Relmada Therapeutics, Inc. ($RLMD)

Good afternoon, and welcome to the Relmada Therapeutics Fourth Quarter and Full Year 2025 Earnings Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded and will be available for replay on the Relmada website. I would now like to turn the call over to Brian Ritchie from LifeSci Advisors. Please go ahead, Mr. Ritchie.

Good day, everyone, and thank you for joining us today. This afternoon, Relmada issued a press release providing a business update and outlining its financial results for the 3 months and year ended December 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 for the year ended December 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 on March 19, 2026. 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; Dr. Raj Pruthi, Relmada's CMO, Oncology, who will provide an NDV-01 program update; and Relmada's CFO, Maged Shenouda, who will provide an update on sepranolone and a review of the company's Q4 financial results. After that, we will open the line for a brief Q&A session. Now I would like to hand the call over to Sergio Traversa. Sergio?

Thank you, Brian. Good afternoon, and welcome, everyone, to the Relmada Fourth Quarter and Year-Ended 2025 Conference Call. 2025 has been a transformational year for Relmada, marked by significant progress for our lead program, NDV-01. As a reminder, NDV-01 is a sustained release formulation of gemcitabine and docetaxel. We are developing this investigational product candidate for the treatment of non-muscle invasive bladder cancer or NMIBC. Most recently, we reported compelling responses and durable 12-month efficacy data for our ongoing Phase II study of NDV-01. We achieved FDA alignment for our planned registrational Phase III RESCUE programs. We fortified our team, and we substantially strengthened our balance sheet. As we reflect on our recent accomplishment and planned next steps, I would like to highlight 4 key areas. First, NDV-01. We believe that the strength of the recently reported 12 months follow-up data could position NDV-01 as a potential best-in-class therapy for the treatment of NMIBC. Furthermore, the strength of the clinical data and the unique easy-to-administer sustained release formulation gives us confidence that NDV-01 has the potential to provide what urologists and patients with NMIBC need, a simple, durable, effective treatment that readily fits into real-world practice setting. We plan to initiate the Phase III RESCUE program in the middle of this year. Our Phase III regulatory strategy agreed upon with the FDA includes 2 independent registrational pathways. Pathway 1 is focused on adjuvant therapy following TURBT in patients with intermediate risk bladder cancer, which affects about 75,000 patients in the United States. Pathway 2 is focused on second-line treatment BCG-unresponsive patients, which represent about 5,000 patients in the United States. Second, sepranolone. Sepranolone has previously demonstrated proof of concept in Tourette syndrome. is a disorder characterized by compulsive behavior. We are getting ready to begin a proof-of-concept study in Prader-Willi syndrome in the middle of this year. And third, our team. We substantially strengthened our development team with the appointment of Dr. Raj Pruthi, a highly regarded physician, scientist and urologic oncologist as Chief Medical Officer, Oncology. In addition, we established a Scientific Advisory Board comprised of similarly distinguished peers to further support the NDV-01 program, Dr. Yair Lotan from the University of Texas Southwestern Medical Center and Dr. Max Kates from John Hopkins University School of Medicine. Fourth and last, financial strength. We just completed a successful $160 million private financing. Based on existing forecasts, these funds plus our existing cash balance provide Relmada with capital through 2029 and importantly, through the completion of the planned NDV-01 program. Looking ahead, 2026 is poised to be another important year of value creation for Relmada with the initiation of our Phase III RESCUE program for NDV-01 in bladder cancer and the Phase II proof-of-concept trial for sepranolone in Prader-Willi syndrome. With that, I also would like to express my appreciation for the trust and support of our investors, employees, collaborators and the patients who participate in our studies. Next, I will turn the call over to Dr. Raj Pruthi, who will provide a review of the NDV-01 program, including 12 months follow-up data from the ongoing Phase II study and the summary of our Phase III plans. Raj?

