Addex Therapeutics (SIX Swiss: ADXN) Q4 2025 Earnings Call

0:00 Good day, and thank you for standing by. Welcome to the Addex Therapeutics Full Year twenty twenty five Financial Results and Corporate Update Conference Call and Webcast. At this time, all participants are in listen only mode. After the speakers' presentation, there will be the question and answer session. To ask a question during the session, you need to press 11 on your telephone keypad. You will then hear an automatic message advising your hand is raised. To withdraw a question, please press 11 again. If you wish to ask a question via the webcast, please use the Q and A box available on the webcast link anytime during the live event. Please be advised that today's conference is being recorded. I would now like to hand the conference over to our first speaker today, Tim Dyer. Please go ahead. Thank you.

0:46 Hello, everyone. I would like to thank you all for attending our twenty twenty five 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 and d programs. I draw your attention to the press release and the financial statements issued earlier today, 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 mBluR5 negative allosteric modulator program for brain injury recovery and the GABA B positive allosteric modulator preclinical program for cough.

1:39 I will then review our twenty twenty five full year financial results. Following that, we will open the call for q and a. So 2025 has seen several important achievements across our pipeline. We made excellent progress in our GABA B pan chronic cough program as we continue to complete preclinical characterization of our selected compound. We recently announced robust antitussive activity in a nonhuman primate chronic cough model as well as solid antitussive activity in an IPF model in guinea pigs. These data further demonstrate the potential of our compound in this important unmet medical need.

2:28 In parallel to completing the preclinical profiling, are working to secure funding to advance the program into the IND enabling studies. Misha will be sharing some of the data with you later in our presentation. We've also, repositioned diproglurant, our mGlar five 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 MblO5 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 in Tipigluron and are preparing for clinical studies.

3:21 Misha will also talk more about this program later in the presentation. So following the decision by our partner J and J to terminate development of ADXN eleven forty nine, 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, are discussing with potential partners for the asset. Our partner Indivior has selected a compound for development in substance use disorders and has completed IND enabling studies. As a reminder, under the terms of the agreement, Alex is eligible for payment of up to $330,000,000 US dollars 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.

4:15 In June 2025, we invested in Stellickla, a private clinical stage neurodevelopmental disorder focused company. Stellickla has developed a 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 to the platform has been demonstrated by applying the technologies to identify and develop drugs in subpopulations of patients suffering from autism spectrum disorder. SOLICIA 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 million cash, which provides us with cash runway through mid-twenty twenty six.

5:05 I'd like to highlight that the cash burn has been significantly reduced following the NeurosDeric spin out transaction. However, current cash does not fund the progression of our unpartnered programmes into the clinic. Now for a quick review of our pipeline. We continue to believe in dipaglarant 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 are 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.

5:52 As a reminder, we spun out our portfolio of neuropsychiatric assets in 2024 to create Neurosterics and raised £65,000,000 from a syndicate of investors led by Perceptive Advisors. We retained a 20% equity interest in Eurosteryx. Eurosteryx has made excellent progress in advancing its pipeline in 2025, including starting phase one studies with n t x two fifty three, its M4 positive alloscent modulator programme, 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 duprevulant and our plans for development in brain injury recovery.

6:42 Duprevulant is an orally available, highly selective mGlu five 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 dipaglutide targets neuroplasticity early in rehabilitation to promote building of neuronal connections and sensorimotor 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.

7:28 There are over one hundred million stroke survivors worldwide, and the number is growing at the annual rate of twelve 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. MgLU-five 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 has been observed in a large, in a range of neurological disorders, including stroke, where it plays a role of so called maladaptive rewiring of the brain following stroke.

8:26 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 the negative allosteric modulator of MgLu5 MTAP 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 m g five nam dipraglutide.

9:16 MRI imaging of the resting state functional connectivity in post stroke rodents shows that daily administration of NTAP also stimulates intra and interhemispheric 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. Dipraglutide 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.

