Brian Ritchie; Investor Relations; LifeSci Advisors
Sergio Traversa; Chief Executive Officer, Director; Relmada Therapeutics Inc
Maged Shenouda; Chief Financial Officer; Relmada Therapeutics Inc
Uy Ear; Analyst; Mizuho Securities
Yair Lotan; Professor of Urology and Chief of Urologic Oncology; UT Southwestern Medical Center
Matthew Barcus; Analyst; Jefferies
Operator
Good afternoon. Welcome to the Relmada Therapeutics first-quarter 2025 earnings call. (Operator Instructions) 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 LifeSci Advisors. Please go ahead, Mr. Ritchie.
Brian Ritchie
Good day, and thank you, everyone, for joining us today. This afternoon, Relmada issued a press release providing a business update and outlining its financial results for the 3 months ended March 31, 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, Relmada'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 Relmada'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 31, 2025, 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, May 12, 2025. Relmada 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 Relmada's CEO, Dr. Sergio Traversa, who will briefly provide a summary of recent business highlights; and Relmada's CFO, Maged Shenouda, 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 will hand the call over to Sergio Traversa. Sergio?
Sergio Traversa
Thank you, Brian as always, and good afternoon, and welcome, everyone, to the Relmada First Quarter 2025 Conference Call. 2025 is off to a good start for Relmada. We added 2 unique product candidates with very encouraging Phase II data and large addressable markets to our portfolio,
NDV-01 for bladder cancer and sepranolone for Prader-Willi syndrome, Tourette syndrome and potentially other CNS indications. Reported initial proof-of-concept Phase II data for our lead product candidate, NDV-01 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 NDV-01 sepranolone. With 2 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 call, I will provide a snapshot of our 2 programs, including a review of the initial Phase II data for NDV-001 at the AUA meeting 2 weeks ago. After that, Maged 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 Urology and Oncology at the University of Texas Southwestern Medical Center in Dallas, who can answer your clinical question regarding NDV-01.
We are encouraged by the potential of the diversified pipeline that we are building at Relmada. Starting with NDV-01, we believe the program is an excellent fit with our strategic plan and has the potential to meaningfully improve the care of patients with bladder cancer. Our decision to in-license NDV-01 was based on strong science, strong field data and the anticipation of positive Phase II 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 AUA 2025 supported our initial enthusiasm for NDV-01's potential to be the class leading bladder-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 mechanism of action.
NDV-01 is a novel sustained-release intravesical formulation of 2 chemotherapy agents, gemcitabine and docetaxel or GEM/DOCE. NDV-01 forms a spherical soft matrix within the bladder that sequesters GEM/DOCE and releases these 2 agents as a matrix gradually disolves. The formulation was specifically designed to maximize local GEM/DOCE concentration and also provide prolonged exposure while minimizing systemic toxicity. Published clinical studies have shown that gemcitabine and docetaxel achieves a response rate and recurrence-free survival that are comparable to, or better than the historical standard of care, Bacillus Calmette-Guerin or BCG. However, the administration of conventional chemotherapy is cumbersome.
The 2 chemotherapy agents require special handling and preparation in a controlled hospital pharmacy setting. In addition, the 2 chemotherapies are administered sequentially over 3 to 5 hours with limited tumor exposure time. In contrast, NDV-01 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 NDV-01 data is the data presented at the AUA 2025 2 weeks ago. The presentation was based on data from an ongoing single-arm, single-center ex-U.S.
Phase II study evaluating NDV-01 in patients with high-grade NMIBC. 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 2 patients with carcinoma in situ, CIS and 18 patients with papillary disease, Ta and T1. Of the papillary disease patients, 8 were BCG naive and 12 were BCG unresponsive.
The efficacy data were presented based on 3- and 6-months assessment. In addition, the highest response rate at any time point was also reported. Based on the 3-month assessment, dosing of NDV-01 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 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 2 out of 2 patients. Importantly, 7 patients were evaluable at 6 months. 100% of these patients achieved disease-free status.
This group include 1 patient with CIS and 6 patients with papillary disease characterized as Ta or T1. One of these patients was retreated at 3 months and responded to the second treatment. From a safety perspective, NDV-01 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 NDV-01 has the potential to significantly improve the care of patients with NMIBC.
