#ongc15

International Growth Strategies: Europe

Chair:Claire Skentelbery - CEBR

PanellistsMark Craighead - Redx Pharma

Keith Martin - AptitopeLeslie Galloway - EMIG

Expansion in Europe through research collaboration and grants

Mark CraigheadDirector Business Development and Alliance Management

3

o One of the largest UK Biotechs• Public listing on London’s Alternative Investment Market (AIM) in March

2015• 180 scientific staff• Focused upon novel small molecule chemistry and supporting biology• Subsidiaries in cancer, immunology and infectious disease

o Championing a new R&D model• Highly versatile “Discovery-Engine” geared towards clinical differentiation• Dynamic commercialisation via strategic alliances, co-developments and

exclusive licensing• Driven by Science, Expertise and Capacity

4

5

• Always looking for opportunities to collaborate at very early stages in our key target areas: immuno-oncology; gram negative infection (for example)• Work with academics; small biotechs and others

• In addition keen on working with larger partners to help progress key assets (AstraZeneca)

• We will identify strategic partners as each project reaches its later stages; either globally or specific regions of world (depending upon project and partner focus)

6

• As with all companies Redx have a range of discussions on-going which must remain confidential

• I am not going to mention or allude to any of these• I shall focus talk on those collaborations/ endeavours

which I am at liberty to discuss

7

Public Consortium with 28 partners:• Uppsala University – managing entity• 11 academic/institute/hospital

organizations• 5 non-profit partners • 12 SMEs

EFPIA: • GlaxoSmithKline (Coordinator) • Sanofi (Co-coordinator)• AstraZeneca • Basilea

Red markers correspond to the geographic location of the public consortium

8

Mechanisms• Public partners• Private partners

(GSK/Sanofi)

Hit-to-Lead

Lead-to-Candidate

Candidate-to-Phase 1

Phase 1 clinical trial

4 hit-to-leadProgrammes running in parallel

2 lead-to-candidateprogrammes running in parallel

Programmesfrom open calls

Programmesfrom open calls

ENABLE ENGINEMedicinal chemistry,

Microbiology, ADME etc.

9

• Chemistry:• Funding for in-house medicinal chem/ project management• 5 FTEs of external medicinal chem • Computational chemistry (external and internal)

• Microbiology:• MIC (including FQ resistance) • FoR• Creation and sequencing of resistant strains

• DMPK• Suite of assays including stability etc

• Ion channel; enzymatic testing; crystallography; compound logistics

10

• Input into project meetings from EFPIA members• Invaluable knowledge of area and of issues with specific classes of

compound• Guidance on which experimental paradigms to employ (e.g. genotoxicity)

• Support in terms of materials:• When reviewing chemical plans it became apparent that GSK had access

to large quantities of relevant intermediates from their previous work in the field

• It was quickly determined that access to these intermediates would allow the project to progress much more rapidly towards producing final compounds

• In addition they provided scope for the generation of new compounds which had previously not been considered

• Transfer of material was carried out rapidly and intermediates are already being utilised to make new compounds

11

Position Paper:• We propose the creation of a specific fund dedicated to

small and medium biopharmas developing innovative antibacterial products.

• We propose stronger market incentives to increase the Return on Investment for products tackling antimicrobial resistance

• We propose to strengthen the already existing actions of the European Medicines Agency (EMA) to accelerate and simplify regulatory pathways

12

• Interact with a range of companies across Europe who are focussed upon AMR

• Potential for joint applications for funding• Plus one-to-one discussions about working together on

specific projects

13

• Secretary Claire Skentelbery• Building partnerships- funding hub• Routinely send out calls covering new initiatives (H2020);

help create working groups• Driving force behind creation of ENABLE

14

• Redx attempt to engage with European partners in range of ways; stretching from large consortia; through groups of like-minded companies; down to one-to-one partnerships

• Rewards (financial, but also enhanced networks etc) far outweigh costs

• But there are costs; you must invest time on investigating options and then more time when building consortia etc

