Synaptogenix Inc (SNPX)

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If the results of the Confirmatory Phase 2 study are successful it will transform the research and treatment of AD

The following excerpts are from Neurotorpe’s FDA approved Confirmatory Phase 2 study proposal of using Byrostatin in treating advanced Alzheimer’s patients (bold added):

Journal of Alzheimer’s Disease 67 (2019) 555–570 DOI 10.3233/JAD-180759 IOS Press

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Ef?cacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer’s Disease

Martin R. Farlowa, Richard E. Thompsonb,1, Lee-Jen Weic,1, Alan J. Tuchmand, Elaine Greniere, David Crockforde, Susanne Wilkee, Jeffrey Benisone and Daniel L. Alkone,* aIndiana University Medical School, Indianapolis, IN, USA bJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA cHarvard University, Boston, MA, USA dNew York Medical College, Valhalla, NY, USA eNeurotrope, Inc., New York, NY, USA
Handling Editor: Paula Moreira

Accepted 12 November 2018

Abstract. Background: Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-oligomers, and anti-hyperphosphorylated tau.

Safety

Overall, patients in the 20 g treatment arm demonstrated minimal differences from the placebo patients in safety assessments (see Table 1). Both groups had similar numbers of TEAEs (28 events in the placebo group versus 30 events in the 20 g group). In contrast, patients in the 40 g treatment arm, observed below (as expected) to have no ef?cacy, had signi?cantly greater TEAEs (57 events) than patients in either of the other treatment arms.

Exploratory analyses

Finally, in the trend analyses, we found that the SIB values did not increase overtime for the placebo patients under the MMRM models, resulting in slopes that were non-signi?cantly different from zero (e.g., ‘zero-slopes’). In contrast, the SIB slopes for the 20 g bryostatin patients who did not receive baseline memantine were found to be statistically signi?cant…

…the memantine naive patients in the 20 g bryostatin arm showed evidence of sustained bene?t of SIB improvement from baseline over the course of the trial. This evidence was also apparent for the patients in the unadjusted FAS (or mITT) and more apparent for the unadjusted memantine free patients (Fig. 7A, B).

DISCUSSION

It is also worth re-emphasizing that the memantine, often used for symptomatic relief, here blocked all signals of bryostatin induced SIB improvement. Chronic memantine drug therapy has not been shown to have lasting bene?t. Testing for the interaction of memantine baseline therapy with bryostatin ef?cacy was pre-speci?ed (in the Statistical Analysis Plan) when the data were still blinded, prior to unblinding and data analysis. For the effective 20 g dose, in the absence of baseline memantine, only 1 in 16 patients showed a SIB decline for the week 13–week 15-week endpoint. In contrast, 9 in 22 patients in the patient group receiving 20 g bryostatin while on memantine, and 20 in 36 placebo patients showed a SIB decline.

The totality of these analyses, therefore, suggest that the trial showed evidence of bryostatin’s SIB improvement signals, in the absence of baseline memantine, that warrant further trials to evaluate bryostatin’s potential utility to improve cognitive function(s) as well as to provide symptomatic relief and/or to delay cognitive decline of patients with moderately severe to severe AD.

https://neurotrope.com/wp-content/uploads/2018/12/JAD180759.pdf