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 is being investigated in an ongoing Phase I/IIa open label dose escalation and expansion clinical trial sponsored by CRUK.
• 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.
• In April 2020, Bicycle announced that one patient with small cell lung cancer experienced a partial response, with a 68% reduction in a target lesion.
• The key objectives were met in the Phase I dose escalation evaluating safety and tolerability of BT1718 in an unselected group of patients with advanced solid tumors. Based on study results, CRUK established a recommended Phase II dose for the expansion cohorts at 20 mg/m² administered once weekly. This recommended dose is within the efficacious dose range predicted by preclinical models, in which an equivalent dose level was associated with complete responses. With once-weekly dosing, BT1718 appeared tolerable, with manageable adverse events.
• BT1718 is currently being evaluated in a Phase II trial sponsored by CRUK. Patients enrolled onto the study are being pre-screened according to tumor type and a pre-specified immunohistochemistry (IHC) assay H-score.

About BT5528:

• 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 is currently being evaluated in a Company-sponsored Phase I/II clinical trial as a monotherapy and in combination with nivolumab. Patients enrolled onto the study are being pre-screened according to tumor type and a pre-specified immunohistochemistry (IHC) assay H-score.
• Doses of BT5528 administered in the ongoing trial to date appear safe and well-tolerated with manageable adverse events.
• Initial doses of BT5528 administered in the Phase I portion of the study are estimated to deliver six to 12 times the amount of toxin that was delivered by an ADC targeting EphA2 in an unsuccessful clinical trial.

About BT8009:

• 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 preclinical head-to-head comparisons with an ADC targeting Nectin-4, BT8009 demonstrated superior anti-tumor activity, including complete regressions of very large and small tumor models.
• In preliminary toxicity studies, BT8009 shows only a subset of the toxicities typically associated with the MMAE payload, avoiding liver, GI and renal toxicity.
• We are currently conducting a Phase I/II trial of BT8009 as a monotherapy, with plans to evaluate BT8009 in combination with nivolumab. Patients enrolled onto the study are pre-screened according to tumor type.