Senti Biosciences Shares Surge Over 360% on Promising Phase 1 Data Showing 66.7% CR Rate for Logic-Gated CAR-NK Therapy SENTI-202

On December 2, 2024, Senti Biosciences, co-founded by synthetic biology experts James J. Collins and Timothy Lu (卢冠达), announced positive preliminary data from the Phase 1 clinical trial of its first clinical-stage candidate drug, SENTI-202, a CAR-NK cell therapy.

On the same day, Senti Bio also announced the completion of an oversubscribed private placement offering with total proceeds of approximately $37.6 million, which will be used to advance the ongoing development and production scale-up of the SENTI-202 program, as well as for other research and development activities and general corporate purposes.

Affected by two major positive news, Senti Bio's stock price surged 362.96% to close at $10 per share on the same day.

SENTI-202 is a logic-gated CAR-NK designed to selectively target and eliminate hematologic malignancies expressing CD33 and/or FLT3, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), while protecting healthy cells.

SENTI-202 consists of three main components:

OR GATE: Activating CAR targeting CD33 and FLT3, recognizing tumor cells;

NOT GATE: By recognizing healthy cells through protective antigens, it is designed to protect healthy cells from being attacked;

IL-15 Precision Release Technology: Increase the persistence, expansion, and activity of therapeutic cells, as well as enhance immune cell function in the patient's tumor environment.

CAR-NK will only kill cells when they express CD33 and/or FLT3 and do not express the protective antigens being recognized, offering better specificity and safety.

SENTI-202 is also an "off-the-shelf" cell therapy, with cells sourced from qualified healthy donors. Senti Biosciences screens donors in advance according to standards and cryopreserves the cells before production to minimize variability and enhance manufacturability and product quality.

SENTI-202 received FDA IND approval in December 2023 for clinical studies targeting hematologic malignancies expressing CD33 and/or FLT3.

Further Reading:Synthetic Biology Expert Lu Guanting's Logic Gate CAR-NK Receives FDA IND Approval

In the Phase 1 clinical trial of SENTI-202, three patients have currently been enrolled. SENTI-202 (a single dose of 1 billion CAR-NK cells) is administered on days 0, 7, and 14 of a 28-day cycle following lymphodepletion with fludarabine/cytarabine ("Ara-C").

Preliminary clinical data showed that two patients achieved complete remission (CR), and these two patients were both assessed as minimal residual disease (“MRD”) negative after treatment.

As of the data release, these two patients were still in remission, with durations of over four months and over three months, respectively.

One patient showed no response after one cycle of treatment.

In terms of safety, SENTI-202 was generally well-tolerated, with no dose-limiting toxicity (DLT), and adverse events were consistent with those observed in other investigational NK cell therapies and potential AML patients receiving lymphodepleting chemotherapy.

In addition, SENTI-202 transgene was detected in the peripheral circulation of 3 patients during all cycles, and its PK characteristics were generally consistent with other investigational CAR-NK therapies.

Senti Biosciences disclosed that, according to the current clinical trial design of SENTI-202, the company expects to enroll approximately 20 patients in the Phase 1 trial, with the high-dose cohort (1.5 billion cells) actively recruiting. More data is expected to be reported in 2025.

With the clinical good news, Senti Bio is seemingly on the rise. Last year's series of cost-saving measures, including cutting pipelines, selling technology, and leasing out facilities, helped Senti Bio survive the tough times.

A 362% surge in stock price and an oversubscription have ensured that Senti Bio will not face a temporary shortage of funds.