Molecular Partners (MOLN) Study update summary

Study background and rationale

• MP0712 is a DLL3-targeting Radio-DARPin therapeutic evaluated for small cell lung cancer (SCLC) and other neuroendocrine cancers, leveraging high tumor uptake and retention via DLL3 replenishment and internalization.

• The approach uses a DARPin vector with engineered half-life, partnered with Orano Med for isotope supply, in a 50/50 collaboration.

• DARPins serve as ideal vectors for radiopharmaceuticals, with 212Pb as a potent therapeutic payload showing proven clinical efficacy.

• SCLC is highly radiosensitive, and MP0712 is designed for manageable side effects and combinability with other mechanisms of action.

• DLL3 is a validated target, but existing modalities (T-cell engagers, ADCs) have limitations in response rate and duration, supporting the need for radiotherapy.

Preclinical and imaging data

• Imaging with 203Pb-MP0712 in SCLC patients demonstrated strong and sustained tumor uptake, including in liver metastases, with minimal healthy organ uptake.

• Quantitative image analysis showed continued tumor uptake up to 116 hours, with healthy organ washout visible from 24 hours onward.

• Tumor lesions demonstrated higher specific uptake than healthy tissues, with rapid and sustained accumulation over 24 hours and beyond.

• Progressive uptake was observed across different tumor types, with ~80% of uptake reached at 24 hours and strong retention up to 7 days.

• Data from five patients using diagnostic isotope 203Pb demonstrated promising tumor uptake and a clean profile in healthy organs.

Dosimetry and safety projections

• Dosimetry analysis indicated kidneys and red marrow as the main dose-limiting organs, but all healthy organs remained within established safety limits at planned starting doses.

• Hematologic recovery will be monitored to guide repeated dosing strategies, with anticipated transient drops in blood counts expected to recover.

• Tumor retention was strong, with up to 80% uptake at 24 hours and little decline over time, supporting the therapeutic window for 212Pb treatment.

• Dosimetry and biodistribution results validate the ongoing U.S. Phase 1/2a study design with 212Pb as the therapeutic payload.