Relmada Therapeutics, Inc.

Good afternoon. Welcome to Romano Therapeutics, first quarter, 2025 earnings call. At this time, all participants are in a listen only mode. After the prepare remarks, we will conduct the 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 Richie from Lightsight of Iyer. Please go ahead. Mr.

Richie. Good day and thank you everyone for joining us today. This afternoon, Romano issued a press release, providing a business update and outlining its financial results for the 3 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. Romano'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 Romano'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 quarter 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. Romano 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, I'll role model CEO, Dr Sergio Traversa, who will briefly provide a summary of recent business highlights. And role model CFO Maggie Chinada who provide a review of the company's Q1 financial results. After that, we will open the line for a brief Q and 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 first quarter 2025 conference call. 2025 is off to a good start for. We had the two unique product candidates with very encouraging phase two data and large addressable markets to our portfolio. MDV01 for bladder cancer and Cepronoma for Prader-Willi syndrome, Tourette syndrome, and potentially other CNS indications. Report the initial group of constant phase two data for our lead product candidate, MDV01 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 MDV01 and Cepronoma. We two innovative product candidates that have shown promise to improve our concept data. 27 million cash balance, clean balance sheet and the disciplined approach to development plan. We are in a good position to advance our pipeline to important clinical milestones. During today's call, I will provide a snapshot of our two programs, including a review of the initial phase two data for MDV01 at the AOI meeting two weeks ago. After that, Maggett 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 Udo Oncology at the University of Texas Southwestern Medical Center in Dallas, who can answer your clinical question regarding MDV01.

We

are encouraged by the potential of the diversified pipeline that we are building at Belmata. Starting with MDV01, 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 enlicense MDV01 was based on strong science, strong field data, and the anticipation of positive phase two data at the upcoming American Urology Association meeting or AOI 2025. I am pleased to report that positive top line proof of concept data presented at AOI 2025 supported our initial enthusiasm for MDV01's potential to be the class leading blood despairing 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 US. About half or 50% of those cases have high grade disease that has a high risk of recurrence. It is a very high recurrence rate for the 600,000 people approximately in the US living with bladder cancer. Moving to mechanism of action, MDV01 is a novel sustained release intra-vascular formulation of two chemotherapy agents, GenCytobine and Dosset Axle or GemDosi. MDV01 forms a spherical soft matrix within the bladder that sequesters GemDosi and releases these two agents as a matrix gradually resolved. The formulation was specifically designed to maximize local GemDosi concentration and also provide prolonged exposure while minimizing systemic toxicity. Published clinical studies have shown that GenCytobine and Dosset Axle achieve the response rate and recurrence free survival that is comparable to or better than the historical standard of care, Basillus Calmat-Geren or BCG. However, the administration of conventional chemotherapies comes. The two chemotherapy agents require special handling and preparation in a controlled hospital pharmacy setting. In addition, the two chemotherapies are administered sequences over three to five hours with limited tumor exposure time. In contrast, MDV01 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 the MDV01 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 MDV01 in patients with high grade MMI BC. 26 patients have been enrolled as of the data of the last data cutoff. The AUA 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. Based on the three months assessment, dosing of MDV01 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 two out of two patients. For data report 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 situ patients remains 100% or two out of two patients. Importantly, seven patients were evaluated at six months. 100% of these patients achieved disease free status. These groups include one patient with the 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, MDV01 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 MDV01 has the potential to significantly improve the care of patients with NM-IBC. MDV01 is currently in continuous phase two single-arm study to assess safety and efficacy in patients with high grade non-muscle invasive bladder cancer. Our goal is to bring MDV01 to patients as soon as possible. Looking ahead to the second half of 2025, our effort will focus on securing a U.S. IND clearance. Turning briefly to Cepranolone. In February, we acquired the right to Cepranolone from Azarina Farms. Our decision was based on Cepranolone's broad safety database and promising phase two results in Tourette's syndrome. I would like to touch on four topics for Cepranolone. The market opportunity, the mechanism of action, the data, and the next steps. Starting with the market, we believe Cepranolone is well suited to three disorders marked by compulsive behavior and excessive activity of the GABA neurotransmitter pathway, including Prader-Willi syndrome and Tourette syndrome. The two neurobehavioral disorders can manifest through repetitive behavior and possibility and represent sizable underserved markets. Prader-Willi syndrome or Prader-Willi is our first candidate indication for Cepranolone. Prader-Willi is a complex genetic disorder often defined by persistent anger and overeating, hyperphagia. 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 US. Turning to the mechanism of action, Cepranolone is first in class endogenous neurosteroid. It's a member of a new subgroup of neurosteroids called GAMSAs or GABA Modulating Steroid Antigamins. GAMSAs selectively act on GABA to alleviate the repetitive symptom of compulsive disorder. We were attracted to Cepranolone because of its unique mechanism of action and promise to improve our concept data. Phase two, the results from the originator Azarina, showed that Cepranolone demonstrated a

