Bicycle Therapeutics (BCYC) Status Update summary

Radiopharmaceutical strategy and platform overview

• Presented first human imaging data for Bicycle Radionuclide Conjugates (BRCs) targeting MT1-MMP, a novel tumor antigen overexpressed in many cancers.

• BRCs leverage bicyclic peptides for precise, selective delivery of radioisotopes to tumors, with rapid body clearance and high tumor retention.

• Platform enables targeting of hard-to-drug oncology antigens and creation of new peptide-based ligands for novel targets using machine learning and structural biology.

• Strategy includes partnerships with Novartis, Bayer, and a letter of intent with Eckert & Ziegler for isotope supply, focusing on novel targets and isotope-agnostic development.

• Bicycle molecules offer low molecular weight, high selectivity, and rapid systemic clearance, ideal for radioisotope delivery.

First human imaging data and clinical progress

• First human imaging with MT1-MMP BRC showed strong tracer uptake in primary tumor, lymph nodes, and bone metastases, with minimal uptake in healthy tissue and clear contrast.

• Data validate MT1-MMP as a promising therapeutic target and demonstrate the translatability of the Bicycle platform from preclinical to clinical settings, consistent with standard FDG-PET/CT.

• Ongoing efforts aim to optimize tumor-to-kidney ratio and advance MT1-MMP BRC into IND-enabling studies.

• Second BRC target, Ephrin A2 (EphA2), is advancing toward human imaging in 2025, with plans for both imaging agents and theranostics.

• Preclinical studies demonstrated BRCs can be optimized for high tumor uptake and significantly reduced kidney retention, effectively delivering various radioisotopes.

Pipeline, partnerships, and future outlook

• Proprietary library of Bicycle molecules enables rapid expansion into new targets, with ongoing collaborations to accelerate development.

• Flexibility to pair Bicycles with various isotopes and suppliers mitigates supply risks and supports clinical scalability.

• Cash position of $555 million supports operations into the second half of 2027, enabling continued investment in radiopharmaceutical and toxin conjugate programs.

• Expect further imaging data updates in mid-2025 and initiation of Bicycle-sponsored clinical trials in 2026.

• Pipeline includes targeted drug conjugates, immuno-oncology agents, and radiopharmaceuticals, with clinical trials ongoing for zelenectide pevedotin, BT5528, and BT7480.