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Amplify McCauley 2018 06 v3

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Raymond McCauley

on 25 July 2018

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Transcript of Amplify McCauley 2018 06 v3

ARTIFICIAL
INTELLIGENCE
Some things it is good for
Some things it is
not
"Cat Pictures"
Complexity,
When fed Big Data,
Pattern Analysis,
Classification,
Some
Diagnostics

Opening the Black Box
De-skilling
Judgement, Big Picture
Big Brother
Big Sister
Downside of too much data?
Copyright 2018, Raymond McCauley. All Rights Reserved.

Find me on
and
Bone Marrow Transplants
Human Organs-on-a-Chip
drug testing
personalized medicine
microfluidics
lung on a chip image
courtesy Harvard Wyss Institute
doi.org/10.1161/01.cir.0000032876.55215.10
3D Printed Hearts?
stem cell-derived
heart tissue grafts
(& pancreas grafts)
First we will see
(Redneck Genetic Engineering)
CAR-T
Chimeric
Antigen
Receptor
T-Cell
Therapy
A type of adoptive cell transfer (ACT)
Collect patients’ own immune cells
Program disease recognition regions
Kymriah
Kymriah (tisagenlecleucel) from Novartis
Targets CD19 protein, on cancerous B cells
First FDA approved CAR-T, 30 Aug 2017
Treats acute lymphoblastic leukemia (ALL)
first gene therapy in US
first FDA approved CAR-T
first personalized drug?
cons:
$475K a dose, complicated process, cytokine storm
pros:
"wonder drug" - about half in remission after 12 months
{
HOW TO PRONOUNCE
Kim

Kardashian
Ma
riah

Carey
+
Source: @abbynac
Yescarta
axicabtagene ciloleucel
large-B-cell lymphomas
approved 18 Oct 2017
Kymriah
tisagenlecleucel
acute lymphoblastic leukemia
approved 30 Aug 2017
JCAR017, PLAT-0x
axicabtagene
NHL, ALL
in trials
Amgen, Celegene, Bellicum Pharma, Cellectis,
Johnson & Johnson, Juno, Kite/Gilead, Novartis, Pfizer, Unum Therapeutics
AGTC, Audentes, Avalanche Biotech, Biomarin, Biogen Idec, Celladon, Dimension Thera, GSK, Noavartis, Shire, Spark Thera, uniQure, Voyager
Crispr Thera, Editas, Intellia, Sangamo,
More CAR-T
Gene Therapy
Gene Editing
What Happens Next in CAR-T
Selected Companies
First (official) gene-therapy in body
At UCSF Beniof, 44 year-old Brian Madeux
Hunter's Syndrome (missing enzyme in carbohydrate metabolism)
Most die before teens
Replaces 2-3x weekly enzyme transfusions $100Ks/year
one delivery virus + one gene + 2 ZFPs
developed by Sangamo Therapeutics
Adapted from "AP Exclusive: US scientists try 1st gene editing in the body",
AP News
, 15 Nov 2017
frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues and brain and thinking problems.
Hunter Syndrome Symptoms
“I’ve been waiting for this my whole life, something that can potentially cure me.”
Nov 2017
Alzheimer's
Autism
Cerebral Palsy
Huntington's
Parkinson's
Stroke
Traumatic Brain Injury
Alopecia
Baldness
Burn
Cosmetic
Incision Recovery
Wound Healing
Facelift
Skin Resurfacing
Macular Degeneration, Cataracts
Deafness
Breast Augmentation
Breast Reconstruction
Kidney Regeneration
Liver Regeneration
Pancreas Regeneration
Intestine Regeneration
Heart Attack Repair
Heart Valve Replacement
Heart Regeneration
Bladder Regeneration
Genital Replacement
Infertility
Arthritis
Joint Injury Repair
Cancer Innate Immunity
HIV Treatment
Lupus
Multiple Sclerosis
Copyright 2016, Raymond McCauley, All Rights Reserved
Adapted from Paul Knopfler, Stem Cells, An Insider's Guide
Back Pain
Spinal Cord Regeneration
Stem Cells = Reprogramming Medicine
Where
does
this
lead?
CRISPR/Cas9
is a Swiss Army Knife for
Genes
and regulatory regions
Knock-out
Knock-in
Repair
Edit
cheap
highly targeted
improvable
they work,
everywhere
Drag and Drop
Genetic Engineering
“Is curing patients a sustainable business model?”
"But as more people were cured and there were
fewer infected individuals to spread the disease
, sales began to languish."
Example
Gilead's Hepatitis C suite:
Sovaldi, Harvoni, Epclusa, & Vosevi
$12.5 B
$14.8 B
$9.1 B
$3.5B
2015
2016
2017
2018
(projection)
The potential to deliver “one shot cures” is one of the most attractive aspects of gene therapy, genetically engineered cell therapy, and gene editing.

