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Novel therapy for alcoholic liver disease-associated hepatorenal syndrome

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4U44AA029833-03
Agency Tracking Number: U44AA029833
Amount: $1,500,000.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 999
Solicitation Number: PAR18-578
Solicitation Year: 2018
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-05
Award End Date (Contract End Date): 2026-08-31
Small Business Information
Palo Alto, CA 94303-3654
United States
DUNS: 085280008
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (650) 208-8348
Business Contact
Phone: (650) 208-8348
Research Institution

Novel therapy for alcoholic liver disease-associated hepatorenal syndrome
Alcoholic liver disease (ALD) results in over 400,000 hospitalizations each year in the US, with a portion of these
patients developing hepatorenal syndrome with acute kidney injury (HRS-AKI). There are no current therapeutic
options that specifically address the cellular dysfunction and systemic inflammatory response that leads to
progressive organ failure mediated by mitochondrial dysfunction and oxidative stress by direct alcohol-mediated
toxicity. This leads to impaired hepatocyte and renal function, worsening organ failure, and the need for protective
renal and hepatic therapies with the goal of improving clinical outcomes for patients who develop HRS-AKI.
Nicotinamide adenine dinucleotide (NAD+) is a hallmark of aging-related disease for the liver and kidney.
Decreased levels and impaired synthesis of NAD+ are found in ALD accompanied by increased de novo
lipogenesis and impaired mitochondrial oxidation made possible by the role of alcohol in NAD+ depletion and
impaired cellular function. NAD+ supplementation with the NAD+ precursor nicotinamide riboside (NR) reverses
alcohol-induced changes by increasing NAD+ levels in tissue culture, enhancing mitochondrial oxidation,
mitochondrial biogenesis, and gene expression. In animal models, NAD+ supplementation with NR has been
shown to improve liver histology, reduce liver injury and protect the kidneys against ischemic injury and DNA
damage preventing progressive worsening of renal injury. 2,4 dihydronicotinamide riboside (NRH), , a recently
identified highly potent NAD+ precursor, consistently increases intracellular NAD+ levels to a greater extent than
NR in liver and kidney, is stable in serum, and in addition acts as a highly potent immune modulator to dampen
the systemic inflammatory state. Given the significant depletion in NAD+ levels in both liver and kidney in patients
with ALD, NRH has the potential to reverse or prevent progression of HRS-AKI in ALD patients in combination
with the standard of care. In this Fast Track study, we will complete IND-enabling studies of our proprietary
intravenous formulation of NRH, MP04, followed by a Phase 1 clinical trial to investigate its safety and tolerability
in humans. The outcome of this work will be a novel therapeutic for ALD-associated HRS.

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

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