Clinical Trial Centers Alliance

offering specialized expertise to fit the unique needs of each client

Bobbie Theodore, M.S. Alliance Director

clinicaltrials@alliancesites.com www.alliancesites.com

The Alliance

Executive Summary

Site Locations

Staff Highlights

Capabilities

Therapeutic Areas

Recruitment and Retention

Advantages

Sample Metrics – Phase I

Sample Metrics – Phase II-IV

Cognitive Research Corporation

NeuroCog Trials

Curricula Vitae

Contact

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Table of Contents

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The Alliance

Clinical Trial Centers Alliance is a group of privately owned and independently operated research centers in geographically diverse locations. Founded in 2001 to share best practices, expertise and business development, Alliance capabilities include inpatient and outpatient sites across psychiatry, neurology, pain, general medical and healthy populations. Alliance members are committed to providing consistent quality in the clinical trials they conduct. The Alliance Sponsor Relations team is a seamless resource to sponsors and CROs.

Drs. Andrew Cutler and David Walling Founding Investigators

Jeanette Caruso Bobbie Theodore Annie Speno Project Manager Alliance Director Operations Director

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Executive Summary

Our Alliance can address all stages of clinical research activities. We propose flexible options to serve your needs as follows:

A menu of services under one liaison

Expertise across a range of therapeutic areas, phase I through post-marketing

Integrated services including clinical site conduct, with or without bundled vendor or CRO services such as protocol development, trial management, data management, statistical analysis, monitoring, rater training – any or all to meet your clinical program needs Central IRB for all sites Large patient databases, affiliated medical practices and proven recruitment methods

Click links below to download fact sheets for each of our sites and services: Collaborative Neuroscience Network, LLC., Phase I Unit—Long Beach, CA Collaborative Neuroscience Network, LLC.—Torrance & Garden Grove CA Pacific Research Partners, LLC.—Oakland, CA Oregon Center for Clinical Investigations, Inc.—Portland & Salem, OR Clinical Trials of the Rockies—Denver, CO Albuquerque Neuroscience, Inc.—Albuquerque, NM FutureSearch Trials of Neurology and Sleep Medicine, L.P.—Austin, TX FutureSearch Trials of Dallas, L.P.—Dallas, TX Florida Clinical Research Center, LLC.—Maitland, FL Meridien Research—Bradenton, FL Synapse Clinical Research, LLC.—Durham, Hillsborough, & Pinehurst, NC Hassman Research Institute, LLC. — Berlin, NJ Cognitive Research Corporation – CRO Collaboration NeuroCog Trials – Cognition and Clinical Outcomes Assessment Services Collaboration

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Staff Highlights

Full-Time Dedicated And Highly Experienced Staff

Investigators are Board Certified in Psychiatry, Neurology, Sleep Medicine, Internal Medicine, Family Practice, Endocrinology, Pulmonology, and Licensed Clinical Psychologists

Protocol consultants to sponsors and CROs, and experts in psychiatry, cognition, neurology, sleep and phase I study designs

Full-time certified, psychometric clinical raters – doctorate and M.A.-level with up to 20+ years rating experience

Multiple full-time study coordinators including CCRCs, RNs, and LVNs

Dedicated recruitment and outreach specialists with established referral networks in their communities

Regulatory, QA, training and IT personnel

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Capabilities

Specialized Capabilities and Experience

State-of-the-art Clinical Pharmacology Unit (CPU) CNS Biomarkers:

EEG and qEEG evoked potentials Imaging, 1.5 and 3T MRI, and fMRI Lumbar puncture and CSF collection Occular Assessment Psychomotor Testing

Telemetry and holter cardiac monitoring Serial PK and ECG PSG (polysomnography) Infusion, injection, oral, device, implant and transdermal patch delivery systems Software / Neurogaming Product Validation

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Therapeutic Areas Psychiatry Phase I-IV

Abuse liability/deterrent (HAL)

Addictions – smoking cessation, alcohol dependence, binge eating, opioid, drug

ADHD – adult and child, including analog classroom, adult workplace

Anxiety – GAD, PTSD, OCD

Bipolar – bipolar depression, mania, mixed

Cognition and cognitive impairment

Depression – MDD, refractory/treatment resistant, depression with sexual dysfunction

Schizophrenia and schizoaffective disorders – acute, stable, cognitive dysfunction, negative symptoms

General Medical Phase I-IV Asthma, COPD

Constipation and irritable bowel

Dermatology

Diabetes

Hypercholesterolemia

Hypertension

Nutraceuticals

Obesity

Ophthalmology

Vaccines

Women’s health

Special Patient Populations Healthy and healthy elderly Asian bridging

Renal and hepatic impaired

Pain Phase I-IV Acute and chronic pain

Fibromyalgia

Episodic and chronic migraine

Neuropathic pain

Osteoarthritis

Post herpetic neuralgia

Neurology Phase I-IV Alzheimer’s – MCI, prodromal, mild, moderate, and severe with agitation