NDV-01 is currently in -- continues the Phase II single-arm study to assess safety and efficacy in patients with high-grade non-muscle invasive bladder cancer. Our goal is to bring NDV-01 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 sepranolone.
In February, we acquired the right to sepranolone from Asarina Pharma. Our decision was based on sepranolone's broad safety database and promising Phase II results in Tourette syndrome. I would like to touch on 4 topics for sepranolone, 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.
This soon neurobehavioral disorder can manifest through repetitive behavior and positivity and represents 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 overheating 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 U.S.
Turning to the mechanism of action. Sepranolone is first-in-class endogenous neurosteroid. It's a member of a new subgroup of neurosteroid called GAMSAs or GABAA modulating steroid antagonist. GAMSAs selectively act on GABAA to alleviate the repetitive symptom of compulsive disorder. We were attracted to sepranolone because of its unique mechanism of action and promising proof-of-concept data.
The Phase II results from the originator Asarina showed that sepranolone demonstrated a competitive peak 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 sepranolone treatment produced an improved quality of life without any off-target CNS effects. These data provide a strong foundation to study sepranolone in compulsion-related disorders such as PWS or Prader-Willi syndrome. Our effort to progress sepranolone are expected to include planned FDA interaction and further development of product supply with plans to advance into clinical development in early 2026.
Now I would like to turn the call over to our Chief Financial Officer, Maged Shenouda, to talk about our financial results. Maged?
Maged Shenouda
Thanks, Sergio. With 2 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 are 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, Relmada 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 NDV-01 and sepranolone 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 sepranolone 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 $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?
Sergio Traversa
Thank you, Maged. I would like to leave you with these key messages from today's call before we enter the Q&A section. 2025 is off to a strong start with the addition of 2 unique product candidates with proof-of-concept Phase II data and large addressable market to our portfolio, NDV-01 for bladder cancer and sepranolone for Prader-Willi syndrome and Tourette syndrome. Reported positive initial proof-of-concept Phase II data for our lead product candidate, NDV-01 at AUA, and we made progress toward our objective of bringing each program to patients as soon as possible with preparation underway to begin the next set of studies for NDV-01 and sepranolone. With 2 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 milestones.
As we prepare to advance our 2 clinical program, we want to thank our investors for your support and for taking time to join today's call. Operator, I would like now to open the call for questions.
Operator
(Operator Instructions)
Uy Ear, Mizuho Securities.
Uy Ear
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 II study would be sufficient for the FDA to agree for NDV-01 to move into registrational studies. 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?
Is this -- are they commercial products? Are they scaling up for clinical study only?
Sergio Traversa
Thank you, Uy for the question. Let me answer the first one, and I believe Dr. Lotan 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 registrational of product and a program.
But a couple of things. One is the combination of drug itself, right? gemcitabine plus docetaxel has been used -- 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 2 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 authorized, used to handle chemotherapy, most of the cases in clinics. So -- and the administration that requires a sequential gemcitabine and docetaxel 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 you have to see it in the clinic holding and for 1 or 2 hours, each of the 2 preparations. That's -- even if a patient affected 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, has been -- is in use and is recognized as one of the most effective, if not the most effective pharmacological treatment of bladder cancer. The second one that comes from this data and is the safety of the formulation. We have no one single patient interrupting the study for side effect. And all the side effects registered are all grade 1. So it seems it's very, very well tolerated.
And so you put the 2 things together and the advantage also of the administration in the doctor office, non-anesthesia, less than 10 minutes is a prefilled 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 like until we get the direct -- the minutes from the FDA, you cannot -- never be sure, but we believe there is a very good chance they will be okay with that. And I don't know if Dr. Lotan has been able to join the call.
He was in the surgery, so.
Yair Lotan
Yes. Good afternoon. Can you hear me okay?
Sergio Traversa
Yes, absolutely. Very well. Go ahead.
Yair Lotan
So I think I can address the issue to some degree. First of all, intravesical 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 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 intravesical chemotherapy, you can't. And 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 catching too.
