The first patients have been dosed with MP0712, a DLL3-targeted lead-212 radiopharmaceutical being developed for small cell lung cancer and other neuroendocrine tumours.

Molecular Partners and Orano Med have announced that the first patients have been dosed in a Phase 1/2a clinical trial evaluating MP0712, a DLL3-targeted radiopharmaceutical for patients with small cell lung cancer and other aggressive neuroendocrine tumours.

The multicentre US study is assessing the safety, tolerability and early clinical activity of MP0712, which combines a DARPin therapeutic targeting delta-like ligand 3 (DLL3) with the alpha-emitting radioisotope lead-212. Five sites are currently recruiting patients, with additional centres expected to open later this year.

The programme represents the lead candidate from the strategic collaboration between Molecular Partners and Orano Med, which aims to develop targeted alpha therapies using DARPin technology.

DLL3 has emerged as an important therapeutic target because it is highly expressed in most small cell lung cancers while showing limited expression in healthy tissue, making it an attractive target for precision radiopharmaceutical approaches.

The trial uses what the companies describe as a matched-pair strategy. Patients first undergo imaging using lead-203-labelled MP0712 to assess tumour uptake before receiving therapeutic doses of lead-212-labelled MP0712. Participants may receive up to four treatment cycles depending on their assigned dose cohort.

Patrick Amstutz, chief executive officer of Molecular Partners, said: “MP0712 is a Radio-DARPin designed to attack tumors by specifically leveraging DLL3 biology. With the first patient now in repeat dosing and Cohort 1 now recruited, we are establishing the clinical safety profile of this novel therapy in real time. Working closely with investigators in our trial, we remain on track to report initial study data in 2026, and, also paving the way for other Radio-DARPin candidates to move forward.”

The study is progressing through four planned dose levels, with dosing continuing as investigators establish the treatment’s safety profile.

Targeted alpha therapies have attracted increasing attention in oncology because they deliver highly potent radiation directly to tumour cells while limiting exposure to surrounding healthy tissue. Molecular Partners believes its DARPin protein platform may help improve tumour targeting while reducing some of the limitations associated with existing radioligand therapies.

Orano Med said the collaboration also demonstrates the flexibility of lead-212 across different targeting molecules and tumour types.

Frédéric Desdouits, chief executive officer of Orano Med, added: “The dosing of the first patients in this study marks an important step for Orano Med and our collaboration. It further illustrates the potential of lead-212 to support a broad clinical pipeline of targeted alpha therapies, leveraging its versatility across different vector formats to address a wide range of cancer types.”

Initial data from the Phase 1/2a study are expected later in 2026, while a more comprehensive assessment of safety and efficacy is anticipated in 2027.