A healthcare revolution is emerging driven by advances in genomics, microbiology, and mobile technology. Radically new diagnostics and therapeutics based on a person's DNA, epigenetics, and microbiome will transform medicine over the next decade. However, the enormous amount of complex biological data being generated far outpaces our ability to apply this new knowledge clinically. Both healthcare providers and patients need intuitive apps and algorithms to help interpret genetic and microbial information and develop personalized treatment plans. This unmet need represents a major business opportunity to develop user-friendly big data analytics tools that can simplify decision making and optimize patient care.

1. THE MICROBIOME, GENETICS, BIG DATA AND
HEALTH CARE
Nigel Ten Fleming, PhD
CEO of ADVENTURA CAPITAL SL
SMASHTECH MOBILE WORLD SEMINAR, OCT 9 2014
Nigel Ten Fleming PhD
NIGEL@ADVenturaCapital.com
(34) 696 34 27 84
F: mobile world talk Oct 9 2014 TTT 1

2. Relevant Personal Biography
• Biochemist, on board of pharma companies
• Founder and Chairman of Athena Diagnostics
• First neurogenetic reference laboratory in the US
• Developed algorithms for disease diagnosis and
management, by consensus with neurology KOLs
• Algorithms used by medical students for exams
• Apps would have been more useful for applying new
knowledge to clinical practice
• Sold for $740 million in 2011
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3. ADVentura Capital
• 2013: Co-founded ADVentura with group of international
serial entrepreneurs, Chairman Oliver Rothschild
• Monthly BIOBASH events
• 2013: Closed a $6.3 M LOI for an initiative
• 2014: Closed a $20 M VC investment for preclinical
therapeutic
• 2014: Closing an $11.5 M VC investment for
preclinical therapeutic
• 2015: to raise own fund
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4. Exciting Healthcare Revolution
• A healthcare revolution is emerging, driven by very
powerful forces colliding
• Radically new diagnostics and therapeutics will rule
medicine within a decade
• The effects on patient care will be dramatic
• The new knowledge is very complex
• Healthcare workers need tools to apply this new
knowledge
• Provides a significant business opportunity
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5. Enormous Data sets
• Giant data sets overwhelm healthcare providers
• Data expanding rapidly every year
• Needs Big Data algorithm analytics combined with
intuitive Apps
• This is a data handling problem not a scientific problem
• Genetic and microbiological KOLs will form consensus
data
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6. Enormous Data Sets
HUMAN GENOME PROJECT
25,000 genes
24 chromosomes
39 million variations
5,300 diseases with known molecular basis
3,273 genes with phenotype causing mutation
8,450 updates in 2011
613 new additions 2011
OMIM: http://www.ncbi.nlm.nih.gov/omim
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7. Enormous Data Sets
HUMAN MICROBIOME PROJECT
100 trillion microorganisms live in human body
500-1000 species
40-50 families
Complex ecosystem
250 infectious diseases
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8. Mobile Medical Technology Game Changer
• Technology is changing at an exponential rate (Ray
Kurtweil Google)
• Many believe we are heading towards a new stage of
human evolution, that humans control
• We already Cyborgs with implants and enhanced
facilities (pumps, eyes, ears, prostheses, exocortex)
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9. We are Already Cyborgs
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10. Exponential Rate of Technology Change
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11. Mobile Tech Meets Biology
• Mobile medical technology is colliding with medical
biology
• Electronics + genetics + microbiome = New Medicine
• Frontiers between different disciplines are ripe for hugely
disruptive innovations
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12. A Prediction
In five years, our Smart Phones will all carry:
•Our personal DNA sequence:
all of our genetic information
•Our personal Microbiome:
all of our body’s microbes
•Our Medical Records
•Real time biometric monitoring
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13. The Human Genome Project
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Healthcare
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14. The Human Genome Project
• 2000: A major disruptive event: medicine will never be
the same again
• World’s largest international biological project
• Sequenced human DNA and mapped all human genes
• Mapped 20,500 genes key for health and disease
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15. The Human Genome Project
• Spawned new genetics industry
• US government invested $5.4BN
• Current Value $1 trillion
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16. The 1,000 Genome Project
• 2014 Consortium developing baselines for normal human
genetic variation:
• 39 million single nucleotide polymorphisms
• 1.4 million short insertions and deletions
• 14,000 large deletions
• new variants being found daily
• Need to consider geographic and ancestral genetic
background
• Which variant is a health risks versus being harmless
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17. DNA Sequencing is Super-Fast
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18. DNA Sequencing is Super-Cheap
DNA Sequencing costs dropping rapidly:
•$3 BN 13 years (2000)
•$1,000 24 hours (2014)
•$100 <24 hours (~2015)
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19. What Does your DNA Sequence Look Like?
