Relmada Therapeutics, Inc.

My pleasure to introduce Brian Ritchie. Thank you, Brian. You may begin.

Good day, everyone, and thank you for joining us today. This afternoon, Ramada issued a press release providing a business update and outlining its financial results for the three months and year ended December 31st, 2024. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Ramada's management team will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Ramada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K, for the year ended December 31st, 2024, filed after the close today. This conference call also contains time sensitive information that is accurate only as of the date of this live broadcast, March 27th, 2024, Ramada 2025. Ramada undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances after the date of this conference call. With me on today's call are Romada's CEO, Dr. Sergio Traversa, who will briefly provide a summary of recent business highlights, and Romada's CFO, Maga Chinada, who will provide a review of the company's Q4 financial results. After that, we will open the line for a brief Q&A session. Now, I will hand the call over to Sergio Traversa. Sergio?

Thank you, Brian. Good afternoon and welcome everyone to the RealMada fourth quarter and year-end 2024 conference call. RealMada is focused on three priorities. Progressing our product pipeline, including NDV-01 and Cepranolon, and exploring product acquisition opportunities to maximize shareholder value. And third, maintaining careful resource priorities. Prioritization. During today's call, I will spend a moment on our strategic product acquisition efforts and provide a pipeline update. After that, Maggot will review our financial results. I will make a few closing remarks, and then we'll take your questions. At the end of last year, we initiated a process to transform the company through strategic product acquisition efforts to maximize shareholder value. I am pleased to report that the process is going well. We have always maintained an active surveillance to consider programs that have the potential to be high value assets and meet our key target criteria of innovation, established proof of concept points, near-term value creation drivers, and the potential addressed well-defined underserved markets. With the discontinuation of the Phase III studies of REL 1017 in major depression disorder, we made the exploration of strategic product acquisition our primary focus. We have been following the progress of several programs, and our recent efforts identified an additional number of attractive opportunities. After in-depth reviews of several compelling candidates, we recently announced the acquisition of rights to two product candidates, NDVOD1 in development for non-muscle-invasive bladder cancer and Cepranolone for compulsion-related disorders. While we maintain a deep understanding of diseases of the central nervous system as we evaluate strategic opportunities, The drug development expertise of our team provides flexibility to be opportunistic and consider innovative programs that meet our target criteria, regardless of the therapeutic area. Moving on to our product pipeline, I would like to provide a brief overview for NDV01 and Sopranolone, and also provide an update on our plan for RELP11. Let's start with NDV01. On March 25th, we announced an exclusive licensing agreement with Trigon Pharma Limited for NDVO1, a novel, sustainably intravascular chemotherapy for the treatment of high-grade, non-muscle-invasive bladder cancer, NMIBC, and potentially other subtypes of bladder cancer. The program is currently in a phase 2 study. We believe that NDVO-1 is an excellent fit with our four key target criteria. Number one, innovation. Trigon intravesical sustained release formulation of Gelsidabine and docetaxel could represent the true innovation in the care of high-grade non-muscle invasive bladder cancer. Number two, group of concept data. that is, support the efficacy of gencytabine and docetaxel dosing in the treatment of NMIDC. Number three, near-term value drivers. We expect the top-line safety and efficacy data for NDVO1 to be reported at the American Urological Association meeting, AUA, that will be held on April 26 to 29, 2025, in Las Vegas. And number four, the potential to address well-defined underserved markets. Sources indicate that there are about 75,000 new cases of bladder cancer diagnosed. About 50 of those cases have high-grade disease that has a high risk of recurrence. There is a very high recurrence rate for the 450,000 people in the U.S. that are living with bladder cancer. NDV01 is currently evaluated in a Phase II single-arm study to assess safety and efficacy in patients with high-grade non-muscle-invasive bladder cancer. The study was designed to evaluate safety and efficacy in subjects with localized, non-metastatic, high-grade, non-muscle-invasive bladder cancer. Top-line data from the first Approximately 20 patients in the study are expected to be presented at the American Urological Association meeting in Las Vegas on April 26 to April 29 this year. Our goal is to bring NDVO1 to patients as soon as possible. With positive results, we believe that NDVO1 could become the treatment of choice for high-grade non-muscle-invasive bladder cancer, both as First-line therapy for