Respiratory, Cardiovascular and Metabolic Disease
Leveraging the high bioavailability of Bicycles as topical inhaled agents, in November 2016 Bicycle partnered with a world leader in respiratory science, AstraZeneca, to evaluate the potential for local delivery of inhaled Bicycles in the lung. In the same collaboration, AstraZeneca is evaluating Bicycles for the treatment of cardiovascular and metabolic diseases. AstraZeneca is using its therapy area expertise and access to significant resources to lead the optimization of Bicycles identified by the Bicycle® platform. In addition to the significant patient benefit that can result from leveraging the Bicycle® technology in these diseases, Bicycle can receive >$1B in milestone payments, as well as single digit royalties should all products reach the market. In May 2018, Bicycle and AstraZeneca expanded their collaboration to include additional targets in respiratory, cardiovascular and metabolic diseases. Two assets have been transitioned to AstraZeneca for further development and are currently being progressed in their discovery pipeline.
The pharmacological and physicochemical characteristics of Bicycles also make them well-suited for ophthalmology indications. Bicycle has partnered with ophthalmology company Oxurion, formerly ThromboGenics, for the development of novel plasma kallikrein inhibitors, including THR-149 for the treatment of diabetic macular edema (DME). A Phase 1 clinical study of THR-149 in patients with DME was completed in July 2019 and positive topline results were announced, showing that THR-149 was well-tolerated and safe, with improvements to patients’ best corrected visual acuity (BCVA) starting at Day 1 and maintained out to Day 90. More on the Phase 1 results can be read here. As of June 2021, Oxurian has completed enrollment in Part A of its two-part Phase 2 study. Bicycle receives milestones and royalty payments from the collaboration.
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. 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.
In May 2019, Bicycle formed a collaboration with the Dementia Discovery Fund (DDF) to use Bicycle technology for the development of novel therapeutics for neurodegenerative diseases. DDF is a specialized venture capital fund focused on discovering and developing novel therapies for dementia. Under the terms of the agreement, Bicycle will identify Bicycles that bind to clinically validated dementia targets. If promising lead compounds are identified, Bicycle and DDF have the option to jointly establish a new company to further develop those compounds. In October 2019, the collaboration was expanded to include Oxford University’s ARUK Oxford Drug Discovery Institute, one of three institutes within the Alzheimer’s Research UK Drug Discovery Alliance and an expert in diseases of the central nervous system.
CNS and Neuromuscular
In July of 2021, Ionis entered into a worldwide license and collaboration agreement for tissue-targeted delivery of oligonucleotide therapeutics using Bicycles with high affinity to the transferrin receptor (TfR1). This collaboration was a result of Bicycles’ demonstrated ability to selectively deliver a variety of payloads into solid tumors when targeted to specific tumor antigens. Ionis and Bicycle will collaborate to develop a pipeline of oligonucleotide therapeutic product candidates. Bicycle is eligible to receive development, regulatory and commercial milestone payments and royalties for each program developed under the collaboration.