Verismo Therapeutics’ CAR-T SynKIR-310 Cleared for Trial in R/R B-NHL
Verismo intends to go forward with plans for the phase 1 CELESTIAL-301 clinical trial, which the company expects to initiate in the second half of this year.
Verismo Therapeutics has received clearance of an investigational new drug (IND) application from the FDA for the evaluation of SynKIR-310, a chimeric antigen receptor T-cell (CAR-T) therapy based on the company's killer immunoglobulin-like receptor (KIR)-CAR platform, in patients with relapsed/refractory (r/r) B-cell nonHodgkin lymphoma (B-NHL).1
In light of IND clearance, Verismo intends to go forward with plans for the phase 1 CELESTIAL-301 clinical trial (NCT identifier pending). CELESTIAL-301, which the company expects to initiate in the second half of this year, will seek to recruit patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Patients who have previously received treatment with a CAR-T therapy but have disease that was refractory or relapsed, and patients who have not previously received CAR-T, will be eligible for participation in the study.
The KIR-CAR platform, which was developed at the University of Pennsylvania, is intended to enable sustained antitumor activity of the CAR T-cells in difficult tumor microenvironments.2 KIR-CAR is a dual-chain CAR T-cell platform that uses a natural killer cell derived KIR and DAP12, which acts as a novel costimulatory molecule for T-cells, to improve expression and persistence.1,2
SynKIR-310 also incorporates a proprietary CD19 binder, referred to as DS191, that was developed to enable CAR-T therapies based on Verismo’s platform to target B-cell driven diseases. Verismo expects DS191 may confer potential for prolonged antitumor function and persistence in comparison to currently available CAR-T products. As such, SynKIR-310 is expected to address gaps in the needs met by current FDA-approved CAR-T therapies for hematologic malignancies; Verismo points out that 40% to 50% of patients treated with approved CAR-T options eventually experience disease relapse attributed partially to shortcomings with long-term T-cell effector function and persistence.
"Verismo Therapeutics is uniquely positioned with SynKIR-310 to address the significant challenges in treating r/r B-NHL. This includes cases where patients have relapsed after receiving approved CAR-T therapies," Laura Johnson, PhD, the chief scientific officer of Verismo Therapeutics, said in a statement.1 "The SynKIR-310 technology is designed to enhance the antitumor activity and extend the efficacy of T-cells. This could potentially improve persistence and prevent 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 has 1 other KIR-CAR therapy in clinical development: SynKIR-110, which is currently being evaluated in the first-in-human phase 1/2 STAR-101 study (NCT05568680).2 SynKIR-110 is based on the same KIR-CAR platform as SynKIR-310, but combines an mesothelin (MSLN)-specific antibody with natural killer cell signals to target MSLN-expressing tumors. STAR-101 is evaluating SynKIR-110 in patients with MSLN-expressing pleural mesothelioma, cholangiocarcinoma, or ovarian cancer, at the University of Pennsylvania. The FDA granted fast track designation to SynKIR-110 in April 2023 for treating MSLN-expressing cancers after clearing its investigational new drug application and granting orphan drug designation to the therapy in September 2022.3,4,5 STAR-101 was initiated in May 2023 and the first patient was reported to have been dosed in September 2023.2,6
"SynKIR-110 is the first product to use the novel KIR-CAR platform,” Johnson said in a statement when the company submitted STAR-101’s IND in April 2023.4 “Our technology incorporates a natural on/off switch that allows KIR-CAR T-cells to rest when not exposed to tumor antigens, as well as providing an enhanced cell-surface stability of the KIR-CAR. These enhancements will allow KIR-CAR T-cells to better cope with the harsh tumor microenvironment of solid tumors and, potentially, lead to better outcomes for our patients."
REFERENCES
1. Verismo Therapeutics receives IND clearance from the FDA for SynKIR™-310 in relapsed/refractory B-cell NHL. News release. Verismo Therapeutics. May 14, 2024. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-receives-ind-clearance-from-the-fda-for-synkir-310-in-relapsedrefractory-b-cell-nhl-302144410.html
2. Verismo Therapeutics announces the activation of its STAR-101 clinical trial at the University of Pennsylvania. News release. Verismo Therapeutics. May 2, 2023. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-the-activation-of-its-star-101-clinical-trial-at-the-university-of-pennsylvania-301812763.html?tc=eml_cleartime
3. Verismo Therapeutics secures fast track designation from the U.S. Food and drug administration (FDA) for SynKIR-110. News release. Verismo Therapeutics. April 5, 2023. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-secures-fast-track-designation-from-the-us-food-and-drug-administration-fda-for-synkir-110-301789884.html
4. Verismo Therapeutics announces FDA clearance of IND application for SynKIR-110™, a KIR-CAR T cell immunotherapy candidate. News release. Verismo Therapeutics. September 20, 2022. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-fda-clearance-of-ind-application-for-synkir-110-a-kir-car-t-cell-immunotherapy-candidate-301627645.html
5. Verismo Therapeutics receives U.S. FDA orphan drug designation for SynKIR-110™, a first-in-class KIR-CAR T cell immunotherapy candidate, for the treatment of mesothelioma. News release. Verisoma Therapeutics. September 28, 2022. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-receives-us-fda-orphan-drug-designation-for-synkir-110-a-first-in-class-kir-car-t-cell-immunotherapy-candidate-for-the-treatment-of-mesothelioma-301635551.html
6. Verismo Therapeutics doses first patient in groundbreaking SynKIR-110 clinical trial for advanced cancers. News release. Verismo Therapeutics. September 6, 2023. Accessed May 16, 2024. https://www.prnewswire.com/news-releases/verismo-therapeutics-doses-first-patient-in-groundbreaking-synkir-110-clinical-trial-for-advanced-cancers-301918684.html?tc=eml_cleartime/
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