You are here

Stable Glucagon for Treatment of Hyperinsulinism

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44DK111304-03
Agency Tracking Number: R44DK111304
Amount: $1,556,747.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 200
Solicitation Number: PA18-574
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-13
Award End Date (Contract End Date): 2021-08-31
Small Business Information
2830 13 ST.
Boulder, CO 80304-3518
United States
DUNS: 831649236
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 PAWEL FLUDZINSKI
 (303) 604-0296
 pawel.fludzinski@amidebio.com
Business Contact
 MIKHAIL PLAM
Phone: (303) 604-0296
Email: misha.plam@amidebio.com
Research Institution
N/A
Abstract

In severe persistent hyperinsulinism (HI), repeated hypoglycemic episodes can ultimately lead to
permanent seizure disorders, learning disabilities, cerebral palsy, blindness and even death. Clinical
studies have demonstrated the effectiveness of both short-term and long-term treatment with
glucagon for severe forms of HI and continuous subcutaneous administration of glucagon has been
recommended both because of the potential improvement in patient outcome and high costs of
surgical intervention followed by long-term annual care costs. However, the instability of glucagon in
solution creates both administration problems and potential complications due to infusion tube
blockage. These instability problems have limited the use of glucagon for severe persistent HI. To
overcome this problem, in our successful Phase I grant we developed a series of solution stable
glucagon analogs using a novel design approach and demonstrated their effectiveness both in vitro
and in vivo. These analogs when formulated in a conventional sterile diluent maintain not only the
standard 95% potency requirement throughout a 2 year storage period at 4ºC but more importantly
offer an extended “in use” stability period of at least 3 months at 40ºC. Such analogs are compatible
with implementation in a pump system for the long-term management of severe persistent HI without
concern for complications due to glucagon instability and pump clogging issues. In addition, such a
product will be suitable for emergency hypoglycemic incidences which result in over 200,000
hospitalizations a year. Finally, the resultant product could be implemented in a bi-hormonal artificial
pancreas for T1 and T2 diabetes. In this Phase II project, we aim to develop large scale (gram level)
GLP production of the lead candidates, complete toxicology, immunogenicity and formulation studies,
and prepare a regulatory package suitable for filing an IND in preparation for clinical trials.In our successful Phase I grant, a series of novel glucagon analogues were designed, produced at
milligram levels, tested for solution stability and for both in vitro and in vivo activity. We have identified
3 lead candidates with superior physical properties and biological activity in vivo using a hyperinsulinism model. In this Phase II proposal we aim to complete large scale (gram level) GLP production of the lead candidates, complete toxicology and formulation studies, and prepare a regulatory package suitable for filing an IND in preparation for clinical trials aimed to demonstrate the
use of our stable glucagon analogs for treating congenital hyperinsulinism, emergency hypoglycemia
and ultimately for treating T1 and T2 diabetics using a bi-hormonal pump.

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

US Flag An Official Website of the United States Government