Relmada Therapeutics, Inc. (RLMD)

Executive Summary / Key Takeaways

• Strategic Transformation: Relmada Therapeutics has undergone a dramatic strategic pivot, terminating its prior lead CNS programs (REL-1017 and REL-P11) to acquire and focus on two new, innovative product candidates: NDV-01 for non-muscle invasive bladder cancer (NMIBC) and Sepranolone for compulsivity disorders.
• Promising Pipeline & Differentiated Technology: NDV-01, a sustained-release Gem/Doce formulation, has shown impressive Phase 2 data with a 90% complete response rate at 6 months in high-grade NMIBC, offering a less cumbersome administration than current options. Sepranolone, a first-in-class neurosteroid, demonstrated proof-of-concept in Tourette Syndrome and is advancing for Prader-Willi Syndrome.
• Significant Market Opportunities: Both NDV-01 and Sepranolone target large, underserved markets with high unmet medical needs, including the multi-billion dollar NMIBC market (600,000 U.S. patients) and Prader-Willi Syndrome (350,000 worldwide).
• Critical Liquidity Challenge: Despite reduced R&D expenses due to program wind-downs, Relmada reported $20.6 million in cash and short-term investments as of June 30, 2025, and explicitly projects insufficient liquidity to sustain operations for one year, raising "substantial doubt about the Company's ability to continue as a going concern."
• Near-Term Catalysts & Financing Imperative: Key milestones include further Phase 2 NDV-01 data (9-month, 12-month in H2 2025), U.S. IND clearance for NDV-01 (H1 2026), and initiation of Phase 3 for NDV-01 and Phase 2 for Sepranolone in H1 2026, all contingent on securing additional financing.

A Strategic Reset: From CNS Setback to Diversified Ambition

Relmada Therapeutics, founded in 2004, initially carved its path in central nervous system (CNS) disorders, notably with its esmethadone (REL-1017) program for major depressive disorder. However, a comprehensive strategic review in late 2024 and early 2025 marked a pivotal turning point. Following a setback in the REL-1017 program and subsequent analyses, the company made a bold decision to terminate its prior lead programs, including REL-1017 (effective July 7, 2025) and the psilocybin-based REL-P11 program (effective May 12, 2025). This strategic pivot was driven by a clear objective: to maximize shareholder value by leveraging its drug development expertise to acquire new, innovative candidates with established proof-of-concept data, near-term value creation drivers, and the potential to address well-defined, underserved markets.

This dramatic shift has reshaped Relmada into a clinical-stage biotechnology company with a diversified pipeline now focused on oncology and CNS indications. The company's new strategic framework emphasizes innovation, addressing unmet medical needs, pursuing large market opportunities, and strengthening intellectual property protection. This involves prioritizing mid-to-late-stage programs, accelerating market entry through cost-effective development paths, and implementing a targeted commercialization strategy. The success of this high-stakes rebirth hinges on the rapid advancement and commercial viability of its newly acquired assets.

NDV-01: Redefining Bladder Cancer Treatment with Sustained Release

Relmada's lead asset, NDV-01, represents a significant foray into oncology, specifically targeting non-muscle invasive bladder cancer (NMIBC). Acquired through an exclusive licensing agreement with Trigone Pharma in March 2025, NDV-01 is a novel, controlled-release intravesical formulation of gemcitabine and docetaxel (Gem/Doce). This combination therapy has garnered substantial interest as an alternative to Bacillus Calmette-Guérin (BCG), especially given the persistent global BCG shortage since 2019.

The core technological differentiation of NDV-01 lies in its sustained-release mechanism. Unlike conventional Gem/Doce administration, which is cumbersome and requires sequential drug delivery over three to four hours with limited tumor exposure, NDV-01 forms a spherical soft matrix within the bladder. This matrix gradually releases both gemcitabine and docetaxel over a 10-day period. This extended, continuous exposure is designed to maximize local drug concentration, enhance therapeutic effect, and minimize systemic toxicity, all while simplifying administration to a single, in-office procedure taking less than 10 minutes, requiring no anesthesia or specialized equipment. This ease of use and prolonged drug exposure are critical advantages over existing and emerging therapies.

