Relmada Therapeutics, Inc.

Good afternoon. Welcome to Vermont Therapeutics' first quarter 2025 earnings call. At this time, all participants are in a listen-only mode. After the prepared remarks, we will conduct a question-and-answer session. To ask a question, please press star 1. As a reminder, this conference is being recorded and will be available for replay on the location website. I would like to turn the call over to Brian Ritchie from Lightside Avire. Please go ahead, Mr. Ritchie.

Good day. And thank you, everyone, for joining us today. This afternoon, Ramada issued a press release providing a business update and outlining its financial results for the three months ended March 31st, 2025. 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 and today's Form 10-Q for the quarterly ended March 31st, 2025, filed after the close today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 12th, 2025. Realmata 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 RealMata's CEO, Dr. Sergio Traversa, who will briefly provide a summary of recent business highlights, and RealMata's CFO, Maga Chinauta, who will provide a review of the company's Q1 financial results. After that, we will open the line for a brief Q&A session. Now, I would like to turn the call over to Sergio Traversa.

Sergio?

Thank you, Brian, as always, and good afternoon, and welcome everyone to the RealMata First Quarter 2025 Conference Call. 2025 is off to a good start for RealMata. We had the two unique product candidates with very encouraging Phase II data and large addressable markets to our portfolio, MDV01 for bladder cancer and Cepranolone, for Prader-Willi syndrome, Tourette syndrome, and potentially other CNS indications. We reported initial proof-of-concept Phase II data for our lead product candidate, NDBO1, at the American Urology Association, and we made progress towards our objective of bringing each program to patients as soon as possible, with preparation underway to begin the next set of studies for NDBO1 and Cepranolol. With two innovative product candidates that have shown promising proof of concept data, 27 million cash balance, clean balance sheet, and a disciplined approach to development plan, we are in a good position to advance our pipeline to important clinical milestones. During today's talk, I will provide a snapshot of our two programs, including a review of the initial phase two data for NDB01 at the AUI meeting two weeks ago. After that, Maggot will review our financial results. I will make a few closing remarks, and then we will take your questions. We also invited on the call today Dr. Yair Lotan, Chief of Urolo-Udo Oncology at the University of Texas Southwestern Medical Center in Dallas, who can answer your clinical question regarding NDVO1. We are encouraged by the potential of the diversified pipeline that we are building at Belmont. Starting with NDVO-1, we believe the program is an excellent fit with our strategic plan and has the potential to meaningful improve the care of patients with bladder cancer. Our decision to in-license NDVO-1 was based on strong science, strong field data, and the anticipation of positive phase two data at the upcoming American Urology Association meeting or AUA 2025. I'm pleased to report that positive top line proof of concept data presented at the AUA 2025 supported our initial enthusiasm for NDBO1's potential to be the class leading blood sparing chemotherapy for non-muscle invasive bladder cancer. During today's call, I will touch on the market opportunity, the mechanism of action, the data, and the next steps. Starting with the market, sources indicated that there are about 75,000 new cases of bladder cancer diagnosed each year in the U.S. About half or 50% of those cases have high-grade disease that has a high risk of recurrence. That is a very high recurrence rate for the 600,000 people approximately in the U.S. living with bladder cancer. Moving to mechanisms of action, NDVO1 is a novel, sustained-release, intravesical formulation of two chemotherapy agents, gencytabine and docetaxel, or GEMDOSY. NDVO1 forms a spherical soft matrix within the bladder that sequesters GEMDOSY and releases these two agents as a matrix gradually dissolves. The formulation was specifically designed to maximize local gem dosing concentration and also provide prolonged exposure while minimizing systemic toxicity. Published clinical studies have shown that gencytobin and docetaxel achieves a response rate and recurrence-free survival that are comparable to or better than the historical standard of care, Bacillus calmatigerin or BCG. However, the administration of conventional chemotherapy is cumbersome. The two chemotherapy agents require special handling and preparation in a controlled hospital pharmacy setting. In addition, the two chemotherapies are administered sequentially over