[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]

Group 1 - The focus is on small and microcap biopharmaceutical companies where mispricing is most intense and institutional attention is minimal [1] - These companies are often in clinical stages and experience significant market movements due to retail ownership and analyst coverage from investment banks with vested interests [1] - The research team consists mainly of high-ranking Life Sciences students from top UK universities, aiming to improve the accuracy of clinical stage equity research [1] Group 2 - Excidium Research maintains a long position in Milestone Pharmaceuticals, indicating a potential bias in their analysis [2] - The report emphasizes the importance of conducting independent due diligence and considering multiple perspectives before making investment decisions [2] - Investing in biotechnology and pharmaceutical companies carries significant risks, including clinical trial failures and regulatory challenges [2]

Core Insights - Milestone Pharmaceuticals Inc. is set to present findings on etripamil's effectiveness in treating Paroxysmal Supraventricular Tachycardia (PSVT) at the American College of Cardiology annual meeting [1][2] - The data suggests that etripamil can convert multiple PSVT episodes to restore normal sinus rhythm, potentially enhancing patient quality of life [2][3] Company Overview - Milestone Pharmaceuticals focuses on developing innovative cardiovascular solutions aimed at improving the lives of patients with complex heart conditions [3] - The company's lead product, etripamil, is a novel calcium channel blocker nasal spray designed for self-administration by patients experiencing symptomatic episodic attacks associated with PSVT and AFib-RVR [3] Presentation Details - The moderated poster presentation titled "Consistency and Predictiveness of Conversion Among Multiple Episodes of Paroxysmal Supraventricular Tachycardia (PSVT) Treated with Etripamil: Outcomes from the NODE-303 trial" will be presented by Dr. James Ip [2] - The presentation is scheduled for March 30, 2025, from 11:42 to 11:49 AM Central Time at the ACC25 event in Chicago [2]

Financial Performance - Milestone Pharmaceuticals reported a net loss of $41.5 million or $0.67 per share for the full year ended December 31, 2024, compared to a net loss of $59.7 million or $1.39 per share for the prior year[6]. - The company recorded no revenue for the fourth quarter or full year 2024, compared to $1.0 million in 2023, which was related to a milestone payment from Corxel Pharmaceuticals[5]. - General and administrative expenses for the full year 2024 were $16.7 million, compared to $15.9 million in 2023, driven by increased outside service costs[5]. - Commercial expenses for the full year 2024 were $11.0 million, down from $15.1 million in the prior year, reflecting cost reductions following the resolution of a Refusal to File letter from the FDA[5]. Cash and Investments - As of December 31, 2024, Milestone had cash, cash equivalents, and short-term investments totaling $69.7 million, an increase from $66.0 million on December 31, 2023[5]. - Total assets as of December 31, 2024, were $75.5 million, slightly up from $75.2 million on December 31, 2023[12]. Research and Development - Research and development expenses decreased to $14.4 million for the full year 2024, down from $31.1 million in 2023, primarily due to lower clinical expenses following the completion of phase 3 studies[5]. - Milestone is preparing for the potential FDA approval of CARDAMYST™ (etripamil) nasal spray for Paroxysmal Supraventricular Tachycardia (PSVT), with a PDUFA review goal date set for March 27, 2025[1]. - A new Method of Use patent for etripamil nasal spray has been allowed, potentially extending intellectual property protection until July 2042[2]. - The company plans to initiate a Phase 3 trial for etripamil in AFib-RVR in 2025, with the protocol finalized and study start-up commenced[4].

Core Insights - Milestone Pharmaceuticals is awaiting FDA approval for CARDAMYST™ (etripamil) nasal spray for the treatment of Paroxysmal Supraventricular Tachycardia (PSVT), with a PDUFA review goal date set for March 27, 2025, and a proposed launch targeted for mid-2025 [1][5] - The company is well-capitalized to commercialize CARDAMYST upon approval, having secured resources for its launch preparations [2][5] - Milestone is also on track to initiate a Phase 3 trial for etripamil in patients with AFib-RVR in 2025, with the study protocol finalized [3] Financial Performance - As of December 31, 2024, Milestone reported cash, cash equivalents, and short-term investments totaling $69.7 million, an increase from $66.0 million at the end of 2023 [4] - The company recorded no revenue for the fourth quarter or full year ended December 31, 2024, compared to $1.0 million in 2023, which was related to a milestone payment [10] - Research and development expenses for Q4 2024 were $3.9 million, down from $5.5 million in the prior year, while full-year expenses were $14.4 million compared to $31.1 million in 2023 [10] - The net loss for Q4 2024 was $12.4 million or $0.19 per share, compared to a net loss of $13.6 million or $0.32 per share for the same period in 2023 [10] Regulatory and Intellectual Property Updates - The New Drug Application (NDA) for CARDAMYST is currently under review by the FDA, with acceptance received in May 2024 [5] - A Notice of Allowance was received from the U.S. Patent and Trademark Office for a new Method of Use patent for etripamil nasal spray, potentially extending intellectual property protection until July 2042 [5] Product Overview - Etripamil is a novel calcium channel blocker nasal spray designed for self-administration to treat symptomatic episodes of PSVT and AFib-RVR, allowing patients to manage their condition without immediate medical oversight [7][8] - The product has undergone a robust clinical trial program, including a completed Phase 3 study for PSVT and a Phase 2 trial for AFib-RVR [7]

