Firefly Bio emerges from stealth to develop degrader-antibody conjugates

Propelled by $94 million in series A financing, Firefly Bio emerged from stealth mode on Feb. 15. The firm will develop a new modality of cancer medicines called 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 make a beeline to cancer cells to deliver a cytotoxic payload. DACs’ payloads are not toxins but targeted protein degraders —compounds designed to enter cancer cells and 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. ADCs first entered clinical trials about 40 years ago, and after some fitful years, they are hitting their stride, with dozens of ADC deals in 2023. But 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 them prone to getting sucked up into cells nonspecifically. “We think it requires different technology to unlock this payload,” Hirsch says, noting that Firefly has custom built its platform for the task. “We think that’s going to be a difference maker in this space.”

The start-up was cofounded by Nobel Prize winner Carolyn Bertozzi, along with industry ADC experts John Flygare and Bernhard Geierstanger, who now hold chief scientific officer and chief technology officer roles at the company, respectively. Firefly received its early nurturing through its founding investor, Versant Ventures’ incubator Ridgeline Discovery in Basel, Switzerland. Firefly’s current round of financing came largely from Versant, along with other parties, including Eli Lilly and Company. The money will support two colead programs advancing toward the clinic as well as the creation of a broad DAC portfolio, Hirsch says.