...a very different outlook with regard to recurring revenue versus chronic therapies...it could represent a challenge for genome medicine developers looking for sustained cash flow.
from “The Genome Revolution,” April 10, 2018, by Goldman Sachs Analyst Salveen Richter
- Salveen Richter
- source: "Goldman Sachs shares its top genome stock...," CNBC, April 11, 2018
- source: Eric Sagonowsky,
Fierce Pharma
, Feb 7, 2018
Competition from AbbVie's Mavyret
+
“Is curing patients a sustainable business model?”
Solution 1:
Address large markets

Hemophilia is a $9-10 B WW market
(hemophilia A, B), growing at ~6-7% annually.

Solution 2:
Address disorders with stable or high incidence
CVD, cancer, spinal muscular atrophy

Solution 3:
Constant innovation and portfolio expansion
Especially "diseases of aging
"

- Salveen Richter
- source: "Goldman Sachs shares its top genome stock...," CNBC, April 11, 2018
“Is curing patients a sustainable business model?”
"
"
RPA Use Cases
Dashboards / Visibilty of Metrics
Documentation of Business Processes
Manufacturing
Predictive maintenance
Cleaning optimization
Continuous Process Verification
Emissions level compliance
Energy optimization
Predictive Overall Equip. Effectiveness (OEE)
Quality Control
Anomaly detection
Batch optimization
Business process testing
IT
Data entry and migration
Data aggregation
Data visualization
Systems integration
Rapid application development
Cognitive capabilities
Pattern recognition,
Language processing
Finance / Sales
Contract processing
Invoice processing
Revenue realization
Banking & finance transactions
CRM Updating
End-to-end customer service
Chatbots
Advanced (& Customer Focused)
Personalized Product Design
Tools for customer communication
Customer journey mapping
Deep Learning /
Machine Learning
RPA
Robotic
Process
Automation
Cognitive Services
The AI Umbrella
Natural Language
Processing (NLP)
Optical Character
Recognition (OCR)
Digital
Assistants
"Open the pod bay doors, Hal"
"Playing
The Doors
on Spotify"
Automated
Scripts
Learning
Bots
Multidimensional
Analysis
Pattern
Recognition
Clustering &
Classification
Contextual
Understanding
Source: National Human Genome Research Institute, Exponential Biosciences,
Aug 2017
lei de Moore
+
2001
=
+
+
2018
=
Applications for DNA Sequencing
Pharmacogenomics
Bacterial Identification
Cancer Tumor Sequencing
Non-Invasive Prenatal Testing
Reprogramming Life
CRISPR
CAR-T
SCNT
programmable scissors for DNA
reprogramming immunity
reprogramming cells
Clustered Regularly Interspaced
Short Palindromic Repeats
Chimeric Antigen Receptor
T-Cell Therapy
Somatic Cell
Nuclear Transfer
RNAi
mute button for DNA
RNA
interference
life-changing
&
industry crushing
These acronyms are
23andMe and Apple
enter drug research business
"crowd-sourced clinical trials"
Apple ResearchKit
- Asthma
- Parkinson's Disease
- Breast Cancer
- Diabetes
- Cardiovascular
Enrolled 7400+ people in 24 hours.
Previous largest study was 1700.
Virtual Clinical Trials
See "Industry embraces virtual trial platforms"
by Elie Dolgin,
27 April 2018
,
in
Nature Reviews Drug Discovery

