Global Innovator in Liver Disease Therapeutics - Breakthrough treatment options for acute and chronic liver diseases - Promethera
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Global Innovator in Liver Disease Therapeutics Breakthrough treatment options for acute and chronic liver diseases Company Presentation January 2019
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PROMETHERA, Hepastem, HepaScreen, H2Stem, H3stem, H3Screen, Cytonet, Heparesc and Hepabridge are registered trademarks or trademarks of
PROMETHERA in the Benelux, the United States and other countries.
JANUARY 2, 2019 2
Promethera BIOSCIENCES … at a Glance (a)
A worldwide company with a global presence in 4 countries and 70 employees
2009 2012 2014 2016 2018
5.3M€ 17.0M€ 26.3M€ 10M€ 10M€
Series-A Series-B Series-C Series-C extension fundraising
February 2009 April 2016 April 2018 May 2018 February 2019
Foundation Cytonet’s key assets Baliopharm Opening Japanese 10 years Anniversary
2012 Acquisition Acquisition Branch
Phase I/II First patients 2013: Phase I/II – trial 2016: ACLF Phase IIa 2017: Shibuya
with 20 patients partnership
2014: Phase IIb/III – 2017: LifeLiver 2018: Itochu partnership
approval in Belgium to partnership
enrol patients 3
Promethera BIOSCIENCES … at a Glance (b)
A unique set of technological assets and exclusive IP & Know How
Promethera’s mission:
Pioneering the development of cell therapies and complementary biopharmaceutical approaches to treat
a broad variety of devastating and severe liver diseases with no effective therapeutic cure
3 TECHNOLOGICAL ROBUST INVESTOR CONSORTIUM
PLATFORMS & PRODUCTS
Well positioned to
Largest liver sourcing benefit from
• HepaStem positive regulatory
& unique supply chain
• H2Stem on a global basis environment and
• Atrosimab strong EU/Asian
markets
JANUARY 2, 2019 4
A Liver Disease Patient's Journey
Promethera to Address Key Intervention Points in Acquired Immune-mediated Liver Diseases
Total market potential
estimated at:
NAFLD, NASH ACLF > $ multi
Inflammation
billion markets*
Fibrosis
Compensated Acute insult/ Second hit
LIVER FUNCTION
cirrhosis
Atrosimab Decompensated
Multiple therapeutic HepaStem cirrhosis
options with 2
Chronic hepatic
property technologies
decompensation/death
(standalone or combo)
ACLF
Total market potential:
estimated at
HepaStem
NASH > $ multi
billion markets *
DISEASE PROGRESSION
JANUARY 2, 2019 5
*Based on Company estimates as applied to a combination of publically available and third-party sourced data
HepaStem for Liver Rescue Therapy in ACLF & NASH
HepaStem could potentially replace liver transplantation based on early clinical data in ACLF
and its immuno-modulation properties
ACUTE +
(ACLF)
Injection of
inflammation
HepaStem Restores hepatocyte function,
Hepatocyte Injury
bilirubin processing,
Functional impairment
restoration MELD score decrease
CHRONIC
-
(NASH)
Injection of
HepaStem Stops inflammation,
Hepatic stellate cells (HSC)
inhibits activation of HSC
activation leading to progressive
inhibition and fibrosis JANUARY 2, 2019 6
fibrosis
HepaStem Shows Multiple Mechanisms of Action in vitro
Immunomodulatory and anti-fibrotic potential builds on regenerative support function
• Supports recovery
Injury
Hepatocyte damage and apoptosis &
• Inhibits lymphocyte proliferation inflammation
• Inhibits DC generation / TNF α production Leading to Fibrosis
HepaStem
T-lymphocyte infiltration and release of
pro-inflammatory cytokines + activation of
dendritic cells
• Inhibits HSC activation
OTHER Leading to Cirrhosis
PROTEINS • Extracellular matrix degeneration Hepatic stellate cell activation
• Antibacterial activity (under investigation)
Collagen deposition
JANUARY 2, 2019 7 7
Fully-Formed Supply Chain and Product Platform
Mastering the supply chain for an off-the-shelf allogenic cell therapy product
STRATEGIC
MANUFACTURING / MANUFACTURING
CELL EXPANSION PARTNER
CELL ISOLATION STORAGE AND
DELIVERY
RECONSTITUTION
LIVER SOURCING AND APPLICATION
Donor N Patients
1 Liver
MAXIMIZATION OF PROCESS
AND COGS CONTROL
JANUARY 2, 2019 8
Current Product Pipeline for Liver Diseases
TECHNOLOGY PLATFORM INDICATIONS R&D PRECLINICAL PHASE 1 PHASE 2 PHASE 3
ACLF*
HepaStem
NASH*/Fibrosis
Atrosimab NASH/Fibrosis
H2Stem Tissue repair
*ACLF: Acute Chronic Liver Failure / NASH: No-alcoholic Steatohepatitis
partnership: development of HepaStem (UCD indication in registration trial)
and H2Stem in South-Korea.
