Download Building a Global Leader in Orphan Oncology

Building a
Global Leader in
Orphan Oncology
May 2017
Euronext Paris
Nasdaq Copenhagen
Ticker
ONXEO
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has been solely provided by Onxeo (the “Company”). This presentation does not constitute an offer of securities, a prospectus or an offering
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The information and opinions contained in this document have not been subject to independent verification and are qualified in their entirety by the
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companies listed on Euronext Paris, including in particular the risk factors and other information in the Company’s Document de référence (Registration
Document) registered by the French Autorité des marchés financiers (Financial Markets Authority) (the “AMF”) on April 29, 2016 under no. D.16-0452,
and available in both French and English language versions on the Company’s website, and in any other periodic report, all of which are available free of
charge on the Company’s website (www.onxeo.com) (the “Exchange Information”).
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Forward-looking statements are not guarantees of future performance and the Company’s actual financial position, results and cash flow, regulatory
situation, as well as the trends in the sector in which the Company operates, may differ materially from those reflected in the forward-looking
statements. The Company does not undertake any obligation to update any forward-looking statements or any other information in this presentation.
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May 2017
Investment Thesis
A publicly-traded biotech company specialized in orphan oncology
Developing innovative drugs to address unmet medical needs in Oncology
Based in Paris, Copenhagen and New York; listed on Euronext (Paris) and Nasdaq (Copenhagen)
A solid, diversified and well-balanced pipeline
Livatag®: Currently in Phase III for Hepatocellular Carcinoma (HCC)
Beleodaq®: Marketed in the US by Spectrum for 2nd line Peripheral T-Cell Lymphoma (PTCL)
AsiDNA™: 1st-in-class DNA Repair Signal Interfering with compelling Phase I data
…with significant sales potential
Livatag®: Potential Sales € 800 M (1)
Beleodaq®: Market Size from € 7.9 B in 2016 to € 19.3 B in 2025 (2)
AsiDNA™: Market Size to exceed € 2.1 B by 2025 just for the first pre-identified
indication(3)
... and potentially value-creating near & mid-term milestones
Solid cash position to support currently planned operations until early 2018
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May 2017
(1)
(2)
(3)
Internal estimate for HCC 1st line and 2nd line indications
Source GlobalData &Navigant for NSCLC +SCCHN+ PTCL indications
SourceGlobaData for TNBC indication
Onxeo’s laser-focused strategy
Bring innovation to orphan oncology patients
Crafting a solid and diversified orphan oncology pipeline
Capitalizing on preferred regulatory pathways (ODD, Fast Track…)
Currently 3 products with 3 different technologies
Balancing the development risk with products at diverse clinical stages (Ph. I to Ph. III)
Securing breakthrough technologies & products through focused M&A strategy:
Topotarget acquisition in 2014
DNA Therapeutics acquisition in 2016
Create shareholder value through
a proven business model
Proven ability to identify and integrate promising pre-clinical technologies /
products
Develop products into clinical up to inflexion points, attractive for partnering by
Pharmaceutical key players
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May 2017
Onxeo’s key differentiating features
The product opportunities
A rich product pipeline generating multiple near / mid-term catalysts:
Candidates range from preclinical to advanced clinical stages (Phase III)
New ASiDNA™, 1st in-class Signal Interfering DNA (SiDNA) repair platform in clinic
New oral form under development for Beleodaq®
Innovative compounds totalling > several € B sales potential
Global reach and in-depth experience
3 products already approved by FDA and/or EMA
Unparalleled skills from preclinical & CMC to Phase II / Proof of Concept
A Board of Directors and Executive Team with deep US expertise – A network of
prominent Scientific Advisors
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May 2017
Experienced and International Leadership Team
Management team
International team of 50+ employees
with deep expertise in strategy,
finance and drug development, from
preclinical to registration
Board of directors
Joseph Zakrzewski, Chairman
Judith Greciet, CEO
Judith Greciet, CEO
(formerly Pharmacia, Wyeth, Eisai)
Financière de la Montagne
(represented by Nicolas Trebouta)
Françoise Bono, CSO
(Sanofi, Evotec)
Elvira Sanz
Olivier de Beaumont, CMO
(Stallergenes Greer, Quintiles,
Aventis)
Danièle Guyot-Caparros
Christine Garnier
