# EARLY CLINICAL DEVELOPMENT OF MODIFIED P8 FOR THE TREATMENT OF ALZHEIMER'S DISEASE

> **NIH NIH R44** · CENNA BIOSCIENCES, INC. · 2024 · $1,041,646

## Abstract

EARLY CLINICAL DEVELOPMENT OF MODIFIED P8 FOR THE TREATMENT OF ALZHEIMER’S DISEASE
SUMMARY: The pathological hallmarks of Alzheimer’s disease (AD) include the formation and accumulation in
the brain of Aß, widely recognized to be the major neurotoxic agent in AD. Earlier therapeutic attempts at
lowering total Aß production all failed as they directly targeted the catalytic activities of ß- or g-secretase,
enzymes known to hydrolyze other substrates besides APP, many with critical cellular functions. Most clinical
trials of both g- and more recently ß- secretase inhibitors have been discontinued due to safety issues. After
years of failures the first new drugs for AD in 20 years, monoclonal antibody (MAb) drugs Aduhelm and Leqembi,
were recently approved by the FDA. Both target Aß, but Leqebi is more effective. Although it shows only a
modest 27% cognitive improvement in patients, it provides the first definitive evidence that lowering Aß improves
cognitive performance. More recently, a third MAb drug Donanamab has shown better cognitive improvement
in clinical trials. These drugs represent promising first steps to developing new treatments to slow down and
stop AD. Approaches other than MAbs to reduce Aß need to be explored since there are many disadvantages
to MAb drugs. These include cost, mode of administration (by IV in the clinic once or twice a month) and safety
since all MAbs are known to cause ARIAs (swelling and bleeding in the brain). New therapeutic approaches that
can inhibit total Aß production without targeting the activities of the ß- or the g-secretase, that are not monoclonal
antibodies, are urgently needed. Cenna’s technology does just that.
 We have a novel technology that does not target the secretases, which has yielded several peptide drug
candidates with the ability to inhibit the production of Aß in vitro and in a transgenic (Tg) mouse model of AD.
Our best candidate, modified P8 (mP8), is 8-amino acids in length and can be delivered to the brain by
subcutaneous injection. mP8 is being developed as a new, first-in-class, disease-modifying peptide drug for the
treatment of AD. IND-enabling GLP ADME, toxicology and safety pharmacology studies on mP8 in rats and
monkeys have been completed. In this Direct-to-Phase 2 SBIR application we propose to carry out activities to
support a first in human clinical study. The proposed studies include CMC activities to support clinical
development of the drug product, to have a pre-IND meeting with the FDA and to submit an IND package and to
develop an early clinical program and carry out Phase 1 clinical trials of mP8.

## Key facts

- **NIH application ID:** 11008129
- **Project number:** 1R44AG087853-01A1
- **Recipient organization:** CENNA BIOSCIENCES, INC.
- **Principal Investigator:** NAZNEEN N DEWJI
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,041,646
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008129

## Citation

> US National Institutes of Health, RePORTER application 11008129, EARLY CLINICAL DEVELOPMENT OF MODIFIED P8 FOR THE TREATMENT OF ALZHEIMER'S DISEASE (1R44AG087853-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11008129. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*