The idea to build a company around degrader-antibody conjugates (DACs)—not to be confused with antibody-drug conjugates (ADCs)—has been bubbling for a while. But not just anyone could pick up the gauntlet and fly with it.
About a year ago, a team with backgrounds at some of the biggest pharmas in the ADC space came together at Versant Ventures’ Ridgeline discovery engine in Basel, Switzerland. It was time.
Firefly Bio, assemble.
Today, that company breaks stealth with $94 million co-led by Versant and MPM BioImpact, plus Decheng Capital and Eli Lilly. Firefly has a novel platform to develop DACs, which combine ADCs with protein degraders to create a new class of therapies to fight cancer.
Versant Ventures Managing Director Jerel Davis, Ph.D., said the firm realized that the next step in ADCs was DACs, but scaling that while maintaining potency was going to be difficult. They knew they were going to need experts from the likes of Genentech, Merck & Co., AbbVie and others—plus a platform.
A little waiting brought together a dream team. Scott Hirsch, who previously served as chief operating officer at Allakos and did time at Genentech and AbbVie, will serve as CEO; co-founder and Chief Scientific Officer John Flygare, Ph.D., led the ADC teams at Genentech and Merck; Bernhard Geierstanger, Ph.D., who will be chief technology officer, did the same at Novartis and Merck; and then the pièce de résistance: Nobel laureate Carolyn Bertozzi, Ph.D., an ADC expert.
“We thought about doing this for a while. We hesitated, until Carolyn, John, Bernhard and Scott all were able to come together and do this with us. But it's on that basis we knew we had a real advantage to try to crack this field,” Versant's Davis said in an interview.
Breaking down the science, Hirsch said Firefly is going to try to flip the script on ADCs.
“Over the last 20 years ADCs, have been dominated by toxins, and what we're trying to do at Firefly is introduce a new payload class with the same level of potency as toxins, but that can do a better job discriminating healthy from diseased tissue,” the new CEO said in an interview.
The focus will be on protein degraders, which use the cell’s natural degradation machinery to eliminate disease-causing proteins.
“If we are able to do that successfully, we think we're going to be able to unlock substantially new biology for the ADC class beyond just the three mechanisms that are approved in ADCs right now,” Hirsch said.
Firefly emerges at a time when ADCs are all the rage and pharmas have been snapping up deals left and right. It’s not a new modality, but Firefly’s leaders insist their approach is different.
However, Davis admitted that some recent deals have stepped into the biotech’s lane. Merck’s $610 million biobucks partnership with C4 Therapeutics focuses on DACs; Seagen (now owned by Pfizer) paid $60 million to collaborate with Nurix Therapeutics; and Bristol Myers Squibb paid $800 million upfront for a couple solid tumor ADC degraders from SystImmune.
But Davis thinks Firefly is slightly ahead of the game with a single company focused on DACs and a lead asset already chosen.
“As evidenced by those deals last year, the ecosystem’s kind of waking up to this approach. And we're happy we've been working on this for two years, so we have an advantage,” Davis said.
The company will focus on solid tumor targets that have already been validated in the clinic, specifically targets that have run up against dose-limiting toxicities and could use a more precise approach. Hirsch declined to name the target specifically, but the company has apparently zeroed in on a program and has been establishing proof-of-concept over the past year.
The ADC interest helped build out Firefly’s syndicate, attracting Lilly—which has also dipped into the ADC frenzy to buy Mablink Bioscience last year.
Firefly is not the only ADC-related biotech to raise funds this week. ProfoundBio picked up $112 million from Ally Bridge Group, Lilly Asia Ventures, RA Capital Management, OrbiMed, Medicxi and LifeSci Venture Partners. The biotech has three clinical-stage candidates to work on already.
With the funds in hand, Hirsch said the next plan is to staff up. He's in the fortunate position of hiring at a time when much of the industry is reeling from layoffs. It means he's already been able to snag some great ADC talent.
It all lends to the fortuitous timing of Firefly, plus the right team and the right science.
“We've understood what the core platform limitations have been for ADCs traditionally, and we've tried to improve upon both the platform and payload toxicity associated with this exciting class,” Hirsch said.
“We think that if we can deliver a more selective payload, more selectively target tissue, we have the opportunity to substantially improve the therapeutic index and clinical outcomes for patients.”