1. A Research and Innovation Center
.com
.gov
.org
First assigned domain
names
First telerobotic
surgical system
New drug for
lymphoma R
Computer mouse
Ultrasound for
medical diagnostics
First ARPANET and
internetworking nodes
U.S. Dept. of
Education 2010
technology plan
Treatment for
d rug-resistant malaria
Emmy Awards for
HDTV
and more
Created Siri
(acquired by Apple)
A Research and Innovation Center
© 2016 SRI International 1

2. making people safer, healthier, and
SRI’s Mission:
create world changing solutions
making people safer, healthier, and
more productive
Not-for-profit :
Return on investment is
measured by impact,
not dollars
Multidisciplinary:
Breadth and depth to solve the
hardest problems
Perspective:
Located in the heart of silicon
valley, 100s of partners around
the globe
Science-focused:
Build on technology platforms
to fill gaps in customer needs 2
© 2016 SRI International

3. SRI – Who We Are Founded by Stanford in 1946 2,100 staff members
A world-leading independent R&D organization •
Founded by Stanford in 1946
− Located in heart of Silicon Valley
− More than 10 locations worldwide
− Not-for-profit corporation
− Independent in 1970
Headquarters — Menlo Park, California
2,100 staff members
− More than half with advanced degrees
Consolidated 2015 revenue ~$550M •
Princeton, New Jersey 3
© 2016 SRI International

4. Bridging Basic Research to Commercialization
Easy to describe, very challenging to do!
“Valley of Death”
Universities
and National
Laboratories
Corporations
Basic
Research
Applied
Research
Product
Development
Discovery
Production
© 2012 SRI International
© 2016 SRI International

5. Bridging Basic Research to Commercialization
Easy to describe, very challenging to do !
SRI
Universities
and National
Laboratories
Corporations
Basic
Research
Applied
Research
Product
Development
Discovery
Production
© 2016 SRI International

6. Our legacy of world-changing innovations
.com
.gov
.org
First computer mouse
Created Siri
(acquired by Apple)
First ARPANET and
internetworking nodes
First assigned domain names
First telerobotic
surgical system
Ultrasound for
medical diagnostics
U.S. Dept. of Education 2010
technology plan
New drug for lymphoma
Vision technologies
(HDTV, Color TV, etc.)
Emmy Awards for HDTV
and more
Developed SWOT analysis
1 st Disneyland theme park
© 2016 SRI International

7. Converting government investment to market impact
Products
Scale Up & Licenses
Non-Profit Retain IP
Ventures
SRI Global
Partnerships
© 2016 SRI International

8. SRI Technology Spin-off Ventures
Publicly Traded
Robotics
DNA testing services*
Surgical robotics
Speech recognition
for customer service
Electroadhesion for
materials handling
Innovative robots for
manufacturing/service*
Soft robotics for
Medical rehabilitation
Information Technology
Virtual personal
travel guide
Real-time web video
streaming and
sharing
Artificial intelligence for
web personalization
Intelligent banking
Artificial intelligence for
calendar integration
Iris biometric
identification*
Virtual personal
assistant for smart phones*
Customer service
tools*
Enterprise social
media technology*
Digital TV technologies*
Stray voltage detection
services
Panoramic image
editing software*
Electronic and digital
signature solutions
Technology for K-12 and
higher education
Materials
Bio/Medical
(formerly Rosedale Medical)
Glucose monitoring system
Electroactive polymers*
Digital color printing
applications*
Anti-counterfeiting
systems*
Super-bright LED
light engines*
Drug dispensing system*
Drug discovery
Environmentally friendly
light products*
Metal “print and plate”
manufacturing process
Optical network
components
Disposable hearing aid*
Bed bug detection devices
*Acquired or merged
© 2016 SRI International

9. 100+ industry projects annually•
S/W stabilization for mobile chat - -
- Google
Medical device for continuous
blood pressure measurement
- Omron
Activity monitoring algorithms
- Client private
Automotive lane sensing
- Volvo
Scientific digital imagers
- Perkin-Elmer
Pharmaceutical development
- Roche
Electro-adhesion Floor Cleaner
- Client Private (Japan) •
Mobile Banking assistant
- BBVA (Spain)
Long-range Iris Biometrics
- Client private
Vehicle-to-vehicle communications -
- GM
Dioxin abatement
- Mitsui Heavy Industries (Japan)
Content summarization
- Yahoo
Underwater Mass Spectromete
- Chevron
Educational Products
- Microsoft
And many more …
© 2016 SRI International

