Molecular Partners' DLL3-Targeting Radiotherapeutic Shows Promising Imaging Data, U.S. Trial Set to Begin

Imaging Data Paves Way for Targeted Radiotherapy Trial

ZURICH – Molecular Partners AG (NASDAQ: MOLN) has released encouraging early clinical data for its lead radiopharmaceutical candidate, MP0712, designed to deliver radiation directly to tumors expressing the DLL3 protein. The data, derived from a compassionate use program in South Africa, support the initiation of a U.S. Phase I/II clinical trial, which the company says is now ready to screen patients.

The findings were detailed in a recent webcast, following a presentation at the Theranostics World Conference. The imaging studies utilized Lead-203 to visualize how the drug candidate distributes in patients with metastatic small cell lung cancer (SCLC) and bladder cancer.

Favorable Biodistribution and Dosimetry Profile

Company executives highlighted that MP0712 showed rapid accumulation and prolonged retention in tumors, with visible uptake up to a week post-administration. Crucially, the agent appeared to clear from healthy organs like the liver and kidneys over time, a key factor for minimizing side effects.

"We observed a consistent pattern: early blood pool activity that dissipates, while tumor signals intensify and persist," said Michael Stumpp, Executive Vice President of Projects at Molecular Partners. He noted that in one SCLC patient, imaging revealed liver metastases that were previously unknown, which could directly impact treatment staging and planning.

Dosimetry estimates, which calculate radiation exposure to healthy tissues, suggested that at the planned starting dose, exposure to critical organs like the kidneys and red bone marrow would remain within established safety limits derived from conventional external beam radiation therapy.

Strategic Rationale in a Competitive Landscape

The DLL3 target has gained significant attention in oncology, particularly for SCLC, following the recent approval of the bispecific antibody tarlatamab. Molecular Partners is betting that a radiotherapy approach could offer a new mechanism of action, potentially for patients who progress on existing therapies or in combination with them.

"SCLC is radiosensitive, and current DLL3 modalities are not curative," said CEO Patrick Amstutz, explaining the strategic rationale. "We believe a targeted radiotherapy could provide a needed additional option, possibly used in concert with other agents."

The company developed MP0712 in collaboration with Orano Med, leveraging its DARPin platform for targeting and Orano's expertise in isotopes like Lead-212, the therapeutic counterpart to the imaging agent used in the study.

Path Forward and Expert Commentary

With the U.S. trial now initiating, the company expects to report initial safety data in the first half of 2025 and hopes to see early signals of anti-tumor activity by year's end. Full response rate data, however, are not anticipated until late 2026 or early 2027.

Independent expert Professor Ken Herrmann, Chair of Nuclear Medicine at the University of Essen and chairman of the company's Scientific Advisory Board, characterized the initial human biodistribution as "favorable." He urged cautious optimism, noting, "The imaging data are promising, but the true test is in the therapeutic phase, where we will understand the toxicity and response profile."

Dr. Evelyn Reed, Oncologist at a Major Cancer Center: "This is precisely the kind of precision we need in SCLC. The ability to visualize unknown metastases could change how we stage patients upfront. The dosimetry data look reassuring, but the proof will be in the therapeutic tolerability."

Mark Devlin, Biotech Analyst: "The data de-risk the program's mechanics—it gets to the tumor and clears from organs. The real commercial question is timing and positioning in a landscape that now includes an approved DLL3 therapy. Combination strategies will be key."

Sarah Chen, Patient Advocate (sharper tone): "More 'promising' data, another trial starting. We've heard this story before. SCLC patients are dying waiting. Show me survival data, not just pretty scans. And 'compassionate use' in South Africa? Let's see equitable access when and if this ever gets approved."

Dr. Arjun Mehta, Nuclear Medicine Physician: "The prolonged tumor retention is notable. It opens the door to using different therapeutic isotopes with longer half-lives, like Actinium-225, which could potentially deliver more radiation to the tumor. This flexibility is a significant advantage of their platform."

Molecular Partners also indicated that its broader pipeline is advancing, with an ovarian cancer program, MP0726, expected to enter human studies this year.