The New York Stem Cell Foundation Accelerating Cures Through Stem - - PowerPoint PPT Presentation

The New York Stem Cell Foundation

Accelerating Cures Through Stem Cell Research

New York Pharma Forum Susan Solomon December 6, 2013

The New York Stem Cell Foundation

Stem Cell Research in the United States

• 1996 – Dickey Wicker Amendment
• 1998 – James Thompson and colleagues isolate hESCs
• 1999 – NIH Director Harold Varmus says NIH can fund

human pluripotent stem cells per HSS General Counsel

• 2000 – NIH guidelines released for hESC research
• 2001 – Bush Executive Order
• 2006 – Senate passes Stem Cell Research Enhancement

Act; vetoed

• 2006 – NYSCF’s privately funded, safe-haven laboratory
• pens

The New York Stem Cell Foundation

Stem Cell Research in the United States (cont’d)

• 2006 – Shinya Yamanaka derives first ever induced

pluripotent stem (iPS) cells

• 2008 – NYSCF supported scientist derives first patient

iPS lines (ALS)

• 2009 – Obama Executive Order and final NIH guidelines
• Allows NIH to fund some research on, but not

derivation of hESCs

• Lines that were eligible under Bush era must be

reviewed by a Working Group

• NIH funds cannot be used for research on stem cell

lines derived from SCNT or parthenogenesis

The New York Stem Cell Foundation

Public Supports Stem Cell Research

• 73% of Americans favor expanding ESC research
• A vocal minority has controlled the message

Source: Research!America

The New York Stem Cell Foundation

Stem Cell Programs

• States responded with their own programs
• California – $3 billion over 10 years
• New York – $600 million over 11 years
• Connecticut – $100 million over 10 years
• Maryland – approximately $10 million per year
• NIH: FY12 - $1.5B for stem cell research
• $146.5M for hESC ~ 13%
• Private Funding
• New York Stem Cell Foundation Research

Institute - $100 million

NYSCF Mission

Accelerating cures for the major diseases of our time through stem cell research

BEN

NYSCF Programs

NYSCF Innovators: Fellows and Investigator s NYSCF Conference and Symposia NYSCF Research Laboratory

NYSCF Conferences and Symposia

Annual Conferences Panels Seminar Series

NYSCF Innovators

$53M dedicated to building the next generation of top stem cell researchers

• 55 3-year NYSCF Fellowships over 12 years ($12M)

at 17 institutions

• 28 NYSCF Early-career Investigators over 6 years ($41M)

at 10 institutions

In just eight years, NYSCF has achieved several breakthroughs in the field

NYSCF’s Proven Track Record

2013 – New therapeutic approach for diabetes

• Discovery of compound that restores beta cell function in genetic

form of diabetes, may be applicable to all forms of diabetes. 2013 - Personalized bone graft advance

• NYSCF Research Laboratory team engineers bone from

skin cells 2013 – First monogenic diabetes model

• Mutated genes genetically corrected

2012 - Stopping mitochondrial disease

• NYSCF Research Lab team develops clinical cure for inherited

disease that impacts children 2011 - Pioneering cell replacement therapy

• NYSCF Research Lab team derives first ever human embryonic

stem cell from human eggs - Time magazine #1 medical breakthrough of the year 2008 - Creating first-ever disease model (ALS)

• NYSCF scientist has Time and Science magazines #1 medical

breakthrough of the year

Why NYSCF Research Institute is Unique

• Focus only on translational research – translating

research into cures

• Fund high-risk, high-reward “tipping point”

experiments that traditional funding mechanisms won’t support

• Independent and unencumbered by bureaucracy or

federal restrictions

• Leverage our proprietary research in collaboration

with institutions around the world

NYSCF Research Institute

Laboratory

• 45 full time researchers
• Raised and invested $100M

for stem cell research

• Leader in developing stem cell

technologies and disease modeling

• An international community of
• ver 100 scientists

collaborating to cure disease

™

Representative Stem Cell Lines

Objectives:

• Reproducible stem cell production
• Parallel derivation & culture at scale
• Quantitative quality control assays
• Reproducible panels of differentiated

cells

• Diverse and disease populations

Connect Genotype to phenotype:

• in vitro GWAS
• “Clinical trials in a dish”

NYSCF Research Institute

Building infrastructure to industrialize stem cell research

• Bone regeneration
• Diabetes / auto-immune diseases
• Heart disease
• Neural disorders
• Alzheimer’s disease
• Autism
• Parkinson’s disease
• Multiple Sclerosis
• Mental Illness

NYSCF Disease Programs

Why Do Cures Take So Long?

Identify Disease Causes Publish Research Papers

Academic Institutions Pharmaceutical & Biotech Companies

• Mainly work on large disease

markets (changing)

• Public companies - generally

risk averse

• Screen on mice and cells

unrelated to the disease

• Use small

collections of cell lines from a narrow group of patients

?