Thank you, Sergio, and good afternoon, everyone. It's a privilege to share an update on the clinical progress we've made this year, headlined by the truly compelling and best-in-class results for NDV-01 in NMIBC. Bladder cancer is a high-frequency cancer that has a major impact on the lives of patients, generally diagnosed in the early to mid-70s. High recurrence rates and burdensome treatments disrupt quality of life at a time when patients are eager to enjoy life. I want to touch on 3 topics during today's call. one, an overview of the NDV-01 12-month data; two, a summary of our planned Phase III program; and three, a discussion of how NDV-01 might fit into the practice of a urologic oncologist. Sergio noted that NDV-01 is a novel sustained-release intravescular formulation of 2 chemotherapy agents, gemcitabine and docetaxel or Gem/Doce, as we say. Our program builds on physicians' established familiarity with the efficacy and safety profile of conventional Gem/Doce,ore specifically in patients who are unresponsive to BCG. This combination offers a salvage of bladder-sparing option that may help avoid a radical cystectomy. Moving on to the 12-month data. We are pleased to report that NDV-01 has demonstrated a high response rate and durable 12-month efficacy from the ongoing Phase II study. We believe these data stand out in comparison to the other benchmark programs that could position NDV-01 as a best-in-class treatment option for patients with bladder cancer, if approved. The study is an open-label single-arm trial in patients with high-risk NMIBC. Patients received 6 biweekly doses every other week time 6, followed by monthly maintenance for up to 1 year. Patients undergo regular assessments with cystoscopy, cytology and if needed, biopsy. The study was designed to enroll up to 70 patients with high-risk NMIBC. The primary endpoints are safety and complete response rate at 12 months. Secondary endpoints are duration of response and event-free survival. The data demonstrated a 12-month complete response rate of 76% with a favorable safety profile. Notably, the study also showed a 12-month complete response rate of 80% in the BCG unresponsive population, one of the most difficult to treat segments of NMIBC. These findings support the advancement into the Phase III registrational program, which we are calling RESCUE. The program will evaluate NDV-01 in both second-line BCG unresponsive disease and in intermediate risk bladder cancer as an adjuvant therapy following TURBT. When we look at the complete responses or CR at any time, in the overall population, we see a CR any time of 95% based on 38 patients. Among those with BCG-unresponsive disease, we see a CR rate at any time of 94%. Given the burden of the nature of recurrent bladder cancer treatment, safety is a critical element of a product profile. We continue to be encouraged by the favorable safety profile observed for NDV-01 across our clinical program. In the 12-month data set for NDV-01, no patients had progression to muscle invasive disease. No patients underwent a radical cystectomy. No patients had a Grade 3 or higher treatment-related adverse events. No interruptions or discontinuations of treatment due to adverse events occurred and most treatment-related adverse events were at the grade 1 level. Moving on to the planned Phase III rescue program. We believe our 12-month response and durability data compare quite favorably to the current commercial and development stage [indiscernible] . We have constructed our Phase III registrational pathways to maximize our probability of success and create the most efficient path to FDA approval. The RESCUE registrational program was designed in alignment with the FDA to provide 2 separate approval pathways. We expect to secure U.S. IND clearance and initiate the Phase III RESCUE program in the middle of this year. Let's review the 2 studies that form the RESCUE program. Registrational Pathway 1 focuses on the evaluation of NDV-01 in patients with intermediate risk bladder cancer as an adjuvant therapy following TURBT surgery. We estimate there are about 75,000 patients each year in the U.S. in this setting. This study is planned to be an open-label randomized controlled trial. Since there are no approved treatments for adjuvant intermediate risk NMIBC, the study will evaluate NDV-01 versus observation. The primary endpoint is disease-free survival or DFS. Secondary endpoints include high-grade recurrence-free survival, progression-free survival and quality of life metrics. We feel that the opportunity to incorporate NDV-01 into patient care post TURBT is very attractive, and it could pave the way for important clinical indication and broader adoption. Registration pathway # 2 is focused on the evaluation of NDV-01 in the second-line setting in patients who are BCG-unresponsive with carcinoma in situ or CIS who are refractory to first-line therapies approved or in development. We estimate that there are about 5,000 patients per year in the U.S. in this setting. Since these patients have few, if any, effective treatment alternatives to radical cystectomy, the study is designed as a single-arm open-label trial. The primary endpoint is CR any time. Secondary endpoints will include the duration of response or DOR, progression-free survival and recurrence-free survival amongst responders. We expect to report the initial 3-month response data from this study by the end of 2026. We're excited about this pathway because it could offer a rapid route to approval. Before I hand the call over to Maged, I'd like to make a note about how we feel NDV-01 might fit into clinical practice. NDV-01 is formulated to create a soft matrix in the bladder to enhance local bladder urothelial exposure and minimize systemic toxicity. It is delivered in the office in less than 5 minutes. This simple formulation and administration model has the potential to optimize the delivery experience for patients and providers, offering a level of simplicity and time savings that stands out amongst the others. [indiscernible] I hand the call over to our CFO, Maged Shenouda. Our Phase II data gives us high confidence in our registrational program. By addressing a clear unmet need with a unique sustained delivery profile, we believe NDV-01 is uniquely positioned to redefine the standard of care in bladder cancer. We look forward to initiating the RESCUE registrational program at an estimated 80 sites in North America in the middle of this year as we work to bring NDV-01 to bladder cancer patients as soon as possible. Maged?

