How has your own background in the industry led you to your current position?

I have been in the investment business for the past 40 years, analyzing companies and operating a fund for over twenty years.  Over that time I have become familiar with the pattern of outlier companies that seem too good to be true. What I mean is that sometimes a small company, with brilliant driven leadership, creates/discovers a breakthrough in science or medicine that most would not expect to originate from a small company. In the 1980s, for example, the large chemistry-based pharma companies were not looking at biotech – Amgen was struggling to find funding as it developed erythropoietin; nobody believed red blood cells could be grown. Celgene’s founder, Sol Barer, developed a drug called thalidomide for AIDS patients, which was previously known for causing deformities in babies when administered to pregnant women in the 1960s, known as the DES cases. In its new application, the drug helped patients to gain weight, and the drug also showed efficacy in certain types of cancer. At the time, Celgene was a US$50 million to US$100 million market cap company, and today it sits at US$50 billion plus. This has occurred a number of times and seemed to be the case when we came across Dr. Daniel Alkon’s research, which is the basis of the work being done at NeuroDiagnostics.

What was the initial research basis and how has the company developed?

Dr. Alkon has been pursuing this area of research for 45 years.  He started as a doctor  out of Cornell Medical School and then spent 30 years at the NIH where he held senior positions including head of a team of scientists at the National Institute of Neurologic Disease at the NIH. When Senator Jay Rockefeller from West Virginia became interested in funding a program in the area of Alzheimer’s, Dr. Alkon agreed to leave the NIH, first moving to a facility in Rockville, Maryland, which is where our diagnostics operations are now located. Ultimately, he built a US$40 million building at the University of West Virginia’s Health Sciences campus, which is now the WVU Rockefeller Neuroscience Institute.  In New York City we have several teaching hospitals and this is a great advantage for quality medical research.  However, the WVU campus in Morgantown has a US$5 billion complex comprising a trauma hospital, medical school, 110-bed clinical trial hospital, nursing school and reference labs. It is a hugely important facility with great scientists and resources. Dr. Alkon stayed there for another 15 years continuing research, which lead to the basis of NeuroDiagnostics, as well as another therapeutic company.

Dr. Alkon believes that plaque and tau are not necessarily the causes of AD and that AD is solely a disease of the synapses.  In fact, several studies have recently come out with the “oldest old” (85 year old plus individual) who had complete cognitive functionality yet had plaque and tau confirmed by autopsy at death.  But no dementia which is amazing given the resources spent imaging these factors yet they do not necessarily confirm AD.

Dr. Alkon believes that Alzheimer’s is a systemic disease and, since the skin mirrors the synapses, the same deficiencies allowing the synapses to deteriorate are present in the skin. Our test is therefore a non-invasive, small skin-punch biopsy.

Alzheimer’s is the sixth-leading cause of death in the United States but the only disease in the top 10 without prevention or treatment. How impactful will an effective diagnosis be on the market?

The benefit of diagnosis can be divided into two categories: cost savings and alleviating the patient’s emotional burden. Cost savings within the system from being able to diagnose Alzheimer’s accurately are estimated in the hundreds of billions of dollars. In fact, a March 2018 Alzheimer’s Disease Association Special Report put the savings that result from an accurate diagnosis in the hundreds of billions of dollars.  From the patient perspective, knowing the pathway enables better planning. GE carried out a ten-thousand-patient survey questioning whether people would want to know if they or a loved one had Alzheimer’s, even in the absence of a therapeutic. The answer was a resounding “yes”, indicated by over 80% of participants, with over 50% saying they would probably pay for that clarity.

Drug research is another area where an accurate AD diagnostic tool will have tremendous impact.  As I mentioned, current technologies including imaging are not accurate.  These are people who die with plaque and tau in their brains but they do not have dementia.  Additionally, the imaging or spinal tap tests being used are invasive and expensive.  Since 25-30% of dementias are not AD, the pharma companies have an issue when they try to conduct a trial where 25-30 patients out of each 100 likely do have a dementia not caused by AD.  Another area of confusion is that many people die with plaque and tau in their brains but show no sign of dementia prior – this indicates that their presence may not even confirm that the patient has Alzheimer’s. Procedures to identify plaque and tau are invasive and expensive, and these kinds of results give rise to the question of whether plaque and tau is the right mechanism. Further to this, pharmaceutical companies looking for an Alzheimer’s therapeutic currently face a conundrum. Out of a pool of 1,000 patients with dementia, about 25% to 30% will not have Alzheimer’s disease. Therefore, trying to apply a drug to patients, particularly in the early stages of onset, builds an error into the clinical trial. An accurate diagnostic test, particularly in the early years, will allow companies to delineate their clinical trial pool more accurately, which will help in finding a successful candidate.

NeuroDiagnostics recently announced its Breakthrough Device designation for the DISCERN™ multiple biomarker test for Alzheimer’s. What is the significance of this designation for the test’s timeline?

This designation allows the FDA to assign teams to focus on novel technologies where there is an unmet medical need.  It leads to faster approvals with the help and resources of the FDA being available to help with our submission (510k de novo).  The Breakthrough Device designation is a testament to our data and results thus far. Nevertheless, it is very hard to guess the FDA’s timelines.

Separately we also plan to launch the test as a Laboratory Diagnostic Test (LDT). This allows a test still to be utilized without FDA approval through labs that are CLIA certified.  This year, we have been certified in 49 to 50 states as CLIA-approved and therefore have several of the large lab companies starting to talk to us.  Practitioners know that if they can absolutely eliminate AD as a cause for dementia, the research into other causes of dementia becomes much more focused.  We also have some interesting doctor groups starting dialogues with us – even ruling out Alzheimer’s is a useful first step towards diagnosis of the real underlying problem.