Financial Data and Key Metrics Changes - The company reported a net loss of $161.4 million or $1.36 per share for Q1 2025, compared to a net loss of $135.6 million or $1.33 per share for the same period in 2024, indicating an increase in losses year-over-year [36] - Cash, cash equivalents, and investments decreased to approximately $1.1 billion from $1.2 billion at the end of Q4 2024, reflecting a decline of about $132.2 million during the quarter [35] - R&D expenses rose to $99.8 million from $81.6 million in Q1 2024, primarily due to advancing clinical trials and higher personnel costs [35][36] Business Line Data and Key Metrics Changes - The company is focused on the commercialization of aficamtan, with ongoing regulatory activities in the U.S. and Europe, including a PDUFA date extension to December 26, 2025 [6][10] - The Acacia HCM trial for aficamtan in non-obstructive hypertrophic cardiomyopathy (NHCM) completed enrollment ahead of schedule, with top-line results expected in the first half of 2026 [14][24] - The company is also advancing its clinical trials for CK-586 and omecamtiv mecarbil, with significant progress reported in both programs [30][32] Market Data and Key Metrics Changes - The company is preparing for potential approval by the EMA in the first half of 2026, with ongoing regulatory interactions in Europe [11][40] - The market opportunity for NHCM is growing due to increasing recognition and diagnosis, with the company optimistic about aficamtan's potential in this underserved population [14][39] Company Strategy and Development Direction - The company aims to transition into an integrated commercial biopharmaceutical company, with a focus on advancing its pipeline and preparing for the launch of aficamtan [38][39] - External innovation and business development are key pillars of the company's growth strategy, with investments in companies like Embryo Pharmaceuticals to support novel therapies [33] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the distinct benefit-risk profile of aficamtan despite the PDUFA extension, emphasizing the ongoing FDA review process [10][39] - The company remains well-positioned financially to support the potential launch of aficamtan and advance its clinical pipeline [37][38] Other Important Information - The company is actively engaging with payers and refining its promotional launch campaign for healthcare professionals and patients [18][20] - The company has established new regional entities in France and the UK to enhance its European commercial readiness [21] Q&A Session Summary Question: What does the failure of OHDSI mean for Acacia? - Management expressed optimism about Acacia's design based on previous Phase II experiences and the successful enrollment ahead of schedule [44][46] Question: Did the FDA initially guide against submitting the REMS? - Management clarified that the FDA did not initially require a REMS submission, but later requested it during the review process [54][56] Question: Will the REMS submitted be consistent with previous communications? - Management indicated that while they cannot disclose specific details, the REMS submitted aligns with the differentiated properties of aficamtan [64][66] Question: Can the MAPLE data be included in the label for the December approval? - Management confirmed that they do not intend to submit MAPLE data as part of the current review cycle for aficamtan [65][66] Question: What are the pros and cons of changing the primary endpoint in Acacia? - Management noted that the dual primary endpoint allows for a more robust assessment and satisfies regulatory requirements, enhancing the trial's efficiency [84][88]

Financial Data and Key Metrics Changes - The company reported a net loss of $161.4 million or $1.36 per share for Q1 2025, compared to a net loss of $135.6 million or $1.33 per share for the same period in 2024, indicating an increase in losses year-over-year [41] - Cash, cash equivalents, and investments decreased to approximately $1.1 billion from $1.2 billion at the end of Q4 2024, reflecting a decline of about $132.2 million during the quarter [40] - R&D expenses rose to $99.8 million from $81.6 million in Q1 2024, primarily due to advancing clinical trials and higher personnel costs [40] - G&A expenses increased to $57.4 million from $45.5 million in Q1 2024, attributed to investments in commercial readiness activities and higher personnel costs [40] Business Line Data and Key Metrics Changes - The company is focused on advancing its new drug application (NDA) for Aficamten, with the FDA extending the PDUFA date to December 26, 2025, to allow for a full review of the proposed risk evaluation and mitigation strategy (REMS) [8][12] - The company completed enrollment for the Acacia HCM trial months ahead of schedule, with plans to report top-line results in the first half of 2026 [17][28] - The Maple HCM trial is expected to report top-line results this month, which may represent a potential label expansion opportunity for Aficamten [16][26] Market Data and Key Metrics Changes - The company is preparing for potential approval by the EMA in the first half of 2026, following the receipt of questions from the EMA regarding the MAA for Aficamten [13][14] - The company is also working with Sanofi to support the NDA review of Aficamten in China, indicating a global approach to regulatory activities [14] Company Strategy and Development Direction - The company aims to transition into an integrated commercial biopharmaceutical company, with a focus on the potential FDA approval of Aficamten and the launch of its commercial strategies [44][46] - The company is enhancing its commercial readiness in both the U.S. and Europe, with ongoing recruitment for its sales force and development of promotional campaigns [19][21] - The company emphasizes external innovation and business development as key pillars of its growth strategy, seeking