Sanofi inks $2.5B Synthorx takeover to gain IL-2 cancer drug

Sanofi global R&D head John Reed
Sanofi R&D chief John Reed (Sanofi)

Sanofi has struck a deal to buy Synthorx for $2.5 billion (€2.3 billion). The takeover, the first of Paul Hudson’s time as CEO, will give Sanofi control of an IL-2 drug it thinks can become a foundation of future immuno-oncology combinations. 

Synthorx is one of a clutch of companies trying to overcome the pharmacological limitations of the cytokine IL-2. A recombinant form of IL-2, branded Proleukin, won approval in the 1990s and is sold to this day. However, in its recombinant form IL-2 suffers from an onerous dosing regimen and causes adverse events including vascular leak syndrome.

In THOR-707, Synthorx thinks it has a drug that has IL-2’s power to turn the immune system against cancer but is free from its downsides. Synthorx created the drug by installing a novel amino acid at one position in recombinant IL-2.

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Sanofi has bought into the idea that Synthorx has discovered a drug with superior selectivity, a wider therapeutic index and reduced dosing, leading it to offer $68 a share to buy the biotech. Synthorx listed on Nasdaq at $11 a share one year ago and rarely traded above $20 in its short time on public markets. Sanofi’s offer represents a 172% premium over Synthorx’s closing price Friday.  

In return for the outlay, Sanofi is getting a drug that its R&D chief, John Reed, thinks could “become a foundation of the next generation of immuno-oncology combination therapies.”

“By selectively expanding the numbers of effector T-cells and natural killer cells in the body, THOR-707 can be combined with our current oncology medicines and our emerging pipeline of immuno-modulatory agents for treating cancer,” Reed said in a statement.

Synthorx is yet to release clinical data to support optimism about THOR-707. A phase 1/2 trial of the candidate in advanced or metastatic solid tumor patients got underway earlier this year. The clinical trial is assessing THOR-707 as a monotherapy and in combination with a PD-1 inhibitor.

Describing the deal as "an unexpected move," analysts at Jefferies picked up on the combination potential in a note to investors. 

"It's clear [Sanofi] believes that IL-2 will be a backbone of IO therapy as well as will be used in combination with other IO therapies. [Sanofi] could evaluate THOR-707 in combination with its antibodies targeting PD-1, CD38 and others," the analysts wrote.

Other companies are also working to retool IL-2 for the immuno-oncology era. Nektar Therapeutics is the most prominent member of the pack, having moved its prodrug of conjugated IL-2 into a big phase 3 program in collaboration with partner Bristol-Myers Squibb. Neoleukin, which executed a reverse merger earlier this year, has a different, computationally designed take on the IL-2 problem. 

The story of Nektar, which has struggled to live up to early expectations, shows how much Synthorx still has to prove and the problems it could hit along the way. However, Sanofi think there is value in Synthorx even if THOR-707 underwhelms, pointing to a preclinical pipeline of autoimmune and cancer candidates spearheaded by THOR-809 to make its case.

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