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TRANSCRIPT
Investor Presentation
Preliminary results
for the year ended 31 March 2017
Olav Hellebø, Chief Executive Officer
Michael Hunt, Chief Financial Officer
Dr Julian Howell, Chief Medical Officer
Disclaimer
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considered a recommendation by ReNeuron Group Plc (the “Company”) or any of its respective directors, members, officers, employees, agents or advisers in relation
to any purchase of the Company’s securities, including any purchase of or subscription for any ordinary shares in the capital of the Company. Accordingly, information
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Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, the
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information or opinions. Further, the information in this presentation is not complete and may be changed. Neither the Company nor any of its respective members,
directors, officers or employees nor any other person accepts any liability whatsoever for any loss howsoever arising from any use of such information or opinions or
otherwise arising in connection with this presentation.
In the UK this presentation is being provided only to investment professional and high net worth companies, as described in articles 19 and 49(2), respectively, of the
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other jurisdiction of the United States of America and may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not
subject to, the registration requirements of the Securities Act. The Company does not presently intend to register any securities under the Securities Act, and no public
offering of securities in the United States will be made. In the United States, this presentation is directed only at, and may be communicated only to, persons that are
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This presentation may contain forward-looking statements that reflect the Company's current expectations regarding future events, its liquidity and results of operations
and its future working capital requirements and capital raising activities. Forward-looking statements involve risks and uncertainties. Actual events could differ
materially from those projected herein and depend on a number of factors, including the success of the Company's development strategies, the successful and timely
completion of clinical studies, the ability of the Company to obtain additional financing for its operations and the market conditions affecting the availability and terms of
such financing.
By participating in and/or accepting delivery of this presentation you agree to be bound by the foregoing restrictions and the other terms of this disclaimer.
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Company overview
3
Global leader in allogeneic cell-based therapeutics
Breadth of pipeline
Strong management team
Unique platform technologies
Well backed and well funded
Focus on high value indications
Global leader in cell-based therapeutics
4
Regenerative Medicine
1. Leaders in stem cell field
2. Ahead of the competition in
our selected indications
3. Secure Intellectual Property
4. Manufacturing capability
Innovation
1. Targeting unmet needs
2. High demand indications
3. Viable production strategies
4. Emerging exosome-based
nanomedicine
5. Broad range of indications
High growth sector
Potential to broaden therapeutic pipeline
beyond cell-based programmes
Extraordinary patient impact
Life-changing improvements in vision and
quality of life
Unique platform technologies
5
CTX clonal cell line
hRPCs
CTX platform
Clinical and pre-clinical pipeline in vascular
and neurological indications
Exosome platform
Potential to broaden therapeutic pipeline
beyond cell-based programmes
Retinal platform
Targeting retinal degenerative diseases
In-licensed technology (Harvard, Boston)
One single stem cell
Breadth of the pipeline
6
Product/
Indication
Discovery Pre-clinical Phase I Phase II Phase III Market
approval
CTX Cells
CTX cell therapy
Stroke Disability
CTX cell therapy
Critical Limb Ischaemia
Exosomes (CTX-derived)
Cancer
Human Retinal
Progenitor Cells
hPRC
Retinitis Pigmentosa
hPRC
Cone-Rod Dystrophy
Well backed and well funded
7
Backed by major generalist and specialist life science institutional investors:
35.5% Woodford Investment
Management
9.5% Wales Life
Science Fund
9.3% Invesco
5.7% Aviva
£53 million ($66 million)
Cash on balance sheet (as at 31 March 2017)
Cash runway into late 2018
Funds therapeutic programs into mid or late-stage clinical development
Strong management team
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Olav Hellebø Chief Executive Officer
(Schering-Plough,
Novartis, UCB, Clavis)
Board member
Michael Hunt
ACA Chief Financial Officer
(Biocompatibles,
Bunzl)
Board member
Dr. Randolph
Corteling Head of Research
Dr. John Sinden Chief Scientific Officer
and co-Founder
Sharon Grimster VP Development and
General Manager,
Wales
(F-Star, Antisoma,
Celltech)
Shaun Stapleton Head of Regulatory
Affairs
(Elly Lilly, Boehringer
Ingelheim, Ipsen,
RRG)
Dr. Julian Howell Chief Medical Officer
(Shield, ProStrakan,
Roche, Pharmion)
Senior Management
Non-executive Board
John Berriman Chairman
(Autolus, Algeta,
Heptares, Abingworth)
Simon Cartmell
OBE (Apatech, Celltech,
Glaxo)
Dr. Tim Corn (Jazz Pharma, EUSA
Pharma, Circassia,
Glaxo)
Prof. Sir Chris
Evans OBE (Arthurian, Excalibur)
Dr. Paul Harper
(Physiomics, Sareum,
CAT, Glaxo)
Dr. Michael Owen Chair - ReNeuron
Scientific Advisory Board
(Zealand Pharma,
Avacta, Kymab, GSK,
ICRF)
Focused strategy helping patients without any treatment options
9
1
2
3
Gain clinical validation for our therapeutic programmes via robust clinical trials in well regulated territories.
