Financial Terms and Partnership Scope
Astellas has agreed to up to $285 million in upfront and option payments to get an opportunity to license the preclinical immuno-oncology program from Audax Biosciences.
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 overcome the problems of dosing and toxicity that have marred the development of IL-12 drugs for decades. The cytokine has been resurfacing in 2022 and 2023, following its rejections by AstraZeneca, Bristol Myers Squibb, and Merck KGaA in the previous couple of years.
Audax believes that the likelihood of IL-12 medications binding to receptors on immune cells of the periphery is a source of the dosing and toxicity challenges. The biotech has engineered DAX-044 to bind with a reduced affinity to IL-12R, thereby avoiding activation of peripheral immune cells and toxic effects on the system.
Extending Half-Life and Enhancing Tumor Targeting
This also means that if affinity for IL-12R is reduced, then DAX-044 will also have a longer half-life, because it will not be consumed by circulating immune cells. Audax also went one step further and extended the drug candidate’s half-life by fusing the Fc region of an antibody.
Additional modifications include the inclusion of an antibody fragment binding domain that targets an antigen that is expressed by some immune cells in the tumor microenvironment (TME). Low binding to peripheral immune cells and high binding to the TME might increase efficacy with less systemic toxicity.
A drug candidate with a broader therapeutic window than the previous IL-12 R&D efforts would result if the design is successful. Previous IL-12 drug development efforts have had a less than successful history, with the 1990s’ 17-patient study showing 12 hospitalizations and two deaths. Teams have since attempted to lower toxicity and frequency of treatments using various technologies but, to date, have been unsuccessful in getting a drug to market.
Audax hasn’t yet demonstrated its asset’s performance in humans. DAX-044 is in IND-enabling development and is on track to enter the clinic next year. If Astellas exercises its option, it will take on 100 percent responsibility for worldwide development, manufacturing, and commercialization. Audax is an option to co-fund and co-promote DAX-044 in Australia and New Zealand.
The Broader IL-12 Competitive Landscape
After the Big Pharma exodus in 2022 and 2023, the vast majority of IL-12 drug development occurred at biotech businesses. Gilead may also be poised to play in the IL-12 space next year when Xilio Therapeutics plans to share the results of its phase 2 trial, to help inform the option that Gilead acquired in 2024.
Last year, Imunon began a phase 3 trial of its own IL-12 candidate, based on an expression plasmid and a synthetic lipopolymer delivery system, in epithelial ovarian cancer (EOC) and other solid tumors. There are also IL-12 programs in the clinic at Iovance Biotherapeutics, PDS Biotechnology, and Philogen.
Astellas Makes a Major Investment in Audax’s Cancer Research
Astellas has entered into an agreement with Australian biotechnology company Audax Biosciences that could be worth up to $1.34 billion, excluding royalties, to advance DAX-044, an experimental immuno-oncology candidate. The agreement gives Astellas an exclusive option to obtain worldwide rights to develop, manufacture, and commercialize the therapy. The deal reflects continued pharmaceutical industry interest in finding new ways to activate the immune system against cancer while reducing treatment-related toxicity.
Audax is expected to continue the development work needed to prepare DAX-044 for a Phase 1 study in 2027. Early clinical testing will be important for assessing tolerability, safety, dosing, and initial biological activity in humans.
The next major milestones include progressing through the necessary regulatory and trial preparations, beginning human studies, and generating data that can inform future development decisions. Astellas will need to decide whether to exercise its option under the agreement, subject to the applicable contractual conditions.
The potential financial value of the deal highlights the opportunity investors and pharmaceutical companies see in differentiated cancer immunotherapies. Nevertheless, milestone payments and royalties depend on future events and should not be interpreted as guaranteed revenue.
