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Bone and Mineral Metabolism

MON-768 - Pre-Clinical Results for EB612: First-in-Class Oral Long-Acting PTH(1-34) Analog as Hormone Replacement Tablet for Patients with Hypoparathyroidism

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Parathyroid hormone (PTH) plays an important role in regulating calcium and phosphate homeostasis. Hypoparathyroidism is a chronic, rare endocrine disorder characterized by insufficient PTH, resulting in hypocalcemia, hyperphosphatemia, and the potential for a broad spectrum of debilitating symptoms, including muscle cramps, fatigue, and cognitive impairment. Although PTH analogs have demonstrated therapeutic efficacy, the only approved replacement therapy requires daily injections.
OPK-8801004 is a proprietary (OPKO) long‑acting PTH analog. Developed with Entera’s N-Tab® platform, EB612 (oral OPK-8801004) is the first once-daily long-acting PTH replacement tablet for patients with chronic hypoparathyroidism. The thyroparathyroidectomized (TPTx) rodent model of hypoparathyroidism was used to evaluate the pharmacological effect of the long-acting PTH analog. The drug was administered on a daily basis for one week, and the effects on serum calcium (Ca) and phosphate (P) levels were assessed. During the treatment phase of this study, serum Ca levels were elevated, accompanied by decreased serum P levels, reaching comparable levels to those of the sham control animals, for both parameters.
Additionally, a pharmacokinetic/pharmacodynamic (PK/PD) feasibility study with the oral EB612 tablet was conducted in mini-pigs. Plasma concentrations of PTH along with serum Ca levels were measured at predetermined time points. EB612 reached maximal plasma levels 2–3 hours post‑dose, and the drug remained detectable in the plasma for more than three days. The single oral administration of EB612 produced rapid and robust increases in serum calcium from baseline, which were sustained for approximately three days. The pharmacologic response observed in the TPTx model along with the prolonged PK profile and calcemic effect observed in vivo with a single dose of the EB612 tablet are promising. Studies are ongoing to advance EB612 into first-in-human clinical studies.

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