NEUROLOGICAL POTENTIAL OF MUSIC, UNLEASHED

A L L R I G H T S R E S E R V E D , 2 0 1 6 .

Founder and TeamYayoi Sakaki: Founder, Creative Director, Pianist.

-Role: product development, product analysis and customer care-Competence: over 15 years of piano teaching experience; accomplished pianist, rich

in knowledge on effects of music activity on cognitive skills; neurological and psychological knowledge from studying numerous neurology-related peer-reviewed medical articles and online courses (all courses have been completed with distinction)

-neuro aficionado, especially well-versed on visual processing, basal ganglia circuits and motor control.

Hagen Wenzek, Dr.: Strategic Advisor.-Role: advise on critical judgements, finances and overall conduct in the entity-Competence: expert on electrical consumerism, former CTO of IPG MediaBrands,

former strategist at IBM; currently serving as a principal at Freestyle Consulting LLC, advising

marketing for numerous NYC startups and serves as advisory board for several companies.

Pierre-Alain Cohen, MD: Medical Advisor. Jack Andrew Skupski: Developer.

-Role: advise on medical related topics. -Role: advise on AR/VR programming, observe on software development

-Competence: clinical professor at University of California, San Francisco. -Competence: versatile in Java, C++Elvira Berlingieri: Legal Advisor, LLM, MBA, Avvocato.

-Role: advise on legal issues relating to intellectual property, corporate governance and privacy laws.-Competence: contract professor in law at University of Florence; also holds MBA.

Will Patera and Moritz Kassner from Pupil Labs: Outside collaborator.-Role: exclusive provider of eye tracking cameras, collaboration on AR/VR with eye tracking issues.

Roadmap Achievements and milestone thus far

April, 2014: company entity registered locally with 1 founder, 1 business advisor and 1 medical advisor 2000 – February 2016: testing the Project Ipsilon Piano Method with local clients/subscribers, observing positive impacts on

ADHD sufferers with reading through visual recognition skill developed in music reading Fall 2014 to February 2016: Testing of prototype of Ipsilon Lab (using *MuseScore© music display, specially marked

keyboard and laptop with **TheEyeTribe© eye tracker) as monitoring and assessment tool for ADHD. Winter, 2016: collected enough medical resources for the evidences for Ipsilon Lab’s scientific efficacy in clinical setting as

multimodal (oculomotor-visual-motor/spatial) monitoring system for dopamine related cognitive and motor impairment monitoring and assessment system. *www.musescore.org,© 2016 MuseScore BVBA **https://theeyetribe.com/, The EyeTribe © 2016

In Planning May 6 to July 15, 2016: participating Erasmus Center for Entrepreneurship Program in Rotterdam, The Netherlands. May 30 to June 11, 2016: to be coached by ENDuRE accelerator (University of Pisa startup program with industry pitching

opportunity). Spring-Summer, 2016: updateing product with the use of eye-tracking camera and Augmented Reality Glasses (Epson

Moverio BT-300), increase the usability (anticipating the developer’s pack delivery) Fall, 2016-Fall 2018: clinical testing of Ipsilon Lab for Parkinson’s disease at medical institutions (Leiden University and

Erasmus Medical Center; in negotiation as of May, 2016) for data collection and its efficacy validation Fall, 2018: in planning to file for FDA approval process Fall, 2018 - Spring 2019: expansion of Ipsilon Lab trial to diseases to dementia detection, ADHD and Huntington’s diseases.

Problems We are solving and our opportunities There have been steep increase of children diagnosed with ADHD in recent years (11% of 4 to 17 years old, total of 6.4 million children globally in 2011 CDC data; 5% annual increase in diagnosis in 2003 -2011 by GBI Research)

ADHD affected children tends to have difficulty in motor control and reading, which are major components in piano playing.

There are limited numbers of “at-home-use” monitoring and assessment systems for quantitative cognitive and fine-motor capabilities available at cost effective price for both ADHD and Parkinson’s diseases.

The diagnosis for ADHD remains reliant on subjective feedbacks from family members and teachers and there is no objective and/or quantitative gold standard (as of May, 2016). There are numerous causes for ADHD-like symptoms and they are easily confused with ADHD, consequently leading to over-diagnoses and misdiagnoses.

While the diagnosis for Parkinson’s disease is heavily reliant on eliminating the other possible diseases with similar symptoms and there is no diagnostic gold standard (as of May, 2016), either.

