Neoleukin Drops de Novo Protein Therapeutic, Slashes Workforce - Updated

Seattle-based microcap Neoleukin plans to slash its workforce by about 40% and drop NL-201, a de novo IL-2/IL-15 agonist currently in Phase I, according to the company's third-quarter report released Monday. 

NL-201 was the first fully de novo protein to be evaluated in clinical trials, according to Neoleukin. The decision to drop the candidate is unexpected, as data showed NL-201 engaged the target receptor, performed as expected in terms of pharmacodynamic changes for a potent IL-2/IL-15 agonist and did not demonstrate significant immunogenicity. 

Neoleukin noted that dropping the candidate will help it focus on “next-generation de novo proteins and core technology.” It expects these savings, combined with the savings from the reduction in staff, to extend its cash runway into 2025. 

NL-201 was being studied in combination with Merck’s Keytruda in patients with relapsed or refractory solid tumors. In May, the company reported it had treated the first patient with the combination therapy in a Phase I trial. 

As for the next steps, Jonathan Drachman, M.D., chief executive of Neoleukin, told BioSpace his team will use the information they learned from developing NL-201 to “build the next generation of de novo protein therapeutics."

"We have also diversified our tool chest by using machine learning to develop additional mechanisms of action with fully de novo proteins," Drachman said. We have other immune activators besides the IL-2/IL-15 molecule that was in the clinic."

Though Drachman did not disclose exactly which molecules the team is developing, he did state that they're drugs known to be active in oncology.

Drachman said the decision to drop NL-201 was based on the preliminary data from the trial that showed the drug would not be "dramatically differentiated" from other molecules in development in the IL-2 space.

"The space has evolved a lot in IL-2; the bar has been raised," he said. "And we really needed to make a strategic decision around the allocation of our resources."

Developments and Setbacks in IL-2 

 

Though Drachman didn't name any specific innovations in the space, there have been several recent developments that may have contributed to the company's decision.

Cue Biopharma announced Thursday that its IL-2-based biologic, CUE-101, combined with Merck’s Keytruda, was effective in patients with recurrent/metastatic HPV16+ head and neck cancer in a Phase I trial. 

And in September, Roche announced its decision to buy Good Therapeutics and its preclinical-stage PD-1-regulated IL-2 receptor agonist program for $250 million upfront. Anaveon, Aulos Bioscience, Medicenna and others also currently have IL-2 therapeutic candidates in clinical trials.

There have also been setbacks and turmoil in the IL-2 therapeutic space in recent years. 

Novartis’ Proleukin, a recombinant form of IL-2 used to treat melanoma and renal cell carcinoma (RCC) that was later acquired by Clinigen, has been limited by regulatory authorities due to its serious side effects.  

Similarly, Bristol-Myers Squibb and Nektar’s bempegaldesleukin, a pegylated form of recombinant IL-2, failed in clinical trials in melanoma, RCC and bladder cancer. It was ultimately discontinued in April.