Entera Bio Announces New Validating In Vivo Pharmacokinetic And Pharmacodynamic Data That Supports Development Of Proprietary Long-Acting PTH Analog Using N-Tab Platform For Patients With Hypoparathyroidism

Entera Bio Ltd. (NASDAQ:ENTX) ("Entera" or the "Company"), a leader in the development of oral peptides and proteins replacement therapies, today announced new validating in vivo pharmacokinetic and pharmacodynamic data that supports further development of a proprietary long-acting parathyroid hormone (PTH) analog using its N-Tab® platform to create the first once-daily tablet treatment for patients with hypoparathyroidism (EB612 program).  The positive preclinical findings showed the proprietary analog achieved a markedly longer plasma half-life and sustained calcium elevation for over three days - in contrast to unmodified PTH(1-34) controls, which showed no calcium response.

Hypoparathyroidism is a heterogeneous, rare endocrine disorder characterized by deficient PTH production, hypocalcemia, and hyperphosphatemia. Historically, the standard of care included high dose calcium and calcitriol supplementation. However, raising serum calcium to normal physiological levels in the absence of PTH frequently leads to elevated urinary calcium and is often associated with ectopic calcification, including nephrocalcinosis and renal failure. Today, the only approved PTH replacement treatment (YORVIPATH®) requires patients to administer injections every day, while investigational candidates may require patients to take weekly injections.  

Entera previously demonstrated proof of concept data for its EB612 program using an unmodified PTH(1-34) analog and an earlier generation of its N-Tab® platform in a Phase 2, 16-week study which enrolled 19 patients with hypoparathyroidism. The Phase 2 study (JBMR, 2021) demonstrated a 42% reduction (p=0.001) from baseline in median calcium supplement use, while maintaining serum Ca levels above the lower limit for hypoparathyroidism patients (>7.5 mg/dL) throughout the study; however, the trial involved a QID regimen or 4 times a day dosing of tablets. The current preclinical data represent a key step toward addressing this dosing burden with a single, once-daily tablet.

Key Study Details

Entera conducted in vitro and in vivo validation of a variety of proprietary long-acting PTH analogs with a new generation of its N-Tab® oral peptide platform. A confirmatory minipig study was recently completed in which a single oral tablet was administered to five animals and the PK–PD profile was monitored over five days, using an unmodified PTH(1‑34) tablet as control.

• The lead variant demonstrated a markedly longer plasma half-life compared to the unmodified PTH(1-34) control at the same dose, providing pharmacokinetic support for once-daily dosing
• Serum calcium levels increased for more than three days in all animals receiving the lead variant; the sustained elevation correlated with prolonged pharmacokinetic exposure
• Unmodified PTH(1-34) control tablets did not increase serum calcium levels
• No adverse events were observed

Entera plans to present these data at an upcoming medical conference.