Analyzing the Potential of a Diagnostic Tool for PD Ben Oren, Ezra Brettler, Uri Ron, and Ying Wang MKTG

Client: Jafar Sabbah, CEO, Dental Devices Ltd. Technology in question: a novel computerized system for automatic quantification and measurement of time-space patterns of facial features during facial expression System is intended as a monitoring and decision support tool for the detection, and progression evaluation of medical disorders that affect the performance of facial muscles Currently system is exploited in a study on Parkinson’s Disease (PD) Project Background

Determining whether there is a real market need for an objective diagnostic computerized system for degenerative diseases such as PD This is the central question in the decision of whether to provide the inventors with seed money and bring the technology into the NGT Project Objectives

Parkinson’s Disease is the most common neurodegenerative disorder after Alzheimer's disease 4-6 million people worldwide have been diagnosed with PD ~1 million people in U.S. It is estimated that an additional 3 million people have undiagnosed PD in the U.S. The prevalence (of those diagnosed with PD) is estimated at being 0.3% in the whole population in industrialized countries Rising to 1% in those over 60 years of age 4% of the population over 80 Mean age of onset is ~60 years, but 5-10% of cases are considered young onset (cases with PD beginning between the ages of 20 and 50) U.S. incidence is ~17 per 100,000 of population per year PD Prevalence and Incidence

Physicians arrive at a diagnosis of PD using both subjective judgment and interpretation Assessing a patient’s history Performing a physical examination on the patient Requires intimate familiarity with the signs and symptoms found Accuracy of diagnosis increases with progression of the disease Current methods and scales: UPDRS UK Brain bank Criteria Gelb Criteria CAPIT Criteria Hoehn and Yahr Scale Current Diagnosis Protocol

Two of the four main symptoms must be present over a specific time period for a neurologist to consider a PD diagnosis Tremor or shaking Bradykinesia - Slowness of movement Rigidity (stiffness) of the arms, legs or trunk Postural instability - Balance problems and possible falls Brain changes that create neurodegenerative diseases are microscopic (on a chemical level) and are Not Revealed by scanning technology Current Scanning Methods: Electroencephalograms (EEGs) MRI and CAT Scans Positron Emission Tomography (PET Scan) Current Diagnosis Protocol - Cont’d

We interviewed 5 professionals that specialize in the area of PD Sample included researchers, and both primary care and specialist physicians Goals of primary research: Determine which of available methods is most preferred for both diagnosis and monitoring progression of PD Gather more information about the awareness of facial twitches and irregularities as a significant symptom of PD Determine whether there is potential to fill an unmet need through the measurement of facial expressions Goals of primary research and sample questions

According to our research based on industry standard survey conducted by NOP World Response to pharmacotherapy and MRIs are the most popular diagnostic and confirmatory procedures used for patients (showed in bottom right panel) Neurologists’ PD patients experience more tremors (52%) than any other symptom. Wearing-off fluctuations and early morning akinesia symptoms are both seen in about a quarter of PD patients (showed in bottom left Panel) According to NEUROs, PCPs are their largest referral source of PD patients. It is very helpful if there is a tool to help PCP diagnose PD disease. Results of primary research 1 of 3 % of PD Patients Who Undergo Each Procedure for Diagnosis % of Patients

One-on-one telephone interviews were conducted focused on Neuros and PCP. Three Neuros and one PCP were interviewed. Head of Parkinson Disease research, education and clinical center in US Assistant Professor, General Internal Medicine, Johns Hopkins University Xxx Xxxx The results are primarily focused on the following areas Symptoms used to diagnose PD Equipment used to diagnose PD What is the biggest unmet need Results of primary research 2 of 3

Symptoms used to diagnose PD asymmetric resting tremor responsiveness to dopaminergic replacement therapy Cogwheel rigidity rigidity Nearly no patients with PD have facial asymmetry and twitching, but most have facial masking and it can occur early Equipment used to diagnose PD Current equipments used to diagnose PD are viewed somewhat reliable, but rely on physicians’ experience for diagnosis. Some of the equipments require a lot of prep work and intensive training What is the biggest unmet need Physicians consistently categorize the level of unmet need as “high demand” They view the most challenge comes from diagnosing he patient early in the disease progression and differentiating PD for other atypical and secondary forms of Parkinsonism Interviewees’ opinion on the proposed method not asymmetry or facial twitching, which normally don’t occur in PD, but masked faces might be useful for diagnosis but probably not as a biomarker of disease progression because it is treatment responsive and the degree of change over time is subtle Results of primary research 3 of 3

Findings and Recommendations 1 of 2

Findings and Recommendations 2 of 2

Potential Next Steps