About Frank Amato
Frank Amato is CEO and president of SYNAPS Dx. Previously, after two decades in the pharmaceutical and biotech industries, he was president, CEO and director of electroCore, a NASDAQ-traded bioelectronic medicine company focused on treating neurodegenerative conditions. Frank is an accomplished leader with a track record for consistently delivering strong results. Prior to his tenure at electroCore, Frank was vice president of the Specialty Commercial Operations Group at Merck, which comprised nine specialty therapeutic divisions. After Merck’s acquisition of Schering-Plough, he led the integration of approximately 3,000 employees into the new company. In addition to his day-to-day business responsibilities, Amato was accountable for various aspects of due diligence, negotiation, integration and launching products in neuroscience, virology and ophthalmology.
After serving as an infantry field medic in the 82nd Airborne Division, U.S. Army, Frank began his career as a sales professional in New York City with the Upjohn Company. Throughout his career, Frank has worked on key initiatives in the U.S., Europe, and Japan, managing teams of senior executives in sales, marketing, operations, finance, legal, medical, regulatory and research and development.
About Dr. Daniel Alkon
Dr. Alkon received his undergraduate degree in Chemistry in 1965 at the University of Pennsylvania. After earning his M.D. at Cornell University and finishing an internship in medicine at Mt. Sinai Hospital in New York, he joined the staff of the National Institutes of Health where during his 30-year career he became a medical director in the U.S. Public Health Service at the NINDS and chief of the Laboratory of Adaptive Systems. In 1999, Dr. Alkon then became the founding Scientific director of the Blanchette Rockefeller Neurosciences Institute and occupies the Toyota Chair in Neuroscience at the Institute. In this position, he and his team conducted multidisciplinary research on the molecular and biophysical mechanisms of memory and memory dysfunction in psychiatric and neurological disorders, particularly Alzheimer’s disease. He was also professor of Neurology at West Virginia University until September 2016, and research professor of Biophysics, Johns Hopkins University.
As an internationally recognized pioneer in research on brain-based neural networks and the molecular basis of memory, he has authored hundreds of scientific articles, as well as several books, including “Memory Traces in the Brain” (Cambridge University Press), and the popular “Memory’s Voice” (Harper Collins).
About SYNAPS Dx
SYNAPS Dx was founded to commercialize the biomarker technology developed through more than a decade of research by a team of scientists at the Blanchette Rockefeller Neuroscience Institute (BRNI), which is now part of West Virginia University.
SYNAPS Dx operates a CLIA laboratory within the Greencourt Innovation Center in North Bethesda, MD.
The SYNAPS Dx lab is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing.
SYNAPS Dx is the exclusive licensee of the worldwide patent portfolio covering the biomarker technology. Visit https://www.synapsdx.com/.
Medical Travel & Digital Health News (MTDHN): How did both of you get involved with SYNAPS Dx?
Dr. Daniel Alkon (DA): I spent much of my career as an academician, program director and laboratory chief at the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), running a multidisciplinary program that focused upon memory storage mechanisms.
Sen. Jay Rockefeller and his family invited me to start a new institute called the Rockefeller Neuroscience Institute where I was the founding scientific director. We translated some of our basic research findings to clinical applications for therapeutics and diagnostics to treat neurodegeneration, particularly Alzheimer’s disease.
During that time, we generated a fairly extensive patent portfolio for therapeutic diagnostics, which were licensed and developed by SYNAPS Dx, where I’ve been serving as chief scientific advisor developing technologies with Frank Amato and Paul Tanico. I also serve as president and chief scientific officer of Synaptogenix, Inc. that develops therapeutics for neurodegeneration.
Frank Amato (FA): I’ve spent the past 30 years as a life sciences executive, two thirds of which I’ve spent working in the pharmaceutical and biotech industry, most recently running all of Merck’s specialty businesses.
When introduced to the background science and the work that Dr. Alkon had done in the past few decades I saw it as the first breakthrough in Alzheimer’s disease from a diagnostic standpoint. Because of the science and breakthrough potential in a disease state that hasn’t any relevant diagnostic or therapeutic interventions in 20 years, I joined SYNAPS Dx.
MTDHN: Why do you think it took so long for the industry to develop a test like this as a solution to diagnosing Alzheimer’s?
DA: At the Rockefeller Institute, it took over 15 years to complete clinical trials for our three Alzheimer’s disease biomarkers confirmed with extensive autopsy-based validation. Sometimes individual trials could take up to six years because we had to make an exhaustive validation with unequivocal certainty — not just to distinguish Alzheimer’s disease patients from healthy controls but also and from other causes of dementia.