Initial Phase 2 clinical data for NDV-01 have been highly encouraging. On August 7, 2025, Relmada announced positive 6-month follow-up data from its Phase 2 study in high-grade NMIBC patients. The study reported an impressive 90% complete response rate (CRR) at 6 months among 21 evaluable patients, and a 91% CRR at any time point among 23 evaluable patients. Critically, no patients experienced progression to muscle-invasive disease, underwent radical cystectomy, or had Grade 3 or higher treatment-related adverse events. This robust safety profile and strong efficacy signal underscore NDV-01's potential to become a class-leading bladder-sparing therapy.

The NMIBC market is substantial, with approximately 85,000 new cases of bladder cancer diagnosed annually in the U.S., and 600,000 Americans living with the disease. Roughly 50% of new cases are high-grade, carrying a high risk of recurrence (50-75% over seven years) and progression. This represents a multi-billion dollar opportunity in the U.S. alone. NDV-01's ability to offer a more convenient, sustained-release option for a proven chemotherapy regimen positions it favorably against competitors.

Sepranolone: A Novel Approach to Compulsive Disorders

Relmada's second key acquisition, Sepranolone, acquired from Asarina Pharma AB in February 2025, brings a novel neurosteroid to its pipeline, targeting compulsivity disorders. Sepranolone is a first-in-class neurosteroid epimer of allopregnanolone, classified as a GAMSA (GABA-A modulating steroid antagonist). Its unique mechanism of action involves selectively normalizing GABA-A receptor activity by targeting specific receptor subtypes (alpha-2 and alpha-4) without directly interfering with GABA signaling. This selective modulation offers a novel approach to alleviating repetitive symptoms in disorders characterized by excessive GABAergic activity.

Sepranolone is Phase 2b-ready, with initial proof-of-concept data from a Phase 2a study in Tourette Syndrome demonstrating a competitive tic reduction of 28% (p=0.051) on the Yale Global Tic Severity Scale (YGTSS), alongside improved quality of life and a favorable safety profile across over 335 participants. The company has identified Prader-Willi Syndrome (PWS) as its first clinical indication for Sepranolone, a complex genetic disorder affecting approximately 350,000 people worldwide (20,000 in the U.S.) and characterized by persistent hunger and compulsive behaviors. Management believes Sepranolone's distinct mechanism of action, focusing on the compulsive component, could offer complementarity with existing or emerging PWS treatments.

Competitive Landscape and Strategic Positioning

Relmada operates in highly competitive and rapidly evolving therapeutic areas. In NMIBC, NDV-01 enters a market with established treatments like BCG (though supply-constrained) and a growing number of emerging therapies. Competitors include UroGen Pharma (UGN) (UGN-102, a single-agent mitomycin gel for low-grade NMIBC), Janssen (JNJ) (TAR-200), Merck (MRK) (KEYTRUDA), and CG Oncology (CGON) (cretostimogene). NDV-01's sustained-release Gem/Doce formulation offers a significant advantage over conventional Gem/Doce, which is difficult to administer in an outpatient setting.

The company's strategy for NDV-01 is to leverage its ease of administration and proven efficacy of its components to become a preferred option. Management is exploring both high-grade NMIBC (where its current data is strong) and the larger, potentially faster-to-approval low-grade intermediate risk market, drawing on precedents set by UroGen. Dr. Yair Lotan, Chair of Relmada's Clinical Advisory Board, highlights NDV-01's potential to fit into BCG-naïve, intermediate-risk, and BCG-unresponsive spaces, noting that its sustained release could be superior to agents with shorter bladder retention times.

For Sepranolone, the competitive landscape for compulsivity disorders includes existing treatments for Tourette Syndrome (dopamine B2 blockers, antipsychotics, often with significant side effects) and emerging therapies for Prader-Willi Syndrome. Relmada believes Sepranolone's unique GABA-A modulating mechanism offers a differentiated approach, potentially complementing other treatments rather than directly competing, especially in PWS where the compulsive element is a key target.

