10-K: Relmada Pivots Pipeline, Secures Funding for New Drug Candidates

Relmada Therapeutics, Inc. has undergone a significant strategic shift, terminating prior drug programs to focus on two new clinical-stage candidates, NDV-01 and sepranolone, while securing substantial new financing.

Summary

• Relmada Therapeutics terminated its esmethadone (REL-1017) development program effective July 7, 2025, following an interim analysis indicating futility in its Phase 3 study.
• The company also terminated its REL-P11 (psilocybin) development program effective May 12, 2025.
• Relmada acquired sepranolone, a Phase 2b-ready neurosteroid for potential treatment of Prader-Willi syndrome (PWS), Tourette Syndrome (TS), and essential tremor, from Asarina Pharma AB on February 6, 2025, for €3,000,000 (approximately $2,756,000 paid).
• The company in-licensed NDV-01, a novel controlled-release intravesical formulation of gemcitabine and docetaxel for non-muscle-invasive bladder cancer (NMIBC), from Trigone Pharma Ltd. on March 25, 2025, for a $3,500,000 upfront payment and 3,017,420 shares of common stock (10% of outstanding shares), plus up to $200 million in milestones and a 3% royalty on net sales.
• Phase 2 clinical trial data for NDV-01 in high-risk NMIBC showed no new safety signals, no Grade 3 treatment-related adverse events, and complete response rates of 87% at 3 months and 76% at 12 months (83% by Kaplan-Meier analysis) among 48 enrolled patients.
• FDA alignment was secured for planned Phase 3 pivotal programs for NDV-01 in two NMIBC indications, expected to begin mid-2026.
• Sepranolone's open-label Phase 2a study in Tourette Syndrome demonstrated a 28% tic reduction (p=0.051) and positive results in four key secondary endpoints, with no off-target CNS effects.
• Relmada reported a net loss of approximately $57,385,200 for the year ended December 31, 2025, a decrease from $79,979,400 in 2024.
• The accumulated deficit as of December 31, 2025, was approximately $698,267,200.
• Cash, cash equivalents, and short-term investments totaled approximately $93.0 million as of December 31, 2025.
• The company successfully closed an underwritten offering on November 5, 2025, raising approximately $94 million in net proceeds.
• A Private Investment in Public Equity (PIPE) Purchase Agreement was entered into on March 9, 2026, for approximately $160.0 million, which closed on March 11, 2026.
• Management believes existing cash and investments, combined with recent financing, will fund operating expenses and capital expenditure requirements for at least 12 months from the issuance date of the audited financial statements (March 19, 2026).
• Relmada regained compliance with Nasdaq's minimum bid price requirement on September 15, 2025.

Sentiment

Score: 7

Explanation: StockSavvy.ai views this as a positive strategic realignment for Relmada, with the termination of failed programs and the acquisition of promising new candidates backed by strong financing. While significant losses continue, the pipeline progress and improved liquidity are encouraging for future development.

Positives

• Successful acquisition of sepranolone and in-licensing of NDV-01, significantly augmenting and diversifying the development pipeline with two new clinical-stage candidates.
• Positive Phase 2 clinical trial data for NDV-01 in NMIBC, showing no new safety signals, no Grade 3 adverse events, and high complete response rates (e.g., 76% at 12 months).
• FDA alignment on key elements of the planned Phase 3 pivotal program for NDV-01, including reliance on prior safety findings for components, potentially streamlining approval.
• Promising Phase 2a data for sepranolone in Tourette Syndrome, demonstrating tic reduction and improved quality of life without CNS side effects.
• Substantial capital raises in late 2025 (approximately $94 million) and early 2026 (approximately $160 million), significantly improving liquidity and extending the financial runway.
• Reduced net loss to $57.4 million in 2025 from $80.0 million in 2024.
• Strong intellectual property portfolio for both NDV-01 and sepranolone, potentially providing coverage beyond 2038.
• Regained compliance with Nasdaq's minimum bid price requirement, mitigating delisting risk.

