CNS Research and Hassman Research Institute · 2020-02-26 · • Biomarkers, imaging, and...

1www.alliancesites.com

CNS Researchand

Hassman Research Institute


Strategic Merger

CNS Research Hassman Research Institute

Dr. Larry Ereshefsky


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


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


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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


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


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


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


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


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


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


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


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


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


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


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



• 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


Omid Omidvar, M.D.

Principal Investigator

Board Certified Neurology

Key Personnel

David Walling, Ph.D.

Chief Executive Officer


Licensed Clinical Psychologist

Armen Goenjian, M.D.

Chief Medical Officer


Board Certified Psychiatry

Steven Reynolds, D.O.


Board Certified Family Practice

Larry Ereshefsky, Pharm.D., FCCP, BCPP


Follow the Molecule: CNS Consulting LLC

Nirav Patel, M.D.


Board Certified Neurology

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Haig Goenjian, M.D.



Lara Shirikjian, D.O.



Jack Stephens, MA

President

Dalia Botros, MBBS

Director of Operations

Oceanview PHF

Edward Kim

Site Manager

Seanglong Te, M.D.



Key Personnel

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Howard Hassman, D.O., AOBFP

Chief Scientific Officer



Michael Hassman, D.O.

Medical Director



Larry Ereshefsky, Pharm.D., FCCP, BCPP


Follow the Molecule: CNS Consulting LLC

Elan Cohen, Ph.D.


Lead Psychometric Rater

Licensed Clinical Psychologist

Roberta Ball, D.O.



Steven J. Glass, M.D.

Psychiatric Medical Director



Key Personnel

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John Styczynski, M.D.

Inpatient Medical Director

Principal and Sub Investigator


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


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


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.


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


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.


• 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


Contact

Bobbie Theodore, M.S.

Alliance Executive Director

[email protected]

P: 916-939-6696

M: 916-803-7149

mailto:[email protected]

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CNS Research and Hassman Research Institute · 2020-02-26 · • Biomarkers, imaging, and...

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