# Increasing size of Phase 2b clinical trial to 60 patients

> **NIH NIH R44** · CASSAVA SCIENCES, INC · 2020 · $374,500

## Abstract

Project Summary/Abstract
PTI-125 is a novel small molecule Alzheimer’s disease (AD) therapeutic candidate with a
novel target and mechanism of action. PTI-125 binds and reverses an altered
conformation of the scaffolding protein filamin A (FLNA) to prevent Aβ42’s tight binding to
and toxic signaling via the α7-nicotinic acetylcholine receptor (α7nAChR) as well as Aβ42’s
aberrant activation of toll-like receptor 4 (TLR4). Hence, by restoring FLNA’s native shape
and blocking these two toxic cascades, PTI-125 reduces both tau hyperphosphorylation
and neuroinflammation. Downstream effects include reduced neurofibrillary lesions and
amyloid deposits, suggesting disease modification, and improved synaptic plasticity and
function of α7nAChR, NMDAR and insulin receptors, suggesting symptomatic
improvement. We will pursue a label claim of symptomatic improvement instead of the
more difficult claim of disease modification and will therefore conduct clinical studies in
mild-to-moderate AD. Under a US IND, the first-in-human clinical trial showed no drug-
related adverse effects (AEs) and dose proportional pharmacokinetics (PK). Our first-in-
patient clinical trial in mild-to-moderate AD patients demonstrated 20-34% reductions in
CSF P-tau, T-tau, neurogranin and neurofilament light chain, as well as 5-15% reductions
neuroinflammatory markers. We have just initiated a 1-month blinded clinical trial to
replicate these striking biomarker effects with two doses and correlate them with
exploratory cognitive measures. This clinical trial has increased from 36 to 60 patients,
and the current proposal requests funds associated with this increased trial size. With
biomarker data replicated and potentially an effect size in cognitive measures, PTI-125
will be well positioned both for Phase 3 clinical trials and partnering efforts.

## Key facts

- **NIH application ID:** 10018305
- **Project number:** 3R44AG060878-02S1
- **Recipient organization:** CASSAVA SCIENCES, INC
- **Principal Investigator:** Lindsay H Burns
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,500
- **Award type:** 3
- **Project period:** 2018-09-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018305

## Citation

> US National Institutes of Health, RePORTER application 10018305, Increasing size of Phase 2b clinical trial to 60 patients (3R44AG060878-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018305. Licensed CC0.

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