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Synthetic Bio Company Acquired in $2.35B Deal

E. coli bacteria

E. coli bacteria (Agricultural Research Service, USDA)

11 Dec. 2019. A company developing protein-like therapies for cancer from synthetic bacteria is being acquired by drug maker Sanofi in a deal valued at $2.35 billion. Synthorx Inc. in La Jolla, California is a five year-old spin-off enterprise from the Scripps Research biochemistry lab of Floyd Romesberg, now with Synthorx full time.

Synthorx develops biologic drugs from genetically altered but benign E. coli bacteria, a well-researched microbe that in some strains is known to cause food poisoning. The Romesberg lab at Scripps Research developed techniques for adding two more base-pairs, nucleic acid components configured into an organism’s genetic code, to DNA. Natural DNA has four base pairs, combinations of adenine (A), thymine (T), cytosine (C), and guanine (G). Amino acids are made from sequences of three of these components, which form the building blocks of proteins in organisms with instructions for cells.

Romesberg and colleagues found a way of adding the two base pairs, labeled X and Y, to DNA. With these extra base pairs, new kinds of proteins can offer additional properties for therapeutics beyond the capability of proteins in their natural form. The added base pairs make it possible to encode up to 152 new amino acids for proteins with unique chemical characteristics for therapies or other applications.

Synthorx adapts this technology to create E. coli bacteria with altered DNA for producing what the company calls synthorins, biologic drugs with protein-like therapeutic characteristics, but also properties from the X and Y base pairs. These added properties include features such as longer active life in the body, and greater uptake and retention by targeted tumors.

The company’s lead product, code-named THOR-707, is a synthorin biologic for treating solid tumor cancers. THOR-707 is a synthetic form of the natural protein Interleukin-2 in the immune system that produces an immune response to attack tumor cells. In THOR-707, however, Synthorx modifies the protein’s chemistry to act for longer periods, spread wider in the tumor, and be retained longer in the tumor than natural Interleukin-2. In addition, says the company, THOR-707 does not cause vascular leak syndrome, a weakening of blood vessels that in the past limited use of Interleukin-2 as a cancer therapy.

THOR-707 is being tested in an early- and mid-stage clinical trial as a treatment for solid tumor cancers, both on its own and with immune-system checkpoint inhibitors. The trial is enrolling 300 participants in the U.S. and Australia with advanced or metastatic solid tumor cancers, looking primarily for safe doses of THOR-707, but also clinical responses to the treatments and survival times by patients.

Sanofi expects THOR-707 and other therapies in development by Synthorx to bolster its current pipeline of cancer immunotherapies and synthetic biologics. Sanofi is purchasing Synthorx stock for $68.00 a share, a premium of 172 percent over Synthorx’s closing price on 6 December. The all-cash transaction is valued at $2.35 billion.

Science & Enterprise reported on Synthorx’s founding by Romesberg and others in May 2014, and publication in November 2017 of key advances in producing proteins from synthetic bacteria in the journal Nature. In August of this year, Romesberg abruptly left Scripps Institute under largely unexplained circumstances, according the Science magazine. His lab continues at Scripps, although the institute says it’s winding down the lab’s work.

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