Introduction to APEX and Alliance Early Phase
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CNS Researchand
Hassman Research Institute
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Strategic Merger
CNS Research Hassman Research Institute
Dr. Larry Ereshefsky
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About APEX Alliance Early Phase
• 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 CRUs on East and West Coast
• Separate inpatient facilities for addiction or other ‘highmaintenance’ populations at HRI
• Separate Asian Studies Unit at CNS
• 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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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 specialty/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
o Adaptive and Combination designs
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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 Potential
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, ENT, Ophthalmology, GI, NASH/NAFLD, and more
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Specialized Studies• Elderly and target patient populations
• PK/PD relationships with QEEG/ERP, fMRI/PET
• Sleep and Arousal with PSG, MWT, MSLT
• Eye tracking, sway balance
• QTc, TQTc, cardiac monitoring
• 505(b)(2) program strategies
• Biologics and biosimilars
• Bioequivalence/DDI/Food Effect
• Digital Device and Software Technologies
• Orphan indications
• Safety: Cognitive/Motor/Driving impairment, Capnography, Pulse Ox, Telemetry
• First into Human, SAD, MAD studies
• Translational and experimental medicine studies:
o Precision medicine
o NIH Research Domain Criteria
o Neurocircuitry applications
o Biomarkers
o CSF sampling
• Enrichment strategies
• Adaptive and umbrella designs
• Pain models in HNV and patients
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Technology/Capabilities
• Imaging (PET, MRI, fMRI, MRS, MRE, MRI-PDFF, DEXA-scan, DAT-Scan, FibroScan)
• Electrophysiology (EEG, PSG, MWT, MSLT, and QEEG / ERP)
• Pain models in HNVs and patients
• Digital Therapies (health devices, software, and applications)
• Safety (capnography, pulse ox, spirometry, safety EEGs, telemetry, biomarkers)
• Cognitive and behavioral assessments, including impairment of function
• Eye tracking, balance assessments
• CSF collection
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Evaluating Drug Impairment: Driving Simulation
Driving labs set up at both HRI and CNS – six simulators at each site
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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AEP Study ExperienceSpecialized 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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Illustrative Site - Pharma InteractionsConsulting and Assisting in Clinical Trials Over the Entire life cycle
of Drug Development – embed CRO and Technology CapabilitiesCritical Path for
Clin Pharm Studies
FIH
MAD/MTD
pts or HNVs
EEG/fMRI/CSF/
biomarkers
BE/BA - FE
DDI/Impairment
Human Abuse
Special
populations
QTc
Clinical consultants and
External Content Experts
Technology Partners
Established CRO support
Sponsor
Data review and
recommendations for
‘critical path’
Technology
Platforms
Parallel process:
Conduct rate limiting studies
Ongoing Regulatory/Scientific
Consultation
HRI/CNS EP
Units provide
input in areas of
expertise
Approval
We support drug development
from FIH to post-approval2 x 60 beds CRUs
11 Phase IIa-IV sites
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Illustrative approaches to accelerate development
Identify Study Needs; Adapt design and tools
as new data is reviewed
• Joint Review of Data • Go/No-Go Decision –
How to proceed forward
SAD/MAD MTD
• PK/PD
• ECG; Vital Signs
• QEEG/EP; Cognition
• CSF collection (‘backup plan’)
• Imaging (PET, sMRI, fMRI)
• Behavioral and pain models
• Measure efficacy effect size
POC
Go Decision
SAD HNV FIHIncorporate first generation AsiansCombine FEExplore elderly or target populationsProof of CNS Penetration
MAD HNV → Patients (MTD, titration)Proof of Mechanism, Biomarker dose responseFocused PD ‘sub-studies’
Mini-POC using target patient population. Multiple populations in one trial (transdiagnostic) or 2 or more IMPs
MAD can overlapPharmacodynamic (PD) panels can overlap
POC
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Ph1-01 Combination study (HNV-SAD; HNE-SAD; FE; MAD;CSF)This scheme has been used multiple times at AEP
Cohort 1 (Dose A) Cohort 2
(Dose B) Cohort 3 (Dose C) Cohort 4
(Dose D)
Cohort 3b1
(Dose C)Fed
Fasted
Fed
Fasted
Cohort 3c2
(Dose C)
HNV - SAD(N=8; 6:2/cohort)
HNV - FE(N=8; 6:2/cohort)
Cohorts 1 -24
(Dose C and ? TBD)
Pharmacodynamic measures – depending on objective, incorporated in SAD and/or MAD to demonstrate exposure; or occasionally in separate cohort(s)
TIME
1. HNV-FE accounts for possible increase of exposure, initiate after SAD Cohort 4 has 24 hour safety2/3. Panels staggered for possible increase of exposure, these cohorts start only after a higher dose has been tolerated in the HNV-SAD 4. Separate cohorts for complex PD measures, such as imaging or CSF
HNV Elderly - SAD(1 up to 3 cohorts) (N=8; 6:2/cohort)
Cohort 5 (Dose E)
Cohort 13
(Dose C)
Cohort 2 (Dose Y)
Cohort 3 (Dose Z)
HNV or HNE or patient population - MAD(N=8; 6:2/cohort)
– depending on objective, add, biomarkers; translational/experimental medicine evaluations
Cohort 3B-3C (Dose Y -Z)
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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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CASE: Phase 1 Program for SAGE-718HRI + CNS Collaborations
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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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 CNS enrolled specialized target population (Huntington’s) cohort
3 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
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EEG/QEEG, PSG, & 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
• MWT/MSLT, Restorative sleep models
• Standardized technician training, PSG technicians and equipment at sites
• Centralized data server for analysis
• Standard QEEG analysis of band amplitudes and derived frequency measures
• Full PSG with bio readouts, cleaning and scoring of date.