MTDHN: For the payers in our audience and those that are making benefits decisions, does this test provide a definitive diagnosis?
DA: Based on our trials with multiple patients, including autopsy validation or genetic validation, our assays have proven highly accurate–greater than 95% sensitive and specific. Over the years, it’s been shown to be highly accurate.
We’ve already launched a commercial beta program to see how everything works in the commercial sector and the test performed well beyond our expectations. Now, it’s just a matter of putting together the right framework commercially to accommodate demand.
FA: We conducted a beta-launch in two cities, Dallas and San Antonio, in 2020 amid the COVID-19 pandemic. Within those two cities we targeted 10 physicians, six of which were primary care-based, two geriatricians and two community-based neurologists.
We received 325 skin samples that were sent back to our lab, unequivocally demonstrating enormous demand.
The beta-launch helped us to determine how to automate the laboratory with the proper technology and personnel to validate and replicate the assays that we had recently moved from a research to a commercial laboratory.
We’re very pleased about how prepared we are to meet commercial demand with the lab—and plan to make DISCERNTM available once we have the proper reimbursement in place.
MTDHN: What are your approvals, CPT codes and pricing?
FA: We were given two specific CPT codes by Medicare for our test, which consist of three assays to definitively diagnose Alzheimer’s disease. Codes 206U and 207U are currently published on the Medicare website.
We are working with Novitas to establish a local coverage determination or medical policy, which is one of the seven Medicare administrators.
Regarding the coverage determination, we are now conducting a clinical utility study which is largely a requirement by Medicare. We anticipate that by year-end, we will have submitted to Medicare the dossier required to help them make a local coverage determination, which if favorable will allow us to have our solution reimbursed across all seven Medicare Administrative Contractors.
MTDHN: Let’s talk a little bit about the test itself.
FA: The first thing I would say is that DISCERN is a minimally invasive test.
A healthcare provider takes a three-millimeter skin punch biopsy, which is almost like taking a blood sample, performed in the doctor’s office. Typically, it’s taken from the inner part of the upper arm using our DISCERN test kit that we provide for the doctor.
Once we receive the sample shipped overnight, we then culture those cells over a period of weeks to get them to about a million cells. And then we divide those cells amongst our three proprietary assays, which can take seven to eight weeks, depending on whether the patient has Alzheimer’s disease or not.
The Alzheimer’s disease samples can take a little bit longer to grow because much like networks in the brain, the skin or the peripheral part of the body also doesn’t grow properly. We then send the results back to the doctor for a discussion with the patient.
Ultimately, this test is a tool for the physician to help diagnose Alzheimer’s disease. The physician makes the diagnosis and decides with the patient the next most appropriate step, whether it is medication, a clinical pathway or another intervention, such as diet, physical exercise, mental exercises and so forth.
DA: We have proven over the years that these changes in the skin cells are very closely related to synaptic changes in the brain or the connections between brain cells. Those synaptic changes have been shown by many studies with autopsy validation to be closely correlated with the real cognitive deterioration of the patients.
Unlike studies looking indirectly or directly with PET imaging at amyloid plaques and tau pathology, which are not closely correlated with cognitive deterioration, our measure of synaptic loss is closely correlated with cognitive loss.
We validated this with a collaborative study at the Harvard Brain Bank, where we had fresh frozen samples from patients with Alzheimer’s disease. We measured changes in the brain that were very similar to those we see in the skin cells.
This is our theoretical framework, which indirectly correlates changes in the skin cells with changes in the synaptic connections and, ultimately, cognitive deterioration.
MTDHN: Does the test require a prescription?
FA: We require the physician to fill out a patient requisition on our website, which triggers our team to send a DISCERN test kit back to the doctor’s office, including everything they need to take the skin sample, process it, and then overnight return of the sample to our lab.
MTHDN: Can this diagnostic test determine the stage of Alzheimer’s?
DA: Our data show consistent worsening of the Alzheimer’s disease biomarker values as the disease progresses. All three biomarkers independently track this disease progression and correlate with each other, as well as with the stage of the disease.
However, I think it’s important to understand that the new drug approved by the FDA is subject to an approval modification that specifies that it only has suggested potential to benefit patients who are early Alzheimer’s disease patients or are in the very early stages of dementia — called mild cognitive impairment that has not yet progressed to Alzheimer’s disease.
Our test would be very helpful to identify patients who have very early Alzheimer’s disease and a score consistent with early Alzheimer’s disease. In our early autopsy-validated studies, the accuracy of the biomarkers was greater than 95%.
