Welcome to the second day of the Jefferies London Healthcare Conference. I'm Sian Hammer from the European Pharma and Biotech team here at Jefferies, and I'm very happy to have here with us today the CEO of Medincell, Christophe Douat, and also the Chief Medical Officer, Richard Malamut. Thank you so much for joining us. Christophe, would you like to kick off with some introductory remarks? Yes, well, welcome to our talk. We are entering very transformative years for Medincell, probably the most transformative of its history, as you will hear through the questions. Got it, thank you. Let's sort of start with UZEDY before we dive into specifics. Could you give us an overview of your proprietary BEPO technology and how this is being used in UZEDY? Yes, we have quite an amazing long-acting injectable technology, which was developed in Montpellier, in the south of France, in the lab of the professor who originated the field of resorbable polymers. This technology allows us to do things that even Johnson & Johnson and Eli Lilly could not do in terms of features and differentiation of the product. Perfect, thank you. If we just speak a little bit more about UZEDY in particular, this is your long-acting risperidone injectable for schizophrenia, now also in bipolar I disorder. It brought in about $170 million in sales in 2024. As widely known, the sort of antipsychotic space is pretty saturated. What do you think is actually driving this demand and uptake for UZEDY? Yeah, so whenever we start a program at Medincell, it's not because we can, it's because it differentiates, because it provides value for patients, clinicians, even payers. UZEDY was formulated to address some of the challenges of the Janssen formulations. They're LAI, it's subcutaneous, not intramuscular, less painful for the patient. There's immediate therapeutic levels attained within the first 24 hours, making it easy to transition. There is no need for titrating injections, no need for oral supplementation. It comes in prefilled syringes, so easy to use for the psychiatrist. Four different doses for the monthly, four different doses for every other monthly, which correlate based on PK to the four oral doses of risperidone, 2, 3, 4, and 5 mg. Finally, there's flexibility on where you can inject, whether it's the arm, the abdomen, or the thigh. You have the same efficacy and safety, and this was identified by a psychiatrist as a feature that they like. For these reasons and some others, there has been a more rapid adoption of UZEDY when a patient needs a risperidone formulation. Understood. I think it's also known that the sort of antipsychotic space is pretty heavily genericized, with cheaper orals being used first line in patients. Could you remind us where UZEDY actually sits within that treatment paradigm? Yeah, sure. We know that the majority of patients start with an oral antipsychotic, but we also know that in schizophrenia, 80% of those patients stop taking their medicine within the first several years of use. When a schizophrenic patient doesn't take their medicine, they tend to relapse and require hospitalization. Generally in the US, where it's approved, payers request that the clinicians start with an oral and then transition to the LAI only if or when the patient is non-compliant. We're seeing experts in schizophrenia begin to promote the idea that these drugs should be used earlier. The American Psychiatric Association came down with a position paper suggesting that LAI should be used earlier in the treatment of schizophrenia rather than wait for the relapse and the hospitalization. Got it. Earlier this year, your partner, Teva, who commercializes UZEDY, had spoken about how payer access is becoming increasingly difficult across the board, with antipsychotics more managed than ever by Medicare and Medicaid. Related to that, in Q3, we saw perhaps lower than expected sales for UZEDY related to this sort of one-off adjustment because of it. Could you elaborate on that dynamic and what's going on there? Yes, there was actually a bump in the road in Q3, and Teva explained that this was a one-time gross to net Medicaid adjustment. They also gave a guidance for Q4 of $55 million-$65 million and renewed the guidance for the year at $190 million-$200 million. So UZEDY is keeping its traction, and hopefully we'll do even better in 2025. Great. Could you remind us of the economics here with Teva and what peak sales estimate you and Teva are baking in for UZEDY? Yes, so we are getting royalties and commercial milestones. Royalties are mid to high single-digit royalties, and we are eligible as well to $105 million of commercial milestones on UZEDY. Understood. I know there have been sort of approvals ex-U.S., including in Canada and South Korea this year for UZEDY. Are there any plans or is there a strategy to potentially enter the European market? Teva has not disclosed any plans to go into Europe. Obviously, I would love UZEDY to go into Europe because it is truly a best-in-class product, and there is a lot of potential. For example, at peak, Johnson & Johnson was getting 37% of its revenue from Europe with the Risperdal Consta and Invega. Great. UZEDY was recently approved in bipolar I disorder, as I mentioned earlier. Could you speak about the total addressable market here versus schizophrenia, and what are the current treatment options for patients with bipolar disorder? Yeah, sure. We know that bipolar has almost twice as many patients in the U.S. With bipolar, the majority of those are bipolar I with mania, which is what the drug was approved for. We already know that more than 300,000 US patients are taking a risperidone formulation, most of that oral, some the two-week from Janssen. Those are patients that are transitionable, if I can make up a word. In addition to that, we know that the long-acting injectable formulation