competitive peak

reduction of 28 percent with a p-value of 0.051 in its primary clinical endpoint, as measured by the YGTSS, standardized to red 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 Cepranolone in compulsive related disorders such as PWS or Prader-Willi syndrome. Our efforts to progress Cepranolone are expected to include planned FDA interaction and further development of product supply, with plans to advance intraclinical development in early 2026. Now I would like to turn the call over to our Chief Financial Officer, Magat Shinuda, to talk about our financial results. Magat?

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 discipline 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-using operations in the first quarter ended March 31, 2025, with $18.1 million compared to $13 million for the same period in 2024. Our efforts in 2025 are dedicated to advancing NDV01 and sacralinone 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 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 REL1017 for major depressive disorder, offset by payments for the sacralinone acquisition and the NDV01 and licensing. General and administrative expense for the first quarter 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 $0.58 per basic, and diluted share, compared with a net loss of $21.8 million, or $0.72 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, Maggots.

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 group of counts that face today the enlarged addressable market to our portfolio. NDV01 for bladder cancer and sopranolone for Prader-Willi syndrome and Tourette syndrome. Reported positive initial group of constant phase two data for our lead product candidate, NDV01, 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 NDV01 and sopranolone. We two innovative product candidates that have shown promising group of constant 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 milestones. 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's 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 time will indicate your line is in the question queue. One moment while we pull for questions. Our first question is from Oyeir with Mizuho Securities. Please proceed.

Hey guys, thanks for taking your questions and congrats on the quarter, the recent data. So maybe the first question from us is, you indicate you'll be approaching the FDA to speak with them in order to move forward. I guess what gives you confidence that the current data from the phase two study would be sufficient for the FDA to agree for NDV01 to move into registration of study? And I guess the second question maybe is, you indicate that 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. Lothan 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 the beginning of the start of registration of a program. But a couple of things. One is the combination of drug itself, right? Gentite has been plus Nostetaxel has been used, has been currently used and has been here 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 has not been more widely used is the limitation in the practicality. The very few doctor office can prepare the solution. So it has to be prepared by pharmacists, otherwise used to handle chemotherapy, most of the cases in clinics. So, and the administration that requires a sequential Just either been Nostetaxel one after the other and it takes time. So you have to keep the doctor office or the clinic occupied for 3, 4, 5 hours. And for the patient too, because he has to sit in the clinic, holding and for one or two hours each of the two preparations. That's even if a patient affect their bladder cancer is willing to go through a lot to avoid to take the bladder off, it's still a convoluted process. And so that's one of the reasons that we feel confidence that the combination of chemotherapy is not new. It's well known, it's been is in use and is recognized as one of the most effective, not the most effective pharmacological treatment of all bladder cancer. The 2nd, 1 that comes from this data and is the safety of the formulation. We have no 1 single patient interrupting study for for. Side effect and all the side effect registered all create 1. So it seems it's very, very well tolerated. And so you put the 2 things together and the advantage also the, or the administration in the doctor office non-esthesia less than 10 minutes is a prepared pre-filled syringe that doesn't need any handling. So all the, all the things together should make the FDA willing to let us go into a large, larger registration study. Of course, there is always until we get it, they direct the minutes from the FDA. You cannot be never be sure, but we believe there is a very good, a very good chance. They will be okay with that and I know if Dr has been able to join the call, he was in the surgery.

So. Yes, good afternoon. Can you hear me? Okay.

Yes, absolutely. Very well.