Site-less / decentralized trials
Home-based data collection
Science37 (Novartis-backed) to launch 10 trials in 3 years
Recruits participants on Facebook and Google Adwords
iPhones for data collection & telemedicine doc visits
Raymond McCauley
@raymondmccauley +1-650-776-4561
Raymond McCauley
biochemistry
biophysics
electrical eng.
computer science
bioinformatics
nanotechnology
Exponential Biosciences
past:
advisor,
consultant,
investor
Creative Commons
Attribution-NonCommercial
4.0 International
Digital Biology:
Hacking DNA for Fun & Profit

copyright 2018, Raymond McCauley. All Rights Reserved.
Investment Syndicate
Projects in new biotechnology sectors
Educational tech for science & engineering
Raymond McCauley - Current Work
Advisor & Investor
Various Media Projects
&
Exponential Biosciences
opthamalogy
radiology
{
Let's talk about
robotics
deep learning

other innovations
pricing:
voluntary results-based pricing, refund if poor response
regulatory:
FDA approved after Phase II, but requires
on-going 10 year patient registry (longest ever)
Robotic
Process
Automation
GHCQ, Cheltenham
GHCQ
http://rockhealth.com/tag/wearables/
Makes vaccines using mRNA from diseases
"Vaccinated with information"
Gates Foundation invests $57M
"Cellular scissors chop up HIV virus"
Salk Institute
Nature Communications "Use of the CRISPR/​Cas9 system as an intracellular defense against HIV-1 infection in human cells", Liao et al
23andMe and Apple
enter drug research business
"crowd-sourced clinical trials"
Apple ResearchKit
- Asthma
- Parkinson's Disease
- Breast Cancer
- Diabetes
- Cardiovascular
Enrolled 7400+ people in 24 hours.
Previous largest study was 1700.
People who never got:
cancer
cardiovascular disease
neurological conditions
Q: Secret to live a long time?
A: Pick good parents!
Implants
Biosensing
and
Command & Control
Biosensing implants in development
blood sugar
blood chemistry
temperature, blood pressure, ECG
heart attack, stroke early warning
Longevity
Squaring the
Survival Curve
Limit at 120, for a while
Overpopulation? No
Proposal: Longevity Lab
Cell
Repair
Technologies
Accidental death
by 192
on average
Pensions & Advanced Health Accounts
It Varies, by Disease & Country
Hans Rosling's
Gapminder
Life Expectancy +29.2 years

Deaths in ages 0-5
1900: 30.4%
2000: 1.9%
Sanitation
Water
Access to
Antibiotics
Death Be Not Proud, Part 1
What We
Die From
Beyond 120?
Death is not a Democrat
I intend to live forever. So far, so good. ~Steven Wright
Life Expectancy +25

