RLMD - NASDAQ

Good afternoon, and welcome to the Relmada Therapeutics, Inc. Fourth Quarter and Full Year 2025 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the prepared remarks, we will conduct a question-and-answer session. As a reminder, this conference call is being recorded and will be available for replay on the Relmada Therapeutics, Inc. 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 Therapeutics, Inc. issued a press release providing a business update and outlining its financial results for the three 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 Therapeutics, Inc.'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 Therapeutics, Inc.'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 Therapeutics, Inc. 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 Therapeutics, Inc.'s CEO, Dr. Sergio Traversa, who will briefly provide a summary of recent business highlights; Dr. Raj S. Pruthi, Relmada Therapeutics, Inc.'s CMO, Oncology, who will provide an NDV-01 program update; and Relmada Therapeutics, Inc.'s CFO, Maged S. Shenouda, who will provide an update on cipranolone 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 Therapeutics, Inc. Fourth Quarter and Year-End 2025 Conference Call. 2025 has been a transformational year for Relmada Therapeutics, Inc., 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 accomplishments and planned next steps, I would like to highlight four key areas. First, NDV-01. We believe that the strength of the recently reported 12-month 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 give 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 settings. 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 two independent registrational pathways. Pathway one 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 two is focused on second-line treatment in BCG-unresponsive patients, which represents about 5,000 patients in the United States. Second, cipranolone. Cipranolone has previously demonstrated proof of concept in Tourette syndrome. It 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 S. 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, including Dr. Yair Lotan from the University of Texas Southwestern Medical Center and Dr. Kates from Johns 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 Therapeutics, Inc. 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 Therapeutics, Inc., with the initiation of our Phase III RESCUE program for NDV-01 in bladder cancer and the Phase II proof-of-concept trial for cipranolone 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 S. Pruthi, who will provide a review of the NDV-01 program, including 12-month follow-up data from the ongoing Phase II study and the summary of our Phase III plans. Raj?

Thank you, Sergio. Good afternoon, everyone. It is a privilege to share an update on the clinical progress we have 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 their 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 three 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 urologic oncology. As Sergio noted, NDV-01 is a novel, sustained-release intravesical formulation of two chemotherapy agents, gemcitabine and docetaxel, or GemDosi, as we say. Our program builds on physicians' established familiarity with the efficacy and safety profile of conventional GemDosi. More specifically, in patients who are unresponsive to BCG, this combination offers a salvage, 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 and 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 receive six biweekly doses, every other week times six, followed by monthly maintenance for up to one year. Patients undergo regular assessments with cystoscopy, pathology, 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 disease as an adjuvant therapy following TURBT. When you look at the complete responses, or CR, at any time in the overall population, we see a CR anytime of 95% based on 38 patients. Among those with BCG-unresponsive disease, we see a CR rate at any time of 94%. Given the burdensome nature of recurrent bladder cancer treatment, safety is a critical element of our 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 event, 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 trials. We have constructed our Phase III registrational pathways to maximize our probability of success and create the most efficient path to FDA approval. The entire RESCUE registrational program was designed in alignment with the FDA to provide two 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 us review the two studies that form the RESCUE program. Registrational pathway one 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 70,000 to 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 an important clinical indication and broader adoption. Registrational pathway number two 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, or 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 anytime. Secondary endpoints will include the duration of response, or DOR, progression-free survival, and recurrence-free survival among responders. We expect to report the initial three-month response data from this study by the end of 2026. We are excited about this pathway because it could offer a rapid route to approval. Before I hand the call over to Maged, I would 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 five 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. Our Phase II data give 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, and we will work to bring NDV-01 to bladder cancer patients as soon as possible. Maged?

