Company Overview - Milestone Pharmaceuticals Inc. is a microcap biotech company founded in 2003, based in Montreal with a subsidiary in Charlotte, NC, employing over 30 staff members [1] Investment Philosophy - The investment philosophy emphasizes the importance of compounding, dividend reinvesting, and patient investing through various market conditions to achieve wealth creation [1] - The approach combines steady accumulation of high-quality assets with high-risk/high-reward opportunities, underappreciated turnaround plays, and transformative technologies [1] Academic Background - The individual has over 20 years of teaching experience at the college/university level and holds a PhD from Brunel University, indicating a strong academic foundation [1]

MONTREAL and CHARLOTTE, N.C., June 16, 2025 (GLOBE NEWSWIRE) -- Milestone® Pharmaceuticals Inc. (Nasdaq: MIST) today announced submission of its response to the U.S. Food and Drug Administration (FDA)'s Complete Response Letter (CRL) regarding its New Drug Application (NDA) for CARDAMYST™ (etripamil) nasal spray, a prescription medication in development for the conversion of acute episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. The response follows a Type A meeting rece ...

MONTREAL and CHARLOTTE, N.C., June 16, 2025 (GLOBE NEWSWIRE) -- Milestone Pharmaceuticals Inc. (Nasdaq: MIST) today announced submission of its response to the U.S. Food and Drug Administration (FDA)'s Complete Response Letter (CRL) regarding its New Drug Application (NDA) for CARDAMYST™ (etripamil) nasal spray, a prescription medication in development for the conversion of acute episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. The response follows a Type A meeting recen ...

Company Overview - Milestone Pharmaceuticals Inc. is a biopharmaceutical company focused on developing and commercializing innovative cardiovascular solutions aimed at improving the lives of patients with complex heart conditions [3] - The company's lead investigational product is etripamil, a novel calcium channel blocker nasal spray designed for self-administration by patients to treat symptomatic episodic attacks associated with PSVT and AFib-RVR [3] Upcoming Events - Amit Hasija, Chief Financial Officer, and Lorenz Muller, Chief Commercial Officer, will present at the Jefferies Healthcare Conference from June 3 to June 5, 2025, in New York [1] - A webcast of the presentation will be available on June 5 at 8:10 AM EDT, with a replay accessible for approximately 90 days on Milestone's website [2]

Core Viewpoint - Milestone Pharmaceuticals (MIST) has been upgraded to a Zacks Rank 2 (Buy), indicating a positive outlook on its earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on changes in earnings estimates, which are closely correlated with stock price movements, particularly due to institutional investors' reliance on these estimates for valuation [4][6]. - An increase in earnings estimates typically leads to higher fair value for a stock, prompting institutional investors to buy or sell, thus affecting stock prices [4]. Company Performance and Outlook - The recent upgrade for Milestone Pharmaceuticals suggests an improvement in its underlying business, which should lead to increased investor interest and a potential rise in stock price [5][10]. - The Zacks Consensus Estimate for Milestone Pharmaceuticals has increased by 25.4% over the past three months, although the company is expected to report a loss of -$0.75 per share for the fiscal year ending December 2025, reflecting a year-over-year change of -11.9% [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with only the top 20% receiving a 'Strong Buy' or 'Buy' rating, indicating superior earnings estimate revisions [9][10]. - Stocks rated Zacks Rank 1 have historically generated an average annual return of +25% since 1988, showcasing the effectiveness of the system in identifying potential investment opportunities [7].