Thomas Hofstaetter
Nicolas Fellman, CFO
(Pfizer, Ernst & Young)
Philippe Maitre, EVP US, Corp. Dev
(Aventis, PPD, mAbRx)
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May 2017
Jean-Pierre Kinet
Jean-Pierre Bizzari
A diversified and well-balanced portfolio in orphan oncology
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May 2017
Livatag® Update
Livatag® mechanism of action optimal for liver cancer
Nanoparticle formulation of doxorubicin
Proprietary Transdrug™ nanotechnology platform
Nanoformulation designed to evade tumor cell
resistance mediated by Multi Drug Resistance
(MDR) efflux pumps
– Up to 12-fold increased exposure to liver tumor cells
compared to doxorubicin
Mechanism of action
Absorption to the cell surface
Release of doxorubicin close to the cell
membrane as ion pair doxo/PEBCA(*)
Ion pair protects doxorubicin - reduced drug
efflux through MDR-related protein
Increased nuclear delivery of free doxorubicin
with subsequent cytotoxic effect
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May 2017
(*) PEBCA
polymer = Poly-Ethyl-Butyl-Cyanoacrylate
Livatag® “ReLive” Phase III Pivotal Study on track to confirm
efficacy
Designed to confirm promising Phase II efficacy results
n=28 Patients with unresectable HCC
Multicenter, controlled and randomized trial; up to 3 injections per week over 4 weeks
Median survival of 31.7 months vs. 15 months for patients on TACE (p < 0.05)
Acute respiratory adverse events leading to study termination and change of administration
scheme in phase III
Phase III Study to assess efficacy (OS) and safety of Livatag® (20 and 30mg/m² - slow
IV) vs Best Standard of Care after failure or intolerance to sorafenib
A favorable safety profile confirmed by Data Safety Monitoring Board (DSMB) reviews
9 consecutive DSMB reviews: positive recommendations to continue study w/o modification
No apparent pulmonary toxicity after close to 1000 infusions, no unexpected AE.
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May 2017
Livatag: ReLive Phase III Study - design
End of
randomization
Jan, 2017
PHASE III
Randomized,
comparative, 3 arms
390 patients
(>= 18 years old)
Mid-17
6-hour IV infusion -20 mg/m²
< 4 weeks>
< 4 weeks>
< 4 weeks>
< 4 weeks>
… up to progression
Preliminary results
overall survival
after 285 events
n =130
6-hour IV infusion - 30 mg/m²
n =130
<4 weeks>
< 4 weeks>
< 4 weeks>
< 4 weeks>
… up to progression
11 countries
EU, US, MENA
70 active centers
TARGET
POPULATION
ENDPOINTS
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May 2017
n =130
Best standard of care
2nd line or more advanced HCC having progressed or intolerant to sorafenib,
stage BCLC B or C with a Child-Pugh score from A5 to B7
Primary endpoint: Overall Survival
Secondary endpoints: Progression Free Survival, Objective Response Rate,
Optimal dose, Safety, PK, Predictive factors of safety and efficacy, Quality of life
Livatag ®, a potential blockbuster
In the large but under-served HCC market
Only one product approved (Sorafenib) in first line HCC
Estimated incidence of 120,000 eligible patients (US + Europe); 480,000 patients WW
Sales estimates around €220m for 2nd line in Europe/US
Livatag full potential sales (WW - HCC all lines) estimated around €800m(1)
Company will initiate Licensing discussions after Phase III results
Exploration of Livatag full potential for HCC …… and beyond HCC (other solid tumors)
Targeting HCC 1st-line in combination with TKI’s
For other type of tumors:
– Preclinical combination studies with cytotoxics, targeted therapies and immunotherapies
ongoing
– Supra-additive efficacy already demonstrated in combination with immuno-oncology agents
in HCC and pancreas models
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May 2017
(1) internal estimate
belinostat / Beleodaq®
Update
Beleodaq® (IV belinostat) approved as 2nd line treatment
for PTCL
Peripheral T-cell lymphoma (PTCL) (1)
Subtype of non-Hodgkin’s lymphoma (NHL) which affects T-cells
Worldwide incidence = 38,000 to 58,000 cases (10-15% of NHL cases) / 17,000 to 27,000
incident cases in key pharmaceutical markets (US + EU28 + Japan + China)
FDA conditional approval in 2nd line PTCL following successful Phase II
(Belief Study: n = 129)(2)
25.8 % ORR (CR&PR) - Median DoR of 13.6 months by IWG criteria (to disease progression)
Low incidence of Grade 3-4 hematologic toxicities (thrombocytopenia 7%; neutropenia 6.2%;
anemia 10.9%)
Phase I Bel-CHOP combination performed to assess MTD and safety profile (n=23)
in 1st Line PTCL
Belinostat MTD is 1000mg/m2 days 1-5 every 3 weeks + CHOP = approved doses
ORR 86%; CR 67% (CR CHOP ~50%), PR 19%
Phase III synopsis in PTCL 1st line under preparation with Spectrum Pharma
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May 2017
(1) International Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study , (J Clin Oncol 26 :41244130) and GLOBOCAN 2012, IARC data.
