A startup in San Diego that’s boldly re-writing the code for life by expanding the genetic “alphabet” just got a big infusion of cash from Orbimed. The company, called Synthorx, raised $63 million on the promise of potential therapies built on breakthroughs in synthetic biology.
Synthorx is building its tech on work pioneered by Floyd Romesberg, a professor at The Scripps Research Institute in San Diego, who found a way to extend the genetic alphabet. In addition to the natural DNA base pairs A-T and G-C, Romesberg developed a third, synthetic base pair coined X-Y. The extra pair creates a huge opportunity to tweak proteins, as they can be built with up to 172 amino acids instead of the measly 20 available with natural base pairs.
When I first encountered Synthorx back in 2014, its then-CEO Court Turner put it this way:
“If you have a question and you can only answer it with 20 words, how good would your answer be?” Now imagine having 172 words.
Even though Synthorx is a tiny company still early in its field, this is not the first time its caught our attention. The company, incubated in its early days at Avalon Ventures’ startup campus COI Pharmaceuticals, attracted A-list talent late last year when Laura Shawver came on board as CEO. Shawver is best known for leading Cleave Biosciences through two sizable rounds of funding. She left Cleave when it was well-capitalized and in the midst of advancing an exciting pipeline to instead lead Synthorx.
“It’s not very often that one gets to participate in something that is potentially game-changing for therapeutics and likely will — this platform technology will be utilized for years to come,” she told Endpoints News at the time.
With the company’s genetic lexicon, Synthorx is creating a pipeline of partially synthetic biologics, including its lead program in interleukin-2 (IL-2) for cancer (which the company is calling Synthorin IL-2). Shawver tells me the approved IL-2 drug is known to work incredibly well at boosting anti-tumor activity, but it comes with side effects so severe that the treatments are hardly used anymore.
“Traditionally, you have to give IL-2 at very high doses, which stimulates the immune system and you get profound anti-tumor activity,” Shawver said. “But comes with very bad side effects. We’re trying to preserve the efficacious part, but not have the side effects.”
Lots of companies (including the ever-popular Nektar) are trying to make IL-2 therapies, and often they do this by PEGylating their drug, thereby improving the half-life. But the treatment still has side effects because IL-2 can both suppress and activate the immune system. With Synthrox’ expanded genetic alphabet, the company can take a different approach, tweaking the makeup of the protein itself by carefully placing synthetic amino acids and the PEG molecule to boost the molecule’s efficacy and limit unwanted (and off-target) side effects.
Synthorx has achieved this already in preclinical studies, and now it’s taking it into the clinic in the first half of 2019. The recent Series C round, led by Orbimed and including new investors Medicxi and Osage University Partners (along with existing investors), will fund the progress of the IL-2 program.
“We are impressed with the data for Synthorin IL-2 and how the Synthorx technology platform can specifically identify and select protein modifications that result in the desired therapeutic effect and pharmacokinetics,” said OrbiMed’s Peter Thompson, who’s joining the Synthorx board. “It is easy to see how this platform could be applied to a variety of protein therapeutics.”
Shawver says the IL-2 drug will primarily be used as a combo therapy used in tandem with immuno-oncology agents. But opportunities extend way beyond oncology. The company has plans to apply the tech to the autoimmune space, perhaps tackling diseases like Crohn’s and rheumatoid arthritis.
Image: Researchers at work in Synthorx’ lab. SYNTHORX
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