On August 29th, 2024, Doma’s second bispecific ADC asset, DM005,  officially received IND clearance from U.S. FDA and about to begin global phase Ⅰ trial.

DM005 is designed on a bispecific strategy targeting tumor-associated antigens, e.g. the epidermal growth factor receptor (EGFR) and mesenchymal epidermal transformation factor (MET). EGFR and MET are co-expressed and overexpressed in various solid tumors, different from normal tissues, and paly important roles in tumor cell proliferation and invasion. By simultaneously targeting these two tumor-associated antigens with synergistic endocytosis, DM005 is expected to specifically deliver cytotoxic payloads to tumor cells, rather than normal tissues.Like DM001, DM005 utilizes bispecific antibodies with synergistic endocytosis, enzyme cleavable hydrophilic linkers, efficient cytotoxic loading, and novel topoisomerase inhibitors.

In the early preclinical studies, DM005 has shown strong anti-tumor activity and good safety. Animal studies indicate that DM005 can achieve tumor regression in various solid tumor models, with good tolerance and no significant toxic observations. These data have laid a solid foundation for clinical study.

The upcoming global Phase Ⅰ study will recruit patients with various types of solid tumors, including non-small cell lung cancer, head and neck cancer, and gastrointestinal tumors, etc., aiming to evaluate the safety, preliminary efficacy and pharmacokinetic characteristics of DM005 monotherapy in patients with advanced solid tumors. The results of this study will provide key indicators for further clinical development.

Dr. Song Jun, Co-CEO of Doma, said:“DM005 is the second bispecific ADC product from Doma to successfully receive IND approval in the United States. This not only enriches Doma’ pipeline of clinical-stage products, but also continuously propels the development of a new anticancer drug. Although several companies are simultaneously developing EGFR and MET bispecific ADCs, DM005 has demonstrated broader applicability in solid tumors in PDX models compared to similar products. We look forward to this drug addressing the unmet treatment needs in the global solid tumor field as soon as possible.”