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A novel approach to restricting the spread of neurofibrillary tau

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AG073080-01A1
Agency Tracking Number: R41AG073080
Amount: $844,655.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIA
Solicitation Number: PA20-265
Timeline
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-09-01
Award End Date (Contract End Date): 2023-08-31
Small Business Information
7770 REGENTS RD 113 319
San Diego, CA 92122-1937
United States
DUNS: 078781043
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 TRAVIS STILES
 (858) 324-6357
 travis.stiles@novoron.com
Business Contact
 ANDREW BRIGHT
Phone: (858) 324-6310
Email: a.taylor.bright@novoron.com
Research Institution
 UNIVERSITY OF CALIFORNIA SANTA BARBARA
 
3227 CHEADLE HALL
SANTA BARBARA, CA 93106-0001
United States

 Nonprofit College or University
Abstract

7. Project Summary
Alzheimer’s disease (AD) is the most common cause of dementia and is a growing problem as populations age.
More than 25 million people are affected by dementia worldwide with most suffering from AD. AD is characterized
by the presence of plaques of insoluble amyloid-beta (Aβ) and tangles of hyperphosphorylated aggregates of
the cytoskeletal protein, tau. Thus far, most AD treatments have targeted Aβ aggregation and plaque formation,
but these therapies have largely failed to translate from preclinical rodent models to humans. Interestingly, tau
pathology has been shown to correlate better with cognitive decline than Aβ, and thus restricting the spread of
neurofibrillary tau has become a growing focus for development of treatments for various tauopathies, including
AD.
It was recently discovered that LRP1 is a master regulator of tau uptake and spread in the brain, indicating that
LRP1 may be an important therapeutic target for slowing the progression of various tauopathies. Novoron
Bioscience is developing novel large-molecule therapies targeting LDL receptor-related protein 1 (LRP1),
a master regulator of tau uptake and spread in the brain, to slow the progression of tauopathies such as
(AD) and improve functional outcomes in patients.
Novoron’s lead compound, NOVO-118, is a high-affinity LRP1 antagonist that is actively taken up into the brain
via both subcutaneous and intravenous administration. The purpose of this proposal is to evaluate the
therapeutic potential of NOVO-118 by assessing its ability to restrict the spread of tau in the rodent brain. We
will accomplish this by uncoupling proof of concept studies for effective tau restriction from assessment of
translatability in terms of clinically relevant utilization. To accomplish this, we have designed this project with two
primary goals: 1) generate necessary proof of concept demonstrating the ability of NOVO-118 to abrogate tau
spread; and 2) de-risk the technology by demonstrating that we can deliver the drug and elicit benefit in a
clinically translatable fashion.8. Project Narrative
Tauopathies, of which Alzheimer’s disease is the most prominent example, are a group of neurodegenerative
conditions characterized by the spread of neurofibrillary tau, which is a process shown to be regulated by the
LRP1 receptor. As tau spread has been shown to correlate strongly with cognitive decline, therapies to restrict
such spread may provide a first-in-class approach to slowing the devastating effects of these diseases. The
purpose of this proposal is to test the ability of NOVO-118, a novel antagonist of LRP1 that readily enters the
brain, to reduce the spread of tau in the brain and consequently slow the cognitive decline associated with
various tauopathies.

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

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