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20. Genes, Genes, & More Genes
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21. The Knowledge Gap
Medical students generally have little genetic training
In 2007, 112 US and Canadian medicals schools were
assessed for genetic education:
• Only 50% had a stand-alone genetics course
• 80% have under 40 contact hours in genetics
• Most did not teach how to apply genetic information
clinically
Acad Med 2007; 82:441-445
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22. The Knowledge Gap
In 2014, study of 137 Cleveland Clinic physicians found:
• 84% thought genetics is changing clinical practice
• 97% thought better understanding of genetics benefits
patients
• Only 39% felt informed about genetic tests
• But, 36% felt that they could answer patients’
questions
doi:10.1097/GIM.0b013e318228821f
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23. Genetic Information Needs Tools
• DNA Sequence data reveals disease genes
• Alterations to those genes indicates disease
susceptibility and needs medical evaluation
• Genetic information is complex
• Vast amount of data correlation is needed
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24. Genetic Information Needs Tools
For patients and clinicians, genetic data must be translated
into personalized:
• Risk profile
• Algorithm for lifestyle changes
• Treatment options
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25. Genetic Disease Example
Duchenne Muscular Dystrophy (DMD)
•Athena Diagnostics first to offer DMD testing
•Fatal, debilitating neuromuscular disease
•Mutation at Xp21 caused DMD
•Genetic testing confirms clinical diagnosis
•No cure today, but highly sought after for clinical
care
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26. Disease Example
Duchenne Muscular Dystrophy
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27. Disease Algorithms Simplify Decisions
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28. The Epigenome: More Complexity
• Epigenetics is a new branch of the Human Genome
Project
• The Epigenome refers to chemical modifications of DNA
and histones due to environmental, stress, lifestyle
factors that turn on and off genes
• Human Epigenome Pilot Project underway to understand
it further
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29. The Epigenome Alters Genes
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30. DNA + Epigenome Project
• In time, epigenomic and DNA sequences will be
considered together
• Great for more sophisticated diagnosis and treatment
• Much more complex for health professionals
• Opportunity for Big Data Analytics
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31. The Human Microbiome Project
The microbiome is the community of bacteria, fungi, algae
that live in the human body
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32. The Microbiome Project
• Scientific landmark 2007-2014
• In 2014, first dataset of microbes inhabiting the nasal
passages, oral cavity, skin gastrointestinal tract, and
urogenital tract
• Scientists shocked by diversity and numbers of microbes
living in the human body
• Radical paradigm shift:
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33. What is a Microbiome?
• Bacteria are the most populous creatures on our planet
• 500-1000 species in 40-50 families of ancient microbes
• Most cannot be cultured so only known by nucleic acid
fingerprint
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34. What is a Microbiome?
• Microbiome weighs 200 – 1,400 grams
• Bacteria outnumber human cells in body
10:1 (100 trillion bacterial cells)
• Bacterial genes outnumber human genes in body
320:1 (8,000,000 vs 25,000)
• Complex ecological balance of players
• When balance upset, disease pathogens enter
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35. How Does the Microbiome Get There?
• Starts with vaginal culture when baby born
• Reinforced by bacteria in mother’s milk
• Built up by exposure to mother’s microbiome
on skin and body
• Continually interfaces with the environment
• Microbiomes are highly individual and cultural
• Affected by diet, stress, toxins and antibiotics
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36. Changing Gut Microbiome in Newborn
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37. Different Microbiome Composition
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38. What Does the Microbiome Do?
• Considered new human organs
• The second brain
• Produces 80% of serotonin for human brain
• The second immune system (75%)
• Produces vitamins for the host
• Protects against allergies
• Ferments unused foods
• Regulates the development of the gut
• Produces hormones to store host’s fat
• Provides a second genome
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39. The Microbiome Protects Against Disease
When ecological balance upset, pathogens enter causing:
• Diabetes
• Rheumatoid arthritis
• Allergies
• Muscular Dystrophy
• Multiple sclerosis
• Fibromyalgia
• Certain cancers
• Obesity
• Irritable bowel syndrome (IBS)
• Depression
• Anxiety
• Autism
• Dental diseases
• (etc) 39

40. Medical Paradigm Shift
Chlorine
In water
Penicillin
Monoclonal
drugs
Salk
vaccine
Small molecule
drugs
Stem cell
drugs
Microbial
Drugs
1910 1940 1950 1960 1986 2010 2014
---------------------------------------------------------------------------------------------
War on pathogens Working with nature
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41. Medical Paradigm Shift
• Since Pasteur, we have been at war with microbes,
considering them the enemy, and adopting a scorched
earth policy
• Antibiotics and chlorine have had unintended negative
consequences
• We now know that most bacteria are good, and we
depend on them for health
• LIVE DRUGS: Probiotics and microbial drugs
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42. Moving on from Antibiotics
• When Alexander Fleming discovered antibiotics, the
pharmaceutical industry took off
• Antibiotics, chlorine and pesticides decimate the natural
human microbiome, disrupting the ecological balance,
and allowing pathogens to dominate
• Single molecules are doomed to fail against an evolving
target
• The antibiotic pipeline is dry
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43. Overuse of Antibiotics
• Antibiotic Superbugs are emerging due to over-use
• Antibiotic resistance is a global crisis
• We over-use antibiotics in meat production (as a
fattener) and in human health.
