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Novel, Safe, Efficacious Heparin Reversal

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HL165961-01
Agency Tracking Number: R43HL165961
Amount: $394,392.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA21-259
Timeline
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-09-01
Award End Date (Contract End Date): 2023-08-31
Small Business Information
540 AVIS DR STE A
Ann Arbor, MI 48108-7906
United States
DUNS: 156551699
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 ELKE LIPKA
 (734) 223-6862
 elipka@tsrlinc.com
Business Contact
 ELKE LIPKA
Phone: (734) 223-6862
Email: elipka@tsrlinc.com
Research Institution
N/A
Abstract

Abstract
Anticoagulants and their reversal agents are key components of standard of care for managing thrombosis.
Heparin in particular is used for thrombosis prevention in multiple clinical indications, including procedures such
as cardiopulmonary bypass and catheter ablation, after which heparin’s anticoagulant activity requires prompt
neutralization. In fact, around a million clinical cases annually require heparin reversal in the US alone. Protamine
sulfate, the only FDA-approved reversal agent for heparin, is a 60-year-old drug with a Black Box Warning. Its
clinical use is constrained by two major limitations: (i) requirement of titration because of its very narrow
therapeutic safety window; and (ii) potentially life-threatening hypersensitivity reactions or anaphylaxis. Thus,
there is an unmet medical need to discover novel heparin-reversal agents with a wider therapeutic window and
better safety profile. Furthermore, although protamine can reverse the action of unfractionated heparin, it is
ineffective in reversing the anticoagulant action of low molecular weight (MW) heparins. Therefore, a novel,
effective reversal agent with a superior safety profile compared to protamine would not only improve current
treatment paradigms, but has also the very attractive commercial potential to expand the clinical use of low MW
heparins as a safer alternative to unfractionated heparin.
We aim to develop a safer and more efficacious heparin-reversal drug to replace protamine. Our proprietary
Polyanion Modulating Dendrimer (PoMoD) chemistry platform is ideal for creating drugs that selectively bind and
inhibit relatively unstructured polyanionic substances such as heparins. The proposed research will provide
preclinical proof-of-concept that our lead candidate, PoMoD-1.1, is a safe and effective heparin reversal
therapeutic with properties that warrant full preclinical product development. We will demonstrate efficacy with
intravenous administration in rat model, and establish the pharmacokinetic (PK) and pharmacodynamic (PD)
relationship. In addition, we will assess the exploratory toxicology profile of PoMOD-1.1 in rats. These data will
provide an initial estimate of the therapeutic window. Furthermore, our learnings from this research can be
applied to the design and testing of other PoMoDs which bind polyphosphate or other poly-anions which are
implicated in several disease states.
The end result of this work will be a novel, best-in-class safe and effective heparin-reversal agent to provide
superior treatment options to patients. We have assembled a team of expert advisors and collaborators to ensure
successful completion of this research plan.

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

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