(Sept. 2016)

Author: Dr. Mehregan Movassagh, PhD

“Google’s Activities in Pharmaceuticals & Biotech R&D”

Executive Summary

Google’sR&D:“BeyondThePill”

TherapyTowardsAnIntegrated

“HealthofThings”

“Big-DataAnalyAcs”Could

RevoluAonariestheFutureHealthEcosystem

GoogleandIt’sSubsidiariesAreEngagedInaWideRangeofR&DAcAviAes

•  GoogleXhasanumberof‘graduatedprojects’,butVerilyisalsoundertakinganumberofhighpublicityprojects(Tricorder,GlucosemonitoringCL,Baseline)

•  Verilyhasanumberofcollabora@onsonsurgical&glucosemonitoringtools,electronicimplantsandmonitoringvirtual&digitaltech

•  CalicohasestablishedR&Dcollabora@onswithtopins@tutesonbiology&gene@csof’aging&agerelateddiseases’

•  AnalysesoflargemedicaldatasetswithDEEPMINDcouldprovideopportunityforearlydetec@on&personalisedtreatmentop@ons

•  GoogleGenomics:Analysesoflargesetsofgenomicsdatamayprovidetheopportunitytowardsearlydetec@on&personalisedtreatmentop@ons

•  Big-datamayresultinbeJerstraAficaAonofpaAentstoinformbeOerdesignofclinicalstudies,andpoten@allyfasterdrugdiscovery

•  Supplemen@ngregulatorypackage,couldresul@nginfasterapproval@melines

•  Bigdatasuppor@ngbenefitsofatreatmentop@oninaspecificpa@entgroup,couldsupport“value-basedmedicine”forpayers

•  Integra@ngdatafrommul@plesources,includingmedicaldevices,willprovideanoverallhealthlandscapetowardsamorepersonalisedtherapeuAcsoluAons

•  More“targetedinvestment”forpartnership/M&A•  Googlecouldpoten@allybecomeamajorfuture“industrydisruptor”by

becominga“FullHealthcareCompany”

COMPANYSTRUCTURE

In 2015 Google Became Alphabet, and Thus far Has 7 Major Subsidiaries, Including Calico and Verily Dedicated to Life Sciences

MorededicatedtoLifeSciences :

“GRADUATED”PROJECTS

“Google Glass” Has Already Had a Big Impact On Surgical Training, And Providing Augmented Reality GoogleGlasses:•  Oneoftheini@alsuccessesofGoogleX,leadingtotheforma@onoftheVerily

company•  Hasalreadyhadahugeimpactonremotelearning•  DevicealsohasprovenusefulinvarietyofotherseUngs,including:

•  Augmentedreality,Procedureanalysis,Acutetreatmentse.g.inER,Telemedicine,Improvedvisibility,paAentexperience,Compliance…

1)15-waysGoogleGlasseswilltransformHealthcare:hJp://www.slideshare.net/ExtremeNetworks/15-ways-google-glass-will-transform-healthcare

Liftware’s “Anti-shake Spoon” Is A Now A Marketed Product

AnA-TremorSpoon:•  GoogleXpurchasedLiZLabs,withtheirLi\wareSpoontechnology,in2014•  CuUngedgeelectronicshiddeninthehandlesensesandcancelstremorsby70%(Clinical

studies),inpa@entsincludingthosewithParkinson’sdisease•  Productisalreadyavailabletopurchaseonline(Amazon:$180)

•  VideoofLi\wareAn@-shakeSpoon

Verily’s Announcement On Google’s intention to Deliver a “Tricorder” prototype To Detect Cancer, Led to A Great Media Interest

StarTrekinspiredconceptfora“MedicalTricorder”:

“Cancer finding Wristband” is an area of research by Verily that has attracted great publicity

Cancerfindingwristband:•  Pa@entsswallowapillcontainingmagne@cnanoparAcles,engineeredtograbonto

circula@ngtumorcellsand“lightup”(fluorescentsignal)•  Wristband(designedforconAnuousmonitoring):Toconcentratebeads+adjacent

tumorcellsnearveinandperiodicallyreadoutfluorescentsignal

VideoofCancerfindingWristands

1)hJp://www.techinsider.io/why-googles-tricorder-is-proving-hard-to-build-2016-6

Despite initial hype on Tricorder detecting cancer, its yet to be determined whether this concept will make it into clinical studies

Currentstatusof‘Cancerfindingwristband’:•  Ini@allyaGoogleXproject:

•  In2013,prototypewaspromisedwithin6-months,butyettodeliver!?•  Prototypeyettobetestedinhuman

•  onlytestedinar@ficialhumanlimbs•  Internallyseenbysomeasaprojecttogenerate‘buzz’(vs.arealviableproject?)

