Programs

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 and is linked to poor outcomes in cancer patients. It is generally expressed at relatively low levels in normal adult tissues but overexpressed in many solid tumors.
• The molecule is comprised of our MT1-MMP targeting Bicycle, a hindered disulphide cleavable linker and a cytotoxin DM1 payload.
• MT1-MMP is an attractive target for cytotoxin delivery due to high levels of expression on subsets of stromal and tumor cells in a range of cancers.
• 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 fewer of the toxicities typically associated with the DM1 payload, avoiding liver, gastric and renal toxicity.
• BT1718 is being investigated in an ongoing Phase I/IIa open label dose escalation and expansion clinical trial sponsored by CRUK. Up to 40 patients with advanced solid tumors are being enrolled in the ongoing Phase I part of this trial at three sites in the U.K. in which two dosing regimens are being evaluated.
• CRUK presented preliminary data from the Phase I dose escalation at the European Society of Medical Oncology (ESMO) 2019 Annual Congress. Early analysis of data as of an August 7, 2019 cutoff shows stable disease in 54% of evaluable patients at eight weeks, across all cohorts of the all-comers Phase I escalation, including a patient who experienced a 45% reduction in a target lesion. With once-weekly dosing, which is the expected schedule for the Phase IIa portion of the study, BT1718 has appeared tolerable, with manageable adverse events.
• After this preliminary Phase I part of the clinical trial concludes, we plan to enroll subjects with specific tumor types into Phase IIa expansion cohorts.

About EphA2:

• BT5528 targets EphA2 (or Ephrin type-A receptor 2), a member of the Ephrin superfamily of receptor tyrosine kinases which regulates cell migration, adhesion, proliferation and differentiation during development. EphA2 is overexpressed in difficult to treat cancers, and expression correlates with malignant progression and poor prognosis.
• The molecule is comprised of our EphA2 targeting Bicycle, a valine-citrulline (val-cit) cleavable linker and a cytotoxin MMAE payload.
• Bicycle’s EphA2 toxin conjugates demonstrate remarkable target-dependent efficacy in preclinical models, including both cell- and patient-derived xenografts that are resistant to standard of care.
• BT5528 has been evaluated in preclinical GLP toxicology studies in multiple species. BT5528 was not observed to have a significant effect on clotting parameters or liver function at tolerated doses, both of which were dose limiting toxicities previously reported for ADCs targeting the same tumor antigen.

About Nectin-4:

• BT8009 targets Nectin-4, a cell adhesion molecule from the Nectin and Nectin-like family, which has been shown to be overexpressed in tumor cells and is believed to play a role in tumor cell growth and proliferation. High in normal embryonic and fetal tissue, Nectin-4 declines in adulthood, showing a limited distribution in healthy tissues.
• The molecule is comprised of our Nectin-4 targeting Bicycle, a valine-citrulline, or val-cit, cleavable linker and a cytotoxin MMAE payload.
• Bicycle’s Nectin-4 toxin conjugates demonstrate remarkable target-dependent efficacy in preclinical models, including both cell- and patient-derived xenografts that are resistant to standard of care.
• In preliminary toxicity studies, BT8009 shows only a subset of the toxicities typically associated with the MMAE payload, avoiding liver, GI and renal toxicity.