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Auditory-Evoked Potential Response To "Standard" Tone Is Altered During the Oddball Paradigm
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Evaluating Drug Impairment: Driving Simulation
Driving labs set up at both HRI and CNS
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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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 Unit,Asian inpatient unit, and 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
• Six driving simulators dedicated to clinical trials
• Affiliated with a large neurology practice in same building
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Phase I Experience
Schizophrenia – 61
Parkinson’s – 16
Alzheimer’s – 16
Depression – 11
Multiple Sclerosis – 4
Healthy – 33
20 First into Human SAD | 25 SAD and/or MAD combination | 22 BA/BE PK studies
Bipolar Disorder – 4
Migraine – 2
Huntington’s – 1
ADHD – 1
Smoking Cessation – 1
Asian Bridging – combined staff experience of hundreds of studies
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Patient Populations
ADHD – 1,400+
Alzheimer’s Disease – 3,150+
Asian – 1,200+
Asthma/Allergy – 1,275+
Bipolar – 2,570+
Chronic Pain – 7,475+
Depression – 2,000+
Diabetes – 4,035+
Fibromyalgia – 1,410+
Generalized Anxiety Disorder – 2,435+
Healthy Normal Volunteers – 8,220+
Migraine – 9,340+
Multiple Sclerosis – 1,765+
Obese – 3,450+
Parkinson’s Disease – 2,500+
Post-menopausal women – 700+
PTSD – 830+
Schizophrenia – 8,300+
Sleep Disorders – 345+
Substance Abuse – 5,925+
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Neurology Experience(last 5 years)
Alzheimer’s MSParkinson’s Indication Phase Setting
Ataxia 1 Inpatient
Ataxia 2 Outpatient
Ataxia 2 Outpatient
Ataxia 3 Outpatient
Narcolepsy 1 Inpatient
Narcolepsy 2 Inpatient
Narcolepsy 2 Inpatient
Narcolepsy 2 Inpatient
Narcolepsy 3 Outpatient
Narcolepsy 3 Outpatient
Narcolepsy 3 Inpatient
Sleep Disorder 2 Inpatient
Sleep Disorder 3 Inpatient
Stroke 3 Outpatient
Tardive Dyskinesia 4 Outpatient
Tardive Dyskinesia 4 Outpatient
Other
Inpatient: 5 Phase I: 2 Phase IIa: 1 Phase II: 1 Phase III: 1
Outpatient: 30 Phase I: 3 Phase II: 12 Phase II/III: 1Phase III: 14
Inpatient: 14 Phase I: 8Phase Ib: 1Phase II: 5
Outpatient: 9Phase IIa: 2 Phase II: 4Phase III: 3
Inpatient: 2Phase I: 1Phase III: 1
Outpatient: 15 Phase I: 2Phase II: 2Phase III: 11
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Orphan Disease Experience
A Phase II Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ***** in Adults with Spinocerebellar Ataxia
o Currently enrolling
A Randomized, Double-Blind, Controlled, Phase II/III Study to Assess Efficacy, Long Term Safety and Tolerability of ***** in Subjects with Friedreich’s Ataxia
o Currently enrolling
A Phase I Double-blind, Placebo-Controlled, Multiple Ascending Dose Study to Determine the Safety, Tolerability and Pharmacokinetics of ***** Oral Solution in Healthy Adults with an Open-Label Cohort of Patients with Huntington’s Disease
o 6 screened, 6 randomized
A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of ***** in Adult Subjects with Spinocerebellar Ataxia
o 8 screened, 8 randomized
A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of ***** in Adult Subjects with Spinocerebellar Ataxia
o 10 screened, 9 randomized
A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of ***** in Patients with Friedreich’s Ataxia
o 8 screened, 8 randomized
Patients for studies provided by sponsors and/or CROs
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Asian Bridging
Asian sensitivity and bridging in Japanese, Chinese, and Korean first-generation subjects
CNS is uniquely qualified to successfully conduct these studies.
