This document discusses several commercial ventures targeting the human microbiome for therapeutic purposes. Traditional small molecule drug development is still a primary strategy, but now targets trillions of microbial organisms rather than a single molecule or pathway. Alternative strategies aim to modulate the microbiome back to a homeostatic state for conditions like ulcerative colitis. Major pharmaceutical companies have also begun investing in microbiome-based therapies for diseases of various severity. Many innovators in this space are small startups receiving venture funding, though persuasive clinical trial data is still lacking and microbiome therapies are likely several years away.

1. In the firstblogpostof thistwo-partseries, we introduced the humanmicrobiome,the increasing
amountof researchfocusedonunderstandingitscomplexity,andhow commercial ventureshave
alreadyriseninan attempttotranslate thisunderstandinginto therapeuticinterventions forawide
varietyof disorders.Tofurtherexplorethe translational side of the microbiome,thispost will discuss
some of the initial commercial ventures beingmade that,if nothingelse, are likelyto evolve the drug-
discoverylandscape definition intoabroaderconceptencompassing“drugs”that could range froman
entire bacterial ecology(inconvenientpillformulation!) toasingle bacteriageneticallyengineeredto
produce beneficial moleculesondemand.
The varietyof strategiestargetingthe microbiome isindicativeof the levelof potentialmanybelieve
researchinthisarea holds. The traditional sense of drugdevelopment, developingsmall molecules(or
one disease,one target),isstillaprimarystrategybeing employed.However,withthe microbiome that
strategynowcomeswiththe twistthat the target ispotentiallythe trillionsof organisms makingupthis
environment, notone molecule.Developmentof these agents,therefore, are focusingmore on howthe
agentfirstinteracts withthe microbiome togenerate desiredchangesthat,theoretically,will inturn
generate adesiredoutcome forthe disease. Alternative strategiesattemptingto modulate the
microbiome backtoa homeostaticstate are alsobeingdeveloped,withaparticularbiastowards GI
conditions suchasulcerative colitisorto combat Clostridiumdifficile infections. Fecal microbiota
transplantation, takingstool samplesfromhealthyindividualsanddonatingthemtopersonsaffected,
may be the original andmost oft discussedexample,withsome evidence supportingitspotentialin
diseasessuchasulcerative colitis,butconflictingevidence alsoexists.
Additional preliminary effortstomodulate the humanmicrobiome are alreadyimpactingthe consumer
healthcare space.Although researchdoesnotyetbroadlysupporttheiruse,probiotictablets,gummies
inthe familiarmode of chewablevitamins,andeveninfantformuladesignedtopromote astable
microbioticecosystem are availablefromboth large andsmall manufacturers.Despite the development
of manymicrobiome-basedtherapeuticsbeingininfancythemselves,some majorpharmaceutical
players(akabigpharma) have alsobegun investinginthe relativelyuntappedpotentialof the
microbiome withthe intentiontotargetdiseasesasmildaslactose intoleranceall the waytolife-
alteringorlife-threateningasvariousimmune disordersandevenvariouscancers. Thesestrategieswill
largelyrelyonthe initiation(orplannedinitiation)of partnerships,some prettyunique;forexample,
AbbVie partneredwithSynlogic,a“syntheticbiotic”makerthatcombinesthe revolutionaryfieldof
syntheticbiologywiththe potential powerof the microbiome togeneticallyengineerbacteriathatcan
produce therapeuticmoleculesasneededtopotentiallytreat diseasessuchasulcerative colitisor
Crohn’sdisease.Othercompaniessuchas Janssen,inadditiontopartnerships, have recentlygone asfar
as creatingan entire research platformwithinthe company itself,sendingastrongsignal of
commitmenttowardsthisarea.
Big pharmainterestaside, the majorityof innovatorsinthisspace are clearly smallerstart-upsandearly-
stage biotechnologycompanies, eagertoobtainfinancingtogettheirflagellasinmotion(see Table 1).
Thisappetite forfundingand affirmation byseveral venture capital firmsisunderscoredby potential
valuationsthatare likelytosurpassone billiondollars,if the currentmarketcapitalization (attime of
writing) of the firstpubliclytradedmicrobiome-focusedcompany, SeresTherapeutics,isanyindication.
However, like otherareasthathave seenearlyventure interest(e.g.,CRISPR,CAR-T),persuasiveclinical
trial data is notyetavailable,makingitdifficulttotrulyevaluate the qualityof the science underlying

