Core Insights - Senti Biosciences, Inc. presented positive preliminary data for SENTI-202, a potential first-in-class CAR-NK cell therapy for relapsed/refractory AML, at the AACR Annual Meeting 2025 [1][2][3] Clinical Data Summary - The Phase 1 study of SENTI-202 involved 9 patients with relapsed or refractory AML, with 7 evaluable for overall response [3] - The study identified a preliminary recommended Phase 2 dose (RP2D) of 1.5 x 10 CAR NK cells administered on Days 0, 7, and 14 in 28-day cycles [3] - 5 of 7 evaluable patients achieved an overall response rate (ORR), with 4 achieving composite complete remission (cCR) [3][7] - All cCR patients were measurable residual disease (MRD) negative, indicating a strong efficacy profile [3][7] Safety and Tolerability - SENTI-202 was well-tolerated with no dose-limiting toxicities reported, and a maximum tolerated dose was not reached [3][7] - Adverse events were consistent with other investigational NK cell therapies, with no grade 5 adverse events observed [7] Financial Highlights - As of March 31, 2025, Senti Bio held approximately $33.8 million in cash and cash equivalents [13] - Research and development expenses for Q1 2025 were $9.3 million, an increase from $8.8 million in Q1 2024 [13] - The net loss for the quarter was $14.1 million, or $1.41 per share [13] Pipeline Update - The Phase 1 study of SENTI-202 is ongoing, with plans for disease-specific expansion cohorts [4] - Senti Bio is also evaluating SENTI-301A for HCC, but enrollment has been stopped due to observed dose-limiting toxicities [10] Company Overview - Senti Bio is focused on developing next-generation cell and gene therapies using its proprietary Gene Circuit platform [1][15] - The company aims to engineer therapies that selectively target and eliminate cancer cells while sparing healthy cells [15]

Financial Data and Key Metrics Changes - For the year ended December 31, 2024, the company reported revenues of $152.3 million, a decrease of $14.5 million from $166.8 million in 2023 [27] - For Q4 2024, revenues were $22.8 million, down $8.1 million from $30.9 million in Q4 2023 [27] - The net loss for the year was approximately $80.9 million, or $3 per diluted share, compared to a net loss of $29.7 million, or $1.12 per diluted share in 2023 [31] - Cash and cash equivalents were $293.9 million as of December 31, 2024, down from $348.9 million a year earlier [32] Business Line Data and Key Metrics Changes - The KOSTAIVE vaccine program achieved European Commission approval, with a reported gross profit share of approximately $28 million for Q4 2024 [24] - Research and development expenses for the year were $195.2 million, up from $192.1 million in 2023, driven by higher clinical trial costs [28] - General and administrative expenses remained relatively stable at $52.8 million for the year, compared to $52.9 million in 2023 [30] Market Data and Key Metrics Changes - The company anticipates increased burn rates in the next two years due to ongoing clinical trials for cystic fibrosis (CF) and ornithine transcarbamylase (OTC) programs [33] - The cash runway is expected to extend until the end of Q1 2027, despite the anticipated decline in development milestones from the COVID program [33] Company Strategy and Development Direction - The company is focused on advancing its self-amplifying mRNA platform pipeline, with ongoing studies for ARCT-2304 (influenza) and ARCT-032 (cystic fibrosis) [12][15] - The strategic partnership with CSL Seqirus is crucial for the KOSTAIVE vaccine's development and commercialization [25] - The company aims to differentiate its mRNA therapeutics through proprietary delivery technologies and unique mRNA sequences [42] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming year, highlighting the potential for multiple clinical data readouts and continued development of vaccine programs [34] - The approval of KOSTAIVE is seen as a transformative milestone, positioning the company for future growth [35] - Management acknowledged the competitive landscape in cystic fibrosis treatments and emphasized the unique advantages of their mRNA technology [106] Other Important Information - The company appointed Dr. Moncef Slaoui as Chair designate, bringing significant industry experience to the board [20] - The company is preparing for the U.S. BLA filing for KOSTAIVE anticipated later in 2025 [10] Q&A Session Summary Question: What is the cadence of development milestones within the CSL collaboration? - Management indicated that milestones will continue to be received throughout the year, with specific updates expected in the first quarter call [40] Question: How does the CF program differentiate from competitors? - Management highlighted differences in mRNA technology, delivery systems, and manufacturing processes as key competitive advantages [42] Question: What is the expected size of the CF trial cohort? - The Phase II trial is expected to involve approximately 12 participants, with flexibility to increase that number [48] Question: What are the next steps for KOSTAIVE commercialization in Europe? - Management stated that CSL is leading the commercialization process, and specific details will be provided as they become available [78] Question: What safety monitoring parameters are in place for the CF study? - A data and safety monitoring committee is overseeing safety and tolerability, with thresholds for adverse events established [84] Question: What is the expected visibility into orders for KOSTAIVE in 2025? - Management noted that visibility into orders will depend on Meiji's guidance, with expectations for updates as the year progresses [63]