6:31 PM
Mar 14, 2019
 |  BC Innovations  |  Tools & Techniques

Synthetic solutions for immuno-oncology

How Synthorx is harnessing synthetic DNA to enhance biologics

Synthorx Inc. is poised to enter the clinic this year with an IL-2 therapy that could validate its synthetic DNA platform. Marrying its click chemistry and unnatural amino acid technology with pegylation, the company is building a pipeline of cytokines with tailored pharmacology, and plans to expand to other modifications and other modalities.

Fresh off a December IPO that raised $150.7 million on NASDAQ, Synthorx is lining up a suite of preclinical candidates, starting with its IL-2 immuno-oncology program THOR-707. The compound is slated for IND submission next quarter, and the company expects Phase I/II data within 12 months.

It also will select IND candidates by year-end for IL-10 and IL-15 programs in immuno-oncology, and a different IL-2 candidate for autoimmune disease.

Synthorx’s platform features synthetic DNA base pairs that encode anchor points on proteins where additional structures, such as polyethylene glycols (PEGs), can be attached to enhance their function (see “Base Instincts”).

Using synthetic DNA the company encodes unnatural amino acids; using click chemistry it can then add a PEG or other groups at any point it wants in a protein, meaning it can tailor biologics to have properties of interest with pinpoint accuracy.

President, CEO and Director Laura Shawver said Synthorx saw an opportunity to apply its platform to cytokines, which play vital roles in activating or inhibiting immune cells but as therapeutics have been limited by non-selective binding and short half-lives. Shawver joined Synthorx in late 2017; she previously was CEO and director of Cleave Biosciences Inc.

IL-2, for example, can directly activate and induce proliferation of anti-tumor immune cells including CD8+ T cells. But the cytokine also binds receptor complexes on endothelial cells, which leads to toxicities, and on immunosuppressive Tregs, which can undermine the therapy’s immune-stimulating effects.

THOR-707 contains a PEG anchor point on IL-2 that blocks the cytokine from binding to endothelial cells and Tregs, and lengthens its circulation half-life.

“We’re able to say with a laser point, ‘We want to attach the PEG here.’”

Laura Shawver, Synthorx

While other companies have created pegylated cytokines, Synthorx builds in attachment points for PEGs at the level of DNA, rather than post-translationally, giving it the flexibility and precision to carry out conjugation reactions at sites of interest.

“We’re able...

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