On March 30, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported progress updates for its Bicycle-based partnered programs outside of oncology (Press release, Bicycle Therapeutics, MAR 30, 2021, View Source [SID1234577366]).
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"Over the last five years, Bicycle’s strategy has been to use our novel technology to discover and develop a pipeline of innovative assets in oncology while additionally using non-dilutive funding and collaborations to explore the therapeutic potential of Bicycles in disease areas outside of oncology. Today, for the first time, we are providing an overview on our progress in demonstrating the broad utility of this platform to create molecules with the potential to treat some of the most serious diseases and address future healthcare challenges," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "It’s incredibly exciting to see how the Company has worked innovatively and highly collaboratively with many diverse institutions to address these challenges and, at the same time, generated significant revenues to offset the costs of developing and progressing our internal oncology pipeline. I would like to thank all of our collaborators for their enthusiasm in this endeavor and look forward to continuing our work to advance these important molecules."
Bicycle has achieved the first milestone in its collaboration with Dementia Discovery Fund (DDF) and the University of Oxford’s ARUK Oxford Drug Discovery Institute (ODDI)
The Company identified and optimized nM affinity Bicycles to TREM2, a genetically validated target for the treatment of dementia, and nM affinity Bicycles to transferrin receptor 1 (TfR1), a molecular shuttle. In 2019, Bicycle established a collaboration with DDF, later expanded to include ODDI, to use Bicycle technology for the discovery and development of potential novel therapeutics for the treatment of dementia. The three parties are collaborating to identify and characterize Bicycles that bind to and activate TREM2, a genetically validated dementia target. As part of the collaboration, Bicycle is also using its technology to identify binders to TfR1, a blood brain barrier transporter, that could potentially enable delivery of Bicycles, or any other molecular payload, into the central nervous system (CNS), or other organ systems, expressing TfR1. Under the terms of the collaboration with DDF, Bicycle retains all rights to the TfR1 molecules outside of the license granted for use with targets defined within the DDF collaboration.
Bicycle advances platform in multiple anti-infective areas, including antimicrobials and antivirals
Innovate UK’s Biomedical Catalyst (BMC) awarded the Company funding to advance a Bicycle inhibitor for a key cell wall biosynthesis target in Enterobacterales, Penicillin Binding Protein 3 (PBP3). Bicycle is using its proprietary platform to try to address the significant healthcare challenge of antimicrobial resistance and has identified several potential Bicycle PBP3 inhibitors. Through grants awarded by the UK government and in collaboration with investigators at the University of Warwick, Bicycle intends to progress these PBP3 inhibitors, potentially representing the first novel class of antibiotics identified in decades, to candidate and initial toxicology testing.
Innovate UK, under a specific program targeting key technologies to rapidly respond to the challenge of COVID-19 (UKRI Ideas to Address COVID-19 – Innovate UK Article 25), provided funding to support Bicycle’s efforts to discover new healthcare solutions to the SARS-CoV-2 pandemic. Bicycle has identified numerous discrete families of Bicycles which bind to at least 10 different epitopes on the SARS-CoV-2 spike protein, binders to the Nucleocapsid protein and the viral attachment site on the host ACE2 human receptor. Through Bicycle’s partnership with researchers at the MRC Laboratory of Molecular Biology, Bicycles identified by these screens have demonstrated nanomolar activity in inhibiting SARS-CoV-2 infection of human lung cells. These monomeric Bicycles have been conjugated together to make a diverse range of bi-paratopic and multi-valent small molecules (less than 10kD), some of which are active in the picomolar range in viral entry assays and may be resistant to the current SARS-CoV-2 variants of concern. Bicycle continues to advance these novel compounds in pre-clinical evaluation. Bicycle has also formed partnerships with diagnostic experts to evaluate its novel SARS-CoV-2 binding Bicycles in Lateral Flow Tests and other diagnostic screening formats.
Bicycle has made significant progress through partnerships with biopharmaceutical therapeutic area leaders in indications outside of oncology
The Company has successfully discovered and advanced targets outside of oncology through the ongoing collaboration with AstraZeneca, a global biopharmaceutical company, to discover novel agents for the treatment of respiratory and cardiometabolic diseases. Two assets have been transitioned to AstraZeneca for further development and are currently being progressed in their discovery pipeline. Two additional assets achieved transition criteria and were transitioned to AstraZeneca but were returned to Bicycle by AstraZeneca.
Bicycle has also identified targets in its collaboration with Bioverativ (acquired by Sanofi in 2018) for the treatment of rare hematological diseases. The Bioverativ collaboration successfully identified nM multi-valent inhibitors to P-Selectin, which inhibited human neutrophil binding and rolling, with potential applications in sickle cell disease and other inflammatory diseases. The Bioverativ collaboration also identified the first small molecule Factor VIII mimetic for the potential treatment of Hemophilia A. This mimetic is comprised of a multivalent Bicycle binding to both Factor IX and Factor X, leading to the production of activated Factor X (FXa), which successfully activated thrombin in plasma from Hemophilia A patients ex vivo. In 2019, Sanofi elected not to pursue further development, and the collaboration agreement was terminated. These "lead stage" assets have now been returned to Bicycle.
Kevin Lee commented, "With four Bicycle molecules now in clinical trials for both oncology and non-oncology indications, the technology has shown initial evidence of clinical tolerability and suitability for pharmaceutical development, and I look forward to seeing how Bicycles may bring important new treatment opportunities to poorly served patients in additional therapeutic areas."