PDUFA Date Nearing for New PSVT Drug
Research Report

1. Doresa Banning wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor.
2.  This article does not constitute investment advice and is not a solicitation for any investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Each reader is encouraged to consult with his or her personal financial adviser and perform their own comprehensive investment research. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company. 
3. This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.

For additional disclosures, please click here.

Disclosures for H.C. Wainwright & Co., Milestone Pharmaceuticals Inc., March 17, 2025

This material is confidential and intended for use by Institutional Accounts as defined in FINRA Rule 4512(c). It may also be privileged or otherwise protected by work product immunity or other legal rules. If you have received it by mistake, please let us know by e-mail reply to unsubscribe@hcwresearch.com and delete it from your system; you may not copy this message or disclose its contents to anyone. The integrity and security of this message cannot be guaranteed on the Internet. H.C. WAINWRIGHT & CO, LLC RATING SYSTEM: H.C. Wainwright employs a three tier rating system for evaluating both the potential return and risk associated with owning common equity shares of rated firms. The expected return of any given equity is measured on a RELATIVE basis of other companies in the same sector. The price objective is calculated to estimate the potential movements in price that a given equity could reach provided certain targets are met over a defined time horizon. Price objectives are subject to external factors including industry events and market volatility.

Investment Banking Services include, but are not limited to, acting as a manager/co-manager in the underwriting or placement of securities, acting as financial advisor, and/or providing corporate finance or capital markets-related services to a company or one of its affiliates or subsidiaries within the past 12 months.

H.C. Wainwright & Co, LLC (the “Firm”) is a member of FINRA and SIPC and a registered U.S. Broker-Dealer. I, Patrick R. Trucchio, CFA , certify that 1) all of the views expressed in this report accurately reflect my personal views about any and all subject securities or issuers discussed; and 2) no part of my compensation was, is, or will be directly or indirectly related to the specific recommendation or views expressed in this research report; and 3) neither myself nor any members of my household is an officer, director or advisory board member of these companies. None of the research analysts or the research analyst’s household has a financial interest in the securities of Milestone Pharmaceuticals Inc. (including, without limitation, any option, right, warrant, future, long or short position). As of February 28, 2025 neither the Firm nor its affiliates beneficially own 1% or more of any class of common equity securities of Milestone Pharmaceuticals Inc.. Neither the research analyst nor the Firm knows or has reason to know of any other material conflict of interest at the time of publication of this research report.

The research analyst principally responsible for preparation of the report does not receive compensation that is based upon any specific investment banking services or transaction but is compensated based on factors including total revenue and profitability of the Firm, a substantial portion of which is derived from investment banking services. The firm or its affiliates received compensation from Milestone Pharmaceuticals Inc. for non-investment banking services in the previous 12 months. The Firm or its affiliates did receive compensation from Milestone Pharmaceuticals Inc. for investment banking services within twelve months before, and will seek compensation from the companies mentioned in this report for investment banking services within three months following publication of the research report. H.C. Wainwright & Co., LLC managed or co-managed a public offering of securities for Milestone Pharmaceuticals Inc. during the past 12 months. The Firm does not make a market in Milestone Pharmaceuticals Inc. as of the date of this research report. The securities of the company discussed in this report may be unsuitable for investors depending on their specific investment objectives and financial position. Past performance is no guarantee of future results. This report is offered for informational purposes only, and does not constitute an offer or solicitation to buy or sell any securities discussed herein in any jurisdiction where such would be prohibited. This research report is not intended to provide tax advice or to be used to provide tax advice to any person. Electronic versions of H.C. Wainwright & Co., LLC research reports are made available to all clients simultaneously. No part of this report may be reproduced in any form without the expressed permission of H.C. Wainwright & Co., LLC. Additional information available upon request. H.C. Wainwright & Co., LLC does not provide individually tailored investment advice in research reports. This research report is not intended to provide personal investment advice and it does not take into account the specific investment objectives, financial situation and the particular needs of any specific person. Investors should seek financial advice regarding the appropriateness of investing in financial instruments and implementing investment strategies discussed or recommended in this research report. H.C. Wainwright & Co., LLC’s and its affiliates’ salespeople, traders, and other professionals may provide oral or written market commentary or trading strategies that reflect opinions that are contrary to the opinions expressed in this research report. H.C. Wainwright & Co., LLC and its affiliates, officers, directors, and employees, excluding its analysts, will from time to time have long or short positions in, act as principal in, and buy or sell, the securities or derivatives (including options and warrants) thereof of covered companies referred to in this research report. The information contained herein is based on sources which we believe to be reliable but is not guaranteed by us as being accurate and does not purport to be a complete statement or summary of the available data on the company, industry or security discussed in the report. All opinions and estimates included in this report constitute the analyst’s judgment as of the date of this report and are subject to change without notice. Securities and other financial instruments discussed in this research report: may lose value; are not insured by the Federal Deposit Insurance Corporation; and are subject to investment risks, including possible loss of the principal amount invested.

Milestone Pharmaceuticals Inc.'s (MIST:NASDAQ) upcoming March 27, 2025, PDUFA (Prescription Drug User Fee Act) date would be "the start of a multibillion-dollar opportunity," with approval of Cardamyst (etripamil), an investigative at-home intranasal treatment for paroxysmal supraventricular tachycardia (PSVT), reported H.C. Wainwright & Co. Analyst Patrick Trucchio in a March 17 research note.

