Molecular Partners (NASDAQ:MOLN) executives outlined the company’s radiopharmaceutical strategy at TD Cowen’s Oncology Innovation Summit, emphasizing its Radio-DARPin platform and lead program MP0712 in refractory small cell lung cancer.
Chief Executive Officer Patrick Amstutz and Seth Lewis, senior vice president of investor relations, communications and strategy, said the company’s DARPin technology is being applied to radioligand therapy because of its small size, high affinity and tunable pharmacokinetics. DARPins, or Designed Ankyrin Repeat Proteins, are “mini-proteins” that can be engineered to bind targets and deliver radioisotopes to tumors, Amstutz said.
Radio-DARPin platform positioned as broader targeting approach
Lewis said the company has engineered DARPins to address issues such as kidney uptake, a key consideration in radiopharmaceuticals. He described the DARPin scaffold as consistent and manipulable, allowing Molecular Partners to build in properties such as reduced kidney reabsorption across multiple programs.
Lewis also said the platform allows the company to test different isotopes and chelators while maintaining the same targeting molecule. He cited earlier company work showing similar biodistribution when swapping lead and actinium isotopes in experiments using two DARPins.
MP0712 is the lead value driver over the next year
Lewis said MP0712, the company’s DLL3-targeted Radio-DARPin, is expected to drive Molecular Partners’ value over the next 12 months. The program is being developed as a lead-212 radiopharmaceutical in refractory small cell lung cancer.
Amstutz summarized imaging work from a physician-initiated study in South Africa that used a lead-203 imaging agent. He said the study showed specific tumor uptake and rapid tumor loading, with roughly 80% tumor loading within 24 hours and continued loading through day five. He said the company observed clearance primarily through the kidney and a favorable tumor-to-kidney ratio that improved over time.
Because DLL3 is a low-copy-number target, Amstutz said Molecular Partners engineered MP0712 with a somewhat longer half-life to take advantage of DLL3 internalization. He contrasted DLL3’s expression of several hundred copies per cell with PSMA at roughly 150,000 copies per cell.
Amstutz said dosimetry supported a starting dose of 75 megabecquerels and a potential top dose of 200 megabecquerels. He said the company estimated 2.1 gray to the kidney and 0.8 gray to red marrow at the 75-megabecquerel dose, and noted that marrow dose is viewed differently from kidney exposure because marrow can recover.
Clinical trial is in early screening and dosing stages
Executives said Molecular Partners is actively screening and recruiting patients at five U.S. centers, with plans to expand to at least eight centers in the second half of the year. Lewis said the company has received inbound interest from additional principal investigators.
Amstutz stressed that the company does not yet have clinical data in hand from the lead-212 MP0712 trial. “We literally are dosing patients these days,” he said. He added that early safety, particularly effects related to blood and marrow exposure, will be important in determining whether the drug has a therapeutic index.
Amstutz said the company does not plan to “dribble out” patient-by-patient data. Instead, it expects to provide updates on trial progress, with dose escalation serving as an indirect signal of safety. He said a more meaningful data set could be available roughly a year from now.
Lewis said the company intends to discuss the trial at ASCO and the Society of Nuclear Medicine and Molecular Imaging meeting. He said Molecular Partners may present safety information in the second half of the year and potentially case studies if appropriate, while preserving the integrity of the data set.
Company sees differentiation in DLL3 landscape
Discussing competition in DLL3, Lewis said the field has become more crowded, including radiopharmaceutical, antibody-drug conjugate and T-cell engager approaches. He identified Molecular Partners and Novartis’ Mariana Oncology as active radiopharmaceutical participants in Phase 1.
Amstutz said MP0712 is differentiated by its intermediate half-life and by the platform’s ability to use lead or actinium. He said Molecular Partners chose lead first but can also work with actinium, which may be relevant in regions where lead supply is more limited or in compassionate-use settings where physicians have access to actinium.
MP0726 and additional programs advancing
Molecular Partners also discussed MP0726, a mesothelin-targeted Radio-DARPin. Amstutz said the program was designed to avoid binding shed mesothelin, which can act as a “sponge” in the bloodstream and reduce tumor delivery. He said the DARPin binds the full form and the remaining cell-surface “stump,” creating what the company views as a cancer-selective mesothelin approach.
For MP0726, Amstutz said the company has not yet decided whether to use lead or actinium. He said the target’s uptake profile may lean somewhat toward actinium, but Molecular Partners would prefer to use dosimetry and clinical data before selecting an isotope for a Phase 1 program.
Lewis said the next steps for MP0726 include compassionate-care imaging work in the second half of the year, followed by IND-enabling studies and a potential IND filing in 2027. He also said Molecular Partners has additional undisclosed programs in animal studies and expects at least one new program disclosure in the second half of the year.
About Molecular Partners (NASDAQ:MOLN)
Molecular Partners AG is a clinical-stage biopharmaceutical company headquartered in Zurich, Switzerland, specializing in the design and development of DARPin® (Designed Ankyrin Repeat Protein) therapies. These small, modular proteins are engineered to bind with high specificity and affinity to disease-relevant targets. The company’s technology platform aims to deliver novel treatments across multiple therapeutic areas by leveraging the unique properties of DARPins, including stability, tissue penetration and multi-specific binding capabilities.
The company’s development pipeline spans infectious diseases, ophthalmology and oncology.