JANUARY 2, 2019 9HepaStem Intravenously Injected Through a Peripheral Vein
Systemic infusion (peripheral vein - IV) for current First in man
studies
Intravenous delivery is
a well established non-
invasive
technique/clinical
practice
IV-administration is
one of the key drivers
of applicability
Cells have a first
passage in the lungs After intravenous infusion of Indium labelled HepaStem-like cells, the cells
and are further
distributed in other are transiently trapped in the lung, which decreases rapidly, while a clear
organs, mainly the homing to the liver can be observed, which remains stable until the end of
liver, without lung the 5-day observation period. A mild presence of labelled cells can be seen
trapping
in the spleen. A hot spot of cells can be observed in the right ankle, which
Pre-clinical and first was the site of chronic hemarthrosis in the patient, showing the homing of
clinical study started
cells to inflammatory sites. (Sokal & al, Transplantation 2017)
JANUARY 2, 2019 10HepaStem – Preclinical Proof-of-Concept in NASH/Fibrosis
Presented in late-breaking poster session at 2016 AASLD Meeting
HepaStem effect on NASH-fibrosis 4,0
in a STAM preclinical model
No effect of immunosuppression Vehicle
alone on collagen deposits + Immuno-
NAS SCORING
suppression
With HepaStem: significantly
decreased collagen deposition in
the pericentral region in a dose-
dependent manner
2,2
Reduction in NAS score and visible
improvement of disease histology HepaStem
+ Immune
Data supports pushing HepaStem Suppression
in NASH clinical trials
JANUARY 2, 2019 12Novel Data on HepaStem’s Ability to Reduce Key Disease
Parameters in Advanced Stage NASH in Vivo Model
Presented in poster session at EASL 2018
Fibrosis (vehicle): NAS score (vehicle):
1.25% 4,86
1 injection: 0.81% 1 injection: 3,75 (22,4%)
3 injections: 0.75% 3 injections: 3,29 ( 32,6%)
New data confirms HepaStem’s therapeutic potential across different stages of the disease
JANUARY 2, 2019 13Strategy for NASH Clinical Trials
Bridging from our ACLF clinical learning in HEP-101 study to F4-NASH early decompensation
Meld >= 22
ACLF Gr 0 Gr1 Gr2 G3
Less severe More severe HepaStem
MeldNASH – The Competitive Landscape
Unique position in the current NASH landscape and complementary to advanced therapies
Fibrosis Inflammation Steatosis - Metabolic dysfunction Tissue repair
BMS Pharmaxis Pfizer Malinrock Pfizer BMS Intercept
Phase 1 Tiziana Durect CohBar Poxel Poxel
BirdRock Bio + 11
HepaStem - Promethera HepaStem - Potential
Immuron Can-Fite
Cirius Cymabay Gilead Pfizer
Mecidinova
Madrigal Novartis Galmed Enyo
Phase 2 Galmed Genfit Boerhinger Inventiva
Viking Therapeutics Pfizer Novartis Gilead
Novartis
+3 + 12
Gilead Intercept
Genfit
Phase 3 Allergan
Galectin
JANUARY 2, 2019 15TNF-R1 Inhibition – A Complimentary Therapeutic Strategy
Atrosimab – A proprietary single-chain antibody fragment and selective TNF-R1 antagonist
TNF-alpha pathway and its receptor 1 (TNF-R1) are implicated in
the progression of many inflammatory diseases, including
chronic liver diseases leading to fibrosis and cirrhosis
TNF-R1 inhibition is a valuable strategy in its own right as well as
in combination with Promethera’s HepaStem technology
Atrosimab development plan can build on existing data from
parental full-IgG antibody ATROSAB
JANUARY 2, 2019 16Initial Data on Anti-TNF-R1 Strategy in NASH
Promising data from parental antibody candidate ATROSAB previews Atrosimab’s potential
