PROJECT SUMMARY Sarya LLC (Sarya) is a nuclear medicine technology company formed to commercialize radiopharmaceuticals. The goal of this Fast-Track STTR is to develop a new specific imaging agent for diagnosis, staging, and treatment of the hematological cancer, multiple myeloma (MM). MM is the 2nd most common blood cancer with an estimated 32,000 new cases and 13,000 deaths per year. Accurate detection is critical for enhancing survival in MM patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Positron Emission Tomography (PET) performed with a PET radiopharmaceutical (imaging agent) is a sensitive, quantitative and non-invasive clinical imaging technology to accurately detect, localize and phenotype MM cells throughout the body. 18F-fluorodeoxyglucose (FDG) is the only FDA-approved PET imaging agent for MM. Unfortunately, MM cells express low levels of GLUT-1 transporter and hexokinase, which are required for FDG uptake and retention. Additionally MM bone marrow harbors FDG-avid inflammatory cells. There is an unmet need for molecularly targeted, sensitive and specific MM imaging agents that can accurately stage and restage MM, identify high-risk MM patients, guide personalized MM treatment, and evaluate clinical response to treatment. The product of this STTR will be a specific and sensitive PET imaging agent (64Cu-LLP2A) for MM. Published data and ongoing first-in-human trial results have significantly informed the Phase I and II aims of this proposal. The Phase I Segment consists of two specific aims: (1) Perform dose escalation and single dose toxicity testing in mice. (2) Compile data for new dose and submit amendment of eIND to FDA. Three milestones will be met in Phase I: (1) A new mass will be selected based on no-observed-adverse-effect level (NOAEL), i.e. clinical signs of organ toxicity (vehicle vs experimental). (2) Based on the new determined mass, and in vivo preclinical image quality data, a new specific activity (Ci/mol) will be established. (3) Obtain FDA approval of Sarya sponsored amended eIND application. The Phase II segment involves a clinical trial and has one specific aim: Quantify the efficacy of 64Cu-LLP2A-PET imaging for detecting active MM in humans in a prospective imaging trial. Phase II milestones are: (1) Demonstrate high detection rates (% of scans that are positive for a focal lesion, p<0.05) for 64Cu-LLP2A versus FDG in MM patients. (2) Accuracy of 64Cu-LLP2A for active MM will be assessed using standard-of-care bone marrow (BM) biopsies and serum biomarker M-protein levels as the standards of reference. A correlation coefficient of 0.7 will be considered reasonably strong. In summary, Phase I will prove feasibility that 64Cu-LLP2A is tolerable with NOAEL resulting in a new eIND. Phase II will provide 64Cu-LLP2A-PET preliminary performance data to support a New Drug Application for 64Cu-LLP2A as a New Molecular Entity (NME) for FDA approval of Phase 2 clinical trials.

PROJECT NARRATIVE In this study, Sarya LLC (Sarya) will develop and commercialize a new specific positron emission tomography (PET) imaging agent 64Cu-LLP2A for diagnosis, staging, and treatment of the hematological cancer, multiple myeloma (MM). The development of this technology will fulfill an unmet need for molecularly targeted, sensitive and specific MM imaging agents that can accurately stage and restage MM, identify high-risk MM patients, guide personalized MM treatment, and evaluate clinical response to treatment.