[Q1 2025 Financial Results and Corporate Update](index=1&type=section&id=Milestone%20Pharmaceuticals%20Reports%20First%20Quarter%202025%20Financial%20Results%20and%20Provides%20Regulatory%20and%20Corporate%20Update) Milestone Pharmaceuticals reported increased Q1 2025 net loss and no revenue, prioritizing FDA's CARDAMYST CRL resolution and pausing other clinical programs [Program and Regulatory Updates](index=1&type=section&id=First%20Quarter%20and%20Recent%20Program%20Updates) Milestone focuses on resolving FDA's CARDAMYST CRL for PSVT, securing a new patent, and pausing the AFib-RVR study - Received a **Complete Response Letter (CRL)** from the FDA for CARDAMYST™ for PSVT, citing two key Chemistry, Manufacturing and Controls (CMC) issues[4](index=4&type=chunk) - The CRL issues include a request for additional information on nitrosamine impurities and a required re-inspection of a third-party manufacturing facility[4](index=4&type=chunk) - The company requested a **Type A meeting** with the FDA to discuss and resolve the CRL issues[2](index=2&type=chunk)[3](index=3&type=chunk) - A new U.S. patent (No. 12,257,224) was issued, potentially extending CARDAMYST intellectual property protection until **July 2042**[4](index=4&type=chunk) - The Phase 3 study for etripamil in AFib-RVR is paused to prioritize resources for resolving the PSVT indication CRL[5](index=5&type=chunk) [First Quarter 2025 Financial Results](index=2&type=section&id=First%20Quarter%202025%20Financial%20Results) Milestone Pharmaceuticals reported no Q1 2025 revenue, a **$20.8 million net loss**, and decreased cash due to higher operating expenses Q1 2025 Financial Highlights (in millions of US dollars) | Financial Metric | Q1 2025 (millions USD) | Q1 2024 (millions USD) | | :--- | :--- | :--- | | Revenue | $0.0 | $0.0 | | R&D Expense | $5.0 | $3.6 | | G&A Expense | $5.2 | $4.0 | | Commercial Expense | $10.4 | $2.9 | | **Net Loss** | **$20.8** | **$10.4** | | Cash, Cash Equivalents, and Short-term Investments | $56.0 | N/A | - The increase in commercial expense resulted from additional personnel, professional costs, and operational expenses for CARDAMYST launch preparation[8](index=8&type=chunk) - Due to the CRL, the company temporarily paused the ramping of operational expenditures related to the launch[8](index=8&type=chunk) [Financial Statements](index=4&type=section&id=Financial%20Statements) The company's financial statements show a decrease in total assets, an increase in liabilities, and a doubled net loss for Q1 2025 [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, total assets decreased to **$61.9 million**, liabilities increased, resulting in a **$6.1 million shareholders' deficit** Condensed Consolidated Balance Sheets (Unaudited, in thousands of US dollars) | | March 31, 2025 (thousands USD) | December 31, 2024 (thousands USD) | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $45,085 | $25,314 | | Short-term investments | $10,873 | $44,381 | | **Total current assets** | **$60,475** | **$73,926** | | **Total assets** | **$61,885** | **$75,499** | | **Liabilities & Equity** | | | | Total current liabilities | $12,963 | $8,126 | | Senior secured convertible notes | $54,287 | $53,352 | | **Total liabilities** | **$68,008** | **$62,352** | | **Total shareholders' (deficit) equity** | **($6,123)** | **$13,147** | [Condensed Consolidated Statements of Loss](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Loss) For Q1 2025, Milestone reported no revenue, with loss from operations doubling to **$20.5 million** and a net loss of **$20.8 million** Condensed Consolidated Statements of Loss (Unaudited, in thousands of US dollars, except per share data) | | Three months ended March 31, 2025 (thousands USD) | Three months ended March 31, 2024 (thousands USD) | | :--- | :--- | :--- | | Revenue | $— | $— | | Research and development | $4,978 | $3,639 | | General and administrative | $5,167 | $3,953 | | Commercial | $10,378 | $2,884 | | **Loss from operations** | **($20,523)** | **($10,476)** | | **Net loss** | **($20,761)** | **($10,354)** | | **Net loss per share, basic and diluted** | **($0.31)** | **($0.21)** | [About Etripamil](index=3&type=section&id=About%20Etripamil) Etripamil is Milestone's lead investigational calcium channel blocker nasal spray for self-administration in PSVT and AFib-RVR [About Etripamil](index=3&type=section&id=About%20Etripamil) Etripamil is Milestone's investigational calcium channel blocker nasal spray for self-administration in PSVT and AFib-RVR - Etripamil is a novel calcium channel blocker nasal spray developed for patient self-administration[10](index=10&type=chunk) - It is being developed for **paroxysmal supraventricular tachycardia (PSVT)** and **atrial fibrillation with rapid ventricular rate (AFib-RVR)**[10](index=10&type=chunk) - The therapy aims to provide on-demand care and patient self-management, potentially bypassing immediate medical oversight[10](index=10&type=chunk)

