Abstract
SENTI-202 is a first-in-class off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy product candidate designed to selectively target and eliminate CD33 and/or FLT3-expressing hematologic malignancies, such as AML and MDS, while sparing healthy bone marrow cells. The novel Logic Gated Gene Circuit approach employed with these cells incorporates three chimeric proteins to address key limitations of AML therapies. First, a bivalent (OR gate) activating CAR (aCAR) is triggered independently by CD33 (a validated AML target) and/or FLT3, providing a “kill” signal. By targeting either or both antigens, SENTI-202 is designed to effectively kill both leukemic blasts and leukemic stem cells, which are difficult-to-eradicate reservoirs of AML disease.
Second, SENTI-202 contains an inhibitory CAR with a NOT EMCN (endomucin) gate, providing a “protect” signal designed to recognize and protect healthy cells from being killed, even if they were to express CD33 and/or FLT3, potentially widening the therapeutic window. Third, SENTI-202 contains calibrated-release IL-15 (providing an “enhance” signal), which is designed to significantly increase cell persistence, expansion, and activity of both the CAR-NK cells and host immune cells.
The Phase 1 study of SENTI-202 is currently enrolling adult patients with R/R CD33 and/or FLT3-expressing heme malignancies. A preliminary recommended Phase 2 dose based upon initial encouraging data is being confirmed and will be followed by disease specific expansion cohorts. Dr. Rajangam will discuss these data and their relevance to the ongoing development of this potential first-in-class allogeneic off-the-shelf treatment for AML/MDS patients.
Speaker Bio
Dr. Rajangam is responsible for leading the research and development of Senti Bio’s pipeline products including off-the-shelf CAR-NK cell oncology programs into and through clinical development. Dr. Rajangam served in leadership roles at various biotech companies, most recently Nkarta Therapeutics where, as Chief Medical Officer, she was responsible for clinical development of CAR-NK cell therapies for oncology. Prior to Nkarta, she was Chief Medical Officer at Atara Biotherapeutics where she led the development of T-cell therapies for oncology, neurology and infectious diseases. Prior to that, Dr. Rajangam was Chief Medical Officer of Cleave Biosciences, where she led oncology clinical development programs. Prior to becoming a Chief Medical Officer, Dr. Rajangam gained relevant senior leadership experience at Onyx and Exelixis, while contributing to the clinical development and global approval of several marketed oncology products including Kyprolis®, Cotellic® and Cometriq®/Cabometyx®.
Dr. Rajangam currently serves on the board of directors of Turnstone Biologics, a clinical-stage biotechnology company developing next-generation tumor infiltrating lymphocyte cell therapies; and on the scientific advisory board of Vibe Bio, an AI enhanced pipeline analysis company
Dr. Rajangam received a medical degree from St. Johns’ Medical College and completed her surgical residency with a focus on oncology at the Postgraduate Institute of Medical Education and Research (PGIMER), both in India. She received a Ph.D. in biomedical cell and tissue engineering from Northwestern University.