Cambridge, Mass. — Crossbow Therapeutics, Inc., a biotechnology company developing antibody therapies for cancer, said it has dosed the first patient in a Phase 1 clinical trial evaluating CBX-663 in multiple hematologic and solid tumors.
The first-in-human 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.
CBX-663 is a first-in-class T-cell engager and the second candidate developed through Crossbow’s T-Bolt platform. The platform is designed to target peptide human leukocyte antigen complexes on tumor cells using antibodies that mimic T-cell receptors.
The wholly owned bispecific antibody targets telomerase reverse transcriptase, or TERT, a protein that Crossbow said is overexpressed in approximately 90% of cancers.
“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 open-label, dose-escalation Phase 1 study is assessing CBX-663 using a fixed step-up dosing schedule.
CBX-663 is designed to bind TERT-derived pHLA complexes on tumor cells while activating T cells through a CD3-binding arm. The molecule includes two TERT-binding domains intended to increase tumor-cell engagement and immune activation.
In preclinical studies, Crossbow said CBX-663 produced antigen-specific tumor killing across multiple TERT-positive cancer models, with minimal activity against TERT-negative or HLA-mismatched cells. The candidate also demonstrated a favorable preclinical 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 screening methods to identify binders to intracellular tumor antigens displayed as pHLA complexes.
The company expects initial clinical data from the TelOscope-001 study around the end of 2027.