three to five hours with limited tumor exposure time. In contrast, NDVO-1 sustained release formulation is intended to be dosed in office as a ready-to-use therapy that is administered in less than 10 minutes without the need for anesthesia or new or dedicated equipment. What is really exciting about NDVO data is the data presented at the AUA 2025 two weeks ago. The presentation was based on data from an ongoing single arm single center, XUS phase two study, evaluating NBVO1 in patients with high-grade MIBC. Twenty-six patients have been enrolled as of the last data cutoff. The AOA presentation was based on the results for the first 20 patients. The group included two patients with carcinoma in situ, CIS, and 18 patients with papillary disease, TA and T1. Of the papillary disease patients, eight were BCG naive and 12 were BCG unresponsive. The efficacy data were presented based on three and six months' assessment. In addition, the highest response rate at any time point was also reported. On the three-month assessment, dosing of Ndb01 resulted in overall response rate of 85%, or 17 out of 20 patients. High-grade recurrence-free survival in patients with papillary disease of 83%, or 15 out of 18 patients. A complete response in carcinoma in situ patients recognizing that the number is small, was 100%, or 2 out of 2 patients. For data reports at any time point, the overall response rate was 90%, or 18 out of 20 patients. High-grade recurrence-free survival in papillary disease was 89%, or 16 out of 18 patients. Complete response in carcinoma in C2 patients remains 100%, for two out of two patients. Importantly, seven patients were evaluable at six months. 100% of these patients achieved disease-free status. These groups include one patient with CIS and six patients with papillary disease, characterized as TA or T1. One of these patients was retreated at three months and responded to the second treatment. From a safety perspective, NDVO1 was well tolerated with no treatment-related adverse events greater than grade 1. We were very pleased with the reception of the data received at AUA. We believe that the results suggest that NDVO1 has the potential to significantly improve the care of patients with NM-IBC. NDVO1 is currently in Continues the Phase II single-arm study to assess safety and efficacy in patients with high-grade non-muscle-invested bladder cancer. Our goal is to bring NDVO-1 to patients as soon as possible. Looking ahead to the second half of 2025, our effort will focus on securing a US IND clearance. Turning briefly to Cepranolone. In February, we acquired the right to Sopranolone from Azarena Pharma. Our decision was based on Sopranolone's broad safety database and promising phase two results in Tourette's syndrome. I would like to touch on four topics for Sopranolone, the market opportunity, the mechanism of action, the data, and the next steps. Starting with the market, we believe Sepranolone is well-suited to treat disorders marked by compulsive behavior and excessive activity of the GABA neurotransmitter pathway, including Prader-Willi syndrome and Tourette syndrome. These two neurobehavioral disorders can manifest through repetitive behavior and pulsivity and represent sizable underserved markets. Prader-Willi syndrome, or Prader-Willi, is our first candidate indication for Sepranolone. Prader-Willi is a complex genetic disorder often defined by persistent anger and overeating . Current treatment is focused on improving obsessive-compulsive behavior and other medical complications. Prader-Willi is estimated to affect approximately 350,000 people worldwide, including approximately 20,000 people in the U.S. Turning to the mechanism of action. Sepranol is first-in-class endogenous neurosteroid. It's a member of a new subgroup of neurosteroid called GAMSAs, or GABA-modulating steroid antagonists. GAMSAs selectively act on GABA to alleviate the repetitive symptom of compulsive disorder. We were attracted to Sepranol because of its unique mechanism of action and promising proof-of-concept data. In phase two, the results from the originator Azarina showed that Cepranolone demonstrated a competitive tick reduction of 28% with a p-value of 0.051 in its primary clinical endpoint, as measured by the YGTSS, a standardized Tourette scale. The data also showed that Cepranolone treatment produced an improved quality of life without any off-target CNS effects. These data provide a strong foundation to study sopranolone in compulsion-related disorders such as PWS or Prader-Willi syndrome. Our efforts to progress sopranolone are expected to include planned FDA interaction and further development of product supply. We plan to advance intrathecal development in early 2026. Now, I would like to turn the call over to our Chief Financial Officer, Maggot Shenouda, to talk about our financial results. Maggot?

