Start-up to develop degrader-antibody conjugates emerges from stealth

Propelled by $94 million in series A financing, Firefly Bio emerged from stealth mode on Feb. 15. The firm will develop degrader-antibody conjugates (DACs). DACs are an emerging modality in cancer therapeutics—they were first described just 5 years ago—and industry's interest in them is growing. The approach is a twist on antibody-drug conjugates (ADCs), which use antibodies to deliver a cytotoxic payload to cancer cells. DACs' payloads are not toxins but targeted protein degraders—compounds designed to escort specific disease-causing proteins to the cells' protein degradation machinery. "The idea is pretty simple—can we improve ADCs by delivering more-selective payloads," says Scott Hirsch, Firefly's CEO. With DACs "there's an opportunity to substantially improve the therapeutic index of ADCs, which has been a challenge since they've been around," Hirsch says. Working with targeted protein degraders is inherently challenging, however. The compounds are large, so they are difficult to conjugate, and their hydrophobicity makes