Senti Biosciences (SNTI) TD Cowen 46th Annual Health Care Conference summary

Key technology and therapeutic approach

• Logic-gated cell therapies selectively kill cancer cells while sparing healthy cells, addressing a major challenge in oncology treatment.

• SENTI-202 is an off-the-shelf allogeneic NK cell therapy targeting CD33 and FLT3, covering over 95% of AML patients.

• The therapy uses an activating CAR for cancer targets, an inhibitory CAR for healthy cells, and IL-15 to enhance NK activity.

• Logic-gating technology is adaptable to both NK and T cells and is being explored for solid tumors.

• SENTI-202 is not genetically restricted, allowing broad patient eligibility.

Clinical data and outcomes

• In a phase I study with relapsed/refractory AML patients, SENTI-202 achieved a 50% overall response rate and 42% CR/CRh at RP2D, with a 7.6-month median duration of CRs.

• 100% of CRs were MRD negative, indicating deep responses and potential for improved patient outcomes.

• The safety profile was favorable, with most adverse events related to lymphodepletion and manageable; no significant CRS observed.

• Responses were observed across patients with adverse genetic features and those refractory to prior therapies.

• Outpatient dosing is feasible, and the product is suitable for rapid delivery due to its off-the-shelf nature.

Mechanism of action and differentiation

• SENTI-202's logic gate design enables selective killing of AML blasts and leukemic stem cells while sparing healthy hematopoietic stem cells.

• CyTOF analysis confirmed maintenance or increase of healthy stem cells in responders, supporting the logic gate's function.

• The therapy is effective even in patients with high-risk genetics, including complex karyotypes.

• The approach is differentiated from existing therapies by not requiring specific genetic mutations and by targeting both AML blasts and stem cells.

• The technology is being adapted for solid tumors, with proof-of-concept shown for CEA-positive cancers using a NOT gate to protect healthy cells.