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A long acting parathyroid hormone (PTH) 1-34 for treatment of hypoparathyroidism

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK125144-01
Agency Tracking Number: R43DK125144
Amount: $245,871.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 200
Solicitation Number: PA19-272
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-07-01
Award End Date (Contract End Date): 2021-06-30
Small Business Information
211 BELGRAVE AVE
San Francisco, CA 94117-3851
United States
DUNS: 831183954
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ERIC SCHNEIDER
 (510) 290-5539
 eric@prolynxllc.com
Business Contact
 CHARLES GARRETT
Phone: (760) 274-7016
Email: charles.garrett@prolynxllc.com
Research Institution
N/A
Abstract

A long acting parathyroid hormone PTH(1-34) for treatment of hypoparathyroidism
Project Summary
Hypoparathyroidism is a rare endocrine disorder characterized by low calcium (Ca2+) and high
phosphate (Pi) levels in the setting of absent or low parathyroid hormone (PTH). Overall, an
estimated 60,000 to 115,000 individuals in the United States have chronic hypoparathyroidism;
most cases (~75%) result from neck surgery, and the remaining are non-surgical or, rarely,
genetic disorders. Most hypoparathyroid patients require lifelong high-dose Ca2+ and vitamin D
supplements. The associated side effects and the difficulty of maintaining stable serum and urine
Ca2+ levels with these regimens makes PTH replacement therapy a desirable or necessary option
for many.
Two PTH replacement drugs are commonly in use, Natpara, the recombinant form of natural PTH,
and teriparatide (Forteo), the 34-amino acid N-terminus polypeptide of the natural hormone. Both
these drugs have short half-lives after subcutaneous administration, requiring once-daily injection.
Neither adequately mimics the physiological levels of PTH secretion. Indeed, 5 of the 13 members
of the FDA Advisory Committee voted against approval of Natpara for hypoparathyroidism, stating
that “dose could be better optimized to closer mimic physiological levels, resulting in more salutary
effects”.
We have developed a chemically controlled, ultra-long acting delivery system to support once-
weekly to once-monthly administration of peptides and other small molecules. With this system a
therapeutic agent is covalently attached to a hydrogel microsphere depot by a cleavable β-
eliminative linker. Upon subcutaneous injection the linker slowly cleaves and releases the drug.
The current proposal seeks to demonstrate the feasibility of utilizing this system for delivery of
PTH.
Specifically, we will prepare and characterize two hydrogel microsphere conjugates of PTH(1-34),
one suitable for once-weekly and the second suitable for once-monthly administration. Since
PTH(1-34) itself is not sufficiently stable for a once-monthly dosing regime, the latter conjugate
will be prepared using a more stable PTH(1-34) analog with similar physiological activity. We will
perform pharmacokinetic and pharmacodynamic studies of the compounds in thyroid-
parathyroidectomized rats to evaluate the potential of one or both these compounds as an
improved therapeutic agent for hypoparathyroidism.A long acting parathyroid hormone PTH(1-34) for treatment of hypoparathyroidism
Project Narrative
Hypoparathyroidism is a disorder characterized by low calcium and high phosphate in the blood
typically resulting from damage to the parathyroid glands during neck surgery. It may be treated
with daily injections of parathyroid hormone or analogs, but the levels of these drugs must be
maintained within close tolerances. We propose to prepare conjugates of these drugs that are
expected to facilitate the treatment of hypoparathyroidism by reducing the dosing frequency
from once-daily to once-weekly or once-monthly while minimizing fluctuations in drug levels.

* Information listed above is at the time of submission. *

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