Multiple Sclerosis – relapsing remitting

Parkinson’s – early stage to advanced

Post-stroke, movement disorders

Sleep– insomnia, narcolepsy, restless legs syndrome, shift worker, sleep apnea, maintenance

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Recruitment and Retention Recruitment

Full-time dedicated recruitment and outreach specialists on staff Extensive databases Affiliated PI private and group practices (psychiatry, neurology, family practice, sleep, endocrinology) Established relationships with physician networks for patient referrals Outreach to and relationships with residential facilities, board and cares, senior communities, Japanese communities Participation in community events and support groups – providing free seminars, lunch and learns History of successful advertising - traditional and social media Ability to pre-qualify patients via IRB-approved pre-screen consent form

Retention Modern inpatient facilities, some with private and semi-private rooms for caregivers Site-provided patient transportation as needed Full-time dedicated staff for regular communication with patient, family and caregiver, reminder and follow-up phone calls Thorough pre-screening Treating physicians allow for ease in transition and follow-up

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Advantages

Advantages and Expertise

Geographically and therapeutically diverse sites

Menu of site and study management services based on sponsor need

Responsiveness and ease of single point of contact for all

Dedicated regulatory, and budget and contract staff for quick turnaround

Central IRB of sponsor’s choice

Best clinical and operational practices shared across sites

Thought leaders in CNS and Phase I designs

Multiple publications and advisory board memberships

Established vendor relationships for seamless execution

Protocol and budget development and consulting

Proven separation data

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Sample Metrics - Phase I Study Title # of Patients Contracted/Screened/Enrolled Year Status

A Phase IIa, Multiple Oral Doses , in Healthy Elderly Subjects (incl. 3 Lumbar Punctures)

Contracted for 30,

Screened 37, Enrolled 15 in 1 month, single site

2016 Closed

Phase I, Online Neurocognitive test battery, Normal healthy adults and healthy elderly

Contracted for 280 across 3 sites

Screened 250 , Enrolled 227 so far in 5 months, across 3 Alliance sites

2016 Enrolling

Phase I, OL, Multiple Dose, Chronic, Stable Schizophrenia or Schizoaffective Disorder

Contracted for 4 cohorts of 10 (40)

Screened 116, 60 patients plus back up subjects in 3 months, single site

2015 Closed

Phase I, Single and Multiple Rising Dose, Healthy Smokers

Contracted for 1 cohort of 5 and 2 cohorts of 8 (21)

Screened 50, Enrolled 21 in 3 ½ months, single site

2015 RESCUE SITE

Phase I, Single and Multiple Dose, Healthy Adult Japanese Subjects - Part I and II

Contracted for 2 cohorts of 8 (16)

Screened 36, Enrolled 16 in < 2 months over the holidays, single site

Nov-Dec 2014

Closed

Phase I, Escalating, Single-dose, Healthy, Male Subjects

Contracted for 5 cohorts of 12 (60)

Screened 110, Enrolled 60 plus back up subjects in 5 months, single site

2013

2014

Closed

Phase I, Single Oral Dose AND Ascending Multiple Oral Dose, Schizophrenia

Contracted for 7 cohorts of 15 (105)

Screened 128, Enrolled 93 plus back up subjects in 3 months, single site

2014 RESCUE SITE

Phase I, Single and Multiple Ascending Dose, Intravenous Infusions, Mild to Moderate Alzheimer’s Disease

Study design 5 cohorts; 1 pt/cohort from ea site

Screened 35, 20 patients enrolled (2 cohorts of 10 each) in 12 months, multi-site

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2013

TOP ENROLLER

Phase I, Major Depressive Disorder - (Extensive PKs & multiple ECGs)

Contracted for 38

Screened 38, Enrolled 22 in 6 weeks, across 2 Alliance sites

2011 TOP ENROLLER

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Sample Metrics Phase II-IV Study Title

# of Patients Screened

# of Patients Randomized

Length of Enrollment Year Status

Phase III, Inpatient, antipsychotic efficacy, Schizophrenia 94 64 8 months 2016 Enrolling

Game-play, ADHD in children ages 6 to 12 years old 63 62 5 months, across 2 Alliance sites

2014 Closed

Phase II, Multiple Dose, POC, Cognition in Stable Schizophrenia 66 41 10 months, across 2 Alliance sites

2013 Closed

Flexible-Dose, Generalized Anxiety Disorder 43 22 6 months, across 2 Alliance sites

2013 Closed

Phase III, Mild to Moderate Alzheimer’s Disease (includes IGIV, and infusion)