10. Key Success Factor = How We Work
5 Disciplines of Innovation enable success 1 2 3 4 5
Important customer or market needs
High value creation
Innovation champions
Innovation teams
Organizational alignment
Top 10 book 10
© 2016 SRI International

11. SRI technology platforms in computing, robotics,
sensors, materials, biomedical science and health.
A.I. & Computer Speech & Vision
Science Technology
Robotics &
Automation
Sensing &
Devices
Energy &
Materials
Biomedical
Science & Health
• Machine
learning
• Virtual Assistants
• Structured
analysis
• Knowledge
representation
• Workflow
automation
• Activity
recognition
• Cyber & security
• Trusted systems
• Data analytics
• Speech
recognition
• Translation
• Language
analytics
• Emotion and
state
• Speaker ID
• Natural language
• Image
processing
• Perception
• Visual search
• Augmented/Virt
• Manipulation
• Mobility
• Actuators
• Automation
systems
• Machine
learning
• Perception
• SLAM
• Micro-robots
• Electro-active
materials
• Multi-spectral
imagers
• Medical devices
• RF, Radars
• Chemical
• Optics and
Lasers
• Molecular/DNA
• Input and
gesture
• Physiological
monitoring
• Custom polymers
• Low cost silicon
• Carbon capture
• Biofuels
• Gas separations
• Water
purification
• Bioinformatics
• Efficient energy
transfer
• Sustainable
materials
• Drug Discovery
• Preclinical Development
• Early Clinical Trials
• Neuroscience
• Infectious Disease
• Oncology
• Biomarkers
• Proteomics
• Glycomics
• Diagnostics
• Circulating Tumor Cells
• Automated
reasoning
• Cyberphysical
systems
ual reality
• Object and
activity
recognition
• Biometrics
• Biomedical Imaging
• Medicinal Chemistry
• HTS/HCS
• Aging Research Initiative
• Computational
imaging
SRI
Technology Platforms
Combine and Customize
Unique Client Solution
© 2016 SRI International

12. Lab to Market Ideation Process
Strategic
Landscape
Customer Need
Statement
Ideation
Workshop
Selection
Identify major
market trends &
the business
context of our
customers
Learn customer
business and
technical challenges
and use cases
Create technical
solution concept,
scope and timeline
Prioritize and
determine phased
implementation
strategy
© 2016 SRI International

13. SRI’s innovation acceleration model
Engage
Ideation Workshop
Identify internal and
external technology /
market baseline. Generate
use case scenarios &
product / service offerings
linked to innovative use of
Execute
Phased Development Program
Rapid & Iterative Lab-to-Market Model
Prototype
Proof of
Concept
Transition
to Client
Discover
SRI technology platforms.
Build short and longer term
roadmaps
Ideation
1 - 3 months
Client Review
SRI Technology Platforms
months
Client Review
Custom Solution
Innovation Programs
Applying SRI’s value creation process to identify, evaluate and transform organizational innovation practices.
Impact
© 2016 SRI International 13

14. Case Study: SRI Lab to Market
2003 to 2008 – DARPA initiates new R&D program called
Cognitive Assistant that Learns and Organizes (CALO).
SRI selected to lead team of 20+ research organizations.
$150M funding over 5 years.
2007 – Several industrial projects with computing and mobile
electronics companies.
SRI hires Dag Kittlaus, former Motorola executive, as an EIR
(entrepreneur-in-residence) to explore market opportunities for
CALO technologies.
2008 – SRI scientist Adam Cheyer joins Dag Kittlaus and Tom
Gruber to found Siri as an SRI spin-off venture. Siri raises $8.5M
series A financing, followed by $15M series B.
Late 2009 – Siri launches in app store
May 2010 – Siri acquired by Apple
Oct 2011 – Siri integrated in iPhone 4s
© 2016 SRI International 14

15. Case Study: SRI Lab to Prototype Strategic Ideation Statement Design
Landscape
Customer Need
Statement
Ideation
Workshop
Concept
Design •
We want to build safer
motorcycles
We want to increase our market
share
We want to be known as
technology leaders
Motorcycle
Fatalities
Automobile
© 2016 SRI International

