1. Game changing disease modification of asthma
Anti-inflammatory and immuno-modulatory molecules derived from mTB bacteria
Biotech & Money
February 2016
Andrew Lightfoot, CEO

2. 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:
(Kola, Nat. Rev. DD, 2004)
Attrition %
De-risked safety
Proven efficacy
Appropriate high value markets
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’
Bacteria represent a potentially de-risked platform for drug discovery & development
Sledgehammer approach
Bacteria: subtlety & finesse

3. 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
Obihara, 2006
Lighter-Fisher, 2012
Meta analysis: Reduction in asthma across the 3 major markets *
von Mutius, 2000
People exposed to TB show statistically significant reduction of allergy and asthma in three large studies
867 Japanese school children (Shirakawa, 1997)
2,414 neonates in the MANCAS study (Lineham, 2007)
5,000 US adolescents under 20 (Lighter-Fisher, 2012)
In 2002 Professor Clive Page at Kings College, London and Professor Anthony Coates at St Georges Hospital started collaborating on the phenomenon that TB bacteria were shown to manipulate the human immune system, with investment from a leading biotech entrepreneur, Gunnar Walstam
A selection of proteins were identified from TB bacteria that showed biological activity in a range of indications
Chaperonin 60.1 identified as the potential causative agent for immune modulation
Patents filed and fundamental research begun
Peptinnovate founded in 2011 with further investment from Gunnar Walstam and Christopher Smith (Cazenove)
mTB has evolved a single agent that can switch off allergy/asthma in man 3

4. TB modulate human immune system
mTB secreted defence proteins are extremely potent anti-inflammatory agents
TB modulate human immune system
TB infection
Human response to TB
TB anti-inflammatory protein (Characterised in 2002) TB
Granuloma: Human cells surround TB
TB secrete anti-inflammatory proteins
In vivo characterisation of mTB proteins
(Riffo-Vasquez, 2004, 2012)
Mycobacterium tuberculosis infection in the lung causes an immune response and granuloma formation
mTB secretes potent anti-inflammatory / immuno-modulatory proteins to dampen down hosts immune response
Title: Three separate human studies have shown statistically significant reduction of asthma and allergy in TB carriers 3

5. 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

6. 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.

7. Exploiting active proteins from TB: Discovery of lead asset PIN201104
Peptinnovate’s platform technology
Design and profile of Drug candidates
Biologically active protein
2011
2014
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 PIN discovered and characterised by phenotypic drug discovery
PIN currently in late preclinical development
First drug candidate molecule identified (PIN201104)
Superior activity and safety in multiple disease models massive TI 7

8. Industry view: The next frontier in asthma treatment Asthma disease modification
2 major unmet needs (Barnes 2012)
Better treatment / management of severe asthma (eosinophilia and neutrophilia)
‘Curative’ therapies for mild asthma that do not result in the return of symptoms when the treatment is stopped
Disease modification of Asthma:
Down grade or symptom free
Severe
Asthma
Mild
Remission: Symptom free
PIN201104
Inflammation
Time
Allergic diseases are currently on the increase with existing approaches to treatment largely symptomatic
Prevention better than cure – existing studies show early treatment of children with atopic dermatitis reduces the incidence of asthma
Increasingly there is appetite in this area – Circassia raised £200m LSE IPO (2014)
Peptinnovate is working on this program with a major pharma company
PIN will be progressed through manufacture and toxicology in 2015 8

9. House Dust Mite re-challenge asthma model: Potential model of asthma disease modification
PIN (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 21 34 41 48
Group 1 Acute d34 PIN201104/FF +4h BAL
Group 2 Chronic d34 PIN201104/FF (d41) BAL
Group 3 Disease d34 PIN (d48) BAL
modifying FF/IL-5mab/Montelukast post 2nd HDM 9

10. PIN201104 reduces cellular influx in animal model of asthma disease modification
A single dose of PIN reduces chronic inflammation (7day not shown), but also accomplishes disease modification
PIN 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 10

11. Ovalbumin immunisation period 24h post RE-challenge Day 28
PIN prevents eosinophil recruitment to the lung following ova challenge and re-challenge (i.v.)
PIN dosed
PIN dosed
BAL 1 5 10
Ovalbumin immunisation period
Day 1, 5 & 10
Ova challenge period
Day 15-17
Ova re-challenge
BAL Eosinophils
24h post RE-challenge Day 28
PIN dosed i.v.:
during immunisation GREEN (3 doses) or
prior to challenge BLUE (3 doses) at 20 ng/Kg, 11

12. PIN201104 prevents neutrophil transmigration into tissues
Acute inflammation (neutrophil recruitment) induced in the mouse lung with bacterial lipopolysaccharide (LPS)
PIN (i.n.) prevents neutrophil numbers in BAL at low concentration (A)
PIN reduces migration of neutrophils in the lung (tissue histology) (B)
A Effects of PIN in the LPS challenged mouse
B Lung histology showing reduction of inflammatory cells (BV = blood vessel)
Bronchoalveolar lavage
(BAL) neutrophils
sham
LPS 2
0.2
0.02
0.002
100
LPS + PIN (ng/Kg) *
LPS inflammation
LPS / PIN201104
Airway
Airway BV BV
Neutrophils
(dark staining)
Clear tissue
No inflammation (0.2ng/Kg) 12

13. PIN201104 shows potential to disease modify asthma
PIN 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
initiation of asthma
Acute
inflammation
Chronic inflammation
Worsening of disease
Vaccine-like prevention
Reduction of inflammation
Reduction of eosinophils/neutrophils
Disease modification
    
   
Steroids (mg/kg)
PIN (ng/kg) 13

14. PIN201104: Potential to be extremely safe
No effects in human cells (in vitro) up to million times the effective concentration
PIN 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 14

15. Peptinnovate progression plans
Completion of preclinical development by 3Q 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
2017
2018
2019
All on track
£2m £6m £8m
Phase 2a
(Asthma Differentiating study)
PIN201104
Respiratory
Preclinical development
Phase 1 safety HV
Phase 2b
Asthma field study Start
Phase 1b LPS challenge
MHRA endorsed
New assets
Supporting biology
Discovery collaborations / new molecules and MOA
Management and General and Administrative activities 15

16. 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

17. 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)
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
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