Thanks, Raj, and good afternoon, everyone. Today, I'll spend a few minutes on sepranolone and then provide you with an overview of our fourth quarter 2025 financial results. Because sepranolone modulates GABA, one of the most important neurotransmitters, it is defined as a [ GAAM cell ] or GABA modulating steroid antagonist. Sepranolone's novel action on the GABA neurotransmitter pathway gives it the potential to normalize the activity of the GABA A receptor and alleviate the repetitive symptoms of compulsivity disorders. These disorders affect millions of people around the world and include indications such as obsessive compulsive disorder, Tourette syndrome and Prader-Willi syndrome. We are preparing to initiate a proof-of-concept study in Prader-Willi syndrome in mid-2026. Our immediate efforts are dedicated to completing study preparations, including engaging with the FDA on our proposed trial design and establishing a robust supply chain. Moving now to our financial results. As noted earlier by Brian, this afternoon, Relmada issued a press release announcing our business and financial results for the fourth quarter and 12 months ended December 31, 2025. During this call, I'll review our fourth quarter 2025 financial results and refer you to our press release and 10-K filing issued this afternoon for financial information for the last 12 months. Starting with our cash balance. Relmada closed 2025 with a cash balance of $93 million. This includes net proceeds of approximately $94 million from an underwritten stock offering announced on November 5, 2025. This compares to cash, cash equivalents and short-term investments of approximately $45 million at December 31, 2024. On March 9, 2025, the company announced a $160 million private financing with net proceeds of approximately $150 million. This financing, along with our cash balance as of December 31, 2025, is expected to provide sufficient resources to fund company operations through 2029, including completion of the Phase III RESCUE program for NDV-01. Moving through our fourth quarter financial results. Research and development expense for the 3 months ended December 31, 2025, totaled $8.1 million compared to $11 million for the 3 months ended December 31, 2024, a decrease of $2.9 million. The decrease was primarily driven by a decrease in study costs associated with the completion of 2 Phase III trials for REL-1017, partially offset by increased costs related to the start-up of the Phase III NDV-01 trials and Phase IIb sepranolone study and additional R&D personnel. General and administrative expense for the 3 months ended December 31, 2025, totaled $12.3 million compared to $8.1 million for the 3 months ended December 31, 2024, an increase of approximately $4.2 million. The increase was primarily driven by an increase in compensation costs, partially offset by a decrease in stock compensation costs. Net cash used in operating activities for the 3 months ended December 31, 2025, totaled $14.6 million compared to $8.8 million for the 3 months ended December 31, 2024. The net loss for the 3 months ended December 31, 2025, was $19.9 million or $0.27 per basic and diluted share compared to a net loss of $18.7 million or $0.62 per basic and diluted share for the 3 months ended December 31, 2024. Before we open the call for questions, I'll turn it back to Sergio for some closing comments. Sergio?

Thank you, Maged. In closing of our prepared remarks, I would like to share that I'm very confident and optimistic about our clinical programs and the long-term prospects for Relmada. As we are getting ready to initiate the rescue registrational program for ADV01, we are focused on execution and looking forward to updating you on our progress in the coming quarters. Operator, I would now like to open the call for questions.

