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Amgen, Arrakis ink multi-target research collaboration to identify novel RNA degrader small molecule therapeutics

Thousand Oaks, California
Thursday, January 13, 2022, 13:00 Hrs  [IST]

Amgen and Arrakis Therapeutics announced a research collaboration focused on the discovery and development of RNA degrader therapeutics against a range of difficult-to-drug targets in multiple therapeutic areas. This new class of "targeted RNA degraders" consists of small molecule drugs that selectively destroy RNAs encoding disease-causing proteins by inducing their proximity to nucleases.

Under the terms of the agreement, Arrakis will lead research activities for the identification of RNA-targeted small molecule (rSM) binders against a broad set of targets nominated by Amgen. Both parties will collaboratively design and functionalize these molecules to specifically degrade targeted RNAs, and Amgen will lead further preclinical and clinical development activities. Amgen will pay $75 million upfront to Arrakis for five initial programs and will have the option to nominate additional programs. For each programme, Arrakis will be eligible for additional payments from Amgen for preclinical, clinical, regulatory and sales milestones, and royalties up to low double digits. Arrakis could potentially receive several billion dollars in future payments if all milestones are met and future program options are exercised.

"Targeted RNA degradation is an exciting area that is pushing the boundaries of drug discovery and design," said Raymond Deshaies, Ph.D., senior vice president of global research at Amgen. "The collaboration with Arrakis combines Amgen's induced proximity expertise in discovering multispecific molecules to target the biologic mechanisms of disease and Arrakis' pioneering discovery platform to predict RNA structures and identify small molecules that bind to them, significantly broadening the possibilities of addressing difficult protein targets considered undruggable because they may not have binding sites needed for conventional medicines. Combining this approach with Amgen's targeted protein degradation induced proximity research already underway has the potential to significantly expand the druggable genome."

By integrating the capabilities of the two innovative discovery platforms from Amgen and Arrakis, the collaboration creates an opportunity to design and engineer targeted RNA degraders. Amgen has built its Induced Proximity Platform to identify multispecific molecules that harness the power of cell biology by forming novel connections between natural effectors and targets. One end of the molecule binds to the target to be altered (inhibited, activated or destroyed) and the other end binds to a cellular effector that acts on the target, offering the potential to engage a broad range of cellular mechanisms to treat disease. With targeted RNA degraders, the effector, such as a ribonuclease or other RNA modulator, is brought into proximity of the RNA to degrade or otherwise modify the disease-causing RNA of interest. This complements Amgen's existing efforts to target RNA with siRNA. In this collaboration, Arrakis' rSM platform will be applied as a drug discovery engine to identify small molecules that bind target RNA. These rSMs will then be functionalized with nuclease recruiters to create heterobifunctional molecules that trigger degradation of disease-relevant RNA targets.

"We are excited to partner with Amgen's strong research team to pursue a shared goal of creating a new class of medicines that induce degradation of disease-causing RNAs. This collaboration further demonstrates the utility of our proprietary rSM discovery platform for targeting RNA with small molecules and paves the way for creating powerful new treatments for patients," said Michael Gilman, Ph.D., chief executive officer of Arrakis. "Based on our long-term goal to build a broad and industry-leading platform that adapts state-of-the-art drug discovery tools to target RNA biology, we have enabled a range of different applications and collaborations to leverage our science, a strong capital position and the ability to grow our business and our impact to advance RNA-targeted drug programmes for diseases unaddressed by today's medicines."

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics.


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