16. First trials -> less than 7 months after workshop
© 2016 SRI International 16

17. Case Study: SRI Lab to License
Enhancing security and privacy for mobile
devices
Samsung sought a robust biometric experience
that was fast and simple to use. Utilizing SRI’s
Iris On-the Move (IOM™) technology, Samsung
and SRI were able to develop a compact, low-
cost H/W and S/W module that was safe, secure,
and easy-to-use.
Result:
• x smaller
• x lower-cost
• 10x faster
Samsung entered into a license for technology
and continues to work with SRI to develop both
industrial and consumer applications of mobile
IOM™.
© 2016 SRI International 17

18. Biosciences discovery development Basic biomedical research
Drug and diagnostics
discovery
Preclinical and clinical
development
© 2016 SRI International

19. Our Impact on World Health
More than six decades of breakthroughs
Halofantrine
SRI-discovered halofantrine,
marketed as Halfan® by
GlaxoSmithKline and
distributed by the World
Ultrasound
SRI made ultrasound
practical for medical
diagnostics.
Health Organization, has saved
countless lives as a treatment
for drug-resistant malaria.
Pralatrexate
Bexarotene
For treatment of T-cell
lymphoma, the FDA
approved pralatrexate,
co-discovered by SRI and
marketed as Folotyn®
by Allos
SRI discovered Bexarotene,
a retinoid receptor ligand
marketed as Targretin® by
Eisai for treatment of
Telerobotic Surgery
Bioinformatics
SRI technology allows
surgeons to remotely
perform minimally invasive
surgical procedures.
SRI ’ s genomic databases
combine with artificial
intelligence and symbolic
computing techniques to
accelerate research.
cutaneous T-cell lymphoma
© 2016 SRI International

20. Real drugs Halfan® halofantrine Antimalarial GSK Targretin® bexarotene
Anticancer
Eisai
Folotyn®
pralatrexate
Allos
© 2016 SRI International 20

21. SRI Biosciences Pharmaceutical Focus 300 person R&D division•
300 person R&D division
− $50M annual base of gov’t-funded R&D
− $20M annual non-gov’t support
In typical years we team with approx.:
− 10 foundations & other nonprofits
− 20 gov’t agencies
− 30 universities
− 70 companies
© 2016 SRI International 21

22. SRI Biosciences
Our team
© 2016 SRI International 22

23. Millions of Lives Saved
100s of Novel Drugs
$100s of Millions in R&D
Millions of Lives Saved
With Help from Many Friends
© 2016 SRI International 23

24. Basic Research in Disease Mechanisms
Infectious Disease
Cancer
• Tropical & neglected
diseases
• Influenza, TB
• Drug resistance
• Vector biology
• Biodefense •
Akt, survivin, estrogen pathway inhibitors
Low oxygen, ischemia
Angiogenesis
Rare cell technology
Radiobiology research
Tumor glycomics
CNS Disease
Autoimmunity & Inflammation •
Aging
Cognition
• Inflammatory & autoimmune diseases
• Innate responses •
Sleep, circadian rhythms • Adaptive responses: •
Neurodegeneration
Pain
Addiction
Antigen-specific responses,
T cell and B cell functions
© 2016 SRI International

25. From Idea to IND & Beyond
SRI Biosciences
Basic
Research
“Institute”
Drug
Discovery
“Biotech Venture”
Drug
Development
Services
“CRO”
© 2016 SRI International 25

26. PharmaceuticalSciences
SRI Biosciences Capabilities
Wide range of experience
Basic Research
Drug Discovery
Preclinical Development
Biomarkers& Diagnostics
NCE & NBE Therapeutics
PharmaceuticalSciences
CRO Services
HCS & HTS
PK/DM & Predictive ADMET
Proteomics
Medicinal Chemistry
DrugDelivery & Formulations
Systems Biology
Small Molecules
Safety Toxicology
Drug Repurposing
Novel Peptides
ClinicalChemistry
Bioimaging
Polyclonal Antibodies
CMC & QA/QC
Pharmacology
Vaccines
GLP & GMP
Radiolabeling
Project Management
Clinical & Regulatory 26
© 2016 SRI International