•  Nopeerreviewedpublica@onsyet

PendingConcerns:•  ‘Falseposi@ves’areconsideredlikely•  Nanopar@clesmustnotdisruptbloodflow•  Overcomingexcre@on/absorp@onbyliver/deac@va@onofnanopar@cles,

towardscon@nuousmonitoring•  ChallengestogainFDAapprovalforinges@blenanopar@cles(considera@onsfor

“risk:benefit”ra@o)DespiteconcernsVerilyExecuAvesremainupbeat,staAngprojectsare“selectedbecausetheyareinherentlydifficult”

“Glucose Monitoring Contact Lens” Was Also Initially Developed AT GoogleX And Is Being Co-Developed With Alcon

GlucoseMonitoringContactLens:•  Non-invasiveglucosemonitoring,isconsideredoneoftheholygrailsindiabetes•  PartneredwithAlcon(NovarAs)inJuly2014•  Concerns:Historicalstudiesdemonstratedpoorcorrela@onbetweentear&bloodglucose

(pronetotemp&humidityfluctua@ons)•  However,Verilyexpectstoreleaseproductwithinthenext5-10years!VideoofGlucoseMonitoringContactLens•  Alcon/Verilyarealsodeveloping“Auto-focuscontactlens”:movingtowardsclinicalstudies

The “Baseline Study” by Verily, Aims To Identify Early Signs Of Disease & Inform Clinical Studies

StudyAim(announcedJuly20141):•  Aimstodefinecharacteris@csof“healthy”individualsasa‘baseline’

•  thereforehelptoidenAfyearlysignsofdisease(e.g.Cancer/CVD)•  ThiscouldbeusedtoinformenrolmentoftargetedpaAentpopulaAons(w/o

symptoms)towardclinicalstudiesàPersonalizedtreatmentStudyDesign:•  Itwillbegincollec@ngmolecular&geneAcdatafrom175healthyindividualsà

Expandton=~10,000•  Itaimstocollectblood/urinesamples,takeothermeasurementsàini@allymonitor

individualsfor5-years•  BIG-DATAanalysis&comparisonsàA.I.So\waremonitoringàIden@fypaJerns

•  Datatobepublishedincollabora@onwithStanford&DukeUniversity•  AimingtoaJractpartnership/investmentfromPharma

•  Inexchangeforprovidingearlyaccesstodatatowardstreatmentsolu@ons•  “Abilliondollarstudy”

Concerns:•  Pa@entnumberstoosmallandstudytooshorttoiden@fyearlysignalsofdisease

•  Largeinter-personaldifferencesamongstindividuals(e.g.inflamma@on)1)hJp://www.ib@mes.com/baseline-study-new-google-moonshot-con@nues-health-first-trend-a\er-google-lenses-1639440

SELECTEDRELEVANTJOINTVENTURES&COLLABORATIONS

BYGOOGLE

Verily Is Actively Perusing Collaborations & Establishing Joint Ventures With Large Pharma & Biotech Companies

Collaborating Company

Project/ Product Collaboration Details Details

•  Compete in the crowded surgical market on novel imaging methods

•  Help surgeons to identify tumours and edges using fluorescence

•  Company formed in Dec 2015 following collaborations with Ethicon

Continuous glucose monitoring device

•  Dexcom paid Verily up to $100m to shrink size of glucose monitoring device that attaches to abdomen + improve data analysis & transmission

•  New device is expected on the market “within 2-3 years”

New digital technology towards continuous glucose &

HbA1C monitoring

•  Towards improving diabetic health outcomes

•  Collaboration started Sept 2015

Verily & Google Remain Active In Establishing Collaborations & Joint Ventures With Pharma & Biotech

Collaborating Company

Project/ Product Collaboration Details Details

Galvani Bioelectronics

•  Develop electronic implants for the treatments of asthma, diabetes and other chronic conditions

•  Modify electrical signals that pass along nerves

•  Established new company (Aug 2016)

•  55% owned by GSK & 45% by Verily

PHARMA 3D

•  Release PHARMA 3D: Digital tool for learning Health-related info and connecting (Virtual Doctors Lounge & Polling Company with 1.8m HCPs)!