new patients and salvage therapy for existing patients whose disease has progressed. Let's spend a moment on the treatment of high-grade non-muscle-invasive bladder cancer. Intravesicular therapy is a mainstay of treatment intended to reduce the risk of recurrence following surgery. Previously, the immunotherapy Bacillus Calmetgerin, BCG, was the cornerstone of treatment. However, significant supply constraints prompted the evaluation of intravesical chemotherapy. The medical community evaluated a number of chemotherapy agents, and published studies suggested that the use of intravesical gemcitabine and docetaxel, known as Gemdosi, is to be the preferred combination, with improved response rate and promising tolerability. Frequent gene dosing is required, and the chemotherapy agents have a short blood retention time, which limits the exposure to the chemotherapy. Together, this factor increased the risk of treatment failure and discontinuation and prompted the development of NDVO1. NDVO1 is administered in a simple two-step process in the urologist's office. It is designed for intravesical dosing and intended to be an in-office, ready-to-use therapy that is administered rapidly, within 10 minutes, and requires no anesthesia or new or dedicated equipment to employ. NDVO1 forms a spherical soft matrix within the bladder that sequesters drugs and releases it in a matrix gradually dissolved over a 10-day period. NDVO1 formulation is specifically designed to maximize local drug concentration and prolong exposure to gem dosing while minimizing systemic toxicity. Unlike conventional intravesical installation, NDVO1 is designed to avoid peaks and tops in drug concentration, ensuring a gradual and sustained release of gem dosing over a 10-day period. This approach may improve overall efficacy, reduce side effects, and reduce the frequency of dosing to improve patient compliance and outcomes. We believe that NDV-01 has the potential to improve on the published GEM dosing results with less frequent dosing, ease of administration, and improved treatment compliance, which could lead to improved clinical outcomes in high-grade, non-muscle-invasive bladder cancers. Our positive perspective is supported by primary field research with our care providers. The next step includes to present the top-line Phase II results in four weeks, meeting with the FDA to align on a regulatory path to approval, completing the production of the next batch of material, and finalizing the design of registration studies intended to begin in late 2025 or early 2026. Moving on to Cepranolone. On February 6th, we acquired Cepranolone as a potential therapy for Tourette's syndrome and other compulsion-related conditions from Azarina Pharma. We believe that Cepranolone is also an excellent fit with our four key target criteria. Number one innovation, Cepranolone or iso-albopregnanolone is a first-class compound from a new subgroup of neurosteroids known as GAMSAs, or GABA-A modulating steroid antagonists. GAMSAs act selectively on the GABA-A pathway to alleviate the symptoms or compulsive disorder. Number two, proof of constant data. Phase IIa results from Azarina signal improvement in Tourette's syndrome, quality of life, and robust overall safety. These data support cephanolin as a new potential first-line treatment option for Tourette's syndrome and opened the door to evaluation in other compulsion-related disorders. Number three, near-term value drivers. With promising Phase IIa data and safe information from more than 350 subjects, cephanolin is a Phase IIb-ready product. Number four, the potential to address well-defined underserved markets. Tourette's syndrome impacts more than 350,000 children in the U.S. No, sorry, not children. Impacts more than 350,000 patients in the U.S. have Tourette's syndrome. Existing treatments include dopamine, B2 blockers, and a typical antipsychotic are often limited by significant side effects. Stepping back for a moment, Cepranolone is a neurosteroid and the first in class, Gamsa. or GABA-A modulating steroid antagonistic acts. By selective inhibiting GABA, neurotransmitter included allopregnanolone, a neurosteroid implicated in Tourette syndrome and other compulsive disorders. Our evaluation of cecranolone has also included a review of other prominent compulsion-related disorders, and we identified Prader-Willis syndrome, or PWS, as another potential indication. as it is often defined by persistent hunger and overeating, apophagia, that may have a strong compulsion-related element. The estimated global prevalence is approximately 350,000 to 400,000, and current treatment is focused on improving obsessive-compulsive behavior and other medical conditions. The Pradalon might be ideally suited for Prader-Willi syndrome, given its good overall tolerability, and unique impact on compulsibility disorder, which would enable it to be incorporated into existing comprehensive treatment regimen for Prader-Willi syndrome. Next step include meeting with the FDA to align on the regulatory path to approval, further development of the product supply plans, and finalizing the design of a Phase IIb study intended to begin late 2025 or early 2026. Now I would like to turn the call over to our CFO, Nagit Shenouda, to talk about our portfolio prioritization efforts and financial results. Nagit?

