8-K: Relmada Secures FDA Path for NDV-01, Reports Strong Phase 2 Data

Relmada Therapeutics announced positive FDA feedback for two Phase 3 registrational paths for NDV-01 in NMIBC and reported strong 9-month safety and efficacy data from its Phase 2 study.

Summary

• FDA feedback supports two distinct registrational study paths for NDV-01 in Non-muscle Invasive Bladder Cancer (NMIBC).
• A single-arm trial may be acceptable for high-grade, 2nd line refractory BCG-unresponsive NMIBC patients, with details to be discussed further with the FDA.
• A randomized, post-transurethral resection of the bladder tumor (TURBT) adjuvant study comparing NDV-01 to observation in intermediate-risk NMIBC patients with a time-to-event primary endpoint is generally acceptable, subject to submission of the intended trial design.
• The FDA agreed with the proposal to rely on prior FDA findings of safety for Gemzar and Taxotere and published literature for the nonclinical safety assessment of NDV-01, supporting a 505(b)(2) approval pathway.
• Nine-month safety and efficacy data from the Phase 2 study of NDV-01 in high-risk NMIBC showed no new safety signals among 36 enrolled patients.
• Complete Response (CR) rates were 92% (23/25) anytime, 84% (21/25) at 3 months, 87% (20/23) at 6 months, and 85% (17/20) at 9 months.
• In the BCG-unresponsive subpopulation, CR rates were 91% (10/11) anytime, 82% (9/11) at 3 months, 78% (7/9) at 6 months, and 88% (7/8) at 9 months.
• No patients experienced Grade 3 treatment-related adverse events (TRAE), and no patients discontinued treatment due to adverse events.
• Among treatment-related adverse events (61% of patients), 62% were transient uncomfortable urination (dysuria), 9% were asymptomatic positive urine culture, and 7% were hematuria.
• Preliminary financial information as of September 30, 2025, indicates approximately $13.9 million of cash, cash equivalents, and short-term investments, which is unaudited and subject to change.

Sentiment

Score: 8

Explanation: The filing presents highly positive clinical and regulatory news for NDV-01, outlining clear paths to Phase 3 and strong Phase 2 data. The preliminary cash balance, while unaudited, is a point of consideration given the upcoming trial costs, but the overall sentiment is very strong due to the significant progress with the FDA and promising efficacy.

Positives

• FDA feedback provides clear, acceptable pathways for two distinct Phase 3 registrational trials for NDV-01, including a potentially faster single-arm trial for refractory BCG-unresponsive NMIBC.
• FDA agreed to a 505(b)(2) pathway, allowing reliance on existing safety data for Gemzar and Taxotere, which could expedite development and reduce costs.
• Strong 9-month efficacy data for NDV-01 in Phase 2, with high complete response rates (85% at 9 months overall, 88% in BCG-unresponsive subpopulation), indicating significant therapeutic potential.
• Excellent safety profile observed in Phase 2, with no new safety signals, no Grade 3 treatment-related adverse events, and no discontinuations due to adverse events.
• Two patients have reached the 12-month assessment, both maintaining a complete response, and no patient has progressed to muscle-invasive disease or undergone radical cystectomy.
• NDV-01 offers competitive advantages such as sustained release of Gem/Doce, ready-for-use pre-filled syringe, and in-office administration, enhancing patient convenience and potentially adherence.

Negatives

• Preliminary financial information as of September 30, 2025, is unaudited and subject to material change, limiting current financial clarity.
• Specific trial designs and endpoint definitions for the proposed Phase 3 studies still require further discussion and submission to the FDA.
• The preliminary cash balance of $13.9 million is relatively low for a company planning two Phase 3 trials, suggesting potential future capital needs.

Risks

• There can be no assurance that the FDA will agree that new protocols and plans are sufficient to support approval of NDV-01.
• The company may not be able to proceed with Phase 3 clinical trials on its proposed timetable.
• There is potential for Phase 2 NDV-01 data not to continue to deliver positive results supporting further development.
• Clinical trials may fail to deliver statistically and/or clinically significant evidence of efficacy and/or safety.
• Top-line results may not accurately reflect the complete results of the trial.
• Planned or ongoing preclinical and clinical studies may fail to demonstrate expected results.
• Failure to secure adequate NDV-01 or sepranolone drug supply could impede development.

Future Outlook

Relmada expects to advance NDV-01 towards registration-track studies in H1 2026, following planned FDA interactions and manufacturing build-out in Q4 2025 and Q1 2026. They also plan to initiate a pilot Phase 2 study for Sepranolone in Prader-Willi Syndrome in H1 2026, after Q4 2025 preparations.

