Building a global leader in orphan oncology

Transcription

1 Building a global leader in orphan oncology March 2016

2 Agenda achievements 2. Financial Results for Acquisition of DNA Therapeutics: presentation of the sidna technology 4. Some perspectives in conclusion 2

3 Forward-looking statements This document includes forward-looking statements relating to the Company s future prospects, development and business strategies. By their nature, forward-looking statements involve risks and uncertainties and are not guarantees of future performance. The Company s financial condition and results of operations and the development of the industry in which the Company operates may differ materially from those made in or suggested by the forward-looking statements contained in this document. In addition, even if the Company s financial condition and results of operations and the development of the industry in which the Company operates are consistent with the forward-looking statements contained in this document, those results or developments may not be indicative of results or developments in future periods. The Company does not undertake any obligation to review or confirm analysts or others expectations or estimates or to release publicly any revisions to any forwardlooking statements to reflect events that occur or circumstances that arise after the date of this document. This document does not constitute an offer or invitation to sell or issue, or any solicitation of an offer to purchase or subscribe for, any shares of the Company. For a discussion of risks and uncertainties which could cause actual results, financial condition, performance or achievements of Onxeo SA to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the 2014 Reference Document filed with the AMF on April 14, 2015, which is available on the AMF website ( or on Onxeo's website ( 3

4 Onxeo our vision, our mission Driven by a strong vision: To be a global leader and pioneer in orphan diseases, with a focus on oncology, to make the difference Dedicated to our mission: We are determined to develop innovative medicines to provide patients with hope and improve their lives 4 CONFIDENTIAL Strategic meeting July 2015

5 Onxeo strategy for success Building an Orphan Oncology innovator 5 Crafting a diversified and deep orphan oncology pipeline Based on innovative science to bring therapeutic response to unmet medical needs Benefitting from favourable measures from regulators Enriching our pipeline with breakthrough technologies thanks to an ambitious M&A strategy Reinforced US footprint Strengthened BoD with US expertise and key R&D background International management team The opportunities Diversified product pipeline with various levels of advancement allowing short to mid terms value catalysts From preclinical to advanced clinical stage pipeline Already 3 commercialized products Our role as catalyst for change We bring together skilled R&D teams to add value to programs Within Onxeo and with a high level network of KOLs Unique track record of 3 products registered in Europe and US We identify and integrate new promising technologies

6 2015 achievements

7 2015: Successful year of consolidation for Onxeo Clinical development Major achievements in all lead programs Progression of Phase III trial of Livatag in HCC in line with development calendar Positive results of Phase I trial of Beleodaq and CHOP in 1st-line PTCL High visibility of Onxeo s preclinical and clinical data in numerous key scientific events New IP protection for Livatag Comprehensive preclinical research program of Livatag and Beleodaq in combination 3 key partnerships with Tier I research centers in Europe Progressive launch of commercialized products Resulting in increase in recurring revenues 7 Strengthening of Board of Directors and senior executive team Bringing significant international and US expertise in-house

8 LIVATAG Advancing and accelerating development Livatag : Nanoformulated doxorubicine developed in Hepatocellular Carcinoma (HCC) Potential blockbuster with about 800M sales potential ReLive: Phase III trial on track to confirm efficacy Multicenter randomized controlled open label to assess efficacy (OS) and safety of Livatag (20 and 30mg/m² - slow IV) vs BSC after failure or intolerance to Sorafenib 65% of 400 patients randomized + study expanded 4 new countries Strong safety profile with 7 positive DSMB (Data Safety Monitoring Board) next one in April 2016 Preliminary results of Relive expected in 2017 IP protection strengthened with new patent: protection potentially expanded to 2036 Initiation of combination program to prepare for the future and expand product value Preclinical combination studies with cytotoxics, targeted therapies and immunotherapies Targeting HCC 1 st -line and other solid tumors Potential to enter the clinic in next months in selected indications 8

