Corporate Presentation
Forward Looking Statements
This document does not constitute or form part of any offer or invitation to sell or issue, or any solicitation
of any offer to purchase or subscribe for, any shares in the Company, nor shall any part of it nor the fact of
its distribution form part of or be relied on in connection with any contract or investment decision relating
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This document may contain forward-looking statements and estimates made by the Company, including
with respect to the anticipated future performance of TiGenix and the market in which it operates. They
include all matters that are not historical facts. Such statements, forecasts and estimates are based on
various assumptions and assessments of known and unknown risks, uncertainties and other factors,
which were deemed reasonable when made but may or may not prove to be correct. Actual events are
difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual
results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out
to be materially different from any future results, performance or achievements expressed or implied by
such statements, forecasts and estimates. Forward-looking statements, forecasts and estimates only
speak as of the date of this document and no representations are made as to the accuracy or fairness of
such forward-looking statements, forecasts and estimates. TiGenix disclaims any obligation to update any
such forward-looking statement, forecast or estimates to reflect any change in the Company’s
expectations with regard thereto, or any change in events, conditions or circumstances on which any such
statement, forecast or estimate is based.
Management Team With Proven Track Record of Success
Managing Director and CEO:
Eduardo Bravo
, MBA
•
More than 25 years experience in the pharma and biotech industries at Sanofi-Aventis, Recordati,
Cephalon and SmithKline Beecham
CFO:
Claudia D’Augusta
, PhD
•
More than 15 years experience in equity and debt financing at Aquanima (Santander Group), Apax
Corporate Finance and Deloitte Corporate Finance
CTO:
Wilfried Dalemans
, PhD
•
More than 25 years experience in the pharma and biotech industries; previous engagements at GSK
Biologicals and Transgène
CMO:
Marie Paule Richard
, MD
•
More than 25 years experience in the global pharma and biotech industries at Bristol-Myers Squibb,
Sanofi Aventis, GSK, Sanofi Pasteur, Crucell and AiCuris
VP Regulatory Affairs & Corporate Quality:
María Pascual,
PhD
•
More than 10 years experience in cell therapy companies; specialized in regulatory affairs for
advanced therapies; external adviser to EMA
VP Medical Affairs & New Product Commercialisation:
Mary Carmen Diez,
MD
•
More than 20 years experience in the biopharmaceutical industry at Meda Pharma, Asta Médica,
Pfizer and Dupont Pharma
Investment Highlights
Positive Phase III
And Advanced EU
Regulatory
Strategy:
Cx601
•
Complex perianal fistulas in Crohn’s disease patients in the US & EU
represents a
multi-billion
dollar market opportunity
•
Pivotal Phase III
allogeneic stem cell asset (local administration of a single dose)
•
Results met primary endpoint
•
Statistically superior to placebo
in achieving combined remission at week 24 (p<0.025)
•
Filing for MAA expected in 1Q16
and launch expected 2H17
•
Fully-owned asset
•
Consistent and robust
manufacturing process
•
Management team has valuable experience in regulatory approval / commercialization process;
first
ever ATMP
1approved by EMA
•
Use of data from positive pivotal Phase III trial in EU to support a BLA in the US
•
