Johnson & Johnson has paid $1 billion upfront to buy itself a degrader antibody conjugate (DAC) platform via the acquisition of Firefly Bio.
DACs sit at the intersection of antibody-drug conjugates (ADCs) and targeted protein degraders (TPDs). Like ADCs, DACs feature payloads connected to targeting antibodies via linkers. In both cases, the design enables targeted payload delivery to cells that express certain receptors. The difference is that DACs carry TPDs, not cytotoxic chemotherapies, to drive degradation of proteins, including so-called “undruggable” targets.
Firefly’s Firelink DAC platform uses catalytic protein degraders as the payloads, with Firefly’s linker technology then used to decrease the amount of free payload in circulation and minimize how much reaches healthy cells. The biotech is working on therapies specifically for KRAS-driven tumors.
The company has previously referred to preclinical studies in both solid and liquid tumors, where a single administration of Firefly’s DACs showed “significant reductions in tumor volume at very low doses.”
“KRAS has notoriously been considered an undruggable target and patients with KRAS-driven cancers continue to face limited treatment options with survival measured in months, not years,” John Reed, M.D., Ph.D., Johnson & Johnson’s EVP of Innovative Medicine, Research and Development, said in the June 8 release.
“We believe the proprietary Firelink platform will overcome the limitations of current treatments and diversify our pipeline with preclinical candidates for treating multiple types of solid tumors,” Reed added.
After being incubated by Versant Ventures, Firefly fluttered onto the scene in 2024, riding a $94 million series A that was backed by the likes of Eli Lilly. The South San Francisco-based biotech is led by CEO Scott Hirsch, who had previously served as chief operating officer at Allakos. Firefly’s Chief Scientific Officer Dan Kaplan, Ph.D., previously worked at NGM Bio, where he led the discovery and development of ADCs and T cell engagers.
Big Pharmas have been paying attention to DACs since at least 2023, when Merck & Co. paid $10 million to partner with C4 Therapeutics, securing exclusive rights to DACs against one target and options on three more targets. Merck terminated the deal last November, but Roche secured its own DAC deal with the biotech two months ago.
Meanwhile, Bristol Myers Squibb paid Orum Therapeutics $100 million upfront in 2023 for ORM-6151, a DAC that uses an anti-CD33 antibody to deliver a GSPT1 degrader. Now renamed BMS-986497, the candidate is in a phase 1 trial in the blood cancers acute myeloid leukemia and myelodysplastic syndrome.
Seagen, now part of Pfizer, paid Nurix Therapeutics $60 million in 2023 to partner on DAC development. Pfizer retained the relationship after buying Seagen, with Nurix’s pipeline listing the collaboration as a discovery-stage project. While most DACs target cancers, Nurix’s internal discovery teams are exploring the modality in inflammatory and autoimmune conditions.
Despite a frenzy of Big Pharma dealmaking this year led by the likes of Lilly, J&J hasn’t been in a rush to add to its pipeline. Instead, the Big Pharma has spent recent weeks weeding out some unsatisfactory assets, including a pair of CAR-T cell therapies, and a gene therapy for a rare eye disease.