The COVID-19 pandemic has driven RNA into the public eye and there is increasing recognition of its importance in medicine. The intense scientific drive and the success of mRNA vaccines during the last two years has also benefitted biotech overall, with an increasing list of new RNA startups entering the field.
RNA technology for use in medicine has been under development for a long time. While first considered a possibility in the 1960’s it took until 1990 for the first proof of concept experiment to take place. Researchers demonstrated that mice injected with a certain mRNA resulted in the animals producing the protein encoded by the mRNA. This was the start of the journey to get RNA therapeutics to the clinic.
The first RNA therapeutic to reach the market was developed by Alnylam Pharmaceuticals and was approved by the FDA in 2017 and the EMA the following year. Most of the attention during the pandemic has fallen on messenger (m)RNA vaccine companies such as Moderna and Pfizer/BioNTech, responsible for the first two COVID-19 vaccines to be approved in the U.S. However, RNA therapeutics are also really hitting the prime time as well with several more therapies approved since 2017 and many more in development.
Here are five RNA therapeutics startups to watch that have opened their doors since 2020 and are developing the next generation of RNA medicines.
Headquarters: Cambridge, Massachusetts
Orna Therapeutics officially launched out of stealth mode in early 2021, announcing the completion of an $80 million Series A financing round with funding from big players such as Bristol Myers Squibb, Novartis, Astellas Venture Management and Gilead, at the same time. It specializes in developing fully engineered, circular RNA therapeutics, which the company calls oRNAs.
According to the company, the oRNAs have several advantages including high levels of protein expression, simple and cost-effective manufacturing and more efficient delivery to targets, as more of the circular RNA’s can be packaged into lipid nanoparticles than linear RNAs.
Orna’s technology is based on MIT research from Alex Wesselhoeft and professor Dan Anderson. The team managed to get the oRNAs to produce proteins even though they are circular and do not have a standard ribosome binding point and also took time to create specialist delivery vehicles for the oRNAs. Orna is initially hoping to apply its technology to improve current cancer immunotherapies and bring CAR-T cell therapy directly to the cells that need it in the body.
Headquarters: San Diego, California
Replicate Bioscience launched in late 2020 and announced it had raised $40 million in Series A funding from ATP, a life sciences venture capital firm, in 2021. It has a focus on self-replicating (sr)RNAs that have the ability to copy and replicate themselves after being injected into the body. While no srRNA therapies have yet reached the market, the theoretical advantages are that lower initial dosing levels are needed, and that therapeutic effects could last for longer.
CEO Nathaniel Wang and Chief Development Officer, Andrew Geall, previously worked on similar technology at Synthetic Genomics and at Novartis Vaccines and Diagnostics. They were joined by Herbert Kim Lyerly and Zachary Hartman, both professors of cancer research and immunology at Duke University, to found the company.
A key aim of Replicate is to develop an srRNA therapy that is able to prevent or remove genetic mutations that promote drug resistance in cancer. It has a program in breast cancer, lung cancer, and solid tumors, as well as in autoimmune disease, and hopes to start its first clinical trials later this year.
Headquarters: Concord, Massachusetts
Comanche Biopharma is a startup focusing on developing small interfering (si)RNA-based treatments for pre-eclampsia, a potentially life-threatening pregnancy condition characterized by high blood pressure, and other symptoms such as fluid retention and proteinuria.
There is currently no specific treatment for pre-eclampsia other than early delivery of the baby, which can be dangerous, making this an area of unmet medical need. Abnormally high levels of soluble fms-like tyrosine kinase-1 (sFlt-1) are accurately thought of as the “final common pathway” in the manifestation of pre-eclampsia and as such is a potentially modifiable target (because when sFlt1 is lowered, the disease resolves). The company founders have created siRNA that is able to silence the sFlt1 gene in the placenta and potentially create a viable treatment for the condition.
The company was founded by T Scott Johnson, current CEO at Comanche, with colleagues such as Mike Young, now President of the company. Both Young and Johnson previously worked at The Medicines Company. Comanche raised $36 million in venture funding in summer 2021.
Headquarters: Cambridge, Massachusetts
hC Bioscience was founded last year and is developing a very new type of RNA therapeutic based on transfer (t)RNA. It announced it had raised a $24 million Series A earlier this year, with support from ARCH Venture Partners, Takeda Ventures and 8VC.
The company is developing two platforms, which it says are complementary to each other. The first plans to use tRNA to restore the function of proteins that have been prematurely shortened due to so-called ‘nonsense mutations’. This method would allow the genetic error to be corrected and full-length proteins produced. The company’s second platform aims to target and correct disease-causing missense mutations that cause abnormal proteins to be produced.
Leslie Williams, president and CEO, and Professor Christopher Ahern, as a spin out from the University of Iowa. The science was based on work on tRNAs performed by Chris Ahern and John Lueck (currently at the University of Rochester).
Headquarters: Cambridge, Massachusetts
Exacis Biotherapeutics has a slightly different approach and is combining targeted RNA with cell therapy. It is using mRNA to reprogram induced pluripotent stem cells (iPSCs) to create therapeutics. The technology can create allogeneic and safe iPSCs that can then be differentiated to created a range of therapies to treat cancers with high unmet medical needs.
The company was founded in 2020 as a spin-off from parent company Factor Bioscience, another Cambridge, Massachusetts biotech with a focus on mRNA, gene editing, cell reprogramming, and nucleic-acid delivery. Gregory Fiore, a Harvard trained physician, pharma exec and entrepreneur, was appointed CEO at the launch.
Exacis was created to focus on cancer treatments and is focused on creating engineered natural killer and T cells designed to resist host immune rejection and is also designing cell therapy products for use with monoclonal antibodies as well as chimeric antigen receptors for tumor targeting.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.