Clasp Therapeutics Doses First Patient in Phase 1 Clinical Trial With a First-in-Class T-Cell Engager Designed to Target Cancer Cells With Absolute Specificity

- CLSP-1025 targets the most common p53 mutation, a key oncogenic driver associated with multiple types of solid tumors, including gastrointestinal, lung, and gynecological cancers

- Clasp's pHLAre™ platform is optimized for tumor-specific antigens, with the potential to yield safer and more effective precision immunotherapies

- Preclinical data presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting demonstrate potent activity and favorable safety profile of CLSP-1025, supporting advancement into clinical studies

CAMBRIDGE, Mass. & ROCKVILLE, Md.--(BUSINESS WIRE)--Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T-cell engagers (TCEs), today announced dosing of the initial patient in the GUARDIAN-101 phase 1 trial of CLSP-1025, the first tumor-specific TCE to enter clinical development. CLSP-1025 exclusively targets cancer cells expressing the p53^R175H mutation, a mutation associated with a wide range of solid tumors, including colorectal, pancreatic, lung, gastric, esophageal, gynecological, and prostate cancers.

Unlike first-generation TCEs that target proteins present on both tumor and normal cells, Clasp’s TCEs target tumor-specific peptides derived from cancer driver mutations, ensuring absolute specificity and minimizing risk of toxicity to healthy tissues. Truncal mutations like p53^R175H occur early in tumorigenesis and are present in every tumor cell, making them ideal targets for immune system attack. Moreover, these pHLAre molecules (precise HLA redirecting engagers) are designed to mimic the natural T cell receptor interface between a cancer cell and T cell, maximizing anti-cancer activity.

“Treating the first patient in the GUARDIAN-101 trial marks a pivotal milestone in Clasp’s mission to transform patient outcomes through precision immunotherapy," said Dr. Lauren Harshman, M.D., SVP of Clinical Development at Clasp Therapeutics. "Advancing CLSP-1025 into the clinic is an important step in validating the potential of our pHLAre platform to overcome the limitations of current T-cell engagers and offer a breakthrough treatment option for patients.”

At the 2025 American Association for Cancer Research (AACR) Annual Meeting this week, Clasp also presented nonclinical data supporting the clinical development of CLSP-1025, including data supporting the therapeutic candidate’s selectivity, activity, pharmacokinetics and safety profile.

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.

pHLAre is a trademark of Clasp Therapeutics, Inc. All rights reserved.