Develop best-in-class cell based therapies for life changing high value products
Realise value for our technologies and therapeutic programmes via direct sales or substantial license deals
10
Indication Assumptions to 2026 Peak
Sales
($bn)
CTX for stroke 1.76 million strokes/year (total US/EU/Japan)
85% survival, 85 % ischaemic
Peak penetration 5% US/EU/Japan
Treatment cost $40,000 EU to $60,000 US/Japan
1.1 - 3.9
hRPC for RP Prevalence 1:4000, ~244,000 cases (total US/EU/Japan)
Peak penetration 7.5% US/ EU
Per-eye treatment cost $50,000 EU to $75,000 US/Japan
0.5 - 1.8
Market potential according to Analysts’ estimates*
• Applicability of hRPCs in other hard-to-treat ophthalmic diseases could
provide upside potential
• Longer-term upside from exosome platform
*Stifel July 2016, N+1 Singer April 2017, Edison May 2017
11 CTX cell product
CTX cell product
12
CTX, an allogeneic, cryopreserved human neural stem cell product
• GMP production, full set of release testing with a 6 month shelf life
• Product to be readily ordered, shipped and stored at the hospital
• Commercial scale of manufacturing allows reasonable cost of goods
• No generation of immune response after administration
CTX delivered in
cryo-shipper
Controlled thawing by
validated methods
Administer to
patient ‘on demand’
Similar to a conventional ‘off-the-shelf’ pharmaceutical /biologic drug
Autologous vs Allogeneic cells
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• Autologous Cells
• Tissues harvested from a specific patient for his/her treatment
• Cell potency dependent upon age and health of each patient
• Usually limited shelf life with fresh cells
• Cost of cell preparation per preparation
• Unknown reimbursement scenario
Allogeneic cells offer commercial advantages over autologous preparation
• Allogeneic Cells
• One tissue harvest for many patients with scaled production
• Characterisation of product provides consistency across lots
• CTX established six month shelf life
• Costs spread over larger production base
• Realistic reimbursement projections
• No evidence of CTX generating an immune response in any patients treated
CTX for Stroke disability: unmet medical need
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• Stroke is the single largest cause of adult disability
• Annual health/social costs: >$70 billion in the US
• Only one pharmaceutical treatment option available within 4 hours of stroke onset
• No treatment options available for stroke patients months to years later
• CTX administration promotes repair in the damaged brain
Lifetime risk of stroke:
1 in 5 women
1 in 6 men
Two distinct cell therapy strategies for stroke
Str
oke D
am
ag
e
Bra
in R
eco
ve
ry
Tre
atm
en
ts
Thrombolysis;
Thrombectomy
Brain
Protection Brain Repair
Neuroplasticity: • Neurogenesis
• Angiogenesis
• Scar remodelling
Stem Cells
Minutes Days Hours Months Years
Inflammation
Neuron death
Neuroplasticity
Neuroprotective
Intravascular route
Regenerative
Intracerebral route
Acute Stroke Chronic Stroke
ReNeuron are pioneers in treating chronic stroke patients
15
Implanted CTX cells
modulate the immune
system to promote repair by
Formation of new blood
vessels (angiogenesis)
Formation of new
neurons (neurogenesis)
Formation of new
connections between
neurons (synaptogenesis)
CTX promotes anatomical plasticity in the brain
Images are for illustration only 16
Strong pre-clinical proof of concept
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• Rat stroke model used that affected similar regions of the brain as seen in patients
• Panel of behavioural tests to characterise dysfunction and recovery
• Injection of CTX into same region of brain as in the patients
• Improvements in “permanent” disabilities
• Restoration of function weeks after CTX administration
• Demonstrated dose response – unique in field of cell therapy
Well validated pre-clinical models predict efficacy in chronic stroke
Improvement in permanent dysfunction
CTX administration led to recovery of tape
removal from the affected forelimb in a
dose dependent manner
CTX for Stroke disability: Phase I data published
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• Phase I dose escalation safety study published with 24 months follow up
• 11 disabled, stable stroke patients, 6 months to 5 years post stroke
• Single, straightforward neurosurgical procedure, Doses at 2, 5, 10, 20 million cells
• No cell-related or immunological adverse events
• Significant improvement in NIH Stroke Scale, 3 patients improved in modified Rankin Score,
Encouraging results across multiple efficacy measures of disability
CTX for stroke disability – Phase II study design
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• Aim of the PISCES II study:
• To demonstrate effect of CTX cells on improving outcome of patients during rehabilitation phase following an ischaemic stroke
