World-leading Expertise
in Gene and Cell Therapy
Biotech Showcase
January 2015
Disclaimer
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2
Cohort
Dose in this presentation
Administration
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6 months
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2 years (UPDRS)
information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. For
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Mean
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means this document,
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oral presentation,
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written or oral material discussed or distributed during the presentation meetings or any presentation to which this document relates.
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that the
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expressed are fair and reasonable, the contents of this presentation
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BioMedica
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“Company”) or any other person. Accordingly, no representation or warranty, expressed or implied, is made as to the fairness,
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Meancontained
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2
Overview
•
OXB is a unique and sector-leading gene/cell therapy business
Cohort2
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1, n=3
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Max. up to 53%
Max. up to 53%
Max. up to 56%
•
Core technology platform based on proprietary lentiviral vector IP
2, n=3
Original
Mean 28%
Mean 34%
Mean 29%
and gene2xdelivery system
Max. up to 30%
Max. up to 50%
Max. up to 44%
Max. up to 30%
-
2x technology
Enhanced
• 3, n=3Proprietary
based on Mean
5T426%
Antigen/Antibody
in- immunotherapy
•
Strong proprietary portfolio of products
•
Business model
•
•
•
Licence revenues from IP and products
•
Revenues from lentiviral vector manufacture and process development
•
Development of gene/cell therapy products for out-licence or continuing in-house
IP and technical capabilities validated by
•
Lentiviral vector IP – Novartis, GSK
•
Product licences – Sanofi (StarGen™/UshStat®)
•
Process development – Novartis, ImmuneDesign, others
Potential to be cash positive by end-2016
3
Gene therapy & cell therapy
•
Treating disease by altering genes/DNA in patients cells
Cohort2
1, n=3
•
Dose
Administration
•
6 months (UPDRS)
1 year (UPDRS)
1x
Original
Mean 27%
Mean 30%
Mean 29%
Max. up to 30%
up to 50%
Max. up to 44%
Most commonly Lentivirus or Adeno-Associated
virus Max.
(AAV)
based vectors
2x
• 2, n=3Cells modified
in vivoOriginal
or ex vivo
3, n=3•
3 months (UPDRS)
Mean 28%
Max. up to 53%
In vivo 2x
– gene therapy,Enhanced
Lenti or AAV based
vectors
Mean 26%
2 years (UPDRS)
Mean 20%
Max. up to 30%
Mean 34%
Mean 29%
-
-
-
-
Max. up to 53%
Max. up to 56%
Ex vivo – cell therapy (e.g. bone marrow stem cells, T cells), only Lenti based vectors
•
Potential for “one shot” treatment giving long-term or permanent efficacy
•
Explosion of interest in gene and cell therapy in last 2 years, e.g.
•
In vivo – GenSight, Spark Therapeutics, NightstaRx, Avalanche Biotech, Dimension Therapeutics,
Voyager Therapeutics
•
Ex vivo – Novartis, Juno Therapeutics, Kite Pharma, Bluebird Bio,
•
Collaborations – Lilly/Immunocore, GSK/Adaptimmune, Pfizer/Cellectis, Astellas/Harvard Medical
School, Amgen/Kite Pharma
4
Gene therapy & cell therapy
In vivo
Cohort2
Dose
Administration
3 months (UPDRS)
1, n=3
1x
Original
Mean 27%
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
Mean 30%
Mean 29%
Mean 20%
Mean 28%
Mean 34%
Mean 29%
-
Mean 26%
-
-
-
Max. up to 30%
2, n=3
ProSavin® (Parkinson’s disease)
2x
Original
Max. up to 53%
3, n=3
2x
Enhanced
Ex vivo
Max. up to 50%
Max. up to 53%
Max. up to 44%
Max. up to 30%
Max. up to 56%
RetinoStat® (Wet AMD)
1.  OXB produces GMP lentiviral vector encoding CAR
targeting CD19
2.  White blood cells isolated from patients
3.  Vector used to transduce expanded T-cells
4.  The modified T-cells are infused back into the patient
5.  Once inside the patient, the T-cells multiply, ‘hunt’ cancer
cells and destroy them.
