Senti slams brakes on CAR-NK program to eke out remaining cash

And then there were two. Senti Bio, seeing the end of its cash runway hove into view, has pulled the plug on its liver cancer candidate and narrowed its focus onto two CAR-NK programs to preserve its money.

Last year, Senti secured fresh funding from Leaps by Bayer and went public via a SPAC merger to bankroll the development of three drug candidates based on its gene circuit platform. The honeymoon was brief. With its share price hovering around the $2 mark for much of its time on the Nasdaq, and its cash reserves falling to $115 million by the end of September, Senti has decided to act before the situation gets critical.

SENTI-301A is the main victim of the rethink. In November, Senti named SENTI-301A as the development candidate from its GPC3-targeting solid tumor program. By targeting GPC3 with an off-the-shelf CAR-NK, Senti hopes to treat cancers such as hepatocellular carcinoma that express the cell-surface glycoprotein.

Senti continues to see a market for SENTI-301A, particularly in parts of Asia where liver cancer is more common, but it will no longer use its dollars to realize that potential. The biotech is looking for partners to take the candidate into the clinic in certain parts of the world while it allocates its remaining money to the development of SENTI-202 and SENTI-401. 

SENTI-202, a CAR-NK treatment for acute myeloid leukemia, is on its way to the clinic, with Senti running the final studies ahead of a planned IND filing in the second half of the year. The candidate is designed to kill leukemic blasts and leukemic stem cells without harming healthy cells, using the expression of CD33, FLT3 and EMCN to differentiate between the diseased and normal cells.

Senti has built a similar safety feature into SENTI-401. The CAR-NK cell therapy candidate targets CEA and expresses the cytokines IL-15 and IL-21. However, SENTI-401 is designed to leave cells that express CEA and VSIG2 alone, resulting in 98% of healthy cells surviving exposure to the therapy in preclinical tests. 

By narrowing its focus, the biotech expects its current cash to last through at least the first quarter of 2024. The extended runway may still prove troublesome. Senti’s first IND filing is scheduled for months before its cash is forecast to run out, although the out-licensing of SENTI-301A could bring in money.