With the collected data from trials with our system, we may be able to find biomarkers and help establish the diagnostic gold standards for Parkinson’s disease and ADHD in collaboration with the leading researchers.

Among recovering cancer patients, effectively detecting early dementia is hard to achieve and an issue.

Solutions We combine music and clinical monitoring to produce cognitive-fine motor-biofeedback (oculomotor)

assessment for effectively profiling cognitive and motor state of the patient with quantifiable data.

Piano playing needs various cognitive aspects to materialize: the most notable aspects are the oculomotor efficiency for instantaneous recognition of patterns and encoding capability to relay understood information to execute physically in time, which are ideal monitoring aspects for dementia, ADHD and Parkinson’s.

ADHD and Parkinson’s share the common issues of dopaminergic and basal ganglia circuits dysfunctions among others (*please see Features of Our Solutions) and the assessment and monitoring aspects are similar to correlate to their respective illnesses.

With eye tracker to monitor oculomotor activities while the user reads and encodes simplified music for motor-spatial action is ideal to track cognitive and spatial skills and fine motor control capability for multimodal quantitative response data. Such are compatible measurements for dementia detection, ADHD and Parkinson’s disease conditions.

Our updated plan to use eye-tracking capable Augmented Reality headset with our monitoring system makes the routine monitoring and assessment easy to set up, easy to use and cost-effective. The collected data can be sent to our specialists and analyzed for long-term individual profiling for algorithm.

Features of our Solutions (1) Piano playing and basal ganglia circuits: basal ganglia are deep areas in the brain which have major roles in action selection,

movements and cognition. Its circuits project to the regions which have close relation to musical activities.

Motor cortex’s role is for motor control including fine motor, motor attention and anticipation. Oculomotor circuit has roles in effective use of eye movements relating to reading skill, visual perception and visual attention. Prefrontal circuits has roles in decision making, executive function and attention. Orbitofrontal circuit has roles in sensory integration from visual and auditory association areas; close projection from visual recognition areas. Cingulate circuit has roles in memory, spatial understanding, timing control of rhythm after the action has been learnt and acquired

Slide taken from: http://grey.colorado.edu/CompCogNeuro/index.php/Fie:fig_bg_loops_ads.86.png#filelinks

Features of our Solution (2) The rapid evolution of Augmented/Virtual Reality headsets with eye-tracker (cameras at 120Hz) enables to

utilize oculomotor feedback as biofeedback monitoring, especially over the deep brain regions such as basal ganglia which are hard to track by EEG.

Regardless of its reliability in monitoring clinical conditions, the main reason why oculomotor feedback has not been in use much for biofeedback market is that most of the eye-trackers are extremely expensive especially the level ideal for psycholinguistic response.

With the use of eye-tracker equipped AR headset, it is easy to setup and calibrate; there will be no spatial and display issue with the placement of laptop computer or tablet for visual input.

The anticipated eye-tracking capable AR headset (Epson Moverio BT-300 at $800 for preorder, Pupil Labs eye camera 120Hz), the combination makes not only oculomotor biofeedback more attractive but also make our monitoring system of cognitive-motor-oculomotor activity as cost effective and accessible for the general public, possibly also integrated with telemedicine feature with the device’s wifi capability.

The use of eye tracking camera equipped AR device may eliminate the costly medical imaging for cognitive assessment and monitoring; it enables such tests done at home at any intervals, makes lives of care taker easier.

Product: Ipsilon Lab

Ipsilon Lab is designed for monitoring oculomotor activity (saccades, fixation, smooth pursuit) while the user reads simplified and modified music (Ipsilon Method music reading training program, displayed with *MuseScore© software) and plays what has been processed on the digital piano. Our system enables to monitor and assess the user’s cognitive and fine motor skills simultaneously at the convenience of home. We track eye movements with eye tracking cameras for quantitative biofeedback data in relation to the playing error on the specific musical pattern. The recorded oculomotor and playing data are sent to our lab for multimodal and systematic analysis and profiling.

EPSON Moverio BT-300 (picture courtesy of EPSON) : We are currently waiting for its delivery to update our product (developer as custom reseller) and equip it with Pupil Labs© eye tracking cameras and Akai© Portable MIDI keyboard

Eye camera (120Hz) by Pupil Labs© to be attached to Moverio BT-300 for eye tracking function(Picture courtesy of Pupil Labs©)

Akai© LPK25 keyboard, picture courtesy of Akaipro.com

Ispilon Method (visual recognition training)

Our numerically organized visual recognition music interval worksheet with its use of color reference points (visually and spatially) makes visual recognition of the music patterns much easier than conventional music reading. The reference points are based on musical notation of clefs which fit perfectly for both hands with each finger on each key on the Middle C position.

