Annovis Bio on Its Positive Results in Alzheimer's and Parkinson's Clinical Trials

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The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

Annovis Bio Inc. ANVS is a clinical-stage pharmaceutical company focused on developing drugs for neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and dementia in Down syndrome (AD-DS).

More than 6 million Americans are currently living with Alzheimer’s and about 1 million Americans have Parkinson’s. By 2050, those numbers are expected to grow to 13 million and 2.7 million, respectively.

Both diseases remain incurable and both lack treatment options beyond medications and procedures that target the symptoms rather than the root causes of the diseases. With its lead compound ANVS401, Annovis Bio hopes to change that. The Pennsylvania-based company completed two Phase 2 clinical trials this year, yielding positive results when treating both Alzheimer’s and Parkinson’s patients with ANVS401.

How ANVS401 Works

In patients with just about any kind of neurodegenerative disease, a common feature is the disrupted axonal transport that ultimately causes nerve cell degeneration and nerve cell death — the communication or “streamline” between nerve cells. When that transport is damaged, the nerve cell gets sick and dies. As that degeneration and cell death continues, it can lead to cognitive impairment and movement disorders like those seen in Alzheimer’s and Parkinson’s patients.

ANVS401 was developed based on the hypothesis that high levels of neurotoxic proteins are responsible for this axonal transport disruption. In a statement about the positive Phase 2 data, Annovis Bio CEO Maria Maccecchini, Ph.D., explained, “When we administer our drug, we expect a reversal of this toxic cascade resulting in efficacy.”

The compound is an oral lipophilic molecule that’s capable of passing the blood-brain barrier in high concentrations and, once in the brain, inhibits the production of amyloid precursor protein (APP), Tau and Alpha (α)-Synuclein (α-Syn) — neurotoxic proteins that have been shown to disrupt axonal transport.

While other drugs that target neurotoxicity exist, they generally target just one protein and do so by trying to remove that protein. ANVS401 targets at least three neurotoxic proteins and works by stopping their production before that harmful buildup can occur in the first place.

Results From This Year’s Phase 2 Clinical Trials

Annovis Bio concluded two Phase 2 clinical trials this year, one for Alzheimer’s and one for Parkinson’s disease. In the Alzheimer’s trial, 14 patients were treated with either a placebo or ANVS401 for 25 days. The patients’ cognition was measured before and after treatment using the Alzheimer’s Disease Assessment Scale—Cognitive Subscale 11 (ADAS-Cog11) and the Wechsler Adult Intelligence Scale (WAIS).

In the group receiving ANVS401, ADAS-Cog 11 scores improved statistically significantly by 4.4 points, or about 30%, from baseline (3.3/22% from placebo). For comparison, Biogen Inc. BIIB — whose Alzheimer’s treatment Aduhelm became the first new therapy approved for the disease in nearly 20 years — showed ADAS-Cog11 improvements of just 1.4 points. Moreover, the patients on ANVS401 also showed a 6.6-point, or 23%, improvement from baseline on the WAIS (4.9 from placebo).

In the second Phase 2 trial, 54 Parkinson’s patients were treated with either ANVS401 or a placebo. This time, researchers used the WAIS and the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to measure motor function before and after treatment. After 25 days of treatment, patients receiving ANVS401 showed a statistically significant 13.5% improvement on the WAIS and a 2.43-point, about 13%, improvement on the MDS-UPDRS, both compared to baseline (16.5% and 22.8% from placebo respectively).

In both trials, researchers collected cerebral spinal fluid and plasma samples from all subjects to measure a range of biomarkers that could tell them whether and how much ANVS401 was actually reducing the toxic cascade responsible for disrupting axonal transport.

Those bio samples showed that all three neurotoxic proteins (APP, Tau, and α-Syn) had been reduced in patients taking ANVS401. Moreover, all four inflammatory markers tested were substantially lower in treated patients. Likewise, the two biomarkers used to measure axonal and synaptic dysfunction were reduced.

The reduced levels of all these markers suggest that ANVS401 is effectively disrupting the production of neurotoxic proteins inhibiting the toxic cascade leading to nerve cell death. This, in turn, results in improved scores on cognitive and motor tests proving that the researchers’ hypothesis is correct. Treating neurodegenerative diseases by reducing the toxicity that interferes with axonal transport may be an effective way to improve the lives of millions of patients with neurodegenerative conditions.

What’s Next for ANVS401?

Once the final analysis of Phase 2a results is complete, Annovis Bio will request two meetings with the Food and Drug Administration (FDA) to present its results and request approval to move into later-stage trials.
In a presentation at the 14th Clinical Trials on Alzheimer’s Disease Conference in November, Maccecchini said, “Meeting primary endpoints and the reversal of the toxic cascade combined with improvements in cognition and function are the foundation for us to ask the FDA for two meetings — one to move into two Phase 3 clinical trials for Alzheimer’s disease and one to move into two Phase 3 clinical trials for Parkinson’s disease.”

The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.