Post on 12-Jul-2020
transcript
1www.alliancesites.com
CNS Researchand
Hassman Research Institute
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Strategic Merger
CNS Research Hassman Research Institute
Dr. Larry Ereshefsky
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About AEP
• Single- and two-site solutions for all your early phasestudy needs including complex Phase I-IIa/POC trials
• Two 60-bed state-of-the-art units on East and West Coast
• Biomarkers, imaging, and electrophysiologic assessmentsstandardized across sites
• Thought-leader expertise in study design and execution
A partnership offering unique capabilities to accelerate drug development
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Leadership
Larry Ereshefsky, Pharm.D.
CSO, Early Phase Development
Hassman Research Institute and CNS Research
David Walling, Ph.D.
Chief Executive Officer, Principal Investigator
CNS Research
Howard Hassman, D.O., AOBFP
Chief Scientific Officer, Principal Investigator
Hassman Research Institute
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Larry Ereshefsky, Pharm.D.
• Internationally recognized thought-leader in clinical translational CNS research
• Leader in the application of translational drug development tools
• Proven track record as clinical advisor in designing Phase I/IIa and clinical pharmacology studies
• Formerly VP, Principal Clinical Pharmacologist, and Global CNS Leader for Early Phase at Parexel
• Retired Regents Professor, Pharmacy, Psychiatry, and Pharmacology, The University of Texas
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Deep Experience & Knowledge
Our KOLs have supported pharma ranging in size from virtual start-up to large global companies with:
Investigators affiliated with CNS and HRI have collectively conducted
over 2,000 protocols in patient and healthy subject populations.
• PK/PD modeling
• Experimental medicine strategies
• Development, validation, and application of biomarkers
• Vendor selection (Imaging, Electrophysiologic, cognitive sciences)
• Clinical Drug Development Planning
• Clinical trials methodologies
o Fit for purpose protocol design
o Protocol feasibility; balancing practicable with the science
o Evaluation of safety signals
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Therapeutic Areas
Dermatology
Alopecia, Acne, Psoriasis, Atopic Dermatitis, Rosacea, Aesthetics
Impairment
Cognitive Dysfunction, Validated Driving Simulation studies
Asian Studies
Bridging to Japanese, Chinese, and other Asian populations, enabling global development
Human Abuse Liability
Addictions, Exploratory assessments, Definitive HAL testing
Pain
Acute/Chronic, Fibromyalgia, Osteoarthritis, Migraine, Pain models such as UV and capsaicin
Healthy Volunteers
Including sub-populations of: Asian, elderly, post-menopausal females, tobacco users
Psychiatry
ADHD, Anxiety, Bipolar, Depression, PTSD, Schizophrenia
Neurology
Alzheimer’s, MS, Parkinson’s, Post-Stroke, Sleep Disorders
General Medical
Endocrinology, Immunology, Pulmonology, Gastrointestinal, NASH/NAFLD, and more
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Specialized Studies
• Elderly and patient populations
• PK/PD relationships with QEEG/ERP, fMRI/PET
• QTc, TQTc, cardiac monitoring
• 505(b)(2) program strategies, biosimilars
• Bioequivalence/DDI/Food Effect
• Digital Device and Software Technologies
• Orphan indications
• First into Human, SAD, MAD studies
• Translational and experimental medicine studies:
o Precision medicine
o NIH Research Domain Criteria
o Neurocircuitry applications
o Biomarkers
• Adaptive and umbrella designs
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AEP Study Experience
• Healthies/Ethno-bridging – 100+
• Bioequivalence – 100+
• Schizophrenia – 100+
• Addiction/HAL – 20+
• Alzheimer’s Disease – 20+
• Parkinson’s Disease – 15+
• Depression – 15+
• Multiple Sclerosis – 5+
• Diabetes – 10+
• Hep C – 20+
• Hypertension – 5+
• Other: Pain, NASH, Rare Diseases, Medical – 10+
Phase I Studies Conducted: Specialized Study Procedures Experience, past 5 years:
Procedure Studies
PET w/FDG, Amyloid 24PET custom chemistry (USC collaboration) 3Structural MRI (3T) 77MRI w/ radioactive fluids via IV or CSF (UCLA imaging Center) 2fMRI (functional MRI, BOLD or task-activated MRI) 15MRS (Glyx, GABA, GLU) 2Safety EEG 20QEEG w/ Evoked Potentials (MMN, P50, P300, ASSR) 22QT/QTc/QRS >50CSF 10MRE (elasticity), MRI-PDFF (proton density fat fraction). 6DEXA 26Ultrasound 16Driving simulators 8
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Asian Bridging
• Asian sensitivity and bridging in Japanese, Chinese, and Korean first-generation subjects
CNS Research has been very successful in conducting these studies. It is in a strong position to perform them.