15

Disease-Modifying Immunotherapies for Autoimmune and Allergic diseases

International Growth Strategies: EuropeGenesis, December 2015

Apitope is developing highly specific disease-modifying immunotherapies to treat life threatening autoimmune diseases

• Abnormal immune response can cause chronic and life threatening conditions e.g. MS, Graves’ disease, uveitis, type 1 diabetes, IBD

• Current therapies do not reinstate tolerance and instead treat symptoms or globally suppress immune system with potential for side effects including increased risk of infections and cancer/immune diseases

• Ideal therapeutic: will re-instate normal immune balance / tolerance avoid global immune suppression treat the underlying cause of the disease

16

Apitope in Summary

• Established leader in discovery and development of antigen specific immunotherapeutic peptides, Apitopes®, focused on autoimmune disease Apitopes® = Antigen Processing Independent epiTOPES located in Belgium and UK experienced management team with strong scientific and commercial track record

• Proprietary Apitope ® discovery platform delivers therapies into development across a broad range of high value autoimmune disorders very high selectivity in modifying only the malfunctioning part of immune system minimal side effects due to high specificity safe and well tolerated in clinical trials; no treatment related SAEs to date scalable manufacturing – chemical process, readily synthesized with low cost of goods strong portfolio of IP: Platform to 2022; Peptides composition of matter to 2027 – 2034

• Extensive clinical and development portfolio of product candidates 3 in clinical/preclinical development phase in attractive end markets 4 in late discovery phase grant funding for Graves’ disease and uveitis programmes

• Validation through partners on specific assets: Merck Serono, FP7

• Opportunity for significant revenues in ultra orphan indication and targeted clinical programme Modest funding of Factor VIII programme through development to commercialisation with

potential peak sales of $1 billion

17

Status of Product Pipeline

18

Project Indication Commerci-alisation

Discovery PreclinicalDevelop-

ment

Phase IFiM/PoP

in patients

Phase II Market SizeUS$

Estimated Approval

Date

ATX-MS-1467

Multiple Sclerosis

9.7 - 13.1B

ATX-MS2 Multiple Sclerosis

ATX-MS3 Multiple Sclerosis

ATX-F8-117

Factor VIII inhibition

3.7 B 2020

ATX-GD-59 Hyper-thyroidism(Graves’ disease)

640 – 800 M* 2024

ATX-UV1 Uveitis

PartnerTBC

100 – 350 M* 2026

ATX-UV2 Uveitis

*no premium priced products available

2019

2017

2016/17

2016

Consistent pre-clinical data across disease areas: clinical findings positive

Programme Suppression of Immune

Response to Antigen

Suppression of Disease in Relevant

Animal Model

Suppression of Clinically Relevant Marker in Patients

Multiple SclerosisATX-MS-1467

~60%>90% inhibition of EAE both prophylactic and therapeutic dosing

78% reduction in new Gd lesions by MRI in Phase I

FVIII IntoleranceATX-F8-117

~70%>90% inhibition of neutralising anti-FVIII antibody formation

Graves’DiseaseATX-GD-459

~65%86% inhibition of anti-TSHR IgG antibodyformation

UveitisATX-UV-xxx In progress

Apitope History & Expansion in Europe

Date Comments2002 Company founded in Bristol2002-2006 Angel investor, (£1M) Wyvern & Wellcome Trust (£1M) funding

