Programs
Powered by the invention of our revolutionary new class of medicines, we are developing first-in-class treatments for cancers with high unmet medical needs.
We are rapidly advancing our robust pipeline of Bicycles, focusing on targeted cytotoxics (Bicycle Toxin Conjugates), targeted innate immune activators and T-cell modulators.
Our lead molecule, BT1718, is a Bicycle Toxin Conjugate being developed to target tumours of high unmet need. Cancer Research UK’s Centre for Drug Development (CDD) is sponsoring a Phase I/IIa study of BT1718.
Bicycle Toxin Conjugates
Discovery
Pre-clinical
Clinical
MT1 Program (BT1718)
About BT1718
- BT1718 targets Membrane Type 1 Matrix Metalloproteinase (MT1-MMP), also known as MMP-14, which has an established role in cell invasion and metastasis, is linked to poor outcomes and is over expressed in many solid tumours.
- BT1718 demonstrates remarkable target-dependent efficacy in preclinical models, including both cell- and patient-derived xenografts that are resistant to standard of care.
- In GLP toxicity studies, BT1718 shows only a subset of the toxicities typically associated with the DM1 payload, avoiding liver, GI and renal toxicity.
Examples of high MT1 expressing tumours
- Breast cancer
- Lung cancer
- Sarcoma
- Gastric cancer
- Head and neck cancer
- Pancreatic cancer
Bicycle strategy:
MT1 is an attractive target for cytotoxin delivery based on its high level of expression on stromal and tumour cell subsets in various cancers. We have a strong preclinical efficacy and safety data package supporting the potential for MT1-targeted cytotoxins to bring benefit to patients with MT1-expressing tumours.
Cancer Research UK’s Centre for Drug Development (CDD) is sponsoring a Phase I/IIa study of our lead molecule BT1718. This proof-of-concept study will allow both efficacy and safety evaluation as well as diagnostic development. It will provide validation of MT1 as a target for toxin delivery and will be the first demonstration of the power of our innovative technology in patients, breaking ground for many future Bicycles.
EphA2 Program
About EphA2:
- Bicycle has developed a Bicycle Toxin Conjugate targeting EphA2, or Ephrin type-A receptor 2, a member of the Ephrin superfamily of receptor tyrosine kinases regulating cell migration, adhesion, proliferation and differentiation of tumour antigen. EphA2 is highly expressed in difficult to treat cancers and expression correlates with malignant progression and poor prognosis.
- Bicycle’s EphA2 toxin conjugates demonstrate target-dependent efficacy across both cell and patient derived preclinical xenograft models.
Examples of high EphA2 expressing tumours
- Non small cell lung cancer
- Triple negative breast cancer
- Bladder cancer
- Gastric cancer
- Ovarian cancer
Bicycle strategy:
EphA2 is an attractive target for cytotoxin delivery and was previously pursued as an antibody drug conjugate (ADC) target. Despite encouraging preclinical activity, these ADCs produced disseminated intravascular coagulation in preclinical toxicology species and in man, and development was terminated. Bicycle’s lead EphA2 targeting toxin conjugate shows remarkable efficacy in preclinical models without any evidence of bleeding in preclinical primate toxicology studies.
Nectin-4 Program
Nectin-4:
- Bicycle has developed a Bicycle Toxin Conjugate targeting Nectin-4 a type I Ig-like adhesion family member that is highly expressed in many difficult to treat solid tumours, including pancreatic and bladder cancer.
- Bicycle’s Nectin-4 toxin conjugates are efficacious in cell derived xenografts
Examples of high Nectin-4 expressing tumours
- Breast cancer
- Bladder cancer
- Pancreatic cancer
- Lung Cancer
Bicycle strategy:
Nectin-4 is a validated target for cytotoxin delivery. An antibody drug conjugate against Nectin-4, is in clinical development for bladder cancer. We are developing a small, synthetic Bicycle Toxin Conjugate that is easily manufactured, avoids hepatic processing and metabolism and may overcome the stromal barrier in pancreatic cancer.
Bicycle targeted Innate Immune Activators
Discovery
Pre-clinical
Clinical
TLR Agonist, STING Programs
Bicycle T-Cell Modulators
Discovery
Pre-clinical
Clinical
