Bicycle® Toolbox: A Novel Chemical Modality to Explore the Role of OX40 Agonism in Disease

BicycleTx Ltd. (Bicycle®) has developed an extensive library of small molecule compounds called ‘Bicycles’, which are constrained bicyclic peptides that bind with high affinity and selectivity to their target. Bicycles combine the pharmacological properties characteristic of biologics with the manufacturing and pharmacokinetic advantages of small molecules. Bicycle® is seeking to establish research collaborations to fully characterise these tools, and explore their potential application across different therapeutics areas with a disease area agnostic mind-set.

Some of the potential advantages of Bicycles vs. other targeting modalities include: 

• Low molecular weight (1.5-2.5 KDa), delivering rapid tissue penetration and tuneable PK
• Large molecular footprint allowing protein-protein interactions to be targeted
• Renal elimination, potentially minimising toxicological burden on liver and gut
• Ability to multimerise together or conjugate to a range of therapeutic payloads

Bicycle® is offering a set of tool monomeric and multimeric Bicycles that selectively bind human OX40/CD134 to agonise the receptor. These Bicycles have the following properties: 

• High affinity for human OX40 (potency determined by a reporter cell assay) 
• Selectivity against other TNF super-family members
• Unique modality (discovered using Bicycle Therapeutics proprietary phage technology platform and not commercially available elsewhere) 

The Bicycle® team is interested in research proposals that utilise the OX40 agonist Bicycle tools to explore the biology of OX40, a secondary co-stimulatory immune checkpoint molecule involved in potentiating T cell responses. The team seeks to explore the potential application of Bicycles in treating diseases including (but not restricted to) cancers and immuno‑inflammation. Initially the team are looking for proposals focused on in vitro biology studies, with the potential to expand into in vivo (pre-clinical mechanistic, efficacy and/or PK-PD studies). The team is also interested in research that reveals new pharmacological and structural insights to understand their mechanism of action and potential application to treat human diseases. 

Successful applicants will receive milligram quantities of Bicycles free of charge, supported by a dedicated scientific point of contact at Bicycle®. Bicycle® endorses an open innovation model and where possible researchers will be encouraged to publish results. Researchers may also be offered further, ongoing collaboration opportunities by Bicycle® with OX40 or other target-specific Bicycles in its Bicycle® Toolbox. Project funding may be considered for high quality proposals, on a case by case basis. 

Submission Information

Applicants should complete the application form which should contain a brief, non‑confidential overview of your proposal, demonstrating how the RFP requirements are satisfied by your approach. To submit your proposal, please visit our website at discover.in-part.com, register, and submit your application form under the appropriate Discover campaign.