2. these investments –fewmicrobiome-basedinterventionshave progressed eventoPhase IIclinical trials,
and giventhe currentfailure rate of investigational drugs,the outlookisdifficult.
Academicresearchwill continue tohelpfuel the marchtowards microbiome-basedinterventions as
well, withone analystwritinghere already atrue believerintheirpotential.She appearstobe ingood
company,withinvestmentsfromthe NationalMicrobiome Instituteandotherfoundations totalingover
$400 millionforresearch andsome of the top researchorganizationsinthe UnitedStatesparticipating
inthiseffort. Hercollaboratingpartnerismore hesitanttopromote a full-scale investmentthesisinthis
area butdoesbelieve the current biotechlandscape isoverdue foratrulyinnovative breakthroughclass
of therapiestomake itto the clinic.Whethernow isthe ideal time toinvestinmicrobiome research can
certainlybe debated;the technologyisstill largelyinitsinfancy, butwithmyriadapproachesbeing
tested,andsignificantunmetneedpresentinmany diseases,strongargumentscanbe made for both
sides.Companiesinvestinginthisareaor formingpartnershipswillbe fallinginwithboth
pharmaceutical giantsandinnovators,joining the likesof GlaxoSmithKline,AbbVie,andJohnson&
Johnson,aswell asa slewof venture capital groups. The payoff forbeing first-to-marketwitha
successful microbiome-basedtherapycouldbe aslarge asthat of blockbusterdrugsof the past,
especiallywhenlaunchingintoanuncrowdedspace.
Although bothanalystsagree microbiome-basedtherapiesare likelyseveral yearsinthe future,the
overgrowthof interestinthistopicby pharmaceutical companiesbothlarge andsmall, ahealthy setof
start-ups,andan exponential increase of academicresearch indicate thatthisareamay notbe a quick
fad.The microbiome isnotlikely tobe a panacea,butthe potential impactsonhumanhealthare
significant,andthiswillbe aninterestingandimportantspace towatch inthe comingyears.
Company Disease Area Intervention Approximate Value /Research
Investment
Link
Vedanta
Biosciences
Immune &
Inflammatory
Diseases
Consortiaof ‘healthy’
bacteriato modulate the
microbiome, likelyoral
$339 M deal withJ&J
$50 Mventure capital infusion
http://www.ved
antabio.com/
Evelo
Biosciences
Oncology Small molecule therapies
designedto activate the
innate immune systemor
disruptingtumors
$35 Mventure capital from
FlagshipVentures
http://evelobio.c
om/#evelo-
biosciences
Moleculera
Labs
Neuropsychiatric
Disorders
Diagnostictestsfor
disorder-linkedmicrobial
dysbiosis
$1.6 M venture capital fromi2E
(2015)
$2.96 M venture capital,
undisclosed(2013)
$1.84 M venture capital from
i2E (2013)
http://www.mol
eculeralabs.com/
Ritter
Pharmaceut
icals
Lactose
Intolerance
Oral small molecule,
galacto-oligosaccharide
$13.7 M marketcap (NASDAQ:
RTTR, July 8, 2016))
http://www.ritte
rpharmaceuticals
.com/

3. Janssen
Human
Microbiome
Institute
Inflammatory
Bowel Disease,
general research
Live microbial
therapeuticproduct
http://www.jans
sen.com/human-
microbiome-
institute
Enterome Crohn’sDisease,
Ulcerative Colitis,
Inflammatory
Bowel Disease
Small molecules+
proprietary screening
tests
€14.5 M SeriesCfundingfrom
multiple investors(including
Seventure,Lundbeckfond
Ventures,andNestleHealth
Sciences,2016)
PartnershipswithTakeda,
Abbvie,andJanssenBiotech
http://www.ente
rome.fr/site/
(Site isinEnglish)
Second
Gemone
IBD, Metabolic
Disease including
ObesityandType
2 Diabetes
Small molecules $42.6 SeriesBfunding(co-ledby
PfizerVenture Investmentsand
Roche Venture Fund,2016)
$59 Mcombinedtotal
investment
http://www.seco
ndgenome.com/
MicroBiome
Therapeutic
s
MetabolicDisease
includingType 2
Diabetes,“Other
Disorders”
includingIBD,UC,
IBS,autoimmune
diseases
Prebiotics(oral small
molecules)
SeekingSeriesBfinancing
(2015)
http://www.mbi
ome.com/
Seres
Therapeutic
s
C. difficile
infections,UC,CD,
IBD
Bacterial ecologyinan
oral capsule
$1.2 B marketcap
(NASDAQ:MCRB, July 8,2016)
http://www.sere
stherapeutics.co
m/
Synlogic Urea cycle
disorder,
phenylketonuria,
metabolic
diseases
Syntheticbiotics –
geneticallyaltered
bacteria
$40 MSeriesB funding(2016)
$30 MSeriesA funding(2013)
http://www.synl
ogictx.com/
Table 1: Selectmicrobiome-focusedorganizationsandinvestmentmilestones.