5
Gene/cell therapy activity and valuations
Gene therapy overview
Company valuations (US$m)
4500
Gene Editing
4000
3500
Ex vivo
3000
2500
2000
1500
1000
500
AAV
Lenti/yRV
0
PAYLOAD
In vivo
In vivo
GT Companies
Ex vivo
GT Companies
Corrective
wt gene
addition
CAR-T TCR-T
Gene Editing
6
Slide forunique
large image
OXB’s
capabilities
Cell/Vector
engineering
Process
development
Proprietary
development
portfolio
Clinical &
regulatory
expertise
Lentiviral vector advantages
over AAV
•  Larger therapeutic payloads
Lentiviral vector
dominant patent
estate & know-how
Analytical
development
OXB
Solutions
Proprietary
analytics
Manufacturing
capacity
•  Only lentiviral vectors can be used
to permanently genetically modify
dividing cells such as T-cells or
stem cells
7
Oxford BioMedica’s business model
Cohort2
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1, n=3
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
OXB
Solutions
Mean 28%
Mean 34%
Mean 29%
Max. up to 30%
2, n=3
3, n=3
Research
&
2x
Development
2x
Proprietary gene
and cell therapy
pipeline
Original
+
Enhanced
Max. up to 53%
IP Ownership
Max. up to 50%
+
Max. up to 53%
Contracts for
Mean 26%
lentiviral
vector manufacture and
process
development
Max. up to 44%
Max. up to 30%
Key IP makes
OXB
an essential partner
for companies
wanting to
commercialise
lentiviral vector
based products
Max. up to 56%
-
Revenues
Government
funding
Licence fees
Manufacturing and
process development
Milestones
Royalties
8
Novartis
contract
© Oxford BioMedica 2011, all rights reserved
9
Novartis contract (October 2014)
•
Initial contract May 2013 – proved our capabilities
Cohort2
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1, n=3
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Mean 28%
Mean 34%
Mean 29%
-
Mean 26%
-
-
-
•
Non-exclusive licence to OXB’s lentiviral vector platform IP in oncology
Max. up to 30%
2, n=3
•
2x
Original
Process development collaboration
Max. up to 53%
3, n=3
Max. up to 50%
Max. up to 53%
•
Enhanced
Arising 2x
IP owned by OXB
•
NVS have exclusive licence to arising IP in CAR-T cell products
Max. up to 44%
Max. up to 30%
Max. up to 56%
•
Initial 3 year manufacturing contract for clinical supply for NVS CTL019
programme – potential to extend
•
Financial terms include
•
$4.3m equity investment
•
IP licence
•
•
$9.7m non-refundable upfronts
•
Undisclosed royalties on CTL019 and other CAR-T products
Manufacturing and process development
•
Up to $76m over 3 years
10
OXB provides a key link in the CTL019 supply chain
•
Novartis licensed CAR-T technology from University of Pennsylvania
Cohort2
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1, n=3
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Mean 28%
Mean 34%
Mean 29%
-
Mean 26%
-
-
-
•
Novartis to develop the CTL019 product (and other CAR-T products)
Max. up to 30%
2, n=3
•
2x
Original
Complex supply chain:
3, n=3
2x
Enhanced
Max. up to 53%
Max. up to 50%
Max. up to 53%
Max. up to 44%
Max. up to 30%
Max. up to 56%
1.  OXB produces GMP lentiviral vector encoding
CAR targeting CD19
2.  White blood cells isolated from patients
3.  Vector used to transduce expanded T-cells
4.  The modified T-cells are infused back into the
patient
5.  Once inside the patient, the T-cells multiply,
‘hunt’ cancer cells and destroy them.
11
CTL019
•
FDA Breakthrough Therapy designation
Cohort2
1, n=3
•
2, n=3
•
•
•
3, n=3
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
1x
Original
Mean 27%
Mean 30%
Mean 29%
Designation supports the advancement
CTL019
to Max.
