The lead collaborators at Massachusetts General Hospital developed a novel class of long-acting PTH analogs that were selected for their unique biological properties at the PTH/PTHrP receptor (PTHR1). A single injection of these long-acting PTH peptides leads to a 24- to 48-hour sustained calcemic response in rodents and monkeys, which is accompanied by a sustained reduction in urinary calcium excretion and in blood phosphorus levels. Injection of either wild type PTH(1-34) or PTH(1-84) failed to induce similarly prolonged effects. LA-PTH was selected from among these analogs based on its superior potency in vitro and in vivo. Collectively, these data predict that LA-PTH can be more effective as a treatment for hypoparathyroidism than current modalities and that the new analog may be especially valuable for individuals with activating calcium-sensing receptor mutations, a particularly difficult-to-treat patient group who have an even higher risk of nephrocalcinosis and nephrolithiasis under conventional calcium and vitamin D therapy. The team is collaborating on the completion of the following studies: - Synthesis of Good Manufacturing Practice (GMP) and non-GMP material - Formulation development - Manufacture of drug supply for clinical studies - Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies - Investigational New Drug (IND)-directed toxicology

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