Post on 08-Sep-2018
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