# IND-enabling Preclinical Studies on Anti-Tau AD Vaccine for Phase 1 Trial

> **NIH NIH U01** · INSTITUTE FOR MOLECULAR MEDICINE · 2020 · $1,272,333

## Abstract

Project Summary
Data from various Alzheimer’s disease (AD) active vaccine clinical trials targeting Aβ pathology suggest that
these trials were unsuccessful because the vaccines: (i) did not induce therapeutically potent titers of anti-Aβ
antibodies in immunized elderly people with immunosenescence and (ii) were initiated too late in AD
pathogenesis. We suggest that an optimal AD vaccine formulation, adjuvant selection and targeting of the right
pathological molecules at the right stage of disease will be crucial to a successful immunotherapeutic approach.
We have developed novel, safe and immunogenic vaccines, based on the MultiTEP platform technology, that
offer substantial benefits over vaccine platforms presently used in clinical trials. Our MultiTEP-based vaccines
are specifically designed for the immunization of humans and our pre-clinical data generated in various Tg mice,
rabbits, and monkeys suggest that these vaccines potentially can (i) overcome high polymorphism of MHC class
II genes by activating a broad repertoire of naïve and memory Th cells specific to carrier (MultiTEP platform); (ii)
induce high titers of antibodies specific to pathological molecules involved in AD (e.g., Aβ/tau), but not to the
MultiTEP platform itself; and (iii) generate therapeutically potent immune responses in the vast majority of
vaccinated subjects without induction of potentially harmful autoreactive Th cells. Currently, a growing body of
evidence suggests that Aβ pathology emerges many years before accumulation of tau pathology and before the
first signs of cognitive impairment. Importantly, the accumulation of tau rather than Aβ correlates most strongly
with cognitive decline in AD. Hence, we hypothesized that while anti-Aβ vaccination should be initiated as a
prophylactic measure in very early AD (prodromal) and/or in non-symptomatic subjects at risk for AD, tau-based
immunotherapeutic(s) can be used as a therapeutic measure in patients with mild-moderate AD. Accordingly,
in this proposal we suggest to conduct pre-clinical IND-enabling studies on MultiTEP-based therapeutic vaccine
targeting N-terminus of pathological Tau (AV-1980R). Importantly, our data showed that the AV-1980R
formulated in the novel cGMP grade AdvaxCpG adjuvant (AV-1980R/A) is likely to be safe and effective, since it
is inducing therapeutic antibodies that efficiently reduce total and phosphorylated Tau in brains of vaccinated Tg
mice without generating potentially harmful autoreactive cellular immune responses. Collectively, published data
from different groups including ours and preliminary results on AV-1980R/A provide the strong support for (i)
manufacturing of engineering run (aka first run cGMP) recombinant protein that is according to FDA guidance
is sufficient for safety/toxicology studies; (ii) completing safety/toxicology studies in diseased mouse model of
Tauopathy and healthy rabbits, (iii) manufacturing cGMP AV-1980R/A, and (iv) obtaining all necessary regulatory
docu...

## Key facts

- **NIH application ID:** 9856984
- **Project number:** 5U01AG060965-02
- **Recipient organization:** INSTITUTE FOR MOLECULAR MEDICINE
- **Principal Investigator:** Michael G Agadjanyan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,272,333
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856984

## Citation

> US National Institutes of Health, RePORTER application 9856984, IND-enabling Preclinical Studies on Anti-Tau AD Vaccine for Phase 1 Trial (5U01AG060965-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856984. Licensed CC0.

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