Clasp Therapeutics Unveils First-in-Class KRas T Cell Engager CLSP-5282 at AACR 2026
Press Release
April 20, 2026
Clasp Therapeutics Unveils First-in-Class KRas T Cell Engager CLSP-5282 at AACR 2026
CLSP-5282 is a first-in-class KRas-directed T cell engager (TCE) and the lead program in Clasp’s broader KRas TCE portfolio spanning multiple mutation-HLA combinations
Preclinical data demonstrate potent mutation-specific tumor killing, exceptional selectivity, and robust anti-tumor activity in vitro and in vivo
Tumor models with acquired resistance to a KRas inhibitor show increased sensitivity to CLSP-5282, supporting clinical evaluation both after inhibitor progression and in rational dual-KRas targeting combinations
IND expected in 2026
CAMBRIDGE, MA and ROCKVILLE, MD – April 20, 2026 – Clasp Therapeutics, a clinical-stage biotechnology company advancing precision immuno-oncology with next-generation T-cell engagers (TCEs), today presented preclinical data at the American Association for Cancer Research (AACR) Annual Meeting on CLSP‑5282, a TCE targeting KRas G12V − one of the most prevalent oncogenic driver mutations in solid tumors. These data mark the first public disclosure of Clasp’s KRas-directed TCE pipeline and support a planned IND submission in 2026.
KRas mutations drive some of the hardest-to-treat cancers, including pancreatic, colorectal, and lung cancers. While recent advances with KRas small molecule drugs have validated this target class, responses are typically short-lived and resistance inevitably emerges. Because KRas mutations arise early in tumorigenesis and remain conserved through metastasis and inhibitor resistance, they represent durable, high-value targets for precision immunotherapy.
Clasp’s platform leverages peptide-HLA presentation to expose intracellular mutant proteins to the immune system, enabling TCEs to target oncogenic drivers inaccessible to conventional antibody approaches. CLSP-5282 targets the KRas G12V peptide presented by HLA-A*03:01, redirecting T cells to eliminate tumor cells harboring this mutation. This mutation-HLA pairing defines a substantial, well-characterized patient population and provides the foundation for a scalable pipeline of KRas TCEs targeting additional mutation–HLA combinations already validated in translational and clinical studies.
Clasp’s precision TCE platform has already advanced into the clinic: CLSP-1025, targeting the p53 R175H mutation, is currently being evaluated in the GUARDIAN-101 Phase 1 trial in patients with advanced solid tumors.
“KRas inhibitors have proven the target is druggable − but frequent resistance limits benefit to patients,” said Vipin Suri, Ph.D., Chief Scientific Officer of Clasp Therapeutics. “Intriguingly, resistance mechanisms including KRas amplification and enhanced antigen presentation are likely to increase tumor sensitivity to TCEs such as CLSP-5282. This creates a compelling opportunity for CLSP-5282 both after inhibitor resistance develops and in rational combination strategies targeting KRas through complementary, orthogonal mechanisms.”
Data Highlights:
Potent and Highly Specific Targeting of KRas G12V
CLSP-5282 drives robust mutation-specific T cell activation and cytotoxicity against tumor cells that express HLA-A*03:01 and harbor the KRas G12V mutation.
Extensive cross-reactivity profiling confirms exceptional selectivity, consistent with targeting a tumor-specific driver mutation with absolute cancer specificity.
Robust Anti-Tumor Activity in Preclinical Models
CLSP-5282 demonstrated potent anti-tumor activity in vitro and controlled growth of established tumors in mouse xenograft models.
Enhanced Activity After KRas Inhibitor Exposure
Tumor models with acquired resistance to a KRas inhibitor show increased sensitivity to CLSP‑5282.
KRas mutations are conserved following inhibitor treatment; resistance mechanisms such as KRas amplification, together with enhanced HLA presentation, sensitize tumors to TCE-mediated killing.
Rational Dual-KRas Targeting
Combining CLSP‑5282 with a KRas‑targeted small molecule demonstrated enhanced anti-tumor activity.
Complementary mechanisms and distinct resistance pathways make dual KRas targeting with inhibitors and TCEs a compelling clinical strategy.
The full poster is available to view on Clasp’s website: https://www.clasptx.com/s/Clasp_AACR_2026.pdf.
Collectively, these findings support clinical evaluation of CLSP-5282 in HLA-A*03:01-positive patients with KRas G12V-mutant solid tumors, both after KRas inhibitor progression and in rational KRas-targeting combination strategies.
About CLSP-5282
CLSP-5282 is a TCE designed to redirect T cells to tumors presenting the KRas G12V peptide in the context of HLA-A*03:01. By targeting a conserved oncogenic driver mutation through peptide-HLA presentation, CLSP-5282 enables selective and sustained immune targeting of tumor cells while sparing normal tissues. It is the first KRas-directed TCE from Clasp’s platform, with additional programs targeting further KRas mutation-HLA combinations in development.
About Clasp Therapeutics, Inc.
Clasp is pioneering precision immuno-oncology through next-generation TCEs that target tumor-specific oncogenic driver mutations common across difficult-to-treat cancers. The company’s lead program, CLSP-1025 (targeting p53 R175H), is currently being evaluated in the GUARDIAN-101 Phase 1 clinical trial in patients with advanced solid tumors. Clasp is advancing a growing pipeline of precision TCE programs, including CLSP-5282, designed to target KRas-driven cancers. Please visit www.clasptx.com to learn more.
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