Summary of Senti Biosciences Conference Call Company Overview - **Company**: Senti Biosciences (NasdaqCM:SNTI) - **Industry**: Biotechnology, specifically focused on cell therapy Core Points and Arguments 1. **Logic-Gated Cell Therapy**: Senti Biosciences specializes in logic-gated cell therapy, which allows engineered cells to perform multiple functions based on various inputs from the host cell [1][2] 2. **Lead Program - SENTI-202**: The lead program, SENTI-202, is a first-in-class therapy targeting acute myeloid leukemia (AML), particularly affecting individuals aged 65 and older [2][5] 3. **Orphan Drug Designation**: SENTI-202 has received orphan drug designation, indicating its potential to address a significant unmet medical need in AML [2] 4. **Clinical Trial Progress**: Positive preliminary efficacy data has been demonstrated in the ongoing phase 1 clinical trial, with additional data expected by the end of the year [2][5] 5. **AML Statistics**: Approximately 20,000 to 21,000 Americans are diagnosed with AML annually, with a median survival of 5.3 months for those who do not respond to first-line therapy [5][6] 6. **Challenges in AML Treatment**: The heterogeneity of AML and the presence of therapy-resistant leukemic stem cells (LSCs) pose significant challenges in developing effective therapies [7][8] 7. **Mechanism of Action**: SENTI-202 utilizes a unique logic gate mechanism to selectively kill AML cells while sparing healthy cells, addressing the issue of shared targets between LSCs and healthy hematopoietic stem cells [9][11] 8. **NK Cell Utilization**: The therapy employs natural killer (NK) cells, which can be used across different patients without the risk of graft-versus-host disease, and have shown a response rate of about 20% in non-engineered forms [10][15] 9. **Efficacy Data**: In the RP2D cohort, 67% of patients achieved complete remission (CR), with 100% being measurable residual disease (MRD) negative, indicating a strong response to treatment [18][19] 10. **Safety Profile**: The safety profile of SENTI-202 is favorable, with no grade 3 adverse events reported and manageable infusion-related reactions [18][21] Additional Important Content 1. **Gene Circuit Design**: The gene circuit in SENTI-202 includes an OR logic gate for targeting multiple antigens and a NOT logic gate to protect healthy cells from being killed [11][13] 2. **Manufacturing Process**: The manufacturing process for SENTI-202 is off-the-shelf, allowing for immediate shipment of cells upon patient approval, which enhances operational efficiency [14] 3. **Future Plans**: The company plans to confirm the recommended phase 2 dose (RP2D) and expand the patient cohort, with further data presentation anticipated by the end of the year [21][22] This summary encapsulates the key points discussed during the conference call, highlighting Senti Biosciences' innovative approach to treating AML through its SENTI-202 program and the promising data emerging from its clinical trials.

SENTI-202 Program Highlights - SENTI-202 is a first-in-class off-the-shelf Logic-Gated selective CD33 OR FLT3 NOT EMCN CAR NK cell therapy targeting AML [4, 5, 52] - The therapy is designed to selectively kill both AML blasts and LSCs while protecting healthy HSPCs [15, 52] - Preliminary Phase 1 trial data shows positive efficacy in R/R AML [5] Clinical Trial & Patient Data - The Phase 1 trial (SENTI-202-101) enrolled heavily pretreated R/R AML patients with poor prognosis [18, 52] - The study identified a preliminary Recommended Phase 2 Dose (RP2D) [20, 22, 52] - The opening dose cohort was anticipated to be biologically active [18, 22] - The median time from AML diagnosis to trial entry was less than 1 year [25] - Patients had received a median of 2 prior lines of therapy [27] Safety & Tolerability - SENTI-202 was generally well-tolerated in R/R AML patients [30, 52] - Most frequent Grade 3+ AEs were hematologic and consistent with R/R AML patients receiving lymphodepletion [29, 52] - The Maximum Tolerated Dose (MTD) was not reached, and the preliminary RP2D was identified as 1.5 x 10^9 cells/dose x 3 weekly doses/28 days [52] Efficacy & Response - Across all patients, the Overall Response Rate (ORR) was 71% (5/7) and the composite Complete Remission (cCR) rate was 57% (4/7) [33, 57] - In the preliminary RP2D cohort, the cCR rate was 67% (2/3) [33, 57] - All cCR patients (4/4) achieved MRD- status as assessed per local standard of care [33, 57] - All cCR patients maintained morphologic remission with the longest follow-up of 8+ months [57]