27. Integrated Pharmaceutical Discovery & Development
Provides seamless transition from idea through the IND
and into the clinic
SRI Capabilities
© 2016 SRI International

28. Biosimilar Capabilities
Genome Biology 2004,
Volume 6, Issue 1, Article R2
Romero et al. R2.9
H. sapiens Pathway: oxidative ethanol degradation I
alcohol dehydrogenase 2: ADH1B
comment
• BioInformatics/
Computational
Biology
ethanol
NAD
Locations of Mapped Genes:
NADH
aldehyde dehydrogenase 2
NAD NADH
acetaldehyde acetate
acetyl coenzyme-A synthetase: ACAS2
acetyl-CoA
phosphate
coenzyme A
ATP
ADP
reviews
reports
Superclasses: Pathways
Created by: wagg on 16-Sep-2003
Comment:
dehydrogenase. The resulting acetaldehyde passes into the mitochondrial compartment where it is converted to
This ethanol degradation pathway begins with conversion of ethanol to acetaldehyde by cytosolic alcohol
acetate (by mitochondrial aldehyde dehydrogenase). Should acetate be activated to acetyl-CoA within the liver, it
metabolised by extra-hepatic tissues [ Salway ] . Extrahepatic tissues take up acetate where it is converted to
liver mitochondrial matrix. Consequently, acetate leaves the mitochondrial compartment and the hepatocyte to be
would not be oxidized by the Krebs cycle because of the prevailing high ratio of NADH + H / NAD+ within the
Four distinct human ethanol degradation pathways have been described - three oxidative pathways and one
acetyl-CoA [ Yamashita01 ] .
oxidized to acetate for subsequent extra-hepatic activation to acetyl-CoA [ Yamashita01 ] . Oxidative pathways
nonoxidative pathway. All oxidative pathways mediate the oxidation of ethanol to acetaldehye which is then
are differentiated based on the enzyme/mechanism by which ethanol is oxidized to acetaldehyde. The present
pathway utilizes cytoplasmic alcohol dehydrogenase with the other two oxidative pathways utilizing endoplasmic
ethyl esters (FAEEs) as primary end products [ Best03 ] .
known as Cytochrome P450 2E1. The nonoxidative pathway is less well characterized but produces fatty acid
reticulum Microsomal Ethanol Oxidizing System (MEOS) and peroxisomal catalase, respectively. MEOS is also
Oxidative and nonoxidative pathways have been demonstrated in a range of tissues including gastric, pancreatic,
hepatic and lung. Inhibition of oxidative ethanol degradation pathways raises both hepatic and pancreatic FAEE
acetaldehyde have also been demonstrated in the pancreas - the cytochrome P450 2E1 & alcohol dehydrogenase
Pancreatic ethanol metabolism occurs predominantly by the nonoxidative pathway but oxidative routes to
levels demonstrating that oxidative and nonoxidative pathways are alternative metabolically linked pathways.
References
pathways [ Chrostek03 ] .
intake." Front Biosci 8;e PMID:
Best03 : Best CA, Laposata M (2003). "Fatty acid ethyl esters: toxic non-oxidative metabolites of ethanol and markers of ethanol
Chrostek03 : Chrostek L, Jelski W, Szmitkowski M, Puchalski Z (2003). "Alcohol dehydrogenase (ADH) isoenzymes and
aldehyde dehydrogenase (ALDH) activity in the human pancreas." Dig Dis Sci 48(7); PMID:
tissues." Biochim Biophys Acta 1532(1-2); PMID:
Yamashita01 : Yamashita H, Kaneyuki T, Tagawa K (2001). "Production of acetate in the liver and its utilization in peripheral
Salway : Salway, J.G. "Metabolism at a Glance, Second Edition." p.90.
Figure 3 (see legend on next page)
Genome Biology 2004, 6: R2
deposited research
Drug Discovery
& Development
Capabilities
• Fermentation
/Production
Technologies
• OMICS
refereed research
interactions
information
© 2016 SRI International

29. SRI Drug Development Pipeline – Track Record of Success
halofantrine
vidarabine
bexarotene
pralatrexate
tirapazamine
TAS-108
SR13668
Oral Vancomycin
IND • IND • IND • IND • IND • IND • IND • IND
NDA • NDA • NDA • NDA • NDA • NDA • NDA
Oral DTPA
SR16157
SR16388
SR13654
BH-0492
Early Discovery
SRI Drugs available for licensing
© 2016 SRI International

