Bicycle Therapeutics highlights 2025 accomplishments and strategic priorities for 2026 

• Dose selection from Phase 2/3 Duravelo-2 trial and update on potential approval pathway expected in 1Q 2026 as company seeks feedback from multiple regulatory agencies
• Emerging radiopharmaceuticals pipeline progressing, with additional EphA2 human imaging data planned for the first half of 2026
• Initial data for Phase 1/2 Duravelo-3 trial exploring zelenectide pevedotin in NECTIN4 amplified breast cancer expected in the second half of 2026
• Expected financial runway into 2028 to support execution of clinical and strategic priorities

“In 2025, we remained steadfast in our goal of helping patients live longer and live well, making meaningful advancements to our pipeline and strengthening the operational capabilities that support our strategic priorities. In addition to the progress we continue to make with zelenectide pevedotin and BT5528, our recently announced collaborations with the United Kingdom Nuclear Decommissioning Authority, United Kingdom National Nuclear Laboratory and SpectronRx provide us with the potential for an end-to-end supply chain for ²¹²Pb, building on the existing supply chains we have established for ¹⁷⁷Lu and ⁶⁸Ga. In summary, by combining these supply collaborations with our proprietary Bicycle technology we have established a unique radiopharmaceutical capability from the identification of Bicycle targeting agents to the potential commercial supply of the radiotherapeutic across multiple radioisotopes,” said Bicycle Therapeutics CEO Kevin Lee, Ph.D. “We look forward to providing updates on the potential approval pathway for zelenectide pevedotin and dose selection from the Phase 2/3 Durvelo-2 trial in the first quarter of 2026.”

2025 Key Accomplishments

• Reported updated topline Phase 1 Duravelo-1 combination data for zelenectide pevedotin plus pembrolizumab in first-line cisplatin-ineligible patients with metastatic urothelial cancer (mUC). The data continue to show zelenectide pevedotin’s promising anti-tumor activity and differentiated safety profile.
• Initiated Phase 1/2 Duravelo-3 trial for zelenectide pevedotin in NECTIN4-amplified breast cancer.
• Initiated Phase 1/2 Duravelo-4 trial for zelenectide pevedotin in NECTIN4-amplified non-small cell lung cancer.
• Reported first human imaging data for an early Bicycle^® Radioconjugate (BRC^®) molecule targeting EphA2 at the Targeted Radiopharmaceuticals Summit Europe. The data supports the potential of EphA2 as a novel cancer target and demonstrates the positive properties of BRC molecules for radiopharmaceutical use.
• Presented additional human imaging data for an early Bicycle^® Radioconjugate (BRC^®) molecule targeting MT1-MMP at the American Association for Cancer Research (AACR) Annual Meeting 2025. The company believes this data further supports the potential of MT1-MMP as a novel target in the treatment of cancer, demonstrates the translatability of BRC preclinical data and highlights the potential of Bicycle® molecules for targeted radionuclide therapies and radiopharmaceutical imaging.

2026 Strategic Priorities and Anticipated Milestones

Nectin-4 Pipeline (zelenectide, BT7480)

• Provide an update on dose selection for Phase 2/3 Duravelo-2 pivotal trial and zelenectide pevedotin’s potential approval pathway in mUC following meetings with multiple regulatory agencies in the first quarter of 2026.
• Report dose selection data from Phase 2/3 Duravelo-2 pivotal trial evaluating zelenectide pevedotin in combination with pembrolizumab in patients with mUC at a scientific conference in the first half of 2026.
• Report additional Phase 1 Duravelo-1 combination data with pembrolizumab in first-line cisplatin-ineligible mUC at a scientific conference in the first half of 2026.
• Report longer-term follow-up Phase 1 Duravelo-1 monotherapy data in late-line mUC at a scientific conference in the first half of 2026.
• Report initial data for Phase 1/2 Duravelo-3 trial for zelenectide pevedotin in NECTIN4-amplified breast cancer at a scientific conference in the second half of 2026.
• Report Phase 1 BT7480 combination data with nivolumab at a scientific conference in the first half of 2026.

EphA2 Pipeline (BT5528, EphA2 imaging)

• Report Phase 1 BT5528 combination data with nivolumab in mUC patients at a scientific conference in the first half of 2026.
• Provide an update on future clinical development plans for BT5528 in the first half of 2026.
• Report additional EphA2 human imaging data in the first half of 2026.