SAT-758 Phase 1 Study Results Of EB612, A First-in-Class Oral PTH(1-34) Analog For The Treatment Of Hypoparathyroidism

Abstract G. Burshtein: Employee; Self; Entera Bio. C. Itin: Employee; Self; Entera Bio. A. Hoppe: Consulting Fee; Self; Entera Bio. A.C. Santora: Consulting Fee; Self; Entera bio. H. Galitzer: Employee; Self; Entera Bio. D. Pery: Employee; Self; Entera Bio. E. Reichman: Employee; Self; Entera Bio. A. Raskin: Employee; Self; Entera Bio. G. Levinton: Employee; Self; Entera Bio. E. Preiser: Employee; Self; Entera Bio. Y. Ver: Employee; Self; Entera Bio. C. Sternberg: Employee; Self; CSC Ltd. M. Toledano: Employee; Self; Entera Bio. Y. Caraco: Employee; Self; Hadassah Medical Center, Hebrew University Medical School. Introduction: Entera is developing EB612, oral PTH(1-34) tablets, as the first oral hormone replacement therapy for the treatment of hypoparathyroidism. Hypoparathyroidism is characterized by deficient PTH production, hypocalcemia and hyperphosphatemia. Standard treatments include several daily administrations of high dose oral calcium supplements and calcitriol (or analogs). Raising serum calcium to normal physiological levels frequently leads to elevated urinary calcium in the absence of PTH and is often associated with ectopic calcification, including nephrocalcinosis and renal failure. Entera, utilizing its proprietary N-Tab™ oral peptide delivery platform, has developed a novel oral formulation of PTH(1-34), which potentially overcomes the limitations of parenteral delivery. Entera’s oral PTH(1-34) tablets are designed to provide hypoparathyroid patients with a more convenient and flexible treatment of hypocalcemia and hyperphosphatemia. Study design: In this Phase 1 (NCT05965167), open-label study, 15 healthy young male subjects received 1.5 mg EB612 (3 tablets of 0.5 mg) orally in the morning after an overnight fast, followed by a second dose of 2.5 mg EB612 (5 tablets of 0.5mg) four hours after lunch. Blood samples were withdrawn to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug. Plasma PTH(1-34) was evaluated for PK. Serum Calcium, phosphate, 1,25(OH)2-Vitamin D, and endogenous PTH(1-84) were measured as PD markers. Results: Significant systemic exposure was achieved with EB612 tablets following both administrations. Additionally, the desired biological effect on serum levels of calcium, phosphate, and 1,25(OH)2-Vitamin D was shown (+3.9%, -20.8%, and +73.2% on average from baseline, respectively). Endogenous serum PTH(1-84) was decreased in response to oral administration of PTH(1-34)(43.0% decrease from baseline). All changes in PD parameters were sustained over the 14-hour study period. There were no treatment-emergent adverse events of hypercalcemia and no treatment-emergent serious adverse events. Conclusions: Several PTH replacement therapies for the treatment of hypoparathyroidism patients are currently in development, however these require daily or weekly injections and are cumbersome to titrate in this chronic and heterogenous disease. We previously published positive Phase 2a study results in hypoparathyroid patients using a QID regimen of EB612 tablets. In the current study a new generation of Entera’s N-Tab™ technology was utilized to enable a BID tablet dosing regimen. These results indicate that BID EB612 PTH(1-34) tablets may offer a convenient, flexible, safe, and effective oral therapy for patients with mild to severe hypoparathyroidism. Saturday, June 1, 2024