Synthorx

# High-Level Overview

Synthorx is a biotechnology company, not a technology company, though it employs cutting-edge synthetic biology technology. Founded in 2014 and headquartered in La Jolla, California, Synthorx develops cancer and autoimmune therapies using its proprietary Expanded Genetic Alphabet platform.[1][3] The company was acquired by pharmaceutical giant Sanofi in January 2020 for $2.5 billion, enhancing Sanofi's position in oncology and immunology.[3]

Synthorx solves a fundamental biological constraint: the natural genetic code contains only 64 codons encoding 20 amino acids. By expanding the genetic alphabet with synthetic base pairs (X and Y), Synthorx can encode up to 172 codons, enabling the creation of proteins with novel amino acids and enhanced therapeutic properties.[1] This capability allows the company to design Synthorin cytokines—optimized protein therapeutics that selectively tune receptor pharmacology and extend half-life, improving efficacy while reducing safety liabilities.[4]

# Origin Story

Synthorx was founded in 2014 based on seminal discoveries by Floyd Romesberg, Ph.D., a professor at The Scripps Research Institute who had spent over 15 years developing synthetic bases.[1][2] Romesberg's breakthrough—creating stable synthetic DNA base pairs that could be replicated and maintained by living cells—provided the scientific foundation for the company's platform.[2]

The founding vision was ambitious: use expanded genetic code to dramatically increase the number of available codons, enabling the creation of proteins with new functionalities and diverse chemical properties.[1] Early validation came in August 2015 when Synthorx successfully produced full-length proteins containing novel amino acids using its semi-synthetic DNA template, demonstrating that the synthetic base pairs were compatible with natural cellular machinery.[2] This proof-of-concept attracted investors including Avalon Ventures and Correlation Ventures, and the company raised $79 million before its acquisition.[2][3]

# Core Differentiators

• Proprietary Expanded Genetic Alphabet Platform: Synthorx's first-of-its-kind technology adds synthetic base pairs (X and Y) to DNA, expanding the genetic code from 64 to 172 codons. This enables site-specific incorporation of multiple novel amino acids into proteins—a capability unavailable through conventional protein engineering.[1][4]

• Precision Protein Optimization: The platform allows Synthorx to tune receptor specificity, bias immune activation, and extend protein half-life with precision, addressing both efficacy and safety limitations of existing biologics.[4]

• Lead Candidate Momentum: THOR-707, a variant of interleukin-2 (IL-2), is in clinical development for solid tumors as a single agent and in combination with checkpoint inhibitors.[1] A second candidate, THOR-809, selectively expands regulatory T cells without activating effector T or natural killer cells in preclinical models, reducing toxicity.[1]

• Diversified Pipeline: Beyond IL-2 variants, Synthorx has filed 33 patents and is developing candidates targeting IL-15R and IL-10R pathways, with applications spanning cancer, Crohn's disease, and other autoimmune conditions.[3][6]

# Role in the Broader Tech Landscape

Synthorx operates at the intersection of synthetic biology and precision medicine, riding the wave of advances in genetic engineering and immunotherapy. The timing is critical: IL-2 has been studied for nearly 40 years and is recognized as potentially the most valuable molecule for boosting immuno-oncology efficacy, yet its clinical use has been limited by safety concerns.[4] Synthorx's ability to create optimized IL-2 variants addresses this unmet need precisely when checkpoint inhibitors, CAR-T therapies, and cancer vaccines are becoming standard-of-care treatments that could benefit from enhanced cytokine support.[4]

The company's acquisition by Sanofi signals broader industry recognition that synthetic biology platforms can unlock new therapeutic possibilities. By expanding the chemical and structural repertoire of protein therapeutics, Synthorx influences how the biotech ecosystem approaches protein drug design—moving beyond incremental modifications to fundamentally new protein architectures.[4]

# Quick Take & Future Outlook

Synthorx represents a rare convergence of foundational science and clinical application. Under Sanofi's ownership, the company has transitioned from proof-of-concept to clinical development, with THOR-707 advancing through trials. The key question is whether the expanded genetic alphabet platform can deliver superior clinical outcomes that justify its complexity and manufacturing requirements compared to conventional biologics.

Looking ahead, Synthorx's influence will depend on clinical trial success and the platform's scalability. If THOR-707 and THOR-809 demonstrate meaningful improvements in efficacy or safety, the platform could become a template for next-generation cytokine design and potentially expand into other protein therapeutic classes. Conversely, if manufacturing complexity or immunogenicity concerns emerge, the platform's impact may remain niche. Either way, Synthorx has already proven that synthetic biology can move beyond academic curiosity into practical medicine—a milestone that will shape how biotech approaches protein engineering for the next decade.