Synthorx Raises $63 Million to Advance Next-Gen Immuno-Oncology Therapy

Pile of money

San Diego-based Synthorx announced it had completed a Series C financing round worth $63 million. The round was led by OrbiMed and joined by new investors, Medicxi and Osage University Partners. Existing partners Avalon Ventures, RAP Capital Management and Correlation Ventures also participated.

The monies raised will be used to advance its pipeline of Synthorin cytokines. These molecules are designed to “tune” receptor pharmacology and extend half-life. The company states, “These properties allow for efficacious immune system activation with convenient dosing schedules and without safety limitations to enhance the antitumor activity of leading immuno-oncology approaches, including checkpoint inhibitors, cancer vaccines, CAR-T therapies, and oncolytic viruses.”

The company’s lead candidate is an improved version of interleukin-2, an anti-cancer drug that was the big hot topic of oncology treatments in the 1980s. Synthorx’s improved version is Synthorin IL-2. The cytokines are involved in cell signaling and play an important role in modulating the immune system.

But interleukin-2, which was originally developed by a biotech company called Cetus, had significant life-threatening side effects, primarily fluid buildup from leaking blood vessels. The U.S. Food and Drug Administration (FDA) turned down Cetus’ application in the U.S. in mid-1990. This led to Chiron acquiring Cetus in 1991. Chiron kept working on developing IL-2 and eventually the FDA approved IL-2 (Proleukin) for metastatic renal carcinoma in 1992.

“It was the first immuno-oncology drug approved, even before we had the term immuno-oncology drug,” Synthrox’s chief executive officer, Laura Shawver, told Xconomy.

But the drug still had issues with side effects, largely because it both stimulates the immune system and represses it, depending on which type of receptor it binds to. IL-2 also degrades quickly and is generally administered in high doses as a result.

Xconomy writes, “Synthorx has set out to address the side effects in a two-step process. The first step is intended to ensure that the interleukin-2 acts only to boost the immune response by incorporating a synthetic amino acid to the protein in a specific location, Shawver said. Because interleukin-2 can bind to more than one receptor, this approach is intended to ensure that Synthorin IL-2 binds to the correct IL-receptor.”

Synthorx is utilizing technology developed in Floyd Romesberg’s laboratory at The Scripps Research Institute. Romesberg is one of the company’s founders.

The second step uses pegylation to keep the drug from breaking down so fast. The bottom line is that Synthorx’s version of IL-2 appears to have more precise immune-activation and last longer, meaning it can be administered in smaller doses.

In addition to the financing, Peter Thompson, private equity partner at OrbiMed, and Vickie Capps, an independent advisor, will join Synthorx’s board of directors.

“The ability to activate tumor-fighting immune cells has been a tremendous breakthrough in curing cancer in some patients, but the rate of responses leading to long-term remission and overall survival is still limited,” Shawver said in a statement. “Combination therapies are needed that demonstrate improved efficacy but are safe and convenient for patients. IL-2 has proven activity but limited use due to safety issues. Our investors immediately recognized the remarkable ability of our lead molecule, Synthorin IL-2, to deliver sustained cancer-killing activity without the safety liability through our unique ability to modify protein therapeutics for tuning receptor pharmacology and extending half-life.”

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