Protecting Nerve Cells in the Fight Against Alzheimer’s Disease: Dr. Maria Maccecchini

Maria L. Maccecchini, Ph.D., is a scientist, researcher, entrepreneur, and founder of two biotechnology companies. Currently, she is the President, CEO, and Executive Board Member of Annovis Bio (NYSE: ANVS), a public clinical-stage drug platform company addressing Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases.

Before founding Annovis Bio in 2008, Dr. Maccecchini was a partner and director of two angel investment groups, Robin Hood Ventures and MidAtlantic Angel Group. The first biotech company Maccecchini founded (in 1992), Symphony Pharmaceuticals, worked on therapeutics to protect nerve cells from dying in stroke.

Dr. Maccecchini completed her Ph.D. in biochemistry at The Biozentrum of the University of Basil, followed by a two-year visiting fellowship at The Rockefeller University. She also completed two postdoctoral fellowships; one at the California Institute of Technology, and one at the Roche Institute of Immunology.

PharmExec caught up with Dr. Maccecchini to talk about why she, as a scientist and biotech company entrepreneur, became focused on protecting nerve cells in the brain and in the body, as a way to treat neurodegenerative disease.

PharmExec: Tell us about nerve cell death and how the loss of nerve cells is affecting neurodegeneration.

Dr. Maria Maccecchini

Maria Maccecchini: Our company has a novel approach to protecting nerve cells from dying because every function we do depends on a nerve cell and if that nerve cell dies, the function goes away. If you just think about it, your brain connects to your fingers, your toes, your internal organs, your eyes so you can see, your tongue so you can feel, and taste. If it doesn't connect, you have nothing. What happens when you injure the brain, or when the brain ages and malfunctions; you have toxic proteins that accumulate and these toxic proteins impair the axonal transport, which can cause inflammation and lead to nerve cell death.

Our drug actually attacks neurodegeneration by improving the axonal transport, which is the “information highway” of the nerve cell, that has been shown to be the cause of nerve cell degeneration and ultimately death.

The nerve cells in our brain have a body in the head, very long extensions, or arms called axons, that crisscross the body and fingers, known as synapses. In order for a nerve cell to function the body has to communicate with the fingers, and the fingers need to communicate back to the body in the brain.

Axonal transport is the process by which nerve cells transfer substances between the cell body and the synapse. When the axonal transport system is not working properly, nerve cells can die, resulting in disease.

How is Annovis Bio’s approach to treating Alzheimer’s disease and other neurodegenerative diseases different?

For decades, the entire industry has rallied around one leading idea, that a protein fragment known as beta-amyloid, accumulates in the brain, creating neuron-killing clumps that are both the cause of Alzheimer’s, and the key to treating it.

This theory really dates back to 1906, when the German doctor Alois Alzheimer, opened the brain of a woman who died of dementia and found plaque. So, he called his discovery Alzheimer’s, and plaque became the most important focus for fighting the disease.

Research focused on amyloid, and the development and testing of experimental drugs targeting amyloid, have sucked up billions of dollars in government and pharma funding. At this writing, there is no treatment for Alzheimer’s disease. The four approved drugs have no effect on treating the actual disease. They simply provide a temporary memory boost.

Are you saying that plaque is not a factor in treating Alzheimer’s disease?

No, what we are saying is that the plaque is the end product. When a brain suffers an injury, whether chronic or acute, toxic proteins may be over-translated, and it is these toxic proteins that impair the axonal transport.

The brain then has its own way of discarding these toxic proteins by forming blobs.

In Alzheimer’s, these blobs are called plaques (Abeta), or tangles (tau) . In Parkinson’s disease, these blobs form Lewy bodies (alpha-synuclein). In chronic traumatic encephalopathy these blobs become tangles. Our drug works by eliminating these toxic proteins that accumulate.

So, for the last 20 years pharma has been attacking plaque, tangles, and Lewy bodies.

Now that the scientific community understands the brain better, we are coming up with novel ways to fight these diseases.

Tell us about Annovis Bio’s lead drug, ANVS401, which is currently in Phase II, and how it is being developed to treat neurodegeneration.

ANVS401 was originally developed to inhibit amyloid precursor protein. Additional research showed that the therapy actually inhibits the synthesis of all neurotoxic proteins; the ones that make plaque, which are amyloid, the ones that make tangles, which are tau, and the ones that make Lewy bodies, which are alpha-synuclein. We are targeting multiple neurotoxic proteins with a single drug with a single target. These three proteins are highly similar in their translational mechanism. By lowering these toxic proteins, we improve the axonal transport, lower inflammation, and protect the nerve cells from dying.

ANVS401 is a small lipophilic molecule that is orally administered. Additionally, we have a 2nd therapy, ANVS405, which uses the same mechanism of action but in injectable form, to treat acute neurodegeneration, traumatic brain injury and stroke. Finally, our 3rd compound, ANVS301, is in development for advanced Alzheimer’s disease.

A recent new study indicated preliminary data shows that ANVS401 improves speed and motor function in Parkinson’s disease patients. What is your expectation of the drug in Alzheimer’s disease? And when do you expect to enter final data from Phase II and to enter into Phase III?

Our recent study in Parkinson’s patients showed that our drug worked in improving their speed, coordination, and overall motor skill functions following 25 days of treatment, with no serious adverse events.

The results from our study in Alzheimer’s patients will be available soon and we expect to reveal that these patient’s cognitive abilities have improved after taking our drug.

And finally, the full study data, including a dose ranging analysis in forty Parkinson’s disease patients, is anticipated in June or July 2021.

What do you expect to be the biggest challenges over the next 6 to 12 months, and what milestones do you hope to achieve?

One of our biggest challenges will be growing our company. We are expanding the number of employees, which is very exciting, but this will also be an adjustment. As for milestones, we are hopeful that our phase 2 data will be positive and that we will be able to present our findings to the FDA in Fall of 2021 to get approval to start two phase 3 clinical studies – one in Down Syndrome with Alzheimer’s disease and one in Parkinson’s disease.

Why has so little progress been made in finding a cure for Alzheimer’s disease?

There are many reasons. People are now talking about dementia, Alzheimer’s, and the astronomical financial impact on our healthcare system. They have begun to recognize and accept the toll this disease is taking on entire health care system, our aging population, and the caregivers.

As a result, finally the money is coming in from the government and pharma companies directed towards finding a cure. Yet, Alzheimer’s funding is still lagging when compared to cancer funding which receives more than twice as much as Alzheimer’s from the NIH. Another reason has to do with being stuck on the amyloid hypothesis. As a drug developer, if you weren’t pursuing the amyloid theory, you simply couldn’t raise money. The encouraging news is we have made real progress with financing and accepting new approaches to treating Alzheimer’s. But we have to continue pushing the boundaries. Alzheimer’s is the most expensive disease in America to treat, and has the potential to cripple our entire healthcare system. It’s up to us as developers to push for novel approaches to fighting the disease.