Izalontamab Brengitecan Granted Breakthrough Therapy Designation

SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, and Bristol Myers Squibb (BMS) announced that the U.S. FDA has granted Breakthrough Therapy Designation (BTD) to izalontamab brengitecan (iza-bren).

This antibody-drug conjugate (ADC) treats locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy.

Iza-bren is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of China.

Iza-bren is a potential first-in-class bispecific ADC that targets epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3) with a topoisomerase 1 inhibitor payload. 

While EGFR TKIs have shown clinical efficacy in the frontline setting, most patients eventually experience disease progression after approximately 18 months. Subsequent treatment options often contain platinum-based chemotherapy, which is of limited efficacy and comes with significant toxicities. 

Breakthrough Therapy Designation from the US FDA is intended to expedite the development and review of drugs that may demonstrate significant benefit over current standards of care.

The FDA’s decision was based on efficacy and safety data from three ongoing clinical trials: BL-B01D1-101 and BL-B01D1-203, conducted in China by Sichuan Biokin Pharmaceutical Co., Ltd., and the global BL-B01D1-LUNG-101 study conducted by SystImmune across the United States, Europe, and Japan. 

Across these trials, iza-bren demonstrated evidence to suggest improved efficacy with a manageable safety profile in patients with EGFR-mutant NSCLC who had progressed after third-generation EGFR TKIs and platinum-based chemotherapy.

“The FDA’s granting of Breakthrough Therapy Designation underscores the potential of iza-bren to meaningfully improve clinical outcomes for patients with previously treated epidermal growth factor receptor mutation NSCLC,” said Dr. Jonathan Cheng, Chief Medical Officer of SystImmune. “The data we have generated to date suggest that iza-bren could address a critical unmet need in patient care, and we look forward to working closely with the FDA to conduct the relevant clinical studies and seek regulatory approval.”