Neurotrope, Inc. (NASDAQ: NTRP) today presented additional clinical results from its recently completed Phase 2 trial demonstrating that moderate-to-severe Alzheimer’s disease (AD) patients treated with 20 µg Bryostatin-1 showed evidence of sustained improvement in cognition compared with placebo in patients not on concomitant memantine treatment, with a safety profile similar to placebo. The data and comprehensive statistical analysis are being presented in the Developing Topics Poster Presentation, “Significant Cognitive Improvement with Bryostatin for Advanced Alzheimer’s Patients in the Absence of Memantine” at the Alzheimer’s Association International Conference 2018 in Chicago.
In preclinical studies Bryostatin-1 lowers beta amyloid levels by the activation of natural enzymatic pathways in the brain such as IDE, ECE and neprilysin. Bryostatin has also shown synaptogenesis and prevention of neuronal death in extensive pre-clinical studies by activating synaptic growth factors such as BDNF, IGF and NGF. Further data analysis of the recent Phase 2 trial results showed that advanced AD patients show improvement (> 6.0 points vs. placebo and baseline) in the Severe Impairment Battery (SIB) even 30 days after all drug dosing has been completed in patients not on memantine.
“Patients not on memantine treatment exhibited significant cognitive improvement, at all time points tested during the trial, as evidenced by the SIB scores, with an average of 6.1 point improvement (p=0.012) over baseline and placebo,” stated Dr. Richard Thompson, Senior Statistician, Bloomberg School of Public Health, Johns Hopkins University. Dr. Thompson continued, “Various sensitive, comparative analyses were also conducted and resulted in consistent conclusions, including sustainability of the treatment effect over time, even 30 days after all dosing was completed.”
In Neurotrope’s previous Phase 2 trial of Bryostatin-1 for moderate-to-severe AD patients, Severe Impairment Battery (SIB) scores were consistently greater than baseline, indicating improvement for patients treated with a specific dose regimen, (20 µg protocol). The magnitude of this SIB increase above baseline was much greater when a pre-specified exploratory analysis separated out patients who were not on standard of care memantine therapy. Patients not on memantine treatment exhibited an improvement of 6.1 points over baseline and placebo, in their SIB scores. This was confirmed using three different comprehensive statistical analyses detailed in the poster being presented. Patients dosed in the 20 µg group in combination with memantine background therapy, and the patients on placebo with donepezil background therapy, did not show an increase above the baseline score on the SIB scale.
“Because of the impressive improvement in the patients treated with the 20 µg dose of bryostatin who were not on memantine, Neurotrope has made the conservative decision to launch a confirmatory Phase 2 trial testing 100 moderate-to-severe AD patients with the 20 µg dose of Bryostatin-1 in a 1:1 ratio versus placebo. We are delighted to have initiated enrollment of the study earlier this month,” said Dr. Charles Ryan, Neurotrope Chief Executive Officer.
Preclinical findings by other labs confirm that memantine would likely block bryostatin’s observed improvement in cognition, due to their use of a shared cell signaling pathway. Both memantine and bryostatin engage the same receptor, the NMDA receptor. Memantine directly blocks the NMDA receptor. In the absence of memantine, bryostatin activates PKC, causing engagement of the NMDA receptor. These clinical study results validate Neurotrope’s proposed mechanism of action for bryostatin and its expected effects at a neuronal level, further bolstering the Company’s clinical program and informing the development of a pivotal trial protocol for Bryostatin-1 in moderate-to-severe AD patients.
The poster presentation information and a link to the poster is below.
Title Significant Cognitive Improvement with Bryostatin for Advanced Alzheimer's
Patients in the Absence of Memantine (Poster presentation Abstract #27295)
Developing Topics Session: P4-199:
Date/Time Wednesday, July 25, 2018: 9:30 AM-4:15 PM CDT
Location Hall F1 - McCormick Place
Link to the poster
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