Financial Performance - The company incurred a net loss of $41.5 million for the year ended December 31, 2024, compared to a net loss of $59.7 million for 2023, resulting in an accumulated deficit of $367.5 million as of December 31, 2024[162]. - The company expects its existing cash and cash equivalents will be sufficient to fund operations for at least the next 12 months, but substantial additional funding will be required for ongoing operations and planned activities[172]. - Economic uncertainty, including inflation and geopolitical tensions, may adversely affect the company's results of operations and access to capital[178]. - The company may need to raise additional capital through equity or debt financing, which could dilute shareholder ownership and restrict operational flexibility[179]. Product Development and Regulatory Approval - Etripamil is the only product candidate currently under development, with no regulatory approval obtained yet[184]. - The FDA accepted the NDA for etripamil in May 2024 after a resubmission following a Refusal to File letter in December 2023[189]. - The lengthy and unpredictable approval process may significantly harm the company's business and financial condition if regulatory approvals are not obtained[186]. - The FDA may require additional clinical trials or impose restrictions on marketing approvals, which could adversely affect the company's prospects[207]. - The company plans to conduct Phase 3 development for etripamil in treating AFib-RVR, anticipating patient enrollment in the first half of 2025[192]. - The establishment of sales and marketing capabilities is critical for the successful commercialization of etripamil, but this process is expected to be expensive and time-consuming[224]. Clinical Trials and Safety Concerns - The NODE-301 trial of etripamil for PSVT did not meet its primary endpoint, highlighting the uncertainty in achieving commercial success for etripamil and future product candidates[174]. - Clinical trials are expensive and time-consuming, with the possibility of delays impacting the commercialization timeline of product candidates[206]. - Three serious adverse events were reported in the Phase 2 clinical trial, which were considered possibly related to etripamil, highlighting potential safety concerns[214]. - In the Phase 2 clinical trial of etripamil for PSVT, only 104 out of 199 enrolled patients completed the trials, with 70 patients unable to induce or sustain episodes of SVT during the trial period[211]. Market and Competitive Landscape - The company anticipates that sales of etripamil will generate substantially all of its revenues for the foreseeable future, making market acceptance vital for business sustainability[229]. - The company faces substantial competition from major pharmaceutical and biotechnology companies, which may hinder its ability to develop and commercialize drugs successfully[232]. - Coverage and adequate reimbursement for etripamil and future candidates may not be available, impacting market acceptance and sales[243]. - The market opportunities for etripamil and future product candidates may be smaller than estimated, potentially adversely affecting the business[231]. Intellectual Property and Patent Risks - The patent protection for etripamil is critical, and any failure to maintain or obtain sufficient patent rights could allow competitors to develop similar products[302]. - The company may need to defend its patents against challenges, which could result in loss of exclusivity or patent claims being invalidated, limiting its ability to prevent competitors from using similar technologies[309]. - Changes in patent laws may affect the scope and enforceability of the company's patent rights, creating uncertainty in the commercial value of its intellectual property[304]. - The company may face claims asserting that its employees have wrongfully used or disclosed trade secrets, which could result in litigation and substantial costs[324]. Regulatory Compliance and Legal Risks - Compliance with federal and state healthcare laws is critical, as non-compliance could lead to substantial penalties and affect business operations[263]. - The company must navigate complex healthcare regulations that vary by state and country, complicating compliance efforts[271]. - The company is dependent on third-party manufacturers for the production of clinical supplies, which must comply with FDA regulations[283]. - Ongoing regulatory oversight will apply to etripamil and future candidates even after obtaining approval, which may impose additional costs and requirements[255]. Cybersecurity and Data Privacy - Cybersecurity threats pose a significant risk to the company's operations, potentially leading to material disruptions and adverse consequences[346]. - The company has implemented security measures to protect its information technology systems, but future breaches could harm its competitive position and delay product development[349]. - The company is subject to various data privacy laws, including the EU GDPR, UK GDPR, and China's PIPL, which impose strict requirements for processing personal data[357]. - Compliance with evolving data privacy laws may increase operational costs and legal risks for the company and its third-party partners[356].