10-Q: Milestone Pharma Q3 2025: Etripamil NDA Progress Amid Rising Losses

Milestone Pharmaceuticals reports increased net losses in Q3 2025, driven by commercialization preparations, while advancing etripamil's FDA approval pathway and clinical development for cardiovascular indications.

Summary

• Net loss for the three months ended September 30, 2025, was $11.9 million, an increase from $9.4 million in the same period in 2024.
• Net loss for the nine months ended September 30, 2025, was $45.6 million, up from $29.2 million in the nine months ended September 30, 2024.
• The accumulated deficit reached $413.2 million as of September 30, 2025.
• Cash, cash equivalents, and short-term investments totaled $82.6 million as of September 30, 2025, which is expected to fund operations for at least the next 12 months.
• The FDA accepted the response to the Complete Response Letter (CRL) for CARDAMYST (etripamil) nasal spray for the treatment of paroxysmal supraventricular tachycardia (PSVT), with a new Prescription Drug User Fee Act (PDUFA) target date of December 13, 2025.
• Enrollment for the Phase 3 atrial fibrillation with rapid ventricular rate (AFib-RVR) study is delayed due to the CRL received on the PSVT NDA.
• A public offering in July 2025 generated net proceeds of $48.6 million from the issuance of common shares, pre-funded warrants, and common warrants.
• The marketing approval deadline for etripamil under the Royalty Purchase Agreement with RTW Investments LP was extended to December 31, 2025, for a potential $75.0 million payment upon FDA approval.

Sentiment

Score: 4

Explanation: While the company secured significant financing and made progress on clinical trials and FDA response acceptance, the increased net losses, continued lack of revenue, and the regulatory delay (CRL and subsequent AFib-RVR study delay) indicate ongoing challenges and uncertainty for a pre-commercial stage biopharmaceutical company.

Positives

• The FDA accepted the response to the Complete Response Letter (CRL) for CARDAMYST (etripamil) nasal spray for PSVT.
• A new PDUFA target date of December 13, 2025, has been assigned for etripamil's NDA for PSVT.
• Positive Phase 3 NODE-303 study data for etripamil in PSVT demonstrated 60.0% conversion to sinus rhythm by 30 minutes and 69.9% by 60 minutes, with a median time-to-conversion of 17 minutes.
• Licensing partner Corxel reported positive topline data from the Phase 3 (JX02002) clinical trial of etripamil in PSVT in China, showing 40.5% conversion within 30 minutes compared to 15.9% for placebo.
• Positive Phase 2 ReVeRA study data for etripamil in AFib-RVR showed significant and rapid ventricular rate reduction (29.91 bpm vs. placebo) and improved patient satisfaction.
• FDA guidance confirmed a supplemental new drug application (sNDA) pathway for AFib-RVR, potentially requiring only a single pivotal efficacy study if PSVT is approved.
• Available liquidity of $82.6 million in cash and short-term investments is expected to be sufficient to support operations for at least the next 12 months.
• A public offering in July 2025 successfully raised $48.6 million in net proceeds.
• A potential future funding of $75.0 million from RTW Investments LP is contingent upon FDA approval of etripamil by December 31, 2025.

Negatives

• Net loss increased to $11.9 million for the three months ended September 30, 2025, from $9.4 million in the prior year.
• Net loss increased to $45.6 million for the nine months ended September 30, 2025, from $29.2 million in the prior year.
• The accumulated deficit reached $413.2 million as of September 30, 2025, indicating continued operating losses.
• No revenue was generated for the three or nine months ended September 30, 2025, or 2024.
• Commercial expenses significantly increased by 142.1% for Q3 2025 and 204.8% for YTD 2025, reflecting high pre-commercialization costs without product sales.
• Enrollment for the Phase 3 AFib-RVR study is delayed due to the CRL received on the NDA for etripamil in PSVT.
• Interest income decreased due to decreasing interest rates and less assets invested in 2025 compared to 2024.

