Crossbow Therapeutics Nominates its Second Development Candidate, CBX-663, a Broadly
Acting Therapeutic for a Wide Range of Solid and Hematologic Malignancies
Potent TCR-mimetic CD3 T-cell engaging antibody targets peptide HLA complexes from TERT, a
broadly expressed tumor antigen
Preclinical studies demonstrate strong efficacy and a favorable safety profile
Nomination expands Crossbow’s pipeline and reinforces the scalability of its T-Bolt™ platform to
treat a wide range of cancers
CAMBRIDGE, Mass., July 23, 2025 – Crossbow Therapeutics, Inc., a biotechnology company
developing T-Bolt™ therapies, a novel class of T-cell receptor (TCR)-mimetic antibody
therapeutics, today announced the nomination of its second development candidate, CBX-663,
for the treatment of a broad range of solid tumor and hematologic malignancies. The next-
generation T-cell engager targets telomerase reverse transcriptase (TERT), a protein that drives
tumor growth and is expressed in up to 95% of cancers. 1 , 2
CBX-663, a bispecific antibody, binds to TERT-derived peptide human leukocyte antigen (pHLA)
complexes on the surface of tumor cells and activates T-cells through a CD3-binding arm. The
molecule includes two binding domains for TERT, which increase its ability to engage tumor
cells and boost immune activation.
“CBX-663 illustrates how Crossbow’s TCR-mimetic platform can unlock new opportunities for
antibody-based cancer therapies,” said Briggs Morrison, MD, Chief Executive Officer of
Crossbow. “With strong preclinical performance selectively targeting a pHLA expressed across a
broad range of cancers, CBX-663 has the potential to offer a meaningful new treatment option
for patients with limited therapeutic options.”
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.
The candidate also demonstrated a favorable safety profile and pharmacokinetics comparable
to conventional antibody therapies. Crossbow presented data summarizing the initial
characterization of CBX-663 at the 2025 Annual Meeting of the American Association for Cancer
Research (AACR).
Although TERT resides inside the cell, HLA molecules can present fragments of the protein,
known as peptides, on the tumor surface. CBX-663 recognizes one of those peptides, the HLA-
A*02:01-restricted TERT540 peptide, and redirects T-cells to attack tumor cells. CBX-663
demonstrated broad cytotoxic activity in vitro in both solid and hematologic cancer cell lines, as
well as in primary patient samples ex vivo. In vivo studies further confirmed its anti-tumor
efficacy and tolerability.
“CBX-663 reflects the depth of antibody discovery and protein engineering that underpins our
T-Bolt TM platform and our ability to generate highly selective, potent molecules against difficult
cancer targets,” said Dmitri Wiederschain, PhD, Chief Scientific Officer of Crossbow. “Its
performance in preclinical models reinforces the promise of TCR-mimetic therapeutics, and
we’re excited to continue advancing this program.”
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.
The nomination of CBX-663 underscores the platform’s potential to deliver a scalable pipeline
of T-cell engagers for difficult-to-treat cancers.
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.
Investor Contact:
Crossbow Therapeutics, Inc.
Geraldine Paulus, Co-Founder, Head of Corporate Development and Operations
Geraldine.paulus@crossbowtx.com
Media Contact:
SmithSolve
Corey Carmichael
(862) 260-7929
Corey.carmichael@smithsolve.com
—
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.