Thank you, Sergio. Portfolio prioritization and resource alignment are important elements for our strategic value creation process. As part of our prioritization, I want to provide an update on REL P11, or P11. a novel low-dose modified release formulation of psilocybin in development for the treatment of metabolic disorders such as obesity. We advanced P11 into a first-in-human study in Canada based on promising preclinical data showing that P11 improved metabolic parameters in animal models with no detrimental psychedelic-like side effects at doses tested. Results of the Phase I study indicate that REL P11 is well-tolerated. However, we are reevaluating further development of P11 given our emphasis on focused patient populations and the increasingly competitive clinical development landscape in metabolic disease. While there has been a significant resurgence of effort to bring psychedelics into approved clinical use, we also recognize caution among regulators and clinicians that may complicate development as a result of these factors. We are reevaluating our resources for P11 as we devote substantial portion of our internal resources to the development of NDV01 and Suprem. Turning to our financial results. As noted by Brian this afternoon, we issued a press release announcing our business and financial results for the fourth quarter and the year ended December 31, 2024. Full details are available in our press release and the 10-K filing we completed today. These documents are available on our website and the news and SEC filings tabs are on our investor relations page. As of December 31, 2024, RealMata had cash, cash equivalents, and short-term investments of approximately $44.9 million, compared to $96.3 million as of December 31, 2023. Tax use and operations in the fourth quarter ended December 31, 2024 was approximately $8.8 million compared to $10.2 million for this same period in 2023. Looking ahead, we expect to devote a substantial portion of our internal, excuse me, of our internal resources to the development of NDV01 and Sopranolone. We will have a greater sense for our spend and cash runway following the planned FDA interactions intended to be completed later this year. Moving through our fourth quarter 2024 financial results. Research and development expense for the fourth quarter 2024 totaled $11 million compared to $14.7 million for the fourth quarter 2023, a decrease of $3.7 million. The decrease was primarily driven by a decrease in study costs associated with the completion of clinical trials for REL 1017 for major depressive disorder. General and administrative expense for the fourth quarter of 2024 totaled $8.1 million compared to $12.1 million for the fourth quarter of 2023, a decrease of approximately $4 million. The decrease was primarily driven by a decrease in stock-based compensation expense. Net cash used in operating activities for the fourth quarter of 2024 totaled $8.8 million, compared to $10.2 million for the fourth quarter of 2023. The net loss for the fourth quarter of 2024 was $18.6 million, or $0.62 per basic and diluted share, compared with a net loss of $25.1 million, or $0.84 per basic and diluted share for the fourth quarter of 2023. Before we open the call for questions, I'll turn the call back to Sergio for some closing comments. Sergio?

Thank you, Maggot.

I would like to leave you with these key messages from today's call. RealMata is focused on three priorities, exploring strategic product acquisition to maximize shareholder value, progressing of a product pipeline, and maintaining careful resource allocation. Our evaluation of strategic product opportunities is focused on key target criteria. Innovation, proof of concept data, near-term value creation drivers, and potential to address underserved markets with flexibility to be opportunistic, given our drug development expertise. Our plans for each program centered around interacting with the FDA to align on regulatory strategy complete production of the next batches of material, and finalize the design of the next studies expected to begin around the year end this year or early 2026. For NDBO1 in development for hydrate non-muscle invasive bladder cancer, we expect initial proof of concept data to be reported at the American Urological Association meeting, AUA, held in April 26, 29, 2025 in Las Vegas. Our next study is expected to be a registrational trial. For Sopranolone, our next study is expected to be a signal-finding study in Prader-Willi syndrome and a phase 2B study in Tourette syndrome. In closing, as we prepare to advance our two clinical programs, we want to thank our investors for support and for taking time to join today's call. We look forward to updating you on our progress throughout the year. Operator, I would like now to open the call for questions. Thank you.

Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that you're in the question queue. You may press star 2 to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys. One moment while we poll for questions. And our first question comes from Oi Ear with Mizzou Securities. Please proceed with your question.