9 BELEODAQ Value potential beyond PTCL 2 nd line Beleodaq : pan HDAC inhibitor already approved in the US Conditional approval in 2014 (pivotal phase 2 Belief trial) in PTCL 2 nd line Commercialized in the U.S. by Spectrum Pharmaceuticals Evaluate product in 1 st -line PTCL in combination with CHOP Phase I performed by Spectrum to assess combination MTD and safety profile (n=23) Belinostat MTD is 1000mg/m2 days 1-5 every 3 weeks + CHOP = at approved doses ORR was 86%; CR 67% (CR CHOP ~50%), PR 19% Well tolerated Oral presentation by Mayo Clinic investigator Dr. Patrick Johnston at ASH in December 2015 Phase III synopsis under preparation with Spectrum Exploratory preclinical research program in combination with other cancer agents Strong rational based on broad mechanism of action of panhdac inhibitor Identify key combinations & indications to enter the clinic in the next months. 9

10 VALIDIVE Ready to enter phase III with the right partner Positive results of phase II trial in severe oral mucositis 2015 : Preparation of the phase III including discussion with Regulatory bodies Status: orphan status in Europe; Fast Track designation in the U.S. Regulators feedback supported Validive phase III but FDA requests to follow the normal guidelines ie 2 phases III to perform Significant lengthening of study length and costs Strategic decision to proceed in co-development for Validive next steps Resource allocation decision: 2 phases III represent too large an investment for Onxeo alone More value can be created with other projects (like DT01) - sooner and at less cost Continue to value Validive s achievements at scientific meetings (ESTRO 2016 ) Actively seek for partner 10

11 Strengthened Board of Directors with an International Focus Strong leadership International team of 50+ employees with strong expertise in drug development and commercialization Experienced international supervisory board 7 Members with expertise in BD, Corporate dev., Strategy, Finance 2 observers with strong clinical development & scientific background J. Zakrzewski Chairman J. Greciet CEO R. Greig Director T. Hofstaetter Director J.P. Bizzari Observer 11 D. Solomon Director D. Guyot-Caparros Director N. Trebouta Director J.P. Kinet Observer

12 Financial Results 2015

13 Key drivers of our 2015 accounts An increased investment in our orphan oncology R&D programs R&D expenses of 16.4m (vs 13m in 2014 or 14.8m proforma) Main driver: Livatag phase III Good control over R&D spend with a mix of preclinical and clinical programs Increased R&D tax credit at 3.7m (vs 2.3m in 2014) Stable non-r&d expenses resulting from an efficient integration of Topotarget activities after 2014 merger Synergies in G&A and other expenses at 9.3m (vs 9.7m in 2014 or 10.2m proforma) Increased revenues from commercialized products Recurring revenues at 2.7m (vs 1.6m in 2014) Impact of Beleodaq and Sitavig launches in the US Comparison with 2014 biased by merger-related items 13

14 2015 Consolidated accounts (Profit and loss) In thousands Euros 31/12/ /12/2014 Revenues, out of which Recurring revenues Non-recurring revenues Operating expenses, out of which R&D expenses G&A and other expenses 3,481 2, (25,657) 16,350 9,307 22,081 1,625 20,455 (22,697) 12,978 9,719 Milestone payments from Spectrum linked with Beleodaq US registration Operating profit/loss (22,365) (5,554) Non-current operating profit/loss (189) (4,938) Merger-related costs Financial income Income tax 2,353 (2,150) Net profit/loss (19,409) (7,699) IFRS impact of Danish taxation 14

15 2015 Consolidated accounts (balance sheet) In thousands Euros 31/12/ /12/2014 Long term assets, out of which Goodwill Non-recurring revenues Current assets, out of which Cash 87,539 20,058 66,300 41,696 33,793 89,052 20,058 67,873 62,946 57,227 Total assets 129, ,999 Acquired IP from Topotarget No impairment in line with current developments of Beleodaq Equity 102, ,971 Deferred tax liability 11,381 13,805 Deferred tax impact of 2014 merger Other liabilities 15,056 16,223 Total equity and liabilities 129, ,999 15

