Addex Therapeutics Ltd

Lénaic Teyssédou, Lénaic Teyssédou, Lénaic Teyssédou To ask a question via the webcast, please access the Ask a Question tab. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Tim Dyer, CEO of Addicts Therapeutics. Please go ahead.

Thank you. Hello, everyone. I'd like to thank you all for attending our half-year 2026 Financial Results Conference call. I'm here with Misha Kalinichev, our Head of Translational Science, who will provide an update on our R&D programme. 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 activities and achievements before reviewing our pipeline. I will then hand over to Misha who will review our Gather B PAM programmes, SUD and COFF. I will then review our 2026 half-year financial results. Following that, we will open the call for questions. Since our last update, we have seen several important achievements Firstly, we have strengthened the balance sheet with US dollar 2.8 million raised to our ATM facility, which provides us with cash runaway into Q4, 2027. We also regained rights to our GABA B-PAM program, which we had previously licensed to Divior. This is a significant value creating event for addicts, which we will speak more about later in this presentation. As a reminder, we spun out our portfolio of preclinical neuropsych assets in 2024 to create NeuroSterics, raised $65 million from a syndicate of investors led by Bersetta Advisors. We retained 20% equity interest in NeuroSterics, the value of which is unfortunately not being properly reflected in our current share price, but we hope that will change. has made excellent progress in advancing its pipeline, including its lead drug candidate, NTX253, a highly selective brain penetrant M4 pan for schizophrenia. We expect this program to complete phase one very soon. Now for a quick review of our pipeline. We continue to believe in Diproglurant, and I've repositioned this proprietary mGlar5 negative acetaminophen modulator for brain injury recovery. As a reminder, in 2025, we entered into an optional agreement giving us access to an exclusive license to intellectual property covering the use of hemoglobin inhibitors in 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 and prepare for clinical studies. As previously reported, we have regained the rights to ADX 71149 from our partner J&J, the high value dataset and significant GMP material. We're currently evaluating a number of therapeutic indications for future development and in parallel we're discussing with potential partners for the asset. As already mentioned, we have recently regained all rights to the GABA-BPAM substance use disorder program from Indivio and are now free to develop all drug candidates in any indication. We plan to continue the development of both the substance use disorder and the COFF program. The next milestone for the SUD program is the filing of an IMD and for the COFF program, the start of IMD enabling studies. Also presented on this slide is the portfolio of our spin-out company, Neurosterex. We're expecting phase one data from NTX253 program in Q4 this year. Backup, M4PAM, NTX529 has been selected for IND enabling studies, which should start shortly. The MGLAR7 NAM program has selected NTX819, a highly selected first-in-class compound, which has demonstrated robust preclinical anxiolytic and antidepressant-like activity supporting is development at the Central Next Generation Therapy. We expect NTX819 to complete IND enabling studies in the coming months. Now let's speak about the GABA-B PAM platform. A bit of history for you. We started this program 20 years ago with the idea that we could use positive allosteric modulation pharmacology approach and a novel chemistry effort to come with better baclofen compounds. Baclofen is a short-acting generic GABA-B agonist which is registered for the treatment of spasticity. However, it has been used to demonstrate the efficacy of GABA-B activation in several disease areas such as SUD, heart pain, overactive bladder and neurodevelopmental disorders amongst others. Therefore, in addition to our active programs in constant substance use disorders, we plan to explore the development in some of these additional indications with potential partners. Now on to the termination of our agreement with Indivio. As a reminder, we entered into a research collaboration license agreement with Indivio in 2018 and executed a funded research effort at ADDx to deliver novel candidates. In late 2024, Indivio selected a drug candidate from the research and entered IND enabling studies in 2025. As part of the collaboration, we received approximately $20 million in funding and the right to select our own drug candidate for development in a restricted set of disease areas. Now that Indivio has terminated the license as part of their announced merger with Superness, we're not only getting back the licensed drug candidate for SUD. We have full freedom to develop all other candidates. This gives Alex the broadest portfolio of drug candidates targeting GABA-BPAM in the industry and the opportunity to pursue collaborations with industry partners. Now I will hand over to Misha who will give you some more details about the GABA-BPAM for SUD and chronic cost programs.