Deaths in ages 85-110
2000: ~50%
2030: ~10%
Death Be Not Proud, Part 2
Genome Project Dividend
Worldwide Infectious Disease
Extend Healthspan
cancer
cardiovascular disease
neurological conditions
Autoimmune, Affluence
Health Surveillance
Alzheimer's
Autism
Cerebral Palsy
Huntington's
Parkinson's
Stroke
Traumatic Brain Injury
Alopecia
Baldness
Burn
Cosmetic
Incision Recovery
Wound Healing
Facelift
Skin Resurfacing
Macular Degeneration, Cataracts
Deafness
Breast Augmentation
Breast Reconstruction
Kidney Regeneration
Liver Regeneration
Pancreas Regeneration
Intestine Regeneration
Heart Attack Repair
Heart Valve Replacement
Heart Regeneration
Bladder Regeneration
Genital Replacement
Infertility
Arthritis
Joint Injury Repair
Cancer Innate Immunity
HIV Treatment
Lupus
Multiple Sclerosis
Copyright 2016, Raymond McCauley, All Rights Reserved
Adapted from Paul Knopfler, Stem Cells, An Insider's Guide
Back Pain
Spinal Cord Regeneration
Genetic engineering
Stem cell therapy
Melanoma repair
DNA cross-checking
DNA repair
DNA
Cryonic recovery
Cell reprogramming
Cryonics for
Organ Replacement
Organ Preservation Alliance
DNA
Nanobots
Stem
Cell Tx
Quantified Self
Biosensors
Jane Doe
Female, 36, Non-smoker, BMI=19
Scenario 2: Deny Coverage
Chilling effect on life-saving genetic testing
Scenario 1: Ignore Genetic Tests
Alzheimers, Familial Cancer High Risk, ...
Personal Genetic Testing
Breaks Insurance
Patient's finding long-term care issues
5X more likely to buy long-term policy
- Dr. Green, Brigham and Women's Hospital, Personal Communication
Legal backlash
Oregon, Vermont - ban genetics use in life insurance
California, Texas, New York, US - next?
25% of test refusers: fear
life insurance discrimination
But BRCA1-positive
~60% breast cancer risk
versus ~12% general risk
Scenario 3: Be the Solution
Genetic Test,
BUT
Hold Premiums Steady
Encourage clients to screen, take action
Preventive measures = Risk drops 87% to 5%
Genetic Testing
and
Insurance
"DNA methylation-based biomarkers, often referred to
as 'epigenetic age' or 'epigenetic clock', are robust
estimators of chronological age of an individual..."
Life Epigenetics, Inc. & "DNA Age"
Bad News for Insurance
Regulation to restrict use of
genetic testing for inborn traits
to set premiums or deny coverage.
Good News for Insurance
genetic testing for acquired traits

People and Nations
Get Richer
Work Longer
More Education Time
Hyperexperience
Financial Behaviors Change
Underestimate Savings Need
Health Care Costs Increase
Active Retirements
Pensions Recalculated
Inheritance Decrease
the Longevity Dividend
+ 3.0 months / year
+ 2.5 months / year
Radical Biotechnology
& Fintech
Old Institutions Break
Insurance
Pensions
Retirement
Social Security
people aged 50+ equal
a global market nearly the size of China
Longevity Escape Velocity
current progress towards
}
demographics shift
Ray Kurzweil prediction: +1 year / year by 2029
- 19 April 2016, "Reinvent Yourself: The Playboy Interview with Ray Kurzweil"
Longevity
The New Biology
"Slash" Technologies
Disrupting Industries
“Is curing patients a sustainable business model?”
Maybe not, for traditional pharma companies...
cost to bring a
drug to market
2003
USD
$1.04B
~10 years
~10% success rate
2014
USD
$2.87B
~8 years
11.8% success rate
source: DeMasi, Tufts Center for the Study of Drug Development, 2014
Drivers
increased clinical trial complexity
larger clinical trial sizes
higher cost of medical sector inputs
focus on chronic diseases
new health technology assessment info
comparison drug testing
post-approval R&D
Now
Next
a new kind of
Pharma Deal
Collgard Biopharmaceuticals
licensed compound halofuginone (
HT-100
)
to
Halo / Akashi Therapeutics
for
$1M
Duchenne
Muscular Dystrophy
(DMD)
Meet the Halo board of directors...
The Seckler
Family
the Wicka
Family
DIY Drug Development
Orphan Drug status in US
Thumbs up from EU's Treat-NMD
Ongoing clinical trial, July 2013
$500K from MDA
“We are ready to be the ones who get to make the decision of go or no go on this one." - Thomas Wicka
+
=
venture philanthropy
precision medicine
customized
patient trust & participation
2013
=
2007
=
2015
=
+
2001
=
+
+
2018
2022
=
=
=
Source: National Human Genome Research Institute, Exponential Biosciences,
Aug 2017
In the era of the
$1000 Genome
and racing toward the
$100 Genome
cheap genomes
cancer systems biology
+
=
simple blood tests for cancer
The End of
Mammograms
Colonoscopies
&
?
Explosion of
consumer genomics
250+ companies
Ancestry
Athletic
Child talent
Matchmaking
Surreptitious
Non-legal paternity
Legal paternity
Nutrigenomics
Family
Carrier
Health testing
Microbiome
Pets
Food
?
?
?
?
Amniocentesis
Non-Invasive
Prenatal Testing
versus
simulated photo, courtesy Natera
Liquid Biposies
image courtesy of
MIT Technology Review
Pharmacogenomics
Traditional Treatment
Personalized Treatment
+
Adapted from Genesis Genome
Reprogramming
Medicine
microorganisms = factories
synthetic biology
industrial biology
industrial chemicals - food - agriculture textiles - biofuels - medical research
or
DNA = blueprints
new factories = exponential
& portable
sustainability
price & supply chain disruption
Digital Agriculture
nutrigenomics
farm robotics
biomimicry
crop de-extinction
soil microbiomes
livestock genomics
water remediation
radical polyculture
bioculture
sensing (vision)
aquaculture
heterotrophic algae
bioenergy
data-intensive farming
pharming / manufacture
food security
genetic engineering
tissue engineering
animal-free protein
food tracking
supply chain automation
hyperspectral imaging
GMOs
digital labels
Digital
Agriculture
microirrigation
Ag biotech tracking map for World Bank, 2017
Copyright Raymond McCauley
exoproteins
cellular agriculture
environmental reclamation
*
*
*
*
*
Cellular Agriculture
positives
fewer environmental impacts
safer, purer product
more consistent supply
no harm to animals
real world examples
meat with healthier fats
milk without lactose
eggs without cholesterol
rhino horn with no extinction
negatives
the "ick" factor
adapted from New Harvest
* not necessarily genetic engineering
Cellular Agriculture
Mark Post
Maastricht University, Technical University Eindhoven, Singularity University
& New Food
Make it up in
Soybeans
?
World
growing exponentially
but not fast enough.
Nations are getting richer,
people want meat,
soy & aquaculture can't keep up,
beef gets expensive.
World Protein Production
especially in
Brazil
(beef) &
Asia
(chickens and pigs) &
Africa

