Anti-tumor activity observed in heavily pre-treated patients with EphA2-positive ovarian and urothelial cancers; overall response rates of 22% (including one complete response) and 67%, respectively
Emergent safety profile of BT5528 suggests notable differentiation from current and prior generation EphA2 targeted molecules, with no treatment-related hemorrhage and low grade, low incidence of peripheral neuropathy, skin rash, and eye disorders
Enrollment in BT5528 expansion cohorts at the recommended Phase II dose (RP2D) of 6.5mg/m2 every other week remains ongoing
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“The therapeutic profile from the dose escalation portion of the Phase I/II trial of BT5528 in patients with late-line disease suggests both differentiated safety and promising activity, most notably in ovarian and urothelial cancers,” said
“Smaller size, tumor penetration, pharmacokinetic and other qualities distinguish BT5528 and other members of our BTC platform from traditional toxin delivery systems and may confer significant advantages,” said
BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated anti-tumor activity and differentiated tolerability. Bicycle has established an RP2D dose (6.5mg/m2 every other week) and is enrolling ongoing expansion cohorts.
Preliminary signs of anti-tumor activity observed. A total of 45 patients (15 at RP2D 6.5mg/m2 every other week) were dosed with a median of four prior lines of therapy. Expression of EphA2 was evaluated retrospectively using an immunohistochemistry (IHC) assay.
- Amongst these patients, anti-tumor activity was observed in urothelial and ovarian cancer patients.
- A total of 21 ovarian cancer patients were dosed. Of these, nine response evaluable patients were determined to be EphA2-positive based on the IHC assay. The median prior lines of therapy for these nine patients was four.
- Among these nine late-line ovarian cancer patients, six patients (67%) were observed to have a reduction in target lesions, including one patient with a complete response (CR) and one with a partial response (PR) under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, resulting in a disease control rate (DCR) of 67% and an overall response rate (ORR) of 22%.
- A total of eight urothelial patients were dosed. Of these, three response evaluable patients were determined to be EphA2-positive based on the IHC assay and of these three patients, two were observed to have tumor reductions constituting a PR under RECIST version 1.1 (ORR and DCR of 67%).
- BT5528 well-tolerated at RP2D of 6.5mg/m2 every other week. Low, or no, levels of incidence of neutrophil count decrease, peripheral neuropathy, skin rash and eye disorders were reported. Low-grade GI treatment-related events were those most commonly reported amongst the 15 patients at this dose. There were three Grade 3 and above events at the RP2D: diarrhea (n=1, 7%) and anemia (n=2, 13%). In addition, and in contrast to the toxicities observed with EphA2 ADCs, Bicycle has observed no signs of treatment-related coagulopathy to date in any patient.
Bicycle advancing BT5528 in ongoing expansion cohorts. In
June 2022, Bicycle announced the dosing of the first patient in the part B dose expansion portion of the Phase I/II trial. Up to 56 patients will be enrolled in the initial expansion cohorts, with the ability to further expand enrollment based on results from these cohorts. Dose expansion is taking place in urothelial (n=14) and ovarian (n=14) cancers as well as in a basket cohort of other solid tumors (n=28), including non-small cell lung, triple-negative breast, head and neck, and esophageal cancers.
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Forward Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the clinical development of BT5528 or any of Bicycle’s other product candidates or programs; the expected design and anticipated progression of and data readouts from Bicycle’s clinical trials of BT5528; the safety, tolerability or efficacy of BT5528; and the potential benefits of BT5528 or any of Bicycle’s other product candidates. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: risks to site initiation, clinical trial commencement, patient enrollment and follow-up, as well as to Bicycle’s abilities to meet other anticipated deadlines and milestones, presented by the ongoing COVID-19 pandemic; uncertainties inherent in the completion of clinical trials and clinical development of BT5528 and Bicycle’s other product candidates; availability and timing of results from clinical trials; whether initial or interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the risk that trials and studies may be delayed and may not have satisfactory outcomes; expectations for regulatory approvals to conduct trials or to market product; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the
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