Negatives

• Termination of the esmethadone (REL-1017) program due to futility in Phase 3, representing a significant setback and loss of invested resources.
• Termination of the REL-P11 (psilocybin) development program.
• Continued significant net losses ($57.4 million in 2025) and an accumulated deficit of $698.3 million, indicating no revenue generation to date.
• Reliance on third parties for manufacturing and clinical trials, introducing external risks and potential for delays.
• Limited operating history with new drug candidates, making future success difficult to predict.
• The company currently has no commercial products or sales/marketing infrastructure.
• Stock-based compensation expense decreased significantly due to equity grants dropping off the amortization schedule and fewer options granted due to lack of shareholder approval to increase the 2021 Equity Incentive Plan.

Risks

• Ending development of former drug candidates (esmethadone, REL-P11) may adversely affect business and financial condition, with no assurance new candidates will offset these setbacks.
• Refocusing on new drug candidates (NDV-01, sepranolone) involves significant uncertainty and risk due to early development stages and limited data regarding their safety, efficacy, or commercial viability.
• Business depends on the success of drug candidates; failure to obtain regulatory approval or significant delays would materially harm the business.
• May require substantial additional funding, which may not be available on favorable terms or at all, potentially forcing curtailment of operations, delay of development, or alternative strategies such as liquidation or bankruptcy.
• No revenue from commercial sales to date and future profitability is uncertain; the company has a history of losses and an accumulated deficit.
• International commercialization of product candidates faces significant obstacles due to limited foreign regulatory, clinical, and commercial resources.
• Ability to use net operating loss carryforwards and certain other tax attributes may be limited due to ownership changes as defined by Section 382 of the IRC.
• May not be successful in hiring and retaining key employees, especially those with specialized knowledge or skills required for new drug candidates.
• Managing growth as operations expand may strain financial, managerial, and operational resources.
• Expansion through acquisitions of rights to new drug candidates could disrupt business, harm financial condition, and dilute current stockholders' ownership interests.
• Business interruptions from computer viruses, human error, natural disasters, or other events could limit the ability to operate.
• If the company or its potential collaborators fail to obtain the necessary regulatory approvals, or if such approvals are limited, commercialization of drug candidates will not be allowed, and product revenues will not be generated.
• Inability to design, conduct, and complete successful clinical trials will prevent regulatory approval for product candidates.
• Conducting clinical trials or commercial sales of a drug candidate may expose the company to expensive product liability claims, and sufficient product liability insurance may not be maintainable on reasonable terms or at all.
• Ongoing FDA obligations and continued regulatory review post-approval, such as safety reporting requirements or post-marketing studies, may result in significant expense and limit commercialization.
• FDA policies may change, and additional government regulations may be enacted that could prevent or delay regulatory approval of drug candidates.
• Fast Track Designation, if obtained, may not lead to a faster development or regulatory review or approval process.
• Even if orphan drug designation is obtained, orphan drug exclusivity may not be maintained or effectively protect the product from competition.
• May need to focus future efforts in new therapeutic areas where the company has little or no experience.
• If a supplier of an active pharmaceutical ingredient (API) or a pharmaceutical excipient fails to provide sufficient quantities, obtaining an alternative supply on a timely or acceptable basis may be difficult.
• Modifications to products, if approved, may require new NDA approvals, leading to additional expenditures and delays.
• Delays in the commencement or completion of pharmaceutical development, manufacturing, or clinical testing could result in increased costs and delay the ability to generate revenues.
• Conducting successful clinical studies may require the enrollment of large numbers of patients, and suitable patients may be difficult to identify and recruit.
• Adverse safety outcomes during clinical trials could affect the ability to conduct trials or obtain approval of product candidates.
• Products will face significant competition in the markets from large pharmaceutical companies, specialty pharmaceutical and biotechnology companies, as well as academic and research institutions.
• Exposure to liability claims associated with the use of hazardous materials and chemicals.
• Dependence on information technology systems and those of third-party collaborators, service providers, contractors, or consultants, which are vulnerable to security breaches, disruptions, or incidents.
• International political and economic instability, including geopolitical tensions, armed conflicts, trade restrictions, and sanctions, could disrupt operations and adversely affect business and financial results.
• Operations and relationships with future customers, providers, and third-party payors will be subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which could expose the company to penalties.
• Enacted and future legislation, such as the Inflation Reduction Act (IRA), may affect the prices the company may set and third-party payment for product candidates.
• Disruptions at the FDA, the SEC, and other government agencies or comparable regulatory authorities caused by funding shortages or global health concerns could hinder timely reviews and approvals.
• There is a limited market for common stock that may make it more difficult to dispose of shares.
• Failure to maintain compliance with the continued listing standards of The Nasdaq Stock Market could result in delisting and adversely affect the market price and liquidity of common stock.
• A sale of a substantial number of shares of common stock may cause the price of the common stock to decline.
• Subject to the reporting requirements of federal securities laws, which can be expensive and may divert resources from other projects.
• Failure to establish and maintain an effective system of internal control may prevent accurate financial reporting or fraud prevention.
• Stock price may be volatile due to recent developments, including the termination of former drug candidates and the shift to new development programs.
• The Nevada Revised Statutes and the company's articles of incorporation and bylaws contain provisions that could discourage, delay, or prevent a change in control of the company.
• Bylaws provide that a Nevada court and the federal district courts of the United States will be the exclusive forum for substantially all disputes, which could limit stockholders' ability to obtain a favorable judicial forum.

