Astellas has struck a deal for Audax Biosciences’ IL-12 program, committing up to $285 million in upfront and option fees to secure a chance to license the preclinical immuno-oncology program.
The deal, which includes up to $1.05 billion in milestones, gives Astellas an option on DAX-044. Audax has designed the cytokine-antibody fusion molecule to address the dosing and toxicity issues that have thwarted IL-12 drug development for decades. A resurgence of Big Pharma interest in the cytokine sputtered out in 2022 and 2023, when AstraZeneca, Bristol Myers Squibb and Merck KGaA cut programs.
Audax sees the propensity for IL-12 drugs to bind receptors on peripheral immune cells as a driver of the dosing and toxicity issues. By engineering DAX-044 to have lower affinity for IL-12R, the biotech aims to minimize activation of peripheral immune cells, preventing systemic toxicity.
Reducing affinity for IL-12R could also increase the half-life of DAX-044 because the drug isn’t being used up by circulating immune cells. Audax further extended the drug candidate’s half-life via fusion to the Fc region of an antibody.
Other modifications include the addition of an antibody fragment binding domain that directs DAX-044 to an antigen expressed on certain immune cells in the tumor microenvironment (TME). Minimizing binding to peripheral immune cells while enhancing TME engagement could boost efficacy while limiting systemic toxicity.
If successful, the design will yield a drug candidate with a wider therapeutic window than earlier IL-12 R&D programs. The history of unsuccessful IL-12 drug development dates back to the 1990s, when a 17-patient phase 2 study featured 12 hospitalizations and two deaths. Since then, teams have used a range of technologies to try to minimize toxicity and reduce dose frequency without managing to get a drug to market.
Audax has yet to show how its asset performs in humans. DAX-044 is in IND-enabling development and is on track to enter the clinic next year. If Astellas exercises its option, the Japanese drugmaker will be fully responsible for global development, manufacturing and commercialization. Audax has an option to co-fund and co-promote DAX-044 in Australia and New Zealand.
Following the Big Pharma exodus of 2022 and 2023, IL-12 drug development largely advanced at biotech companies. Gilead could enter the IL-12 space next year, when Xilio Therapeutics expects to share phase 2 data to inform the option that Gilead secured on a tumor-activated asset in 2024.
Imunon started a phase 3 trial of its own IL-12 candidate, which uses an expression plasmid and a synthetic lipopolymer delivery system, last year in epithelial ovarian cancer and related solid tumors. Iovance Biotherapeutics, PDS Biotechnology and Philogen also have IL-12 programs in the clinic.
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