• US infants before two years of age have had two doses
of antibiotics & all US cesarian sections use antibiotics
• Antibiotics in infancy and C-Sections lead to later health
problems
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44. Rise of Bacteriophages
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45. What Are Phages?
• Phages are very specific viral parasites of bacteria
• Phages never infect human cells
• Phages are ubiquitous, in everything we touch and eat
• Unlike static antibiotic molecules that bacteria learn to
avoid, phages co-evolve with bacterial hosts
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46. Rise of Phages
• Phages were abandoned by pharma when single
molecule antibiotics were discovered
• Russia was denied access to antibiotics and continued
with phage therapy, now the world leader
• France, Russia, Poland have 75 years of safe effective
experience with phage therapy for numerous diseases
• Phage therapy for infectious bacterial diseases is being
re-examined as an alternative to antibiotics
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47. Rise of Phage Drugs
• Phages widely marketed in Russia in pharmacies and on
line by Microgen Pharma
• 1970-90’s: FDA trials for Downs Syndrome, HIV and other
immunodeficiencies
• 2008: Phase I US phage trials for human leg ulcer therapy
proved safe, using cocktail of 8 phages
• Phages are approved by FDA for food microbe
decontamination and for parasite crop control
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48. Microbial Medicines
• Microbes + Genetics = NEW MEDICINE
• Probiotics shown effective for numerous conditions
(dental, irritable bowel, liver disease, cholesterol, etc)
• Clearer understanding of microbiome in health and
disease has opened new perspectives
• All of genetics and all of the microbiome is specific for
the individual
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49. Fecal Biotherapy
“It’s like the beginning of the space
program.”
(Dr. Orenstein, Mayo Clinic)
•Fecal microbota transplantation (FMT) is a microbiome
innoculation from a healthy person to an unhealthy person
•Useful for Clostridium difficile infections (over 100,000
deaths/yr) and an epidemic in seniors
•Promoted as first-line therapy, effective in days, with 90-
100% success rate in antibiotic resistant cases
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50. Fecal Biotherapy
• Fecal biotherapy is in its infancy, and is expected to
expand quickly
• Fecal biotherapy is ideally paired with diagnostics to
monitor the changed gut microbiome
• Currently used for colitis, constipation, irritable bowel
syndrome and some neurological diseases
• Obesity, diabetes, Parkinson’s disease, and rheumatoid
arthritis are now under investigation
• Concentrated bacterial pills are being developed
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51. Confluence of Big Events
Failure of antibiotics
The microbiome
Genome analysis
Personalized, predictive
medicine
Monoclonal antibodies
Stem cells
Phage therapy
Fecal microbiota transplants
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52. The Personalized Healthcare Revolution
• PM is gaining traction in traditional settings, especially in
customized cancer therapies matching the genetics of
the tumour
• All microbiome, probiotic, fecal transplant, and phage
related treatments demand customization to the patient’s
specific condition and genetic or microbial ecosystem
• This involves complex data analysis and diagnostics
• There is a need for sophisticated tools
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53. The Emergence of Patient Empowerment
• PM is patient-centric not provider-centric
• The patient becomes more engaged in the therapeutic
process as medical information is democratized through
apps and web resources
• Patients are more comfortable using web-based Apps
and algorithms for diagnostics and treatment options
• Doc-in-a-Box options are emerging
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54. Implications of the Personalized Healthcare
• PM is predictive not reactive: massive change to
healthcare system
• PM must crunch a lot of data to derive meaningful
personal medical solutions
• Unless efficient tools are developed which are cost-saving,
they will not be implemented
• The delivery format must be very clear and simple and
easy to use for healthcare workers and patients alike
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55. The Need for Big Data Analytics
• Successful healthcare technology solves important real
world problems and saves money
• Complexity of human genetics and the human microbiome
presents significant opportunities for Big Data analytics
and Smart Apps
• Healthcare workers and patients alike urgently need
assistance with applying New Medicine
• Scientific knowledge is not required due to reliance on
expert consensus algorithms
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56. Summary
• Disruptive innovation in healthcare by using
microorganisms and genetics
• Enormous amounts of data need coordinating and
mapping
• The rate of innovation is outpacing clinical use
• Healthcare workers and patients are overwhelmed
• Sophisticated but user-friendly tools that save the
healthcare system money and provide better patient
outcomes will be big winners
THANK YOU
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