Platform for Neurodegenerative Disorders
Neurodegeneration refers to the progressive atrophy and loss of function of neurons, which are present in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
Chronic and acute brain insults lead to high levels of neurotoxic proteins, inflammation, and neurodegeneration.
Normal Axonal Function and the Onset of Neurodegeneration
A normal nerve cell receives signals, processes them in the cell body and transports them through the axon, a long-arm nerve fiber that extends out from the cell body and connects to the synapses.
Neurotoxic Proteins Impair Axonal Transport Causing a Toxic Cascade
When nerve cells become injured or stressed, their response is to increase synthesis of neurotoxic
aggregating proteins, which leads to impairment of axonal transport or slowing of the information flow through the nerve “information highway”.
Once a cell is sick, it gets attacked by the immune system and eventually dies; we call this the toxic cascade that starts with faulty nerve cell function and ends with nerve cell death.
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 is the only drug to attack multiple neurotoxic proteins simultaneously.
Alzheimer’s - Parkinson’s
Parkinson’s - Alzheimer’s
Tauopathies - AD, PD, FTD, CTE
ALS, AD, PD, FTD, CTE
Chronic and acute brain insults lead to high levels of neurotoxic proteins, inflammation and neurodegeneration.
Attacking one neurotoxic protein results in minimal effect.
Buntanetap is the only drug to attack multiple neurotoxic proteins simultaneously.
Buntanetap inhibits the translation of neurotoxic proteins by increasing the binding of a special mRNA sequence that is preserved among neurotoxic aggregating proteins and its binding protein that keeps it from going to the ribosome and being translated. Details see: Cheng 2021
Buntanetap, thus, offers a transformative and superior mechanism to treat neurodegenerative disorders. It is being developed for Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions.
Our Solution to Reverse Neurodegeneration
Lowering the levels of neurotoxic proteins restores axonal transport to normal speed. In several studies, we have shown that buntanetap and ANVS405 improve all the functions that are negatively affected by disturbances of axonal transport. Our research consistently shows that by reducing APP, tau and αSYN levels, buntanetap treatment improves axonal transport and impedes the toxic cascade which leads to neurodegeneration, thereby improving or restoring the affected function.
Our Pipeline consists of drugs for chronic neurodegeneration – Alzheimer’s disease (AD), Parkinson’s disease (PD) and other neurodegenerative conditions. 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, currently in a Phase 3 clinical trial for Parkinson’s Disease and Phase 2/3 for Alzheimer’s Disease.
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.
ANVS301 is expected to increase cognitive capability in later stages of AD and dementia.
ONGOING PHASE 3 STUDIES
We are conducting a Phase 3 study in early Parkinson’s patients and are enrolling a total of 450 patients in the US and EU. The first patient was enrolled in August 2022, and we expect to finish this study by the end of 2023.
The Phase 2/3 in moderate Alzheimer’s patients is enrolling a total of 320 patients in the US only. The first patient was enrolled in early February 2023, and we expect to finish this study by the end of 2023.
For additional information see – Patient Portal
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
All buntanetap treatment groups combined showed statistically significant improvement in the MDS-UPDRS Part III and WAIS coding test. 10 and 20mg groups are the best performing groups. (* P<0.05; ** P<0.01; *** P<0.001).
Details see: JPAD 2022
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.
Details see: Maccecchini 2012
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 14 AD and 54 PD patients.
Clean safety profile up to 160mg, which is a dose that is expected to be about 10 times higher than the efficacious dose.
Proof of Concept - ANIMALS
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 it protects nerve cells, lowers inflammation, and restores memory and learning. Details in AD animal: Teich 2018 and in PD mice: Kuo 2019. In total buntanetap was shown to improve and normalize the affected functions in eight different animal models.