•  Google collaboration together with McKinsey & Wharton1

Convert injectable drugs into oral pills (TNFa, insulins…)

•  Invest towards delivery of large molecules (Abs, Peptides/ proteins, vaccines, RNAi)

•  Supported by Google Venture (InCube Venture)

1)hJp://www.pharma3d.com/#chapter-856435

Calico Has Been Establishing R&D Collaborations With Top Institutes, On Biology and Genetics of Age Related Diseases

CompanyAim(est.2013,restructuredintoAlphabetinOct20151):•  R&DbiotechwiththeaimofcombaAngagingandassociateddiseases

•  Hasac@velysetupaseriousofcollabora@onswithbothacademicins@tutes,biotechandpharmaceu@calcompaniestoenhanceR&DtowardsbeJerunderstandingofgeneAcsandbiologyofagerelateddiseases(includingneuro-degenera@on)

•  InmanyinstancesCalicohasretainingexclusiverightstowardsdevelopingpotenAaltherapies

Calico Has Been Actively Establishing A Broad Range of Collaborations Partnerships With Pharma & Academic Institutes

Collaborating Company

Project/ Product Collaboration Details Details

R&D facility collaboration focusing on aging and age-related diseases (e.g. neuro-degeneration)

•  R&D in age related diseases e.g. neuro-degeneration

•  Initially each company invest $350m

•  Sept 2014

Collaboration to tackle age-related illnesses

•  P7C3 compounds (NAMPT enhancer1), licenced by UT Southwestern, has been shown to help age-related illness in animals

•  New device is expected on the market “within 2-3 years”

MIT & Harvard

Partnership to advanceresearchonage-relateddiseasesandtherapeu@cs

•  In 2015

Calico Has Been Actively Establishing A Broad Range of Collaborations Partnerships With Pharma & Academic Institutes

Collaborating Company

Project/ Product Collaboration Details Details

Towards developing their technology which modulates the Integrated Stress Response (ISR)

•  ISR is activated during stress response and the research has the potential to tackle "age-related cognitive decline"

•  March 2015

Collaboration to tackle age-related illnesses

•  Calico will get an exclusive option on the rights to any discoveries made in collaboration

•  April 2015

AncestaryDNA Conducting research into the genetics of

human lifespan

•  Evaluate data from millions of public family trees and a growing database of over one million genetic samples

•  July 2015

Research into biology of age-related

diseases

•  4-year partnership to better understand the biology of aging and potential therapies for age-related disease

•  March 2015

Calico Has Been Establishing R&D Collaborations With Top Institutes, On Biology and Genetics of Age Related Diseases

CompanyAim(est.2013,restructuredintoAlphabetinOct20151):•  R&DbiotechwiththeaimofcombaAngagingandassociateddiseases

•  Hasac@velysetupaseriousofcollabora@onswithbothacademicins@tutes,biotechandpharmaceu@calcompaniestoenhanceR&DtowardsbeJerunderstandingofgeneAcsandbiologyofagerelateddiseases(includingneuro-degenera@on)

•  InmanyinstancesCalicohasretainingexclusiverightstowardsdevelopingpotenAaltherapies

ItslikelythatCalicowillleveragefuturedataobtainedfromBaselinestudyandu@lizeDeepmindalgorithmtowardsdataanalysistoiden@fypoten@alnoveltherapeu@cs

DEEPMINDLearningAlgorithmsToAnalyzeBig-dataSetsCouldPresentTheBiggestOpportunityForGoogleToProvideNovelTreatmentOpAons

Analyses Of Large Medical Data Sets With Google Deepmind’s Learning Algorithms May Provide The Biggest Opportunity Towards Early Detection & Personalised Treatment Options History&Aim:•  DeepmindTechnologieswasaBri@shA.I.companyfoundedin2010,thatwas

acquiredbyGoogleinJan2014andrenamedasGoogleDeepMind•  IthascreatedaNeuralNetworkthatlearnsinafashionsimilartohumansanda

computerthatmimicshumanshorttermmemory•  Goalisto‘solveintelligence’&buildpowerfullearningalgorithms

•  Learnsfromexperienceusingrawdata•  AlphaGobeathumanGochampionforthefirst@me(2015)

UseintheMedicalResearch:1.  DevelopanAlgorithmtodifferen@atebetweenhealthy&cancerousAssueinH&N

(Collabora@onwithUCL,Aug2016)2.   BlindnessResearch:Analysisofmillionsofbiometriceyescanstodetectearlysigns

ofmaculardegeneraAonleadingtoblindness(Collabora@onwithMoorfieldEyeHospital,July2016)

3.   MedicaldatasharingagreementwithRoyalFreeNHSFoundaAon(1.6mpa@ents/yr)accesstoprivatepa@entdataw/opa@entconsent(April2016)àDevelopmentofStreamsApp(acutekidneyInjury),hasbeensuspendedun@lregisteredasamedicaldevicebyMHRA!!

