Milestone Pharmaceuticals(US:MIST)2025-11-12 11:56Product Development and Regulatory Status - The company is focused on developing and commercializing CARDAMYST (etripamil) as a portable nasal spray treatment for supraventricular tachycardia (SVT) and atrial fibrillation with rapid ventricular rate (AFib-RVR) [82]. - In March 2025, the company received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) for CARDAMYST, with a new PDUFA target date set for December 13, 2025 [83][97]. - The company plans to leverage data from the PSVT program to support a supplemental New Drug Application (sNDA) for etripamil in AFib-RVR [85]. - The FDA highlighted two key Chemistry, Manufacturing and Controls (CMC) issues in the CRL, including concerns about nitrosamine impurities and the need for facility inspection [96]. Clinical Trials and Efficacy - The company completed a successful Phase 2 study for etripamil in AFib-RVR, showing rapid and statistically superior ventricular rate reduction compared to placebo, with a median time-to-conversion of 17 minutes in the NODE-303 study [84][98]. - The Phase 3 RAPID trial of etripamil demonstrated a significant difference in time to SVT conversion, with 64.3% of patients converting within 30 minutes compared to 31.2% for placebo (HR 2.62; p<0.001) [99]. - In the NODE-301 studies, patients self-administering etripamil sought additional medical interventions 43% less frequently (15% vs. 25%; p=0.013) and had 39% fewer emergency department visits (14% vs. 22%; p=0.035) compared to placebo [100]. - The Phase 3 trial (JX02002) in China showed that 40.5% of patients self-administering etripamil converted from PSVT to sinus rhythm within 30 minutes, compared to 15.9% for placebo (HR 3.00; p<0.001) [103]. - The ReVeRA study reported a significant reduction in ventricular rate of 29.91 bpm (p<0.0001) for patients treated with etripamil compared to placebo [105]. - The Phase 3 AFib-RVR study will enroll patients with a history of symptomatic AFib episodes, using a self-administered regimen of 70 mg per dose [109]. Market Potential and Financial Overview - The estimated addressable market for CARDAMYST in PSVT is approximately 500,000 to 800,000 patients, with a peak demand potential of 2.5 million to 4 million episodes treated per year [89]. - The prevalence of AFib is expected to grow from 10 million to over 12 million Americans by 2030, with a target addressable market of up to 4 to 5 million patients for etripamil in AFib-RVR [93]. - Total healthcare expenditures for PSVT patients range from $20,000 to $30,000 per patient annually, with at least $5 billion spent annually in the U.S. on PSVT management [90]. - The American Heart Association reported that atrial fibrillation resulted in $25 billion in direct medical costs in 2016, with projected costs reaching $46 billion in direct costs by 2030 [95]. Financial Performance and Expenses - As of September 30, 2025, the company reported an accumulated deficit of $413.2 million and net losses of $11.9 million for Q3 2025 [111]. - The company expects to continue incurring significant losses as it focuses on obtaining regulatory approvals and preparing for commercialization of etripamil [112]. - For the three months ended September 30, 2025, commercial expenses increased by $2.7 million, or 142.1%, compared to the same period in 2024, primarily due to additional personnel and operational expenses related to the launch of CARDAMYST [135]. - For the nine months ended September 30, 2025, commercial expenses rose by $13.5 million, or 204.8%, compared to the same period in 2024, driven by increased personnel and operational costs for CARDAMYST [136]. - Research and development expenses, net of tax credits, increased by $2.2 million, or 20.8%, for the nine months ended September 30, 2025, compared to the same period in 2024, mainly due to higher consulting and outside service costs [132]. - Total operating expenses for the three months ended September 30, 2025, were $11.8 million, a 23.0% increase from $9.6 million in the same period in 2024 [128]. - The net loss for the three months ended September 30, 2025, was $11.9 million, representing a 26.3% increase from a net loss of $9.4 million in the same period in 2024 [128]. - The company reported a net loss of $45.6 million for the nine months ended September 30, 2025, compared to a net loss of $29.2 million for the same period in 2024 [157][158]. Cash Flow and Funding - As of September 30, 2025, the company had cash, cash equivalents, and short-term investments totaling $82.6 million, with an accumulated deficit of $413.2 million [142]. - The company expects to fund operations through equity and/or debt financing until substantial revenue from product sales is generated [155]. - The company incurred non-cash charges of $3.9 million related to share-based compensation during the nine months ended September 30, 2025 [157]. - Cash provided by financing activities increased to $49.1 million in the nine months ended September 30, 2025, up 53.0% from $32.1 million in 2024 [161][162]. - The net proceeds from the 2025 Offering were $48.6 million after deducting underwriting commissions and estimated offering expenses [144]. - The company anticipates an increase in commercial expenses if the FDA approves the NDA, as it will invest in infrastructure and personnel for the product launch in the United States [138]. - Net cash used in operating activities for the nine months ended September 30, 2025, was $36.3 million, a 64.8% increase from $22.0 million in the same period of 2024 [156]. Operational Model and Risks - The company operates with a significant outsourcing model, relying on a smaller core team to manage a larger number of outsourced vendors and consultants [110]. - The company is subject to foreign exchange rate risk due to transactions in Canadian dollars, with a net monetary exposure of $2.7 million as of September 30, 2025 [173]. - The company anticipates that any inability to secure adequate funding may lead to reductions in spending or suspension of planned programs, adversely affecting its business [155]. - The company has not entered into off-balance sheet arrangements as of the reporting date [163].