Blog January 18, 2021

What We’re Watching for in 2021 – Part 1 of 2

Happy New Year to all of our readers! The Bionest team wishes you a prosperous, happy, and, especially, healthy 2021. 

The past year has been an especially challenging one due to the COVID-19 pandemic. With the first vaccines against the virus now being put to use in many countries, we look forward with hopeful anticipation to the decline of this considerable healthcare and economic threat, and a gradual return to more normal life. And so, with a fresh year in front of us, we wanted to reflect briefly on some recent trends from 2020 that we believe will continue to advance to the forefront in 2021.

mRNA Therapeutics – A Rapidly Evolving World

While RNA therapeutics have been an active area of research for many years, this corner of drug development became a focus of mainstream news in 2020 with the successful introduction of the first mRNA vaccines from Pfizer/BioNTech and Moderna. Such vaccines work by delivering mRNA that encodes a particular viral sequence into cells, enabling the cells themselves to manufacture the antigens that trigger an anti-viral immune response. Given the relative simplicity of their design, mRNA vaccines are easy to produce and test once a relevant viral antigen sequence is known. While the new COVID-19 mRNA vaccines were quickly developed to address the pandemic, they rest on nearly a decade of in-depth research on mRNA vaccines in general. Similar mRNA technology is being applied by Moderna, BioNTech, and others to address other viral diseases, as well as to design immuno-oncology and rare disease therapeutics. Moreover, further technological advances emerging from places like the Massachusetts Institute of Technology and Strand Therapeutics that combine mRNA with synthetic biology are enabling the development of bio-engineered mRNA therapeutics capable of safely delivering long-lasting, multi-functional treatments for cancer and immunological illnesses in a single shot.

But mRNA is just one part of the larger field of RNA therapeutics. Overall, RNA-based treatments offer several important advantages as therapeutics. They can address targets that are undruggable by monoclonal antibodies or small molecules. They are easier to deliver and safer than DNA-based therapies, as they do not need to get into the nucleus of the cell or interact directly with the genetic material there. At the same time, RNA therapeutics are very versatile, in that they can be used to increase or decrease gene expression or to deliver transcripts for the expression of new proteins, such as the SARS-CoV-2 spike antigens in the new COVID-19 vaccines. While the cell’s own RNAs are rapidly broken down, chemical modification of therapeutic RNAs has rendered them more stable, increasing their potency and applicability to a wider range of uses.

Although an RNA aptamer drug, pegaptanib, was approved in 2004, the field of RNA therapeutics mostly languished until advances in nucleic acid chemistry and better delivery vehicles boosted development efforts, resulting in the 2018 approval of Alnylam’s Onpattro, an siRNA (small interfering RNA) drug for the treatment of the rare condition hereditary transthyretin-mediated amyloidosis. Since then, two more of the company’s RNA-based drugs have reached the market, Givlaari for a rare liver disease in 2019, and Oxlumo for a rare kidney condition in February 2020. We expect the pace of approvals to continue to build, as therapeutics based on a variety of RNA types advance through clinical development from a growing number of companies: Ionis Pharmaceuticals, Sarepta Therapeutics, and Akcea Therapeutics (antisense RNAs); Alnylam, Arrowhead Pharmaceuticals, Dicerna Pharmaceuticals (siRNAs); Moderna, BioNTech, CureVac, and Arcturus Therapeutics (mRNAs); and Cardior Pharmaceuticals and miRagen Therapeutics (microRNAs). While many development efforts to date have been focused on rare diseases and cancer, they are beginning to expand into new areas including heart failure and the treatment of metabolic disease.

The Brave New World of Psychedelic Medicines

We have written in the past about the re-emergence of clinical research with psychedelic medicines (such as psilocybin, MDMA, LSD, DMT, ibogaine and others, including non-hallucinogenic derivatives of those substances) for mental health issues and the treatment of substance abuse disorders. During 2021, we expect to see data readouts from a few important clinical studies in this field, including Compass Pathways’ Phase 2 trial of psilocybin in treatment-resistant depression, an indication for which the company received an FDA Breakthrough Therapy designation in 2018.

In September, Compass also reached a business milestone, with the first successful IPO of a psychedelic medicines company on Nasdaq, which raised $146.6 million. Mind Medicines, which previously had a public offering on the new Canadian NEO exchange, has now also filed for listing on Nasdaq. 

The number of other companies focused on psychedelic medicines has exploded, with a reported 30+ new companies founded in 2020 alone.

While Johnson & Johnson may have catalyzed the movement of psychedelic drugs into mainstream medicine with the 2019 approval of Spravato (esketamine) for the in-clinic treatment of severe depression, big pharma appears to have so far stayed mostly on the sidelines. Will that situation change as later-stage clinical trial results with these drugs emerge?

We’ll continue our observations in our next post.