Science & Strategy

Science

Neuroplasticity/Neurorestoration

Neuroplasticity, along with the terms neurorestoration and neuroregeneration, is the capacity of the brain to rebuild, remodel, and rewire. A process, which for adult humans, has only recently gained acceptance. NIV is commercializing the first drug designed to boost neuroplasticity, NIV-001, to improve the effectiveness of rehabilitation therapies and quality of life.

Through extensive research we developed a three drug combination from our portfolio of FDA approved medications, all of which have shown to affect mechanisms of plasticity. Our new drug is labeled NIV-001. By using our matrix of mechanisms of plasticity we selected drugs that targeted multiple mechanisms of plasticity particular to the mechanism of chronic stroke. We then balanced multiple other considerations, e.g., safety/toxicity profiles, half-lives, capacity to reach the brain, side effects, and or drug to drug interactions.

Strategy Pipeline

Beachead Indication

Our beachhead indication is to aid in the restoration of motor function impaired due to a stroke. 

We selected this stroke condition for two key reasons:

  1. Outcome metrics are highly objective.
  2. Unmet Need is significant. 

Objective Metrics

Neurologic drugs frequently fail because they lack appropriate objective metrics. The restoration of motor function can be easily and accurately measured. The FUGL-Meyer score, the gold standard in stroke evaluation and accepted by the FDA, includes measurements of objective changes in motor function. Being able to use objective metrics both increases our chances of FDA approval and allows for smaller clinical trials with less time and expense.

Unmet Need

There are 7 million stroke survivors in the US, and over 100 million globally. The healthcare costs associated with stroke survivors in the US alone is approximately $60 Billion. Stroke is now the single largest contributor to long term disability in the US. Market models put the Serviceable Addressable Market (SAM) for its NIV-001 at over $20 billion.

Together, objective metrics and market size make chronic stroke rehabilitation an ideal beachhead indication for Neuro-Innovators.

Future Indications:

Our next targeted indication will likely be Traumatic Brain Injury (TBI) / Concussion. TBI shares many key mechanisms with stroke. While the TBI metrics are more challenging, We expect the lessons from our stroke study will facilitate an effective TBI trial design. 

De-Risked Commercialization Path

NIV has de-risked its commercialization process in 2 ways.

  1. By working with existing FDA approved drugs already proven safe for human use, NIV’s drug combinations are expected to qualify for the FDA’s Fast Track 505(b)(2) process. While the individual drugs are generic, the combination is a new drug. NIV’s commercialization timeline can be cut by as much as 70% and clinical trial costs by 90% versus a new molecule.
  2. Pursuing an indication with clear, objective outcome metrics. Objective measurements do two things. First, objective data (assuming the data is positive) increases the likelihood of FDA approval. As a data driven organization, objective data helps the FDA fulfill its obligation to approve safe drugs. Second, objective outcome metrics also lower the cost of clinical trials. A key variable in clinical study costs is the number of patients required to achieve statistical power. The more objective the data, the higher the quality of the data, the fewer data points required to reach statistical significance, and, hence, the lower the cost of a study.
    These competitive advantages will be ongoing as NIV pursues multiple indications.

Intellectual Property

NIV’s has filed three broad provisional patents (including PCT fillings for all three) protecting its concepts of combinatorial therapies:

  • The first patent, a method patent, protects the combined use of a Neuroplastic Enhancing drug with an extensive range of neuro-devices, from robotics to embedded electrodes to virtual reality and more.
  • The second patent, also a method patent, protects the combination of two or more drugs from a list of over 150 drugs to enhance neuroplasticity. This patent also protects the use of a matrix incorporating 7 neuroplasticity mechanisms (action) to build or engineer compound neuroplastic drugs targeting specific diseases.
  • The third patent, a composition of matter patent, protects the specific combination of drugs selected by NIV to effectively address chronic motor deficits due to stroke, NIV-001.

As an early entrant/ first mover into the evolving world of neuroplasticity, NIV has the opportunity to uncover even more exciting IP as we continue to progress. 

Pipeline

NIV’s team believes that repairing or restoring the brain – Neuroplastic Medicine can help millions of patients who are suffering from a multitude of neurologic impairments including injuries to the central nervous system, movement or neuro-psychiatric disorders, age related conditions such as dementia, depression or other cognitive deficits, and or neurodegenerative diseases. NIV has taken important first steps in taking the lead and paving a path for Neuroplastic medicine and has initiated a patent portfolio to protect its vision for this space.

Beachhead Indication

Our first, or Beachhead, indication is the restoration of motor deficits caused by a stroke that persist 6 or more months after a stroke. We selected this condition for two key reasons:

  1. The outcome metrics to be used to measure our success are high objective.
  2. The Unmet Need is huge. 

 

Objective Metrics

An important contribution to the multitude of failed neurologic drugs is the lack of appropriate objective metrics. The restoration of motor function is readily and accurately measurable. For stroke the gold standard is the FUGL Meyer score, and for our studies the FUGL Meyer Upper Extremity score will be front and center. Such an objective metric lowers our risk with the FDA and lowers our study costs. We simply do not need as many subjects to achieve statistical power. The recent addition of robotic neuro-rehabilitation technologies make both intensive rehabilitation and consistent and sensitive measurements easier.


Huge Unmet Need

There are 7 million stroke survivors in the US, and over 100 million globally. The healthcare costs associated with stroke survivors in the US alone is approximately $60 Billion. Stroke is now the single largest contributor to long term disability in this country. NIV’s market models put the total addressable market for its NIV-001 at over $20 billion.