Hey, guys. Thanks for taking our question. First, congratulations on the two deals. Yeah, a question that we've been getting is maybe just help us understand the process that was involved in the deal, why... were there other competitive bidders, particularly for NDV01, and why these companies chose to go with you if there are other bidders over the other bidders? That's the first question. And I guess the second question we have is, at the upcoming AUA meeting, what should we kind of expect in terms of you know, potential data. And I think the abstract will be out on April 11 or something. Will there be data in the abstract or the sort of the key data will be at the conference? Thanks.

Well, thank you all. Thanks for the question. I'll start with the first one, why partners decided to come with RealMada instead of other companies. Well, the first acquisition of Soprano was a little bit more simple and was a straight acquisition of an asset that we knew we have known for a long time. And to be very direct, that acquisition was planned in advance, regardless of what the outcome of the RelTest 17 would have been. So that was, it's been a long time, you know, a rather sweet, we've been talking with that Serena. So there was a little bit more simple. NDB01, it was a lot more competitive. And the reasons, well, we should ask to Drago on the real reason or the specific reason he decided to come with us. But our impression, what we can offer and we can put on the table is clearly a strong development capability. And we have done four Phase II trials, probably 10 Phase I, additional Phase II abuse deterrent studies. So we do have quite a bit of expertise that can be applied to other therapeutic categories. And that clearly has a value. The infrastructure is intact. And so that was clearly one component. The other components are a little bit like softer and more customized to the relation we have with Trigon. It also has been a long-term relation. NDVO-1 is one of the two products that RealMata has now. So clearly we'll put a lot of focus on these two products. So there is no risk that NDVO-1 will be one of the 10, 20 products in development that larger companies they have. So focus on the program. That's clearly one of the reasons. And then the second one, is that yeah when we do this kind of transaction for both companies as arena and trigon we work together so both management of assarina and trigon they were very close without this real partnership and we don't want to lose the know-how is the expertise of people that have been working on these plans on this program for years and years so i mean being part of the of the program being part of the team that will try to bring this product to the market together with the focus and the development capability, made RealMada the company of choice, at least for... Yes, you can.

Can I add one thing? You know, the other, I think, you know, important factor is now Trigon, or Trigon shareholders, are also shareholders of RealMada and will participate significantly in the upside related to NDVO1.

Thank you, Megan.

I hope we answered your answer, the first question. And the second one, I have to be a little bit more cautious because in the abstract, there's not going to be any particular data, reason being that the data will be collected in real time, and so they will be ready to be presented when they will be available. This is right before the AUA conference. So they won't be ready to be included in the abstract because the patients are still in treatment and they're still being evaluated. And in terms of expectations, look, it is a very competitive market. There is several products in development for the treatment of bladder cancer. We do have the data published available on the combination GEN-DOSI used as an immediate release that has been used for years and extensively used by urologists. So that would be the starting point. We do expect the data to be at least as good as what is the immediate release formulation as of today, and the data are available and published in the literature. So you find different numbers, but the kind of rule of thumb that we heard from urologists is that when you have a complete response of month three or four, somewhere in the range of 75%, you definitely are in the competition. And this is a good number, right? This is just based on historical and from urologists. We'll see what MDBO1 will deliver.

So is the expected data, is that primarily from the three months of induction and any particular?

Yeah, maybe I can step in here. We really, you know, we want to be respectful of the meeting. We want to be respectful of, you know, whatever restrictions there are about data release. So, you know, just to be mindful of that, we'd rather not, you know, delve into the expected data release. Okay. We'll learn a lot more, you know, when the abstracts are presented and then when the data are released.

Thank you.

Sure.

A few more weeks of patience, please. Okay. All right. Thank you.

And our next question comes from Mark Goodman with Lee Rink Partners. Please proceed with your question.

Hi. Good afternoon. This is Basma on for Mark. Our first question, could you please elaborate a little bit on the safety profile of Sopranolone? And also, we have the question on the second indication, which is . Now, given that the space is a little bit crowded after the recent approval of the first agent in this indication, do you think that it's going to be a valuable second opportunity for the drug? That's it. Thank you.

