Crossbow Therapeutics, Inc., a biotechnology company focused on developing a novel class of potent and precise antibody therapies to treat a broad range of cancers, today announced dosing of the first participant in its TelOscope-001 Phase 1 clinical trial of CBX-663, a first-in-class T-cell engager (TCE) for the treatment of multiple hematologic and solid tumors.

CBX-663 is the second candidate developed through Crossbow’s T-Bolt™ platform, a portfolio of novel TCE molecules that uniquely target peptide human leukocyte antigen (pHLA) complexes on tumor cells, using antibodies that mimic T-cell receptors (TCR-mimetics). The wholly owned TCE is a potent bispecific antibody that targets telomerase reverse transcriptase (TERT), a protein that drives tumor growth and is overexpressed in approximately 90% of all cancers.1,2

“TERT is a priority target for anticancer therapy due to its widespread overexpression, which allows cancer cells to bypass cellular aging, promotes uncontrolled tumor proliferation, and correlates with disease severity,” said Briggs Morrison, M.D., Chief Executive Officer of Crossbow Therapeutics. “CBX-663 selectively targets a TERT-derived pHLA complex expressed across a broad range of hematologic and solid malignancies, making it a promising therapeutic candidate in an area of heightened unmet medical need.”

The Phase 1, open-label, dose-escalation TelOscope-001 study is evaluating the safety, tolerability, and clinical activity of CBX-663 in patients with relapsed or refractory myeloid malignancies, advanced solid tumors, or recurrent or progressive glioblastoma multiforme (GBM).

CBX-663 binds to TERT-derived pHLA complexes on the surface of tumor cells and activates T cells through a CD3-binding arm, one half of an engineered bispecific antibody designed to grab onto the CD3 protein on T cells. The molecule includes two binding domains for TERT, which increase its ability to engage tumor cells and boost immune activation.

In preclinical studies, CBX-663 drove potent, antigen-specific tumor killing across multiple TERT-positive cancer models, with minimal activity against TERT-negative or HLA-mismatched cells. CBX-663 also demonstrated a favorable safety profile and pharmacokinetics comparable to conventional antibody therapies.

Crossbow discovered and developed CBX-663 through its proprietary T-Bolt™ platform, which uses optimized antibody libraries and precision screening to find high-affinity, specific binders to intracellular tumor antigens displayed as pHLA complexes. Crossbow designed and is conducting the TelOscope-001 clinical study, which is investigating CBX-663 on a fixed step-up dosing schedule. The company expects initial clinical data from TelOscope-001 around the end of 2027.

For additional trial details, visit the TelOscope-001 (NCT07779798) study page on ClinicalTrials.gov.

About Crossbow Therapeutics, Inc.

Crossbow Therapeutics, Inc., is a biotechnology company determined to improve the lives of people with cancer by unlocking the therapeutic potential of T-cell receptor (TCR)-mimetic antibodies. The company’s T-Bolt™ therapies are next-generation, easily assembled immunotherapies directed with high precision at previously unreachable cancer cell targets. Crossbow’s efficient and selective approach is designed to target the entire universe of cancer proteins, dramatically expanding the potential of antibody therapy to address many types of cancer. For more information about Crossbow Therapeutics, visit www.crossbowtx.com.

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1 Liu T, Yuan X, Xu D. Cancer-specific telomerase reverse transcriptase (TERT) promoter mutations: Biological and clinical implications. Genes (Basel) 2016;7(pii):E38. www.doi.org/10.3390/genes7070038.

2 Shay JW, Wright WE. Telomeres and telomerase: Three decades of progress. Nat Rev Genet. 2019;20:299–309. www.doi.org/10.1038/s41576-019-0099-1.

 

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