10:11 We have a drug product ready and a strong patent position and believe dupramulant can become a first in class drug to facilitate post stroke recovery. We can also speculate that the pragglot 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, Addex 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.

10:58 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 anti use of drugs as current standards of care are ineffective in thirty percent of patients or only moderately effective in up to sixty percent of patients. In addition, the current treatments carry risks of serious side effects. 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.

11:55 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 tox, and CMC have been completed. And our clinical candidate has shown favorable efficacy, tolerability, and developability profiles. Our clinical candidate has demonstrated a consistent minimum effective dose of one mg per kg and ED fifty of six mg per kg in cold frequency in guinea pigs.

12:40 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 antiducive efficacy of compound one in the nonhuman primates. The ID 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 anti use of efficacy, reducing the cough number dose dependently and achieving seventy percent reductions at the maximal doses.

13:29 The attitudes of profile of compound A was similar to that of nalbuphine, orvapitant, baclofen, and codeine. 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 sixty mgs per kg. In contrast, dalbuphine or repitant baclofenacodine resulted in robust reductions in respiratory rate at their highest doses indicative of sedative like effects.

14:26 When evaluation of the antiducid efficacy across compounds was done at the respective highest doses free from respiratory effects, compound A was shown to be superior to nalbuphine or reputant baclofenacodin 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 p two x three inhibitor had similar efficacy and tolerability profiles. 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.

15:21 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, ten mg per kg, or V Go orally once daily for twenty eight days. Intact animals received only V Go. On days seven, fourteen, 21, and 28, animals were exposed to low concentration of citric acid to stimulate cough.

16:15 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 condition. Chronic treatment with compound A resulted in robust and enduring reductions in the number of coughs with forty to sixty percent efficacy. The latency to first cough showed significant reductions in bleomycin exposed vehicle treated animals versus intact controls starting day 14.

17:10 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 nonhuman primates, compound A had no effect on the number of coughs at zero point six and one, while producing significant and more than 60% reductions at two mgs per kg.

18:05 In summary, we have selected a clinical candidate for chronic cough with a robust reproducible anti juices efficacy of one mg per kg and good PKPD. The compound showed a favorable developability profile in non GLP tox studies performed in rats, dogs, and nonhuman primates. The compound has a potential to have the best in disease efficacy and tolerability profile and broad application in cough patients. The compound showed a favorable developability profile in non GLP tox studies performed in rats, dogs, and nonhuman primates. Subject to raising financing, we are ready to start the IND enabling studies.

18:52 This concludes our prepared remarks on the progress of our R and D programs. Now I hand it back to Tim. We recognized 200,000 of income in 2025 compared to 400,000 in 2024. The decrease is primarily due to the completion of the funded research phase of our collaboration with Indivior in June 2024. This has been partially offset by the fair value of the services received from Neurosterics Group at zero cost. R and D expenses sorry. R and D expenses of 700,000 primarily related to our GABA B PAM program, decreased by 200,000 in 2025 compared to 2024, mainly due to the completion of the research phase of our collaboration with Indivior.

19:59 G and A expenses remained stable at 2,300,000 in 2024 and 2025 and primarily relate to professional service fees linked to corporate development activities. As a reminder, on 04/02/2024, we received an equity interest of 20% in Eurosterex US Holdings LLC as part of the Eurosterex spin out transaction. Under IFRS accounting standards, we are required to account for the investment using the equity method of accounting and recognise our share of NeuroStarix results in our income statement. For the twelve month period ended 12/31/2025, our share of these net of the net loss of neurosteics amounted to 4,000,000 compared to 2,200,000 for the period April 24 through December 24.