Compared to large pharmaceutical companies like Eli Lilly (LLY) and Johnson & Johnson, Relmada, as a clinical-stage biotech, possesses greater agility in targeted R&D but significantly lags in financial scale, global market reach, and diversified revenue streams. Against other CNS-focused biotechs like Axsome Therapeutics (AXSM) and Alkermes (ALKS), Relmada's new pipeline offers specialized innovation, but its financial stability and operational execution remain critical factors. The company's intellectual property, with patents for NDV-01 extending beyond 2038 and Sepranolone beyond 2030, provides a foundational competitive moat.

Financial Performance and Liquidity: A Tightrope Walk

Relmada's financial performance reflects its transition from a late-stage development company to one focused on early-to-mid-stage asset acquisition. The company does not generate revenue from product sales and continues to incur significant losses from its clinical stage drug development activities. For the six months ended June 30, 2025, Relmada reported a net loss of $27.43 million, an improvement from $39.60 million in the comparable 2024 period.

Total operating expenses for the six months ended June 30, 2025, decreased to $28.44 million from $41.81 million in 2024. This reduction was primarily driven by a $9.26 million decrease in Research and Development (R&D) expenses, largely due to the wind-down of the REL-1017 studies and lower stock-based compensation. However, this was partially offset by $3.98 million in costs associated with the acquisitions of Sepranolone and NDV-01, and increased compensation for R&D employees. General and Administrative (G&A) expenses also decreased by $4.11 million, mainly due to lower stock-based compensation.

Despite these cost reductions, the company's liquidity position is a significant concern. As of June 30, 2025, Relmada held $1.35 million in cash and cash equivalents and $19.27 million in short-term investments, totaling approximately $20.6 million. Cash used in operating activities for the six months ended June 30, 2025, was $24.47 million. Management explicitly states that, given its projected operating requirements, the company projects "insufficient liquidity to sustain its operations through one year following the date that the financial statements are issued." This raises "substantial doubt about the Company's ability to continue as a going concern."

Management is actively evaluating financing strategies, including equity or debt sales, bank loans, or strategic collaborations. However, there is no assurance that sufficient financing will be secured on favorable terms, and these plans are not yet finalized or within the company's control, thus not alleviating the going concern doubt. The company also faces a Nasdaq listing compliance challenge, having received a notice for not maintaining a minimum bid price of $1.00 per share. While transferred to the Nasdaq Capital Market, it has until January 19, 2026, to regain compliance.

Outlook and Future Catalysts

Relmada's future hinges on the successful advancement of its new pipeline and its ability to secure necessary financing. The company has outlined several key milestones for NDV-01:

• 2nd Half 2025: Nine-month data from the ongoing Phase 2 NMIBC study.
• Year-end 2025: Twelve-month data from the ongoing Phase 2 NMIBC study.
• 1st Half 2026: United States Investigative New Drug (IND) clearance.
• 1st Half 2026: Initiation of a Phase 3 study.

For Sepranolone, the company anticipates initiating a proof-of-concept clinical trial in Prader-Willi Syndrome in the first half of 2026. These timelines are contingent on successful interactions with the FDA to align on trial designs and the establishment of robust product supply chains, including contract manufacturers. Management expects R&D expenses to increase significantly once patient enrollment begins for these pivotal studies in early 2026.

Conclusion

Relmada Therapeutics stands at a critical juncture, having executed a bold strategic pivot to redefine its future. The termination of its previous lead programs and the acquisition of NDV-01 and Sepranolone represent a high-stakes gamble on differentiated technology and unmet medical needs in oncology and CNS. The early Phase 2 data for NDV-01 in NMIBC are compelling, suggesting a potential class-leading therapy that could significantly improve patient care and convenience. Sepranolone also offers a novel mechanism for compulsive disorders with promising early signals.

However, the path forward is fraught with significant challenges, most notably the company's precarious liquidity position and the explicit "going concern" warning. While management is actively pursuing financing, the ability to secure sufficient capital on favorable terms will be paramount to advancing these promising programs through expensive late-stage clinical trials. Investors must weigh the substantial potential of Relmada's revitalized pipeline and its technological advantages against the immediate and pressing need for capital, making this a high-risk, high-reward investment proposition where successful execution of clinical milestones and financing strategies will dictate its trajectory.