FDA´s endorsement through SPA obtained
for pivotal phase III trial in the US
•
Same primary endpoint as positive EU Phase III trial
•
Phase III to start 1Q17
•
Fully-owned asset
•
Lonza
selected as contract manufacturing organization for Cx601 in the US
Clear US
Regulatory and
Clinical Strategy:
Cx601
•
AlloCSC-01:
allogeneic cardiac stem cells, a new platform acquired through the acquisition of
Coretherapix, being developed for cardiovascular indications
•
Randomized, double blind, placebo controlled Phase II trial in acute myocardial infarction ongoing
•
Interim data expected 2H16
•
Final one year follow up data expected 1H17
•
Cx611: Intravenously-administered
allogeneic stem cell product for
severe sepsis (Phase I study
completed)
•
Severe sepsis Phase ll trial design
has been finalized; expected to
enroll first patient in 4Q15
Valuable Pipeline
Opportunities:
AlloCSC-01 and
Cx611
Multiple Product Candidates
Product
1
Indication
Preclinical Phase I
Phase II
Phase III
Market
Allogeneic Adipose-Derived Stem Cells
Cx601
(local)
Complex Perianal
Fistulas in Crohn’s
disease
Cx611
(intravenous)
Severe Sepsis
Allogeneic Cardiac Stem Cells
AlloCSC-01
(intracoronary)
Acute Myocardial
Infarction
AlloCSC-02
(intramyocardial)
Cardiology
Characterized Autologous Chondrocytes
ChondroCelect
Knee Cartilage Lesions
EMA-granted Orphan Drug
Partnered
2
FDA-endorsed SPA
Cx601: Positive Phase lll Data
Local injection of eASCs for the treatment of
complex perianal fistulas in Crohn’s disease patients
Mechanism of Action: Adipose-Derived Stem Cells
The ability to interact with many players in
the immune system qualify MSCs (including
ASCs) as a potent anti-inflammatory agent
*
Inhibition of pro-inflammatory cytokines
* p<0.05 relative to supernatant from activated PBMCs
Source: De la Rosa et al. Tissue Engineering 2009
PBMCs
Activated PBMCs
PBMCs+ASCs
activated PBMCs+ASCs
ASCs
0
5
10
15
20
IFN-
γ
(ng/ml)
0
1
2
3
4
5
TNF-
α
(ng/ml)
*
*
0
5
10
15
20
ACTIVATED
PBMCs
PBMCs + ASCs
ACTIVATED
%
O
F
C
D
4+C
D
25
+++
O
N
T
O
TAL
C
D
4
* p<0.05 relative to activated PBMCs without ASCs
Source: Tigenix data
Manufacturing
Consistent and Robust Process
•
Up to 360 billion cells
can be
obtained from 1 donor
•
Quality control parameters defined:
•
Identity
•
Purity
•
Potency
•
Approximately 2,400 finished products
of Cx601
Liposuction
Cell isolation and expansion
Frozen Drug Substance (FDS)
Finished Product
Master cell bank (cryo)
Perianal Fistulas
A Common Severe Complication of Crohn’s Disease
•
Fistulas: sores or ulcers that tunnel
through the affected area into
surrounding tissues
•
Around 11% of adult Crohn’s
disease patients
are affected by
perianal fistulas
•
70% – 80% of these are complex
•
Affect anal sphincters
•
Present multiple tracts
•
Are recurrent
•
Are often associated with perianal
abscess
Almost
120,000 adult Crohn’s disease patients
suffer from complex perianal
fistulas in Europe and the US alone =>
compromised QoL, pain, depression
and risk of anal epithelial carcinoma
Perianal fistulas: treatment options and shortfalls
10
1 L.J. Brandt et al. Metronidazole Therapy for Perineal Crohn’s Disease: a Follow-Up Study, 83 GASTROENTEROLOGY 383-7 (1982) 2 E.S. Goldstein et al., 6 ‑ Mercaptopurine Is Effective in Crohn’s Disease Without Concomitant Steroids, 10 INFLAMM BOWEL DIS 79‑84 (2004) 3 B.I. Korelitz et al., Favorable Effect of 6-Mercaptopurine on Fistulae of Crohn’s Disease, 30 DIGEST DIS SCI 58-64 (1985)
4 B.E. Sands et al., Infliximab Maintenance Therapy for Fistulizing Crohn’s Disease, 350 N ENGL J MED 876‑85 (2004)