growing exponentially
But Not Fast Enough
Nations are getting richer
People want more protein
China
= 2 X
USA
Total meat consumption
Most used in China as livestock feed
Make it up in
Fishing
?
Farmed Fish production passes Wild-Catch
Ocean fisheries hit capacity in 1990s
Land Use per gram of Beef
= 8 X Pork
= 13 X Chicken
in 6 graphs
Protein
Crisis
The Great Demographics Shift
Population over 60
1900 9%
2000 20%
2020 25%
2050 >35%
World population, more developed regions
World Population Aging 1950-2050,
United Nations
http://www.un.org/esa/population/publications/worldageing19502050/pdf/81chapteriii.pdf
Accelerates with new health tech
Concentrates wealth
Affects immigration policy
*
Longevity
The Last 100 Years
has seen an unprecedented increase in human survival and lifespan...
But can this trend continue?
BREAKS
and Pensions
Applications for DNA Sequencing
Pharmacogenomics
Bacterial Identification
Cancer Tumor Sequencing
Non-Invasive Prenatal Testing
Digital Biology; Reading & Writing DNA
Life Sciences / Imaging / Big Data / AI / Automation/ Sensors / etc.
Manufacturing, Energy, Agriculture, Medicine
Epigenetics Test
Biological Age Prediction
Detects smoking and alcohol use
Huge Impact on Life Insurance and Pension Underwriting
"Cultured Foods"
Plant-based foods
versus
Pros
Cons
environmental impact
animal-cruelty free
regulation? labeling?
scale
Different nutrient profile
= Good or bad for you?
market perception
NEW HARVEST 2018
cellular agriculture & cell cultured products
MIT Media Lab
Cambridge, Massachusetts
July 20 & 21, 2018
new-harvest.org
Cellular Agriculture
Ask some
hard questions
Taste
Cooking and prep differences
{
www.fredsense.com
portable, fast, easy, accurate biosensors
programming
bacteria
to monitor
water quality
industrial biology
selected companies
source: calvinschmidt.info
More Human Embryos Edited by CRIPSR
Zika
& gene drives
rapidly push
new DNA through
whole population
in the wild
Human
Infertility
Prenatal Genetic Dx
Mitochondrial Therapy
Germ-Line Therapy
Enhancement
- Disease Risk
+ Intelligence
+ Longevity
NOW
NEXT
genetic
engineering
24 Aug 2017
Human Embryos Edited by CRIPSR - HIV immunity?
April 2016
in United States, previously in China
to correct heart disease (MYBPC3 cardiac myopathy)
MSTN
LRP5
APP
CCR5
PCSK9
FUT2
SLC30A8
Lean muscles
Extra-strong bones
Alzheimer’s-resistant/immune
HIV-resistant/immune
Lower coronary risk
Stomach flu resistant
Type 2 Diabetes
Genes to Knock Out
adapted from George Church, private communication
Behavioral and Mental Traits
MAOA gene & aggression
last to implement
poorly understood
Therapeutics,
then
Enhancement
Gene Expression
"gene doping"
EPO, red blood cell production
Myostatin, muscle growth inhibition
VEGF, blood vessel production
IGF-1, targeted muscle mass increase
redneck
genetic
engineering
Expresión genética
"dopaje genético"
EPO, producción de hematíes
Miostatina, inhibición del crecimiento muscular
VEGF, producción de vasos sanguíneos
IGF-1, incremento de masa muscular orientada
Locus of Control:
Individuals, Parents, Doctors, Legislators
Widening the Economic Gap
Different Nations & Societies
= Diverse Approaches
Ethics, Laws and Policies
Overcoming
Fear of Other / Fear of Change / Every SciFi Movie Ever
Carbon Capture
Feasible?