• Dr. Ereshefsky co-created the ex-Japan, US-based strategy, and has been designer/investigator on 100+ Asian studies
• Experienced clinical/medical leadership
• Asian staff, bilingual
• Custom-built Asian inpatient unit
• Referral relationships with Asian community groups
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Asian Studies Strategy• Conduct early phase studies supporting global drug development
o Simultaneous conduct of SAD/MAD using Asian and Caucasian volunteers, can beaccomplished in same cohort
o First generation Japanese, Chinese, and Korean studies with all grandparents, parents,and volunteer born in country of origin (typically passport holding) can be conductedin Los Angeles
• Perform separate complementary SAD/MAD studies running in parallel or lagging behindfull development program
• True Bridging study takes a drug in later development and performs SAD/MAD PK andsafety study to enable approval in Asia
• Adds value to compound by including Asian data in Phase I enabling global Phase II
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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 the SouthJersey and Philadelphia area, which offers unique access to a widerange of patient populations
• Locations use separate patient databases
o Berlin: Family Practice Database with 75,000+ subjects
o Marlton: Research Database with 65,000+ subjects
• Full-time enrollment staff using sophisticated outreach, social andtraditional media, access to clinical practice
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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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HRI Phase I Experience
Healthy – 52
13 First into Human SAD | 20 SAD and/or MAD combination | 20 BA/BE PK studies
Schizophrenia – 39
Hep C – 18
Depression – 11
HAL – 9
OUD/Addiction – 7
Diabetes – 7
Analgesia/pain models – 6
Obesity – 5
Hypertension – 4
Renal/Hepatic Impairment – 4
Tourette’s – 3
Parkinson’s – 3
Alzheimer’s – 3
Atopic Dermatitis – 3
NASH – 3
Cancer Pain – 2
Multiple Sclerosis – 2
Osteoarthristis – 2
Bipolar Disorder – 2
Psoriasis – 1
Insomnia – 1
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Studies at the Marlton location are enrolled with patients from HRI’s research database, many of whom have been cared for Drs. Howard Hassman and Steven Glass for 25+ years.
HRI Marlton Recruitment Model
Research Database – 65,000+
Addiction– 8,940
ADHD – 5,500
Alzheimer’s – 650
Bipolar – 10,500
Depression – 11,000
Diabetes – 2,850
HNVs – 5,500
NASH – 505+
Pain – 4,520
Parkinson’s – 554
Recreational Users – 5,300
Schizophrenia – 9,500
Major Metropolitan Area:
The Philadelphia-Camden-Wilmington MSA:
• Home to both HRI's locations
• One of the largest in the US
• Over 6M residents
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HRI Pharmacy
• Schedule I-IV drug storage
• Triple locked drug storage
• Surveillance cameras monitor all access
• Blinding of Investigational product
• Services include a multitude of administration routes and formulation preparations (USP 795, 797)
• USP 1163 QA
• USP 800 in progress
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Pain Models of Neuronal Sensitisation:Assessment Techniques Performed at HRI
Pinprick Hyperalgesia Touch-evoked Allodynia
UVB Sunburn Inflammatory Model
(induction: physical)
Ref Poster: Francke K et al. Pain Therapeutics Summit, 2012
Electrical Hyperalgesia Model
(induction: electrical)
Capsaicin Hyperalgesia Model
(induction: chemical (patch/intradermal)
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Berlin Campus
Unit 1: CNS/Neuroscience
Unit 2: Early Phase/Inpatient
Unit 3: General Medicine, Pain, and Addiction
1
2
3
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HRI Berlin Recruitment Model
Acne – 1,650
ADHD – 3,300+
Alzheimer’s Disease – 430
Atopic Derm – 1,300+
Bipolar – 5,600+
Depression – 5,000+
Diabetes – 3,200+
Diabetic Foot Ulcer – 485
HNVs – 5,700+
Hypertensive Patients – 10,000+
NASH – 400+
Obese – 9,000+
Osteoarthritis – 7,000+
Pain – 8,500+
Parkinson’s Disease – 110
Post Menopausal Women – 8,000+
Psoriasis – 550
Schizophrenia – 7,000+
Senior Citizens – 15,000+
Substance Abuse – 5,000+
Family Practice Database – 75,000+
Affiliate:
Advocare Berlin Medical Associates
• Large network of multi-specialty practices in the South Jersey / Philadelphia area
• 4 addiction treatment units
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HRI Addiction Study Experience• Total Experience
• 35 'illicit' drug studies over the past 8 years, including 10 OUD studies, several alcohol, and 7 opioid
addiction studies.