5 E. Domenech et al., Clinical Evolution of Luminal and Perianal Crohn’s Disease after Inducing Remission with Infliximab, 22 ALIMENT PHARMACOL THER 1107-13 (2005)
6 J.F. Colombel et al., Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn’s Disease: The CHARM Trial, 132 GASTROENTEROLOGY 52-65 (2007)
7 C.B. Geltzeiler et al., Recent Developments in the Surgical Management of Perianal Fistula for Crohn’s Disease, 27 ANN GASTROENTEROL 1-11 (2014) 8 T. Sonoda et al., Outcomes of Primary Repair of Anorectal and Rectovaginal Fistulas Using the Endorectal Advancement Flap, 45 DIS COLON RECTUM
1622‑28 (2002)
9 A. Soltani and A. Kaiser, Endorectal Advancement Flap for Crypto Glandular or Crohn’s Fistula‑in‑Ano, 53 DIS COLON RECTUM 486‑495 (2010)
Treatment options
Efficacy
Safety
Antibiotics
•
Safety concerns with prolonged use
•
Poor quality of evidence on fistulas
remission
•
High rate of fistula relapse on drug
cessation: 72%
1
Infliximab
(Remicade
®
)
•
Low remission rate of perianal fistulas:
23% after 54 weeks of treatment
4
•
High rate of relapse: 54% after 54 weeks
of treatment
4
, and 66% one year after
drug cessation
5
•
Safety remains a concern with long term
use of biologics
Adalimumab
(Humira
®
)
•
Low remission rate: 33% after 56 weeks
of treatment
6
•
Safety remains a concern with long term
use of biologics
Immunossuppressants
•
Poor quality of evidence on fistulas
remission
•
High rate of fistula relapse on drug
cessation : 67-71%
2,3
•
High risk of infectious complications
Surgery
•
Risk of complications (eg. incontinence,
abscesses formation, non-healing
wounds
7,9
)
•
Risk of recurrence remains (up to
~50-70%, depending on the type of
surgery)
7,8
unless radical, mutilating
•
Mode of administration
1.
Fistula curettage and closure of
internal opening (sutured)
2.
Half of Cx601 dose (2 vials) is injected
in the tissue around the internal
opening, making several small blebs
3.
The other half (2 vials) is injected along
the walls of the fistula tracts, also
making several small blebs
•
Product description
o
Expanded adipose-derived stem cells
(eASCs) for the treatment of complex
perianal fistulas in Crohn’s disease
o
4 vials containing 30 million cells in 6 mL
suspension each (total dose 120 million
cells)
Injection sites:
Injection sites:
a. Fistula internal opening b. Fistula tract
Cx601 Phase III ADMIRE-CD
1
Trial
Robust Phase III Study Designed to Qualify as a Single Pivotal Study
TRIAL SUMMARY
Condition
Complex perianal fistulas in Crohn’s disease patients
Study design
•
•
Randomized, double-blind, placebo-controlled trial
All tracts treated. Single injection
2
Status
24 weeks primary analysis finalized. Follow up ongoing
Enrollment
289 patients recruited
Number of sites
50 active sites in 8 countries
Primary endpoint
Combined Remission
3
at week 24 with
α
<0.025
Secondary endpoints
at Weeks 24 and 52
•
Clinical Remission
4
•
Response
5
•
Time to Clinical Remission / to Response
•
PDAI
6
and other scores
•
Safety and tolerability
1 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn’s Disease 2 120 million cells
3 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI 4 Closure of all treated external openings draining at baseline despite gentle finger compression
5 Closure of at least 50% of all treated external openings draining at baseline despite gentle finger compression
Patients Selection: Key Eligibility Criteria
•
Men and women aged 18 years or older
•
Non active or mildly active luminal Crohn’s disease (CDAI
≤
220)
diagnosed for
≥
6 months
•
Patients with complex perianal fistulas with
≤
2 internal openings and
≤
3
external openings
•
Fistula draining
≥
6 weeks prior to inclusion
•
