Melanoma incidence in the United States is growing rapidly. Surgery combined with radiation can be curative at early stages but, metastatic melanoma is usually fatal. Since 2011, targeted MAPKi and immunotherapies have improved outcomes, but low response rates, acquired resistance, and adverse events limit quality of life for these patients (5-yr. survival <25%). Under predicate R&D, Viewpoint (VMT) demonstrated the potential of peptide-receptor- targeted alpha(a)-particle ([212Pb]VMT01) therapy (PRRT) targeting the melanocortin subtype 1 receptor (MC1R); alone and in combination with FDA-approved drugs. VMT01 innovations include our biorthogonal “click” cyclization; Pb-specific chelator (PSC) that enhances 203Pb/212Pb radiometal coupling; and linker-chemistry that improves VMT01 internalization on receptor binding. The commercial potential of PRRT is evidenced by the recent FDA approval of beta(b)-particle PRRT for neuroendocrine tumors (LutatheraÔ). While objective responses were seen in only 18% of patients in the Phase 3 trial, Lutathera developer (AAA) was acquired by Novartis for $3.9Bln. Alpha(a)-particle therapy is an exciting-emerging form of PRRT that is producing objective (and even complete) responses clinically. Viewpoint secured financing to support a Phase 1 [203Pb]VMT01 human imaging/dosimetry trial according to FDA guidance (begins May, 2020; Mayo Clinic) prior to therapy trials of [212Pb]VMT01. This Direct to Phase II research is significant because VMT’s a-therapies have the potential to improve outcomes for thousands of metastatic melanoma, neuroendocrine tumor patients for whom all therapies fall short. PREDICATE MILESTONES: Secured $650k investment; a Phase II SBIR (CA203430) to conduct an [203Pb]VMT01 imaging/dosimetry trial (Mayo Clinic); an NIH R01 with the University of Iowa to (CA243014; Viewpoint CSO Schultz is Co-PI) to conduct a Phase 1 a-therapy trial (VMT-a-NET) for neuroendocrine tumors; automated radiopharmaceutical production (GMP kits); exclusively licensed IP; 203Pb supply agreement with Lantheus; established radiopharmacy operations; completed working prototype of 212Pb production device (VMT- a-GEN) and established manufacturing facilities. The following Specific Aims ready VMT for therapy trials. AIM 1. Manufacture & validate GMP VMT01 peptide and conduct pharmacology/toxicology in non-human primates in parallel with funded Phase 1 imaging trial. AIM 2. Scale and validate manufacturing of 224Ra/212Pb production device (VMT-a-GEN) for clinical trials. IMPACT: With success, we expect to have obtained validated GMP grade VMT01 peptide and the pharmacology/toxicology data needed for CMC/IND submission/approval for VMT01 therapy trials. We further expect to have scaled VMT-a-GEN manufacturing to meet the need of 1 generator per week for our funded VMT- a-NET for neuroendocrine tumors trial and yet to be funded VMT01 for metastatic melanoma therapy trial. Thus, Viewpoint will have developed the competitive advantage of control of on-demand supply of therapeutic radionuclide 212Pb for expanded trials and commercialization of VMT-a-NET and VMT01.

This project will complete radiopharmaceutical toxicology, automate Th-228 isolation, and validate of a Pb-212 production device for alpha-particle therapy for metastatic melanoma. Other agents are not available.