[Operator Instructions] Our first question is from Uy Ear with Mizuho Securities.

Congrats on the great data and the pipe. It seems like you guys did a lot of work this quarter. So maybe I'm getting some questions on whether you will present additional data from your Phase II study. Should we kind of expect going forward maybe updates every 3 months? And will you also have data, I guess, at AUA by any chance? So that's the first question. And the second question that we've been kind of getting is there's been, I guess, some investors are a little bit concerned that the second-line patients may not be necessarily second line, but maybe by the time they get to your regimen, it could be their third line. Maybe just help us understand how -- what you're doing exactly to ensure that those patients are truly second-line patients. And the third question is, you indicated that you'll have 3 months data from your Phase III BCG unresponsive second-line and responsive patients, will this be from the entire patient population? Or would this be sort of interim and is partial or a portion of the number of patients that you expect to enroll?

Thank you, Uy, for the questions. I think Raj is the -- he can answer these questions. I pass it to Raj.

Thank you, Sergio. Good to hear from you, Uy. Regarding the data, we will be presenting an updated data, this 12-month data at the AUA that has been accepted for that. We'll also be presenting a trial in progress as we get rescue going. Our plan is to focus on introducing data, and I think this is your last question in the BCGs responsive second-line group starting at the end of the year. So as we start the trial in midyear, we should have some 3-month data to be able to share externally by the end of the year as it's a single-arm open label. And our thought is to then actually at a cadence of about every 3 months, share the data as we get 6, 9 and 12-month follow-up on that data set. I think you provide an excellent question on second line, third line, fourth line. And we are indeed limiting the number of prior therapy lines to 2. So you can have had one line of therapy at [ Stiligrnd, ] for example, and we're allowing the second of those say still followed by Antiva. we're also allow a maximum of 2, but we're also going to look at 15 patients at 3 months of those who received first-line therapy versus 2 just to make sure they're -- it's an open-label study that there's nothing concerning that we want there that those should be excluded. And this is reflective of the conversations we've had with the FDA. But I think it's a good question, limiting the number of or third or fourth.

Our next question is from Farzin Haque with Jefferies.

Congrats on the progress. So I had one on the operational standpoint. The NMIBC space is becoming congested with active trials and drugs approved too. So are there -- like what is your expectation for enrollment cadence across your 2 studies? And can the drug's in-office profile potentially serve as a recruitment advantage?

Thank you, Farzin. Raj, do you want to take that?

Yes, yes. Thank you. Yes, Farzin, good to hear from you. I think you're right. It's -- I think the high-risk BCGen response has been a crowded space, but I think ours coming in as a second-line therapy provides a unique advantage, and there's no drugs that have been approved in that setting and none that I'm aware of that are even being investigated with -- as a pivotal study in that setting. So I think we have a competitive advantage in that we can go to sites that even in development, drugs in development and follow them in this unique path. And same for intermediate risk, I think right now, there's -- it's becoming a bigger expansive interest. But what I've seen in, for example, CG Oncology has an intermediate risk trial that looks like it's ahead of schedule and accrued very rapidly. I think there's a lot of interest in -- from investigators and looking at intermediate risk patients. So I think we -- I expect us to enroll that pretty rapidly ahead of schedule like CG did. Thanks for the question, Farzin.

Got it. And then for the second-line high-grade settings, beyond the primary endpoint of CR rate at any time, has the FDA stipulated a minimum duration of follow-up required for all patients by submitting the NDA?

Another great question. They haven't required a minimum of follow-up. They said they want to see CR any, as you said, and durability of response or duration of response. I think the wording they use, which I think is important is they want to see the totality of the data. So they want to see, do you have a response? And is there some level of durability, they haven't specified what that number is.

Your next question is from Christopher Liu with Lucid.

I was just wondering, given the population differences between your Phase II and Phase III rescue, what are you expecting to see in terms of the CR rate at the 3-month mark as well as what we should be benchmarking against with the data set?

Thank you, Chris. Raj, do you want to take this one as well?