Patients with inadequate response to at least one of the following:
antibiotics, immunosuppressants or anti-TNFs
•
Medical standard of care was allowed to continue without modification of
treatment dose or regimen
Treatment
W24
Primary Endpoint
W52
Preparation
Screening
D0
Follow-Up
W6 W12 W18
W36
W-3
W-5
Baseline
MRI
W24
MRI
W52
MRI
MRI: Magnetic Resonance Imaging
week
Randomization
Clinical Assessment
Design: Double-Blind, Placebo-Controlled
14
Screened
n= 289
Screening
Failures
n= 77
Randomized
n= 212
Cx601
n= 107
Not Treated
n= 4
Treated
n= 103
Treated & post
baseline assessment
n= 103
Placebo
n= 105
Treated
n= 102
Treated & post
baseline assessment
n= 101
Not Treated
n= 3
Safety set
n= 205
ITT
1
set
n= 212
mITT
2
set
n= 204
Largest Study in Complex Perianal Fistulas
Demographics, PDAI and Fistula Topography
Demographics (ITT)
Cx601
n= 107
Placebo
n= 105
Age (years) mean (SD)
39.0 (13.1)
37.6 (13.1)
Men (%)
60 (56.1)
56 (53.3)
Caucasian (%)
100 (93.5)
96 (91.4)
Weight (kg) mean (SD)
73.9 (15.0)
71.3 (14.9)
PDAI
1
(ITT)
Mean (SD)
6.5
6.7
Topography of Internal &
External Openings (%) (Safety set)
Cx601
n= 103
Placebo
n= 102
One-tract fistula
53.4
68.6
Multiple-tract fistula
46.6
31.4
•
Similar demographics and PDAI score between arms
•
Higher proportion of multiple-tract fistulas in Cx601 group
(ITT
1
Population n= 212)
49.5%
34.3%
0
10
20
30
40
50
60
Cx601
Placebo
p < 0.025
51.5 %
35.6 %
0
10
20
30
40
50
60
Cx601
Placebo
p < 0.025
(mITT
2
Population n= 204)
Cx601: A Major Breakthrough
Primary Endpoint Met
•
Cx601 significantly superior to placebo in achieving Combined Remission
•
Patients receiving Cx601 have 44% more chances to achieve Combined Remission
than placebo patients
•
Efficacy results consistent across all statistical populations
%
%
Overview of TEAEs up to W24
(Safety Population n=205)
Number of Patients with (%)
n= 103
Cx601
Placebo
n=102
TEAEs
68 (66.0)
66 (64.7)
Related TEAEs
16 (15.5)
26 (25.5)
Withdrawn due to a TEAEs
4 (3.9)
4 (3.9)
TESAEs
17 (16.5)
13 (12.7)
Related TESAEs
5 (4.9)
6 (5.9)
Withdrawn due to TESAEs
3 (2.9)
2 (2.0)
TE(S)AE: Treatment-Emergent (Serious) Adverse Events
•
If a patient has multiple events of the same severity, relationship or outcome, then they are counted only once in that
severity, relationship or outcome. However, patients can be counted more than once overall.
Favorable safety and tolerability profile of Cx601 and comparable to placebo
Cx601: A Regulatory De-Risked and Fully-Owned Asset
Preparing for the European Launch in 2017
•
Clear and fast pathway to the market built on a solid regulatory strategy
•
Letter of intent submitted to the EMA
1
and MAA
2
filing planned for 1Q 2016
•
5 Scientific Advice Meetings held with EMA (2 pre-clinical, 2 CMC, 1 clinical)
•
Team with previous experience in obtaining MAA of cell therapy product
•
Major commercial opportunity
•
More than 70,000 adult patients in Europe with high medical need
•
Protection obtained through EU patent and orphan designation
•
Fully-owned commercial rights
•
Commercialization strategy
•
Partner in certain EU countries
Cx601: Capturing the Value of the Biggest Market
Preparing for the US launch in 2020
•
Clear and fast pathway to the market built on a solid regulatory and clinical
development strategy
•
Type B meeting with FDA
1
confirmed:
•
Adequacy of existing non-clinical package to support an IND
2
filing
•
Acceptability of using data from the ADMIRE-CD trial to support BLA
3
•
FDA endorsement through SPA
4
of US Phase III protocol:
•
Primary end-point identical to ADMIRE-CD trial
•
p-value < 0.05 (vs. p-value <0.025 in ADMIRE-CD trial)
•