• Dr. Ereshefsky co-created the ex-Japan, US-based strategy, and has been designer/investigator on 100+ Asian studies
• Site Manager, Edward Kim, has been involved in hundreds of Asian studies
• Asian staff
• Referral relationships with Asian community groups
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Addictions & Abuse Liability
Experienced Staff:
• PIs with decades of substance abuse clinical experience
• Full-time clinical research pharmacist
• Doctorate and Masters-level dedicated raters with decades of experience
Capabilities and Services:
• HAL and HAP studies including opioids, methadone/buprenorphine, alcohol interaction, stimulants, and hypnotics
• Physiologic monitoring and pupilometry and biophysical testing
• A multitude of administration routes and formulation preparations
Recruitment:
• Large research database of recreational drug users
• Referral relationship with network of addiction treatment centers
HRI is a leader in the conduct of substance abuse and abuse liability trials.
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Technology/Capabilities
• Imaging (PET, MRI, fMRI, MRS, MRE, MRI-PDFF, DEXA-scan, DAT-Scan, FibroScan)
• Electrophysiology (EEG, PSG, and QEEG / ERP)
• Pain models in HNVs and patients
• Digital Therapies (health devices, software, and applications)
• Safety (capnography, pulse ox, continuous safety EEGs, telemetry, biomarkers)
• Cognitive and behavioral assessments, including impairment of function
• Eye tracking, balance assessments
• CSF collection
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Imaging Capabilities
Primary Imaging Center(40 min. drive time to scanner)
Siemens MAGNETOM® Verio• 12 and 32 channel head coils
• Packages: BOLD, DTI, MRS SVS packages, DIXON
• CMRR licenses includes LASER, VAPOR and PCASL
• Run multiple BOLD studies with paradigm SW• MR Compatible Infusion System
• MR Compatible Bolus Injection System
• 1080P Stereo AV system
• Current designs response system
Secondary Imaging Center(15 min. drive time to scanner)
GE Discovery™ MR750 3.0T
• Packages: BOLD, MRE
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Primary Imaging Centers(15 min. drive time to scanner)
Two matched Siemens MAGNETOM® Skyra• 16+4 (head+neck) coil
• Packages: BOLD, DTI, MRS SVS packages, DIXON
• CMRR licenses includes LASER, VAPOR and PCASL
• Run multiple BOLD studies with paradigm SW• MR Compatible Infusion System
• MR Compatible Bolus Injection System
• 1080P Stereo AV system
• Current designs response system
Secondary Imaging Center(25 min. drive time to scanner)
GE Discovery™ MR750 3.0T
• Packages: BOLD, MRE
Imaging Capabilities
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EEG/QEEG & ERP Biomarkers
Turnkey strategy for selecting, collecting, and analyzing EEG related endpoints:
We work closely with: • Q-Metrx (for data acquisition, harmonization)• Pacific Development & Technology (for data analyses)
We can also accommodate any specialized equipment and paradigms you prefer to use.
Drs. Ereshefsky and Walling are advisory members of Cognision’s ERP Biomarker Qualification Consortium established to operationalize and qualify ERP Biomarkers for use in large-scale therapeutic CNS trials.
