# Long-acting PTH for hypoparathyroidism

> **NIH NIH R44** · EXTEND BIOSCIENCES, INC. · 2021 · $2,000,000

## Abstract

Project Summary
Hypoparathyroidism is a rare disease that results from a deficiency or inability to make sufficient amounts of
parathyroid hormone (PTH). Untreated or inadequately treated hypoparathyroidism leads to clinically
significant mineral-related metabolic issues including hypocalcemia, which leads to heart arrhythmias, spasms
of the vocal cords, and seizures. Current management of the disease for the majority of patients consists of
supplemental doses of calcium and active vitamin D to manage the hypocalcemia. While this approach is
intended to maintain serum calcium, it does not correct the underlying PTH deficiency and the physiological
aspects of hypoparathyroidism can still occur. Moreover, supplementation is associated with long-term
complications from the use of supraphysiological doses of calcium in the absence of endogenous PTH
hormone, which contribute to renal function deterioration, kidney stones, soft tissue calcifications and
abnormalities in bone remodeling. Natpara (PTH 1-84), is approved by the FDA for a subset of
hypoparathyroidism patients, but only partially alleviates the need for vitamin supplementation due to its short
half-life, and some patients still must take >10 pills/day. Clinical trials have demonstrated that if PTH(1-34) is
dosed continuously via a pump in humans, it can mimic physiological levels of PTH to restore normal levels of
calcium, phosphorus and markers of bone turnover. However, a pump-mediated, continuous infusion of PTH
would be costly and inconvenient for patients. Extend Biosciences has developed a long-acting version of
PTH(1-34) (EXT608) that could be dosed once a week and achieve a prolonged pharmacokinetic profile that
approximates endogenous PTH levels. SBIR Phase II results showed that EXT608 is more efficacious than
native PTH, and based on the retention time in rat and NHP, EXT608 is projected to be dosed once-weekly in
humans. In a rat model of hypoparathyroidism, EXT608 was able to normalize calcium and phosphate levels
while returning markers of bone turnover and bone mineral density to wild-type levels over the four-week study.
Additional studies completed are the standard toxicology studies and the development of a GMP process. The
studies proposed in this Phase IIB application will focus on completing the few remaining IND-enabling studies,
produce a GMP batch for clinical trials, and to prepare and file an IND. Once the IND application is approved
by the FDA, we will begin a Phase 1 clinical trial to determine safety and tolerability of EXT608 in healthy
volunteers. This long-acting PTH(1-34) derivative will provide a true replacement therapy to treat
hypoparathyroidism that returns serum and urinary calcium and phosphate to physiological levels and
maintains it over the course of week, thereby significantly improving quality of life for patients.

## Key facts

- **NIH application ID:** 10262953
- **Project number:** 5R44DK107231-05
- **Recipient organization:** EXTEND BIOSCIENCES, INC.
- **Principal Investigator:** Laura M Hales
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,000,000
- **Award type:** 5
- **Project period:** 2015-09-24 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10262953

## Citation

> US National Institutes of Health, RePORTER application 10262953, Long-acting PTH for hypoparathyroidism (5R44DK107231-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10262953. Licensed CC0.

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