OUR SCIENCE and Our
Platform Compounds to Treat Neurodegenerative Disorders
PLATFORM COMPOUNDS
Buntanetap (previously known as ANVS401 or Posiphen) is our lead compound. It is a translational inhibitor of neurotoxic aggregating proteins (TINAPs). Different from monoclonal antibody therapies, buntanetap is an orally available small molecule, and its unique mechanism of action allows it to inhibit multiple neurotoxic proteins at once. Recent research has shown that multiple neurotoxic proteins are at play in all neurodegenerative diseases. Buntanetap, thus, offers a transformative and superior mechanism to treat neurodegenerative disorders. It’s being developed for Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions such as Alzheimer’s in Down syndrome.
PIPELINE
Our Pipeline consists of drugs for chronic neurodegeneration – Alzheimer’s disease (AD), Parkinson’s disease (PD) and other neurodegenerative conditions such as Alzheimer’s in Down syndrome. Additionally, we have a compound to treat acute neurodegeneration – traumatic brain injury (TBI) and stroke – and a third compound for advanced AD.
Buntanetap is our lead compound. It is in clinical trials for PD and AD. 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/Aβ, tau/phospho-tau, and α-synuclein, the neurotoxic proteins that impair axonal transport and lead to inflammation and cell death. The compound was tested in three Phase 1 and two Phase 2 clinical studies that show it is well tolerated. In the two Phase 2 clinical studies buntanetap showed efficacy in AD and PD patients. buntanetap-treated PD patients showed statistically significant improvements in both the speed and the accuracy of execution in the WAIS Coding Scale and MDS-UPDRS test. Buntanetap-treated AD patients showed a statistically significant cognitive improvement of 30% as measured by ADAS-Cog11 and in the WAIS Coding Scale, when compared with baseline results. Buntanetap is the only drug so far to show improvement in cognition in AD patients and motor function in PD patients.
ANVS405 is being developed for acute indications, focused on protecting the brain after TBI and/or stroke. ANVS405 is the same compound as buntanetap, 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).
PLANNED STUDIES
We submitted our safety and efficacy data from our Phase 2 PD study to the FDA and they approved us to continue development into Phase 3.
We are planning to conduct two Phase 3 studies, one in early PD and one in advanced PD. If you are interested in joining and/or learning more about upcoming clinical trials, please contact us.
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Our Phase 3 in early PD will start in summer 2022.
COMPLETED PHASE 2 STUDIES
In 2020, we began treating a total of 68 AD and PD patients for one month with descending doses of buntanetap. We treated 14 AD patients randomized to 80mg or placebo once per day (QD) and 54 PD patients who were randomized to 0, 5, 10, 20, 40 and 80mg QD of buntanetap.
In both populations, we measured levels of specific biomarkers in plasma and Cerebrospinal fluid (CSF) known to contribute to the toxic cascade that leads to nerve cell death, along with clinical functional and cognitive measures.
IN AD PATIENTS - IMPROVED COGNITION BY ADAS-Cog11 AND IMPROVED SPEED AND ACCURACY BY WAIS CODING TEST
The data from the 14 AD patients show that from baseline to 25 days in the buntanetap-treated group, ADAS-Cog11 improved by 4.4 points, a statistically significant improvement of 30% (p<0.05). Compared to placebo at 25 days the treated group is 3.3 points better than the placebo.
The WAIS coding test measures speed in movement and thinking. Treated AD patients show a statistically significant 23% improvement compared to baseline.
IN PD PATIENTS – IMPROVED MOVEMENT BY MDS-UPDRS AND IMPROVED SPEED AND ACCURACY BY WAIS CODING TEST
WAIS Coding Test in 54 PD Patients
All buntanetap treatment groups showed improvement in the WAIS coding test. Except for the 40mg treatment group, all the rest showed statistically significant improvement both comparing to baseline and comparing to placebo group.
EFFICACY IN PD PATIENTS – MDS-UPDRS TEST (TOTAL SCORE)
Total MDS-UPDRS Score in 54 PD Patients
Buntanetap-treated group showed improvement in both Part III (mobility) and total scores of MDS-UPDRS. 10mg QD treatment statistically significantly improved both Part III and total scores of MDS-UPDRS comparing to baseline and 20mg QD treatment statistically significantly improved total scores of MDS-UPDRS comparing to baseline.
PROOF OF CONCEPT STUDY IN MILD COGNITIVE IMPAIRMENT (MCI) PATIENTS
In the human POC study, four patients with MCI were treated for 10 days with buntanetap with the safe dose of 4x60mg (240mg/day). CSF and plasma were drawn over 12 hours on day 0 and day 11.
Buntanetap lowered levels of neurotoxic proteins, APP, tau and αSYN with statistical significance in all four patients. The levels of neurotoxic proteins decreased to levels found in healthy, normal volunteers.
The CSF of the same MCI patients was used to measure inflammatory factors. Inflammation was shown to be substantially reduced after 10 days of buntanetap dosing.
In healthy volunteers we had previously measured the plasma half-life and it was about 5 hours. In CSF, however, buntanetap showed a half-life of > 12 hours [Maccecchini, 2012]. This let us to reconsider the frequency of administration as discussed below.
SAFETY
Buntanetap 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 buntanetap, including three Phase 1 trials and two Phase 2 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 2 trials in AD and PD patients.
Safety was evaluated in all three studies and buntanetap’s pattern of adverse events (AEs) was similar to that seen in typical studies in healthy normal volunteers, with an overall incidence rate of 33.3% among placebo-treated subjects and 35% for all buntanetap treatment groups combined. In the single ascending dose study, the 160mg/day group – the highest dose group in the study – had a treatment-related AE rate of 31.7%. In the multiple ascending doses, and in the POC study there were no dose-related AEs. Most AEs were of short duration, mild or moderate in severity, and resolved without medical intervention. These data were reported to the FDA in SN 0016 and SN 0018.
Clean safety profile up to 160mg, which is a dose that is expected to be about 10 times higher than the efficacious dose.
ANIMAL STUDIES
Proof of Concept - ANIMALS
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We have shown in several animal studies that lowering neurotoxic proteins restores homeostasis and fully recovers the affected function: in AD mice buntanetap restores brain function, memory, and learning; in PD 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, buntanetap reduces levels of neurotoxic proteins and lowers inflammation.
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