Transcript Disease modification of asthma

Game changing disease modification of asthma
Anti-inflammatory and immuno-modulatory molecules derived from mTB bacteria
Biotech & Money
February 2016
Andrew Lightfoot, CEO
[email protected]
A new generation of anti-inflammatory medicines
Peptinnovate
De-risking drug development:
Building on Nature’s ingenuity
Major causes of attrition due to safety, efficacy
and commercial reasons

Desirable Drug Development starting points:
De-risked
safety
Proven
efficacy
Appropriate high
value markets
(Kola, Nat. Rev. DD, 2004)
Attrition %

Current gold standards
 Steroids front-line therapies for inflammatory diseases

Anti-TNFa’s have revolutionised the treatment of RA
Peptinnovate’s approach
 Micro-organisms have been manipulating the immune
system for millennia with limited impact on the ‘host’

Sledgehammer approach
Bacteria: subtlety & finesse
Bacteria represent a potentially de-risked platform for drug
discovery & development
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Peptinnovate
People exposed to TB have 75% less
asthma in large long term human studies

Exposure to mTB significantly reduces allergy / asthma in multiple large
published studies in over >263,000 individuals

Up to a 5-fold reduction in asthma/allergy in children aged 6-20 ever showing
symptoms of asthma / allergy when exposed to mTB (meta analysis of literature)
Shirakawa, 1997
Linehan, 2007
Meta analysis: Reduction in asthma across the 3 major markets
von Mutius, 2000
Obihara, 2006
Lighter-Fisher, 2012
Prevalence (000,000)
40
30
20
*
10
0
Normal
USA
TB
*
Normal
TB
Europe
Normal
*
TB
Japan
mTB has evolved a single agent that can switch off allergy/asthma in man
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Peptinnovate
mTB secreted defence proteins are
extremely potent anti-inflammatory agents
TB infection
Human response to TB
TB secrete anti-inflammatory proteins
TB modulate human
immune system
TB anti-inflammatory protein
(Characterised in 2002)
TB
TB
Granuloma: Human cells surround TB
 Mycobacterium tuberculosis infection in the lung causes an
immune response and granuloma formation
In vivo characterisation of
mTB proteins
(Riffo-Vasquez, 2004, 2012)
 mTB secretes potent anti-inflammatory / immuno-modulatory
proteins to dampen down hosts immune response
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Peptinnovate
Company History
 Founded in 2011 by MBO from Helperby Therapeutics
 Andrew Lightfoot founder with Metellus Life Sciences, Zurich
 Raised seed capital to create and progress lead asset to the end of
preclinical development (3Q16)
 IP, including composition of matter patents, 100% owned
 Built an exceptional management team, board and advisors
 Based at Stevenage Bioscience Catalyst
 Raising Series A capital to prove efficacy in man
–
Reasons to believe
–
Future plans
[email protected]
Peptinnovate
Highly experienced team to deliver
Peptinnovate’s goals
Dr Andrew Lightfoot MBA (CEO + Board)
Dr Lightfoot has 20 years’ experience in leading and pioneering discovery initiatives both in large
pharma (GSK) and biotech as well as leading preclinical development projects and managing clinical
trials. Dr Lightfoot plus seed investors formed Peptinnovate in 2011.
Dr Clare Burgess (COO, Development)
Dr Burgess has over 25 years’ pharma and biotech experience, with expertise in clinical project
leadership and toxicology. Dr Burgess has led a number of complex projects including multi-centred
clinical trials for GSK and recently has been COO of an antibiotic clinical stage biotech company.
Dr Nicky Cooper (CSO, Discovery)
Dr Cooper has 25 years’ experience within the pharma industry and has managed inflammation based
projects to Phase I studies. Dr Cooper has been a senior member of successful PDE4 (inflammation)
and AD237 (COPD) out-licensing teams.
Professor Clive Page (Director)
Professor Page is Professor of Pharmacology at King’s College, London and is internationally
recognised for his work on asthma and other inflammatory diseases. Professor Page is a co-founder
of Verona Pharma.
Richard Nagle (Commercial)
Successful entrepreneur with expertise in drug and product development and a co-founder of Wound
Solutions. He has a strong commercial and marketing background, including royalty-based deals and
trade sales of a number of product and device businesses.
Peptinnovate
Exploiting active proteins from TB:
Discovery of lead asset PIN201104
Biologically active protein
Peptinnovate’s platform
technology
Design and profile of
Drug candidates
2014
2011
TB anti-inflammatory protein
Active in models of asthma
Identification of biologically
active domains
Clinical candidate
PIN201104
 mTB protein Cpn60.1 has diverse biological properties
 Candidate molecule PIN201104 discovered and characterised by
phenotypic drug discovery
 PIN201104 currently in late preclinical development
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Peptinnovate
Industry view:
The next frontier in asthma treatment
Asthma disease modification
2 major unmet needs (Barnes 2012)
2) ‘Curative’ therapies for mild asthma that
do not result in the return of symptoms
when the treatment is stopped
Inflammation
1) Better treatment / management of
severe asthma (eosinophilia and
neutrophilia)
Disease modification of Asthma:
Down grade or symptom free
Severe
Asthma
PIN201104
Mild
Asthma
Remission: Symptom free
Time
8
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Peptinnovate
House Dust Mite re-challenge asthma model:
Potential model of asthma disease modification

