Our mission has always been to democratize biologics discovery technology and capabilities so that the widest possible audience of scientists can access them to develop promising therapeutics for patients. We both create platforms and build discovery services groups that are expert in using and improving these platforms for the benefit of all. We are excited to share that we are taking this approach to a new area of medicine: antisense oligonucleotides (ASOs).
Within genetic medicines, ASOs are a promising therapeutic modality, due to their ability to target the root cause of disease for up to 70% of the genome. These short, synthetic, single-stranded oligonucleotides are made of 16-20 DNA and modified RNA nucleotides. The sequences are designed to be anti-sense such that they bind to a specific sequence on the target gene mRNA.
Historically their upside has been throttled by off-target and toxicity effects—problems now being addressed through chemistry advances that strengthen ASO safety profiles and therapeutic efficacy. The pharma industry has taken note of this progress, with a flurry of new business development deals around ASOs as well as many new programs in the clinic.
Nonetheless, many drug discovery teams are limited in their ability to advance ASO therapeutics projects. Current discovery services offerings in the field require access to patented chemistries, proprietary formats, highly specialized knowledge in house, very large R&D budgets, or all of the above. Given the historic struggles in ASOs, expertise in the field is limited.
To help solve these innovation and access problems, Alloy is developing and validating next-generation, novel chemistries, and proprietary formats in collaboration with Dr. Sudhir Agrawal, all of which will be broadly accessible to Alloy’s partners. Our teams in San Francisco and Boston are already working with Dr. Agrawal to build on his decades of research and to incorporate our scientists’ ideas and the shared insights from Alloy’s partners. Dr. Agrawal is the perfect partner for Alloy, with a tenacious passion for broad access to his intellectual property. He has published over 300 research papers and has co-authored over 400 patents worldwide, including the invention of gapmer antisense technology widely employed in antisense candidates and multiple approved drugs.
Alloy is further removing these roadblocks through the creation of our ASO Discovery Services group, which will offer drug developers access to end-to-end ASO discovery capabilities and tools at an affordable price. Bioinformatics are a critical part of our ASOs Discovery workflow, enabling us to automate and optimize the design of ASOs to avoid safety issues that have stalled the modality historically. The process will be finetuned first in service of new asset-focused companies launched out of 82VS, our Venture Studio, then opened to drug discovery teams everywhere. Our first two ASO companies are focused on applying the modality to treat neurodegeneration and ocular disease.
We are proud to have this modality helmed by Dr. Ben Chih, who previously led Genentech’s efforts in ASO drug development and pioneered the use of antibody conjugates for delivery across the blood-brain-barrier. As our discovery services groups in antibodies and TCRs do, ASO Discovery Services will work in close collaboration with clients to optimize ASO leads, integrating client functional data. and advise them according to their evolving needs, ultimately providing them with promising candidates and a robust data package.
ASO Discovery Services workflows and innovations will inform the creation of new ASOs platform technologies that can be licensed and brought in house, as our foundational ATX-Gx™ humanized mouse platform is today. We are leveraging our rich history in antibodies to develop novel ASO-antibody conjugates for targeted in vivo ASO delivery for our initial 82VS companies, ultimately working to translate this workflow into a licensable ASO delivery platform. This platform offering will be bolstered by other novel ASO formats and chemistry advances, developed in collaboration with Dr. Agrawal, our advisor and chair of our genetics medicines platform SAB.
We have always seen breakthroughs in enabling technology as the source of new therapeutic innovations, and we are thrilled to tackle the problem of opening the therapeutic landscape of ASOs. We are so grateful for foremost inventors and technology pioneers in this field such as Drs. Chih and Agrawal to share our vision of making innovations available to a vast community of discovery scientists, all in service of enabling the best medicines to get to patients.
To inquire about our forthcoming ASO Discovery Services, schedule a call with our business development team here.