Download Dr Patrick Soon Shiong, Chairman and Chief

A FUNDAMENTAL CHANGE IN CANCER CARE IN THE ERA
OF GENOMICS, PROTEOMICS, AND IMMUNOTHERAPY
THE EVOLUTION OF REAL WORLD BIG DATA AND
AUGMENTED INTELLIGENCE
Presented by:
Patrick Soon-Shiong, MD
Email: [email protected]
A GLOBAL PUBLIC HEALTH CARE CRISIS:
The Increasing Global Burden of Cancer
2012
By 2030
New Cancer Cases
14 Million
New Cancer Cases
22 Million
Cancer Deaths
8.2 Million Per Year
Cancer Deaths
13 Million Per Year
World Cancer Report 2014, ESMO
Information Overload & Big Data in Cancer:
A Looming Crisis
What molecular subtype?
Surgery or Chemotherapy?
Has tumor spread?
What stage?
NY001WT1_3.cdr
What dose?
What schedule?
Pre-operative
chemotherapy?
In combination
with other drugs?
The Current Paradigm:
Costly Trial and Error Treatment
Reactive Medical Care
A 40 year illusion of Clonal Dominance
Burrell RA, et al. Nature. 2013;501(7467):338-345.
A 40 year illusion of Clonal Dominance
Cancer - A Multi-Clonal Disease
Burrell RA, et al. Nature. 2013;501(7467):338-345.
A 38-year-old man with BRAFmutant melanoma and
subcutaneous metastatic
deposits. Photographs were
taken (A) before initiation of
PLX4032, (B) after 15 weeks,
and (C) after relapse, after 23
weeks of therapy.
Wagle et al., JCO (2011) 29, 3085-3096
A 38-year-old man with BRAFmutant melanoma and
subcutaneous metastatic
deposits. Photographs were
taken (A) before initiation of
PLX4032, (B) after 15 weeks,
and (C) after relapse, after 23
weeks of therapy.
Wagle et al., JCO (2011) 29, 3085-3096
A 38-year-old man with BRAFmutant melanoma and
subcutaneous metastatic
deposits. Photographs were
taken (A) before initiation of
PLX4032, (B) after 15 weeks,
and (C) after relapse, after 23
weeks of therapy.
Wagle et al., JCO (2011) 29, 3085-3096
“…an illusion of clonal dominance when assessed
by single biopsies. The presence of sub clonal
driver events in solid tumours may provide an
explanation for the inevitable acquisition of
resistance to targeted therapeutics in advanced
disease.”
Gerlinger et al. Nature Genetics (2014)
“Resistance is therefore a fait accompli – the
time to recurrence is simply the interval
required for the subclone to repopulate the
lesion.”
- Diaz et al. Nature 486, 537-540 (2012)
Precision Medicine:
Crossing the Chasm of Scale
Population
Patient
Tissues
Cells
DNA
Proteins
Peptides
The Anatomy
Cellular & Molecular Biology
Current State
Molecular 21st Century Precision Medicine
An Integrative Omics Approach
Population
Current State
Molecular 21st Century Precision Medicine
An Integrative Omics Approach
Population
Real-time actionable
knowledge to provide the
highest quality care at the
lowest possible cost
Lab Data
Pharmacy Data
Financial Systems and
Operational Systems
Accessible on
Mobile Devices
Electronic Patient Record
Patient Administration System
(PAS)
Personal Smart Wearable Sensors
Monitoring Medical Devices
Current State
Genomic Data
Imaging Data
Molecular 21st Century Precision Medicine
Integrated Clinical Operating System – cOS
Real-time actionable knowledge
to provide the highest quality
care at the lowest possible cost
Lab Data
Pharmacy Data
Financial Systems and
Operational Systems
Accessible on
Mobile Devices
Electronic Patient Record
Patient Administration System
(PAS)
Personal Smart Wearable Sensors
Monitoring Medical Devices
Genomic Data
Imaging Data
An Integrative Omics Approach
Population
Current State
Molecular 21st Century Precision Medicine
Next Generation Sequencing:
Identifying the target
Whole Genome:
3 Billion base pairs that make up DNA
Whole Exome:
20,000 Genes that code for proteins
Which of these 1,000’s of
mutations are actionable?
Next Generation Sequencing:
Protein Receptor
Identifying the target
Protein Pathways
RNA
DNA
Which of these 1,000’s of
mutations are actionable?
Next Generation Sequencing:
Identifying the target
Next Generation Sequencing:
Identifying the target
From DNA to RNA
From DNA to RNA to Protein to Drug
By combining
proteomics with
genomic interpretation,
we can give a holistic
understanding of the
progression of disease
and universe of options
for individualized care
Molecular Diagnostic Case Studies
Gastric/Gastroesophogeal junction case study
Patient results: Pre/Post MET TKI x 6 weeks
Baseline PET
7-22-2014
Post-MET TKI
9-10-14
Collaboration with D. Catenacci
“Resistance is therefore a fait accompli – the
time to recurrence is simply the interval
required for the subclone to repopulate the
lesion.”
