Clasp Therapeutics Presents Nonclinical Data Supporting GUARDIAN-101 Phase 1 Clinical Study of CLSP-1025 at the 2025 AACR Annual Meeting
Press Release
April 28, 2025
Clasp Therapeutics Presents Nonclinical Data Supporting GUARDIAN-101 Phase 1 Clinical Study of CLSP-1025 at the 2025 AACR Annual Meeting
CLSP-1025, Clasp’s first-in-class T-cell engager (TCE) targeting mutant p53, demonstrates potent preclinical activity with a favorable pharmacokinetic and safety profile, supporting its transition into clinical studies
CLSP-1025 is under evaluation in the GUARDIAN-101 trial — the first clinical investigation of a TCE targeting an oncogenic driver mutation
CAMBRIDGE, MA and ROCKVILLE, MD – April 28, 2025 – Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology with next-generation T-cell engagers (TCEs), today announced new data supporting the development of its lead program, CLSP-1025. Nonclinical data underpinning the GUARDIAN-101 Phase 1 study of CLSP-1025 were presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL on April 27, 2025.
Clasp’s approach centers on developing precision TCEs with absolute tumor specificity by targeting oncogenic driver mutations presented by human leukocyte antigen (HLA) on cancer cells. CLSP-1025 exemplifies this strategy, selectively engaging the p53 R175H mutant peptide, presented by HLA-A*02:01, to direct a potent T cell response. Given that p53 is frequently mutated in cancer—with R175H as its most common variant—and HLA-A*02:01 is highly prevalent in the US, Europe, and Asia, CLSP-1025 has broad clinical potential.
The promising nonclinical data presented at AACR support the clinical development of CLSP-1025 as a potentially transformative therapy designed to deliver durable anti-tumor responses while minimizing impact on healthy tissue. As the first clinical-stage TCE to target an oncogenic driver mutation, CLSP-1025 is currently being evaluated in the GUARDIAN-101 Phase 1 clinical trial. This study is assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of CLSP-1025 in HLA-A*02:01–positive patients with advanced solid tumors harboring the p53 R175H mutation.
“At Clasp, we’re pioneering a new era of precision immuno-oncology – one that goes straight to the source by targeting the mutations that drive cancer formation and progression,” said Vipin Suri, Ph.D., Chief Scientific Officer of Clasp Therapeutics. “The nonclinical data we presented reinforce the promise of our approach and the potential of CLSP-1025 in the GUARDIAN-101 Phase 1 trial. These data mark a meaningful step forward in our mission to deliver targeted, more effective therapies for patients with limited options.”
Data Highlights:
Selectivity: CLSP-1025 precisely targets HLA-A*02:01+ tumors expressing the p53 R175H mutation.
Activity: Preclinical studies show that CLSP-1025 induces robust, targeted T cell activation, resulting in significant regression of KMS-26 tumor xenografts in vivo.
Safety Profile: CLSP-1025 did not cause target independent T cell activation or cytokine release in peripheral blood mononuclear cells (PBMCs) or show any activity towards normal healthy tissue.
Pharmacokinetics: Rodent studies confirm CLSP-1025’s extended half-life, supporting dosing intervals of every 2 to 3 weeks in humans.
Prevalence: CLSP-1025 targets the most common p53 mutation, with the highest frequencies in gastrointestinal cancers, including colorectal (6.3%), pancreatic (4.3%), and esophageal (4.9%). HLA-A*02:01 is highly prevalent, with a population frequency of 41% in the US, 48% in Europe, and 22% in Japan.
Phase 1 design: A quantitative systems pharmacology (QSP) model was developed to predict an efficacious dose range for GUARDIAN-101. The model forecasts a half-life of approximately 16 days and suggests potential tumor regression at target peptide-HLA densities as low as 2 target molecules per cell.
About GUARDIAN-101 and CLSP-1025
Clasp’s Phase 1 GUARDIAN-101 dose escalation study evaluates the safety and initial anti-tumor activity of CLSP-1025. CLSP-1025 is a bispecific antibody-like molecule that directs a patient’s T cells to the tumor, generating a precise immune response to selectively and potently eliminate cancer cells. CLSP-1025 is designed to target the p53 R175H peptide in the context of HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have an advanced solid tumor that harbors the p53 R175H mutation. This Phase 1 study will identify the dose of CLSP-1025 for use in future studies. Visit clinicaltrials.gov (NCT06778863) for more details.
About Clasp Therapeutics, Inc.
Clasp is pioneering precision in immuno-oncology through next-generation T-cell engagers (TCEs) that target tumor-specific oncogenic driver mutations common across hard-to-treat cancers. Clasp’s platform identifies mutation-associated neoantigens and develops TCEs that can selectively bind HLA (human leukocyte antigen)-presented peptides derived from these oncogenic drivers. With their unique properties, Clasp’s TCEs are adaptable for application across a variety of cancers with high unmet need. Please visit www.clasptx.com to learn more.
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