First-in-human imaging with 203Pb-labeled MP0712 showed focal uptake in primary and metastatic lesions at 24 hours, sustained through day 4, with limited signal in the kidney and liver. The case, drawn from compassionate-use access in South Africa, also led to upstaging from Stage 3 to Stage 4 SCLC due to newly identified liver metastases. The images are being positioned as predictive for therapy using the matched 212Pb isotope.
Molecular Partners has filed a US IND for MP0712, a DLL3-targeted Radio-DARPin developed with Orano Med, and plans to initiate a multicenter Phase 1/2a by the end of 2025 with initial data anticipated in 2026. The study design includes an imaging and dosimetry step with 203Pb-MP0712 before treatment with 212Pb-MP0712 to establish safety and select a recommended Phase 2 dose. Preclinical and in vitro data emphasize rapid internalization and intracellular accumulation in DLL3-expressing cells, with half-life engineering intended to balance tumor uptake and circulating exposure.
Strategically, the company is using early human imaging to de-risk a radiopharmaceutical program in a crowded DLL3 landscape and to support a theranostic enrollment paradigm. The emphasis on internalization and receptor replenishment aims to differentiate DARPins from antibody-based vectors in terms of tumor penetration and kinetics. At the same time, the matched imaging–therapy pair provides a direct readout for patient selection and dose planning. Choosing 212Pb places the program within the accelerating alpha-therapy segment, where short half-life and high linear energy transfer are viewed as a potency and safety optimization—if logistics and marrow exposure can be controlled.
For sites, the operational footprint is nontrivial. The protocol’s imaging/dosimetry step adds visits and coordination across nuclear medicine, radiation safety, and pharmacy, and will favor centers with established alpha-therapy workflows. Supply chain reliability for 212Pb and 203Pb—generator capacity, distribution timing, and on-site labeling—will dictate scheduling rigidity and throughput. The shorter half-life of 212Pb tightens shipment windows and will stress just-in-time processes, pushing sponsors and CROs toward sites with proven radiochemistry partners. The imaging-first approach could reduce screen failure and unnecessary exposure, but it also introduces selection bias and may complicate accrual pacing in a fragile SCLC population.
For sponsors and regulators, DLL3 remains a validated but complex target. With a DLL3-directed T-cell engager already in the market, the bar for incremental benefit is rising, particularly on durability, tolerability, and ease of delivery. A radiopharmaceutical that performs well at low DLL3 expression could expand the addressable population and reduce dependence on tissue-based assays. Still, regulators will expect a coherent biomarker strategy tied to imaging or IHC. Hematologic, renal, and hepatic dosimetry will be scrutinized, as will any signal of off-target toxicity once 212Pb is introduced. Manufacturing scale and isotope availability are likely to be rate-limiting and will affect multi-center feasibility.
The near-term watch list is straightforward: FDA clearance of the IND, clarity on site activation and isotope logistics in the US, and detailed imaging and dosimetry outputs slated for presentation in early 2026. The first clinical readout needs to establish a tolerable therapeutic window and confirm that favorable organ dosimetry persists with 212Pb, not just 203Pb. Competitive dynamics could shift quickly if DLL3-directed agents are initiated earlier in the SCLC treatment sequence, thereby compressing the window for late-line enrollment. How Molecular Partners sequences imaging-driven selection, manages radiation operations at scale, and positions MP0712 relative to existing DLL3 modalities will determine whether this program can convert a promising case study into a viable clinical pathway.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