Core Viewpoint - Milestone Pharmaceuticals is actively addressing the Chemistry, Manufacturing, and Controls (CMC) issues raised by the FDA regarding its lead product CARDAMYST for the treatment of paroxysmal supraventricular tachycardia (PSVT) and is preparing for a Type A meeting with the FDA to resolve these issues [1][2][6]. Financial Results - As of March 31, 2025, the company reported cash, cash equivalents, and short-term investments totaling $56.0 million, a decrease from $69.7 million as of December 31, 2024 [11]. - The company reported no revenue for the first quarter of 2025, consistent with the same period in 2024 [11]. - Research and development expenses increased to $5.0 million in Q1 2025 from $3.6 million in Q1 2024, primarily due to higher consulting costs [11]. - General and administrative expenses rose to $5.2 million in Q1 2025 from $4.0 million in the prior year, driven by increased outside service costs [11]. - Commercial expenses surged to $10.4 million in Q1 2025 from $2.9 million in Q1 2024, reflecting preparations for the launch of CARDAMYST [11]. - The net loss for the first quarter of 2025 was $20.8 million, compared to a net loss of $10.4 million in the same period last year [11]. Product Development and Regulatory Updates - The FDA issued a Complete Response Letter (CRL) for CARDAMYST in March 2025, citing two key CMC issues: the need for additional information on nitrosamine impurities and a new facility inspection to ensure compliance with Good Manufacturing Practices (GMP) [6]. - The Phase 3 study protocol for etripamil in patients with atrial fibrillation with rapid ventricular rate (AFib-RVR) has been finalized, but enrollment is paused to focus on resolving the CRL for PSVT [4]. - A new method of use patent for etripamil nasal spray was issued, potentially extending intellectual property protection until July 2042 [6]. - CARDAMYST was recognized in an independent survey as a new drug expected to significantly impact patient health, with 40% of respondents selecting it [6]. Company Overview - Milestone Pharmaceuticals is focused on developing innovative cardiovascular solutions, with etripamil as its lead investigational product designed for self-administration in treating symptomatic episodes of PSVT and AFib-RVR [9][8].