• To provide further safety data in a larger group of patients
• Inclusion Criteria
• Male and female patients; aged 40-89; 2-12 months after a stroke
• Upper limb dysfunction (Inability to pick up a 1” cube and place on a shelf)
• Study Procedures
• CTX 20 million cells injected into brain (putamen) on affected side, Follow up for 12 months
• Outcome measures
• Modified Rankin Score, Barthel Index, ARAT, Fugl-Meyer
• Treated 23 patients in 8 centres across the UK
• Median Age: 62 yrs (41-79), Median time from stroke to treatment: 7 months (2-13)
Robust trial of the capabilities of CTX in stroke patients
Modified Rankin Score
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Improvement by one category is a significant change in a patient’s life
Algorithm from Bruno et al, 2010
Category
6 Death
5 Bedridden, completely dependent on others
4 Needing help to walk, use toilet, bathe
3 Can walk, but need still need help at home
2 Mostly recovered, but still has limitations
1 Slower than before, but no limitations
0 Back to pre-stroke life
Bedridden, requires constant help from others
Needing help to walk, use toilet, bathe
Can walk with appliance,
Needs some help at home
Slight to no disability
from Lekander et al 2017, 42,114 patients from 2007-2012
Costs from Sweden, translated into pounds
Costs of disability – mRS scale
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Improvements in disability result in substantial reductions in patient care costs
PISCES II interim efficacy – (mRS)
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n= 21 21 10 3
33 percent of subjects (7 of 21) had a significant improvement in their quality of life
Most within 1 month of cell administration
Life changing results seen with CTX administration
Baseline 3 months 6 months 12 months
1 - no signficant disability
2 - slight disability
3 - moderate disability
4 - moderately severe
5 - severe
PISCES II efficacy – Barthel Index
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• Measure of Activities of Daily Living
• mobility, self care, dressing
• 38% of patients had significant improvement (8 of 21)
• 100 point range of measure
• >9 point change is clinically significant
• 6 of 21 patients had BI >90 at baseline (therefore unable to reach ‘responder’ status)
• 53% of evaluable subjects had significant improvement (8 of 15)
0
2
4
6
8
1 month 3 months 6 months
Barthel Index Responders
Improvements in everyday activities after CTX administration
PISCES II – Conclusions
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• Rate of patient improvement in patients with established disability due to stroke has greatly exceeded what we expected
• 15 of 21 patients responded to one or more of the four efficacy measures
• Response rate on mRS was greater than expected – use as primary measure in future studies
• Patients ready to enter study from 6 months post-stroke
• CTX intracerebral injection was well tolerated
• Adverse Events were attributed to surgical procedure
or stroke complications
• 1 death due to sepsis, 7 months after CTX treatment.
Assessed as not attributable to treatment.
• 33% response rate in mRS outcome measure
• 53% response rate in evaluable patients for BI measure
Potential of CTX in stroke warrants moving into a Phase III study
Phase III Study - PISCES III
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• Randomised, controlled study with placebo surgery
• Entry criteria: mRS of 3 or 4 Primary endpoint will be a change in modified Rankin Score category
• Examine patients at 6 months post cell administration
• US and European sites use “Hub and Spoke” – reduced number of surgical sites
• Improves blinding by eliminating interaction of surgical staff and assessors
• 220 patients, 1 to 1 randomisation, CTX 20 million cell dose as used in PISCES II
• Discussions held with FDA / EMA, received favourable responses
• Commencing in early 2018 – Data expected early 2020
• A similar response rate in mRS to that seen in PISCES II would provide basis for a clinically and commercially viable cell therapy
• Presumed 20% increase over placebo response of 15%
• Alteplase had an 11% increase in favourable outcome to placebo response (n=333)
Discussions held with FDA on pivotal study design
26 Human Retinal Progenitor Cells
Retinal platform
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Broad application across a range of retinal diseases
• The eye does not regenerate lost cells
• Small changes in the retina will have a great impact in vision
• Programme based on human retinal progenitor cells (hRPCs)
• Preclinical testing programme demonstrated:
• Rescue of photoreceptors to preserve vision
• Maturation of injected hRPCs
• Approval of hRPC frozen formulation