If you're a patient, you can't really get it in your urologist's office and you can't get it at your medical oncologist office. Now the formulation of gemcitabine and docetaxel is actually one of the more commonly used drugs in BCG-unresponsive, which is a space with a lot of development between nadofaragene and KEYTRUDA and TAR-200 and cretostimogene and ANKTIVA, there's a lot of drugs being developed in this space. And yet many people are still using gemcitabine and docetaxel because the other drugs have -- 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 docetaxel. Now in terms of efficacy, as mentioned, there are many studies looking at intravesical chemotherapy and demonstrating efficacy. However, we know that formulations like TAR-200, which allude over 3 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 2 weeks will be superior potentially over agents that stay in your bladder for just 1 hour. So there are several potential advantages for this, both in terms of ease of use and the potential increased efficacy.
Sergio Traversa
Thank you, Dr. Lotan. Uy, did that answer your question?
Uy Ear
Yes. So maybe just a follow-up on what you guys said in response to potential differentiation. So maybe Dr. Lotan, 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 NDV-01 fit in the treatment paradigm when it comes to market, you have BCG, you have CG Oncology and other potential competitors who could be ahead.
Yair Lotan
Right. I think -- I'm happy to respond. First of all, I think that if you ask patients, they want to keep their bladder. And in the BCG-unresponsive space, which I completely agree, there's probably 3 or 4 potential treatments, TAR-200 and cretostimogene both will likely be accepted by the FDA. But nonetheless, patients are frequently going to want 2 or 3 lines of therapy, and they're going to want to get 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 is -- has a higher prevalence by far than the BCG unresponsive place, there really aren't drugs that are commonly used. Intravesical gemcitabine is available, not approved, but available. But as I said, it's hard to get access to. So in academic centers, we give intravesical chemotherapy, but many community sites don't.
And so it would be a very natural fit to give intravesical 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 they had a good performance. And there's a BRIDGE trial comparing GEM/DOCE 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, cretostimogene 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 naive space. But if the BRIDGE trial shows equivalence of efficacy, this drug could actually fit in the BCG naive space without much competition from some of these newer agents.
So I see many potential uses right now.
Sergio Traversa
Thank you, Dr. Lotan. And your second question was regarding the manufacturing and -- sorry, was for sepranolone or for NDV-01 for the NDV-01, right.
Uy Ear
NDV-01.
Sergio Traversa
Right. Yes. The -- clearly, the quantity needed for commercial will be large. So like we will -- and we always want to have 2 manufacturer at minimum. So 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 all known components.
Operator
Andrew Tsai, Jefferies.
Matthew Barcus
This is Matt Barcus on for Andrew. I guess, regarding the latest data set for NDV-01presented at the AUA meeting earlier, when should we look forward to 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?
Sergio Traversa
Well, the -- I can answer part of it and maybe Dr. Lotan can expand. So 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 end of June, July.
We'll present that and then that -- and then we'll give 9 and 12 months of this -- of the 20 patients. And so these are the expectations. Look, the data, 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 pretty good. And not surprising because it's known that the combination GEM/DOCE is very efficacious. And even if like with the duration of tumor contact of a couple of 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 there. And do you want to add something, Dr. Lotan?
Yair Lotan
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 a lot of -- there's a lot of data about efficacy of GEM/DOCE formulations. And we know that you could look even at TAR-200 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 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, BCG unresponsive CIS. This is still Phase II with a heterogeneous population.
But at some point, obviously, once -- 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.
Sergio Traversa
Thank you, Dr. Lotan. Did I answer your question? There was the first part that I didn't catch entirely.
Matthew Barcus
No, yes, yes, you caught it. And then I guess, like as you're 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, endpoints and the types of patients you're thinking about enrolling?
Sergio Traversa
Dr. Laton, that here, you can add a lot of value because Dr. Laton is helping us very closely to design the Phase III program. Do you want to answer that?
Yair Lotan
Sure. I think there's -- there are easier routes and there are harder routes. I think somebody highlighted the challenge with the BCG unresponsive route. The benefits of that route are -- that the FDA has approved single-arm Phase II 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 2 easier routes. One route would be to go through a single-arm chemoablation 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 4 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 is reasonable rationale from the FDA that they won't approve such an approach, then a randomized trial like PIVOT-6 in intermediate risk, randomizing NDV-01 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.
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.
Operator
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.
Sergio Traversa
Thank you all. Thank you very much. Thank you, Dr. Lotan.
Yair Lotan
Thank you.
