Clasp Therapeutics Publishes Preclinical Data on CLSP-1025, the First Clinical-Stage T-Cell Engager Targeting an Intracellular Driver Mutation, in Clinical Cancer Research
Press Release
July 24, 2026
Clasp Therapeutics Publishes Preclinical Data on CLSP-1025, the First Clinical-Stage T-Cell Engager Targeting an Intracellular Driver Mutation, in Clinical Cancer Research
Peer-reviewed publication details the preclinical characterization of CLSP-1025, a first-in-class T-cell engager (TCE) designed to selectively target cancer cells expressing the p53 R175H neoantigen, the most common p53 hotspot mutation
Data demonstrate potent, mutation-specific anti-tumor activity with extensive characterization of selectivity and safety
Findings support the ongoing Phase 1 GUARDIAN-101 trial and further validate Clasp's pHLAre™ platform approach to targeting shared oncogenic driver mutations
CAMBRIDGE, MA and ROCKVILLE, MD – July 24, 2026 – Clasp Therapeutics, a clinical-stage biotechnology company advancing precision immuno-oncology with next-generation T cell engagers (TCEs), today announced the publication in Clinical Cancer Research of preclinical data supporting its lead program, CLSP-1025. The manuscript, titled "Preclinical characterization of CLSP-1025, a first-in-class, mutation-specific T-cell engager targeting a neoantigen derived from a common p53 mutation," details the molecule's binding properties, selectivity, anti-tumor activity, and safety profile supporting the scientific rationale and clinical development of CLSP-1025 in the ongoing Phase 1 GUARDIAN-101 trial.
CLSP-1025 is designed to selectively bind cancer cells presenting the p53 R175H mutant peptide on HLA-A*02:01, redirecting a patient's own T cells to eliminate tumor cells while sparing healthy tissue. The p53 R175H mutation is the most common p53 hotspot mutation and a truncal driver present across multiple solid tumor types, including colorectal, gastroesophageal, and pancreatic cancers.
"This publication reflects the depth of characterization behind CLSP-1025 and reinforces the core premise of our platform: that intracellular driver mutations can be selectively and safely engaged by antibody-like biologics," said Vipin Suri, Ph.D., Chief Scientific Officer of Clasp Therapeutics. "Across biochemical, cellular, and in vivo models, CLSP-1025 consistently demonstrated the selectivity and potency required to safely enable durable efficacy in solid tumors with a T-cell engager that directs T-cells exclusively to cancer cells with an intracellular oncogenic mutation: a first for the field."
Key Preclinical Findings Published in Clinical Cancer Research
Potent, Mutation-Specific Activity: CLSP-1025 bound both CD3 and the HLA-A*02:01–p53 R175H complex with nanomolar affinity, and structural modeling indicated that the resulting T cell–tumor cell spacing recapitulates a physiologic immune synapse. The molecule drove dose-dependent cytotoxicity across tumor cell lines and patient-derived organoids expressing p53 R175H, with no measurable activity against wild-type p53 cell lines.
Extensive Specificity and Safety Profiling: Selectivity was assessed for both the target peptide and the target HLA, including a proteome-wide search for cross-reactive HLA-A*02-presented peptides and profiling against an HLA class I library covering >99% of US/EU haplotypes. Cell-based safety studies showed no T-cell activation against cells from 14 normal human tissues, no platelet activation in healthy donor blood, and minimal cytokine release relative to a control anti-CD3 antibody.
Robust In Vivo Anti-Tumor Activity: In humanized mouse xenograft models, CLSP-1025 drove dose-dependent tumor growth inhibition, accompanied by increased intratumoral CD8+ and CD4+ T-cell infiltration.
Favorable Pharmacokinetic Profile: CLSP-1025 demonstrated an IgG-like half-life and dose-proportional, linear pharmacokinetics in murine models, supporting an intermittent dosing schedule in the clinic.
"For patients with p53 R175H-mutated cancers, there are no approved therapies capable of directly targeting this mutation," said Lauren Harshman, M.D., Chief Medical Officer of Clasp Therapeutics. "These data underscore the potential of CLSP-1025 to achieve a level of precision previously unattainable in oncology: targeting an intracellular cancer-driving mutation while sparing healthy tissue. This precision-guided approach underpins our pipeline and is now being evaluated in the GUARDIAN-101 clinical trial."
The manuscript is available online at Clinical Cancer Research, a journal of the American Association for Cancer Research https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-26-1252/786951/Preclinical-characterization-of-CLSP-1025-a-first
About GUARDIAN-101 and CLSP-1025
Clasp's Phase 1 GUARDIAN-101 dose-escalation study (NCT06778863) is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of CLSP-1025 in adult patients with advanced solid tumors that harbor the p53 R175H mutation. CLSP-1025 is a bispecific, half-life-extended T-cell engager that targets the p53 R175H peptide presented by HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have a tumor harboring the p53 R175H mutation. Visit clinicaltrials.gov (NCT06778863) for more details.
About Clasp Therapeutics, Inc.
Clasp Therapeutics is pioneering precision immuno-oncology through next-generation TCEs that target tumor-specific oncogenic driver mutations across hard-to-treat cancers. Clasp's pHLAre™ platform identifies mutation-associated neoantigens and develops TCEs designed to selectively bind HLA-presented peptides derived from oncogenic drivers and reach intracellular targets invisible to conventional antibody therapies. Clasp is advancing a growing portfolio of precision TCE programs designed to bring precision immunotherapy to the patients who need it most. For more information, visit www.clasptx.com.
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