"If approved, we estimate peak annual revenues of US$500 million (US$500M)-plus for Cardamyst in PSVT," Trucchio wrote.

1,052% Implied Return

H.C. Wainwright & Co. has a US$25 per share price target on the Canadian biopharma, trading at the time of the report at about US$2.17 per share, noted Trucchio. Thus, the target implies a potential return of 1,052%.

Milestone remains a Buy.

Lower Patient, Healthcare Burden

Trucchio explained what PSVT is and how Cardamyst works to stop instances of it. A chronic cardiac arrhythmia, PSVT is characterized by the unpredictable and sudden onset of rapid heart rates, often above 150 beats per minute (150 bpm). It can cause palpitations, chest discomfort, dizziness, and fainting. An underappreciated, unmet medical need, PSVT affects about 2 million (2M) people in the U.S. With about 650,000–1,000,000 (650K–1M) patients seeking treatment each year, the financial burden on the healthcare system is an estimated US$5 billion (US$5B) annually.

Cardamyst is a fast-acting nasal spray that blocks calcium from entering the atrioventricular node, which in turn slows conduction and returns the heart rate to normal sinus rhythm, thereby stopping PSVT episodes. It is designed so that patients may dose themselves when symptoms come on, allowing for treatment any time, anywhere.

The current standard of care for PSVT includes intravenous therapies like adenosine, calcium channel blockers and beta blockers, requiring administration in an emergency department (ED) or hospital setting, and less often, cardiac catheter ablation.

"If approved, Cardamyst would be the first self-administered, rapid-acting therapy designed to terminate PSVT episodes outside a medical setting, offering patients a novel approach to managing their condition," Trucchio noted.

Cardamyst also could lower the cost to the healthcare system by reducing ED visits by and hospitalizations of PSVT patients.

Preparing for Commercialization

Trucchio pointed out that Milestone has been preparing for and continues to prepare for a commercial launch of Cardamyst. If the drug is approved, the biopharma should receive a US$75M synthetic royalty payment under an existing agreement with RTW Investments, an investment firm established in March 2023. The biopharma secured the payment to fund at least four quarters (into mid-2026) of a commercial launch of Cardamyst for PSVT in the U.S. Once the new drug hits the market,  Milestone intends to target community-based cardiologists and electrophysiologists initially, as they manage most PSVT patients.

Market research shows that cardiologists expect to prescribe Cardamyst to about 50% of their PSVT patients, translating to a potential target population of 500–800K patients in peak years. Further, patient use patterns in clinical trials showed that Cardamyst likely will be used for a median of three to five episodes a year, equating to a possible peak demand of 2.5–4M episodes treated annually.

"With US$75M in expected milestone payments upon approval and a commercial launch targeted for mid-2025, we see significant upside potential in shares of MIST, which we continue to view as undervalued relative to the long-term opportunity," Trucchio commented.

Pursuing Second Indication

The analyst highlighted that a Cardamyst approval on March 27 also would open the door to a "significantly larger opportunity in atrial fibrillation with rapid ventricular rate (AFib-RVR)," as Milestone is advancing the same self-administered, intranasal treatment in this indication, an area of significant unmet need, as well. With AFib-RVR, patients have acute episodes of high ventricular rates, causing symptoms such as palpitations, shortness of breath, chest pain, lightheadedness, and severe fatigue. Nearly 1.1 ED admissions annually are due to atrial fibrillation symptoms, and of these, about 60% are attributed to AFib-RVR. Available treatment options are limited.

There already are supportive Phase 2 data from the ReVeRA study that evaluated Cardamyst in patients presenting urgently with AFib-RVR. Specifically, the trial's primary endpoint was met with high statistical significance (p<0.0001); ventricular rates were reduced by an average of 29.91 bpm compared to placebo. Rate control lasted at least 150 minutes, and symptom relief was shown to be statistically significant.

Phase 3 Trial Greenlighted

Milestone has U.S. Food and Drug Administration approval to conduct a Phase 3 clinical trial of Cardamyst in AFib-RVR, reported Trucchio. The agency indicated that such a trial may be enough for approval via the supplemental new drug application pathway in light of the extensive existing safety data resulting from the PSVT clinical program. About 150 patients will be enrolled, each with at least one verified episode of AFib-RVR.

Trucchio wrote that with AFib-RVR, the projected addressable target market is 3–4M U.S. patients by 2030, according to H.C. Wainwright estimates. Given that AFib-RVR affects a broader population having more frequent symptoms than PSVT, the revenue potential for Cardamyst in AFib-RVR, if approved, could exceed US$1B. In both indications, the total potential is US$2B.

Events Worth Watching

The analyst presented three key upcoming events for Milestone. They are the PDUFA outcome on Cardamyst in PSVT on March 27, 2025. Another is commercial rollout of the drug in the middle of this year assuming its gets FDA approval.

The third, related to the AFib-RVR program, is patient enrollment for the Phase 3 trial, slated to start in Q2/25.

These near-term catalysts "can drive robust value creation for shareholders" in the near term, wrote Trucchio.

Company Data

Milestone has 53.3M shares outstanding. Its market cap is US$116M. Its 52-week range is US$1.12–US$2.75 per share.