TECHNOLOGIES and Our
Platform Compounds
PIPELINE
Our Pipeline consists of drugs for chronic neurodegeneration - Alzheimer’s disease (AD), its orphan indication Alzheimer’s disease and dementia in Down syndrome (AD-DS) and Parkinson’s disease (PD). Additionally, we have a compound to treat acute neurodegeneration - traumatic brain injury (TBI) and stroke - and a third compound for advanced AD.
ANVS401 is our lead compound. It is being developed for AD, AD-DS and PD, because in preclinical studies it improved axonal transport in these diseases by inhibiting the neurotoxic proteins that kill nerve cells. It was shown in human and animal studies to lower APP/A, tau/phospho-tau, and -synuclein, the neurotoxic proteins that impair axonal transport and lead to inflammation and cell death. The compound was tested in three Phase 1 clinical studies that show it to be well tolerated [Investigator Brochure 2015]. This safety data is applicable to the clinical development of ANVS401 for AD, AD-DS, PD, and other chronic neurodegenerative disorders. It is also being tested in two Phase 2a clinical studies in AD and PD patients. Results of part one of the Phase 2 studies show that ANVS401 is efficacious in treating both AD and PD patients. ANVS401-treated PD patients showed statistically significant improvement in both the speed and the accuracy of execution. ANVS-treated PD patients also showed a statistically significant improvement in the WAIS Coding Scale results, which measures visual-motor dexterity, associative nonverbal learning, and nonverbal short-term memory. ANVS401-treated AD patients showed a statistically significant cognitive improvement of 30% as measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 11 (ADAS-Cog11) when compared with baseline. ANVS401-treated AD patients also showed a statistically significant improvement in the WAIS Coding Scale results. ANVS401 is the only drug so far to show efficacy in both AD and PD treatment.
ANVS405 is being developed for acute indications, focused on protecting the brain after TBI and/or stroke. ANVS405 is the same compound as ANVS401, but it is given intravenously in cases of acute head and brain trauma. ANVS405 was given to rats as an injectable after TBI to ensure that it would reach the brain quickly. TBI rats that were treated after the insult exhibited enhanced memory and learning and lowered microglia activation, a measure of inflammation. To date the development of ANVS405 has been funded by the US Army and we plan to further apply for grants to continue the development.
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ANVS301 is expected to increase cognitive capability in later stages of AD and dementia. In preclinical studies, ANVS301 improved memory and learning in very old rats. ANVS301 is in a Phase 1 clinical trial that is being conducted and financed by the National Institutes of Health (NIH).
ANIMAL AND HUMAN STUDIES
Proof of Concept - ANIMALS
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We have shown in a number of animal studies that lowering neurotoxic proteins restores homeostasis and fully recovers the affected function: in AD mice ANVS401 restores brain function, memory, and learning; in Parkinson’s mice the drug restores gut motility and in TBI rats the drug protects nerve cells, lowers inflammation and restores memory and learning. In humans, in spinal fluid of mildly cognitive impaired patients, ANVS401 reduces levels of neurotoxic proteins and lowers inflammation.
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Proof of Concept - HUMANS
In the human POC study, four patients with MCI were treated for 10 days with ANVS401 with the safe dose of 4x60 mg (240 mg/day). Cerebrospinal fluid (CSF) and plasma were drawn over 12 hours on day 0 and day 11. In CSF, however, ANVS-401 showed a half-life of T1/2 > 12 hours [Maccecchini, 2012].
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Phase 2a - HUMANS
In two Phase 2a trials, ANVS 401-treated AD patients showed a statistically significant cognitive improvement of 30% as measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 11 (ADAS-Cog11) when compared with baseline. ANVS401-treated PD patients showed statistically significant improvement in both the speed and the accuracy of execution when compared with either baseline or placebo. Both ANVS401-treated AD and PD patients showed improvement in the WAIS Coding Scale results, which measures visual-motor dexterity, associative nonverbal learning, and nonverbal short-term memory. It measures fine-motor dexterity, speed, accuracy, and ability to manipulate a pencil and perceptual organization
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RECENT EFFICACY RESULTS
EFFICACY IN PD PATIENTS – UPDRS
Data from first 14 PD patients
Posiphen-treated group showed trends of improvement in all four parts of the UPDRS test compared to placebo group
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Unified Parkinson’s Disease Rating Scale (UPDRS) was developed in 1987 as a gold standard by neurologists for monitoring the response to medications used to decrease the signs and symptoms of PD. These tools are used for patients diagnosed with idiopathic PD of any stage, according to the Hoehn and Yahr Staging Scale (H&Y)
EFFICACY IN AD PATIENTS – ADAS Cog11
Data from first 14 AD patients
Within Data:
From baseline to 25 days in the ANVS401-treated group, ADAS-Cog11 improved by 4.4 points, a statistically significant improvement of 30% (p<0.05)
Between Data:
ANVS401-treated group compared to placebo group at 25 days showed an improvement of 3.3 points, or 22% (p= 0.13)
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This is the first double-blind, placebo-controlled study that shows cognitive improvements in AD patients as measured by ADAS-Cog and functional improvements in PD patients as measured by the Unified Parkinson's Disease Rating Scale (UPDRS)
EFFICACY IN AD AND PD PATIENTS – WAIS CODING TEST
Data from first 14 AD and PD patients
The Wechsler Adult Intelligence Scale (WAIS) WAIS coding test measures speed in movement and thinking. Treated AD patients show a 6.6 point and PD patients a 6.1-point improvement in coding after Posiphen treatment
This is the first double-blind, placebo-controlled study that shows cognitive improvements in AD patients as measured by ADAS-Cog and functional improvements in PD patients as measured by the Unified Parkinson's Disease Rating Scale (UPDRS)
SAFETY
ANVS401 is orally available, well behaved, and well qualified as a candidate to treat neurodegeneration (AD,AD-DS and PD). Five clinical studies have been conducted with ANVS401, including three Phase 1 trials and two phase 2a trials. The first was a single ascending dose (SAD) study in 72 healthy volunteers. The second was a multiple ascending dose (MAD) study in 48 healthy volunteers. The third was a proof of concept (POC) study in four mildly cognitive- impaired (MCI) patients. The most recent studies are two Phase 2a trials in AD and PD patients.
ONGOING STUDIES
In 2020 we began treating 68 AD and PD patients for one month with descending doses of ANVS401. We have finished part one of the studies in which we treated 14 AD and 14 PD patients who were randomized to 80 mg of ANVS401 or placebo. By the end of July 2021, we will have finished and fully evaluated all the markers reflecting measures of the toxic cascade in AD and PD patients.
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Part two of the Phase 2 studies is ongoing and is focused only in PD patients (n=40), who are being randomized to 5, 10, 20 or 40mg of ANVS401, in a dose-range-finding design. Complete data for the study is expected in late Summer 2021. Both parts of the study are intended to measure levels of specific biomarkers in plasma and CSF known to contribute to the toxic cascade that leads to nerve cell death, along with clinical functional and cognitive measures.
The results will allow the company to move into Phase 3 studies in AD, in AD-DS, an orphan indication of AD, and in PD.