Express targeting RNA-modifying enzymes, US$17 million upfront payment to help develop small molecule anti-cancer therapies

▎Editor of WuXi AppTec's content team On October 14, 2021, Exelixis and STORM Therapeutics announced a research and development cooperation agreement to jointly develop innovative small-molecule anti-cancer therapies that change the function of RNA
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STORM’s proprietary technology platform aims to develop innovative small molecule drugs that regulate RNA modification
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This collaboration will first focus on advancing early work on its main drug candidate ADAR1 inhibitor and exploring an additional undisclosed target
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For RNA drugs, the main challenges it faces include: targeting the right tissue, pharmacokinetics, and stability
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Small molecules that change the function of RNA are expected to become a breakthrough, avoiding the above-mentioned challenges
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The strategy adopted by STORM is to influence the modification of RNA through small molecules
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All RNA, whether coding RNA or non-coding RNA, undergoes modification after transcription
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These modifications are not only very large (>100), and are performed by specific modifying enzymes, but also affect the structure and function of RNA (such as stability, translation, and splicing)
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Therefore, drugs that regulate the function of RNA-modifying enzymes may become a new treatment model
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Tumor cells produce a large amount of adenosine deaminase called ADAR1, which reduces the ability of dsRNA to activate the immune system by editing double-stranded RNA (dsRNA) molecules
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If ADAR1 is knocked out or inhibited, it can activate the innate immune response in tumor cells, thereby triggering tumor cell death
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It is worth mentioning that up to 30% of tumor cells in The Cancer Genome Atlas may rely on ADAR1 to suppress their own innate immune response
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This means that ADAR1 targeted therapy as a single-agent therapy may have potential in a variety of solid tumors
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In addition, inhibiting ADAR1 may also increase the sensitivity of tumors to immune checkpoint inhibitors and overcome resistance mechanisms to such therapies
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▲STORM's RNA-targeted therapy focuses on proteases that modify RNA (picture source: STORM's official website) According to the terms of the agreement, Exelixis will pay STORM an upfront payment of US$17 million to obtain two discoveries for RNA-modifying enzymes (including ADAR1) Project approval and funding for STORM’s discovery research activities
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Exelixis will be solely responsible for the global development, manufacturing, and commercialization activities of any molecule that is co-produced
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In addition, STORM will be eligible for future drug development, regulatory and commercialization milestone payments, as well as tiered royalties on annual net sales of compounds
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"ADAR1 has great potential as a new target for cancer
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However, the discovery of ADAR1 inhibitors is still a challenge
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" said Dr.
Peter Lamb, Executive Vice President and Chief Scientific Officer of Exelixis Scientific Strategy.
"STORM has a wealth of RNA-modifying enzymes.
Expertise
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We believe that this collaboration may expand our differentiated small molecule therapy portfolio in the field of oncology and provide potential'first-in-class' ADAR1 inhibitors
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"▲Related reading by Mr.
Keith Blundy, CEO of STORM: Another way, small molecules targeting proteases can also change RNA function | Interview "The cooperation with Exelixis has verified the important value of our technology platform and expanding pipeline
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"STORM CEO Keith Blundy said, "Obtaining Exelixis' development expertise and funding will enable our ADAR1 inhibitor R&D project and other R&D activities under the cooperation to make faster progress
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"Reference: [1] Exelixis and STORM Therapeutics Enter into Exclusive Collaboration and License Agreement to Discover and Develop Inhibitors of Novel RNA Modifying Enzymes.
Retrieved October 14, 2021, from https:// 20211014005548/en/Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
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