• Analysis of P300A, B and MMN
• Exposure-response analysis of change in endpoints from baseline vs. PK
• Univariate analysis and formal ANOVA/ANCOVA models
• Standardized technician training and equipment at sites
• Centralized data server for analysis
• Standard QEEG analysis of band amplitudes and derived frequency measures
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Evaluating Drug Impairment Driving Simulation
State-of-the-art CRCDS MiniSim driving simulators at both sites – used to evaluate the effectsof a wide variety of drugs on driving performance in both normal and patient populations
What drugs need to be evaluated?
• Drugs intended for chronic (or chronic-intermittent)outpatient use by adults who drive
• Drugs that might increase risk-taking
Driving studies may also be needed if a drug approvedfor a particular use is proposed for:
• a different indication
• a different dose or dosing schedule
• a new patient population
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NASH Center of Excellence
HRI is a top-enrolling site for NASH/NAFLD studies.
• Rapidly expanding patient database
• Referrals from multi-physician gastroenterology practice
Free FibroScan® Screenings Offered Daily
Dedicated technicians identify and pre-screen potential NASH/NAFLD patients by offering
free FibroScan® screenings daily.
Capabilities:
• Imaging:MRI-PDFF, MRE with T1/T2 Mapping, SWE, Ultrasound
• Liver Biopsies
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CNS Research
• Founded in 2000
• Largest clinical research provider in Southern California
• Operates three outpatient clinics located in Long Beach,Garden Grove, and Torrance
• Long Beach facility includes a Clinical Pharmacology Unitand Psychiatric Health Facility
• Database of over 90,000 subjects; dedicated recruitmentstaff comprised of 20+ outreach and recruitment specialists
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Long Beach Inpatient Unit
• 40,000 sq. ft. state-of-the-art facility
• Specially designed for early phase research
• 60+ beds for healthy subjects and stable patients
• Provides an array of services that are critical to the successful completion of complex and adaptive design studies
• Secure medication dispensary and CLIA Waived lab
• Four driving simulators dedicated to clinical trials
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Hassman Research Institute
• Over 35 years of experience conducting Phase I-IV trials
• Locations in Berlin and Marlton, NJ
o Marlton is home to new 60-bed state-of-the-art Inpatient Unit
• Affiliated with a large network of multi-specialty practices in theSouth Jersey and Philadelphia area, which offers unique access toa wide range of patient populations
• Family Practice Database of over 75,000 subjects, and ResearchDatabase with over 65,000 subjects; full-time enrollment staff
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Marlton Inpatient Unit
• 21,000 sq. ft. of space with 60 inpatient beds
• Purpose-built facility constructed in 2011
• Provides an array of services that are critical to the successful completion of complex and adaptive design studies
• Pharmacy with laminar flow hood and compounding capabilities
• 3 CLIA Waived labs
• Offers safety resources required for the unique needs of Human Abuse Liability (HAL) studies
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Omid Omidvar, M.D.
Principal Investigator
Board Certified Neurology
Key Personnel
David Walling, Ph.D.
Chief Executive Officer
Principal Investigator
Licensed Clinical Psychologist
Armen Goenjian, M.D.
Chief Medical Officer
Principal Investigator
Board Certified Psychiatry
Steven Reynolds, D.O.
Principal Investigator
Board Certified Family Practice
Larry Ereshefsky, Pharm.D., FCCP, BCPP
CSO, Early Phase Development
Follow the Molecule: CNS Consulting LLC
Nirav Patel, M.D.
Principal Investigator
Board Certified Neurology
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Haig Goenjian, M.D.
Principal Investigator
Board Certified Psychiatry
Lara Shirikjian, D.O.
Principal Investigator
Board Certified Psychiatry
Jack Stephens, MA
President
Dalia Botros, MBBS
Director of Operations
Oceanview PHF
Edward Kim
Site Manager
Seanglong Te, M.D.
Principal Investigator
Board Certified Family Practice
Key Personnel
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Howard Hassman, D.O., AOBFP
Chief Scientific Officer
Principal Investigator
Board Certified Family Practice
Michael Hassman, D.O.