Risks

• International trade policies, including tariffs, sanctions, and trade barriers, may adversely affect business, financial condition, and operations, particularly due to reliance on third-party suppliers outside the U.S. (e.g., active pharmaceutical ingredients from China).
• Future success is substantially dependent on the successful clinical development and regulatory approval of etripamil, which is the only product candidate.
• There is no assurance that the FDA will approve the NDA for etripamil, and the time required to obtain approval is unpredictable.
• Disruptions at the FDA and other government agencies (e.g., layoffs, funding shortages, proposed reductions in force) could negatively impact the business by slowing product review and approval times.
• Healthcare legislative reform measures (e.g., PPACA, OBBBA, IRA, Loper Bright decision) could negatively impact the business by reducing healthcare costs, limiting drug pricing, or increasing regulatory challenges.
• Future changes to tax laws (e.g., OBBBA restoring R&E deductibility for domestic but not foreign expenditures) could materially adversely affect the company and reduce net returns to shareholders.
• Inability to secure adequate additional funding could force reductions in spending, extended payment terms, asset liquidation, or suspension/curtailment of planned programs.
• Clinical and preclinical development timelines, probability of success, and development costs are highly uncertain and can differ materially from expectations.
• Reliance on third parties for manufacturing product candidates for clinical testing and commercialization poses supply chain risks.

Future Outlook

Milestone Pharmaceuticals expects to continue incurring significant operating losses for the foreseeable future, with a substantial portion of capital focused on completing development, obtaining regulatory approval, and preparing for potential commercialization of etripamil for PSVT, AFib-RVR, and other cardiovascular indications. Commercial expenses are anticipated to increase significantly upon FDA approval and product launch. The company plans to establish a direct sales force in the U.S. and consider collaborations for international commercialization. The company also expects its available liquidity to be sufficient to support operations for at least the next 12 months.

Management Comments

• Management has evaluated the Company’s operating plan and future cash flow requirements against its existing cash and cash equivalents and short-term investments and expects its available liquidity will be sufficient to support its operations for at least the next 12 months from the date of issuance of these unaudited interim condensed consolidated financial statements.
• Milestone temporarily paused the ramping up of operational expenditures related to launch. During this period, Milestone has focused on compliantly engaging healthcare providers and payors in profiling and disease state discussions with the goal of optimizing the launch plan for CARDAMYST. Milestone continues to maintain the capability of launching quickly following the potential approval of CARDAMYST by the FDA.

Industry Context

Milestone Pharmaceuticals operates in the cardiovascular medicines market, targeting paroxysmal supraventricular tachycardia (PSVT) and atrial fibrillation with rapid ventricular rate (AFib-RVR). These conditions represent large and under-recognized markets, with PSVT having seen no pharmaceutical innovation for over 30 years. Current treatments for PSVT are often burdensome, requiring intravenous administration in emergency departments. Etripamil, a rapid-onset nasal spray, aims to provide a patient-administered solution, potentially reducing emergency department visits and associated healthcare costs. The prevalence of AFib is expected to grow to over 12 million by 2030, indicating a substantial and growing market for AFib-RVR treatments. The company's strategy aligns with a broader healthcare trend towards patient-centered care and cost-effective, time-efficient treatment options.

Comparison to Industry Standards

• Etripamil aims to address a market (PSVT) that has experienced 'no pharmaceutical innovation in the treatment of PSVT for more than 30 years,' positioning it as a novel and potentially disruptive solution.
• Current PSVT treatments (adenosine, verapamil, diltiazem) require intravenous administration under medical supervision, typically in an emergency department, whereas etripamil is designed for self-administration at home, offering a significant convenience and accessibility advantage over existing standards.
• Oral drugs sometimes used for 'pill in the pocket' for PSVT are not proven effective or safe and are not approved for this use, highlighting etripamil's potential to fill a regulatory and efficacy gap in at-home treatment.
• For AFib-RVR, etripamil's rapid onset and short duration of action could serve as a 'bridge to the longer onset times of acute oral agents' (which can take 30-90 minutes to act), potentially moving acute treatment out of burdensome and costly emergency departments.
• Market research indicates cardiologists would prescribe CARDAMYST to approximately 50% of PSVT patients (500,000-800,000 patients) and 67% of AFib-RVR patients, suggesting strong physician interest and a high potential for market adoption compared to existing options.

