Bicycle Therapeutics Presents Updated Clinical Results Across Oncology Pipeline at ESMO Congress 2024

Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, today announced updated Phase 1/2 clinical results for Bicycle Toxin Conjugate (BTC) zelenectide pevedotin (formerly BT8009) in metastatic urothelial cancer (mUC); BTC molecule BT5528 in advanced solid tumors, such as mUC and ovarian; and Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA) BT7480 in advanced solid tumors. The company also shared an analysis of peripheral neuropathy, a key adverse event of interest associated with monomethyl auristatin E (MMAE)-based drug conjugates, in patients treated with BTC molecules. These data will be presented during a poster session at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona today.

“We are pleased that the data presented at ESMO continue to support the promising response and differentiated safety profiles of our Bicycle molecules. Importantly, our lead investigational therapy zelenectide pevedotin continues to demonstrate an overall response rate that is in line with other drug conjugates used to treat metastatic urothelial cancer, but with a marked improvement in tolerability. Overall, we believe the data continue to demonstrate the potential of our Bicycle technology platform to create differentiated medicines designed to help patients not only to live longer but also to live well,” said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. “These clinical data are just the first set of updates that we have guided to delivering this year. In the coming months, we look forward to sharing initial imaging data from our growing radiopharmaceutical pipeline and additional data for zelenectide pevedotin in bladder, breast and lung cancer.”

ESMO 2024 Data Highlights

Zelenectide pevedotin is a BTC molecule targeting Nectin-4, a well-validated tumor antigen, designed to overcome the significant toxicity associated with other drug conjugate approaches. Updated results from the ongoing Phase 1/2 Duravelo-1 trial evaluating 5 mg/m² weekly of zelenectide pevedotin monotherapy in 45 mUC patients who had not previously been treated with enfortumab vedotin showed:

• Among 38 efficacy-evaluable patients, a 45% overall response rate (ORR), including 1 confirmed complete response and 16 partial responses (13 confirmed). Stable disease was maintained in 9 patients, and 12 patients experienced progressive disease.
• A median duration of response of 11.1 months among the 14 patients with confirmed responses.
• An emerging differentiated safety profile, particularly around adverse events of interest such as peripheral neuropathy, skin reactions and eye disorders. Notably, there were no Grade ≥3 treatment-related adverse events (TRAEs) of peripheral neuropathy (any kind), skin reactions or eye disorders, and patients with pre-existing peripheral neuropathy were unlikely to develop worsening peripheral neuropathy during treatment with zelenectide pevedotin.

The global Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in patients with mUC is currently enrolling. Additional data updates for zelenectide pevedotin in combination with pembrolizumab in first line mUC and monotherapy in late line triple-negative breast cancer and non-small cell lung cancer (NSCLC) are planned for later this year.