of aripiprazole, Abilify, is also indicated for bipolar I, and we know that one-fourth of the prescriptions are for bipolar I, the rest for schizophrenia. There is a market opportunity there. It just was approved last month, as you said, so we'll see where that goes. Great. You also have another product with Teva, mdc-TJK, or long-acting olanzapine, which Teva aims to file with FDA by the end of this year. Could you speak a bit about this drug and the profile and why it's differentiated from Eli Lilly's Zyprexa? Yeah, so the Lilly drug, again, a long-acting injectable formulation of olanzapine is very much needed and very much desired by psychiatrists, but the one approved LAI olanzapine from Lilly had safety challenges, a condition called post-injection delirium and sedation syndrome, which limited its use because the FDA put somewhat restrictive monitoring requirements on the drug, requiring a REMS program, but also requiring that every patient for every injection be monitored in the office for three hours. That just wasn't happening. The patients didn't want to do that. The psychiatrists' offices weren't set up for that. When we formulated our LAI olanzapine, it was to eliminate that risk of PDSS, which is believed to be due to a burst of olanzapine from an intramuscular Lilly product. Ours is subcutaneous. Teva had met with the FDA and agreed upon a minimum number of injections to fully explore PDSS. They exceeded that and have conducted 4,000 injections in the clinical program with no cases of PDSS. Here, zero is a really good number and implies that there will not be these onerous monitoring requirements that impair the use of the Lilly product. Perfect. In the phase three study sort of pulled across the three doses, we saw weight gain of around 5.6 kilograms over the 52-week period. Now, weight gain is a very well-known side effect of olanzapine, of course. Do you think this will impact sort of prescribing activity at all? Yeah, so we know that the weight gain was comparable to that with the oral olanzapine and with Lilly's LAI olanzapine. Remember that this drug is intended for the more severe patients with schizophrenia, the refractory patients, which make up to 30% of patients. Clinicians have told us that the modest weight gain would not interfere with them prescribing because they need this potent drug for these more severe patients. They've also told us that there's an opportunity here. Because it's a monthly injection, the patients will be coming back for their injection, allowing the clinicians to monitor the weight gain. If they see it, they can evaluate a blood glucose or serum lipids and really intervene quicker. That opportunity isn't there for the oral olanzapine. Great. I believe you've previously stated that mdc-TJK or long-acting olanzapine is a significantly bigger opportunity than UZEDY. I think you flagged it as sort of multi-billion dollar peak sales with a faster ramp compared to UZEDY. What drives your conviction here for mdc-TJK? Three things. As Richard said, olanzapine is the most used antipsychotic. Second, it is used mostly for the most severe patients and the ones refractory to other treatments. Those patients are the ones that need the long-acting the most. Third, thanks to Eli Lilly's failure, there is no competition. Our olanzapine LAI has truly the potential to be a multi-billion first-in-class product. Perfect. And likewise, I asked with UZEDY, is there any appetite for Teva to launch olanzapine ex-U.S., particularly in Europe? Yes, on olanzapine, they said they would. It is a great step forward, as I mentioned earlier, and the field is wide open. Exciting. Okay, and then let's move on to your other asset, mdc-CWM. This is your long-acting intra-articular celecoxib. We know that phase three data was reported last year and it did not meet the primary endpoint, but you saw the strong signal in a large subgroup population. Could you outline the study and your sort of latest communications with FDA? Yeah, so just a reminder, this is an intra-articular celecoxib. We can go other places other than subcutaneous because of our rapid solidification. It doesn't get into the peripheral bloodstream, and so we don't see the systemic safety findings of celecoxib. Yes, in the first phase three study, the primary endpoint of two-week pain was not met, but day three, day seven pain in that large, large subpopulation, 70%-80% of patients who had not had prior knee replacement surgery. Maybe more important, there were positive results on the measures of inflammation, which might even be a bigger problem, so orthopedic surgeons tell us. It accounts for the 20% of patients after total knee replacement who don't return to normal function. Given this, we've been meeting with the FDA. We met earlier this year. We'll meet again before the end of the year to confirm the study design for the next phase three, confirm the study endpoints, and plan to run the next phase three study in 2026. Understood. Where would that put the potential time to market? Yeah, so we are hopeful that one more phase three study will be all that's required. The study recruits quickly. Orthopedic surgeons do conduct a number of knee replacement surgeries. To give you an idea, the first phase three recruited 150 patients in nine months with only five active sites. This could recruit pretty quickly. Okay, fantastic. The price point for these pain drugs is often quite low, so I think it's about $500 a year per patient. It's pretty cheap when you compare it to therapeutics and other indications. Bearing that in mind, what's the sort of total addressable market for this drug, and what is a reasonable peak sales estimate? Yes, so you're right about the unit price. The potential is still a few hundred million in the U.S. And remember, so a lower potential than UZEDY and olanzapine, of course. But remember that