15 10 14 months 2013 TOP ENROLLER

OL, Daily Subcutaneous Injections, Relapsing-Remitting Multiple Sclerosis

7 6 2 weeks 2013 Closed

Phase III, OL, Moderate to Severe Chronic Nonmalignant and Non-neuropathic Pain

22 20 3 months 2012 Closed

Phase IV, Smoking Cessation 58 45 2 months 2011 Closed

Phase III, Bipolar I Disorder 23 16 9 months 2011 TOP ENROLLER

Phase III, Once Daily Controlled Release, Fibromyalgia (includes Actigraphy, PK, Multiple Psychiatric, Sleep & Pain Assessments, and Diary)

49 33 7 months 2011 TOP ENROLLER

Phase III, OL, Single-Arm, ER Capsules, Moderate to Severe Chronic Non-cancer Pain

28 24 3 months 2011 TOP ENROLLER

Phase IIa, Two Dose Regimens, Parkinson's Disease 11 10 1 month 2010 RESCUE SITE

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Cognitive Research Corporation Collaboration

Cognitive Research Corporation (“CRC”) is a CNS-specialty, full-service CRO with decades of clinical trial experience specializing in conducting drug, device, and nutraceutical trials from early development to final analysis Based on sponsors’ requests for full service proposals, our Alliance offers a streamlined solution to offer site and CRO services when needed

Collaborative (non-exclusive) relationship with Alliance sites allows flexibility for separate CRO proposals, site-only services, or bundled options per sponsor preference

Menu of services

Trial Design (Phase I-IV) Clinical Trial Management Established Network Investigators Data Management Biostatistics Medical Writing Regulatory Affairs Quality Assurance Early Drug Development (Phase I, healthy subjects, and specialty populations) Expertise in neuro-cognitive testing including state of art, world class driving simulation

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• NeuroCog Trials (NCT) is a cognition and clinical outcomes assessment (COA) services company founded in 2005 by Rich Keefe, Ph.D. and Caren Gadigian devoted exclusively to applying rigorous standards for reliable and valid endpoints in multi-site clinical trials. Its proven methodologies improve signal detection, increase reliability & reduce trial sample sizes

• Dr. Keefe is Professor of Psychiatry, Psychology, and Neurosciences at Duke University Medical Center with more than 25 years’ experience. Dr. Keefe developed the FDA-approved Brief Assessment of Cognition in Schizophrenia (BACS). An iPad version (BAC App) and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT©) are now available for use in clinical trials. NCT is also the exclusive provider of the UPSA scales.

• Services addressing the unique needs of cognition testing and COA include:

• Assessment scale expertise and consulting – outcome selection, trial design, feasibility • Global site and rater selection based on data quality metrics • Scale management: licensing, templating, distribution and standardization of materials • Rater training: Cognition and Clinician Reported Outcomes (ClinROs) • Audio/video surveillance and expert data review • International support: linguistics service and translators for local language interaction with sites • Statistical analyses, publication, regulatory guidance • Test development

• 85+ phase 2 and 3 clinical trials conducted in schizophrenia, Alzheimer’s, MCI, depression, bipolar and more • 6,000+ raters trained and certified (MCCB, ADAS-Cog, SCoRS, PANSS, CGI-S, AIMS, BARS, C-SSRS, CDSS) • 150,000+ data quality reviews • 200+ scientific articles published

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Curricula Vitae

CNS, LLC. David P. Walling, Ph.D. Armen K. Goenjian, M.D. Lara Shirikjian, D.O. Omid Omidvar, M.D. Nirav S. Patel, M.D. Steven Reynolds, D.O. Mark Leibowitz, M.D.

Pacific Research Partners, LLC.

Ira D. Glick, M.D. Anand Mehta, M.D. Simret Nanda, M.D. Corinna Gamez, M.D.

FutureSearch Trials, L.P.

John Douglas Hudson, M.D. Edward Ortiz, M.D. Michael Downing, M.D.

Click on name below to download CV

Hassman Research Institute, LLC. Howard Hassman, D.O. Michael Hassman, D.O. Roberta Ball, D.O.

Synapse Clinical Research, LLC.

Robert Millet, M.D. Hansen Su, M.D. Gary Clary, M.D.

Oregon Center for Clinical Investigations, Inc.

Beal Essink, M.D. Alexander Horwitz, M.D. Drissana Tran, M.D.

Florida Clinical Research Center, LLC. Richard D. Knapp, D.O. Martin Kane, M.D. Andrea Marraffino, Ph.D.

Meridien Research

Andrew J. Cutler, M.D. Jose T. Zaglul, M.D. Conrado O. Beckles, Ph.D.

Albuquerque Neuroscience, Inc. Glenn Michael Dempsey, M.D. Paula Lane, M.D.

Clinical Trials of the Rockies

Jennifer Lytle, M.D. David Weiss, M.D.

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Contact

For further information on Alliance

services contact:

Bobbie Theodore, M.S. (916) 939-6696

clinicaltrials@alliancesites.com www.alliancesites.com