30. Bloomberg Global Innovation Index
© 2016 SRI International

31. Top Global Trends in BioPharma
Pharmacoeconomics / Outcomes
Personalized Medicine
Prevention
Patient Centric
Access AND Affordability
Generics
Chronic Disease
Digital Pharma
Biosimilars •
© 2016 SRI International

32. Innovation Case Study examples
Oral DTPA (agent to counter radiation exposure)
Innovation of Diagnostics and Medical Devices (FastCell)
Continuous Drug Manufacturing process (SynFini) •
© 2016 SRI International 32

33. Case Study: New Drug Formulation for Radiation Exposure
Reformulation of Zn-DTPA into an oral
formulation from an IV medication
Zinc diethylenetriaminepentaacetate (Zn-DTPA) has been
the chemical compound commonly used to treat
radionuclide exposure delivered through an IV. Many
attempts to re-formulate Zn-DTPA into an oral medication
has failed. In 2005, SRI took on the project and was able
to successfully develop and manufacture a novel, oral
formulation of Zn-DTPA that has proven efficacy in
animal studies. SRI identified promising enhancers by
using their “IVtoPO Platform Technology” program to
perform high-throughput solubility and intra-intestinal
permeation screening.
© 2016 SRI International

34. Case Study: FAST cell ™-CTC Technology
Customized Liquid Biopsy
2 x 10 7 cells
scanned in a
minute
FAST CTC
Analysis
HER2 / CEP17
Morphology/
Pathology
Nano-PCR
Peripheral blood from a cancer patient is collected for multiple endpoint analysis ̶
FAST cell ™ locates CTCs, enables precision analysis, pathological review & confirmation of CTCs
– Staining for protein markers, FISH for genomic amplification and translocation
– Sequencing, nano-PCR and expression analysis in development
© 2016 SRI International

35. Proprietary FAST cell ™ Cytometer
Automated Imaging at High Resolution
Scanning laser spot focuses
on top of transparent substrate
FAST – Fiber Array Scanning Technology
FAST
Substrate
Motion
Rotating
Mirror
Light Collector
Fiber Optic Bundle
ADM
Multiplex biomarker imaging
CTC
• Cytokeratin (Red)+
• DAPI (Blue)+
• CD45 (Green)-
WBC
• Cytokeratin (Red)-
• CD45 (Green)+
Collimating, Bandpass, collection
Filters/Lens
Photomultiplier
Tubes (PMT )
Laser speed = 10m sec -1 ~ 1 cm 2 sec -1
F-Theta linearity ~ 0.1%
Spot size ~ 8 µ m
Location accuracy = 40 µ m
Scan Width = 76 mm
© 2016 SRI International

36. Continuous Manufacturing in Pharmaceutical Research
1800s – 1900s
2000s
The Future
Streamlining the small
molecule drug
discovery progress…
…By creating an end to
end automated
chemical synthesis
platform
Synthetic Chemistry – Status Quo
Batch process methodology hasn’t changed in two
centuries
© 2016 SRI International

37. SynFini - Revolutionizing Drug Design/Manufacturing•
Potential Economic Impact −
Save $Bs in drug discovery and development
Reduce time from lab to market
Decrease discovery synthesis time ~80%
Decrease transfer to pilot scale time by ~85% •
Stage of Project −
Received SBT funding
DARPA Make-It •
Four year, multimillion dollar program
Technology and know how proposed by SRI •
Next Steps −
Engage one or more strategic partners
Build industry consortium
© 2016 SRI International
Revolutionizing drug
manufacturing for increased
efficiency and reduced costs.

38. Conclusion Thoughts on Future Innovations in BioPharma•
Pharmacoeconomics / Outcomes −
− Personalized Medicine
− Prevention
− Patient Centric
− Access AND Affordability
− Generics
− Chronic Disease
− Digital Pharma
− Biosimilars
Interface of traditional and emerging disciplines
© 2016 SRI International •

39. working together on important problems to change the world… repeatedly
Ted Ira
Executive Director of Business Development, Global Partnerships
© 2016 SRI International 39