US Phase III trial scheduled to start by 1Q 2017
•
Lonza selected as US contract manufacturing organization for Cx601 in the US
•
Major commercial opportunity
•
More than 40,000 adult patients in the US with high medical need
•
Protection obtained through US patent until 2030
•
Retain US rights to develop and commercialize
1 FDA: Food and Drug Administration 2 IND: Investigational New Drug 3 BLA: Biological License Application
TRIAL SUMMARY
Condition
Complex perianal fistulas in Crohn’s disease patients
Study design
•
•
Randomized, double-blind, placebo-controlled trial
All draining tracts treated. Single injection
2
Status
In preparation
Enrollment
224 patients screened to allow for 168 randomized patients
Number of sites
At least 50 – 60 active sites in 2 countries (USA & Canada)
Primary endpoint
Combined Remission
3
at week 24
4
with
α
<0.05
Secondary endpoints
at Weeks 24 and 52
•
Clinical Remission
5
•
Response
6
•
Time to Clinical Remission / to Response
•
PDAI
7
and other scores
•
Safety and tolerability
Cx601: Phase III US Trial
Trial Design Endorsed by FDA through SPA
1
Procedure in August 2015
1 Special Protocol Assessment 2 120 million cells
3 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI 4 The primary efficacy analysis, which has a week 24 endpoint, will be conducted at the time of the week 52 final analysis
5 Closure of all treated external openings draining at baseline despite gentle finger compression
* Estimated average prevalence in EU: 180/100,000
1-4
Estimated prevalence in US: 190/100,000
3,6
Crohn’s disease: 1,540,710 *
1-6
Adults: 1,432,860 (93%)
5-6
Perianal fistulas: 157,615 (11%)
7-8
Complex: 118,211 (75%)
9-12
Controlled luminal CD: 78,019 (66%)
13
Refractory fistulas: 70,217 (90%)
13-15
22
Cx601: Estimated Patients Population (EU & USA)
An Attractive Commercial Opportunity
1 Stone MA et al. 2013 2 Hein R et al. 2014 3 Molodecky NA et al. 2012 4 Lucendo AJ et al. 2014 5 Kappelman MD et al. 2007 6 Kappelman MD et al. 2013 7 SEESGCD.1999 8 Gibson PR et al. 2007 9 Eglinton TW et al. 2012 10 Bell SJ et al. 2003 11 Lahat A et al. 2012 12 Molendijk I et al. 2014 13 Sands BE et al. 2004 14 Present DH et al. 1999 15 Domènech E et al. 2005
Estimated Market Share
Assumptions:
•
Estimated patients population to be treated with Cx601: ~70,000 patients
•
Estimated first launch date in Europe: 2H17
•
Estimated launch dated in US: 2020
35%
20%
50%
Estimated Selling Price
25 K$
33 K$
50 K$
Estimated Sales Potential
350 Mio $
809 Mio $
1,750 Mio $
Cx611: Phase ll Ready
Intravenous injection of eASCs for the treatment of severe sepsis
1 The Lancet Infectious Diseases; Volume 12; issue 2; page 89; February 2012
2 Vincent JL et al Sepsis in European intensive care units. Critical Care Medicine 2006; 34: 344-353
3 University Hospital of Valme & Biomedical Research Institute of Seville: Presentation at Farmaindustria meeting July 2014
Severe Sepsis: A High Unmet Medical Need
•
Systemic illness due to an attack of host
pro-inflammatory cytokines and other humoral
substances commonly induced by a bacterial
infection
•
An estimated 15—19M sepsis cases occur
worldwide each year
1
•
Incidence has dramatically increased over
the last decade (CAGR of 8-13%)
2
•
Sepsis mortality was estimated at 36% in a
recent major European study
2
•
In the case of septic shock, mortality can
reach up to 80% (28 –50% of patients die
within the first month of diagnosis)
3
•
Current molecular approaches to the
treatment of sepsis have inadequately
addressed the complex immuno-modulatory
pathways involved in sepsis pathogenesis
eASCs Can Protect In Severe Sepsis
•
Cx611 reduces mortality in animal models of sepsis