Thank you, Jim. Now let me speak about why we are so excited about the opportunity of our GABA-V-PAM substance use disorder program. Starting with unmet medical need. SUD, which includes opioid, alcohol, cocaine, and other use disorders, is described as uncontrolled use of a substance despite its harmful consequences and is characterized by development of tolerance and withdrawal. There is high unmet medical need for treatment of SUD as nearly 17% of the US population is affected by this disorder and nearly 90% of patients remain untreated. There is a limited selection of approved drugs for SUD which includes methadone, buprenorphine, naltrexone, and acomposate. Furthermore, there are no approved drugs for cocaine or psychostimulant use disorders. Novel approaches for pharmacotherapy of SUD include mGluR5-negative ulceric modulator malognurant, mGlu2,3-positive ulceric modulators, kappa-opioid receptor antagonists, GLP-1 inhibitors, and ketamine. So why GABA-B PA? GABA-B receptor activation is a clinically validated target for SUD as baclofen, is used off-label for alcohol use disorders. Also, GABA-BPAM ADEX 71441 has shown to attenuate alcohol self-administration and relapse in rats and alcohol consumption in mice. Also, ADEX 71441 reduced cocaine self-administration in non-human primates. The mechanisms Mediating anti-SUD effects of GABA-B activation include reductions in firing of mesolimbic dopamine neurons, dopamine release in the nucleus accumbens, incentive reward value of the drug, and stress anxiety that leads to craving and ultimate relapse. The GABA-B PAM drug candidate has successfully completed IND-enabling studies and is ready for IND filing and phase one clinical trials. Also, there are several differentiated leads and backup compounds, all with robust novel IP potential. Now, our GABA-B PAM program for the treatment of chronic cough. There is 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 S3 flux, but also possibly by called hypersensitivity syndrome. There is a large unmet medical need in novel antitrusive 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 PAM 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. We believe that GABA-B PAMS could offer superior efficacy in COS patients. The pre-IND activities including in vivo proof of concept, known GLP talks, 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 1 mcg per kg and ED50 of 6 mcg per kg in cough frequency in a guinea pig model of cough. 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. Recently, we confirmed that antidepressant efficacy in the non-human primate and are currently evaluating the compound in the rapid. IND enabling studies are planned and ready to start subject to securing finance. Now to the data. 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, orvipitant, baclofen, and codeine. Now to cough latency. Compound A increased the latency to first cough dose-dependently, thus delaying the onset of cough. The antitrusive profile of compound A in delaying cough onset was similar or better and that of reference drugs. As a reminder, our objective in this program is to design a GABA-BPAM with the efficacy of reference compounds but without the CNS side effects such as sedation. In the same experiment where the compound A showed efficacy, we monitored respiratory rate and biomarker of sedation. As you can see from the slide, compound A was well tolerated as there were no marked changes in respiratory rate at up to 60 mgs per kg. In contrast, nalbufin or reputant baclofen and codeine resulted in robust reduction in respiratory rate at doses required to achieve maximal efficacy, indicative of sedative-like effects. When we evaluated the antigen efficacy across compounds at the respective highest doses, In the model of ATP-potentiated citric acid COF in guinea pigs in a head-to-head comparison experiment, acutely administered compound A and the P2X3 inhibitor had similar efficacy and tolerability profiles. As a reminder, P2X3 inhibitors are antidepressant activities peripherally mediated, which explains their lack of sedative activity, but also the reason more than 30% of COV patients do not respond to treatment. In the citric acid-induced COV model, subchronic administration of compound A for seven days showed no signs of tolerance. neither in cough frequency nor in latency to first cough. Also, there were no changes in the respiratory rate, body temperature, and growth hormone released in animals treated subchronic with compound A. Compound A was also assessed in the IPF-related exacerbated chronic cough model in guinea pigs. Here is the study design. On day 0, animals received a single or pharyngeal administration of leomycin, or were left intact. Leomycin-exposed animals were then treated with compound A, a 10-mixter kick, or vehicle, orally once daily for 28 days. Intact animals received vehicle. On days 7, 14, 21, and 28, animals were exposed to low concentrations of citric acid to stimulate On day 28, at the end of the experiment, lung tissue was collected for histopathological analysis. The total number of coughs was significantly higher in realized and exposed vehicle-treated animals than in healthy control. The difference between the groups grew progressively larger over time, indicative of exacerbated cough in IPF life conditions. Chronic treatment with compound A resulted in robust and enduring reduction in the number of coughs with 40 to 60% reduction magnitude. The latency to first cough showed significant reduction in bleomycin-exposed vehicle-treated animals versus intact controls starting day 14. Chronic treatment with compound A reversed the effect of bleomycin throughout the testing period returning the latencies to the levels of intact control animals. Histopathology analysis of the lung tissue collected on day 28 revealed that chronic administration of compound A was associated with markedly lower astral scores and lower percentage of affected lung in comparison to bleomycin-exposed vehicle-treated animals. This suggests that compound A administered over 28 days reduced lung fibrosis. Now to the non-human primate data. Similar to what we saw in the guinea pig, in the model of citric acid-induced cough in non-human primates, Compound A demonstrated a more than 60% reduction in number of coughs at two mgs per gig. In summary, We have selected a clinical candidate for chronic cough with a robust reproducible anti-juicer efficacy at 1 mg per kick and good PKPD. The compound showed a favorable developability profile in non-GLT-tox studies performed in rats, dogs, and non-human primates. The compound has the potential to have the best disease efficacy and tolerability profile and broad application in chronic cough patients. Subjects to Raising Financing, we are ready to start the IND Enabling Settings. This concludes our prepared remarks on the progress of our R&D Program. Now I hand it back to Tim. Thank you, Misha.