help
Max.of
up to
30%
up toaddress
50%
Max. up to 44%
the unmet need of patients with relapsed/refractory acute lymphoblastic
2x
Mean 28%
Mean 34%
Mean 29%
leukaemia
(r/r ALL) Original
Max. up to 53%
Max. up to 53%
Max. up to 56%
Intensive guidance from FDA through development
2x
Enhanced
Mean 26%
Rolling review;
Expedited approval
2 years (UPDRS)
Mean 20%
Max. up to 30%
-
•
90% of patients experienced complete remissions and sustained remissions of
two years with CTL019 (The New England Journal of Medicine, October 2014)
•
Estimated completion of Phase II study in June 2017 with launch thereafter
•
Likely to be indicated in ALL, CLL and DLBCL
•
Peak year sales potential
•
•
•
“$10bn pa” – Andrew Baum, CitiGroup London (Bloomberg)
“Will exceed multi-billion $” – Novartis job advertisement for Cell Therapeutics Global Launch
Leader, CTL019 (LinkedIn)
May generate $10 billion a year if its uses expand beyond leukaemia (Bloomberg)
12
Product Portfolio
© Oxford BioMedica 2011, all rights reserved
13
Portfolio of pipeline assets (excluding those already out-licensed)
Cohort2
Dose
Product
Indication
Administration
Lentiviral
vector 1x
TECHNOLOGY Original
1, n=3
OPHTHALMOLOGY
2, n=3
3 months (UPDRS)
Mean 27%
Max. up to 30%
RetinoStat®
2x
CNS
NEW IDEAS
Mean 30%
Mean 29%
Mean 20%
Max. up to 50%
Max. up to 44%
Max. up to 30%
2015
EncorStat® Enhanced Corneal graft
Meanrejection
26%
Glaucoma-GT
Chronic glaucoma
Phase
I/II preparation
FPI Phase I/II-
2016
Pre-clinical
End pre-clinical
2016
ProSavin®
OXB-102
Parkinson’s disease
Phase I/II complete
Phase I/II
preparation
FPI Phase I/II
2016
MoNuDin®
Motor neuron disease
Research
End pre-clinical
2015
TBD
TBD
Original
Mean 28%
Max. up to 53%
3, n=3
1 year (UPDRS)
Next inflection
Phase I follow up
Phase I CSR
stage
(primary endMean 29%
Mean 34%
Max. up to
53%
Max. up to 56%
point
met)
2x
Wet AMD
6 months (UPDRS)
Est.
date
2 years (UPDRS)
Stage
In addition, several other Lentiviral vector gene and cell therapy
product concepts are being explored
5T4 TECHNOLOGY
ONCOLOGY
TroVax®
Cancer (multiple)
Phase II ongoing
End Phase II
2015/16
CAR-T 5T4
Cancer (multiple)
Pre-clinical
End pre-clinical
2016
14
TroVax and 5T4 technology
•
5T4
Cohort2
1, n=3
•
2, n=3
•
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
A 72kDa glycosylated onco-foetal tumour
expressed
surface
Max. up toantigen,
30%
Max. up to 50% on theMax.
up to 44% of tumours
Max. up toand
30%
implicated
in the process
of metastatic
spread
2x
Original
Mean 28%
Mean 34%
Mean 29%
Max. up to 53%
Absent or low level of expression in healthy tissue
Enhanced
Mean 26%
® 2x
Max. up to 53%
Max. up to 56%
• 3, n=3TroVax is a 5T4 tumour associated antigen-encoding
sequence
delivered
by a
poxvirus (MVA) vector
•
•
Late-stage clinical asset; de-risked through multiple trials showing safety in >500 patients
•
Potential application in majority of solid cancers - multiple $bn market opportunity
•
Simple biomarker has been identified (and tested prospectively) which predicts both immune
reactivity and clinical benefit
•
Investigator-led Phase II studies ongoing in colorectal cancer, ovarian cancer and mesothelioma
CAR-T 5T4
•
A gene modified autologous T cell engineered with lentiviral vector to express an antibody against
5T4 along with multiple intracellular co-stimulatory domains; delivered by IV infusion
•
Acts by re-directing a patient’s T cells to recognise the 5T4 tumour antigen and kill the cell
expressing it through “normal” T cell killing mechanisms
15
New product development strategy
•
In vivo gene therapy
Cohort2
1, n=3
Dose
•
2, n=3
•
3, n=3
•
Administration
3 months (UPDRS)
6 months (UPDRS)
1 year (UPDRS)
2 years (UPDRS)
1x
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Investigating several therapy areas where
Lenti based
haveMax.