PIN201104 (i.n.), fluticasone furoate (FF, i.n.) or IL-5mab (i.v.) or Montelukast
(p.o.) dosed once on day 34 - two HDM challenges on D34, D48
HDM: house dust mite
BAL: Bronchoalveolar lavage
HDM challenge
HDM re-challenge
HDM sensitisation Period 1/day 5d/week
Results
next slide
dose
0
9
21
34
41
Group 1 Acute
d34 PIN201104/FF +4h BAL
Group 2 Chronic
d34 PIN201104/FF
Group 3 Disease
modifying
d34 PIN201104
FF/IL-5mab/Montelukast
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48
+7(d41) BAL
+14 (d48) BAL
post 2nd HDM
Peptinnovate
PIN201104 reduces cellular influx in animal
model of asthma disease modification

A single dose of PIN201104 reduces chronic inflammation (7day not shown),
but also accomplishes disease modification

PIN201104 uniquely shows potential disease modifying effect in the house dust
mite assay on both inflammatory cell types: eosinophils and neutrophils

Fluticasone, Montelukast (Singulair) and IL-5 antibody do not show these
effects
Gold standard
compounds not
efficacious
Fluticasone:
$9bn / year 2013
IL-5 Antibody:
FDA approved 2015
Montelukast:
$4bn / year 2012
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Peptinnovate
PIN201104 prevents eosinophil
recruitment to the lung following ova
challenge and re-challenge (i.v.)
PIN201104 dosed
PIN201104 dosed
BAL
1
5
10
Ovalbumin immunisation period
Day 1, 5 & 10
15 16 17
27
Ova challenge period
Day 15-17
Ova re-challenge
BAL Eosinophils
PIN201104 dosed i.v.:
24h post RE-challenge Day 28
during immunisation GREEN
(3 doses) or
prior to challenge BLUE (3
doses) at 20 ng/Kg,
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Peptinnovate
PIN201104 prevents neutrophil
transmigration into tissues
 Acute inflammation (neutrophil recruitment) induced in the mouse lung with
bacterial lipopolysaccharide (LPS)
 PIN201104 (i.n.) prevents neutrophil numbers in BAL at low concentration (A)
Bronchoalveolar lavage
(BAL) neutrophils
 PIN201104 reduces migration of neutrophils in the lung (tissue histology) (B)
A Effects of PIN201104 in the LPS
B Lung histology showing reduction of inflammatory cells
challenged mouse
(BV = blood vessel)
LPS inflammation
100
Airway
*
Airway
BV
*
BV
0
LPS + PIN201104 (ng/Kg)
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LPS / PIN201104
Neutrophils
(dark staining)
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Clear tissue
No inflammation (0.2ng/Kg)
Peptinnovate
PIN201104 shows potential to disease
modify asthma
 PIN201104 outperforms fluticasone, IL-5Ab and Montelukast in the house
dust mite (HDM) model of asthma
 Demonstrating potential disease modification of asthma with long lasting
effects in HDM at 14-days – modification of a second HDM challenge
 Dosing on sensitisation prevents allergic phenotype developing (vaccine-like)
 Effective against both neutrophilia and eosinophilia
Progression of
disease
Therapeutic
intervention
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initiation of
asthma
Vaccine-like
prevention
Acute
inflammation
Chronic
inflammation
Worsening
of disease
Disease
Reduction of
Reduction of
inflammation eosinophils/neutrophils modification
Steroids (mg/kg)