20:53 The finance net result is close to nil in both '25 and 2024, and is primarily related to foreign exchange differences on our US cash deposits. Now moving on to the balance sheet. Our assets are primarily held in cash, and we completed 2025 for CHF1.6 million cash held in Swiss francs and US dollars. Our current assets amounted to CHF41,000, primarily related to decreased prepaid patent costs and retirement benefits. Our non current assets of £4,600,000 as of December primarily relate to our investment in Eurosteryx, which has been accounted using the equity method, and the investment in Stellicola of 800,000.

21:40 Current liabilities of 1,200,000 at the end of the year 2025 increased by 400,000 compared to December of the previous year 2024 and primarily relate to r and d related accruals and payables. Noncurrent liabilities of 400,000 as of December 3125 increased by 200,000 compared to December 2024, primarily due to an actuarial experience adjustment in the calculation of the defined benefit obligations. Now to the cash flow statement. On 12/31/2025, the cash balance amounted to £1,600,000 and decreased by £1,700,000 compared to the beginning of the year. This is primarily due to the cash used in operations and investing activities for a combined amount of £2,900,000 which has been partly offset by the sale of treasury shares for a total amount of £1,300,000 during the year.

22:48 Now to summarize, we've made excellent progress advancing the GABA B PAM program for cough and our diproglurant post stroke recovery program. Our spin out company, Neurosterics, continues to advance its portfolio with their m four positive modulator program on track to complete phase one this quarter. We're very pleased by the progress Delicca is making at advancing on its business strategy and pipeline, and we are looking forward to completing our evaluation of potential indications for our mBluR2 PAM programme and securing the financial resources to advance our portfolio into clinical studies. This concludes the presentation, and we will now open the call for questions.

23:36 Thank you. And now we're going to take our first question. And it comes from the line of Raghuram Selvaraju from H. C. Wainwright. Your line is open. Please ask your question. Hi. Thank you for taking my question. This is Yansi sitting in for Ram. I have two questions. The first is, which subsets of patients with chronic cough is the gabapam most likely to be aimed at? Would you say it's IPF, sarcoidosis or something else?

24:26 And how large could that total market be if the compound had a broad anti test of label? Yeah. So, Misha, would you like to answer? Yes. Of course. Well, considering the profile of this compound, which has balanced central peripheral activity profile, we believe that it will be suitable for a broad range of chronicle patients, especially due to the fact that it it has central component, which we believe is very important, in reducing central sensitization seen in certain chronic cough patients.

25:17 These patients do not respond to a peripherally restricted P2X3 inhibitors, but can respond to morphine, which we believe is centrally acting. So this way, the profile is able to address problems in chronicle circuit that are both peripheral and central. Our initial intention is to confirm the efficacy of the compound in chronic cough patients that come from unexplained or refractory chronic cough category.

26:05 But once this efficacy is confirmed, we intend to broaden our patient population in subsequent studies. Thank you. And which which psychiatric clinical indications might be best suited to address for Addex's portfolio of MgLU-seven candidates? Yes. The mglu7, candidate is not in Addex. It's sitting in the spinout company Neurosterics, so we're not at liberty to talk in detail about that. But, you know, in general, maybe, Misha, you can say what you can say.

26:51 Absolutely. Absolutely. There are a number of academic studies looking at MGUS7 knockout mice that show quite remarkable and very broad potential for inhibitors as MGUS7 knockout show reduced anxiety and depression like reactivity. They show reduced expression of conditioned fear. They show reduced aggressivity and agitation and certain signs of reduced responsiveness to psychostimulants. So even with this data that have been then confirmed in several pharmacological studies, some of those that were published by us show that we can orient the MGOR7 negative modulators towards anxiety and panic, agitation, aggressivity, depression, and perhaps psychosis and mania.

27:59 Got it. Thank you so much. Thank you. Dear speakers, there are no further questions for today. Thank you, ladies and gentlemen. This brings the main part of our conference to a close. And I would like to hand back to Tim Dyer for closing remarks. Thank you. So I'd just like to thank everyone for attending our 2025 conference call. And I wish you all a very nice day, and we look forward to speaking to you again soon. Thank you. This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.