Well, thanks for the questions. The safety profile of cipranolone, we know it very well. It's very well known. And there are safety data on over 350 patients. And the only side effect that was more frequent, we're still talking about low single digit, is a sub-Q injection. So it was... injection site redness and some irritation, temporary. So that was it. So that can be read as an extremely well-tolerated drug. And on the second question, the Prader-Willi. Well, the answer is yes. There is definitely space for other products. And we are, you know, very happy about the approval that we have seen yesterday because it means that the FDA and, you know, the patients association and, you know, the outside world wants and needs new drugs for the treatment of this terrible syndrome or bad syndrome, the Prader-Willi. In terms of the space for Cepranolone, Cepranolone acts on the GABA-A and it acts on the compulsory component that is very different from what the other products are working on. So I would not only say that there is space, I would say that there is some complementary, at least based on the mechanism of action, there is some complementarity between Cepranolone and what is available and what potentially will become available. I hope I answered your question.

Thank you. That's very helpful.

Thank you. And as a reminder, if you'd like to ask a question, please press star 1 on your telephone keypad. That is star 1. And our next question comes from Andrew Sai with Jefferies. Please proceed with your question.

Hey. Congrats on in-licensing these compounds. Pretty cool. Maybe for Soprano alone, What is the approvable endpoint for pivotal studies, and what did you see in the Phase IIa on that endpoint, and how would that compare to the dopamine blockers and antipsychotics used for Tourette's?

Well, thanks, Andrew. Great hearing from you, and thanks for the question. Let me be sure that I understand what the endpoints are. Well, for Prader-Willi, the endpoint, the FDA knows the path very well, and so you have seen the approval yesterday, so we do believe that that is pretty much the endpoint that would define the process or the regulatory process. We haven't spoken with the FDA yet, so it's just trying to, you know, to use the logic and to try to learn from what's happening out there. For the Tourette's syndrome, usually the endpoints, there is a scale, a Yale scale. That is the usual endpoints and measure, like the number of ticks. And based on the mechanism of action, we'll try to incorporate in the endpoints also the compulsive aspect of the Tourette's syndrome. And you may know that about 40% of patients with Tourette's, they also are affected by obsessive-compulsive components. So we may probably have to use the scale, but we may also try to focus on what the drug does best, that is controlling compulsive behavior.

Okay. And then for the bladder cancer compound drug, After you report the data at the medical conference, does it make sense in your upcoming FDA meeting to discuss whether an accelerated approval pathway is possible?

Well, not right after the data, but probably after we will discuss with the FDA what the path for approval is. And if you look at how other drugs have been developed, are in development, and the drugs have been approved. And also, considering that Gendozy, the combination of Gencytabine and Docetaxel, has been widely used over the last, I would say, 10 years by urologists, we have some hope, we have a good hope, like the other companies, that the FDA will require only one study, open label, with no placebo. That's what we have seen, but we'll talk with the FDA, and then we will update you on what the regulatory process for NDVO1 is. It's a little bit too early to make big statements.

And then my last question is, can we expect you to in-license more compounds this year?

Well, we always keep our eyes open. We have done a lot of evaluations. There is a lot of product available. for in-licensing. There are great ideas, and there are small companies, private, that have issues in capability of developing or doing phase two, and the availability of financing, and as a public company with development capability, I would say that other potential licensors, they come to us, and as of now, We don't know if we'll do anything anytime soon, but we clearly keep our eyes open. Our goal is to build the pipeline and we have two products now and to try to bring in any assets, any development program that fits in our strategy. I have to be vague because there is nothing that will happen this week or next week, but in the In the future, you never know. We keep an eye on everything. But we will only do, we are selective, right? We don't want to in-license something just to license something. We want to have something that has potential and it fits our development criteria that, you know, I discussed during the call.

Right. Very good. Look forward to more updates. Thanks.

Thank you, Andrea.

Thank you, Andrew.

Thank you. And with that, there are no further questions at this time. I'd like to turn the floor back to Sergio Traversa for closing remarks.

Well, thank you very much. We can end the call, but I would like to end it with a big thank you for the support and for the people that have believed and believe in the company and in us that we can develop products and we can bring to the market help for patients and return for investors. Thank you very much.

Thank you. And with that, that does conclude today's teleconference. We thank you for your participation. You may disconnect your lines at this time.