2006 Approval for First in Man study of ATX-1467 for MS

2007 Completed first clinical trial on time and budget

2008 Series A €10M led by Vesalius Biocapital & LRM; Parent created in Belgium

2008 Fast Forward (venture arm of US MS Society) commits up to $1M

2009 Merck Serono Licence Agreement €150M + milestones in addition to industry standard royalties

2012 IWT (Flemish Govt.) €1.2M grant: Graves’ disease and uveitis discovery

2013 Positive efficacy data from second ATX-1467 clinical trial in MS reported

2013 FP7 (European Commission Framework 7) €6M grant: Graves’ disease development

2014 ATX-1467 Phase II clinical trial initiated by Merck Serono

2015 Series B financing €12 million led by Wales Life Sciences Fund (Arthurian); relocated UK HQ to Wales

20

Apitope Corporate Structure

21

Apitope International NVCorporate HQ

Discovery CentreLocated in HasseltIP held in Belgium

Apitope Technology (Bristol) Ltd.Wholly owned subsidiary

Development Centre Located in Chepstow, WalesProvides R&D services to NV

Apitope’s HQ in Hasselt, Flanders

22

Apitope’s Expansion in Europe

• Series A financing closed October 2008

• Apitope International NV established in Flanders Q1, 2009

– Initial base in UHasselt while BioVille completed

– Collaboration agreement with UHasselt

– Scientists recruited

• Apitope receive 2 IWT grants to support diagnostic research in 2009

• Flanders team switch to therapeutic discovery Q3, 2010

• All discovery activity located in Flanders November 2012

• Apitope receive grant from IWT to support discovery research in 2012

• FP7 grant awarded in 2013

23

Support in Flanders for Apitope

• Supportive investors: Vesalius and LRM

• LRM guided us through setting company up in Flanders

• IWT grants received

• FiT support with e.g. trade missions (e.g. Japan in 2012)

• Flemish & Belgian government minister support

• Biotech incubator with grow on space

• Continued expansion of BioVille growing with resident companies

• UHasselt support with facilities and equipment

24

Support in Flanders for Apitope

• People• Social security rebates for scientists• Favourable corporation tax for IP derived income

25

Summary

• Apitope is the leader in developing disease-modifying immunotherapies for treating life threating autoimmune diseases that is differentiated from other players

• Proprietary Apitope® discovery platform applicable to autoimmune (our focus) and allergic disorders (opportunity for broad partnership)

• Strong clinical and development portfolio of product candidates

• Validated with big pharma partners and large grants

• Experienced management team with strong scientific and commercial track record

• Significant opportunity - funding through to launch ultra orphan indication with high potential sales in relatively short time frame

26

ABPI EMIG BIA

EMIG Statistics

• 250+ Member companies & organisations

• Combined UK turnover of c. £4.0 billion

• Employ c. 20,000 people in the UK

• 90% Members – EMIG only

• EMIG represents 40%-50% of branded volume*

*(Ref: IMS BPI 2013)

Membership Profile

• 80% – Alexion, Alliance, Almirall, EUSA

• 10% – AMCo, Astellas, Gilead, Takeda, Teva

• 10% – Aegerion, Kowa, United Therapeutics, Vertex

EMIG – ecosystem…

MedTech• South East Health Technologies Alliance

Patient charities• Cancer52, Myeloma UK, National Voices, AKU Society

Research Policy• Society of Biology, The AMS, AMRC, UUK

Technology Transfer Organisations• Cambridge Enterprise, MRC Technology

Universities/research institutes/AHSNs• de Montfort, Imperial, ICR, King’s, Manchester, Oxford, Plymouth, QMUL, 

Southampton, UCL

EU Confederation of Pharmaceutical Entrepreneurs (EUCOPE)

• World class universities and science base• Financial environment• Strong regulatory environment• NHS• NICE• NIHR• HRA• Reference price state• Medical research charities – AMRC Members spend £1.5bn 

pa on medical research

UK Strengths

1. Reference pricing

2. International influence of NICE

UK Strengths

UK - Reference Price Market

Ref: Map BioPharma

42 Major Global Pharma Markets

UK - Reference Price Market

55% ‐ UK

Ref: Map BioPharma

• Countries informally refer to NICE:– Australia, Canada, France, Ireland, Italy, Nordics, Spain, Czech Republic and Poland

• Almost all countries will use a NICE ‘No’ to negotiate 

NICE – International Influence

If the UK could offer companies:

–Greater speed to market– Strong reference price

–Uptake 

NICE – International Influence