Senti Biosciences, Inc. (Nasdaq: SNTI) and Celest Therapeutics (Shanghai) Co. Ltd have announced the dosing of the first patient in a pilot clinical trial of SN301A for hepatocellular carcinoma (HCC) in mainland China. SN301A, a chimeric antigen receptor natural killer (CAR-NK) cell therapy, incorporates Senti Bio's anti-GPC3 + crIL-15 SENTI-301A Gene Circuit and is manufactured by Celest in China. The trial aims to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of SN301A in patients with advanced glypican 3 (GPC3)-expressing HCC. This collaboration seeks to address the significant unmet need for effective liver cancer treatments in China, where over 40% of global HCC cases are reported.
Trial Design and Endpoints
The investigator-initiated, open-label, single-center study (NCT06652243) will administer three dose levels of SN301A in cycles, each consisting of three weekly doses (Days 0, 7, 14) during a 28-day treatment cycle, following a lymphodepletion conditioning regimen of fludarabine and cytarabine. Patients may continue to receive multiple cycles based on safety and efficacy results. The primary endpoints include safety assessments for adverse events and dose-limiting toxicities, with efficacy analyses using standard response criteria for liver cancer.
SENTI-301A/SN301A: A Novel CAR-NK Cell Therapy
SENTI-301A is an off-the-shelf, healthy donor-derived CAR-NK cell therapy designed to target GPC3-expressing tumors. GPC3 is highly expressed in 70% to 90% of HCCs and has minimal expression in normal adult tissues. The therapy also includes a calibrated release of interleukin-15 (crIL-15), an immunostimulatory payload designed to stimulate surrounding immune cells and promote CAR-NK cell expansion, persistence, and tumor killing. Preclinical data has demonstrated robust in vitro and in vivo killing of relevant tumor cells with SENTI-301A.
Strategic Collaboration and Future Development
Celest is leading the clinical development, operations, and manufacturing of SN301A, with technical, strategic, and clinical input from Senti Bio. Celest and Senti Bio have the option to expand clinical development of SN301A to Hong Kong, Macau, and Taiwan. Senti Bio retains all development and commercialization rights outside of these regions for SENTI-301A.
According to Erdong Hua, Chairman of Celest and Managing Partner of 6 Dimensions Capital, this collaboration integrates Senti Bio’s Gene Circuit technology with Celest’s NK cell manufacturing and clinical operations expertise. Timothy Lu, MD, PhD, Chief Executive Officer and Co-Founder of Senti Bio, expressed pride in the rapid development and the potential of the partnership to bring Senti Bio’s Gene Circuit technology to patients with limited therapeutic options.
