Download The Global Leader in Liver Cell Therapies

The Global Leader in Liver Cell Therapies
Breakthrough immunomodulation & anti-fibrotic
treatments for devastating immune-mediated liver
diseases
Short Briefing
January 2017
John Tchelingerian, PhD
CEO
Promethera at a Glance
Pioneering cell therapies to treat a broad range of devastating immune-mediated liver diseases
Advances in stem cell therapeutics
medicine have opened a novel pathway to
treat liver diseases
Promethera is building unique cell therapy
platforms in this area
Proprietary process to harvest stem cells with
different immunomodulatory properties from
human liver
Unique sourcing and supply chain
Off-the-shelf allogenic products
Clinical stage programs building clinical
evidence in immunomodulation and antifibrosis
Broad and dominant IP position
Pipeline
HepaStem: Phase 2 initiated in ACLF,
Targeted entry in clinic for NASH in H2, 2017
Multiple mechanisms of action with distinct cells
Transatlantic organization
Headquarters near Brussels, Belgium
Production facility near Durham, NC
Around 60 employees
Broad investor consortium
Established broad shareholder base in Europe and Asia
Well positioned to benefit from positive regulatory
environment and growing markets in Asia and
expanding in EU/US
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Disease-centrality of the liver will make it a key intervention point for
novel treatments
Liver is the center of many diseases and at the
epicenter of many health problems
Important organ to treat due to life-critical function
Natural regenerative component is beneficial for cell
therapies
Liver transplantation still a prominent component
in life-saving treatments of devastating liver
conditions
Risky and expensive procedure
Average billed charges for liver transplants in the U.S.
are ~$577k *
Demand of liver transplants already impossible to
meet by healthcare systems/organ shortage
Filtering
Detoxification
Metabolism
Blood Clotting
*source: https://transplantliving.org/before-the-transplant/financing-a-transplant/the-costs/
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Strategic Move into Larger Liver Indications & related Markets
Capitalize on historical expertise in orphan pediatric indications & actively building opportunities in NASH, ACLF and
other major liver indications
Heparesc/
HepaStem
Enzyme Replacement Focus
UCD
• Near term revenues
source
• Targeting potential
marketing approval
for Heparesc in
Canada in 2018
• Partnering
opportunity in Asia
and other markets
HepaStem
Orphan indications
other…
Transfer
• Development
and regulatory
expertise
• Manufacturing
process
• Safety data of
procedure
• KOL network
Major indications
Immunomodulatory Focus
ACLF
NASH/Fibrosis
• High-mortality burden
• Market lacks innovation
• Pre-clinical proof-ofconcept for immunomodulatory capability of
HepaStem
• Multi billion market size
• HepaStem enables multifactorial intervention in
NASH
• Combination potential with
most advanced drugs in
development
other…
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Fully-Formed Supply Chain and Product Platform
Mastering the supply chain for an off-the-shelf allogenic cell therapy product
5
Our approach as a concept
Cooling down the immune system with a safe cell therapy already in clinical trials
Lead product
(HepaStem)
Cooling immune system
CAR-T’s
Heating Immune system
6
HepaStem Development Pipeline
Phase 2 initiated in ACLF, enter clinic for NASH in 2017
INDICATIONS
INDICATIONS
HepaStem
ACLF
HepaStem
NASH/Fibrosis
Start of clinical
development in
H2, 2017
Genetically modified
HepaStem
Hemophilia A/B
(FVIII / FIX)
Early partnering
option
R&D
PRE-CLINICAL
PHASE I/II
PHASE II
PHASE III
MAA
ongoing
ACLF: Acute-on-Chronic Liver Failure / NASH: Non-alcoholic Steatohepatitis
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Key Intervention Points in Acquired Immune-mediated Liver Diseases
Theoretically a reversible event using the right therapeutic modalities
Inflammation
NAFLD, NASH
LIVER FUNCTION
Fibrosis
Total market potential
estimated at:
ACLF > $ multi
billion markets*
Acute insult/ Second hit
Compensated
cirrhosis
HepaStem
Decompensated
cirrhosis
ACLF
Total market potential:
estimated at
Chronic hepatic
decompensation/death
HepaStem
NASH > $ multi
billion markets *
DISEASE PROGRESSION
*Based on Company estimates as applied to a combination of publically available and third-party sourced data
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HepaStem Shows Multiple Mechanisms of Action in vitro
Immunomodulatory and anti-fibrotic potential builds on regenerative support function
•
Supports recovery
Inhibits lymphocyte proliferation
Injury
&
inflammation
Inhibits DC generation
Leading to Fibrosis
Hepatocyte damage and apoptosis
•
•
HepaStem
T-lymphocyte infiltration and release of
pro-inflammatory cytokines + activation of
dendritic cells
•
Inhibits HSC activation
Leading to Cirrhosis
OTHER
PROTEINS
•
•
Extracellular matrix degeneration
Hepatic stellate cell activation
Antibacterial activity
Collagen deposition
9
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ACLF – High-Mortality Condition in Need of Paradigm Shift
Acute-on-Chronic Liver Failure is a market underserved by innovative therapies
Acute deterioration of liver function,
rapidly evolving multi-organ failure
Est. 60-90k patients p.a. in the
USA/EU/Japan, grade 1 &2*
High short-term mortality rate
(>50 % in severe forms)
Standard of care: High dose steroids,
liver transplant in some cases after