Thank you. So, so I think I can address the issue to some degree. First of all, intravascular 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, and dustitaxel are all being used as off label use, but, but there are reimbursed and commonly utilized. The biggest challenge for you all to know is that you need a hood to mix these formulations. And unless you have a cancerous interpneumacy, you can't give it in your office. Immune therapies like BCG come in a vial and a powder that you can reformulate, but intravascular chemotherapy you can't. Medical oncologists who give IV doses of the chemotherapy are not typically giving intravascular therapies in their offices. They're not familiar with placing catheters. There's little reimbursement. And so you have a bit of a catch going to if you're a patient, you can't really get it in your urologist office and you can't get it in your medical oncologist office. Now, the formulation of gemcitabine and dustitaxel is actually one of the more commonly used drugs in BCGN responsive, which is a space with a lot of development between natoferro gene and Catruida and TAR-200 and Crita-Stimagine and Anktiva. There's a lot of drugs being developed in this space. And yet many people are still using gemcitabine and dustitaxel 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 and dustitaxel. Now, in terms of efficacy, as you know, as mentioned, you know, the there are many studies looking at intravascular chemotherapy and demonstrating efficacy. However, we know that formulations like TAR-200, which elutes 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 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, you know, what you guys said in response to potential differentiation. So maybe Dr. Lawton, if you're still there, maybe, you know, one of the feedbacks that we've gotten from investors is that, you know, this is kind of a crowded market. So maybe just help us understand how you see NVD-01 fit in the treatment paradigm when it comes to market. You know, you have BCG. You have BCG, you have CGA oncology and other potential competitors who could be ahead. Thanks.

Right. I think I'm happy to respond. First of all, you know, I think that, you know, if you ask patients, they want to keep their bladder. And in the BCG on responsive space, which I completely agree, there's probably three or four potential treatments. You know, TAR-200 and Cretaceinogen, both will likely be accepted by the FDA. 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 efficient, 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 gemcitobin, 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 another hand in the intermediate risk space, which is, has a higher prevalence by far than the BCG on responsive place, there really aren't drugs that are commonly used. Intravescal gemcitobin is, you know, is available, not approved, but available. But as I said, it's hard to get access to. So, and 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 chemoablative space as well, which, even though that's not sort of a place that we commonly use drugs, but UGN 102 is doing, 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 naïve space. And the other drugs that you're mentioning, Tart 200, cretosimagine, 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 3 SAEs and no improvement in progression, no improvement in survival. So I don't think any of the checkpoint inhibitors are going to compete in the BCG naïve space. But if the bridge trial shows equivalence or efficacy, this drug could actually fit in the BCG naïve 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. And your 2nd question was regarding the manufacturing and sorry, was for a soprano or for NDB 01 for the NDB

01.

Right, yeah, the clearly the quantity needed for commercial will be large. So we'll like, we will, and we always want to have 2 manufacturers at minimum. So, yeah, we are looking for like, capacity and a second manufacturer for like, risk management. It's not a complicated product to make. It's gel and so they are

all

known

components. Okay, thank you. Thank you.

Our next question is from Andrew with Jeffries. Please proceed.

Good afternoon. This is Matt for Andrew. Thanks for taking our questions. I guess, regarding the latest data set for NDB 01 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, the, I can answer part of it and maybe Dr. Lothan can expand. So the next, the next data point will be the 6 months. We had 7 patients now at the AUA with a 100% complete response. We'll have 6 months data of the 20 patients somewhere around the end of June, July. We'll present that and then date that and then we'll give 9 and 12 months of this of the 20 patients. And so these are the expectations of the data, like the, we can only look at what we have now that is like 90% at 3 months and 100% of the 7 patients at 6 months, but they look, they look pretty good. And not surprising because it's known that the combination, the GenDose has, you know, is very efficacious. And even if like, with the duration of 2 more. A contact of a couple hours, we use the same dose and it stays there for 10 days and is done 6 times in 3 months. So the expectation that the results are good are definitely, definitely there. And you want to add something Dr. Lothan?

No, I think this is obviously, you know, an interesting cord from an efficacy standpoint. I actually think the more important aspect of it is actually the safety standpoint, because a lot of, there's a lot of data about efficacy of GenDose formulations. And we know that, you know, you could look even at TAR 200 data and see what happens when you give GenCi to being 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 it 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, BC Gen-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 the 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. Lothan. Did I answer your question? There was the first part that they didn't catch entirely.

No, yeah, yeah, you caught it. Thanks.

Oh, thank you.

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

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

I think there's, you know, there are easier routes and there are harder routes. I think somebody highlighted the challenge with the BC Gen-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 chemoablation route, similar to what Urogen with the InVision 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, and then a single arm trial in that setting with our formulation makes a lot of sense. It'd 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 pivot six and intermediate risk, randomizing NDV01 to placebo or observation would probably be the next quickest route. That trial actually enrolled extremely quickly in the US. I think that this formulation would actually be more attractive than an oncolytic virus. But that that type of trial design was enrolling very rapidly. They're almost done with enrollment. And 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 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. Lothan.