Medical Director
Principal Investigator
Board Certified Family Practice
Larry Ereshefsky, Pharm.D., FCCP, BCPP
CSO, Early Phase Development
Follow the Molecule: CNS Consulting LLC
Elan Cohen, Ph.D.
Principal Investigator
Lead Psychometric Rater
Licensed Clinical Psychologist
Roberta Ball, D.O.
Principal Investigator
Board Certified Psychiatry
Steven J. Glass, M.D.
Psychiatric Medical Director
Principal Investigator
Board Certified Psychiatry
Key Personnel
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John Styczynski, M.D.
Inpatient Medical Director
Principal and Sub Investigator
Board Certified Family Practice
Ashok Joseph, M.D.
Sub Investigator
Psychometric Rater
Pain/Addiction Rater
Joseph Savon, M.D.
Sub Investigator
Pain/Addiction Rater
Board Certified Gastroenterology and Addiction Medicine
Djouher Hough, Psy.D.
Post-Doc Fellow
Addiction Specialist
Michael Alfano, RPh., J.D.
Pharmacist
Larry Shusterman, D.O.
Assistant Medical Director
Sub Investigator
Internist
Key Personnel
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IRB/Regulatory Approval Timelines
Investigator’s Brochure
Final Protocol
1 week
Sponsor approved consent
IRB submission
1 week
IRB meeting and approval
Screening begins
2 weeks Randomization
4 weeks or less until first patient dosed
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CASE: Sage's Phase 1 Program for SAGE-718
Five Phase 1 healthy volunteer studies with SAGE-718 were completed, including SAD, MAD, and three target engagement biomarker studies.
Results show SAGE-718 was well-tolerated and improved executive function.
SAGE-718, a first-in-class NMDA receptor PAM, is in development as a potential therapy for cognitive disorders associated with NMDA receptor dysfunction.
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MAD Study
The MAD HNV study was completed by HRI.
Part B MAD enrolling patient populations was a two-site collaboration conducted by CNS and HRI:
A Phase 1, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Determine the Safety, Tolerability, and Pharmacokinetics of SAGE-718 Oral Solution in Healthy Adults With an
Open-label Cohort of Patients With Huntington's Disease
HRI enrolled the healthy subjects (24 randomized in 4 months)
CNS enrolled specialized target population (Huntington’s) cohort (6 patients randomized)
Procedures: EEG, qEEG, QT, QTc, QRS
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Target Engagement Studies
A Phase 1, Double-blind, Placebo-controlled Crossover Study of SAGE-718 Using a Ketamine Challenge, to Evaluate the Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Subjects
Sites enrolled 22 in 2 months | 4 weeks from SIV to FPFD
Procedures: EEG, qEEG, Evoked Potentials, MMN, QT, QTc
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Crossover Study of Sage-718 Using a Ketamine Challenge, to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Response Using Magnetic Resonance Imaging In Healthy Subjects
Sites enrolled 19 in 4 month | 3 weeks from SIV to FPFD
Procedures: MRI, EEG, QTc
A Phase 1, Randomized, Double-blind, Placebo-controlled Study of Multiple Doses of SAGE-718 Using Ketamine Challenge to Evaluate the Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Subjects
Sites enrolled 40 in 4 month | 4 weeks from SIV to FPFD
Procedures: EEG, MMN, QT, QTc
These studies were two-site collaborations conducted by CNS and HRI.
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• Results demonstrate SAGE-718 had effects on electrophysiological, functional neuroimaging, and cognitive measures consistent with CNS activity.
• Healthy volunteers dosed with SAGE-718 also received low-dose ketamine as a selective antagonist of the NMDA receptor. SAGE-718 was found to modulate the effects of ketamine on regional and global measures of resting brain activity.
• 19 healthy volunteers administered SAGE-718 once-daily for 10 days exhibited significantly better performance on tests of working memory and complex problem solving compared to 20 healthy volunteers administered placebo, at times reaching statistical significance (p<0.05).
Target Engagement Studies
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Contact
Bobbie Theodore, M.S.
Alliance Executive Director
bobbie@alliancesites.com
P: 916-939-6696
M: 916-803-7149