(2) Lee et al (FDA approval) Clin. Cancer Res. March 2015.
belinostat (Beleodaq®), an HDAC inhibitor dedicated to
improve immune response against solid tumors
A dedicated-target product profile
belinostat is an HDAC class 1 inhibitor with an HDAC6 component
Oral formulation of belinostat displays good bioavailability, very good tolerance and short
half-life compatible with combination with immune check point therapies
An anticipated broad potential mechanism of action on tumor immune response
Strong potential for combination with anti-cancer immunotherapies
First positive data in immuno-competent mouse syngeneic model of Beleodaq® + CTLA4 Ab
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May 2017
belinostat / Beleodaq®: Build value potential beyond PTCL
Expand PTCL beyond the US (Europe – South America - ….)
Today’s sales limited to US Market (Last 12-month sales around $14.0M)
Expansion to South America through licensing agreement with Pint Pharma
Patient early access programs under consideration for Europe (PTCL)
Development of an oral formulation of Beleodaq® to expand product potential in
particular for combination with immune checkpoint therapies
An important step providing opportunities for new indications & extended patent protection
Exploratory preclinical research program in combination with Immuno-Oncology agents
Follow-up studies ongoing to assess combination interest in various tumors, to enter clinic by
year-end
Full market potential (IV and Oral forms combined): from € 7.9 B in 2016 to € 19.3 B
in 2025 (1)
(1) Source GlobalData and Navigant for NSCLC +SCCHN+ PTCL indications
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May 2017
AsiDNATM
An Innovative Concept Leading
to a First-in-Class Product
AsiDNATM concept: leading tumor cells to death through the
blinding of the DNA repair system
Why DNA repair inhibition?
•
•
•
Many cancer treatments rely on DNA damaging agents
Tumor cells survive genotoxic treatment by repairing DNA damage
DNA repair is a main mechanism of resistance to radiotherapy and chemotherapy for advanced stage
tumors (exposition to DNA damage and replication accidents that need to be repaired)
Multiple DNA
repair pathways
are activated in
cancer cells via the
recruitment of
several enzymes
allowing them to
repair efficiently
damaged DNA and
escape cell death
3
1
2
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May 2017
AsiDNA mimics DNA breaks into the cells and activates DNA
damage signaling enzymes, thus inducing a “false” damage
signal that prevents the repair enzymes from being recruited at
the site where they should act to repair the damage on the
tumor cell’s chromosomes
Cancer cells are no
longer able to
continue dividing
with damaged
DNA, resulting in
cell death
AsiDNA™ - A first-in-class molecule
32 bp DNA duplex with a 5´-Chol-TEG & a non-nucleotidic loop - Protected
from disassociation and degradation and designed for optimal cellular uptake
Cholesterol - Vector that
promotes cellular uptake
Active 32 bp DNA duplex
3’
5’
Binds and activates DNA-PK and
PARP signaling enzymes
Sequence not specific, chosen to
be non-homologous
Genomic DNA length optimized
5’
3’
Loop- Coupling Agent
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Phosphorothioate substitutions at the 5’ and 3’ ends to prevent degradation1
Efficient nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
AsiDNA – First lead of a new class of DNA repair inhibitors
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May 2017
1. Quanz M, et al. PLoS ONE. 2009 4(7), doi: 10.1371/journal.pone.0006298
2. Berthault N, et al. Cancer Gene Therapy (2011), 1-12, doi: 10.1038/cgt.2011.3
AsiDNA™- Solid synergy in combination with PARP inhibitors
Preclinical in vivo efficacy of AsiDNA™ vs. PARP inhibitors in mouse triple negative breast
cancer model(1) : potential as monotherapy in genetically unstable tumors
Synergistic effect of AsiDNA™ combined with various PARP inhibitors including oloparib(2)
Increased unrepaired DNA break sites, DNA damages and cell lethality in 21 different tumor cell lines
including BRCA mutated
No lethality observed in healthy cells
Strong indication that drug resistance to the combination would be a very rare event
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May 2017
(1) Article under finalization: “ Predictive Biomarkers to AsiDNA”.
