Slides on the future of healthcare, entitled "Personalized Medicine: Are we there yet?" form a lecture given by Reid Robison, MD MBA at Brigham Young University in the College of Life Sciences in December 2014. The presentation covers the arrival of genome-guided precision medicine as well as the digital health movement and the shift towards a patient-centric, consumer-driven healthcare system.

1. Personalized Medicine:
Are we there yet?
Lecture at Brigham Young Unversity
December 9, 2014
Reid J. Robison, MD MBA

2. Personalized medicine: Are we here yet?
Right now, we wait for a disease to occur, then we act
The future is predictive, preventive & personalized

3. Precision Medicine
The use of genomic information to identify disease
origins, develop targeted therapies, and improve
outcomes

4. The Sequencing Explosion

5. What is happening in healthcare?
• Cancer moved from a single disease to hundreds of specific
diseases
• Medicine moves from targeting symptoms to targeting
causes
• Healthcare moved from defining diseases by organ system
to defining them by mutations and networks
• Genome sequencing moves to the clinic
• Data science is transforming healthcare

6. Digital health goes mainstream
• Sensors/trackers/devices
• Your car has a dashboard, why don’t you?
• We can do on our cell phone now what we could only dream of
years ago
• Look how fast we have gone from room-sized computers to
powerful smart phones. What will healthcare look like in 20 years?
• Of the 7 billion people on the planet, 6.2 billion have cell phones
(and 91% keep them within 3 feet 24 hours a day)

7. Progress
• Digital Health + Proactive patients = Progress
towards Predictive, Preventive & Personalized medicine

8. From “patient” to “consumer”
From “sickness” to “wellness” based
• PAST
• Doctor-centric
• Doctor is the CEO of your
health
• One size fits all
• Pay for costs &
procedures
• FUTURE
• Patient-centric
• Patient is in charge of his/
her health
• Personalized medicine is
the norm
• Pay for outcomes & value

9. Drug development challenges
• More costly than ever to bring a drug to market
• Pharma is innovating less, buying/licensing instead
(universities & small companies)
• Orphan drug incentives
• Disease advocacy groups are funding development

10. The Tipping Point
• “We are on the tipping point of a whole new game in
how we develop drugs.”
Janet Woodcock, MD
Director, Center for Drug Evaluation and Research, FDA

11. Venture Philanthropy
• >$500 million per year in drug discovery
• CF Foundation gave $75 million to Vertex
• Kaleydeco FDA approved in 2012
• “This is a breakthrough therapy for the cystic fibrosis
community because current therapies only treat the
symptoms of this genetic disease.”
Janet Woodcock, MD
Director, Center for Drug Evaluation and Research, FDA
• Pfizer & CF Foundation in $58 million pact

12. Early signs of Outcome-based payment
• Genzyme offers refund for treatment failure with
kidney cancer drug Mozobil
• Celgene offers partial refund to non-responders of
CML/AML drug Vidaza
• Breakthrough Hepatitis C treatment (Sovaldi) costs
$1000 a pill but is worth it, and payers are paying
• Can cure up to 90% of patients, with fewer
side effects, in a fraction of the time

13. Personalized Medicine: Have we arrived?
• 50% of cancer drugs approved in 2013 target specific deficits
• Beyond targeted therapies:
• Immunotherapy
• Cell therapy
• Gene therapy
• Regenerative medicine
• Antibody drug conjugates

14. Pharmacogenetics: Progress thus far
Blood thinners
• Coumadin: Works well, but narrow “therapeutic window,” risk of
bleeding. Genetic variants in 2C9 and vitamin K genes influence
response, guide dosing
• Plavix: Genetic testing for 2C19 may identify patients who may not
respond
HIV treatment
• Ziagen: before prescribing, doctors now routinely test for a genetic
variant that makes you more likely to have side effects from the drug
• Codeine: certain 2D6 mutations result in no analgesia, others result in
side effects

15. More progress in Pharmacogenomics
Cancer
• Herceptin: Only works for women with HER2+ breast cancer
• Iressa & Tarceva: Work much better for lung cancer with specific genetic variants
• Erbitux & Vecitibix: Don’t work for 40% of colon cancers where the tumors have
specific genetic mutations
Neurology
• Tegretol: Genetic variant (HLA-B*1502) increases risk for Stevens-Johnson
syndrome
Psychiatry
• Celexa: 2C19 affects dosing, ABCB1 gene alters response

16. Still Learning: Beyond Genomics
• “Junk” DNA matters
• Genomes England: 100K genome project
• Human epigenome project
• Human microbiome project
• Human proteome project
• $100 million Obama BRAIN project
Can we make healthcare more predictive & preventive to reverse or
halt disease before it occurs and becomes too hard and costly to
treat?