Management Comments

• Raj Pruthi, MD, Chief Medical Officer – Urology, stated: "The positive outcome of our Type B meeting and alignment with the FDA on the Phase 3 pivotal program mark a key milestone for Relmada and NDV-01. We believe the FDA’s guidance provides a path to advance NDV-01 for patients with NMIBC who currently have limited options. We believe a single-arm registrational study in high-grade, refractory BCG-unresponsive patients offers a rapid route to potential approval, while alignment on a separate second pivotal study in intermediate-risk NMIBC could enable an additional indication and broader clinical adoption."
• Sergio Traversa, Chief Executive Officer, stated: "We added NDV-01 to our portfolio based on its strong potential to transform the treatment of NMIBC. The outcome of our Type B meeting with the FDA further reinforces our confidence in the path forward and in NDV-01’s potential to become a best-in-class, durable, ready and easy-to-use, in-office, bladder-sparing therapy. We look forward to initiating the Phase 3 programs in the first half of 2026."

Industry Context

Non-muscle invasive bladder cancer (NMIBC) represents 75-80% of all bladder cancer cases, with high recurrence rates (50-80% over 5 years) and over 744,000 prevalent cases in the U.S. The current treatment landscape involves TURBT surgery followed by intravesical BCG, which faces supply issues and complications. The Gem/Doce combination therapy is already embraced by urologic oncology, and NDV-01 aims to improve upon this with sustained release and ease of administration, addressing significant unmet needs in a large market.

Comparison to Industry Standards

• NDV-01 is a sustained-release intravesical formulation of gemcitabine/docetaxel (Gem/Doce), a combination already recognized as an effective salvage treatment for BCG-unresponsive NMIBC (reported 2-year RFS ~50%) and an alternative first-line agent (reported 2-year RFS of 82% in BCG-naive high-risk patients).
• Unlike conventional Gem/Doce, which requires specialized pharmacy preparation and a 4-hour total procedure time (including 90-120 minute dwell times for each drug with a break), NDV-01 comes ready for use in pre-filled syringes and can be instilled in less than 5 minutes, offering significant convenience for both patients and healthcare providers.
• Compared to other NMIBC treatments like ZUSDURI (Mitomycin C hydrogel) and INLEXZO (Gemcitabine), NDV-01 utilizes a Gemcitabine/docetaxel combination, is in Phase 2 (vs. FDA approved for ZUSDURI and INLEXZO), and is a sustained-release hydrogel. ZUSDURI requires in-office reconstitution and no device removal, while INLEXZO requires catheter-based insertion and cystoscopic removal. NDV-01 is also administered via pre-filled syringe and does not require device removal.
• The reported 9-month complete response rate of 85% (and 88% in the BCG-unresponsive subpopulation) for NDV-01 in Phase 2 is highly competitive, especially given the high recurrence rates and progression risks associated with NMIBC, and compares favorably to existing options.

Stakeholder Impact

• Shareholders: Positive impact due to significant progress in clinical development and regulatory clarity for NDV-01, potentially increasing company valuation and future revenue prospects.
• Patients (NMIBC): Highly positive impact as NDV-01 shows promise as a safe and effective bladder-sparing therapy, potentially offering a new, more convenient treatment option for a disease with high recurrence rates and limited alternatives.
• Healthcare Providers (Urologists): Positive impact as NDV-01 could provide an easy-to-use, in-office treatment option based on a familiar Gem/Doce combination, simplifying administration compared to current methods.

Next Steps

• Request Type B meetings with the FDA for the randomized intermediate-risk NMIBC trial and for the BCG-unresponsive trial.
• Develop protocols for the single-arm study in BCG-unresponsive NMIBC (approximately 100 patients) and the randomized intermediate-risk NMIBC trial (approximately 266 patients).
• Complete 12-month follow-up data for NDV-01 Phase 2 study (expected Q1 2026).
• Planned FDA interactions and manufacturing build-out for NDV-01 (Q4 2025 Q1 2026).
• Initiate Phase 3 (Registrational) studies for NDV-01 (expected H1 2026).
• Prepare for Sepranolone Phase 2 studies, including FDA interactions and product supply expansion (expected Q4 2025).
• Initiate pilot Phase 2 study for Sepranolone in Prader-Willi Syndrome (expected H1 2026).

Key Dates

Recommendation

The filing provides exceptionally strong positive news, including clear FDA pathways for two pivotal Phase 3 trials for NDV-01, a 505(b)(2) regulatory advantage, and compelling 9-month Phase 2 efficacy and safety data. This significantly de-risks the lead asset and outlines a credible path to market for a therapy addressing a large unmet medical need in NMIBC. While the preliminary cash balance suggests future capital needs, the clinical and regulatory advancements are highly favorable and likely to drive substantial investor interest and potential share price appreciation.

Keywords

NMIBC, bladder cancer, NDV-01, Gem/Doce, FDA, Phase 3, clinical trials, biotechnology, oncology, Relmada Therapeutics, Sepranolone, Prader-Willi Syndrome, BCG-unresponsive, intermediate-risk NMIBC