Ascendis axes IL-2 program in retreat from oncology expansion

Ascendis Pharma has ended internal development of its IL-2 candidate, pivoting away from oncology and calling time on an asset the Danish biopharma had once tipped for accelerated approval.

Copenhagen-based Ascendis made its name developing treatments for rare endocrinology diseases. But having validated its prodrug technology in that context, the company identified opportunities to apply the platform to oncology and ophthalmology. Ascendis created Eyconis to explore the use of its platform to treat eye diseases, but kept its oncology programs in-house.

Thursday, Ascendis rowed back from the expansion strategy by ending internal development of TransCon IL-2 β/γ. Also called onvapegleukin alfa, the asset is part of a long, industry-wide line of drug candidates designed to overcome the toxicity and dosing challenges that have limited IL-2’s impact on cancer care. 

Ascendis said it axed the asset because “internal oncology development does not align with our strategic focus.” The biotech stopped enrolling patients in a study of another cancer candidate, TransCon TLR7/8 Agonist, in 2024 to prioritize the IL-2 program. Ascendis’ pipeline is now focused on rare endocrinology diseases, bringing its R&D activities in line with its commercial portfolio.

The company said it will explore other ways to maximize the value of TransCon IL-2 β/γ. Ascendis shared the news alongside phase 1/2 data on the candidate, which it linked to a median overall survival (OS) of up to 10 months in patients with platinum-resistant ovarian cancer. The company compared its results to historical control data, showing an OS of six to seven months. 

TransCon IL-2 β/γ was generally well tolerated, Ascendis said. Tolerability is a major problem for IL-2. A recombinant form of the cytokine, Proleukin, pioneered the concept of immuno-oncology when Chiron won FDA approval for the drug almost 30 years ago. But toxicities, including cytokine storm and vascular leak syndrome, plus a short half-life, limited the therapeutic and commercial impact of the medicine. 

In 2018, Bristol Myers Squibb bet $3.6 billion that Nektar Therapeutics had solved the IL-2 problem, only for the biotech’s prodrug to deliver lackluster data and contribute to the collapse of other efforts to tame the cytokine.