to complement its internal R&D pipeline through investments and partnerships [38] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the distinct benefit-risk profile of Aficamten despite the PDUFA extension, maintaining optimism regarding its potential approval [12][44] - The company highlighted the importance of rigorous clinical research and disciplined resource management in achieving its ambitious goals for 2025 [17][44] - Management noted the ongoing uncertainties in the macro market but emphasized a strong balance sheet and cash position to support key priorities [44] Other Important Information - The company is on track to complete enrollment in the adolescent cohort of the CEDAR HCM trial in the second half of this year [47] - The company plans to continue its ongoing preclinical development and research activities focused on muscle biology [47] Q&A Session Summary Question: What does the failure of OHDSI mean for Acacia? - Management expressed excitement about Acacia's enrollment completion ahead of schedule and maintained optimism regarding the trial's design and dosing regimen [50][52] Question: Did the FDA initially guide against submitting the REMS? - Management clarified that the FDA did not initially require a REMS submission, and it was during the review that the FDA requested it [61][64] Question: Will the REMS submitted be consistent with previous communications? - Management indicated that while they cannot disclose specific details about the REMS, it aligns with the differentiated properties of Aficamten [71][75] Question: Can the MAPLE data be submitted for inclusion in the label for the December approval? - Management confirmed that they do not intend to submit MAPLE data as part of the current review cycle for Aficamten [72][110] Question: What are the implications of changing the primary endpoint in Acacia? - Management explained that the change to a dual primary endpoint was made to satisfy regulatory requirements and enhance the trial's efficiency without losing power [94][98]

Financial Data and Key Metrics Changes - The company reported a net loss of $161.4 million or $1.36 per share for Q1 2025, compared to a net loss of $135.6 million or $1.33 per share for the same period in 2024, indicating an increase in losses year-over-year [41][42]. - Cash, cash equivalents, and investments decreased to approximately $1.1 billion from $1.2 billion at the end of Q4 2024, reflecting a decline of about $132.2 million during the quarter [40]. Business Line Data and Key Metrics Changes - The company is focused on advancing its clinical trials for aficamtan, with significant milestones achieved in ongoing clinical trials, including the completion of enrollment in the Acacia HCM trial months ahead of schedule [17][28]. - The company plans to report top-line results from the Maple HCM trial this month, which may represent a potential label expansion opportunity for aficamtan [16][26]. Market Data and Key Metrics Changes - The company is preparing for potential approval by the EMA in the first half of 2026 and is working with Sanofi to support the NDA review of aficamtan in China [14][46]. - The market opportunity for non-obstructive hypertrophic cardiomyopathy (NHCM) is growing, with increasing recognition and diagnosis of the condition [16][33]. Company Strategy and Development Direction - The company aims to transition into an integrated commercial biopharmaceutical company, with a focus on the potential FDA approval of aficamtan by the end of 2025 [44][45]. - The company is enhancing its commercial readiness activities in both the U.S. and Europe, including recruiting a sales force and finalizing promotional campaigns [19][21]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the distinct benefit-risk profile of aficamtan despite the PDUFA date extension, emphasizing that it does not change expectations for a potentially differentiated label upon approval [12][44]. - The company remains optimistic about the ongoing clinical trials and the potential to reach more patients living with hypertrophic cardiomyopathy (HCM) worldwide [33][34]. Other Important Information - The company is maintaining its full-year 2025 financial guidance, with GAAP operating expenses expected to be between $670 million and $710 million [42][43]. - The company participated in a Series B financing of Embryo Pharmaceuticals to support the advancement of Ninerifaxtat for NHCM, highlighting its strategy of external innovation and business development [38]. Q&A Session Summary Question: What does the failure of OHDSI and the BMS verbiage around obstructive HCM mean for Acacia? - Management expressed excitement about Acacia's enrollment completion ahead of schedule and maintained optimism regarding the trial's design and dosing regimen, which is based on previous successful studies [50][52][56]. Question: Did the FDA initially guide the company to not submit the REMS? - Management clarified that the FDA did not initially require a REMS submission, and the request for a REMS came during the review process, which the company was prepared for [61][63][65]. Question: Will the REMS submitted to the FDA be consistent with previous communications to investors? - Management indicated that while they cannot disclose specific details about the REMS, it aligns with the differentiated properties of aficamtan [71][75]. Question: Can the company use the MAPLE data for the December approval? - Management confirmed that they do not intend to submit MAPLE data as part of the current review cycle for aficamtan, as it would be disruptive [72][110]. Question: What are the pros and cons of changing the primary endpoint to a dual primary of peak VO2 and KCCQ in Acacia? - Management explained that the change to a dual primary endpoint allows for a more robust assessment of treatment effects and satisfies regulatory requirements, enhancing the trial's efficiency [94][98].