any granularity around the economics of the contract with them. We have a contract, we have confidentiality clauses in the contract and we respect the confidentiality that we’ve signed up to. And I hope Mr. Hofer can respect that position.

Thank you. There are no further questions. I would now like to hand the conference over to Tim Dyer for any closing remarks.

Well, thank you everyone for attending our 2023 conference call and thank you very much for your questions. We look forward to speaking to you again soon. Have a very nice day.

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