Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO

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Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
Building a
                         Global Leader in
                        Orphan Oncology

                                    May 2017

     Euronext Paris   Ticker
Nasdaq Copenhagen     ONXEO
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
Important Information
This presentation has been prepared for information and background purposes only and the information contained herein (unless otherwise indicated)
has been solely provided by Onxeo (the “Company”). This presentation does not constitute an offer of securities, a prospectus or an offering
memorandum in whole or in part, and does not contain comprehensive or complete information about the Company, which can be found elsewhere as
described below.
The information and opinions contained in this document have not been subject to independent verification and are qualified in their entirety by the
business, financial and other information that the Company is required to publish in accordance with the rules, regulations and practices applicable to
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”).
All information (including on markets) not separately sourced is based, in whole or in part, on internal Company data and estimates, and is provided as
of the date of this presentation only, and is subject to change without notice.
No representation, warranty or undertaking, express or implied, is made by the Company or any other person as to the accuracy, completeness or
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responsibility for and shall not, under any circumstance, be held liable for any loss or damage that may arise from the use of this document or the
information or opinions contained in it. In particular, this document contains information on the use of the Company’s products and its competitive
position. This information has been drawn from various sources or from the Company’s own estimates which may not be accurate and thus no reliance
should be placed on such information. Any prospective investors must make their own investigation and assessments and consult with their own
advisers concerning any evaluation of the Company and its prospects, and this document, or any part of it, may not form the basis of or be relied on in
connection with any investment decision.
All statements in this presentation other than statements of historical fact are or may be deemed to be forward-looking statements. These forward
looking statements can be identified by the use of forward looking terminology, including the terms “development”, “estimates”, “expects”, “intends”,
“may”, “planned”, “will”, “milestones”, “move to”, “on track”, “potential”, “targeting”, “time to market”, “value”, or other variations or comparable
terminology, or by discussions of strategy, plans, objectives, goals, future events or intentions. These forward-looking statements relate to the
Company's future prospects, developments, marketing strategy and funding, as well as the Company’s technology, and are based on financial and non-
financial information, including projections as to the future regulatory situation and other information and assumptions. They are subject to various
risks and uncertainties, including those described in the Exchange Information.
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.

2    May 2017
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
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
                               (1)   Internal estimate for HCC 1st line and 2nd line indications
3   May 2017
                               (2)   Source GlobalData &Navigant for NSCLC +SCCHN+ PTCL indications
                               (3)   SourceGlobaData for TNBC indication
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
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
4   May 2017
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
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

5   May 2017
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
Experienced and International Leadership Team
     Management team                                  Board of directors
               International team of 50+ employees
               with deep expertise in strategy,           Joseph Zakrzewski, Chairman
               finance and drug development, from
                                                          Judith Greciet, CEO
               preclinical to registration

                 Judith Greciet, CEO                      Financière de la Montagne
                 (formerly Pharmacia, Wyeth, Eisai)       (represented by Nicolas Trebouta)

                 Françoise Bono, CSO                      Elvira Sanz
                 (Sanofi, Evotec)
                                                          Danièle Guyot-Caparros
                 Olivier de Beaumont, CMO
                 (Stallergenes Greer, Quintiles,          Christine Garnier
                 Aventis)
                                                          Thomas Hofstaetter
                 Nicolas Fellman, CFO
                 (Pfizer, Ernst & Young)                  Jean-Pierre Kinet

                 Philippe Maitre, EVP US, Corp. Dev       Jean-Pierre Bizzari
                 (Aventis, PPD, mAbRx)

6   May 2017
Building a Global Leader in Orphan Oncology - May 2017 Ticker ONXEO
A diversified and well-balanced portfolio in orphan oncology

7   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
9   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.

10   May 2017
Livatag: ReLive Phase III Study - design

                                                                         End of
                                                                     randomization                                   Mid-17
                                                                       Jan, 2017
       PHASE III                                                                                                Preliminary results
                                    6-hour IV infusion -20 mg/m²
                                                                                                                  overall survival
     Randomized,                      < 4 weeks>   < 4 weeks>   < 4 weeks>   < 4 weeks>                           after 285 events
                                                                                          … up to progression
     comparative, 3 arms   n =130

     390 patients                   6-hour IV infusion - 30 mg/m²
     (>= 18 years old)                             < 4 weeks>   < 4 weeks>   < 4 weeks>
                           n =130                                                … up to progression

     11 countries
     EU, US, MENA
                                    Best standard of care
     70 active centers     n =130

                              2nd line or more advanced HCC having progressed or intolerant to sorafenib,
       TARGET
                              stage BCLC B or C with a Child-Pugh score from A5 to B7
       POPULATION

                              Primary endpoint: Overall Survival
       ENDPOINTS              Secondary endpoints: Progression Free Survival, Objective Response Rate,
                              Optimal dose, Safety, PK, Predictive factors of safety and efficacy, Quality of life

11   May 2017
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

12   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

                           (1) International Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study , (J Clin Oncol 26 :4124-
                               4130) and GLOBOCAN 2012, IARC data.
14   May 2017
                           (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

15   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

16   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)
                                                                                                Cancer cells are no
     Multiple DNA                                                                         3     longer able to
                             1
     repair pathways                                                                            continue dividing
     are activated in                                                                           with damaged
     cancer cells via the                                                                       DNA, resulting in
     recruitment of                                                                             cell death
     several enzymes
     allowing them to
     repair efficiently
     damaged DNA and
     escape cell death

                                                            2
                              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
18     May 2017
                              tumor cell’s chromosomes
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                                    3’
                                                         5’
                                                                                     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
                                   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
19   May 2017
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
20   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)

21   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).

23   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

24   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             Oral formulation            Phase I/II initiation
                preclinical results          preclinical results
                             mono                        combo

                      H1 2017                                        H2 2017                      H1 2018       H2 2018

                      AsiDNA™                                                     AsiDNA™                      AsiDNA™
                  Preclinical PoC                                          Phase I Initiation               Phase I Results
                    of IV activity                                 (Systemic administration)

                                       Livatag®
                            ReLive Phase III trial
                             preliminary results

26   May 2017
A differentiated biotech company in orphan oncology

              A strong
            & diversified                       Targeting significant
          product portfolio                    unmet medical needs

           Multi-billion                      A proactive, experienced
          market potential                          global team

27   May 2017
Contacts:
Judith Greciet – CEO
Nicolas Fellmann – CFO
Tel: +33 1 45 58 76 00 - contact@onxeo.com

Company Information:
www.onxeo.com
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