•
This effect is due to a combination of reducing pro-inflammatory and increasing
anti-inflammatory mediators, production of anti-microbial effectors, and increased
phagocytosis
Source: Gonzalez-Rey, 2009
* p < 0.001
LPS
1
Model
CLP
2
Model
26
1 LPS: lipopolysaccharide. LPS model is based on endotoxemia induced by high-dose of endotoxin
CLP
model
•
↓
of pro-inflammatory mediators
•
#
of anti-inflammatory mediator
•
↓
of inflammatory cells
L
PS
m
o
d
el
* p<0.001
Cx611: Phase I results and Next Steps
Phase II In Severe Sepsis Expected to Start 4Q 2015
•
CELLULA Phase I trial results
•
250k, 1M, 4M eASC/kg and placebo administered to 32 healthy volunteers (8 per group)
•
Favorable safety and tolerability profile of Cx611, consistent with Phase I/IIa in refractory RA
patients
•
SEPCELL Phase Ib/IIa study in severe sepsis to start 4Q 2015
•
Randomized, double blind, parallel groups, placebo controlled, multicenter study
•
180 patients (90 per group) with sCABP
1
requiring mechanical ventilation and/or
vasopressors, admitted to the ICU. At least 50 centers in at least 4 countries
•
80M eASC or placebo on days 1 and 3 (160M in total) in addition to standard of care
therapy. 90 days follow up
•
Primary endpoint: Adverse event and potential immunological host responses against the
administered cells
•
Secondary endpoint: reduction in the duration of mechanical ventilation and/or vasopressors
needed and/or improved survival, and/or clinical cure of the CAPB, and other
infection-related endpoints
28
AlloCSC-01: Phase ll interim data in <12 months
Intracoronary administration of allogeneic cardiac stem cells for the
AlloCSC-01: Preventing Congestive Heart Failure
Myocardial Repair may be the only Feasible Alternative
•
1,9M Acute Myocardial Infarctions (US+EU)
1
occur annually, mostly treated by PCI
2
and stent
implantation
•
Successful treatment of AMI has contributed to a Chronic Heart Failure epidemic (26M
patients worldwide
3
)
•
CHF post-AMI is a terminal disease
with an annual mortality rate of ~5% after the first
episode, for which no curative treatment exists with the exception of heart transplantation
•
In 2015, the AHA estimated that the direct and indirect cost of coronary heart disease, the
main cause of myocardial infarction, was $182 billion and is expected to reach $322 billion in
2030. Similarly the cost of heart failure in the United States was estimated at $24 billion for
2015, reaching $47 billion in 2030
4
An attractive market for a treatment able to mitigate or delay the onset of CHF
30
1 Datamonitor: Stakeholder Insight: Acute coronary syndromes, DMHC2347, 2007 2 PCI: Percutaneous Coronary Intervention
3 Ambrosy PA et al., J Am Coll Cardiol. 2014;63:1123-1133. 4 Circulation. 2015 Jan 27;131(4):e29-322.
AlloCSC-01: A Regenerative Treatment Post-AMI
Preventing the Onset of Chronic Disease
•
The formation of a non-functional scar tissue gives rise to a process of ventricular remodeling
whereby the myocardium tries to compensate the effect of the injury
•
Over time the heart dilates losing its contractile capacity causing the onset of CHF. This is a
terminal condition with no treatment other than transplantation
•
The severity of this process is related to the size of the scar resulting from the AMI. Smaller
scars are related to better outcomes
1
Myocardial repair seems to
be the only feasible
treatment to address the
post-acute phase of the
disease and prevent the
onset of chronic heart
failure (CHF)
CARDIAC REMODELING
CARDIAC FUNCTION
AlloCSC-01: Efficacy Demonstrated in Pig Model
Efficacy Data from MRI
1
Histological Analysis
!