(2) Jdey W, et al. Clin Can Res. 2016;22:DOI: 10.1158/1078-0432.CCR-16-1193.
AsiDNA™- First clinical outcome and development strategy
DRIIM phase I (2015)(1)
23 metastatic melanoma patients, 12 centers in France
AsiDNA™ in combination with radiotherapy, (3 doses/week for 2 weeks, Intra-Tumoral admin.)
Good tolerance, strong immune tolerance and no evidence of inflammatory phenomena
ORR = 59%; CR = 30%; PR = 29% ( CR rate from low-dose radiotherapy alone less than 10%
(Konefal et al, 1987; Olivier et al, 2007)
Strong evidence supporting activity by systemic administration
Preclinical animal models
Observations from DRIIM Phase I
Mechanistic and predictive biomarkers available to support clinical development
Next step to demonstrate potential when dosed via intravenous route
Phase I in mono and combination in preparation (2017)
Broad spectrum of potential indications. Market Size for TNBC from € 0.8 B in 2016 to
€2.1 B by 2025 (2)
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May 2017
(1) Le Tourneau C, et al. BJC. 2016;1-7; doi:10.1038/bjc.2016.120.
(2): Source GlobalData
IP & Financial Position
Solid IP protection(*) for all products in the pipeline
Livatag®
Composition patent through 2019 with additional patents through 2032
New patent filing on composition potentially protecting Livatag® WW until 2036
Orphan status in both Europe and US; Fast Track designation in US
Beleodaq®
Drug substance patent until 2021, drug product patent until 2027 (2026 o/US)
Orphan status in both EU & US - accelerated FDA approval July 2014
for 2nd line PTCL
AsiDNA™
Proprietary technology (Method of Use) patent until 2024
Drug product and related compounds protected until 2031
(*) Not including potential supplementary protection certificate (SPC) or patent term extension (PTE).
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May 2017
Shareholder structure and financial profile
Shareholder structure
(as of Oct. 5, 2016)(1)
Key statistics(1):
Dual listing Paris/Copenhagen (ticker ONXEO)
47M shares outstanding
Market capitalization : ± €120M
3.9% of shares owned by BoD, Management &
Staff (on a fully diluted basis excluding Financière
de la Montagne)(2)
Cash position on 12/31/2016: €29,2M (incl.
gross proceeds from Sept. 2016 private
placement)
Cash to early 2018
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May 2017
(1) At closing of the €12.5M Capital Increase
(2) 3.9% represents shares held by top management, board of directors (excluding Financière de la Montagne),
executive committee and shares resulting from stock options, free shares and warrants granted to Onxeo staff.
Upcoming Milestones
Significant near & mid-term newsflow
Beleodaq® Oral
Beleodaq® Oral
Beleodaq® Oral
Oral formulation
preclinical results
mono
Oral formulation
preclinical results
combo
Phase I/II initiation
H1 2017
H2 2017
AsiDNA™
AsiDNA™
Preclinical PoC
of IV activity
Phase I Initiation
(Systemic administration)
Phase I Results
ReLive Phase III trial
preliminary results
May 2017
H2 2018
AsiDNA™
Livatag®
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H1 2018
A differentiated biotech company in orphan oncology
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A strong
& diversified
product portfolio
Targeting significant
unmet medical needs
Multi-billion
market potential
A proactive, experienced
global team
May 2017
Contacts:
Judith Greciet – CEO
Nicolas Fellmann – CFO
Tel: +33 1 45 58 76 00 - [email protected]
Company Information:
www.onxeo.com