anupadvantage
over
AAV
due
Max. up to 30%
Max. vectors
up to 50%
to 44%
Max. up to
30%
to payload
capacity Original
2x
Mean 28%
Mean 34%
Mean 29%
Max. up to 53%
Max. up to 53%
Max. up to 56%
For example, ophthalmology where large genes or multiple genes can only be delivered by a Lenti
Enhanced
Mean 26%
based2xvector
Ex vivo cell therapy
•
Exploring possibilities to enter cell therapy field in our own right
•
E.g. CAR-T 5T4, combining our lentiviral expertise and IP with our 5T4 antigen
16
Licences to OXB’s IP and products
Cohort2
Dose
Administration
1, n=3
Company
1x
Products
Original
3 months (UPDRS)
Terms
Mean 27%
Mean 30%
Mean 28%
Mean 34%
Mean 26%
-
Max. up to 30%
Lent based vector
2, n=3
IP &
Know-how
3, n=3
Products
2x
Novartis
Original
6 months (UPDRS)
Max. up to 50%
1 year (UPDRS)
Estimated
launch
date
Mean
29%
Max. up to 44%
Mean 29%
2 years (UPDRS)
Estimated
Peak
Sales
MeanYr
20%
Max. up to 30%
-
CTL019/
Other CAR-T
Max. up to
53%
Max. up to 53%
$10m
upfront
Undisclosed royalties
2017Max. up to 56%
GSK
Up to 6 rare
orphan
diseases
Not disclosed
2017
$10m—$50m
per product
Sanofi
StarGen™
Undisclosed development
milestones and royalties
2021
$500m
Sanofi
UshStat®
2021
$90m
2x
Enhanced
-
“Multi billion $”
-
5T4 Tumour antigen
IP
Pfizer
5T4 antibody
Undisclosed
2023
>$300m
IP
ImaginAb
5T4 imaging
diagnostic
Undisclosed
2024
$10m
Bavarian Nordic
PROSTVACTM
Undisclosed
2017
$60m
PrimeBoost
IP
17
Upcoming potential value driving news flow
Cohort2
Dose
1, n=3
1x
2, n=3
2x
2015
Administration
3 months (UPDRS)
2x
1 year (UPDRS)
2 years (UPDRS)
Original
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Max. up to 30%
Max. up to 50%
Max. up to 44%
Max. up to 30%
Further IP licences/manufacturing/process
development contracts
Meanresults
28% expected,
Mean 34%
29%
RetinoStat®Original
Phase I final data
ready for Mean
Phase
II and/or- partnering
Max. up to 53%
3, n=3
6 months (UPDRS)
Max. up to 53%
Identification of new product development candidates
Enhanced
Mean 26%
Read out from TroVax® Phase II studies
Max. up to 56%
-
-
Read out from MoNuDin® preclinical results
Long term follow up on Prosavin
2016
FPI OXB-102 clinical programme
FPI EncorStat® clinical programme
StarGen™/UshStat® development milestones
Glaucoma-GT pre-clinical results
CAR-T 5T4 pre-clinical results
Regular updates on Novartis CTL019 product
18
Summary
•
Lentiviral vector IP position acknowledged by Novartis,
1, n=3
1x
Original
Mean
27% products
Mean 30%
GSK – royalties
on CTL019/other
CAR-T
Cohort2
Dose
Administration
3 months (UPDRS)
6 months (UPDRS)
Max. up to 30%
Max. up to 50%
1 year (UPDRS)
2 years (UPDRS)
Mean 29%
Mean 20%
Max. up to 44%
2x
34%
29%
• 2, n=3Two ophthalmology
inOriginal
vivo PhaseMean
I/II28%
productsMean
licensed
toMean
Sanofi
Max. up to 53%
Max. up to 53%
Max. up to 30%
-
Max. up to 56%
2x gene therapy
Enhanced
26%
- in Phase I/II
- and Phase- II
• 3, n=3Three other
productMean
candidates
development
•
Two phase I clinical trials utilising 5T4 antibody technology
•
Further potential product development opportunities being evaluated
•
Significant revenue potential from manufacturing
and process development
19
Contact us
Cohort
Dose
Oxford
BioMedica
plc
1, n=3
1x
Medawar
Centre
Robert Robinson Avenue
2, n=3Oxford Science
2x
The
Park
Oxford OX4 4GA
3, n=3
2x
United Kingdom
2
3 months (UPDRS)
1 year (UPDRS) CEO 2 years (UPDRS)
Manufacturing
facility6 months (UPDRS)
John Dawson,
OriginalHarrow House
Mean 27%
Mean 30%
Mean 29%
Mean 20%
Tim Watts,
CFO
Max. up to 30%
Max. up to 50%
Max. up to 44%
Max. up to 30%
County Trading Estate
OriginalTransport
Mean
28%CowleyMean 34%
Mean 29%
Way,
Max. up to 53%
Max. up to 53%
Max. up to 56%
Oxford OX4 6LX
Enhanced
Mean 26%
United Kingdom
Administration
www.oxfordbiomedica.co.uk
www.oxbsolutions.co.uk
enquiries@oxfordbiomedica.co.uk
enquiries@oxfordbiomedica.co.uk
Tel: +44 (0) 1865 783 000
20