Thanks, Sergio. With two innovative product candidates that have shown promising proof-of-concept data, a $27.1 million cash balance, a clean balance sheet, and a disciplined development plan, we're in a good position to advance our pipeline to important clinical milestones. Turning to our financial results, as noted by Brian, This afternoon, we issued a press release announcing our business and financial results for the first quarter ended March 31, 2025. As of March 31, 2025, RealMata had cash, cash equivalents, and short-term investments of approximately $27.1 million, compared to $44.9 million as of December 31, 2024. Cash used in operations in the first quarter ended March 31, 2025, was $18.1 million compared to $13 million for the same period in 2024. Our efforts in 2025 are dedicated to advancing NDV01 and Sucranolone through key development milestones. Over the coming months, as we finalize our clinical and regulatory strategy for each program, we expect to have better visibility into our requirements and runway. Moving through our first quarter 2025 financial results. Research and development expense for the first quarter of 2025 totaled $12 million compared to $13.3 million for the first quarter of 2024, a decrease of $1.3 million. The lower spend was primarily driven by lower study costs, with the completion of clinical trials for REL 1017 for major depressive disorder offset by payments for the sopranolone acquisition and the NDV-01 in licensing. General and administrative expense for the first quarter of 2025 totaled $6.3 million, compared to $9.7 million for the first quarter of 2024, a decrease of approximately $3.4 million. The decrease was primarily driven by a decrease in stock-based compensation expense. The net loss for the first quarter of 2025 was $17.6 million, or 58 cents per basic and diluted share. compared with a net loss of $21.8 million, or 72 cents, per basic and diluted share for the first quarter of 2024. Before we open the call for questions, I'll turn back to Sergio for some closing comments. Sergio?

Thank you, Maggie.

I would like to leave you with these key messages from today's call before we enter in the Q&A section. 2025 is off to a strong start with the addition of two unique product candidates with proof-of-concept phase 2 data and large addressable market to our portfolio. NDVO1 for bladder cancer and Cipranolone for Prader-Willi syndrome and Tourette syndrome. Reported positive initial proof-of-concept phase 2 data for our lead product candidate, NDVO1 at AUA, and we made Progress toward our objective of bringing each program to patient as soon as possible. With preparation underway to begin the next set of studies for NDVO1 and Cepranol. With two innovative product candidates that have shown promising proof of concept data, 27 million cash balance, a clean balance sheet, and a disciplined approach to development plan, we are in a good position to advance our pipeline to important clinical models. As we prepare to advance our two clinical program, we want to thank our investor for your support and for taking time to join today call. Operator, I would like now to open the call for support questions.

Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation will indicate your line is in the question queue. One moment while we pull for questions. Our first question is from Oyer with Mizuho Securities. Please proceed.

Hey, guys. Yeah, thanks for taking your questions and congrats on the quarter, the recent data. So maybe the first question from us is, you know, you indicate you'll be approaching the FDA to speak with them in order to move forward. I guess what gives you confidence that you know, the current data from the Phase 2 study would be sufficient for the FDA to agree for MDV-01 to move into registration of study. And I guess the second question maybe is, you know, you indicate that, you know, you're going to scale up supply. Could you sort of elaborate what you mean by that? Are they commercial products? Are they scaling up for clinical study only? Thanks.

Thank you for the question. Let me answer the first one. And I believe Dr. Lawton should have joined the call. And anything you would like to add would be very welcome. But What makes us confident that the conversation with the FDA will drive, like, the beginning or the start of registration of a program? But a couple of things. One is the combination of drug itself, right? Gencytabine plus docetaxel has been currently used and has been used for some time by many, many urologists everywhere. and everybody is convinced about the efficacy and the safety of the local administration of the two drugs. The reason that it's not been more widely used is the limitation in the practicality. Very few doctor offices can prepare the solution, so it has to be prepared by pharmacists, authorized, used to handle chemotherapy, most of the cases in clinics. So, and the administration that requires is sequential, Gethidabine and docetaxel, one after the other, and it takes time. So, you have to keep the doctor office or the clinic occupied for three, four, five hours, and for the patient, too, because he has to sit in the clinic, you know, holding, and for, you know, one or two hours, each of the two preparations. That's, even if a patient affected by bladder cancer, is willing to go through a lot to avoid to take the bladder off, is still a convoluted process. And so that's one of the reasons that we feel confident that the combination of chemotherapy is not new. It's well known, it's in use, and is recognized as one of the most effective, not the most effective, pharmacological treatment of bladder cancer. The second one that comes from this data is the safety. of the formulation. We have no one single patient interrupting the study for a side effect. And all the side effects registered are all grade one. So it seems it's very, very well tolerated. And so you put the two things together, and the advantage also of the administration in the doctor office, non-anesthesia, less than 10 minutes, is a pre-filled syringe that doesn't need any handling. So all the things together should make the FDA willing to let us go into a larger registration study. Of course, there is always, until we get the direct, the minutes from the FDA, you cannot be, never be sure, but we believe there is a very good, a very good chance that we'll be okay with that. And I know if Dr. Oletan has been able to join the call, he was in a surgery, so.

Yes, good afternoon. Can you hear me okay?

Yes, absolutely, very well.