With reinforcement learning theory (or chunking), each imagery of visual input is recognized against motor output and aural feedback of the equivalent. This seems to reduce the cognitive load in visual processing.

Market Size

TAM: $48.9B (USD)

SAM: $33.2B (USD)

SOM: $16M (USD)

TAM: total of telemedicine, biofeedback, cognitive games, VR/AR, ADHD and Parkinson’s disease marketsSAM: total of ADHD, Parkinson’s disease, biofeedback, VR marketsSOM: 1% of target age group (6 to 65+ years old) of both ADHD and Parkinson’s affected patients in test run negotiating country/region (Austria) with 3 clinical testing sites

Business Model (1)Revenue Model:

[WITH THE INDIVIDUAL SUBSCRIBERS (includes subscription advised by physicians to individual patients)]• One time registration fee of €70-.• Monthly, 3months, annual subscription (analysis & feedback included): €500/month, €1350/3mo, €5400/year• Pre-packaged equipment (eye-tracking AR headset) for individual purchase: €2500-• Optional Equipment rental (see Contract for Clinical Institutions)

[Contract for the use at Clinical Institutions]• The equipment rental fee €300/ patient per month.• Quarterly, biannual and/or annual contract: charge varies according to subject patient numbers

-1 to 7 patients: €3000/3mo, €5,750/6mo, €11,000/1 year-8 to 25 patients: €8,500/3mo, €11,450/6mo, €21,870/1year-26 to 50 patients: €12,000/3mo, €22,900/6mo, €43,550/1year-51 and up: €24,000/3mo, €45,800/6mo, €87,550/1year

*pricing is subject to change, pricing rate as of May 2016

[Licensing fee]• Patent filing as oculomotor-cognitive-motor profiling system for, early dementia detection, ADHD and

Parkinson’s disease (in planning).

Business Model (2)Customer Segments: Individual patients in clinical procedure recovery, ADHD and Parkinson patients for routine monitoring and

assessing their conditions at home setting Clinical research on brain function oculomotor response in visual processing, motor control and cognition. Pediatricians who needs the child-friendly routine assessment and monitoring system of ADHD children Hospitals and clinics for cognitive assessment (early dementia) as followup during recovery after major

procedure and/or routine monitoring on Parkinson’s patients for cognitive-motor conditions.

Value Proposition: Main Customers: early dementia detection among cancer recovering patients, ADHD and Parkinson’s Patients Customer Problems: it is very difficult to effectively detect dementia among cancer patients during recovery.

For Parkinson’s patients, condition monitoring and assessment of cognitive, motor and quantitativebiofeedback for home use similar to telemedicine is hardly available; often expensive

Uniqueness of Ipsilon Lab: integrating eye-tracker equipped AR headset with the innovative blend of music and clinical aspects into monitoring and assessment system for cancer patients, ADHD and Parkinson’s patients.

Competitive Advantage: there is no other cognitive-motor-biofeedback monitoring system in one package for dementia detection or monitoring specifically on ADHD and Parkinson’s on market; musical activities are very reliable when it comes to assessing and detecting abnormalities in cognitive-motor activities; cost-effective

Competitor Analysis Medical Imaging (MRI, fMRI, PET): diagnostic and monitoring for cognitive and fine motor condition assessment

Clinical Cognition training game for ADHD and Alzheimer’s Disease:. Akili: raised $30.5M, backed and collected data used by Pfizer and Shire; FDA approval application in progress; traction unknown(Source: Business Wire)

Neurofeedback: Neuroelectrics: $2M sales in Europe for treatment of stroke and neuropathic pain, in clinical trial with hospitals in

US (Source: Fortune)

Myndlift: electric brain stimulation with brainwave monitoring for games on tablets, ICONYC accelerator winner; entering US market in 2015; claiming to help eliminate controversial ADHD medications. (Source: MSNBC News)

Tele Medicine, Parkinson’s disease monitoring network:Sense Park: run by University of Tubingen, IQ Innovation award, funded from the European Community‘s

Seventh Framework Programe under grant agreement No. INFSO-ICT-2011-288, amount and traction unknown.

(Sources: ncbi.nlm.nih12883_2015article343.pdf; SENSE-PARK website)

Attention evaluation tests:TOVA: commonly used clinical tests for attention evaluation.