Senti Biosciences Conference Call Summary Company Overview - **Company**: Senti Biosciences (NasdaqCM:SNTI) - **Focus**: Development of gene circuit-based therapies for cancer treatment, specifically targeting acute myeloid leukemia (AML) with Senti 202 Key Industry Insights - **Industry**: Oncology, specifically the treatment of relapsed refractory AML - **Current Treatment Landscape**: - Existing therapies yield low complete remission (CR) rates of 12%-25% and CR/CRh rates of 20%-35% [16][17] - Median overall survival for relapsed refractory AML patients is approximately five months [16] Core Points from the Call - **Senti 202 Overview**: - A first-in-class off-the-shelf logic-gated CAR-NK cell therapy targeting CD33 and FLT3 [8] - Achieved a 50% overall response rate and a 42% CR/CRh rate in a phase 1 trial with 20 heavily pretreated relapsed refractory AML patients [8][39] - 100% of complete remission patients were MRD negative, indicating significant clinical benefits [9][40] - **Mechanism of Action**: - Utilizes a logic-gated approach to selectively kill cancer cells while sparing healthy cells [6][7] - Incorporates an OR gate to recognize cancer targets and a NOT gate to protect healthy cells [6][11] - **Clinical Trial Results**: - Phase 1 trial demonstrated durable responses with a median duration of composite CR of 7.6 months [9][39] - High MRD negative rates correlate with better long-term outcomes [9][40] - Safety profile supports outpatient dosing, with most adverse events being low-grade and manageable [21][39] - **Regulatory Designations**: - Received FDA's Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug designation, facilitating closer collaboration with the FDA [9][40] - **Market Potential**: - Addressable market for Senti 202 includes approximately 28,000 relapsed refractory AML patients in the U.S. and EU, with potential expansion into newly diagnosed AML and pediatric AML populations [13][14] Additional Important Insights - **Patient Population**: - The trial enrolled patients with multiple adverse risk characteristics, with a median age of 49 years and a history of multiple prior therapies [26][27] - Senti 202 is not restricted by mutation status, allowing it to benefit a broader range of patients [21] - **Future Directions**: - Plans to initiate pivotal studies in 2026, with ongoing discussions with the FDA regarding trial design [41][43] - Potential for expanding indications to include solid tumors and other hematological malignancies [45] - **Technology Platform**: - Senti's broader gene circuits platform includes various types of genetic circuits that enhance the efficacy and safety of cell and gene therapies [44][45] Conclusion - Senti 202 shows promising efficacy and safety in treating relapsed refractory AML, with a strong potential for market impact and future expansion into other indications. The innovative logic-gated approach may address significant unmet needs in oncology, particularly for patients with limited treatment options.

Summary of Senti Biosciences FY Conference Call Company Overview - **Company**: Senti Biosciences (NasdaqCM:SNTI) - **Lead Program**: Senti 202, an off-the-shelf allogeneic CAR NK cell therapy targeting acute myeloid leukemia (AML) [2][3][31] Industry Context - **Focus Area**: Oncology, specifically targeting cancer cells while sparing healthy cells - **Challenge**: Many cancers lack a single target that is unique to cancer cells, complicating treatment options [2][5][33] Core Technology - **Logic Gate Technology**: Utilizes a NOT gate mechanism to protect healthy cells while targeting cancer cells [4][39] - **Targets**: Senti 202 targets CD33 and FLT3, which are expressed in over 95% of AML patients [9][38] Clinical Development - **Current Phase**: Phase 1 dose expansion study, actively enrolling patients [3][40] - **Patient Population**: Focus on relapsed/refractory AML patients, with a disease burden of approximately 20,000 patients per year in the U.S. [6][34] - **Efficacy Data**: Preliminary data shows an overall response rate (ORR) of 71% in evaluable patients, with 57% achieving a composite complete response (CR) [15][45] Safety Profile - **Adverse Events**: Generally well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) attributed to Senti 202 [43][44] - **Lymphodepletion Effects**: Expected drop in healthy blood cell counts post-lymphodepletion, followed by recovery [14][50] Future Outlook - **Upcoming Data**: Additional phase 1 data expected by the end of the year, with a focus on durability and correlative data using CyTOF analyses [26][59] - **Expansion Potential**: Opportunities to apply logic gate technology to newly diagnosed AML, myelodysplastic syndromes (MDS), and solid tumors [21][52] Key Takeaways - **Unmet Need**: Significant opportunity exists in the relapsed/refractory AML space, especially for patients who do not qualify for existing therapies [35][36] - **Regulatory Pathway**: Potential for FDA breakthrough designation based on precedents set by other therapies in the same space [52] - **Technology Versatility**: Logic gate technology may be adapted for various cancer types, enhancing treatment specificity and efficacy [22][56] Conclusion - Senti Biosciences is positioned to make significant advancements in the treatment of AML through its innovative logic gate technology, with promising early clinical data and a clear path for future development [20][24]

Summary of Scenti Biosciences Conference Call Company Overview - **Company**: Scenti Biosciences - **Industry**: Biotechnology - **Focus**: Development of cell and gene therapies for incurable diseases using a synthetic biology platform called GeneCircuits [1][2] Core Technology and Product Development - **Technology**: Logic gating technology allows targeting of previously untreatable cancers, enhancing precision and control in therapy [3][4] - **Lead Program**: Santi 202, targeting relapsed/refractory Acute Myeloid Leukemia (AML) and related cancers, currently in early-stage clinical trials [4][5] - **Manufacturing**: Scalable off-the-shelf manufacturing streamlines treatment for patients [5] Clinical Data and Efficacy - **Clinical Results**: Positive data reported at AACR 2025 meeting, with five patients achieving overall response rate (ORR) and four achieving complete response [15] - **Durability**: Longest-term patient response lasted over eight months, indicating potential for outpatient use [14][15] - **Patient Population**: AML affects over 20,000 newly diagnosed patients annually, with a 60% relapse rate within 12 months [10] Mechanism of Action - **Logic Gates**: Designed to differentiate between cancerous and healthy cells, minimizing toxicity [7][8] - **Cell Engineering**: Utilizes natural killer (NK) cells genetically modified to express proteins targeting AML cells while protecting healthy cells [11][12] - **Key Proteins**: Includes activating CAR (ACAR) targeting CD33 and FLT3, and an inhibitory CAR that protects healthy cells [12][13] Clinical Trial Design - **Phase One Trial**: Multicenter, multinational study assessing two dose levels (1 billion and 1.5 billion CAR positive NK cells) [16][17] - **Dosing Schedule**: Patients receive multiple doses, with assessments for response at 28 days [18] Safety and Tolerability - **Patient Monitoring**: Recovery of healthy blood cell counts observed post-treatment, indicating maintenance of healthy bone marrow [22][23] - **Toxicity Management**: Logic gating technology aims to reduce toxicity associated with traditional therapies [7][8] Future Directions - **Expansion Plans**: Focus on increasing patient numbers and showcasing the efficacy of logic gating technology [30][31] - **Broader Applications**: Potential to apply logic gating technology to solid tumors and other cancer types [25][28] Competitive Landscape - **Differentiation**: Scenti's approach is agnostic to genetic mutations, providing a complementary mechanism to existing therapies targeting genetic mutations in AML [32] - **Comparison with CAR T**: NK cells are preferred for AML due to their rapid action and safety profile, while T cells may be more suitable for solid tumors [33][34] Conclusion - **Outlook**: Scenti Biosciences is positioned to advance its lead program Santi 202 and explore broader applications of its technology in the oncology space, with ongoing clinical trials and promising early results [27][28]