Thank you. Go ahead. So I think I can address the issue to some degree. First of all, intramuscular chemotherapy has been routinely used for treating both intermediate risk and high-risk bladder cancer for decades. Now, it's interesting because the therapies that are currently used, mitomycin, gemcitabine, docetaxel, are all being used as off-label use, but they are reimbursed and commonly utilized. The biggest challenge for urologists, though, is that you need a hood to mix these formulations, and unless you have a cancer center pharmacy, you can't give it in your office. Immune therapies like BCG come in a vial and a powder that you can reformulate, but the intramuscular chemotherapy, you can't. Medical oncologists who give IV doses of the chemotherapy are not typically giving intravesical therapies in their offices. They're not familiar with placing catheters. There's little reimbursement. And so you have a bit of a catch-22 if you're a patient. You can't really get it at your urologist's office, and you can't get it at your medical oncologist's office. Now, the formulation of gemcitabine docetaxel is actually one of the more commonly used drugs in BCGN responsive, which is a space with a lot of development between natoferrogene and Gatruda and TAR200 and creatostimogene and Anktiva, there's a lot of drugs being developed in this space. And yet many people are still using gemcitabine dosetaxel because the other drugs are, well, some of them are not approved yet. Some of them are more problematic to give in the clinic. But many patients are kind of out in the cold. They're not able to get access to these drugs, either the newer drugs or drugs like gemcitabine, docetaxel. Now, in terms of efficacy, as mentioned, there are many studies looking at intravascular chemotherapy and demonstrating efficacy. However, we know that formulations like TAR200, which elute over three weeks, work better than single agents, and I think that this combination, which has the advantage of both being easy to deliver and a sustainable release in the bladder over two weeks, will be superior, potentially, over agents that stay in your bladder for just one hour. So there are several potential advantages to this, both in terms of ease of use and the potential increased efficacy.

Thank you, Dr. Lawton. Did that answer your question?

Yeah, so maybe just some follow-up on what you guys said in response to potential differentiation. So maybe, Dr. Lawton, if you're still there, maybe one of the feedbacks that we've gotten from investors is that this is kind of a crowded market. So maybe just help us understand how you see NVD01 fit in the treatment paradigm when it comes to market. You know, you have BCG, you have CG oncology and other potential competitors who could be ahead. Thanks.

Right. You know, I think, yeah, I'm happy to respond. First of all, you know, uh, I think that, you know, if you ask patients, uh, they want, uh, to keep their bladder and in the BCGN responsive space, which I completely agree, there's probably three or four potential treatments. Um, you know, TAR 200 and critisimidine both will likely be accepted, uh, by the FDA. Uh, but nonetheless, patients are frequently going to want two or three lines of therapy. and they're going to want to cut sort of the most effective treatment. I don't necessarily think that that's going to be the best first place to go with this drug, mainly because, as you say, it's going to be a bit of a busy space, even though I suspect that since many people are already using gemcitabine, docetaxel as their main treatment off-label, if they actually have an approved compound that they're familiar with, with durable excretion of drug and an easier mechanism of delivery, then they'll be very open to giving that drug that they're familiar with over some of the other agents. But on the other hand, in the intermediate risk space, which has a higher prevalence by far than the BCGEN responsive place, there really aren't drugs that are commonly used. is available, not approved, but available. But as I said, it's hard to get access to. So in academic centers, we give intravascular chemotherapy, but many community sites don't. And so it would be a very natural fit to give intravascular chemotherapy such as this formulation for intermediate risk patients. It has potential in the chemo ablative space as well, which even though that's not sort of a place that we commonly use drugs, but UGN-102 did a chemoablation trial, and it's going to FDA. And it's a single drug, mitomycin. This is actually a combination which I think could potentially compete nicely if it had a good performance. And there's a bridge trial comparing gemdose to BCG that's being enrolled right now. And if it shows equivalence or superiority, then this drug could fit in the BCG-naive space. And the other drugs that you're mentioning, TAR-200, crudosimagine, are not competing in that space. And the trials that have been completed with BCG and checkpoint inhibitors have shown, CREST has been reported, had about a 7% increase, reduction in recurrence at 18 months, but about a 15% rate of grade three SAEs, and no improvement in progression, no improvement in survival. So I don't think any of the checkpoint inhibitors are gonna compete in the BCG NAIF space. But if the BRIDGE trial shows equivalence of efficacy, this drug could actually fit in the BCG knife space without much competition from some of these newer agents. So, I see many potential uses right now.

Okay. Thank you. Thank you, Dr. Lawton.

Your second question was regarding the manufacturing and, sorry, was for Cepranolone or for NDV-01, for the NDV-01?