That’s the value that the DISCERN diagnostic can add to the care of the Alzheimer or dementia patient.
MTDHN: Where is the test available?
FA: Right now, the test is available in the United States in 49 of 50 states. We will service the 49 of 50 states for the launch period of our diagnostic test.
We plan to expand to other countries at some point in the future.
MTDHN: Do the results of the test indicate what type of treatment is indicated?
DA: This is a great question because it highlights the potential triaging and disposition of a patient using our test.
One out of three patients with memory issues do not have Alzheimer’s disease. They may have B12 deficiency, hypothyroidism, Lyme disease, depression and so on. In that one-third cohort, we offer the possibility of getting some kind of treatment that’s more appropriate for a non-Alzheimer patient.
For Alzheimer patients, it’s well understood that no drug available today, including the one recently approved by the FDA, can treat the underlying disease. Two drugs, Aricept and Memantine, have been approved to provide some temporary symptomatic relief.
MTDHN: Is age an issue for getting this diagnostic test approved for the payer?
DA: In general, I just look at the landscape of all Alzheimer’s patients: 3% are early onset and 97% are age dependent, sporadic or the later onset form of the disease.
Typically, these patients start to have a higher incidence of the disease by age 60, but when they’re 65 or older, that incidence increases exponentially every 10 years until by age 85, they have a 50% chance of having Alzheimer’s disease.
FA: We are initially focused on getting reimbursed for Medicare patients, although it’s likely that patients under 65 could get the test if a physician decided it was appropriate.
When you consider patients under age 65, our test is positioned to support a physician who has already diagnosed a patient with dementia.
After diagnosing dementia, physicians have to make a very difficult decision of determining what is causing the dementia. Seventy percent of the time it’s Alzheimer’s disease. This is precisely where our test can be very helpful to assist the doctor in trying to determine what is causing the dementia.
MTDHN: Do you foresee other disease states or conditions where this science could be applied?
DA: There may be signals that we can follow that would help diagnose other types of neurodegeneration, including Parkinson’s and multi-infarct dementia. We have other tests that we have not fully developed that may eventually help identify such patients.
MTDHN: What do you think the impact will be on the industry?
DA: Historically, over the last 20 years, there have been billions of dollars invested in testing drugs to treat Alzheimer’s disease.
One of the challenges that large pharma has encountered is they have to start with a patient population that they believe has Alzheimer’s. But PET imaging has about a 25% inaccuracy and some patients go on to live to 90 or 100 years being cognitively normal. Then, at autopsy we see brains riddled with plaques and tangles, but they don’t have Alzheimer’s.
The challenge is deciding who should be in the trial. If you treat patients who are later in the progression of the disease, the clinicians can make a more accurate diagnosis. The problem is that the longer you wait to treat, the less likely it will have an impact.
This is where we believe our test can make a tremendous difference: we may be able to differentiate patients with Alzheimer’s from those who do not. An accurate diagnosis with biomarkers, such as ours, can make a huge difference in increasing the accuracy and the potential efficacy of drugs to treat the disease.
MTDHN: Are you partnering with other entities to bring this to market?
FA: Currently, we have an investment from an $800 million market cap, publicly traded, diagnostic company on the west coast. There’s a possibility to partner with them or someone like them on a commercial launch. They currently have salespeople who are focused on the primary care segment of the market and are targeting the same Medicare patients and physicians that we would approach.
We are reviewing partnership opportunities to help commercialize the technology and create assays that have are less expensive and have faster turnaround time.
We could potentially work very closely with pharmaceutical companies that are developing clinical trials right now for various different, therapeutic interventions. We can help them identify the correct patients for their clinical trials.
We are also looking to work with different service providers and laboratories. We have a contract research organization, Syneos Health, a CRO currently enhancing and developing our current assays and biomarkers.
MTDHN: Is there anything else you would like to share with the readers?
DA: There are many claims for Alzheimer’s Disease diagnostics but very few have either been autopsy validated or validated against other neurodegenerative diseases.
There is a huge unmet medical need in Alzheimer’s Disease diagnostics and associated therapeutics. We are rigorously validated and anticipate having an enormous impact on the treatment and care of Alzheimer’s patients.
FA: Our beta-launch alone demonstrated that there is a significant need in the market for an Alzheimer’s disease diagnostic to inform physicians in an effort to help patients find the right treatment pathways. Synaps Dx has attained reimbursement codes and pricing that will also help patients get answers that can assist with treatment pathways that are best suited for their disease.