CBX-663 / Crossbow Therap - LARVOL DELTA

CBX–663, a novel TCR-mimetic T-cell engager targeting a telomerase reverse transcriptase (TERT) peptide-HLA complex, that exhibits potent efficacy against AML cells (ASH 2025) - "Additional studies confirmed the specificity anddevelopability of CBX-663, including a pharmacokinetic (PK) study in humanized FcRn mice, whichdemonstrated a conventional IgG-like PK profile with a half-life ≥12 days.Collectively, these data strongly support the therapeutic potential of CBX-663 in myeloid malignancies,including AML. IND enabling studies are currently underway with the goal of advancing CBX-663 intoclinical development."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD123 • CD33 • CD34 • HLA-A • IL3RA • TERT • TP53

Crossbow Therapeutics Nominates its Second Development Candidate, CBX-663, a Broadly Acting Therapeutic for a Wide Range of Solid and Hematologic Malignancies (Businesswire) - "Crossbow Therapeutics...announced the nomination of its second development candidate, CBX-663, for the treatment of a broad range of solid tumor and hematologic malignancies....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....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....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."

Pipeline update • Preclinical • Hematological Malignancies • Solid Tumor

Discovery and preclinical characterization of novel TCR-mimetic T-cell engagers targeting TERT peptide-HLA complex for the treatment of solid and hematologic malignancies (AACR 2025) - "Although several TERT-targeting approaches are being investigated in clinical trials, only one therapeutic (RYTELO®, imetelstat) has received FDA approval for the treatment of low-risk myelodysplastic syndrome...Here we report the preclinical characterization of potent and specific TCRm-based TCEs targeting TERT540 pHLA...Comprehensive analytical and biophysical assessments revealed favorable developability profiles for both TCEs. In summary, these data provide strong preclinical evidence of potency, specificity, safety, and developability of novel, TCRm-based TCEs for TERT-targeted cancer therapy."

Preclinical • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • CD34 • HLA-A • IFNG • TERT