DEEPMINDLearningAlgorithmsToAnalyzeBig-genomicdataSetsMayPresentGreatOpportunityForGoogleToProvidePersonalizedTreatmentOpAons

Analyses Of Large Sets of Genomics Data May Provide The Opportunity Towards Early Detection & Personalised Treatment Options For Multiple Diseases Aimof‘GoogleGenomics’:•  GooglehascreatedaCloudbasedconsorAumforstorageofgenomicdata

(containinggenomicsdatafrommillionsofhealthyanddiseasedindividuals)•  Costofstorageofgenomicdataoncloud:$25/year

•  Collect,analyze&Comparegenomestohelpfurtherpropermedicalresearch•  Theanalysisofbig-Data(millionofpa@ents,usingDeepmindalgorithm)could

leadtoearlyidenAficaAon&personalizedtreatmentopAons,basedonindividual’sgenomicdata

•  Compe@@onfromAmazon,IBM,Microso\

ANALYSIS&

RECOMMENDATIONS

Big-Data Research & Analysis By Google Has the Potential To Revolutionise The Future Healthcare Ecosystem

•  Big-data from genomic &/or disease patient populations may result in better stratification of patients to inform better design of clinical studies, and potentially quicker drug discovery

InformFutureClinicalstudy

designs

•  Supplementing clinical study data with large data sets, may strengthen regulatory package and potentially resulting in faster approval timelines

PotenAallyFaster

Regulatoryapproval

Big-DataanalyAcs

CouldleadtoNovel&

PersonalisedTreatmentOpAons

•  The analysis of ‘Big genomic data’ from healthy and diseased patients may result in early identification of individuals susceptible to disease and/or personalised treatment options

•  Analysis of a big data from a ‘specific patient population’ (e.g. macular degeneration, acute kidney disease, chronic diseases…) could lead to identification of signals for early detection, personalised treatment or novel treatment options

•  Data from the Baseline study (healthy individuals) may provide tools to identify early signals for chronic diseases1

•  Big data could inform design of Apps &/or development of biomarkers/ signals/ assays towards identification of patients and more rapid future targeted treatment

•  Big data supporting benefits of a treatment option in a specific patient group, could support “value based medicine” by providing health economics data to convince Payers and Healthcare bodies on treatment benefits

EnhancePayerCoverage

1)If the study is conducted in large enough individuals for sufficient duration

Google’s R&D Efforts May Introduce “Beyond The Pill” Therapy Towards A More Integrated “Health Of Things” Solution

“IntegratedPersonalized

Healthlandscape”

WhatDoesItMeanForThePaAents?

More“TargetedInvestment”forpartnership

Ø  Instead of only targeting disease via drug therapy, integrating data from multiple sources, making sense of the overall health landscape towards providing a more personalised therapeutic solution, including medical tools and devices

Ø Better design of clinical studies towards targeted approach/

treatment

Ø  Potentially faster drug development/therapeutic discovery

Ø  Focused investment on companies & therapies which are likely to provide the required solution

Ø  Henceforth rather than “throwing money” at blue sky investment, can target appropriate companies for partnership/ in-license/ collaboration/ acquisition, to provide the necessary solution

LargetechnicalchallengesassociatedwithoralformulaAonofbiologicalmedicines

ChallengestoPhama

Google will remain a predominantly data company and will form collaborations with Biotech Pharmaceutical industry

Google will utilize and expand on its expertise to discover and develop new therapies &drugs

Google will become an All-encompassing healthcare company, supporting patient’s journey

Opportunity for Pharma to form collaborations with Google on data mining & development of novel therapeutic solutions

Google could change the competitive landscape, becoming a potential future competitive threat in multiple TAs, (such as neurodegenerative diseases)

1

2

3

Challenge

Challenge

Challenge

ImpactonPharma

Google could become a major “industry disruptor” by buying a number of biotech & healthcare industries - Hence becoming a “Full Healthcare Company” providing a comprehensive range of healthcare solutions to support patients, from diagnosis up until pharmaceutical delivery

GoogleisnotafraidofbreakingoutofitsclustertobecomeamajorplayerinthePharmaceuAcalindustry.Pharmawillneedtobepreparedforfuturechallenges

Scenarios Will Need To Be Explored On How Google & Other ‘Next Generation Data Companies’ Could Change The Future

Competitive Landscape