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Cells for Therapy and Research

International Stem Cell Corporation5950 Priestly DriveCarlsbad, CA 92008

OTCQB: ISCOwww.internationalstemcell.combd@intlstemcell.com1-760-940-6383

http://www.internationalstemcell.com/

mailto:[email protected]

Corporate Overview

• Clinical-stage biotechnology company developing stem cell-based therapies

• Three locations: GMP manufacturing lab in MD, GMP manufacturing lab in Oceanside, CA, headquarters in Carlsbad, CA

• Unique stem cell platform that is proprietary, scalable and ethical

• Robust clinical and pre-clinical pipeline addressing large unmet medical needs including:

• Parkinson’s disease

• Traumatic brain injury

• One therapeutic and two commercially-successful subsidiaries:

• Cyto Therapeutics: conducting clinical trials in Australia

Investment Highlights

www.internationalstemcell.com 2

Headquartered in California

Commercializes biomedical products

Commercializes cosmeceutical products

Corporate Overview

Therapeutic Programs

• Ongoing Phase 1/2a study in Parkinson’s disease with ISC-hpNSC• Conducting preclinical studies in traumatic brain injury and stroke with ISC-hpNSC• Conducting basic research in liver disease and osteoarthritis


Corporate Overview

Market Opportunity

Indication Market Potential Current approach

Parkinson’s disease1 60,000 new patients / year$2.5 billion / year

No cure

Stroke2 600,000 strokes / year$500 million / year

3 hour treatment window

Traumatic Brain Injury3

10 million new patients / year worldwide$70 billion / year

No effective treatment

1. Parkinson’s disease foundation2. Global Data 2012

3. WHO data


Corporate Overview


Scientific Collaborators

Eugene Redmond Jr, MDProfessor, Yale School of Medicine

Yale University

Andrew Evans, MDHead, Movement Disorders Program

Royal Melbourne Hospital

Sanford Burnham Prebys Medical Discovery InstituteEvan Y. Snyder, MD, PhDDirector, Stem Cells and Regeneration Program

University of South Florida

Cesar V. Borlongan, MA, PhDDistinguished Professor, Center of Excellence For Aging & Brain Repair

Corporate Overview


Intellectual Property

✓ 162 patents and licenses in 36 families✓ 48 issued patents✓ 114 patents pending in 36 families

Significant peer-reviewed publications:

• Scientific Reports by NPG• Cell Stem Cell• Cell Transplantation• Cloning and Stem Cells

✓ Freedom to operate in major jurisdictions✓ Competitive advantages in EU

Scientific Background


Human Parthenogenetic Stem Cells

• ISCO developed and exclusively owns a new class of pluripotent stem cells known as human parthenogenetic stem cells (hpSC)

• hpSC are derived from unfertilized eggs and no embryo is destroyed in the process

• hpSC cannot give rise to a human being

• hpSC can be expanded indefinitely and become any cell type in the body

No Life Possible

hpSC

Revazova, et al., Cloning Stem Cells. 2007;9(3):432-49

Scientific Background

• hpSC can be derived homozygous with identical copies of Human Leukocyte Antigen (HLA), making it easier to immune-match with patients

• A single homozygous hpSC line can potentially match millions of patients with the same HLA type minimizing the chances of immune rejection

• On December 2014, European Court of Justice issued a ruling allowing parthenogenetic technology to be patented because no human embryo is destroyed in the process

• Human embryonic stem cells can NOT be patented in the EU


Human Parthenogenetic Stem Cells

HistocompatibleHLA-homozygous hpSC

Revazova, et al., Cloning Stem Cells. 2008;10(1):11-24

Callaway, et al., Nature. 2014 doi:10.1038/nature.2014.16610

ISC-hpNSC

• Approved treatments do not stop disease progression or reverse symptoms

• Progressive degeneration of nigrostriatal dopamine (DA) neurons

• Fetal tissue transplants re-innervate the striatum and generate symptomatic relief for several years in some patients

• Fetal tissue is clinically impractical and alternative tissue sources are needed


Rationale

Ma et al., J Nucl Med. 2010;51(1):7-15.

Fetal tissue transplantDegeneration of DA Neurons in Parkinson’s Disease

Motor Symptoms:Bradykinesia, rigidity, tremors

2nd Most CommonNeurodegenerative disease

ISC-hpNSC

• Virtually unlimited quantities of ISC-hpNSC

• Extremely pure cell populations

• Manufactured in-house in cGMP facilities

• Patented


cGMP Manufacturing

Highly Optimized cGMP Process

• Cryopreservable

• Centralized manufacturing

• Scalable

• Multiple CNS indications

ISC-hpNSC has ideal product characteristics

Differentiate ThawQC

On-sitePrep.