Together, objective metrics and market size make chronic stroke rehabilitation an excellent beachhead indication for Neuro-Innovators.

 

Future Indications:

Our next targeted indication will be Traumatic Brain Injury (TBI) / Concussions. TBI shares many of the mechanisms of both injury and recovery with stroke. While the TBI metrics are more challenging, NIV expects the lessons from its stroke study will facilitate an effective TBI trial design.

Science

NIV’s scientific path has evolved from decades of the NIV team’s deep experience in all aspects of the neurosciences from business to science.
We engineered our strategy around a number of key tenets:

  1. New single molecules take decades and hundreds of millions of dollars to commercialize.
  2. The success rate for new single molecule neurologic drugs is low.
  3. Clinical trials in neurologic diseases frequently lack appropriate, objective outcomes, leading to longer development timelines, larger more expensive trials and failed FDA approvals.
  4. Even when a new neurologic drug demonstrates efficacy and secures approval, its clinical/ commercial potential is thwarted due to an inability to get a clinically sufficient amounts across the BBB (Blood Brain Barrier).
  5. Single molecules affect limited mechanisms of action leading to commercial failures as a single molecule is unable to address the complexity, biologic variation, and adaptability of a given condition and or the varied biology of the human brain.


Addressing these headwinds, NIV:

  1. Through extensive research of the peer-reviewed journals, uncovered over 150 drugs, nutraceuticals, and psychedelics and filed a patent protecting the use of any two or more of these drugs in combination to promote/enhance neuroplasticity. NIV continues to expand its list.
  2. Has and will continue to engineer compound drugs that are compatible and that affect multiple and specific Mechanisms of Plasticity.
  3. Uses drugs known to be brain available, i.e., cross the BBB.
  4. Uses only FDA approved drugs eligible for the de-risked, Fast Track approval pathways to shorten time and cost to market, allowing NIV to focus on efficacy in humans, i.e., avoiding time consuming, costly and high risk safety and efficacy studies in non-human animals.)
  5. Targets indications with clear, objective outcome measures, e.g., the clear objective motor/ motility metrics used for stroke rehabilitation.

 

De-Risked Commercialization Path

NIV has de-risked its commercialization process in 2 ways.

  1. By working with existing FDA approved drugs already proven safe for human use, NIV’s drug combinations are expected to qualify for the FDA’’s Fast Track 505(b)(2) process. While the individual drugs are generic, the combination is a new drug. NIV’s commercialization timeline can be cut by as much as 70% and clinical trial costs by 90% versus a new molecule.
  2. Pursuing an indication with clear, objective outcome metrics. Objective measurements do two things: First, objective data (assuming the data is positive) increase the likelihood of FDA approval. As a data driven organization, objective data helps the FDA fulfill its obligation to approve safe drugs. Second, objective outcome metrics also lower the cost of clinical trials. A key variable in clinical study costs is the number of patients required to achieve statistical power. The more objective the data, the higher the quality of the data, the fewer data points required to reach statistical significance, and, hence, the lower the cost of a study.
    These competitive advantages will be ongoing as NIV pursues multiple indications.

Intellectual Property

NIV’s has filed three broad provisional patents (including PCT fillings for all three) protecting its concepts of combinatorial therapies.


The first patent, a method patent, protects the combined use of a Neuroplastic Enhancing drug with an extensive range of neuro-devices, from robotics to embedded electrodes to virtual reality and more. A second patent protects the combination of two or more drugs from a list of over 150 drugs used in a combination to enhance neuroplasticity.


This second patent, a method patent, also protects the use of a matrix incorporating 7 mechanisms of Plasticity (action) to build or engineer compound neuroplastic drugs targeting specific diseases.


The third patent, a composition of matter patent, protects the specific combination of drugs selected by NIV to effectively address chronic motor deficits due to stroke, NIV-001.


As an early entrant/ first mover into the evolving world of the neuroscience of neuroplasticity, NIV is in a unique position. NIV has the opportunity to uncover even more exciting IP as it executes its science and collects progressively more unique data on biomarkers and the mechanisms of neurologic actions of the drug/ drug combinations it selects to study. The opening of the field of neuroplasticity follows decades of erroneous assumptions about the capacity of our brains, particularly of the mature human brain, to adapt, the understanding of neuroplasticity is being rediscovered, a shift supported by solid research.


The data sets to be collected by NIV will be extensive and the cross calibration of new data to NIV’s highly objective outcome metrics will create an additional value set of unique data.


New technologies and new thinking have created a substantial opportunity in the field of neuroplasticity to develop and protect new thinking. The opportunity for additional patents in this expansive white space is exciting.

Neuroplasticity/Neurorestoration

Neuroplasticity, along with the terms neurorestoration and neuroregeneration, is the capacity of the brain to rebuild, remodel, and rewire. A process, which for adult humans, has only gained acceptance within the last roughly 20 years.


A key underlying premise of neuroplasticity is something known as Hebbian Plasticity, i.e., neurons or cells that fire together wire together. To build, rebuild, rewire, or restore the pathways of the brain and to cause new behaviors we must exercise and or train those behaviors to ostensibly guide the rewiring. NIV is driving to commercialize the first new drug specifically designed to enhance the brain’s biology and to enhance the rebuilding, remodeling, and rewiring.