ATP and Biolojic Design have teamed up to create IL-2-focused cancer biotech Aulos Bioscience. The startup begins life with IL-2-binding monoclonal antibodies designed by Biolojic Design and a $40 million funding commitment from ATP, positioning it to move into the clinic this year.
Aulos is focused on antibodies designed to redirect IL-2 from high-affinity regulatory T cells (Tregs) and toward low-affinity effector T cells, thereby minimizing the suppressive effect the cytokine has on the immune system while maximizing its activating effect. The biotech will study the antibodies in solid tumors.
Biolojic Design developed the antibodies and spun them out to create Aulos with the support of ATP, a VC shop with $2.7 billion in committed capital. The $40 million funding commitment from ATP will enable Aulos to move into human trials this year and go on to deliver clinical proof-of-concept data. If successful, the program could finally realize the full potential of an early cancer immunotherapy.
IL-2 was discovered in the 1970s, and a recombinant form of the cytokine, branded Proleukin, came to market in metastatic renal cell carcinoma in 1992. Toxicity, notably vascular leak syndrome, and a burdensome dosing schedule stemming from a short half-life have restricted uptake, though, leading researchers to try to get at IL-2 from other angles.
Biolojic Design shared details of its attempt last year, describing the use of its computational design capabilities to create antibodies that bind to a specific IL-2 epitope. The goal was to design molecules that combine with human IL-2 to form a complex that binds to dimeric receptors on effector cells but not the similar trimeric receptors found on Tregs.
In doing so, Biolojic Design aimed to redirect IL-2 away from Tregs, which cause immune suppression, and toward effector T cells that contribute to the fight against solid tumors. Research suggests Treg activation may limit the efficacy of IL-2.
There is early evidence that Biolojic Design met its goal of activating effector cells without acting on Tregs. In mice, Biolojic Design saw activation of memory phenotype CD8+ cells, natural killer cells and natural killer T cells along with minimal effect on Tregs. The antibody-IL-2 complex was more efficacious in a melanoma model than IL-2 alone was. The complex had a longer half-life, too.
Biolojic Design is far from the first research group to try to use monoclonal antibodies to overcome the limitations of IL-2. Papers describing the approach date back at least 15 years, but Aulos’ backers think its approach has clear advantages.
“Other drug candidates that redirect IL-2 fail to target naturally occurring IL-2 and introduce complex, modified, exogenous versions of IL-2 that are often difficult to manufacture and can have unfavorable pharmacokinetic properties,” Michael Ehlers, chief scientific officer and venture partner at ATP, said in a statement.
Interest in other approaches to IL-2 suggest ATP could be richly rewarded if Aulos’ antibodies live up to their promise. Bristol Myers Squibb identified IL-2 as a way to mobilize the army of T cells needed to make checkpoint inhibitors effective, leading to its mega-deal with Nektar Therapeutics. Hopes for Nektar’s prodrug approach have since faded somewhat, but the promise of IL-2 remains.