San Diego-based Synthorx has brought in $63 million in Series C financing to advance its efforts to produce semi-synthetic protein therapies for cancer and immune conditions. The funding round was led by OrbiMed with others such as Medicxi, Osage University Partners, Avalon Ventures, RA Capital Management and Correlation Ventures also participating.
The company is built on the synthetic base pair developed by TSRI researcher Floyd Romesberg, which adds an X and Y to DNA’s traditional alphabet: C, T, G and A. This enhanced genetic lexicon can be used to create new amino acids, which can then be inserted into proteins to modulate their function.
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In the near term, Synthorx is leveraging this technology to tame interleukin-2 (IL-2). Arguably the first immunotherapy, IL-2 boosts the effector T-cells that destroy cancer, offering some patients the opportunity to be cured. Unfortunately, it also turns on regulatory T-cells, which dial down the immune response.
“When you give IL-2 to a person with cancer, the first thing that happens is you hit the brakes,” said Synthorx CEO Laura Shawver in a phone interview. “In order to give it the gas and tune up those T-cells that are responsible for eating the tumor, you have to give it at very high doses. It’s the high dose that gives serious side effects. The same receptors that are on the T regulatory cells that cause the immune suppression are present on vascular endothelial cells and cause vascular leak syndrome.”
The resulting side effects can be pretty horrific and some patients simply can’t tolerate them. In addition, only a small percentage of patients ultimately benefit from IL-2. However, if IL-2 could be fine-tuned to avoid immune suppression and mitigate toxicity, it might be a more effective cancer therapy.
By adding synthetic amino acids and a polymer to IL-2, Synthorx seeks to maximize the cytokine’s ability to attack cancer and reduce side effects, as well as increasing its half-life in the body. The modified protein, called Synthorin IL-2, has performed well in preclinical studies, and the company plans to initiate human trials early next year.
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“The series C will allow us to take this program into clinical trials to demonstrate what we’ve already demonstrated preclinically,” Shawver said. “We can expand this T-cell population that fights the tumor without expanding the T-cell population that’s responsible for the immuno-suppressive effect.”
The San Diego-based company isn’t alone in its efforts to optimize IL-2. In February, Bristol-Myers Squibb (BMS) invested heavily in Nektar Therapeutics’ IL-2 agent, NKTR-214. BMS and Nektar will be testing NKTR-214 with immunotherapy drugs Opdivo and Yervoy to boost their effectiveness.
Synthorin IL-2 may take a similar path. Though Synthorx has not recruited any pharma partners yet, they feel their biologic could be quite useful when combined with other therapies.
“We want to use it with other immuno-oncology agents and that includes checkpoint inhibitors,” Shawver said. “Turns out that almost all IO modalities – vaccines, oncolytic viruses, CAR-Ts – they all need cytokines to be at their best.”
Meanwhile, Peter Thompson, an OrbiMed private equity partner is bullish on potential applications
“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,” Thompson said in a news release. “It is easy to see how this platform could be applied to a variety of protein therapeutics.”
Image: Abscent84, Getty Images
