J&J lights up $1bn offer for pan-KRAS developer Firefly

Johnson & Johnson has continued to build its presence in KRAS-targeting drugs for cancer with a $1 billion agreement to buy Firefly Bio and its degrader-antibody conjugate (DAC) platform.

The all-cash deal comes just over two years after South San Francisco-based Firefly emerged onto the scene with $94 million in first-round financing backed by investors including Versant Ventures, MPM and Eli Lilly.

The company has been operating in quiet mode since then, but according to J&J, it has been working on directing its Firelink DAC platform towards KRAS-driven tumours, which have become a big target for cancer drug developers.

"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," said John Reed, J&J's head of innovative medicine R&D.

"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 tumours," he added.

KRAS mutations occur in nearly a quarter of all human cancers, with G12D the most commonly encountered. J&J said that Firefly expands its position in 'pan-KRAS' molecules, designed to target all variants of the KRAS protein.

The class hit the headlines at ASCO this year when Revolution Medicines' daraxonrasib – in the related pan-RAS class – delivered a big result in pancreatic cancer, which in around 90% of cases has a mutation in the KRAS oncogene. The RASolute 302 study demonstrated unprecedented survival improvement in the notoriously aggressive and hard-to-treat disease.

J&J is already active in KRAS, developing an oral KRAS G12C inhibitor in partnership with Jacobio Pharma, glecirasib, which is currently heading for phase 3 clinical trials in patients with non-small cell lung cancer (NSCLC) and colorectal cancer.

Glecirasib is in the same class as the only two approved KRAS inhibitors to date – Amgen's Lumakras (sotorasib) and Bristol Myers Squibb's Krazati (adagrasib) – and one of a series of next-generation candidates coming through the industry pipeline, including Eli Lilly's olomorasib, Genfleet's fulzerasib, and InxMed's garsorasib.

Some KRAS-directed degraders have already started clinical testing, notably including Astellas Pharma's KRAS G12D-targeted ASP4396, which reached phase 1 before being discontinued, and follow-up setidegrasib (ASP3082), which is in phase 3 for NSCLC and pancreatic cancer. Another is Arvinas' ARV-806, another G12D-targeted degrader in phase 1.

J&J said Firefly's platform can "overcome limitations of existing treatments by delivering a highly selective protein degrader to tumour cells, while avoiding healthy cells."

Image by Diana Wolfskin from Pixabay