PIN201104 (ng/kg)




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Peptinnovate
PIN201104:
Potential to be extremely safe
 No effects in human cells (in vitro) up to million times the effective
concentration
– PIN201104 added to human PBMCs both in the presence and absence of LPS no effects on inflammatory mediator release (TNFα, IL-1β, IL-8, IL-6, MIP-1α)
– no evidence of reactive oxygen species release from isolated human neutrophils
 No adverse effects in formal toxicity studies
– No effects on clinical signs, body weight, blood & urine parameters (including
neutrophils & eosinophils), organ weight and no findings in macroscopic or
histopathologic examination (including bone marrow smear)
– Mouse: single i.v.
– Rat: GLP 14 days i.v.
– Dog: GLP 14 days i.v. (awaiting histopath.)
– No effects on neurobehavioral or respiratory parameters
 Excellent safety window versus the estimated clinical dose
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Peptinnovate
Peptinnovate progression plans

Completion of preclinical development by 3Q 2016 - no issues to date

A Ph1 safety study supports healthy volunteers and asthma patients

Ph2a study in patients and Ph1b LPS challenge in HV gives initial efficacy read
for eosinophilic and neutrophilic inflammation

Looking for Series A funding of up to £16m
2016
All on track
PIN201104
Respiratory
Preclinical
development
2017
£2m
Phase 1
safety
HV
MHRA endorsed
New assets
Supporting biology
2018
2019
£6m
Phase 2a
(Asthma
Differentiating study)
Phase 1b
LPS
challenge
£8m
Phase 2b
Asthma field study Start
Discovery collaborations / new molecules and MOA
Management and General and Administrative activities
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Peptinnovate
Summary
 Expert management team made up seasoned pharma/biotech
professionals (CEO/CSO/COO/CMO)
 Secure IP position with 100% owned, granted patents unencumbered
by 3rd parties
 Targeting huge unmet medical needs in disease modification of asthma
– potential first in class
 Engaged world renown Key Opinion Leaders and pharma to design the
clinical studies
 Uniquely safe and efficacious asset with supporting preclinical data
from GlaxoSmithKline
 Raising capital to pursue the lead asset through the clinical stages to
M&A / licensing exit
16
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Peptinnovate
Peptinnovate has built a highly experienced &
proven Management Team, Board and Advisors
Board of Directors
Prof Clive Page (Chairman)
Dr Andrew Lightfoot (CEO)
Dr Thierry Plouvier
Mr Richard Nagle
Mr Michael Albisser (CFO)
Peptinnovate Management
Dr Andrew Lightfoot (CEO)
Dr Clare Burgess (COO)
Dr Nicky Cooper (CSO)
Dr Ginny Norris (CMO interim)
Dr Jeannette Watson
Dr Donata Federici-Canova
Scientific Advisors
Prof Clive Page
Prof Paul O’Byrne
Prof Ashley Woodcock
Prof Richard Knowles
Dr Dave Singh
Dr Pietro Ventreska
Technology:
Game Changing
First in class
Disease modifier of asthma
Requires Series A capital to prove efficacy in man
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Peptinnovate