Thanks, Raj, and good afternoon, everyone. Today, I will spend a few minutes on 2025 financial results. Because cipranolone modulates GABA, one of the most important neurotransmitters, it is defined as a GABA or GABA-modulating steroid antagonist. Cipranolone's novel action on the GABA neurotransmitter pathway gives it the potential to normalize the activity of the GABAA 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 Therapeutics, Inc. issued a press release announcing our business and financial results for the fourth quarter and twelve months ended December 31, 2025. During this call, I will review our fourth quarter 2025 financial results and refer you to our press release and Form 10-K filing issued this afternoon for financial information for the last twelve months. Starting with our cash balance, Relmada Therapeutics, Inc. 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, 2026, 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 three months ended December 31, 2025, totaled $8.1 million compared to $11.0 million for the three 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 two 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 2b cipranolone study, and additional R&D personnel. General and administrative expense for the three months ended December 31, 2025, totaled $12.3 million compared to $8.1 million for the three 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 three months ended December 31, 2025, totaled $14.6 million, compared to $8.8 million for the three months ended December 31, 2024. The net loss for the three months ended December 31, 2025, was $19.9 million, or 27¢ per basic and diluted share, compared to a net loss of $18.7 million, or $0.06 per basic and diluted share, for the three months ended December 31, 2024. Before we open the call for questions, I will turn back to Sergio for some closing comments. Sergio?

Thank you, Maged. In closing of our prepared remarks, I would like to share that I am very confident and optimistic about our clinical programs and the long-term prospects for Relmada Therapeutics, Inc. As we are getting ready to initiate the RESCUE registrational program for NDV-01, 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.

Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press 1 on your telephone keypad. One moment, please, while we poll for questions. Our first question is from Uy Sieng Ear with Mizuho Securities.

Hey, guys. Congrats on the great data and the financing. Yeah, it seems like you did a lot of work this quarter. Maybe we are getting some questions on whether you will present additional data from your Phase II study. Should we expect, going forward, updates every three months, and will you also have data at AUA by any chance? That is the first question. The second question that we have been getting is there is some concern 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. Please help us understand what you are doing to ensure that those patients are truly second-line patients. And the third question is, you indicated that you have three-month data from your Phase III BCG-unresponsive second-line patients. Will this be from the entire patient population, or would this be an interim from a portion of the number of patients that you expect to enroll. Thanks.

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

Thank you, Sergio. Good to hear from you, Uy. Regarding the data, we will be presenting updated 12-month data at the AUA. It has been accepted to AUA. We will also be presenting a trial in progress as we get RESCUE going. Our plan is to focus on introducing data, and to your last question, in the BCG-unresponsive second-line group, starting at the end of the year. As we start the trial in midyear, we should have some three-month data to share externally by the end of the year, as it is a single-arm, open-label study. Our thought is then to have, at a cadence of about every three months, additional updates as we get six-, nine-, and twelve-month follow-up on that data set. You provided an excellent question on second line, third line, fourth line. We are indeed limiting the number of prior therapy lines to two. So you can have had one line of therapy and still have been BCG-unresponsive, for example, while allowing a second line to be an alternative intravesical. We are also going to look at 15 patients at three months for those who received one prior line of therapy versus two, just to make sure there is nothing concerning in this open-label study that would warrant exclusion. This is reflective of the conversations we have had with the FDA. But it is a good question, and we are limiting the number of third or fourth lines.

Thank you.

Our next question is from Farzin Hak with Jefferies. Congrats on the progress, and thank you for taking my questions.

I have one on the operational standpoint. The NMIBC space is becoming congested with active trials and drugs approved, too. What is your expectation for enrollment cadence across your two 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?

Thank you. Yeah, Farzin, good to hear from you. I think you are right. The high-risk, BCG-unresponsive space has been crowded, but I think ours, coming in as a second-line therapy, provides a unique advantage. There are no drugs that have been approved in that setting and none that I am aware of that are even being investigated as a pivotal study in that setting. So I think we have a competitive advantage in that we can go to sites that, even with drugs in development, can follow them in this unique path. The same for intermediate risk. Right now, it is becoming an area of broader interest. CG Oncology, for example, has an intermediate-risk trial that looks like it is ahead of schedule and accrued very rapidly. I think there is a lot of interest from investigators in intermediate-risk patients. I expect us to enroll that study pretty rapidly and 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 have not required a minimum follow-up. They said they want to see CR anytime, as you said, and durability of response or duration of response. I think the wording they used, which I think is important, is they want to see the totality of the data. They want to see that you have a response and there is some level of durability. They have not specified what that number is.

