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Synthorx: Synthetic Biology for Better Medicine

Synthorx is an example of a company with a disruptive technology that was cofounded by Avalon Ventures and is incubated at COI Pharma. The Synthorx expanded genetic alphabet technology enables highly precise protein design to improve pharmacological properties and develop more efficacious, safer, and convenient therapeutics for patients.

Expanding the Genetic Alphabet

The ability to specifically design proteins is based on a synthetic biology breakthrough from the lab of Floyd Romesberg, Ph.D., faculty at The Scripps Research Institute and scientific founder of Synthorx, who pioneered the development of the first semi-synthetic organism that can store and retrieve increased genetic information. This semi-synthetic organism was made to maintain, replicate, transcribe, and translate a synthetic DNA base pair in order to incorporate various non-natural amino acids (nnAAs) into a full-length protein.

The regular ‘genetic alphabet’ of DNA consists of two base pairs (A–T and G–C). Dr. Romesberg and his team designed another base pair, d5SICSTP and dNaMTP (abbreviated X and Y), that can be stably replicated and maintained by a single-celled organism. The four natural DNA bases are used to code for or “spell” proteins assembled from the 20 natural amino acids. With X and Y, it is now, in principle, possible to encode for an additional 152 nnAAs to make proteins with improved pharmacological properties.

Read more about this technology on their new website.

Financing to Advance Cytokine Pipeline

In November 2017, Laura Shawver, Ph.D., was appointed president and chief executive officer of Synthorx and hit the ground running.  Dr. Shawver joined Synthorx following a position as CEO and director at Cleave Biosciences where she led the company through two financing rounds.  Prior to Cleave, she was an entrepreneur-in-residence for 5AM Ventures, CEO and director of Phenomix Corporation, and president of Sugen (acquired by Pharmacia). Shawver has been involved with a number of clinical development programs including two FDA-approved therapies. In the brief time she has been at the helm of Synthorx, Dr. Shawver secured a significant Series C financing.  The $63 million raise was led by Orbimed and joined by new investors, Medicxi and Osage University Partners, and existing investors, Avalon Ventures, RA Capital Management, and Correlation Ventures.

When she first join the company, Endpoints News sat down to chat with Laura about her enthusiasm for the technology and next steps for the company.

“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,” said Dr. Shawver commented.

The proceeds of the financing will be used to advance a pipeline of SynthorinTM cytokines.  Cytokines are very important molecules in many biological processes and diseases, but they often have multiple pharmacological effects and short half-lives.  Using the Synthorx expanded genetic alphabet technology, Synthorin cytokines are designed to have selective receptor tuning in addition to an extended half-life.

The lead drug candidate, Synthorin IL-2, is tuned specifically to bias IL-2’s activity to immune activation versus repression. This allows for precise delivery and efficacious immune system activation to enhance antitumor activity of leading immuno-oncology approaches, including, checkpoint inhibitors, cancer vaccines, CAR-T therapies, and oncolytic viruses.

“Since its discovery nearly 40 years ago, IL-2 is the most studied cytokine and potentially the most valuable molecule for boosting the efficacy of immuno-oncology therapies,” said Marcos Milla, Ph.D., chief scientific officer of Synthorx.

Dr. Shawver adds, “Our investors immediately recognized the remarkable ability of our lead molecule, Synthorin IL-2, to deliver sustained cancer-killing activity without the safety liability through our unique ability to modify protein therapeutics for tuning receptor pharmacology and extending half-life.”

Peter Thompson, M.D., private equity partner at OrbiMed, who recently joined the Synthorx board of directors, said, “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. It is easy to see how this platform could be applied to a variety of protein therapeutics.”

Visit www.synthorx.com for more information about the company, their recent financing, and innovative technology.

More top media coverage of the Series C financing can be found at:
Endpoints News
FierceBiotech
MedCity News
The San Diego Union-Tribune
Xconomy