Firefly shooting for targeted degradation sweet spot with $94M series A
15 Feb 2024
ADC
Firefly Bio emerged from stealth Thursday with $94 million in its pocket and an in-house platform that combines two of the most promising anti-cancer technologies into one next-generation modality.
Antibody-drug conjugates (ADCs) can home in on cancer cells, but carry a risk of payload toxicities. Protein degraders are strong intracellular cancer killers, but lack targeted delivery. Put ‘em together and what have you got? Degrader-antibody conjugates (DACs): a unique mix of chemistry and biology that together could overcome the shortcomings faced by each modality individually.
DAC dream team
To turn the DAC dream into reality, Firefly assembled a “crack team” of experts, he said.
Along with Hirsch, who oversaw multiple clinical ADC programmes as chief operating officer of Allakos, each Firefly co-founder knows their way around antibodies and proteins, to put it lightly. Chief scientific officer John Flygare, who was a principal scientist at Genentech and Merck & Co., has brought both modalities to the clinic. Chief technology officer Bernhard Geierstanger led ADC teams at Novartis and Merck and has built protein modification and conjugation platforms. And Nobel Prize-winning co-founder Caroyln Bertozzi is a world-leading expert in ADCs.
Firefly’s goal from its founding in 2022 was to improve upon current ADC technology, in particular the safety concerns due to their highly toxic payloads. At the same time, data was emerging for protein degraders showing that the molecules are highly capable of co-opting a cell’s natural degradation machinery to eliminate cancer-causing proteins – but they’re difficult to develop and deliver because they lack extracellular targeting.
“We thought, we know what the major limitations are with existing ADCs – why can't we build a technology and a platform that addresses all of that in one system, and use that same system to unlock a new payload class?” Hirsch said. “And so it made sense to fuse two cutting-edge technologies: ADCs, which are built for delivery and exposure, and protein degraders, which if you can get them inside of the right cells, they have so much potential.”
Lighting the way
In the past year, Firefly has demonstrated early proof-of-concept efficacy for its DACs against a wide range of targets and has built out its scalable R&D platform. Thus far, it seems to be the only biotech capable of all facets of DAC development under one roof.
DACs first made a splash last year thanks to two collaborations that combined each partners’ technology: ADC giant Seagen teamed up with degrader developer Nurix Therapeutics, and Merck paired with C4, with the latter providing protein degrader payloads.
Those deals were “just the tip of the iceberg,” Hirsch said. “We feel that DACs are the new frontier for ADCs, and we’ll see more activity in this space.”
With its $94 million series A – co-led by founding investor Versant Ventures and MPM BioImpact alongside Decheng Capital, with participation from Eli Lilly – Firefly plans to advance two DAC programmes into the clinic, while continuing to build out its portfolio of diversified payloads.
While Hirsch didn’t disclose specifics, he said the company is developing DACs with derisked payloads. “These are targets that have been drugged in the clinic systemically, but they reach a dose-limiting toxicity before they can get sufficient efficacy,” he said. “The biology is validated, the target is validated, but the approach hasn't been sufficient.”
By attaching those biologically-validated payloads to an antibody, Firefly aims to deliver them more specifically to improve the therapeutic index against those targets.
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