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Into the Future with Next-generation Small Molecules

Heightened interest in small molecules is likely to continue in 2023 and beyond as several biotech companies look beyond biologics to bring medicines to patients in need.

Advances in the field of biotechnology have tended to excite interest in their potential as targeted therapies. Vaccines, monoclonal antibodies, cell and gene therapy and other biotechnology innovations have been researched and developed to offer patients targeted treatments.

Despite the high profile of these therapies, small molecules continue to be the mainstay in disease treatment and increasingly are gaining the attention of traditional biotech and specialty companies looking to build their therapeutic portfolio and provide a wide range of treatment options for patients in need.

In fact, the majority of US Food and Drug Administration (FDA) approvals of new molecular entities (NMEs) continue to be small molecules. In 2022, 22 out of 37 novel drugs approved by the FDA were small molecules.

What is particularly notable is a trend amongst traditional biotech companies to expand their research and development portfolio into the area of small molecules. These innovative products are more complex than traditional small molecules but with fewer regulatory and manufacturing challenges faced by more innovative biologic products, such as cell and gene therapies.

Biotech Expands its Portfolio

Among the companies turning their attention to small molecules are Amgen and Biogen. In January 2022, Amgen announced a collaboration with Arrakis Therapeutics focused on research into RNA degrader therapeutics against a range of difficult-to-drug targets in multiple therapeutic areas. This is a new class of RNA degraders consisting of small molecule drugs, which “selectively destroy RNAs encoding disease-causing proteins by inducing their proximity to nucleases.”1

The company has been exploring a range of small molecule products across its oncology platform. For example, its product Lumakras® (sotorasib) is a small molecule indicated to treat adults with KRASG12Cmutated locally advanced or metastatic non-small cell lung cancer (NSCLC).

At Biogen, small molecules are part of the research arsenal aimed at treating neurological diseases. The company has several small molecules in phase 3 studies, including for depression and stroke, as well as research in phase 2 for multiple sclerosis and various other neurological conditions. In relapsing MS, the company is studying orelabrutinib, a small molecule Bruton’s tyrosine kinase inhibitor (BTKi) which researchers believe will help to reduce damage caused by BTK cells.2

It’s not only the biotech heavyweights that have been getting into small molecules. Mirati, a small biotech company from California, in December 2022 received breakthrough therapy designation from the FDA for its small molecule product Adagrasib (MRTX849) in combination with cetuximab for patients with KRASG12C-mutated advanced colorectal cancer.3 In November 2022, biopharmaceutical innovator Agios Pharma was granted marketing authorisation for its small molecule product Pyrukynd to treat PK deficiency in adults suffering from chronic anemia.