Initial NASH data obtained using TNF-R1 Anti-Apoptotic Effect
full-length antibody
Atrosimab was optimized resulting in
several favorable characteristics including:
a 3,6-fold stronger inhibition of TNF-R1
activation than parental antibody
a 5-fold more effective inhibition of TNF-
Anti-Fibrotic Effect
induced cell death
a 6-fold more potent inhibition of TNF-
mediated release of pro-inflammatory
cytokines IL-6 and IL-8
a longer half-life than standard Fab and scFv
fragments
17Financing and Shareholding
Broad Investor base supporting move into the new indications NASH & ACLF
Promethera Financing Shareholding Structure
Funding till date :
- Round A (2009-2010) 5,3 M€
- Round B (2012) 17,0 M€
- Round C (2014 & 2016) 26,3 M€
- Round D (2018 – First Closing) 10 M€
Total Capital raised 58,6 M€
Convertible Bonds 23,9 M€
Non-dilutive funding 24,1 M€
Total Amount of Proceeds 106,6 M€
* Essentially HNWI and private investors 02 JANUARY 2019 18Promethera – Strategic Alliance with Itochu
One of the biggest Japan-based business conglomerate
A strategic investment of 10M€ in Promethera Biosciences
Supports the company to advance Promethera’s product and business development
strategy in Asia
R&D support for HepaStem development program in selected Asian markets including:
Acute on Chronic Liver Failure (ACLF)
Non-Alcoholic Steatohepatitis (NASH)
Urea Cycle Disorder (UCD)
JANUARY 2, 2019 19Experienced Management Team
John Tchelingerian – President Etienne Sokal - Founder, Chief Mutsuki Takano – Group CFO &
&CEO Scientific & Medical Officer Japan Branch General Manager
Serial entrepreneur, CEO of Promethera 20 years experience in the field of Business operation, new business launch,
since Sep. 2015. Co-founder Neurotech, hepatology and liver transplantation J/V set-up and foreign company
Key-Obs, Silver Ocean Venture More than 200 peer-reviewed operation
Previously: President & CEO Key publications Previously: Mitsui & Co., Ltd,
Neurosciences; Chairman & CEO TcLand
Expression, Chairman & CEO Diatos,
Development Director Neurotech
Mark Johnston - CCO Bertrand Lellouche – CFO EU /
Henrik L. Luessen – Chief Promethera Biosciences US Financial Operations
Business Officer Group & MD of Promethera 14+ years of CFO & Executive advisor for
Serial entrepreneur, Founder and fast growing biotech companies
Biosciences LLC
Managing Director of Tytonis Previously: Eligo Bioscience, Step
20+ years of experience in the field.
Previously: LTS Lohmann, Nanomi, Pharma, ideXlab, Enterome
Held various senior level in several
Activaero, OctoPlus. regenerative medicine companies.
Previously: ADMET Technologies,
Vesta Therapeutics, Cytonet LLC
Jef Pinxteren - VP Operations Decebal Bora – VP Regulatory Nathalie Belmonte –
20+ years of international operational
and managerial experience
Affairs VP Product Development
20+ years experience in the field of 10+ years experience in the field of cell
Previously: ReGenesys, Stem Cell
regulatory affairs. therapy from both an academic and
Institute Leuven, VIB, University of Ghent
Previously: ActoGenX, Baxter, Hoffmann- biotech position.
La Roche, Biogen Previously: TxCell , French academic
laboratory (INSERM), the Telethon
Institute for Gene Therapy in Milan.
JANUARY 2, 2019 20Thank you for your attention John Tchelingerian, PhD – CEO +32 10 39 43 00 info@promethera.com www.promethera.com
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