rescue
Phase 2 Study initiated in Q4 2016
Primary endpoint: safety of 2 dose regiments
Secondary endpoints:
clinical and biological efficacy parameters
Safety (Day 28, Month 3, Year 1)
*Source: 4 CANONIC study : % of patients with ACLF grade 1 & 2 is +/- 86%
Even modest response in tough to treat patient population will
add validation to approach
Status: ongoing trial
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HepaStem - Preclinical Proof-of-Concept in NASH/Fibrosis
Presented in late-breaking poster session at 2016 AASLD Meeting
HepaStem effect on NASH-fibrosis
in a STAM preclinical model
Data supports pushing HepaStem
in NASH clinical trials
Vehicle
NAS SCORING
No effect of immunosuppression
alone on collagen deposits
With HepaStem: significantly
decreased collagen deposition in
the pericentral region in a dosedependent manner
Reduction in NAS score and visible
improvement of disease histology
4,0
+ Immunosuppression
+ Immune
Suppression
2,2
HepaStem
+ Immune
Suppression
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HepaStem’s USP in the NASH Therapeutic Landscape
Unique position in the current NASH landscape and complementary to advanced therapies
Most advanced competitors are single or
bi-factorial approaches
Ocaliva received accelerated FDA approval
in May 2016
Elafibranor in Phase 3
Broader MoA’s provided by HepaStem
To our knowledge no compound in entire
NASH field has the tissue repair potential
HepaStem or second generation cells
might have
Tissue repair
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Tapping Into the Attractive Asian Markets
Positive regulatory environment has given Asia a head start in cell therapy
Introduction of Western lifestyle expected to cause rise
in liver diseases such as NASH
Advantageous regulatory environment for regenerative
medicine in Japan since 2014
Strategic move towards Japan and South Korea initiated
Potentially faster development route to market for
HepaStem with positive knowledge and data
Other commercial partnering opportunities
Currently 13% of Promethera’s shares held by leading
Asian Investors; including one strategic investor
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Financing and Shareholdings
Broad investor base supporting move into NASH and ACLF
Hopp Family**; 1%
Vesalius BioCapital;
16%
Others*; 14%
- Round A
- Round B
- Round C
5,3 M€
17,0 M€
26,3 M€
Total capital raised
48,6 M€
Non-dilutive funding
24,4 M€
Total amount of proceeds
73,0 M€
Founders; 8%
Fund +; 13%
Cell Innovation
Partners; 2%
Mitsubishi UFJ Capital;
3%
LifeLiver; 3%
MGI Global Fund
(Mitsui); 9%
SRIW; 12%
Shire LLC; 5%
Boehringer Ingelheim
VF; 9%
SMS Investments; 5%
* Essentially HNWI and private investors
** up to 11,2% after conversion of receivable in 2018 or earlier
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Experienced Management Team
John Tchelingerian - CEO
Etienne Sokal - Founder, Chief
Scientific & Innovation Officer
Serial entrepreneur, CEO of Promethera
since Sep. 2015. Co-founder Neurotech,
Key-Obs, Silver Ocean Venture
Previously: President & CEO Key
Neurosciences; Chairman & CEO TcLand
Expression, Chairman & CEO Diatos,
Development Director Neurotech
Frank Hazevoets - CFO & Head of
Corporate Development
20+ years of finance experience in the
financial and pharmaceutical industry
Previously: ING, InBev and TigeniX
Patrick Stragier - VP Operations
25+ years of international operational
and managerial experience
Previously: Solvay, DSM-Biologics,
Genzyme and Lonza
Co-founder of MaSTherCell
20 years experience in the field of
hepatology and liver transplantation
More than 300 peer-reviewed
publications
Henrik L. Luessen – Chief
Business Officer
Torsten Hombeck - Chief
Commercial & Strategy Officer
Nancy Veulemans – VP Clinical
& Medical Affairs
Decebal Bora – VP Regulatory
Affairs
Serial entrepreneur, Founder and
Managing Director of Tytonis
Previously: Symbiotec, Nanomi,
Activaero, OctoPlus.
25+ years experience in the
biopharma and healthcare industries
Previously: TigenX, Bristol Myers
Squibb, Pfizer, Charles River Lab.
15+ years of U.S. and European
experience with public and private
biopharmaceutical companies
Previously: Co-CEO and CBO of Cytonet,
Co-CEO and CFO of Agennix, CFO of
GPC Biotech
20+ years experience in the field of
regulatory affairs.
Previously: ActoGenX, Baxter,
Hoffmann-La Roche, Biogen
CONFIDENTIAL
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Near and Medium Term Strategy and Goals
Rapid development in ACLF and NASH to reach longer-term and high value inflection points
Pre-clinical / Clinical development
Start of Phase 2 trial evaluating HepaStem in ACLF
Further pre-clinical work to advance HepaStem in NASH towards the clinic in H2, 2017
Continued improvements of manufacturing capabilities to launch scalability for commercial success preparation
Heparesc filing for NDS approval in Canada
Commercial / Business Development
Active partnering discussions for HepaStem in Hemophilia
Pursue partnering discussions for Heparesc
Targeting potential marketing approval for Heparesc in Canada in 2018
Follow-on product lines
Continued work on HepaStem’s range of applications including gene engineering
Continued development of our R&D-stage H2Stem platform and for a follow-on clinical stage platform
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Thank you for your attention
John Tchelingerian, PhD – CEO
+32 10 39 43 00
[email protected]
www.promethera.com
Heparesc® is a registered trademark of Promethera Biosciences S.A./N.V