17. What does the future of healthcare look like?
• The creative realization/consumerization of medicine:
Retail healthcare is front-line
• Decision-making shifts from doctors to patients &
machine intelligence
• Flood of data from sensors/apps
• Price transparency (healthcare now is a menu without
prices)
• Reward for being healthy

18. The Future of Genomic Medicine
• What does the $1,000 genome mean?
• Now cheaper to do the whole genome than certain
single gene tests
• Newborn genome sequencing
• Before long, everyone will get their genome
sequenced and you (& your doctor) will query it at
every important medical event throughout your life

19. Newborn sequencing
“One can imagine a day when every newborn will have
their genome sequenced at birth, and it would become a
part of the electronic health record that could be used
throughout the rest of the child’s life both to think about
better prevention but also to be more alert to early
clinical manifestations of a disease.”
Alan Guttmacher
Director, U.S. National Institute of
Child Health and Human Development

20. Rapid Sequencing in the Newborn ICU
• > 4 million babies are born each year in the U.S.
• 1/20 babies born is admitted to the NICU
• 1/3 of babies admitted to a NICU have genetic
diseases
• Every night in the NICU costs
> $10,000

21. Why sequence newborns?
• > 3,500 single-gene diseases have been characterized
• Traditional genetic testing is only available for some.
And how do you pick the rights test(s)?
• Most genetic tests cost hundreds, even thousands of
dollars each
• At least 500 of these genetic diseases have a known
treatment

22. NICU Sequencing: PKU
• Babies born with the rare genetic disorder
phenylketonuria (PKU) are unable to break down a
certain amino acid, which can lead to brain damage
and seizures
• If found early enough, PKU is easily treated and
children can move on with their lives

23. NICU Sequencing: SPR Deficiency
• Muscle contractions due to mutations in the
sepiapterin reductase gene respond to drugs that are
ineffective against other movement disorders that
may look the same, but have a different genetic
underpinning

24. NICU Sequencing: CMT Disease
• Symptoms of many genetic conditions, such as
Charcot-Marie-Tooth (CMT), sometimes do not
present until adulthood so a genetic test early-on
could help to save the lives of older individuals

25. Newborn sequencing
“Overall, [newborn sequencing] can save time, it can save
lives, and a lot of times, it can save suffering.”
Dr. Stephen Kingsmore
Director, Center for Pediatric Genomic Medicine, Children’s Mercy Hospital

26. Data sharing & open access
• Information is more valuable when
shared
• Metcalfe’s law: the value of a network is
proportional to the square of the number
of connected users of the system (n²)
• Free the Data: Move from genetic
scarcity to genetic abundance
• Secrecy & silos hinder scientific progress

27. Reid J. Robison, MD MBA
reid@tutegenomics.com

28. Photo Credits
• Man and Helix - http://d1435t697bgi2o.cloudfront.net/wp-content/uploads/2013/05/personalized-medicine.
jpg
• 'Your Name Here' pill - http://www.genomicslawreport.com/wp-content/uploads/2011/06/Personalized-
Medicine.jpg
• Blue pills - http://mylocalhealthguide.com/wp-content/uploads/2011/05/Pills-http-www.
sxc.huprofilepawel_231.jpg
• FDA logo - http://www.fda.gov/graphics/FDAlogos1999/graphics/logo1c.gif
• Cystic Fibrosis Foundation logo - http://fightcf.cff.org/gs13/image/national/cystic-fibrosis-foundation-2x.png
• Pfizer logo - http://globalgenes.org/wp-content/uploads/2011/06/pfizer-logo.jpg
• Sovaldi bottle - http://www.gannett-cdn.com/-mm-/b0a6e4c13b58024c480e09bb1b15d165a6b5c0a2/
c=0-86-3000-2336&r=x404&c=534x401/local/-/media/Phoenix/2014/06/19/
pnihepatitisdrug0620secondary.jpg
• DNA in syringe -
http://cdn.static-economist.com/sites/default/files/images/2014/03/blogs/economist-explains/
20140322_stp502.jpg

29. Photo Credits - cont’d
• Stem cells - http://www.bitlifesciences.com/rmsc2014/images/gd/gd_2.jpg
• Organs in petri dishes - http://media4.s-nbcnews.com/j/MSNBC/Components/Photo/_new/120910-hlt-regenerative-medicine-
kb-1250p-4x3.grid-6x2.jpg
• Human Epigenome Project logo - http://www.epigenome.org/images/HEC_title_B.gif
• Newborn in DNA blanket - http://news.recombine.com/wp-content/uploads/2013/09/BabySeq.png
• Newborn in incubator - http://www.nicuhelpinghands.org/wp-content/uploads/2013/02/20110923Gramkow0005.jpg
• PKU test - http://upload.wikimedia.org/wikipedia/commons/1/16/Phenylketonuria_testing.jpg
• Sepiaterin reductase - http://en.wikipedia.org/wiki/Sepiapterin_reductase#mediaviewer/File:Protein_SPR_PDB_1z6z.png
• Charcot-Marie-Tooth disease - http://charcotmarietoothdisease.org/wp-content/uploads/2012/08/marie-charcot-tooth-disease.
jpg
• Purple chromosome - http://www.newautism.com/wp-content/uploads/2010/03/chromosome-300x272.jpg
• Free the Data lock - http://ganis.spno.ca/wp-content/uploads/2012/02/data-unlocked.png