Bicycle Therapeutics Updates Oncology Pipeline Results at ESMO 2024

Bicycle Therapeutics plc, a pioneering pharmaceutical company utilizing its proprietary bicyclic peptide technology, has announced updated clinical results for its investigational therapies in metastatic urothelial cancer (mUC) and other advanced solid tumors. These findings were presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona.

The investigational therapies discussed include zelenectide pevedotin, BT5528 and BT7480, each of which demonstrated promising efficacy and safety profiles. Zelenectide pevedotin, a Bicycle Toxin Conjugate (BTC) targeting Nectin-4, showed a 45% overall response rate (ORR) among efficacy-evaluable patients in its Phase 1/2 Duravelo-1 trial. The therapy was well-tolerated with no severe treatment-related adverse events such as peripheral neuropathy, skin reactions, or eye disorders. Median duration of response was noted to be 11.1 months. The global Phase 2/3 Duravelo-2 trial is currently enrolling patients to further investigate its efficacy in mUC, with additional data expected later this year.

BT5528, another BTC molecule targeting EphA2, showed a 34% ORR in patients with advanced solid tumors, particularly mUC. It also exhibited a differentiated safety profile with no occurrences of hemorrhage events or severe hematological toxicities. The ongoing trial is now assessing BT5528 in combination with nivolumab, with results anticipated in 2025.

BT7480, a Nectin-4 targeted CD137 agonist, demonstrated an emerging safety and tolerability profile in its Phase 1/2 dose escalation trial. Among 39 patients, low rates of severe adverse events were reported, and stable disease was observed in 13 patients. Preliminary biomarker analyses suggested effective dual targeting of CD137 and Nectin-4, supporting the proposed mechanism of action.

Additionally, an analysis of treatment-related peripheral neuropathy (TRPN) in patients treated with zelenectide pevedotin or BT5528 revealed low occurrence rates. Nearly all TRPN cases were of low grade (1-2), with no severe events reported for BT5528. The data suggested that the antibody-drug construct might be the primary driver of TRPN rather than the toxicity of monomethyl auristatin E (MMAE).

Bicycle Therapeutics, headquartered in Cambridge, UK, and with significant operations in Cambridge, Massachusetts, continues to develop its novel class of drugs. These therapies use fully synthetic short peptides with small molecule scaffolds to achieve high affinity and selectivity in target binding, offering potential solutions for diseases underserved by existing treatments. The company is also exploring the use of its Bicycle technology in radiopharmaceutical applications and other therapeutic areas through various partnerships.

The posters detailing these updates were made available in the Publications section of the Bicycle Therapeutics website.