Amgen and Arrakis Therapeutics Announce Strategic Collaboration to Develop Small Molecule Targeted RNA Degraders

On January 11, 2022, Amgen and Arrakis Therapeutics announced a research collaboration primarily focused on discovering and developing RNA degradation therapies for a range of difficult-to-drug targets across multiple therapeutic areas. These innovative targeted RNA degradation therapies consist of small molecules that selectively degrade RNA encoding pathogenic proteins by bringing it in proximity to nucleases.

Currently, most drugs developed for protein targets focus on a few categories of proteins (such as receptor proteins). However, the human genome contains over 20,000 genes and the transcriptome includes more than 200,000 different RNA transcripts. Targeting RNA directly with small molecule drugs is a promising approach for difficult-to-drug protein targets.

Arrakis Therapeutics is adopting multiple approaches to establish a new paradigm for small-molecule drug discovery targeting various mechanisms of the RNA lifecycle. The company’s discovery platform integrates cutting-edge RNA bioinformatics and structural tools, curated chemical libraries, RNA-specific assays, and RNA-directed medicinal chemistry. Its end-to-end RNA-targeting small molecule (rSM) drug discovery platform is capable of identifying small molecules that bind to and modulate RNA, predictively impacting the RNA lifecycle and downstream disease-related biology. The platform has already built a database comprising hundreds of RNA targets.

▲Schematic diagram of Arrakis' small molecule drug platform targeting RNA (Image source: Authorized use by Arrakis)

And Amgen's established Induced Proximity Platform can develop multispecific molecules. One end of these molecules binds to the target that needs to be inhibited, activated, or destroyed, while the other end binds to an effector in the cell that can act on the target, offering the potential to leverage a wide range of cellular mechanisms for disease treatment. For instance, RNA degraders pull nucleases or other RNA-modulating proteins close to the target RNA to degrade or modulate their function.

Under the terms of the agreement, Arrakis will be responsible for research activities aimed at discovering small molecule compounds that bind to RNA for a broad set of targets nominated by Amgen. The two companies will collaborate to design and functionalize these molecules to specifically degrade targeted RNA. Amgen will lead further preclinical and clinical development activities. Additionally, Amgen will pay Arrakis an upfront payment of $75 million for the five initial programs and will have the option to nominate additional programs. Arrakis is eligible to receive from Amgen up to billions of dollars in preclinical, clinical, regulatory, and sales milestone payments, as well as royalties on future products.

References

[1] AMGEN AND ARRAKIS THERAPEUTICS ANNOUNCE MULTI-TARGET COLLABORATION TO IDENTIFY NOVEL RNA DEGRADER SMALL MOLECULE THERAPEUTICS. Retrieved January 11, 2022, from https://investors.amgen.com/news-releases/news-release-details/amgen-and-arrakis-therapeutics-announce-multi-target

(The original text has been abridged)

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