For NDV-01.

Right, yeah, clearly the quantity needed for commercial will be large. So we always want to have two manufacturers at minimum. So we are looking for capacity and a second manufacturer for risk management. It's not a complicated product to make.

It's gel, and so they're all known components. Okay, thank you. Thank you, Wei.

Our next question is from Andrew Tai with Jefferies. Please proceed.

Good afternoon. This is Matt Barkas on for Andrew. Thanks for taking our questions. I guess regarding the latest dataset for NDV01 presented at the AUA meeting earlier, when should we look forward to you sharing the complete response rate for the entire population? And how do you anticipate sharing the future updates from the program? Like what more can we look forward to in those data sets throughout the year? And what are your expectations for success?

Well, I can answer part of it and maybe Dr. Lothan can expand. So the next data point will be the six months. We had seven patients now at the AUA with a 100% complete response. We'll have six-month data of the 20 patients somewhere around end of June, July. We'll present that, and then we'll give nine and 12 months of the 20 patients. And so these are the expectations. So the data, we can only look at what we have now. That is like 90% at three months and 100% of the seven patients At six months, but they look pretty good. And not surprising because it's known that the combination, the gen dose, it has, you know, it's very efficacious. And even if, like, with a duration of tumor contact of a couple hours, we use the same dose and it stays there for 10 days. And it's done six times in three months. So the expectation that the results are good are definitely, definitely there. And you want to add something, Dr. Luton?

No, I think this is obviously an interesting cohort from an efficacy standpoint. I actually think the more important aspect of it is actually the safety standpoint because there's a lot of data about efficacy of gem dosing formulations. And we know that you could look even at TAR200 data and see what happens when you give gemcitabine over a sustained period of time. But the safety is actually the more important component because you worry whether or not prolonged exposure of the bladder to the chemotherapy might cause, you know, irritation, frequency, urgency, pain. And so far we haven't seen that. And that's probably, if you had asked me at the beginning of this, what would be my biggest concern, it would not have been an efficacy concern. It would have been a safety concern. And so that's probably the most reassuring aspect of this. It's a heterogeneous population, so it's going to be a little challenging to compare this to some of the mature trials like Sunrise 1 or Bond 3 in terms of efficacy, because only some of these patients have CIS, BCGEN-responsive CIS. This is still, you know, phase two with a heterogeneous population. But at some point, obviously, you know, once, you know, after conversation with FDA, we can decide on which indication to actually do a larger cohort. But the safety profile is obviously quite reassuring.

Thank you. Thank you, Dr. Lothar. Did I answer your question? That was the first part that I didn't catch entirely.

No, yeah, yeah. You caught it. Thanks. Oh, okay.

Thank you.

And then I guess like as you were thinking about talking with FDA on with these data and the design of the Phase III, I guess what would you want the Phase III to look like in terms of time points and points? and the types of patients you're thinking about enrolling.

Dr. Lawton, here you can add a lot of value. Dr. Lawton is helping us very closely to design the phase three program. Do you want to answer that? Sure.

I think there are easier routes and there are harder routes. I think somebody highlighted the challenge with the BCGN responsive route. The benefits of that route are that the FDA has approved single arm phase two trials for approval in CIS alone to look at efficacy. The challenge is that these patients are relatively rare and it takes many sites and quite a bit of time to enroll. I think there's two easier routes. One route would be to go through a single arm chemo ablation route, similar to what UroGen with the Envision trial. I think we're going to learn a lot later on this month when it goes to ODAC. And if the drug, their combination gets approved with a single-agent mitomycin that stays in your bladder about four hours, then a single-arm trial in that setting with our formulation makes a lot of sense. It would be probably the quickest route to approval. And if that doesn't, if there's reasonable... rationale from the FDA that they won't approve such an approach. Then a randomized trial like PIVOT6, an intermediate risk, randomizing NDVO1 to placebo or observation would probably be the next quickest route. That trial actually enrolled extremely quickly in the U.S. I think that this formulation would actually be more attractive than an oncolytic virus. But that type of trial design was enrolling very rapidly. They're almost done with enrollment in, I think, somewhere around 15 to 18 months. And I think that would be the next approach, especially since the FDA approved a randomization against placebo, which is easy to do a superiority trial against nothing in a population of patients who have high risk for recurrence.

Great. Yeah, thanks for the call. Thank you.

There are no further questions at this time, so this will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.

Thank you all. Thank you very much. Thank you, Dr. Lowden.