T R A N S L A T I O N A L M I C R O B I O M E A T A G L A N C E

W H A T S H A P E S T H E M O U S E M I C R O B I O M E ?MICROBIOME: DISEASE ASSOCIATIONS

I N V E S T M E N T A R E A S

D R U G E F F I C A C Y

A P P L I C A T I O N S O F G E R M - F R E E M I C E : F M T

Cleaning and sterilization procedures

of materials

Time of last cage bedding change

Housing system/ cage type

Cage density

Feed (type and means of sterilization)

Water source and treatment with chlorine

or acids

Bedding material

Enrichment material (type and availability)

Room temperature and humidity

Air movement and drafts

Light cycle

Number of

Investments

Therapeutic Areas with a Microbiome Link

Microbiome Investment Levels Set for Record 2017Investment Deals by 2010–1H 2017*

H

usb

andry Factors

E

nvir

onmental Facto

rs

$400

$350

$300

$250

$200

$150

$100

$50

$–

30

25

20

15

10

5

0 1999– 2010 2011 2012 2013 2014 2015 2016 2017 2009 YTD

To

tal In

ve

ste

d C

ap

ital ($

M)

Nu

mb

er

of

Inve

stm

en

ts

$31 $16 $20 $47 $11 $180 $237 $245 $194

0

50

100

150

200

250

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Microbiome and mouse or mice

*Includes all completed, disclosed financings regardless of whether investors o rinvested capital were disclosed.

Microbiome in Claims

$400

$350

$300

$250

$200

$150

$100

$50

$–

30

25

20

15

10

5

0 1999– 2010 2011 2012 2013 2014 2015 2016 2017 2009 YTD

To

tal In

ve

ste

d C

ap

ital ($

M)

Nu

mb

er

of

Inve

stm

en

ts

$31 $16 $20 $47 $11 $180 $237 $245 $194

0

50

100

150

200

250

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Microbiome and mouse or mice

*Includes all completed, disclosed financings regardless of whether investors o rinvested capital were disclosed.

Microbiome in Claims

Checkpoint Inhibitors Work Best when You Have the “Right Microbiome”

I N T E L L E C T U A L P R O P E R T YIn 2007 there was one patent published and in 2016 there were 316. This is indicative of growing success despite the challenges in patent law.

• Phenotype transfer—prove causative role of microbiome

• Study host-microbiome interactions

• Use disease-prone microbiota for induction or acceleration of disease models

• �Generate�a�stable,�reliable,�and�controlled�source�of�mice�with�specific�microbiomeMicrobiome patent publishing

grew rapidly over the past decade

and 165% from 2016 to 2017. A

significant�portion�of�those�claims�

were supported by research using

mouse models.

• Key areas of microbiome-based therapeutic development:

Pheromones

Human microorganisms

Personnel

Cancer

Metabolic Disease

Autoimmune Disease

Mental Health

Infectious Disease

Inflammation

The microbiome of the dam/mother

(vertical transmission)

Exchange of microbes between

cages (horizontal

transmission)

Coprophagia

Health standard (list of excluded

SPF agents)

Environmental organisms

Mode of birth

M

icrobiology

Pregnancy

Diseases

Subclinical disorders

and infections

Genetics

Age

Stress

Gender

Activity level

Circadian rhythm

In

tern

al Factors—

Mo

use

Therapeutic treatment

Compound administration

Diet

E

xper

imen

tal &

Veterinary Proced

ures

The number and dollar amount

of microbiome investments

surged in 2014.

Fecal Microbiota Transplantation

(FMT) with non-responder

microbiota

Fecal Microbiota Transplantation (FMT) with responder microbiota

Tumor engraftment

Tumor size in responder-microbiota mice T

um

or

size

T

Ce

lls Immune activation

in responder-microbiota mice

Anti-PD-1 therapy

• 4D Pharma issued U.S Patent #9,839,655 in Dec 2017 demonstrating reduction of tumors in four different murine models

• University of Chicago issued U.S Patent #9,855,302 in Jan 2018 for treating cancer. Mouse models were critical in supporting claims that gut microbe composition can be manipulated for therapeutic effect.

Di-association• Controllable• Host physiology and immunology not normal,

but improved compared to the germ-free state

Complex, partially defined,�or�undefined�microbiota-association

• Normal physiology and immunology expected, but is dependent on the nature and origin of the microbial community

Complex�defined�microbiota-association

• Controllable• Unclear how many and what species are

required to induce normal host physiology and immunology

Mono-association• Controllable• Host physiology and immunology not normal,

but improved compared to the germ-free state

Simplified� microbiota-association

• Controllable• Host physiology and immunology improved

compared to the germ-free and mono/di-associated state, but still not fully normal

Person• 3×1013 cells• 23,000 genes

Microbiome• 4×1013 bacteria• 2×1014 viruses• 4×1012 fungi• Other microorganisms

(archaea, protists)• ~8 million genes in total

Superorganism

Y O U A N D T H E M I C R O B I O M E

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+

• $840M invested in microbiome therapeutics since 2010

• Gastrointestinal (GI)/infectious diseases account for 50% of investments

Germ-Free

1999 2017

Re

lati

ve

In

ve

stm

en

t

GI/Infectious Disease

Cancer/Autoimmunity

Dermatology

CNS

Lear

n m

ore

abou

t Mic

robi

ome:

Dis

ease

Ass

ocia

tions

Sources: Gopalakrishnan et al. Science 2017; Routy et al. Science 2017; Matson et al. Science 2017

Source: Emerging Healthcare: Microbiome Investment Trends. Silicon Valley Bank, 2017Source: The American Academy of Microbiology: Human Microbiome FAQ Source: Foundational Gnotobiotic Concepts taconic.com/gnotobiotics-concepts