FDA Clears IND for Verismo's SynKIR-310 CAR-T Therapy in Relapsed/Refractory B-NHL
核心洞察
The FDA has cleared the IND application for Verismo Therapeutics (搜索)' SynKIR-310, a novel CAR-T therapy, for relapsed/refractory B-cell non-Hodgkin lymphoma (搜索) (B-NHL).
The Phase 1 CELESTIAL-301 trial, expected to begin in the second half of 2024, will evaluate SynKIR-310 in patients with DLBCL (搜索), FL, MCL, and MZL.
SynKIR-310, based on the KIR-CAR platform, incorporates a CD19 (搜索) binder (DS191) designed to enhance antitumor activity and persistence compared to existing CAR-T therapies.
Verismo Therapeutics (搜索) has received FDA clearance for its Investigational New Drug (IND) application for SynKIR-310, a chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of patients with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (搜索) (B-NHL). This clearance paves the way for the Phase 1 CELESTIAL-301 clinical trial, anticipated to commence in the second half of 2024.
CELESTIAL-301 Trial Details
The CELESTIAL-301 trial will enroll patients with various B-NHL subtypes, including diffuse large B-cell lymphoma (DLBCL (搜索)), follicular lymphoma (搜索) (FL), mantle cell lymphoma (搜索) (MCL), and marginal zone lymphoma (搜索) (MZL). The study will include both patients who have previously received CAR-T therapy and experienced relapse or were refractory to it, as well as those who are CAR-T naïve. This trial aims to address the significant unmet need for more effective therapies in patients with aggressive lymphomas, particularly those who have failed prior CAR-T treatments.
SynKIR-310: A Novel CAR-T Approach
SynKIR-310 is based on Verismo's killer immunoglobulin-like receptor (KIR)-CAR platform, developed at the University of Pennsylvania. This dual-chain CAR T-cell platform utilizes a natural killer cell-derived KIR and DAP12, which acts as a novel costimulatory molecule for T-cells, to enhance expression and persistence. The KIR-CAR platform is designed to promote sustained antitumor activity of CAR T-cells, even in challenging tumor microenvironments.
SynKIR-310 incorporates a proprietary CD19 (搜索) binder, DS191, specifically developed to target B-cell driven diseases. Verismo anticipates that DS191 will confer prolonged antitumor function and persistence compared to currently available CAR-T products. This is particularly relevant given that 40% to 50% of patients treated with approved CAR-T therapies experience disease relapse, often attributed to limitations in long-term T-cell effector function and persistence.
Addressing Unmet Needs in B-NHL
"Verismo Therapeutics (搜索) is uniquely positioned with SynKIR-310 to address the significant challenges in treating r/r B-NHL, including cases where patients have relapsed after receiving approved CAR-T therapies," said Laura Johnson, PhD, Chief Scientific Officer of Verismo Therapeutics. "The SynKIR-310 technology is designed to enhance the antitumor activity and extend the efficacy of T-cells, potentially improving persistence and preventing early disease relapse in patients with aggressive lymphomas. SynKIR-310 could be especially beneficial for patients that relapsed after previous infusions of CAR T-cell therapies."
Verismo's Broader Pipeline
Verismo is also developing SynKIR-110, another KIR-CAR therapy, which is currently in a Phase 1/2 trial (STAR-101; NCT05568680). SynKIR-110 targets mesothelin (MSLN)-expressing tumors and is being evaluated in patients with MSLN-expressing pleural mesothelioma, cholangiocarcinoma, or ovarian cancer. The FDA granted Fast Track designation to SynKIR-110 in April 2023 for MSLN-expressing cancers.