Expand

ISC-hpNSC

• Cryopreserved Allogeneic Cell Population

• Derived from Human Parthenogenetic Stem Cells (hpSC)

• Characterized Composition of Cells:

• Neural Stem Cells

• Three Identified Functions:

• Neurotrophic Support

• Anti-Inflammation

• Neuroregeneration

• “Off the shelf” administration

• First Indication: Parkinson’s disease

• Potential Indications: Traumatic Brain Injury, Stroke, Spinal Cord Injury, Macular Degeneration, Lysosomal Storage Diseases, Alzheimer’s Disease


hpSC-Derived Neural Stem Cells

ISC-hpNSC


Increases DA Neuron Innervation and Number

ISC-hpNSC increases DA neuron innervation in the striatum and the total number of DA neurons in the substantia nigra of PD monkeys compared to controls

Control ISC-hpNSC

TH

ISC-hpNSC

• 10 Animal Studies

• >300 Rodents and Monkeys

• Activity/Efficacy

• Biodistribution

• Dosing/Delivery

• Toxicity

• Tumorigenicity

• Ectopic Tissue

• Immune Rejection


Safety & Efficacy Profile in Nonclinical Studies

✓ Survives in the Brain✓ Differentiates into Neural Cell Types✓ Improves Locomotor Activity✓ Increases Dopamine Concentration✓ Increases DA Neuron Innervation✓ Increases DA Neuron Number✓ Migrates throughout Nigrostriatal Pathway✓ Provides Neurotrophic Support✓ Reduces Inflammation✓ Differentiates into DA Neurons✓ Does Not Distribute Outside CNS✓ Does Not Increase Mortality✓ Does Not Induce Dyskinesia✓ Does Not Induce Systemic Toxicity✓ Does Not Produce Teratomas

ISC-hpNSC

• Open Label Phase I/IIa Study

• Moderate PD, UPDRS Part III < 49

• 12 patients: 3 cohorts of 4 patients each

• Dose Escalation: 30, 50, 70 million cells

• Transplantation into Putamen, Caudate Nucleus and Substantia Nigra

• Immunosuppression

• Primary Endpoint: Safety

• Assessment of Test Article or Treatment Related Adverse Events

• Secondary Endpoints:

• UPDRS

• PDQ-39

• QUIP-RS

• MoCA

• BDI

• CGI

• Patient Motor Diary

• 18F-DOPA-PET


First Clinical Trial to Establish Product Safety

Study Conducted at:

ISC-hpNSC for Parkinson’s Disease


Phase 1/2a PD Study Schema


• No Serious Adverse Events (SAE) Associated with ISC-hpNSC

• No Graft-Induced Dyskinesia

• No Evidence of Expansive Tumors , Cysts, Enhanced Inflammation or Infection


Delivery is Feasible and Safe

9 patientsReceived ISC-hpNSC

6 patientsCompleted 12 months

2 patientsCompleted 6 months

1 patientCompleted 3 months

• Successful Delivery of ISC-hpNSC to Striatum and Substantia NigraWithout Intra-operative Complications

• Delivery to Target Sites Confirmed by MRI



Phase 1/2a Interim Results

0

10

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60

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% O

FF T

ime

Days Post-Transplantation

1st Cohort

2nd Cohort

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50

0 100 200 300 400

PD

Q-3

9 S

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mar

y In

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Days Post-Transplantation

1st Cohort

2nd Cohort

PDQ-39% OFF time

The % OFF-Time is the time of day when levodopa medication is not performing optimally and PD symptoms return. PDQ-39 is the quality of life index.

ISC-hpNSC

ISC-hpNSC® significantly improves cognitive performance, locomotion, and neurological function in rodents with TBI. The preclinical studies were conducted by the world renowned Prof. Cesar Borlongan. The results of these studies demonstrate the therapeutic potential of ISC-hpNSC® in TBI and should expedite its translation into the clinic.

There is currently no approved treatment for TBI. TBI is a leading cause of death and disability in the United States, contributing to approximately 30% of all injury deaths. According to the World Health Organization, the global incidence for TBI is approximately 10 million people annually.


Traumatic Brain Injury Program

Corporate Overview

Upcoming Milestones

December 2018❑ Dosing of last patient in 3rd cohort

January 2019❑ IND submission


Business Performance

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Net Sales

-$1,800,000

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Net Income

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