on this product, we are eligible at the end of the day to 50% of the profits, which will compensate the lower market. Okay, that makes sense. Now let's move on to something that's also very exciting. It's your collaboration with AbbVie. You have a collaboration for six programs, and the first candidate's sort of been chosen as in preclinical development. When could we see this in the clinic, and when or at least when can we expect the candidate to be revealed? We are bound, of course, by confidentiality with AbbVie. If I go back in time, we selected the lead candidate of this first program in September of 2024. It is, as we speak, in preclinical. If you extrapolate based on our past experiences, this is a program that could enter phase I in 2026. We do not know when AbbVie will decide to disclose the name of the drug and indication, but of course, I would love it if they did at the time of the phase I. Makes sense, hopefully. Could you remind us of the economics here with AbbVie and how the payments are recognized? Yes, so on AbbVie, we received $35 million upfront for this first product in April 2024. And then we are eligible to mid-single-digit to low double-digit royalties, plus $315 million of milestones, total milestones, both development and commercial. Understood. If we just touch on your financials a little bit, what's your cash position at the moment, and when do you foresee reaching profitability? Our fiscal year is March 31st, so we haven't disclosed our accounts as of September 30th. I can share with you our cash position as of March 31st, 2025, which was $72 million. Okay, and then on profitability? On profitability, so we've announced that we had for objective to reach operational profitability next year. So our fiscal year, March 31st, 2027. Okay, got it. I know you've previously spoken about sort of business development and other technologies that might be interesting. Is M&A or in-licensing something that you're actively working on or have an interest in doing? Yes, in our business, it's important to keep our lead, and we've shown that we were the best positioned company in our space of small hydrophobic molecules. We keep scouting the world for other technologies companies in the space that could complement what we do. At the end of the day, I'll always say that probably 50% of our innovation will be in-house and 50% external. Okay, understood. Are there any milestones that you're expecting in the near term? Yes, of course, the big one is the filing or acceptance of the filing of olanzapine LAI. We will keep getting the UZEDY sales quarterly as well. We are hoping as well to get the phase three of mdc-CWM going during 2026. We have two programs which should start phase ones, actually, based on what I said, hopefully three. Maybe AbbVie number one, our contraceptive program, and our malaria program. As a reminder, we do quite a bit of work in global health, and the malaria program is a pure global health program. Got it, perfect. And then just switching gears a bit, I know you also have Bepostar, which is your more novel formulation of the BEPO technology. Could you run us through this, and how could this extend BEPO's patent life? Yes, so original BEPO, the patents were 2033. Of course, on every program, we have additional either method of use or composition of matter patents. For example, on the UZEDY, the last patent is 2042, olanzapine 2044, which I love because that's many years of potential royalty revenues. The new generation of BEPO, which we call Bepostar, extends our visibility to 2040. Our amazing team in the lab is working on the next generations, and hopefully, we'll have some exciting things to share in the next while. Looking forward to it. Recently, one of your peers struck a notable deal with Eli Lilly for four potential obesity programs. Could you speak a little bit about the compatibility of BEPO or even future generations of BEPO with peptides and larger molecules, and what do you see there? Yeah, so as I said, BEPO targets first small hydrophobic molecules. We can do some hydrophilic peptides. We have a bit more difficulty with the larger ones, but we are working on it. Good to hear. I know you touched on it a little bit earlier, your contraceptive and malaria programs. Could you sort of give us a little bit more color about them and any sort of partnerships that are involved with those programs? Yeah, so this is a six-month subcutaneous contraceptive. Existing subcutaneous products go two, maybe three months. Beyond that, women need to use surgical implants or devices like rings, which may not always be preferable. This program is funded by the Gates Foundation because even outside the US, where there is a need, there is an even greater need in the developing world. We do plan to start phase one in 2026. Great, and the new malaria program? The malaria program, again, a pure global public health program. It is funded, not disclosed yet, but that one uses an ivermectin formulation to kill mosquitoes and dectocidal envisioned to be given once at the beginning of the rainy season in endemic areas and prevent the spread of malaria, particularly in children who are most impacted. Fantastic. Finally, just to close things off, how do you define Medincell's mission today, especially given how beautifully it's evolved post UZEDY? Yes, so we've been entering a very exciting time. As I said earlier, we believe the next two years will be the most transformative of Medincell's history. Our shift to growth strategy has three engines which are firing in parallel. UZEDY, which will take us to profitability, olanzapine, which will accelerate growth dramatically, and then the pipeline and new technologies. AbbVie number one, CWM, the new technologies I talked about, which will fuel the future growth. So exciting times. Thank you. Brilliant. Thank you so much, everyone.