MedinCell S.A. (MEDCL) Earnings Call Transcript & Summary

I will do this in English, and someone will translate, Christoph or someone else. So, I will go slow. But yes, we did receive results of the Phase III study of which, as a reminder, is an intra-articular in the joint injection of selacoxib for patients having had total knee replacement surgery to treat both inflammation and pain. So, a reminder of the value. The value is that patients currently require high doses of opioids and end up being addicted to opioids in up to 15% of cases. So, an intra-articular celecoxib is designed to limit the use of opioids and mitigate the risk of addiction. A reminder of the study design. This was a Phase II that started in November -- I'm sorry, that started in November of 2022, finished in recruiting patients in August of 2023, and last patient finished end of 2023. We've spent some time over the past months analyzing data and are ready to present the results to you. The primary endpoint was pain at average pain at 2 weeks. And there were key secondary endpoints of pain at 3 days and 7 days, and then there were key inflammation endpoints. Remember, celecoxib is an anti-inflammatory. So, we looked at outcomes consistent with inflammation, such as range of motion of the knee joint, joint fusion and functional ability to emulate. And next slide, please -- so here are the results. So, the primary endpoint of time-weighted average pain intensity over 14 days was not met. However, there was numerical improvement enaboring the F-14 treated group for the primary endpoint as well as for the other payment of pain over 3 days and 7 days. So, moving to the endpoints for inflammation. Here, there was a statistically significant improvement compared to control group for a range of motion, and you can see the p-value there at 6 weeks and 3 months, joined a fusion, which is swelling at 6 weeks and 3 months as well as for the timed up and go test, which is a test in which patients are asked to stand up from a chair, walk 10 feet and return to the chair, and it's measured by the time it takes to do that. Now very important is that when we looked at the patients who were enrolled in the study, 108 out of the 151 enrolled, randomized -- had not had a prior total knee replacement in the contralateral knee. And when we looked at that large subpopulation, we found statistically significant improvement in endpoints of all the time weighted AUC average pain intensity at 3 days and 7 days, we saw improvement in opioid consumption, and we saw even greater improvement on the previously significant findings of range of motion, a fusion and timed up and go. Safety was excellent in the study. There were no safety findings of adverse events and severe adverse event reporting various adverse events reported were not related to F-14 rate treatment. These results further confirm the safety of injection of the med and cell polymer into an intra-articular space and supports further use of polymers in other intra-articular indications. So, looking at the results and knowing that celecoxib is predominantly an anti-inflammation drug, though it also has pain relief analgesia. It perhaps isn't surprising to see the greater improvement in outcomes of inflammation and improvement in pain outcomes only in the population that had not had prior total knee replacement. And perhaps it's not surprising to see this difference in the large subpopulation of patients who had not had total knee replacement because patients who have had total knee replacement have an expectation of greater pain. And when a patient has an expectation of greater pain, they typically have more pain. This phenomenon is called catastrophization like catastrophe in which patients come into a study, having had prior replacement and believe that they're going to have greater pain. And this is also impactful because there was no placebo group. All patients received multimodal analgesia and F-14 was added to half of the patients. Of note is that this population was the population studied by Hera in their study of their approved product Zebula for postoperative pain related to total knee replacement. And quite important is that even though Heron only studied a population of no prior total knee replacement, their label, their approval label does not specify this limited population and in fact, allows treatment of all patients who have had total knee replacement. And so even though the primary endpoint was not reached, there's quite a bit of encouraging data here on both pain in the subpopulation as well as measures of inflammation in the total population. And this provides a pathway to approve it in the coming years. And so MedinCell and our development partner, AIC are planning to meet with the FDA this year from this study and to discuss what additional study or studies will be needed for ultimate approval. Next slide.

Maybe one question we see about the next steps, can. I know that it's early to answer, but we have a question about what could be the next steps for this program?

Yes. So, the first step is to meet with the FDA, gain their agreement on what additional study or studies would be required. It's likely that based on the results of the study, that 2 additional Phase III studies will be required but that will need to be discussed with the FDA. However, because unlike this study, those studies would be done in parallel at the same time. There shouldn't be any impact on ultimate time lines to approval.

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And another question for you, Rick. Why 2 more Phase III studies? Why not just one, maybe you can elaborate a little bit?

Yes. from an FDA point of view, you need to have a positive primary endpoint for a study to be included as a registration study. This study did not meet its primary endpoint, and therefore, can't be considered a registration study.