Future Outlook

Relmada Therapeutics expects to initiate Phase 3 programs for NDV-01 in two NMIBC indications and a Phase 2 pilot study for sepranolone in Prader-Willi Syndrome by mid-2026. Initial 3-month data from the NDV-01 high-risk NMIBC Phase 3 trial is anticipated by year-end 2026. The company believes its current cash and investments, bolstered by recent capital raises, will fund operations for at least 12 months from the report's issuance date.

Management Comments

• "We substantially redesigned our development programs following a comprehensive strategic review in late 2024 and early 2025."
• "We concluded in our review that the most promising path to create shareholder value was to lever our extensive drug development expertise and clinical operations capabilities by acquiring new development candidates, while terminating further work on esmethadone (d-methadone, dextromethadone or REL-1017)."
• "Management believes that the Company’s existing cash and cash equivalents and short-term investments will enable it to fund operating expenses and capital expenditure requirements for at least 12 months from the issuance of its audited consolidated financial statements."

Industry Context

StockSavvy.ai notes that Relmada's strategic pivot reflects a common trend in the biotechnology industry where companies re-evaluate their pipelines and divest non-performing assets to focus on more promising candidates. The acquisition of NDV-01, targeting NMIBC, positions Relmada in a competitive but high-need area, especially given the global BCG shortage since 2019, which could provide a market advantage. Sepranolone's focus on neurological disorders like Prader-Willi and Tourette Syndrome also taps into areas with significant unmet medical needs, aligning with broader industry efforts to address rare and complex conditions. The company's reliance on in-licensing and acquisitions for pipeline expansion is a recognized strategy for clinical-stage firms to diversify risk and accelerate development.

