Minerva Neurosciences, Inc

Welcome to the Minerva Neurosciences first quarter 2023 conference call. At this time, all participants are in a listen-only mode. There will be a question and answer session following today's prepared remarks. This call is being webcast live on the Investors section of Minerva's website at ir.minervaneurosciences.com. As a reminder, today's call is being recorded. I would now like to turn the call over to Jeff Reiss, President of Minerva Neurosciences. Please go ahead.

Good morning. A press release with the company's first quarter 2023 financial results and business highlights became available at 7.30 a.m. Eastern Time today and can be found on the Investors section of our website. Our quarterly report on Form 10Q was also filed electronically with the Securities and Exchange Commission this morning and can be found on the SEC's website at www.sec.gov. Joining me on the call today from Minerva are Dr. Remy Lutringer, Executive Chairman and Chief Executive Officer, and Mr. Fred Alholm, Senior Vice President and Chief Financial Officer. Following our prepared remarks, we will open the call for Q&A. Before we begin, I would like to remind you that today's discussion will include statements about the company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. We caution that these forward looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated. These forward looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors that are more fully detailed under the caption risk factors in our filings with the SEC, including our quarterly report on Form 10Q for the quarter ended 31st of March, 2023, filed with the SEC earlier today. Any forward-looking statements made on this call speak only as of today's date, Monday, the 15th of May, 2023. And the company disclaims any obligation to update any of these forward-looking statements to reflect events or circumstances that occur after today's call, except as required by law. I would now like to turn the call over to Remy Lutringer.

Thank you, Jeff, and good morning, everyone. Thank you for joining us today. I would like to begin with the great news about our ROLI paradigm program. We received confirmation on the 27th of April from the FDA that our NDA was filed And on the 8th of May, we received confirmation that the review will proceed on a standard review timeline with a goal date of February 26, 2024. At this stage, the FDA stated that it is not planning to hold an advisory committee. The FDA also noted that they had identified as potential review issues Those issues are already cited in the FDA's refusal to fight letter and communicated in the Type C meeting in March 2022, which I will discuss in a moment. Roliparidone has a novel mechanism of action in a new indication, and this has not been a straightforward finding process. So let me provide you with some additional insight in our recent interactions with the agencies. Negative symptoms of schizophrenia are notoriously difficult to treat, and as Dr. Harvey commented following the finding of our NDA, an approved treatment for negative symptoms could revolutionize the treatment of schizophrenia. This is underscored by the lack of any approved drugs in the U.S. to treat these symptoms, and to the best of my knowledge, there are no drugs currently in development that have a specific and direct benefit on negative symptoms of schizophrenia and very importantly, that translate into a functional improvement in patients. While other drugs in development may reduce negative symptoms as a consequence of improving positive symptoms and those related to the side effects of antipsychotics, none have been shown to be effective directly and specifically on disease-related negative symptoms. Furthermore, our two late-stage studies have shown that improvement in the measures of negative symptoms translates into an improvement of daily functioning. Again, to the best of my knowledge, Roliparidone is the only drug that has shown both improvement of disease-related negative symptoms and, as a consequence, daily functional ameliorations in patients. Last but not least, it is well documented in the scientific literature that antipsychotic drugs that block dopaminergic pathways in the brain may cause drug-related worsening of negative symptoms beyond the negative symptoms that are disease-related. Roliferidone administered in monotherapy is intended to treat specifically those negative symptoms that are disease-related in a well-identified patient subpopulation which isn't prone to relapse as has been demonstrated in both of our late-stage clinical trials. While we intend for Roliferidone to be prescribed as a monotherapy, one of the issues FDA raised is its potential use by patients on antipsychotics. When we began Roliferidone's clinical development, we deliberately chose to position Roliferidone as a monotherapy. We chose this approach based on both KOL feedback and my personal experience in clinical practice that highlighted an important underserved population, the substantial number of patients diagnosed with schizophrenia who do not need continuous antipsychotic drug therapy to manage their positive symptoms, but whose negative symptoms render them incapable of leading normal lives. As previously mentioned, these are the patients that we recruited and studied in our clinical trials. We estimate that around 60% to 70% of patients diagnosed with schizophrenia suffer from moderate to severe negative symptoms. Of those, a significant number do not require antipsychotics to control and stabilize the positive symptoms. Supported by data from our Phase IIb and Phase III studies that included this well-defined group of patients, we submitted our NDA seeking the approval of 64 mg of quadriperidone. We believe that these trials were adequate and well-controlled for the purposes of submitting an NDA. The overall data set included results from two doses, 32 mg and 64 mg. Each study was placebo-controlled and included a 12-week double-blind period comparing monotherapy voliparadone to placebo. Also included were the data from the six-month open-label extension phase of the Phase 2b study and data from the nine-month open-label extension of the Phase 3 study. The Phase IIb study was positive and met the primary endpoint, as well as most of the secondary and exploratory endpoints for both doses. The Phase III study achieved the nominal p-value of 0.044 on the primary endpoint for 64 mg, but did not reach statistical significance for 32 mg. The p-values are only nominal p-values due to the fact that the Type I error correction used in the trial requires that both doses must show a p-value below 0.05 to declare a positive study, or a single dose must show a p-value below 0.025 to declare a positive finding in that dose arm only, and this was not achieved. The sole key secondary endpoint measuring daily functioning PSP showed nominally statistically significant superiority of proliferidone compared to placebo at both doses. One final point regarding our studies that is worth mentioning which FDA has raised as a potential issue and which we have discussed extensively with the FDA is the countries in which our studies were conducted. We enrolled the Phase IIb study exclusively in Europe, whereas the Phase III study included patients from both the U.S. and Europe. Schizophrenia as a disease does not vary from country to country. Patients demonstrate same symptoms and are treated with the same drugs irrespective of where they live. The U.S. patients and European patients in our Phase III study had virtually identical baseline symptom scores and had comparable responses to ralipiridone as measured by both the primary and the key secondary endpoints throughout the study. I would like to personally thank the FDA for the opportunity to have our NDA reviewed, and we look forward to continuing to work with the agency to address their questions. It's critical for many reasons we have discussed here today that we find an effective and safe treatment for patients with negative symptoms of schizophrenia. Thank you. I will continue to update all of Minerva's stakeholders of our progress in the coming months. I will now turn it over to Fred for the financial update.