Senti Biosciences (SNTI) The Citizens JMP Life Sciences Conference 2025 summary

Key technology and pipeline highlights

• Logic gating technology enables targeting of multiple cancer antigens while sparing healthy cells, addressing the challenge of limited clean targets in oncology.

• SENTI-202, an off-the-shelf CAR-NK therapy, targets AML by recognizing CD33 and FLT3 on cancer cells and EMCN on healthy cells to prevent toxicity.

• The gene circuit platform includes multi-arming (payloads like cytokines), a regulator dial for in vivo control, and smart sensors for precise activation.

• Pipeline expansion is planned for solid tumors and other hematologic malignancies, leveraging the same logic gating approach.

• Recent investment from NEA, Celadon Partners, and Bayer Leaps supports ongoing clinical development and future commercialization.

SENTI-202 clinical data and trial design

• Phase 1 trial in relapsed/refractory AML shows 5/7 patients achieved ORR, 4/7 achieved MRD-negative CR, with responses lasting 4–8+ months.

• SENTI-202 is manufactured from healthy donor NK cells, transduced with a construct encoding activating and inhibitory CARs plus IL-15 for immune stimulation.

• Two dosing levels (1B or 1.5B cells) and schedules are tested, with lymphodepletion using fludarabine and Ara-C; patients may receive multiple cycles.

• Safety profile is favorable, with most adverse events related to lymphodepletion and not the therapy; no major DLTs observed.

• Detailed bone marrow analyses confirm reduction of AML blasts and leukemic stem cells, with preservation or increase of healthy hematopoietic stem cells.

Mechanistic insights and future directions

• Logic gating enables selective killing of cancer cells while sparing healthy cells, demonstrated in both AML and solid tumor models (e.g., CEA/VSIG2 in colorectal cancer).

• PK profile aligns with allogeneic NK cell therapies, with detectable cells for ~14 days post-infusion and potential for multiple treatment cycles.

• Expansion plans include earlier lines of AML, MDS, pediatric cohorts, and solid tumors lacking clean targets.

• Internal R&D is focused on identifying new targets and indications for the logic gating platform, with potential for partnerships in T-cell therapies.

• Leadership team includes experienced cell therapy developers, positioning the company for scale-up and commercialization.