Then what? Drug Development

• 13 Years
• $4 Billion
• 99% Fail

NYSCF Provides a Bridge to Cures Academic Institutions can scale their discoveries reduces time, cost, and risk Biotech & Pharmaceutical Companies

connecting research to cures and treatments

The stages of development of a ‘typical’ new drug

DRUG DISCOVERY PRECLINICAL DEVELOPMENT CLINICAL DEVELOPMENT Phase I Phase II Phase III Phase IV 1.5 years 5-7 years 2-5 years Target selection Lead-finding Lead optimization Pharmacological profiling Pharmacokinetics Short-term toxicology Formulation Synthesis scale-up Pharmacokinetics, tolerability, side- effects in healthy volunteers Small-scale trials in patients to assess efficacy & dosage Long-term toxicology studies Large-scale controlled clinical trials Postmarketing surveillance 1

• 50 projects

12 compounds 1.7 3 5 Drug candidate Development compound Drug approval for marketing

Paul et al., Nature Rev Drug Discovery, 2010

This process is amazingly inefficient and shockingly expensive

First time a drug may see a human cell

Pluripotent Stem Cells

NYSCF Research Institute Goals

21

• Model diseased

tissue

iPS Cell Disease Modeling

• Test drugs on

diseased tissue

Functional Cells in a Dish

Alzheimer’s Neurons Dopamine Producing Neurons Cardiac Cells Insulin Producing Cells

Existing Challenges with iPS cells

• Artisanal product via

various methods with variable quality

• Few cell lines from

relatively homogeneous populations

• Lack of standardization
• Limited scalability and slow

production

A New Technology Platform: The NYSCF Global Stem Cell Array

• Automated robotic systems for iPS

cell generation, differentiation, and analysis

• Minimize manual manipulation
• Massive parallel processing

(100s-1000s)

• Produce reproducible panels of

differentiated cell lines

• Cell line collection
• 95% of genetic diversity
• Major and rare diseases

NYSCF Global Stem Cell ArrayTM

26

Automated differentiated cells

Differentiated Cells:

• Other iPSC derived cell types produced at NYSCF: astrocytes, endothelial cells, osteoblasts, oligodendrocytes,

and others. Cholinergic Neurons Tuj1/CHAT/DNA Cardiomyocytes cTnT/Nuclei Beta Cells Insulin/Glucagon/Nuclei

ATCGTACGTTGCATGCATC GTACGTTACCGCAACCTG CATGCCACGTACGCATGC ATGCATGCATGCACTGCAT GCATTGCATCTAACGTACG TATACGGCGCATGTATAGT GTACGTACGTACGTACGTA TGCCAGTTGCATGGCATG CATTGCATGCTTACGT ATCGTACGTTGCATGCATC GTACGTTACCGCAACCTG CATGCCACGTACGCATGC ATGCATGCATGCACTGCAT GCATTGCATCTAACGTACG TATACGGCGCATGTATAGT GTACGTACGTACGTACGTA TGCCAGTTGCATGGCATG CATTGCATGCTTACGT Puts the human genome into biological context

• Current genomic analysis allows

scientists to see a connection between DNA and disease

• With the addition of

NYSCF’s Stem Cell Array, scientists can see how the DNA actually functions in the disease.

Finding the Genetic Causes of Disease The NYSCF Global Stem Cell Array

28

• Replicate diseases in a dish using actual diseased

human cells (not mouse cells)

• Anticipate how people from genetically diverse

backgrounds will respond to different drugs before clinical trials

• Predict drug toxicity in the dish

“Clinical Trials in a Dish” The NYSCF Global Stem Cell Array

Scaling the Research The NYSCF Global Stem Cell Array

Allows scientists to:

• Scale their discoveries
• Test their findings in a large

population

• Translate their research into

medicine and cellular treatments for disease

30

Extensive Institutional Collaborations & Key Relationships (50+)

Other Countries Australia Israel Qatar Sweden United Kingdom

Select large scale collaborations: Michael J. Fox Foundation

NIH Undiagnosed Disease Program

Cure Alzheimer’s Fund Stem Cell Consortium Personal Genomes Project

Tissue samples Banking iPS production Distribution

NYSCF Array Distribution Team Full Documentation MTA [Academic / Government / Commercial]

NYSCF Global Stem Cell ArrayTM Freedom to Operate - Robust Management

NYSCF Collection Sites (clinical data), SCRO Committee, and Human Subjects Team

In-house US Collaborator International IRB Protocols MTA USDA / Customs Consent Forms MTA

NYSCF Production Management Team SOPs – Freedom to Operate – Licensing LIMS Tracking and batch records Bank QC

Partnership Opportunities

• Large-scale production, differentiation and genomic

engineering of iPS cells

• Adaptation of existing protocols to automation
• Development of new protocols
• Optimization and validation across genetically diverse

populations

• Assay development and validation
• Access to repository of iPS cell lines - controls with wide

genetic diversity and disease cohorts (PD, AD, MS, Diabetes,

• thers)
• Establishment of collaborative production sites

NYSCF Research Institute