Bicycle Therapeutics (BCYC) Status Update summary

First human imaging data and radiopharmaceutical strategy

• First human imaging data for a Bicycle Radionuclide Conjugate (BRC) targeting MT1-MMP showed high tumor uptake, low normal tissue uptake, and clear visualization of tumors and metastases, with strong imaging contrast and renal excretion.

• Imaging results were consistent with standard FDG-PET/CT, supporting the translatability of preclinical data.

• BRCs leverage bicyclic peptides for precise, selective delivery of radioisotopes to tumors, with rapid body clearance and tumor retention, supporting both diagnostic and therapeutic applications.

• The first BRC program targets MT1-MMP, with a second program announced for Ephrin A2, both considered first-in-class opportunities.

• Collaborations with Novartis, Bayer, and academic partners, as well as a letter of intent with Eckert & Ziegler for radioisotope supply, support the development and validation of new radiopharmaceuticals.

Clinical and preclinical progress

• Preclinical optimization aims to improve tumor-to-kidney ratios, with advanced molecules showing high tumor uptake and low kidney retention.

• BRCs can deliver various radioisotopes, such as indium, lutetium, and lead, to tumors with rapid penetration and elimination.

• The Ephrin A2 BRC is expected to enter human imaging studies in 2025, following a similar development path as MT1-MMP.

• Further imaging data updates are anticipated in mid-2025, with first BRC clinical trials planned for 2026.

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

Platform and strategic positioning

• The Bicycle platform can generate new peptide-based ligands for targets lacking natural peptide leads, using machine learning and structural biology.

• The approach is to focus on novel, less competitive targets beyond those pursued by most radiopharmaceutical companies, aiming for leadership in new indications.

• Flexibility in isotope and supplier selection is emphasized to mitigate supply chain risks and optimize clinical development.

• Resource allocation is supported by a strong cash position, with funding expected to last into the second half of 2027.

• Partnerships extend the platform's reach to diseases beyond oncology.