Amgen collaborates with Arrakis to develop targeted RNA degraders

USA – Amgen and Arrakis Therapeutics have announced a collaboration to develop RNA degrader therapeutics for a variety of difficult-to-drug targets.

The collaboration will focus on developing a new class of small-molecule drugs discovered using Arrakis’ discovery engine that can selectively destroy RNAs encoding disease-causing proteins by bringing them into close proximity to nucleases.

Amgen and Arrakis will collaborate to design and functionalize these molecules to precisely degrade targeted RNAs, and Amgen will move forward with additional preclinical and clinical development activities.

According to the terms of the agreement, Arrakis will receive a US$75 million upfront payment for five initial programs. In addition, the company will be able to nominate additional programs.

Arrakis will be eligible for additional payments of up to low-double digits for preclinical, clinical, regulatory, and commercial milestones and royalties for each program.

The deal could end up costing Arrakis “several billion dollars” if all milestones are met and options are exercised, according to the company.

Arrakis will be eligible for additional payments for each program if certain clinical, regulatory, and sales targets are met, as well as royalties in the low double digits.

Arrakis will also direct research efforts aimed at identifying RNA-targeted small-molecule binders against a “broad set” of Amgen-nominated targets.

“Targeted RNA degradation is an exciting area that is pushing the boundaries of drug discovery and design,” remarked Raymond Deshaies, senior vice president of global research at Amgen.

“Combining this approach with Amgen’s already underway targeted protein degradation induced proximity research has the potential to significantly expand the druggable genome,” Deshaies believes.

The companies will then work together to design and “functionalize” these molecules so that they specifically degrade target RNAs, with Amgen leading further preclinical and clinical development.

This is Amgen’s second deal this year, following a US$2 billion agreement to use Generate Biomedicines‘ machine learning platform to develop protein therapeutics across multiple modalities and treatment areas.

Drugs don’t have to do all of the work of inhibiting or activating a target with Amgen’s Induced Proximity Platform (IPP). Instead, it brings the target into contact with powerful cellular mechanisms, which then act on it.

Arrakis is interested in the far-reaching therapeutic opportunities offered by RNA biology. The effector, such as a ribonuclease or other RNA modulator, is brought closer to the RNA to degrade or otherwise modify the disease-causing RNA of interest with targeted RNA degraders.

The collaboration program will enhance the capabilities of the two companies in developing heterobifunctional molecules that cause the degradation of disease-relevant RNA targets.

Meanwhile, in 2020, Arrakis announced a collaboration with Roche focused on RNA-targeted small-molecule medicines against a variety of targets.

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