Corporate Governance

Legal Proceedings

• Not currently a party to any material legal proceedings, and not aware of any pending or threatened legal proceeding that could have an adverse effect on the business, operating results, or financial condition.

Related Party Transactions

• On March 27, 2023, the company entered into a Note Purchase Agreement with RTW Investments LP and its affiliates, issuing $50.0 million principal amount of 6.0% Convertible Senior Notes due 2029.
• On March 27, 2023, the company entered into a Royalty Purchase Agreement with RTW, which was amended on July 10, 2025, for RTW to purchase royalty rights for $75.0 million upon FDA approval of etripamil by December 31, 2025.
• The License and Collaboration Agreement with Corxel Pharmaceuticals (formerly Ji Xing Pharmaceuticals Limited), dated May 15, 2021, is with an entity affiliated with RTW Investments, LP.

Stakeholder Impact

• Shareholders face potential for dilution from recent and future equity raises, but also significant value creation if etripamil receives FDA approval and is successfully commercialized. Continued operating losses and accumulated deficit represent ongoing financial risk.
• Employees benefit from equity incentive plans (stock options, ESPP, RSUs) as part of their compensation and incentives. Potential for increased hiring exists if etripamil is approved and commercialized.
• Patients with PSVT and AFib-RVR could gain access to a novel, self-administered treatment option (etripamil) that may significantly improve their quality of life and reduce the need for emergency department visits.
• Healthcare providers could benefit from a new, convenient treatment option for PSVT and AFib-RVR, addressing a long-standing unmet medical need in cardiovascular care.
• Payors (insurance companies, government programs) could see reduced healthcare expenditures by shifting acute care from costly emergency departments to more efficient at-home self-administration.
• Creditors, specifically RTW Investments LP, hold senior secured convertible notes and have a royalty purchase agreement contingent on FDA approval, indicating a vested financial interest in etripamil's successful development and commercialization.

Next Steps

• Await FDA decision on CARDAMYST (etripamil) nasal spray for PSVT by the PDUFA target date of December 13, 2025.
• Advance etripamil into a Phase 3 program for atrial fibrillation with rapid ventricular rate (AFib-RVR) once the PSVT NDA is resolved.
• Seek marketing approvals for etripamil for the treatment of PSVT, AFib-RVR, and other cardiovascular indications.
• Establish sales, marketing, manufacturing, and distribution capabilities to commercialize etripamil if approved.
• Continue ongoing and planned development of etripamil, including potential Phase 4 clinical trials for PSVT.
• Build a portfolio of product candidates through development, acquisition, or in-license.
• Initiate preclinical studies and clinical trials for etripamil for additional indications or future product candidates.
• Maintain, protect, and expand the intellectual property portfolio.

Key Dates

Recommendation

Milestone Pharmaceuticals is at a critical juncture with a PDUFA date for etripamil for PSVT in December 2025, which could unlock significant value and a $75 million royalty payment. The company has secured sufficient funding for the next 12 months and has positive clinical data for both PSVT and AFib-RVR. However, the increased net losses, the prior Complete Response Letter (CRL), and the delay in the AFib-RVR program highlight the inherent risks of a pre-revenue biopharmaceutical company. The stock is likely to be highly volatile around the PDUFA date. A 'Hold' recommendation acknowledges the significant upside potential from approval while recognizing the substantial risks and current lack of profitability. Investors should await the FDA decision before making further investment decisions.

Keywords

etripamil, CARDAMYST, PSVT, paroxysmal supraventricular tachycardia, AFib-RVR, atrial fibrillation, rapid ventricular rate, nasal spray, calcium channel blocker, FDA, NDA, PDUFA, clinical trials, biopharmaceutical, cardiovascular, Milestone Pharmaceuticals