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New Therapy for the Treatment of Primary Biliary Cholangitis.

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK134242-01A1
Agency Tracking Number: R43DK134242
Amount: $448,110.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA22-176
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-05-01
Award End Date (Contract End Date): 2024-04-30
Small Business Information
6725 Mesa Ridge Road, Suite 260
San Diego, CA 92121-3938
United States
DUNS: 963248807
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (858) 657-0918
Business Contact
Phone: (858) 657-0918
Research Institution

Project Summary
Primary biliary cholangitis (PBC) is a chronic disease in which the small bile ducts in the liver become injured
and inflamed and eventually destroyed. When bile ducts are depleted, the resulting bile build up results in liver
damage, leading to scarring, cirrhosis, and eventually liver failure. Among the common early symptoms of PBC
is itchy skin (pruritus), tiredness, abdominal pain, low appetite, weight loss and arthritis. This chronic
cholestatic liver disease predominantly affects women in their fourth and sixth decades. Currently therapeutic
options to treat PBC are limited and much of the pharmacotherapy is restricted to management of disease
symptomology.Lysophosphatidic acid (LPA) acts as a potent signaling molecule with wide-ranging effects on many
different target tissues, and is implicated as a mitogen acting mainly through LPAR1 in the development of
fibrosis in various organs. LPAR1 is also implicated in the development of arthritis. Many of these observed
effects appear to involve LPAR1 activation and modulation of inflammatory responses through numerous
signaling molecules including TNFα, IFNγ, IL-17, CTGF and TGFβ. IFNγ and IL-17 are signaling molecules
implicated in the development of PBC. Pruritus is a serious symptom associated with PBC which has been
linked to Autotaxin, the enzyme responsible for plasma LPA production. LPA may act on neurons through its
receptors of which LPAR1 is the principal receptor expressed. Thus, LPAR1 may represent a key locus in the
development of both pathologic inflammation and serious quality of life symptoms.Epigen has identified several classes of potent and selective LPAR1 antagonists from which an initial
lead compound EPGN696 and backup EPGN2154 have demonstrated pre-clinical efficacy in other disease
models. These compounds do not show cholestatic risk in human cellular hepato-toxicity models compared to
a clinical compound BMS-986020 which has been withdrawn. We propose to profile the two LPAR1
antagonists for utility in PBC for their ability to modulate key inflammatory signaling molecules IFNγ and IL-17
and itch responses in pre-clinical models.Completion of lead profiling will result in selection of a single lead that will be evaluated in a pre-clinical
model of PBC, conducted at University of California Davis. These studies will determine the feasibility of
developing a LPAR1 antagonist for treatment of PBC.

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

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