Bicycle Therapeutics to Present Phase 1/2 Trial Data on BTC® Molecules at 2024 ASCO

Bicycle Therapeutics, a biotechnology company headquartered in Cambridge, England, and Boston, has recently provided updates on its innovative Bicycle Toxin Conjugates® (BTC®) including emerging clinical pharmacokinetic and safety profiles. The company utilizes proprietary bicyclic peptide technology to develop these novel therapeutics, which show promising differentiation from traditional antibody-drug conjugates (ADCs).

During the upcoming 2024 American Society for Clinical Oncology (ASCO) Annual Meeting from May 31 to June 4 in Chicago, Bicycle Therapeutics will present clinical pharmacokinetic (PK) and safety data for two of its BTC molecules: BT8009 and BT5528. BT8009, also known by its International Nonproprietary Name, zelenectide pevedotin, targets Nectin-4 in patients with locally advanced or metastatic urothelial cancer. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to BT5528 for treating adult patients with previously treated metastatic urothelial cancer.

Dr. Kevin Lee, CEO of Bicycle Therapeutics, expressed optimism about the promising clinical profiles of the company’s Bicycle® molecules. These molecules are characterized by their small size, which allows for rapid tissue penetration, tunable pharmacokinetics, and high target selectivity. These attributes contribute to the molecules’ potential to offer enhanced benefits and improved quality of life for cancer patients.

The company is also making strides with its Phase 2/3 Duravelo-2 trial for zelenectide pevedotin in patients with metastatic urothelial cancer (mUC). Bicycle Therapeutics anticipates several clinical updates in the latter half of 2024, including developments from the Phase 1/2 trials of both zelenectide pevedotin and BT5528.

Key findings from the clinical pharmacokinetic studies reveal that BTC molecules like zelenectide pevedotin and BT5528 exhibit significantly different profiles compared to ADCs. The half-life of BTC molecules is substantially shorter than that of the ADC enfortumab vedotin (EV), leading to rapid elimination of the BTC molecules within hours as opposed to weeks. Moreover, the maximum serum concentration (Cmax) of unconjugated MMAE was higher for BTC molecules, potentially facilitating rapid tumor tissue penetration. Conversely, conjugated MMAE PK exposure was lower in BTCs, potentially reducing associated toxicities.

Emerging safety and tolerability data for zelenectide pevedotin and BT5528 also show promising results. Adverse events (AEs) related to zelenectide pevedotin occurred in 84% of patients, with 31% being Grade ≥3, while BT5528-related AEs were found in 91% of patients, with 22% being Grade ≥3. Notably, treatment-related AEs such as peripheral neuropathy, skin reactions, ocular disorders, and hyperglycemia were observed at relatively low frequencies and severities in both BTC molecules, in contrast to typical ADCs.

The ongoing Phase 2/3 Duravelo-2 study, focusing on the efficacy of BT8009 in patients with advanced or metastatic urothelial cancer, continues to progress with active patient enrollment and site activation.

Bicycle Therapeutics is committed to leveraging its innovative Bicycle® technology to develop treatments for diseases with unmet needs. Beyond oncology, the company is exploring Bicycle® technology's potential through various partnerships to develop radiopharmaceuticals and other therapeutic applications.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!