AACR: Synthekine hopes new IL-2 will be the high-alpha in a beta class

IL-2 medicines have shown the ability to kill tumors. Unfortunately, they aren’t very specific and have come to be associated with toxicities. Synthekine is hoping to avoid activating lymphocytes such as natural killer cells that can cause these issues, creating a safer and more tolerable medicine.

That’s what early data from a phase 1a/1b trial of STK-012 seem to show, CEO Debanjan Ray told Fierce Biotech on the sidelines of the American Association for Cancer Research annual meeting Monday.

The results are very early, with just a handful of partial responses. And Ray is well aware of the struggles of other IL-2s in the clinic—see Sanofi’s many challenges with the target.

Responding to some of the hurdles faced by his peers, Ray said that with STK-012, Synthekine has built a molecule called an IL-2 alpha/beta that is meant to stimulate CD25+ antigen-activated T cells but avoid the same reaction with the NK cells that can drive toxicity in IL-2 meds.

The early-stage trial tested the med in 47 patients with advanced solid tumors including non-small cell lung cancer, renal cell carcinoma and ovarian cancer. Most of the patients had three or more lines of therapy prior to entering the trial, which tested seven dose levels on two dosing schedules.

Of the 40 evaluable patients, three had a partial response as of data cutoff and 12 had stable disease. In a group of 15 patients who had not previously responded to immune checkpoint inhibitors and were minimally pretreated, three had a best overall response of partial response and six had stable disease.

“The promise of IL-2 in the treatment of solid tumors has yet to be realized as IL-2 analogues developed to date have had limited efficacy and an unacceptable toxicity profile,” said Naiyer Rizvi, M.D., Synthekine’s chief medical officer, in a Tuesday statement.

The therapy was associated with favorable safety, pharmacokinetics and pharmacodynamics, with a profile that was different from aldesleukin and non-alpha IL-2 analogues. The early data suggest that STK-012 is selective for T cells that express CD25. Ray also noted that the response was durable in multiple subjects, with some continuing to benefit for as much as a year after the data cutoff.

Synthekine’s presentation included one patient case study of a 72-year-old female who had stage 4 clear cell renal cell carcinoma and had previously had two prior lines of therapy. The patient had “innumerable lung metastases and a large primary renal mass.” At Week 12, the photos show a reduction in tumors.

“You don't need to be a radiologist to really see this difference,” Ray said.

Synthekine has selected the every-three-weeks schedule to go forward. Ray said next steps include focusing on the ongoing dose expansion, monotherapy arm including one cohort focusing on renal cancer.

While early, Synthekine’s work has attracted some Big Pharma partners, including Sanofi. The French pharma signed a $40 million deal with Synthekine in January to work on IL-10 receptor agonists designed to treat inflammatory diseases.

Merck & Co. has also linked up with the biotech but for autoimmune diseases, signing a deal that could be worth up to $525 million in biobucks in November 2021.

Editor's note: This story was updated at 5 p.m. ET to clarify details about the dose expansion and Synthekine's partnership with Sanofi.