Expansion Therapeutics: The Race to “Drug RNA”

Founded in 2016, Expansion Therapeutics (Expansion) is a drug discovery and development company pursuing the vast potential of small molecule medicines for RNA-mediated diseases. The San Diego, California, venture has raised over $55 million in just a couple of years—a considerable sum for a brand-new venture. The venture was founded by Kevin Forrest and RNA drugging guru Matthew D. Disney, who was recently awarded BioFlorida’s entrepreneur of the year. Mr. Disney’s intellectual property, developed over the years at Scripps, undoubtedly represents the key to this enterprise when combined with Mr. Forrest’s entrepreneurial energy and eye for value. Having spent many years working on “drugging the RNA world” at Scripps Research Institute, Jupiter, Florida, few have accumulated the knowledge and expertise in this field as Mr. Forrest.

Expansion is pre-revenue and has between 20 to 35 employees. Expansion recently hired Elliot Ehrich as Chief Medical Officer. Dr. Ehrich had been CMO and executive vice president of research and development of publicly traded Alkermes. As a venture partner with 5AM Financing, he was incubating Expansion and recently co-led its $55.3 million Series A financing with Kleiner Perkins, Novartis Venture Fund and Sanofi Ventures.

Why are some of the largest European biopharmaceutical company venture capital groups investing in this new San Diego up-start? First, a brief overview of what they do: Expansion believes that the field of small molecules interacting with RNA (SMiRNA) has the potential to transform the therapeutic landscape by opening up the small molecule “druggable” universe beyond the classic protein-based targets. Key platform enabling technologies originally conceived at Scripps Research Institute introduce the foundation to the future value that the prominent venture capital is betting on.

Drug Developers have long believed that RNA targeting with small molecule drugs was nearly impossible, but with new insight into RNA biology, new possibilities exist. The investors have bought into Expansion’s vision that they can develop chemical-based drugs for a group of genetic diseases that are caused by dysfunctional RNAs with a certain kind of mutation. RNAs carry the genetic instructions for proteins to the cell’s protein-making machinery. If small molecules can change the activity of RNA, a new class of largely untapped drug targets are possible—helping drug developers address diseases that cannot be treated with traditional protein-binding drugs.

Expansion Therapeutics has taken the capital from Kleiner Perkins, Novartis and Sanofi to use chemical compounds to modify the function of disease-driving RNA molecules and concentrate on the root cause of disease. This has been considered extremely difficult by the drug development industry. RNA molecules have not been easy “to drug” because common belief is that RNAs don’t have the right type of chemical structures to be bound by a diverse range of small molecule drugs. With a growing knowledge and transformative expertise in the structure of RNA molecules (combined with superior technologies to sequence and produce large amounts of RNA molecules), the drug development industry sees the potential of targeting RNA molecules with small molecules. The general vision is that small molecule drugs will evade RNA delivery challenges.

The foundational intellectual property (IP) in which Expansion Therapeutics valuation is premised on is years of work at the research lab of Scripps Florida. He and colleagues identified key folder RNA structures that small molecules can bind to. By developing two large chemical libraries, the group could then focus on developing tools to enable researchers to expeditiously sift through millions of combinations and compounds that can bind to specific RNA folds.

Disney and Scripps’ team collective work was published in Nature Chemical Biology. They shared research results that evidenced their successful designs of a small molecule that enabled the binding of specific folder sections of a mutant RNA molecule—which causes myotonic dystrophy type 1 (DM1), the most common form of adult onset muscular dystrophy. In the results, the authors paved the way for the birth of Expansion Therapeutics.  Leveraging the work done at Scripps, the venture is targeting DM1 and has already developed compounds that they believe can restore the function of the RNA associated with DM1, according to an Xconomy article. Seeking to scale the platform and disease target candidates (and of course economic opportunity), the company seeks to target genetic diseases called expansion repeat disorders. Approximately 30 of such diseases are triggered by RNAs that have certain repeated sequences. The venture is also targeting myotonic dystrophy type 2. As of this TrialSite News writing, the Expansion pipeline includes four programs, all still in Discovery phase:

  • DM1 (Myotonic Dystrophy Type 1)
  • DM2 (Myotonic Dystrophy Type 2)
  • Undisclosed (Expansion Repeat Disorder)
  • Undisclosed (Expansion Repeat Disorder)

Expansion seeks to execute full throttle. Most recently, they have licensed discovery-lead optimization technology from German-based Origenis. Expansion will use Origenis AI drug discovery platform, MolMind® and MOREsystem® in combination with other “innovative embedded technologies.” Expansion will depend on Origenis to deliver identified development candidates with defined properties for Expansion targets, and will ensure “novelty” by directing the process with their Clippix® product, which is “a unique tool creating value from the hidden chemical and biological information embedded in patents.” Leveraging this German-made tool, Expansion can capitalize on purpose-designed AI, ensuring compounds have “unique chemical properties and have been tested for biological activity, toxicity and stability for real-world application.”

As was reported by Corie Lok of Xconomy, they (Expansion) are now in a race against Arrakis Therapeutics of Waltham, MA to drug RNA. Arrakis has raised $38 million according to online venture resource CrunchBase. As Expansion IP is based on the work of Mr. Disney at Scripps, Arrakis has licensed its technology from the University of Pennsylvania. Unlike Expansion, Arrakis is disclosing broader therapeutic targets including:

  • Neurology
  • Oncology
  • Rare Genetic Diseases

A key premise in their underlying strategy is to collaborate and partner with deep-pocketed biopharmaceutical companies. Undoubtedly, Arrakis founder Jennifer Petter has a rich network—she has worked at some heavy-hitting drug developers including Celgene and Biogen. 38 employees self-identify as Arrakis employees. TrialSite News will monitor both Expansion and Arrakis to see how the race to “Drug RNA” is coming along.

About the Author:

Daniel O’Connor

Mr. O’Connor has spent nearly 20 years providing technology and services to the clinical trials and health technology industry. An entrepreneur, he has been instrumental in building different ventures focusing on FDA 21 Part 11 enterprise document management, technology-enabled patient recruitment services, clinical document and safety data exchange, as well as population health and community care coordination for at-risk populations with Eccovia Solutions. He is a co-founder of a group launching a global clinical research site accreditation standard–ACRES ReServ. Mr. O’Connor has built a comprehensive research site data base and intelligent clinical research site news curation engine with TrialSite News. He earned his combined MA and JD from the University of California (Los Angeles and Hastings College of the Law) and undergraduate from San Francisco State University.