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Development of small molecule Protease-activated-receptor-2 antagonists as oral asthma therapeutics

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL169048-01A1
Agency Tracking Number: R41HL169048
Amount: $300,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-15
Award End Date (Contract End Date): 2024-09-14
Small Business Information
41593 Winchester Rd. Suite 220
Temecula, CA 92590-4841
United States
DUNS: 117611839
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (951) 660-6652
Business Contact
Phone: (951) 660-6652
Research Institution
PO Box 210066 Administration Building, Room 601
TUCSON, AZ 85721-0066
United States

 Nonprofit College or University

Lay Abstract: Asthma is a widely prevalent condition that affects 1 in 12 adults in the United
States and an estimated 300 million individuals worldwide. Mild asthma is well controlled by
current standard of care (SOC), including long-acting b-adrenergic receptor agonists, anti-
leukotrienes and/or inhaled corticosteroids. As patients progress to severe disease add-on
treatment options can include newer biologics/antibody treatments. While these treatments are
useful for certain conditions, their application and known side effects limit their applicability
resulting in 50% of asthmatics remaining untreated. There is a clear need for developing novel
asthma drugs to treat this population. Protease-activated receptor-2 (PAR2) is a G-protein-
coupled receptor activated by serine proteases released from asthma-inducing pathogens as well
as by endogenous proteases associated with asthma inflammation. We have shown that PAR2
is a viable target for asthma drug development by identifyin two small molecule PAR2 antagonists,
C391 and C781, that limit allergen-induced asthma indicators following direct nasal application in
pre-clinical animal models. In this application we propose to characterize two novel PAR2
antagonists (C937 and C938) with improved pharmacodynamics and pharmacokinetics that could
allow for novel PAR2-directed antagonism treatment following oral drug administration.
Successful completion of the proposed feasibility studies (Phase I) will establish a novel drug lead
for asthma and allow for development of a small business Phase 2 application that will include
drug optimization and formulation, in vivo efficacy of lead compounds in allergen challenges of
chronic exposure mouse models as well as larger animal asthma models (rats and dogs) and
advanced in vivo PK studies. Our overall goal is to move these drug leads forward so that they
can be tested (Clinical Phase I studies) and used in humans to control asthma.

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

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