Yes, sure. Yes. Thanks, Chris. Thanks for the question. So in the intermediate risk, we are looking at -- we structured the trial to look at the statistics around it, a 2-year RFS of 75%. And that actually is reflected in the literature with gem dosing. I think with what we've seen in this population and with sustained relief, we should exceed that, but that's our target number. that drive the statistics. It's an event-driven study, but that's kind of the -- and 128 events is a target. Regarding the BCG response in second line, it is -- we have looked at that of what is the -- it's interesting that in first line, the first drug approved was Valrubicin in 1998 at 8% 12-month CR, followed by KEYTRUDA at 19% at children 24%. So I think I'm glad that there's not -- the FDA wasn't fixated on a certain number, but I think that number should be at those levels or lower than what we've seen in first-line therapy just as a precedent, if that makes sense.

Our next question is from Kelsey Goodwin with Piper Sandler.

Congrats on the recent clinical update. Regarding -- I guess, specifically to that update, regarding the patient baseline characteristics and the CIS versus papillary split, I guess, how should we be comparing this data set to that of competitors with primarily CIS patients there? And I guess, any data to support that Gem/Doce looks similar in CIS and papillary patients?

Kelsey, Sergio here. Raj, it seems that this one also is for you.

Yes. Great question, Kelsey. Regarding -- starting the last part of your question first, there is. In fact, it's interesting as a clinician, you often think, okay, if the patient is BCG-unresponsive, this might be more virulent. But we don't often like think it as CIS versus papillary. Some people show pure C behaves better, but T1 pathway worse. So it's a mixed bag. It's actually interesting for Gem/Doce. There's an article by Steinberg in 2020 in the Journal of Urology that looked at heavily pretreated basically patients. And at 12 months, the RFS in those patients or CRs was 60% in the CIS population and 61% in papillary. So there isn't a market difference typically between that. But even if you go back and look at our data of what we showed, ours at the 12 months is 80%, 12-month 84% that does include 4 patients with -- at 12 months, patients with CIS. We had 4 out of 4 with complete response at any time, 2 out of 2 at 12 months. Completely understood, these are small numbers, but I think it still compares quite favorably. Even if you take NDV-01 and the BCG unresponsive capillary our entire population, including CS and compare it to the best-in-class papillary, which is in J&J's Exo, I think their 12-month CAM was 74%. So even taking our entire cohort, we have -- we're significantly higher. So I think still best-in-class. I hope I answered your question.

Yes. No, that's super helpful. And then maybe just one follow-up, if I can. With respect to the intermediate risk setting and that kind of market overall, I guess, how much do you think that market might need to be built out by these early launches just given we haven't had an approved agent until last year?

You bet, Kelsey. Another great question, if you don't mind me jumping in, Sergio. No, right now, I mean, we mentioned it's about a 75,000 to 80,000 patients with intermediate risk disease. And if you look at the data now, only about 35% of those patients will receive adjuvant therapy. What's important in our studies and in CV study is that in our intermediate risk population, we do include small less than 3-centimeter TA high-grade patients. I think that's very important because 20% of the intermediate risk disease in these high-grade PA patients. And those are the ones that probably more than anybody needs adjuvant therapy to prevent recurrence. So you go back to 45% receive an adjuvant therapy. I think it's exactly what you're alluding to. Right now, there isn't an approved therapy. There isn't a lot of data. There isn't a lot of agents that are -- can be reimbursed to the urologists in a buy-and-bill model, for example. So I think that 35% number is going to only grow as you see data from MoonRISe or from PIVOT-006 or from rescue, our intermediate study as we get data that gives patients confidence and, hey, here is an agent that might reduce my risk of having another TURBT and give urologists confidence that I have an agent that I can deliver in my office that will reduce TURBT risk for my patients. It's only going to grow...

This concludes our question-and-answer session. I would now like to hand the floor back over to Sergio Traversa for any closing remarks.

Well, closing remarks is a big thank you to everybody that has allowed Relmada to get where we are now with great data with a drug that can really help patients with bladder cancer. So we're looking forward to update everybody on our progress. Thank you, and enjoy the rest of the day.

Thank you.

This concludes today's conference. You may disconnect your lines at this time. Thank you again for your participation.