• Consistently a top-enrolling site; #1 enrolling site on at least 9 trials in the last 5 years
• Study Performance
• Recruiting patients with OUD • Over 5 years experience successfully recruiting quality OUD subjects
• Managing patients with OUD during their residency period in the clinical unit
• Longest residency period with vulnerable population was over 60 days
• Multiple OUD trials requiring a residency period, all with a higher than average retention rate
• Managing follow up of patients after their residency period through to their EOS/ET visit
• Multiple successful OUD trials completed with higher than average retention rates
• Subjects were provided with a 24-hour number to call for support and/or questions
• Recruiting smokers and managing for the type of study during the residency period
• Completed many trials with smoking subjects
• Two secure, monitored smoking areas with regularly scheduled smoke breaks
• Currently implementing an OUD craving study using fMRI, PSG, and ERP
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Dependence & Abuse Potential
Experienced Staff:
• PIs with decades of substance abuse clinical experience
• Full time Psy. D. Specialist in Addiction and Pain
• Full-time clinical research pharmacist
• Doctorate and Masters-level dedicated raters with decades of experience
Capabilities and Services:
• HAL /HAP studies including opioids, methadone/buprenorphine, alcohol interaction, stimulants, hypnotics
• Physiologic monitoring, i.e., capnography/pulse ox, 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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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
*Non-alcoholic steatohepatitis
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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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HRI’s Placebo Control Reminder Script (PCRS, V5)
• Read to ALL subjects at ALL study visits immediately before efficacy scale administration, reminding subjects of key biases and placebo and nocebo effect reduction factors
• HRI and CNS conducted an IRB-approved single-blind all placebo empirical investigation and found that subjects in a Major Depressive Episode who were read the PCRS (Experimental Group) stayed more depressed at a significant level (p<.02) than did subjects who were not read the PCRS (Control Group) – i.e., the PCRS significantly helped control for the placebo effect
• The PCRS also significantly helped control for the placebo effect in a trial with schizophrenia and schizoaffective subjects conducted in 2019. Similar results demonstrated.
• PCRS has been licensed from sponsors and CROs and specified to exact protocol design
The Solution: Applying Systemic Interventions Mitigating Placebo and Nocebo Effects
Crucial Work Implemented to ManagePlacebo and Nocebo Response
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HRI 2018 Phase 2 Inpatient Placebo-Controlled Double-Blind Acute Schizophrenia Results
HRI Enrollment Achievement
• HRI RAND 20 study participants
• With 12 US sites, HRI tied 5 other sites with highest RAND
• HRI had second highest number of Completers (n=17), beat by only one subject at another site
Study Results
• Study design used 1:1 active drug vs placebo
• Study showed that active drug significantly separated from placebo (p<0.0001)
• Sponsor moving to Phase 3 given the results
HRI Performance Success
• While HRI’s data could not be analyzed for statistical significance given the low n, HRI’s drug-placebo difference was slightly more than twice the average drug-placebo difference in the clinical trial
• Rater change comparing BSL to Primary Efficacy Visit occurred ONLY twice (11% of the time)
Separation Between Drug and Placebo!*
*Sponsor permitted HRI to share site results without sharing sponsor / study identity
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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
Introduction to APEX and Alliance Early Phase
(c) Apex Innovative Sciences 23
5/21/2020
47www.alliancesites.com
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
Seanglong Te, M.D.
Principal Investigator
Board Certified Family Practice
Key Personnel
48www.alliancesites.com
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
Introduction to APEX and Alliance Early Phase
(c) Apex Innovative Sciences 24
5/21/2020
49www.alliancesites.com
Jaclyn Lobb, M.S.
Sub Investigator
Psychometric Rater
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
50www.alliancesites.com
Contact
Bobbie Theodore, M.S.
Alliance Executive Director
M: 916-803-7149
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