[PART I. FINANCIAL INFORMATION](index=7&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Financial Statements (Unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The company reported a significant net loss in Q1 2025, driven by higher operating expenses, leading to a shareholders' deficit [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased while liabilities increased by March 31, 2025, leading to a shareholders' deficit from prior equity Condensed Consolidated Balance Sheet Highlights (in thousands of US dollars) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $45,085 | $25,314 | | Short-term investments | $10,873 | $44,381 | | **Total Assets** | **$61,885** | **$75,499** | | Total current liabilities | $12,963 | $8,126 | | Senior secured convertible notes | $54,287 | $53,352 | | **Total Liabilities** | **$68,008** | **$62,352** | | **Total shareholders' (deficit) equity** | **($6,123)** | **$13,147** | [Condensed Consolidated Statements of Loss](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Loss) Net loss doubled in Q1 2025, primarily driven by a significant increase in operating expenses, especially commercial costs Condensed Consolidated Statements of Loss (in thousands of US dollars) | Category | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Revenue | $— | $— | | Research and development, net | $4,978 | $3,639 | | General and administrative | $5,167 | $3,953 | | Commercial | $10,378 | $2,884 | | **Loss from operations** | **($20,523)** | **($10,476)** | | **Net loss** | **($20,761)** | **($10,354)** | | Net loss per share, basic and diluted | ($0.31) | ($0.21) | [Condensed Consolidated Statements of Shareholders' (Deficit) Equity](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Shareholders%27%20%28Deficit%29%20Equity) Shareholders' equity transitioned to a deficit by March 31, 2025, primarily due to the net loss incurred during the quarter - The company's total shareholders' equity decreased from **$13,147 thousand** at the end of 2024 to a deficit of **$(6,123) thousand** as of March 31, 2025[20](index=20&type=chunk) - The primary driver for the decrease in equity was the net loss of **$20,761 thousand** for the three-month period ended March 31, 2025[20](index=20&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities was offset by investing activities, resulting in a net increase in cash and cash equivalents for Q1 2025 Cash Flow Summary (in thousands of US dollars) | Activity | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($13,952) | ($8,934) | | Net cash provided (used in) by investing activities | $33,583 | ($27,014) | | Cash provided by financing activities | $140 | $32,319 | | **Net increase (decrease) in cash** | **$19,771** | **($3,629)** | | **Cash and cash equivalents – End of period** | **$45,085** | **$10,131** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Notes detail the company's lead product etripamil, its cash position deemed sufficient for 12 months, and key financial agreements - The company's lead product candidate is etripamil, a nasal spray being developed to treat paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation, and other cardiovascular indications[24](index=24&type=chunk) - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments of **$56.0 million** and an accumulated deficit of **$388.3 million** Management believes these funds are sufficient to support operations for at least the next 12 months[36](index=36&type=chunk)[37](index=37&type=chunk) - The company has a Royalty Purchase Agreement with RTW, which agreed to purchase royalty rights for **$75.0 million** following FDA approval of etripamil on or prior to September 30, 2025[66](index=66&type=chunk) - In March 2023, the company issued **$50.0 million** in 6.0% Convertible Senior Notes due 2029 to RTW Investments As of March 31, 2025, the net carrying amount of the notes was **$54.3 million**[40](index=40&type=chunk)[41](index=41&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=28&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company received an FDA Complete Response Letter for CARDAMYST, impacting launch plans and increasing Q1 2025 operating expenses - In March 2025, the company received a Complete Response Letter (CRL) from the FDA for its New Drug Application (NDA) for CARDAMYST (etripamil) for PSVT[77](index=77&type=chunk)[90](index=90&type=chunk) - The CRL cited two key CMC issues: a request for more information on nitrosamine impurities and the need for an inspection at a manufacturing facility The FDA did not raise concerns about clinical safety or efficacy[90](index=90&type=chunk)[181](index=181&type=chunk) - The company has paused the ramp-up of operational expenditures related to the launch of CARDAMYST following the CRL but maintains the capability to launch quickly upon approval[128](index=128&type=chunk) - Management expects existing cash and investments (**$56.0 million** as of March 31, 2025) to be sufficient to fund operations for at least the next 12 months[133](index=133&type=chunk)[137](index=137&type=chunk) [Results of Operations](index=42&type=section&id=Results%20of%20Operations) Total operating expenses nearly doubled in Q1 2025, driven by increased commercial expenses, significantly widening the net loss Comparison of Results of Operations (in thousands) | Category | Three months ended March 31, 2025 | Three months ended March 31, 2024 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development, net | $4,978 | $3,639 | $1,339 | 36.8% | | General and administrative | $5,167 | $3,953 | $1,214 | 30.7% | | Commercial | $10,378 | $2,884 | $7,494 | 259.9% | | **Total operating expenses** | **$20,523** | **$10,476** | **$10,047** | **95.9%** | | **Net loss** | **($20,761)** | **($10,354)** | **($10,407)** | **100.5%** | - The increase in R&D expenses was primarily due to higher consulting costs in drug manufacturing and regulatory areas[125](index=125&type=chunk) - The increase in commercial expenses resulted from additional personnel, professional costs, and other operational expenses in preparation for the launch of CARDAMYST[128](index=128&type=chunk) [Liquidity and Capital Resources](index=45&type=section&id=Liquidity%20and%20Capital%20Resources) The company's liquidity includes cash and investments deemed sufficient for 12 months, supplemented by prior offerings and contingent future funding - The company had cash, cash equivalents and short-term investments of **$56.0 million** as of March 31, 2025[133](index=133&type=chunk) - In February 2024, the company received net proceeds of **$31.9 million** from an underwritten public offering of common shares and pre-funded warrants[134](index=134&type=chunk)[135](index=135&type=chunk) - A contingent future source of funding includes a **$75.0 million** payment from RTW upon FDA approval of etripamil on or before September 30, 2025[138](index=138&type=chunk)[140](index=140&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=53&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risks are interest rate fluctuations on its investment portfolio and foreign currency exposure to the Canadian dollar - The company is exposed to interest rate risk on its **$56.0 million** portfolio of cash, cash equivalents, and short-term investments[161](index=161&type=chunk) - The company is subject to foreign exchange risk from transactions in Canadian dollars, with a net monetary exposure of **$3.6 million** as of March 31, 2025[162](index=162&type=chunk) [Controls and Procedures](index=53&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes in internal control - Management concluded that as of March 31, 2025, the company's disclosure controls and procedures were effective at a reasonable assurance level[165](index=165&type=chunk)[166](index=166&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, the internal controls[167](index=167&type=chunk) [PART II. OTHER INFORMATION](index=55&type=section&id=PART%20II.OTHER%20INFORMATION) [Legal Proceedings](index=55&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings and is unaware of any pending or threatened actions - The company is not currently a party to any material legal proceedings[169](index=169&type=chunk) [Risk Factors](index=55&type=section&id=Item%201A.%20Risk%20Factors) Material changes to risk factors include international trade policy impacts on the supply chain and updated risks concerning etripamil's FDA CRL - A new risk factor was added concerning international trade policies, including tariffs and sanctions, which could adversely affect the business, particularly as some active pharmaceutical ingredients (APIs) for etripamil are manufactured in China[171](index=171&type=chunk)[173](index=173&type=chunk)[175](index=175&type=chunk) - The risk related to dependency on etripamil has been updated to include the March 2025 CRL from the FDA It highlights the uncertainty of satisfactorily addressing the FDA's concerns regarding nitrosamine impurities and a required facility inspection[179](index=179&type=chunk)[181](index=181&type=chunk) - Disruptions at the FDA and other government agencies due to funding shortages, layoffs, or other factors could negatively impact the review and approval timelines for product candidates[185](index=185&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=61&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) Not applicable for this reporting period - Not applicable[186](index=186&type=chunk) [Other Information](index=62&type=section&id=Item%205.%20Other%20Information) No directors or executive officers adopted, modified, or terminated Rule 10b5-1 trading arrangements during the quarter - No directors or executive officers adopted, modified, or terminated a Rule 10b5-1 trading arrangement during the quarter ended March 31, 2025[187](index=187&type=chunk) [Exhibits](index=62&type=section&id=Item%206.%20Exhibits) The report lists several exhibits filed with the Form 10-Q, including the Amended and Restated Open Market Sale Agreement and required certifications - Key exhibits filed include the Amended and Restated Open Market Sale Agreement, CEO/CFO certifications (Sections 302 and 906), and XBRL data files[188](index=188&type=chunk)

