Financial Data and Key Metrics Changes - Revenue for Q2 2025 was $8.7 million, a decrease from $19.7 million in the prior year quarter, attributed to the timing of revenue recognized under the collaboration agreement with GSK [28] - Research and development expenses increased to $43.5 million from $40.4 million in the same period in 2024, driven by spending in the inhibin E program and RNA editing programs [28] - General and administrative expenses rose to $18 million from $14.3 million in the prior year quarter, primarily due to share-based compensation and other external expenses [28] - The net loss for Q2 2025 was $50.5 million, compared to a net loss of $32.9 million in the prior year quarter [28] - Cash and cash equivalents at the end of Q2 2025 were $208.5 million, down from $302.1 million as of December 31, 2024, with expectations to fund operations into 2027 [29] Business Line Data and Key Metrics Changes - The AATD clinical program is advancing with promising data from the RESTORATION trials, showing significant increases in circulating AAT levels [7][9] - The Enlight clinical program for obesity has expanded its second cohort from 8 to 32 participants due to favorable safety and tolerability results [10][11] - FORWARD 53 clinical results for DMD demonstrated a statistically significant improvement in time to rise, marking it as a best-in-class therapeutic option [13][14] Market Data and Key Metrics Changes - The company is actively engaging with the DMD community, highlighting the importance of their FORWARD 53 clinical results [12][13] - The obesity market is being targeted with the Enlight program, which is positioned to offer a differentiated approach compared to current standard care [22][24] Company Strategy and Development Direction - The company aims to unlock the potential of RNA medicines through proprietary oligonucleotide chemistry, focusing on both rare and common diseases [4][5] - Plans to initiate clinical development of new programs in 2026, with a focus on expanding their wholly owned discovery pipeline [12][25] - The strategy includes preparing for regulatory filings and engaging with the FDA for accelerated approval pathways [15][16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the ongoing clinical programs and the potential for upcoming data readouts to inform the therapeutic pipeline [31] - The company is encouraged by the engagement from the community and clinicians regarding their AATD program, indicating a strong need for effective therapies [6][9] - Future data from the RESTORATION and Enlight trials are expected to serve as key inflection points for the company [12][25] Other Important Information - The company welcomed Dr. Chris Wright as Chief Medical Officer, bringing extensive experience in drug development [5] - The company is focused on addressing both hepatic and extrahepatic targets with their RNA editing and siRNA programs [25][26] Q&A Session Summary Question: Can you elaborate on your reasons for expanding cohort two over advancing to cohort three sooner? - The decision to expand cohort two was based on safety data indicating the ability to dose escalate, and cohort two was modeled to align with weight loss similar to semaglutide [34][36] Question: Should we expect a linear dose response, or does the preservation of lean mass offset the weight loss aspect? - The expectation is that weight loss will be driven by fat without impacting muscle, but human data will clarify the translation of these effects [38] Question: What is your guidance on the different expectations from the two data readouts for the AATD program? - The focus will be on the multidose data, which is expected to show larger liver exposure and higher protein levels compared to single doses [44][46] Question: What is the desirable knockdown level for inhibin E? - The goal is to replicate preclinical data, aiming for a knockdown that aligns with therapeutic weight loss, and the company is open to continuing dose escalation beyond cohort three [51][52] Question: Can you provide specifics on the dosing completion for the two hundred milligram multidose? - All patients in the cohort have received their seven doses, and the study remains on track for data readout in the third quarter [58][59] Question: Is there anything qualitatively about the consistency of effect for the AATD program? - The company is encouraged by the consistency observed in preclinical models and early clinical data, indicating substantial protein production [65][66]

