HTI-1511 Drug Description

HTI-1511 is a novel antibody-drug conjugate or ADC being developed by Halozyme, a clinical-stage biotechnology company focused on developing and commercializing novel cancer therapies.  The investigational agent is designed to target the epidermal growth factor receptor (EGFR) to potentially treat solid tumors, including those with drug-resistant mutations.

HTI-1511 was engineered to bind to EGFR at the low pH of the tumor microenvironment while, at the same time, decreasing or attenuating the binding at the neutral pH of skin. The result shown in pre-clinical studies is a targeted therapy with an encouraging safety profile.  Based on these initial result, HTI-1511 has been selected for further study as an investigational new drug candidate (Pre-IND).

HTI-1511 has been developed as a next-generation ADC with a potent cytotoxin, monomethyl auristatin E (MMAE) to treat EGFR-positive tumors, including those with KRAS and BRAF mutations.

The trial drug utilizes next generation, ThioBridge chemistry, allowing for a more homogeneous, active and stable (in primates) ADC compared to maleimide based conjugation. [1]

In preclinical studies, the drug has demonstrated tumor growth inhibition or regression in colon, lung and cholangiocarcinoma models, including patient-derived xenograft (PDx) models with known KRAS and BRAF mutations.

The company has initiated a range of studies to prepare for an IND filing.

Reference:

[1] Huang L, Veneziale B, Frigerio M, Badescu G, Li X, Zhao Q, Bahn J, Souratha J, et al. Preclinical evaluation of a next-generation, EGFR targeting ADC that promotes regression in KRAS or BRAF mutant tumors.  AACR 2016, Abstract 1217.