Synthorx reels in $63M to push synthetic cytokines into the clinic

Synthorx's expanded genetic alphabet technology allows it it to incorporate a novel amino acid at a specific place in the IL-2 polypeptide, giving it functionality that the native protein does not have. (Synthorx)

Synthorx raised a $63 million series C that will advance its pipelines of synthetic cytokines, which are designed to improve the efficacy of immuno-oncology treatments without the negative side effects that sometimes come with native cytokines. 

The funding will push Synthorx's lead molecule, Synthorin IL-2 into clinical trials in the first half of 2019. IL-2 (interleukin-2) was discovered decades ago, but the native protein has barriers that preclude its widespread use. For example, before IL-2 activates the immune system, it is immunosuppressive, and so, requires high doses to work, said Synthorx CEO Laura Shawver. Moreover, it has a short half-life, so patients need multiple doses per day. 

"It's not used very often anymore as we develop new and safer agents," Shawver said. "But we know it works if you dial down the side effects." 

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And that's what Synthorx's expanded genetic alphabet technology allows it to do. The company incorporated a novel amino acid at a specific place in the IL-2 polypeptide, giving it functionality that the native protein does not have, said Shawver. 

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"To make the best IL-2 we have seen to date, the scientific team at Synthorx applied the company’s expanded genetic alphabet technology to create specific receptor interactions with great precision that bias IL-2’s activity to immune activation versus repression," said Marcos Milla, Ph.D., Synthorx chief scientific officer, in a statement. 

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Synthorx is looking to make existing cancer therapies work for more people. It thinks its synthetic cytokines could boost the anti-tumor activity of treatments such as checkpoint inhibitors, cancer vaccines, CAR-T therapies and oncolytic viruses.  

And it's not the only one. Checkmate Pharmaceuticals recently presented data at AACR showing its CMP-001 injection, given in tandem with Merck's checkpoint inhibitor Keytruda, reversed PD-1 resistance in multiple tumor types. But Checkmate's early success doesn't mean the world of cancer combo treatments is a cakewalk—Incyte's IDO1 inhibitor epacadostat in combination with Keytruda put up disappointing phase 3 results, showing it had no benefit over Keytruda alone. The biotech ditched the trial.

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