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This is a reminder for everyone about the benefits of USD versus other long-acting injectable risperidone on the market and why USA is a clear best-in-class product among long-acting injectable risperidone. First, it's administered subcutaneous. So smaller needle, less painful. The Janssen products are administered intramuscular more painful injection, not favored by patients. Second, it doesn't require reconstitution as the Janssen products do. It comes in prefilled syringes, 4 doses for the monthly injection, 4 doses will be every other monthly injection so easy for physicians to transition from oral antipsychotics or even from other long-acting injectables. And third, it has an immediate onset of action within 24 hours. It reaches therapeutic levels, and therefore, it's not required to give oral supplementation of risperidone or additional titrating injections as is true for many of the long-acting injectable risperidone from Janssen. And finally, the same levels of risperidone on the blood are seen, we used is injected in the arm, in the abdomen or in the thigh. This is not true for the Janssen products, where there's different levels depending on site of injection. Next slide. There was additional differentiation from Teva's Phase III study, apart from the primary endpoint of risk of relapse, Teva demonstrated improvement in positive and negative symptom scores, not only on early parts of the study, but also into the second year, there was continued improvement. And importantly, there was improvement in quality of life measures of schizophrenia, which is rarely demonstrated in studies of CNS. And it's for all of these reasons that we believe that physicians have recognized USAT as a true best-in-class long-acting injectable risperidone, and we believe accounts for the rapid rise in prescriptions we're seeing.

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So a reminder of post-injection delirium and sedation syndrome. It's not very common, less than 0.1% of injections and 2% of patients, but the risk is present for every injection. Yes. And so, Lilly did receive a black box warning on their label. Physicians who prescribe it have to enroll patients in a REMS program for monitoring and most impactful, all patients for every injection must be monitored in the clinic for 3 hours after injection. And so patients don't want to come into the clinic for 3 hours, psychiatrists don't wish to don't have the facilities for this. And so, the Lilly product is just not being used as Christoph is. And so MedinCell when developing the formulation, our goal was to limit or eliminate the risk of PSS, which is believed to be caused by a burst by a high level of olanzapine in the blood on injection. Next slide. Here is some data supporting our belief and Teva's belief that we will not see PDSS in our clinical studies. This is injection into human plasma in a petri dish ex vivo. The red line on the top is Lilly's long-acting injectable olanzapine that when injected directly into human plasma has nearly complete release of all olanzapine into the blood immediately. You can imagine this could be consistent with the burst of olanzapine on intramuscular injection. And on the bottom in green is the med and cell formulation of olanzapine, same experiment when injected directly into plasma, very little is released right away, suggesting that even if the subcutaneous injection of olanzapine from MedinCell, got into the blood, there still would not be a high release and unlikely to produce a burst of olanzapine. And on the next slide, it's nice to see data in a [indiscernible]. It's better to see it in humans. This is a Phase I study showing on single injection on the top, repeat injection on the bottom in schizophrenia patients, there was no burst of olanzapine. I would also point out that in the higher doses, an immediate attainment of therapeutic level was reached at 10-nanogram ML similar to UTI. And I would also point out the nice smooth pharmacokinetics on repeat injection. And I would point out that in the 100 or so injections given there was no PDSS in this small Phase I study. Next slide shows the Phase III study design that was created based on the Phase I results. You can see that it was a 2-period study, the first an 8-week randomized double-blind study comparing doses of olanzapine to placebo. The primary endpoint of this period 1 was the positive and negative symptom scale. Key secondary endpoints included a clinical global impression severity as well as personal and social performance scales. These are all very typical of an acute schizophrenia trial. And the primary objective of the study, different than the endpoint was safety and period 2, which could last up to 48 weeks, was designed in open-label fashion to capture multiple injections looking for and not seeing hopefully, any PDSS. So Teva discussed last week results from the period 1 study, the double-blind, placebo-controlled, and you can see here that primary endpoint was met on all 3 doses, the separation of 9.7%, 11.2% and 9.7% are not only highly statistically significant, so quite clinically meaningful in comparison to other long-acting injectable antipsychotics. The study also demonstrated statistically significant results at all 3 doses on the key secondary endpoints of CGI and PSP. Next slide, Remember, the primary objective was safety and out of 3,600 targeted injections, which is what the FDA has asked Teva to obtain to mitigate the risk of PDSS 80% have been complete mill reach PDSS. Next slide. So, the Phase III study completed 9 months ahead of schedule, which is a tribute to Teva's Clinical Development Group. The full safety database is expected to be available and reported on second half of this year. Next slide.

So Michel, you were several questions on risperidone versus olanzapine. Do they target the same patients -- and what will be the strategy on the products.

Right, right. So, olanzapine is not a competitor of risperidone. It's used for more severe symptoms or for refractory patients, which is up to 30%. So, it should not be a competitor of Risperidone.

So the question here, Richard, is can we get a bit more color on the time line when the filing will be done and how long it will take. So, we don't have that information, but maybe you can give us your perception or your opinion based on benchmarks?

Knowing development time lines, knowing where they are in the study, it would be reasonable to expect they would file the NDA very early in 2025 after enough patients have gone through the study. And with a 10-month review time by the FDA that would allow for approval by fourth quarter of 2025 with launch to follow very quickly after. And certainly, attaining the primary endpoint and key secondary end points, it makes the product very approvable. And the only thing left to see is whether there is any PDSS in the remaining objection.

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[Foreign Language] [Statements in English on this transcript were spoken by an interpreter present on the live call.]