• Ship and thaw on demand
• Collaborations:
Schepens Eye Research Institute (Harvard Medical School)
• Targeting Retinitis Pigmentosa, Cone Rod Dystrophy
Retinitis pigmentosa
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• RP is an inherited, degenerative eye disease
• Onset from 20s to middle age
• Initial damage in outer retina
• Results in tunnel vision then blindness
• Incidence of RP is 1:4000 in the US with an estimated treatment population of 275,000 in the US and EU
• First therapeutic target for hRPCs
• Orphan Drug Designation in EU and the US & Fast Track Designation in US
• Phase I / II study ongoing in the US
• Phase I safety data readout in H2 2017
• Phase II commences H2 2017
• Phase II readout H2 2018
RP vision
There is no approved drug treatment for Retinitis Pigmentosa
RP: IND-enabling pre-clinical efficacy data
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• RCS rat model of retinal degeneration
• Damage starts within weeks after birth
• hRPCs injected into the retina anticipating clinical administration
• Treatment significantly improved visual function
• Injected cells still present 12 weeks after dosing
• hRPC cells extend into the ganglion cell layer, demonstrating full integration
• Collaboration with UCL/Moorfields Eye Hospital
Dystrophic rats
hRPCs preserved visual acuity in degenerating retina
RP: Clinical development – Phase I / II
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• Dose escalation study in adult patients with established RP in the US
• Phase I - 3 dose groups of 3 subjects each
• Phase II - 20 additional patients at highest safe dose (to be expanded from 6 patients)
• Primary endpoint is safety, with visual acuity, visual field, retinal sensitivity and retinal structure as secondary efficacy measures
• Measurements in both treated and untreated eyes for comparison
• Phase I clinical site – Massachusetts Eye & Ear Infirmary, Boston (PI: Dr Eric Pierce)
Light guide
Infusion cannula
Subretinal cannula
delivering hRPC
Subretinal space
Choroid
Collaborating with elite institutions in ground breaking research
Cone rod dystrophy
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• CRD is an inherited, degenerative eye disease
• First noticed in childhood
• Initial damage to cones in central retina
• Loss of visual acuity and colour vision
• Progresses to blindness
• Incidence of CRD is 1:40,000 in the US
• Second therapeutic target for hRPCs
• Use safety data from RP Phase I study
• Conduct Phase II trial alongside RP study
• Commence in H1 2018
• Readout in H1 2019
CRD vision
image from MD Support
Working to prevent lifelong blindness
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Exosome Platform
Exosome nanomedicine development
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• Exosome therapeutic candidate selected (ExoPr0)
• Pre-clinical data
• ExoPr0 inhibits glioblastoma cell migration
• ExoPr0 reduces tumour volume in a CDX (cell-line derived xenograft) mouse model of glioblastoma
• Published data* identifies micro-RNAs contained within ExoPr0 responsible for regulating cell growth and apoptosis in cancer
• ExoPr0 crosses blood brain barrier allowing treatment of a number of conditions
• Development of platform technology for the delivery of therapeutic silencing RNA
• Target genes over-expressed in cancer indications
• £2.1m Innovate UK grant awarded to pursue ExoPr0 pre-clinical development
• Collaborators – Netherlands Cancer Institute, UCL, Cell & Gene Therapy Catapult
* Stevanato et al. PLOS ONE (2016)
ReNeuron are leaders in a new field of medicine
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Preliminary Results
Preliminary results – highlights
35
(£’m)
Year ended March
31, 2017
(unaudited) Year ended March
31, 2016
Revenues and grant income 0.9 0.6
Research and development costs (16.7) (10.3)
General and administrative costs (4.1) (4.0)
Operating loss (19.9) (13.7)
Finance income 1.7 0.8
Tax credit 2.6 1.5
Loss for the year (15.6) (11.4)
Operating cash burn (12.6) (11.9)
Equity issues net of costs - 65.2
Net (decrease)/increase in cash (12.6) 53.3
Cash and deposits at start of year 65.7 12.4
Cash and deposits at year end 53.1 65.7
Key clinical milestones – next 18 months
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• H2 2017 CTX for Stroke disability – Phase II 12 month follow-up data
• H1 2018 CTX for Stroke disability – Phase III commencement
• H2 2017 hRPC for Retinitis pigmentosa – Phase I safety data
• H2 2017 hRPC for Retinitis pigmentosa – Phase II commencement
• H1 2018 hRPC for Cone-rod dystrophy – Phase II commencement
• H2 2018 hRPC for Retinitis pigmentosa – Phase II efficacy data
• H2 2018 Exosomes for cancer – Phase I commencement
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www.reneuron.com
Ticker: RENE.L 37