A$800/ton >> A$125/ton
Suck C02 out of air
Make carbon neutral fuel
7 June 2018
Ultimate Use of
Biotechnology?
Why not use it now,
on Earth, to combat
global warming
&
ocean acidification
?
Industrial Prototype
Biological Prototype
Raymond McCauley, @raymondmccauley, +1-650-776-4561
Who we are
How we survive
How long we live
What we become
Where is our place in the universe
How we survive
How long we live
What we become
Where is our place
in the universe
Who we are
Raymond McCauley +1-650-776-4561
desktop bioproduction lab
$1699
reprogram
microbes
Rise of the
Biotech
Garage
Inventor
bioprinter project
OpenPCR
$599 DNA Copy Machine
+
Cow-Free
Milk & Cheese
Boston
Paris
San Diego
Seattle
Oakland
Portland
Manchester UK
Biologigaragen
Biospace
Victoria, Canada
Copenhagen
Switzerland
Brooklyn
Sao Paolo
San Francisco
Shenzhen
Tokyo
Bio
Garage
Baltimore
Syn
Bio
Brasil
Indie.bio, 479 Jessie Street, San Francisco, CA
sf.indiebio.co
Indie.bio, San Francisco
Counter Culture Labs, Oakland
Berkeley Biolabs, Berkeley
Janssen Labs + QB3, 953 & UCSF
Bay Area Biohackers
& Small Startup Labs
as New Models
Techshop
indie.bio
Hacker Dojo
Noisebridge
DARE2mansion
Hackteria
FabLab / HTGAA
Target CoLab
Janssen Labs
Silicon Valley
International
Corporate
National
Startup Chile
Hackerspaces
Garage Labs
PCR Machine
Gel Electrophoresis
Fridge & Freezer
Water & Bleach

Biosafety Cabinet
Scale & pH Meter
Photospectrometer
basic equipment set
bicycles & woodworking optional
Laptop & Wifi
Biohazard Disposal
Centrifuge
Pipettors
Autoclave
Multimeter
3D Printer
getting fancy
A hackerspace for biotech

First biohacker lab in the world

Committed to making biotech
accessible, affordable, and open to everyone

Located in Sunnyvale, California

501c3 all-volunteer community lab, supported by monthly memberships and classes
most innovative
education company
in the world
Top
100
#4
for Innovation
and Accelerators
Full transcript