Got it. Thank you so much.

Thank you, Farzin. Your next question is from Christopher with Lucent.

Hey, guys. Thanks for the question. I was 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 three-month mark, as well as what we should be benchmarking against with the status of the field?

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

Yes. Thanks, Chris. Thanks for the question. In the intermediate-risk study, we structured the trial statistics around a two-year RFS of 75%. That is reflected in the literature with GemDosi. With what we have seen in this population and with sustained release, we should exceed that, but that is our target number and it drives the statistics. It is an event-driven study with a target of 128 events. Regarding the BCG-unresponsive second-line, if you look historically, in first line the first drug approved was valrubicin in 1998 at 8% 12-month CR, followed by Keytruda at 19% and then other programs in the 24% range. So I am glad the FDA was not fixated on a certain number, but I think that threshold should be at those levels or lower than what we have seen in first-line therapy, just as precedent.

Got it. Thanks for the question.

Our next question is from Kelsey Goodwin with Piper Sandler.

Hey, thanks so much for taking my question and congrats on the recent clinical update. Regarding that update, on the patient baseline characteristics and the CIS versus papillary split, how should we be comparing this data set to that of competitors with primarily CIS patients? And do you have any data to support that GemDosi looks similar in CIS and papillary patients?

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

Great question, Kelsey. Starting with the last part of your question, as a clinician you often think if the patient is BCG-unresponsive, this might be more virulent, but we do not often parse whether it is CIS versus papillary. Some people show pure CIS behaves better, but T1 actually is worse, so it is a mixed bag. For GemDosi, there is an article by Steinberg in 2020 in the Journal of Urology that looked at heavily pretreated patients, and at 12 months the RFS or CRs were 60% in the CIS population and 61% in papillary, so there is not a marked difference typically. If you go back and look at our data, our 12-month CR in BCG-unresponsive is 80%, and our 12-month CR in the overall population is 84%. That includes four patients with CIS; we had four out of four with complete response at any time and two out of two at 12 months. These are small numbers, but they still compare quite favorably. Even if you take NDV-01 and the BCG-unresponsive population, including CIS, and compare it to the best-in-class categories, I think their 12-month CR was 74%. Taking our entire cohort, we are significantly higher, so I think it is still best in class. I hope I answered your question.

That is super helpful. Thank you so much for that. And one follow-up: with respect to the intermediate-risk setting and that market overall, how much do you think that market might need to be built out by these early launches, given we have not had an approved agent until last year? Thanks so much.

You bet, Kelsey. Right now, we mentioned there are about 75,000 to 80,000 patients with intermediate-risk disease. If you look at the data now, only about 35% of those patients receive adjuvant therapy. What is important in our studies and in CG’s study is that in our intermediate-risk population, we include small, less than 3-centimeter Ta high-grade patients. That is very important because 20% of the intermediate-risk disease is these high-grade Ta patients, and those are the ones, probably more than anybody, who need adjuvant therapy to prevent recurrence. Going back, while about 35% receive adjuvant therapy, I think that number will grow as you see data from Moonlight or from PIVOT-006 or from our RESCUE intermediate study. As we get data, it gives patients confidence that there is an agent that might reduce the risk of another TURBT and gives urologists confidence that there is an agent they can deliver in the office that will reduce TURBT risk for patients. It is only going to grow.

That is great. Thank you so much.

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

The closing remark is a big thank you to everybody that has allowed Relmada Therapeutics, Inc. to get where we are now. We created data with a drug that can really help patients with bladder cancer. We are looking forward to updating everybody on our progress. Thank you, and enjoy the rest of the day. Thank you.