Strategic Merger - Alliance€¦ · • Biomarkers, imaging, and electrophysiologic assessments ......

Introduction to APEX and Alliance Early Phase

(c) Apex Innovative Sciences 1

5/21/2020

1www.alliancesites.com

CNS Researchand

Hassman Research Institute


Strategic Merger

CNS Research Hassman Research Institute

Dr. Larry Ereshefsky



5/21/2020


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


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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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


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


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


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


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)


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


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.


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


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


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+


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 3 Outpatient

Narcolepsy 3 Outpatient


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


A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of ***** in Adult Subjects with Spinocerebellar Ataxia


A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of ***** in Patients with Friedreich’s Ataxia


Patients for studies provided by sponsors and/or CROs


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



• 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


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


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)


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


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.


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


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


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

Seanglong Te, M.D.



Key Personnel


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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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


Contact

Bobbie Theodore, M.S.

Alliance Executive Director

[email protected]

M: 916-803-7149

mailto:[email protected]

Strategic Merger - Alliance€¦ · • Biomarkers, imaging, and electrophysiologic assessments ......

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