- Diaz et al. Nature 486, 537-540 (2012)
Introducing Quantum Oncotherapeutics
Changing The Paradigm Of Cancer Care To A Regimen Of
Low Dose Metronomic Combination Therapy
Preserving The Immune System
Wide Spread Pancreatic Cancer
Complete Remission
7/3/2007
8/15/2007
Metastatic Pancreatic Cancer is Not Necessarily a Death Sentence
Changing The Paradigm Of Cancer Care To A Regimen Of Low
Dose Metronomic Combination Therapy
Preserving The Immune System
Screening 2/27/07
Follow up 4/11/07
Metastatic Pancreatic Cancer is Not Necessarily a Death Sentence
Side-chain Theory
Hypothesis:
Tumors occur at high frequency in
humans, but are kept under control
by the immune system
Paul Ehrlich
First Director of the Georg-Speyer-Haus
1906 - 1915
Nobel Prize in Physiology or Medicine
1908
IDENTIFYING EACH PATIENT’S UNIQUE
CANCER ANTIGEN BY NEXT GENERATION
GENOMIC SEQUENCING
IMMUNE
EFFECTOR
CELL
Immune Synapse
A DANCE OF PROTEINS
CANCER
CELL
CONFIDENTIAL
Immuno Protection System
T-CELL
•
•
•
Learned (Adaptive)
Require switching-on
Delayed killing
Natural Killer
Cell (NK)
VS
•
•
•
Innate
Always switched-on
Rapid killing
A Living Killing Machine: NK Cell Innate Immune Protector
1
Adhesion & Targeting Receptors
Targets and binds to tumor cell
& tumor cell matrix, and viral
infected cells
7
NATURAL
KILLER CELL
2
6
Inhibitory Receptors
Turns off cell killing
Binds to Antibodies
Activates cell death (ADCC)
Activation Receptors
Triggers release of killing
mechanism
3
Release of Chemokines
Attracts killer T-Cells
4
Release of Cytokines
Induces apoptosis
5
Release of Perforin & Granzyme
Direct cell killing & targeted killing
A Unique NK Cell: Activated Natural Killer (The aNKTM Cell)
1
Adhesion & Targeting Receptors
Targets and binds to tumor cell
& tumor cell matrix, and viral
infected cells
7
ACTIVATED NATURAL
KILLER CELL
aNKTM
2
6
Inhibitory Receptors
Turns off cell killing
Binds to Antibodies
Activates cell death (ADCC)
Activation Receptors
Triggers release of killing
mechanism
3
Release of Chemokines
Attracts killer T-Cells
4
Release of Cytokines
Induces apoptosis
5
Release of Perforin & Granzyme
Direct cell killing & targeted killing
MOA: Broad range of killing attributed to lack of KIR
and persistence of the activated state of aNK
NK cells from blood express KIR which - upon interaction with HLA on target cells inhibit NK cell activation. NK-92 does not express this inhibitory receptor
A Unique NK Cell: Activated Natural Killer (aNK) Cell
A Living Drug Delivered in a Blood Bag
aNK
aNK
aNK
Tumor
Target
Tumor
Target
Tumor
Filled With
Granzyme
STAGE 1
STAGE 2
STAGE 3
Adhesion
Activation
Apoptosis
Synapse
Connection
Perforin &
Granzyme
Delivery
Cell Death
Activated NK Clinically Validated: Phase I
Advanced metastatic disease refractory to chemo,
biologics, cytokines, radiation, and surgery
Nearly half the patients received multiple dosing
regimens (up to 6 months)
More Than 40 Patients
No DLTs; only 1 “grade 4 SAE”
(hypoglycemia likely related to
tumor lysis)
Promising activity against different cancer types,
including acute myelogenous leukemia (AML),
lymphoma (NHL, HL), melanoma, renal cell
cancer (RCC), and lung cancers (SCLC, NSCLC)
RUSH UNIVERSITY
MEDICAL CENTER
Phase I Study Results:
Good efficacy against relapsed hematological malignancies
• Complete remission in one Hodgkin’s lymphoma patient
• Partial response in one diffuse large B cell lymphoma
patient
Study nearing completion
• Stable disease in one Hodgkin’s lymphoma patient and one
CLL patient
• Activity seen in Hodgkin’s, Diffuse Large B-Cell Lymphoma,
CLL w/Richter’s transformation, and Myeloma
PATIENT
Excellent safety and tolerability
• Only two patients have experienced infusion-related events
Complete remission
4+ years after receiving aNK
treatment.