Summary of Sarepta Therapeutics (SRPT) Conference Call Company Overview - **Company**: Sarepta Therapeutics (SRPT) - **Event**: 2025 Conference at Bank of America Healthcare Conference - **Date**: May 14, 2025 Key Points Financial Performance - **Net Product Revenue**: $612 million for Q1, representing a 70% growth year-over-year [8] - **Elevatus Revenue**: $375 million, a 180% increase compared to the same quarter last year [8] - **GAAP Operating Income**: Approximately $2.75 million, a 70% increase from the previous quarter [9] - **Non-GAAP Basis**: $335 million, about 45% of sales, indicating strong financial performance [9] - **Revised Guidance**: Expected revenue for the year is between $2.3 billion and $2.6 billion, with profitability and cash flow positivity anticipated [13] Industry Context - **Biotech Market Condition**: The current biotech market is described as "chaotic" and "nearly uninvestable," with 30% of public biotechs trading below their cash value [10][12] - **Funding Challenges**: Over 90% of biotechs rely on equity markets for funding, leading to potential failures of many companies and their programs [12] Regulatory Environment - **FDA Interactions**: Positive interactions with the FDA regarding the limb girdle programs, with no delays or changes in perspective noted [24][31] - **Accelerated Approvals**: Discussions ongoing regarding the transition from accelerated to traditional approvals for PMOs, with a focus on totality of evidence [40] Safety Concerns - **Recent Safety Event**: A safety incident involving a patient death due to liver injury has impacted the company's operations and necessitated increased communication with families and physicians [51][52] - **Impact on Patient Enrollment**: The safety event has caused delays in patient enrollment and treatment initiation, with a longer cycle time from start form to infusion now expected [54][60] Pipeline and Product Development - **Innovative Approaches**: The company is focused on gene therapy and gene editing, with a strong pipeline for limb girdle muscular dystrophy (LGMD) treatments [14][30] - **Upcoming BLA Submission**: A Biologics License Application (BLA) for the 09/2003 program is expected to be submitted later this year, with potential approval in the first half of next year [29][30] Market Strategy - **Focus on Secondary Sites**: The company is working to increase patient access by focusing on secondary and tertiary sites to expedite treatment [61][66] - **Sales and Support Strategy**: A multidisciplinary approach is being employed to support sites, including education on efficacy and safety [66] Future Outlook - **Guidance for Q2 and Beyond**: Anticipated revenue decline in Q2 due to the safety event, with expectations for recovery in Q3 and Q4 [81] - **Seasonality Considerations**: Potential for increased patient enrollment during the summer months, but ongoing impacts from the safety event are expected to linger [80][81] Additional Insights - **Manufacturing Resilience**: All products are manufactured in the U.S., with minimal impact from tariffs [19][20] - **Long-term Patient Monitoring**: Emphasis on the need for long-term studies to assess the efficacy of therapies in degenerative diseases [39] This summary encapsulates the critical insights from the conference call, highlighting Sarepta Therapeutics' financial performance, industry challenges, regulatory interactions, safety concerns, and strategic focus moving forward.

Clinical Trial Updates - ALPACAR-360 Phase 2 study of Zerlasiran delivered positive results in high Lp(a)[9, 10] - SANRECO Phase 1 study of Divesiran delivered positive results in PV and was granted orphan drug designation for PV in EU[9, 10] - SANRECO Phase 2 study of Divesiran dosed first PV patient, with full enrollment anticipated by year-end 2025[10, 12, 48] - SLN548 (complement factor B) Phase 1 study start anticipated in 2H 2025[12, 48] Divesiran in Polycythemia Vera (PV) - Divesiran is a first-in-class siRNA for PV with FDA Fast Track and Orphan Drug Designations[26, 27] - Phase 1 study showed Divesiran reduced phlebotomy frequency in PV patients who had 79 phlebotomies prior to dosing, but only 5 in the treatment period and 2 in follow-up[29, 31] - Divesiran decreased hematocrit in all cohorts in Phase 1 study[32, 34] - Divesiran treatment produced sustained increases in Hepcidin[36, 38] - Divesiran demonstrated a favorable safety and tolerability profile, with 84% of treatment emergent adverse events (TEAEs) being grade 1[40, 41] Financial Performance and Guidance - Revenue for FY 2024 was $43258 thousand, compared to $31634 thousand in FY 2023[16] - Net loss for FY 2024 was $45309 thousand, compared to $54228 thousand in FY 2023[16] - Cash position at the end of December 2024 was $147334 thousand, including $121300 thousand in cash and cash equivalents and $26000 thousand in short-term investments[16, 17] - Projected cash runway extended into 2027[18]