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March 5, 2024

Press Release

Crossbow Therapeutics Selects First Development Candidate from its Portfolio of Next-Generation T-cell Engagers Directed at Intracellular Cancer Targets


CBX-250 is a first-in-class, potent, and specific T-cell engager for the treatment of myeloid leukemia


Abstract summarizing preclinical characteristics of CBX-250 selected for an oral presentation at the American Association for Cancer Research (AACR) 2024 Annual Meeting


Novel T-Bolt™ therapy being developed in strategic collaboration with MD Anderson


CAMBRIDGE, Mass., March 5, 2024 – Crossbow Therapeutics, Inc., a biotechnology company focused on advancing T-Bolt™ therapies, a novel class of antibody therapeutics that mimic T-cell receptors (TCR-mimetics), today announced the nomination of its first development candidate, CBX-250, a first-in-class, potent, and specific T-cell engager (TCE) for the treatment of myeloid leukemia. 


Researchers from Crossbow and The University of Texas MD Anderson Cancer Center will present an abstract describing preclinical characteristics of CBX-250 at the American Association for Cancer Research (AACR) 2024 Annual Meeting in San Diego, Calif., which takes place April 5-10, 2024. The oral presentation will provide an overview of the preclinical characteristics of CBX-250, which targets a cathepsin G (CTSG) peptide-human leukocyte antigen (pHLA) complex. The complex is abundantly expressed on leukemic cells, but not on normal cells, allowing CBX-250 to target cancer cells efficiently while sparing normal myeloid cells. CBX-250 may offer an enhanced therapeutic window compared with TCEs that have shown limited clinical benefit in the treatment of myeloid malignancies, due to the lack of tumor-specific surface antigens. 


“Nominating CBX-250 as a development candidate validates our initial scientific hypothesis, and it brings us a step closer to entering the clinic and ultimately helping to cure cancer,” said Briggs Morrison, Chief Executive Officer of Crossbow. “We have selected a promising therapeutic that is highly accurate and potent in preclinical models. We’re pleased to collaborate with the team at MD Anderson and look forward to continuing to advance CBX-250 to the clinic.”


The discovery and preclinical development of CBX-250 are the results of an ongoing strategic collaboration between Crossbow and MD Anderson. Gheath Alatrash, DO, PhD, and Jeffrey Molldrem, MD, led the discovery and validation of the CTSG-derived peptide, known as CG1, via functional studies with CG1-specific T-cells and via mass spectrometry through interrogation of patient samples. 


Working with MD Anderson’s ORBIT platform, a core component of the institution’s Therapeutics Discovery division, Dr. Molldrem led the development of a TCR-mimetic binder to the CG1 pHLA complex, which Crossbow licensed for the development of off-the-shelf cancer immunotherapies. The team at Crossbow further enhanced the developability of the precursor molecule, incorporated it into an optimized TCE format, and carefully verified the construct’s potency, specificity, and manufacturability. 


“We are proud of our work with Crossbow on the CBX-250 development program, which represents a true collaboration between two innovative teams,” commented Jeffrey Molldrem, MD, Chair of Hematopoietic Biology and Malignancy and leader within Therapeutics Discovery at MD Anderson. “Through our strategic collaboration, we are working to advance CBX-250 rapidly into the clinic, and we hope to see these promising preclinical findings translated into a therapy that will positively impact the lives of patients.”


CBX-250 is the first candidate in Crossbow’s portfolio of novel investigative therapies that target intracellular cancer antigens using TCR-mimetics. The upcoming AACR presentation will focus on the potency, specificity, and safety of CBX-250 in targeting leukemic myeloid cells versus normal tissues, as demonstrated preclinically both in vitro and in vivo. 


“The emergent field of TCR-mimetic antibody-based therapies is full of untapped therapeutic potential, with no approved drugs to date,” said Dmitri Wiederschain, PhD, Chief Scientific Officer of Crossbow. “Nominating CBX-250 as our first development candidate, based on our rigorous selection criteria, puts us at the forefront of an important opportunity to broaden the benefits of immunotherapy for those living with cancer and to target the entire universe of cancer antigens.”


AACR 2024 Annual Meeting presentation details 

  • Title: Characterization of CBX-250, a first-in-class TCR-mimetic-based T-cell engager targeting a cathepsin G peptide-HLA complex for the treatment of myeloid leukemia (abstract #1236)

  • Presenting Author: Geraldine Paulus, PhD

  • Session Title: Tumor-Targeted Immune Cell Engagers

  • Session Date/Time/Location: Sunday Apr. 7, 2024, 3:00PM-5:00PM PDT, San Diego Convention Center


For more information on the abstract, the full text is available here.  

Investor Contact:
Crossbow Therapeutics, Inc. 
Geraldine Paulus, Co-Founder, Vice President of Corporate Development and Operations 

Media Contact: 
Corey Carmichael 
(862) 260-7929 

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