Comparison to Industry Standards

• NDV-01's Phase 2 complete response rates (e.g., 76% at 12 months in high-risk NMIBC) appear competitive with or better than BCG, which is a standard treatment facing global shortages. For example, studies on BCG have shown varying complete response rates, often in the 70-80% range, but with significant recurrence rates and side effects. The sustained delivery mechanism of NDV-01 could offer a differentiated profile compared to conventional intravesical therapies like single-agent gemcitabine or docetaxel, which require more frequent and cumbersome administration.
• Sepranolone's 28% tic reduction in Phase 2a for Tourette Syndrome, alongside improvements in quality of life and impairment, suggests a promising efficacy signal. This compares favorably to existing treatments for TS, where typical tic reductions can vary widely, and often come with significant CNS side effects. For instance, alpha-2 adrenergic agonists (e.g., guanfacine, clonidine) offer modest tic reduction, while dopamine receptor blockers (e.g., haloperidol, pimozide) can achieve higher reductions but are associated with severe side effects like tardive dyskinesia. Sepranolone's lack of CNS off-target effects could be a key differentiator.
• The company's accumulated deficit of nearly $700 million and continued net losses are typical for clinical-stage biotechnology companies that are pre-revenue and heavily investing in R&D, similar to peers like Soleno Therapeutics (developing for PWS) or CG Oncology (developing for bladder cancer) at comparable stages of development, which also report substantial R&D expenses and net losses.

Management Changes

Corporate Governance

Legal Proceedings

• The company is currently not aware of any legal proceedings or potential claims against it whose outcome would be likely, individually or in the aggregate, to have a material adverse effect on its business, financial condition, operating results, or cash flows.

Related Party Transactions

• Dr. Paolo Manfredi, co-inventor of REL-1017, and Dr. Marco Pappagallo, are among the scientists affiliated with Arbormentis, LLC, with whom the company had a psilocybin license agreement that was terminated on May 12, 2025.

Stakeholder Impact

• Shareholders: Strategic pivot and new drug candidates introduce both potential for future value creation and significant development risks. Recent capital raises provide funding but also result in dilution. Nasdaq compliance is positive for market access.
• Employees: Strategic shift led to termination of some programs, but new acquisitions and planned clinical trials indicate continued R&D focus and potential for growth in specialized personnel. Discretionary bonuses totaling $4.8 million were approved for certain executive officers and board members.
• Customers (future): Potential for new treatments for NMIBC, Prader-Willi Syndrome, Tourette Syndrome, and essential tremor, addressing unmet medical needs.
• Creditors: Improved liquidity from recent capital raises reduces immediate financial risk.
• Suppliers/Partners: Continued reliance on third-party contract manufacturers and CROs for development and manufacturing.

Next Steps

• Initiate Phase 3 trials for NDV-01 in high-risk, 2nd line BCG-unresponsive NMIBC by mid-2026.
• Initiate Phase 3 trials for NDV-01 in intermediate risk NMIBC in the adjuvant setting by mid-2026.
• Initiate a Phase 2 pilot study for sepranolone in Prader-Willi Syndrome by mid-2026.
• Anticipate initial 3-month data from the Phase 3 High-risk, 2nd line BCG-unresponsive NMIBC trial for NDV-01 by year-end 2026.
• Shareholders will vote on a management proposal to increase shares authorized for awards under the 2021 Plan by an additional 3,000,000 shares at the 2026 Annual Meeting.
• Management will evaluate the size and scope of any subsequent trials that will affect the timing of additional financings beyond the current 12-month runway.

Key Dates

Recommendation

Relmada Therapeutics has made a decisive strategic pivot, shedding unsuccessful programs and acquiring new, promising clinical-stage assets (NDV-01 and sepranolone) with positive early data and FDA alignment for Phase 3. The substantial capital raises significantly de-risk near-term liquidity concerns. However, the company remains pre-revenue with a large accumulated deficit, and the new drug candidates are still in development, facing inherent clinical and regulatory risks. While the strategic direction is positive, the long and uncertain path to commercialization warrants a 'hold' rating, advising investors to monitor clinical trial progress and further financial developments before making a more definitive investment decision.

Keywords

Biotechnology, Clinical-stage, NDV-01, Sepranolone, NMIBC, Prader-Willi Syndrome, Tourette Syndrome, Neurosteroid, Oncology, Neurological Disorders, Drug Development, SEC Filing, Annual Report, RLMD, Therapeutics, Clinical Trials, FDA Approval, Capital Raise, Financial Results, Corporate Governance