Core Viewpoint - Milestone Pharmaceuticals (MIST) received a Complete Response Letter (CRL) from the FDA for its New Drug Application (NDA) for CARDAMYST (etripamil) nasal spray, intended for treating paroxysmal supraventricular tachycardia (PSVT) [1][2] Regulatory Issues - The CRL does not raise concerns about the clinical safety or efficacy of etripamil but highlights two Chemistry, Manufacturing, and Controls (CMC) issues that need to be resolved before approval [2][11] - The first issue involves nitrosamine impurities, with the FDA requesting additional data based on new draft guidance issued after MIST's NDA submission [3] - The second issue relates to a facility inspection involved in the drug's release testing, which underwent a change in ownership during the NDA review, necessitating a compliance evaluation [4] Market Reaction - Following the CRL issuance, MIST's shares fell by 66.2%, with a year-to-date loss of 67.8%, contrasting with the industry's growth of 2.2% [2][7] - Analysts remain cautiously optimistic about the drug's prospects, suggesting a potential commercial launch in 2026, delayed from the original expectation of mid-2025 [8][11] Company Response and Financial Position - MIST has expressed its intent to request a Type A meeting with the FDA to clarify the path forward and is committed to addressing the outstanding issues [9] - As of December 31, 2024, MIST reported $69.7 million in cash and short-term investments, providing a runway for ongoing development efforts, although additional capital may be needed if delays continue [10] Investor Perspective - The CRL is viewed as a temporary obstacle rather than a fundamental rejection of CARDAMYST's therapeutic potential, with the absence of clinical concerns being a positive indicator for eventual approval [11]

Core Viewpoint - Milestone Pharmaceuticals received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) for CARDAMYST™ (etripamil) nasal spray, which is intended for the treatment of acute episodes of PSVT in adults, with no clinical safety or efficacy issues raised by the FDA [1][2] Company Overview - Milestone Pharmaceuticals Inc. is a biopharmaceutical company focused on developing innovative cardiovascular solutions to improve the lives of patients with complex heart conditions [4] - The company's lead investigational product, etripamil, is a novel calcium channel blocker nasal spray designed for self-administration to treat symptomatic episodes associated with PSVT and AFib-RVR [3][4] Financial Position - As of December 31, 2024, Milestone Pharmaceuticals had $69.7 million in cash, cash equivalents, and short-term investments [1][2] Regulatory Feedback - The FDA's CRL highlighted two key Chemistry, Manufacturing and Controls (CMC) issues that need to be addressed, but did not raise concerns regarding the clinical safety or efficacy of etripamil [2][6] - The company plans to request a Type A meeting with the FDA to discuss the issues raised in the CRL and is committed to addressing these concerns for a potential resubmission [2][6] Product Development - Etripamil is designed as a self-administered rapid response therapy, allowing patients to manage their condition without immediate medical oversight [3] - The product has undergone a robust clinical trial program, including a completed Phase 3 clinical-stage program for PSVT and a Phase 2 trial for AFib-RVR [3]