!
CONTROL
AlloCSC-‐01
80#
90#
100#
110#
120#
130#
140#
150#
CO
NT
RO
L#
25
M#
50
M#
EDVi#
30#
40#
50#
60#
70#
80#
90#
100#
CO
NT
RO
L#
25
M#
50
M#
ESVi#
30#
35#
40#
45#
50#
55#
60#
CO
NT
RO
L#
25
M#
50
M#
EF###
*
*
*
1 MRI: Magnetic Resonance Imaging 2 EDVi: End-Diastolic Volume Index 3 ESVi: End-Systolic Volume Index 4 EF: Ejection Fraction
*
p-value < 0.05
•
AlloCSC-01 prevents cardiac remodelling after infarction preserving heart function
•
AlloCSC-01 reduces scar size promoting formation of new contractile tissue
•
Significant dose effect observed
32
CAREMI Phase I/II Trial Finalizing Recruitment
Safety and Efficacy of
Intracoronary Infusion of Allogeneic Cardiac Stem Cells in
Patients with Acute Myocardial Infarction (AMI)
TRIAL SUMMARY
Condition
Acute Myocardial Infarction
Study design
AlloCSC-01 administered 5-7 days after
PCI
4
•
Phase 1
. Open label dose
escalation in 6 patients
•
Phase 2
: Placebo controlled, 49
patients randomized 2:1 (35M cell
dose in active arm)
Recruitment
•
Phase 1:
Completed
•
Phase 2:
36 of 49 treated, set to
complete recruitment in 4Q 2015
# of centers
8 sites
Primary endpoint
Mortality and MACE
30 days
5
from any cause at
Secondary
endpoints (6 and
12 months)
Safety: Mortality and MACE
Efficacy: evolution of infarct size,
biomechanical parameters by MRI
Clinical parameters: 6m walk test, NYHA
6
scale
Completion
1H17 (Interim data 2H16)
PATIENT SELECTION
Initial clinical pre-screening:
•
Males, females
≥
18 years and
≤
80 years
•
Patients who present a STEMI
1
•
Killip
≤
2 on admission
•
Successful revascularization by PCI (TIMI
2
= 3)
within 12h after the onset of symptoms
•
EF
≤
50% by echocardiography (day 2 after
infarct symptoms)
•
EF
≤
45% by MRI on D3-5 post-STEMI
•
Infarct size (1
st
MRI) >25% in LV
3
•
Bare-metal stents or second generation drug
eluting stent at PCI
•
The infarct culprit coronary artery is adequate
for treatment administration and the procedure
is technically feasible
•
The patient is stable and in adequate clinical
condition to undergo the procedure
1 STEMI: ST-Segment-Elevation Myocardial Infarction 2 TIMI: Thrombolysis In Myocardial Infarction 3 LV: Left Ventricle
4 PCI: Percutaneous Coronary Intervention 5 MACE: Major Adverse Cardiac Events
•
In the dose-escalation open-label phase, 6 patients were treated and 5 of them were
followed up for 6 months
•
Patients received a single injection of 11 million (M), 22M or 35M cells of AlloCSC-01 (n=2
each) by intracoronary infusion 5 to 7 days after Percutaneous Coronary Intervention (PCI)
•
Data presented at the
European Society of
Cardiology
meeting in London, showed that
AlloCSC-01 has a good safety profile as no
adverse events or Major Adverse Cardiac
Events (MACE) were observed during the 6
month follow-up period
•
Preliminary efficacy data showed a reduction
in the infarct size, and a LVEF improvement
on MRI, over the 6-month follow-up period
(n=5; p<0.05 for both parameters)
*
p-value < 0.1
**
p-value < 0.05
34
CAREMI Phase I/II Trial
Positive Preliminary Results from Phase I Presented at ESC
1 2 3
1 LVEF (%): Left Ventricular Ejection Fraction % change versus screening MRI 2 IS (mL): Infarct Size
