Neurosciences – Need is Growing, but not Investments: Part #2

Why do Neuro Drug Trials/ Studies Fail?

We are living longer, and a consequence is that neurodegenerative diseases, e.g., dementia or Parkinson’s, are more prevalent.

New pharmacotherapeutics are needed to treat and manage, or, preferably, cure these growing neurologic diseases and conditions. As mentioned in Post #1, successful neurologic drug studies are not keeping pace.

So, why do these studies fail?

Quoting Jacob Bell again, “Across neuroscience, clinical failures have stacked up because drug makers didn’t know enough about how the diseases work.”.  In our age of advanced technologies, clinical diagnoses for neurologic conditions remain arcanely subjective. And, subjectivity is not a strong scientific foundation for efficient, predictable FDA approvals.

There is a critical unmet need. We lack an accepted tool that provides sufficient objective neurologic/neuro-functional data. Such a tool must have high sensitivity, first and foremost, and an “acceptable” level of specificity aligned with the appropriate use case, and packaged in an easy to use, cost effective, form-function enabling us to map brain function in multiple settings. Technology that meets these parameters will allow us to map the neuro-functional natural history of a given neurologic disease or condition, a vital first step in “drug makers… [learning] how the diseases work”, Jacob Bell. Such a tool would monitor changes in neuro-function providing quick, accurate measurements of brain health, and, thus, the effectiveness of any pharmacotherapeutics.

NIH’s “Neurological Diagnostic Tests and Procedures Fact Sheet” (the “Fact Sheet”) describes “a neurological examination as assessing motor and sensory skills, hearing and speech, vision, coordination, and balance. It may also test mental status, mood, and behavior.”  NIH’s list of “accepted” techniques/ examination tools include: a tuning fork, flashlight, reflex hammer, and a tool for examining the eye. Screening tests include: Lab screening tests (blood, spinal fluid, or urine genetic testing), Brain scans (computerized tomography (CT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET) scans), Angiography, Biopsy, electroencephalograms (EEG), EMG, ENG, Evoked Potentials, Myelography, Polysomnogram, Thermography, Ultrasound, and X-rays.

[As a side note… this Fact Sheet, updated in April 2019, references eye-tracking as a biomarker, i.e., use of ENG (electrode nystagmography). My nearly 20 years of leading the development of clinical eye tracking, began with ENG technology. Electrode generated data has always been problematic given the high noise to signal ratio, its use has all but disappeared, replaced by VNG (video nystagmography- digital video to track/measure the eyes). High quality, high speed digital video with sophisticated algorithms is far superior. Significant Medicare reimbursements for electrodes did help to extend EOG use long past its utility. Regardless, it does not help when one of our most trusted scientific institutions is not keeping up with advances in diagnostic science.]

Some of these tests, e.g., MRI, PET, CT scans, and EEG), are “objective”, but they are not practical. While data from these tools inform a diagnosis, too often the detectable data is only after a disease has progressed to an advanced, often irreversible, state. The subtle neuronal changes happening at synaptic levels cannot yet be structurally observed (MRI), or the associated signals of a condition are too subtle to isolate from other noise (electrodes). Additionally, MRI’s, PET, CT scan devices are expensive and too bulky to be practical.

It is generally accepted that the greatest potential for successful treatment of a neurodegenerative disease is during its early stages. The right tool(s) will be sensitive enough to monitor and measure the disease during these early stages. None of these tools have the necessary sensitivity to detect and measure a disease at its critical early stages, or the subtle and progressive effectiveness of a new drug.

I raise these issues because we are so close to filling the void of a practical tool that can provide sensitive, objective neuro-metrics, that can measure subtle changes in neuro-function associated with a pharmacotherapeutic, and, with time and money, to diagnose many of these neurodegenerative diseases.

As mentioned in my last post, I built a list of about 70 companies of which 27, the largest cohort, use eye-tracking, and 7 companies use EEG as their core technologic platforms to measure neuro-function. Virtually all of these companies are undercapitalized and looking for $5-15 million to grow.

The list also includes 20 neuro-modulation companies, e.g., Neuralink, that do not compete in the neuro-functional measurements space (they implant electrodes into the brain for therapeutic advantage). These companies are included because when talking about investments in the neurosciences/ neuro-devices, these companies have attracted significant investment capital. Mr. Musk’s $100 million investment, along with the SciFi cool factor of operating a prosthetic arm, leg or hand with one’s own brain has helped this segment garner attention. And now his old partner Peter Thiel is backing Blackrock Neurotech.

Again, with such big money being invested in therapeutics, drugs and neuromodulation, one would think de-risking these investments by having objective metrics for the brain would be a high priority, attracting necessary capital to deserving companies on my list. But no, these diagnostic/ neuro-functional measurement technologies continue to struggle and scrounge for capital, even ones that are commercial and potentially staged for growth.

So why are these companies struggling to get capital. Awareness is, I think, an issue. With so little cash these companies must choose between marketing and creating awareness, or solidifying their technologies and product offerings. These thinly capitalized innovators simply do not have enough capital to both. With scores of companies competing for $5 to $15 million and little public information, there is a significant research burden on investors. It gets costly for investors to develop a sufficient knowledge base to make prudent investment decisions, i.e., pick winners. And, the fear of what one does not know, potentially even costlier. Even investor’s familiar with medical devices, can be overwhelmed by the number of competitors, issued patents, and potential markets. As a result, many investors sit on the sidelines. And, of those that have invested, many did so without understanding the competitive landscape and too many of these have yet to generate a return, which sours the market for further investments.

So how were any of us able to develop our products with no private capital? The answer: the US Department of Defense (DoD). For the last 15 years the DoD was the source of capital for our companies driving technologic advances. DoD took on the early stage risks to solve the unmet need and served as de facto “lead investor” for these edgy neuro-functional measurement technologies. Funded technologies ranged from enabling the human brain to operate prosthetics, e.g., ThinkLink, to diagnosing a concussion, e.g., BrainScope, Dana, InfraScan, Neural Analytics, and Neuro Kinetics (NKI) to name a few. The DoD’s Combat Casualty Care unit invest about $400 million in technologies to secure FDA clearances and commercialization for an “aid in the diagnosis of concussions”.

A 2015 change in the DoD “brain team” radically curtailed funding for promising objective concussion and neuro-functional measurement technologies. Even though the DoD’s retreat was a policy decision, i.e., not one based on technological viability, private investors virtually disappeared.

As of today, the story is unchanged, there simply is not an accepted, objective, practical neuro-functional measurement tool with sufficient sensitivity and specificity to identify and monitor important symptomatic changes in brain function. Viable, working technologies are out there, but they have yet to be “accepted”, and more importantly… funded!

To advance sensitive, practical and objective neuro-functional measurement technologies for the benefit of our brain health, we need private capital…will it be there?

J. Howison Schroeder

https://rzacquisition.com/
7/15/2021

In science we trust, unless, it seems, it is neuroscience…