• No significant adverse events reported
38
NK 92: THE Universal Killer Cell
NK CELL
CANCER CELL
Tumor Synapse:
Tumor Antigen Targeting
taNK: Mechanism of Action
Tumor Targeted Killing
Known & Unknown
Tumor Antigens
(Neo-Epitopes)
TUMOR
CELL
10 16
Antibody
Library
Tumor Targeted
Antibody
taNK
Tumor Targeted
Antibody
TM
Tumor Targeted
Antibody
Tumor Targeted
Antibody
taNK: Mechanism of Action
Tumor Targeted Killing
Known & Unknown
Tumor Antigens
(Neo-Epitopes)
TUMOR
CELL
10 16
10 16
Antibody
Library
Tumor Targeted
Antibody
Heavy & Light Chain
Antibody Library
taNK
TM
Tumor Targeted
Antibody
Tumor Targeted
Antibody
taNK: Mechanism of Action
Tumor Targeted Killing
Known & Unknown
Tumor Antigens
(Neo-Epitopes)
TUMOR
CELL
10 16
Antibody
Library
taNK
10 16
Tumor Targeted
Antibody
TM
Tumor Targeted
Antibody
Heavy & Light Chain
Antibody Library
Tumor Targeted
Antibody
Tumor Antigen Targeting
CD33.taNK in AML
Primary AML
Memorial Sloan-Kettering
Cancer Center
CD33.taNK
IDENTIFYING EACH PATIENT’S UNIQUE
CANCER ANTIGEN BY NEXT GENERATION
GENOMIC SEQUENCING
IMMUNE
EFFECTOR
CELL
Immune Synapse
A DANCE OF PROTEINS
CANCER
CELL
CONFIDENTIAL
Delivering Living Drugs in a Blood Bag
Targeted and Serial Killing of Her2+ Cancer Cells
Schoenfeld et al. Mol Therapy, in press
Precision Medicine:
Adoptive
Immunotherapy
retargeted
Delivering
Targeted Living with
Drugs
in a BloodNK-92
Bag
cells
Quality control
Expansion
Working Cell Bank
Tumor Targeted
Antibody
Master Cell Bank
Tumor Targeted
Antibody
aNK
taNK
TM
Tumor Targeted
Antibody
Irradiation
Tumor Targeted
Antibody
Transfusion
IDENTIFYING EACH PATIENT’S UNIQUE
CANCER ANTIGEN BY NEXT GENERATION
GENOMIC SEQUENCING
IMMUNE
EFFECTOR
CELL
Immune Synapse
A DANCE OF PROTEINS
CANCER
CELL
CONFIDENTIAL
Super Computing, Machine Learning
Cancer Knowledge Action Network
The Global Cooperative:
Cancer Knowledge Action Network
Genomics England
NANTHEALTH APPOINTED BY
GENOMICS ENGLAND TO
DELIVER CLINICAL GENOMIC
INTERPRETATION AND
REPORTING CAPABILITIES TO
SUPPORT 100K GENOMES
PROJECT
Secure, Sophisticated NantHealth and
NantOmics UK Based Technology Empowers
Clinical Genomic Research to Happen in Realtime
London, UK – 3 June, 2015 - NantHealth, a high
speed secure cloud-based information technology
provider combining science and big data to
transform healthcare, today announces its
appointment by Genomics England to deliver
the clinical interpretation and reporting of sequenced
genomes for the much anticipated and
coveted 100K Genomes Project.
UNIVERSITY HOSPITAL
SOUTHAMPTON NHS
FOUNDATION TRUST (UHS) AND
NANTHEALTH PARTNER TO
DELIVER PRECISION MEDICINE
FOR CANCER PATIENTS
NantHealth and UHS to jointly deliver genomic and
transcriptomic sequencing platform and analytics
capabilities, incorporating NantHealth’s intelligent
clinical operating system (cOS) to transform
cancer care coordination
London AND Southampton, UK 3 JUNE, 2015 –
University Hospital Southampton NHS Foundation
Trust (UHS) and NantHealth today announced a
strategic partnership with the aim of delivering and
transforming cancer services using the most advanced
molecular genomic and proteomic diagnostics,
treatment decision support and unique IT integration
capabilities for better informed precision treatment
selection and care coordination.
Cancer: The Path To The Cure
Analysis
Quantitative Real Time Genomic Monitoring Of
Cancer is Now a Reality
52
Thank You
Patrick Soon-Shiong, MD
Email: [email protected]
Antibody Killing (ADCC)
NK
CD-16
Herceptin
Tumor
Mechanism of Action: haNKTM (ADCC)
Antibody Killing
TUMOR CELL
Her2 Antigen
}
ADCC
Herceptin Antibody
High Affinity
CD-16 Receptor
haNKTM
Antibody Killing (ADCC)