16 Cash perspective Good financial position to invest in R&D and develop our programs In million 16.35M: R&D Investments 2.7M: Recurring Revenues : +68% M: R&D tax credit Confirmed estimated cash runway until mid /12/ /12/2015

17 Acquisition of DNA Therapeutics and sidna technology

18 Acquisition of DNA Therapeutics Second deal to enlarge company s pipeline, 2 years after Topotarget acquisition DNA Therapeutics: the acquisition of a highly innovative and promising technology A clinical-stage French biotech ( spin-off of Curie, CNRS, Museum Histoire Naturelle ) developing sidna technology: a innovative mechanism of action in one of the most promising field of cancer research Supported by international key scientific leaders A potential blockbuster with a large scope of utilization in monotherapy & combination in various tumor types 18

19 DNA repair: a new leading field of scientific research 2000 First clinical trials with PARP inhibitors 1940 s DNA-alkylating agents used in treatment of cancer (nitrogen mustards, nitrosureas, platinums) 1960 s DNA repair field born Largely academic work not considered as an approach for treatment of cancer 1970 s 2014 Discovery of DNA repair-mediated resistance to alkylating agent Approval of first PARP inhibitor (Olaparib) by FDA in advanced ovarian cancer with BRCA mutated tumors 2015 Nobel prize for Chemistry awarded for «mechanistic studies of DNA repair (Tomas Lindahl, Paul Modrich & Aziz Sancar) DNA repair now one of key focus areas for pharmaceutical industry 19

20 Presentation of the sidna technology Presentation by Dr. Marie Dutreix, Institut Curie. 20

21 DRIIM trial results Phase I/IIa 23 patients, 12 centres in France, metastatic melonoma DT01 in combination with radiotherapy 5 dose levels (16-96mg), 3 times/week over 2 weeks - delivered intra-tumorally or peri- tumorally DT01 was well tolerated, showed good immune tolerance and no evidence of inflammatory phenomena ORR = 59%; CR = 30%; PR = 29% Rate of complete response from radiotherapy alone approx 10% - based on literature data These data support the further evaluation of DT01 in the clinic 21

22 Development options for new sidna compound Evidence supporting activity by systemic administration Preclinical animal models Observations from the DRIIM trial Opportunities as monotherapy Tumors with high frequency of mutations advanced/metastatic disease lung, bladder, kidney, head & neck, colorectal, glioblastoma, lymphoma Clear differentiation from PARP inhibitors as potential to be effective without underlying tumor mutation eg. BRCA genes Opportunities in combination Strong rationale for combinations with DNA-damaging agents (alkylating agents, antimetabolites, topoisomerase inhibitors, ionizing radiation) In tumors resistant to cytotoxics through DNA repair-mediated mechanisms Preclinical data showing synergy with treatment modalities resulting in DNA damage e.g. carboplatin Mechanistic and predictive biomarkers available to support clinical development 22

23 Development options for new sidna compound Evidence supporting activity by systemic administration Preclinical animal models Observations from the DRIIM trial Opportunities as monotherapy Tumors with high frequency of mutations advanced/metastatic disease lung, bladder, kidney, head & neck, colorectal, glioblastoma, lymphoma Clear differentiation from PARP inhibitors as potential to be effective without underlying tumor mutation eg. BRCA genes Opportunities in combination Strong rationale for combinations with DNA-damaging agents (alkylating agents, antimetabolites, topoisomerase inhibitors, ionizing radiation) In tumors resistant to cytotoxics through DNA repair-mediated mechanisms Preclinical data showing synergy with treatment modalities resulting in DNA damage e.g. carboplatin Mechanistic and predictive biomarkers available to support clinical development 23

24 Two examples of development options Triple Negative Breast Cancer High unmet need No approved drugs DNA damaging cytotoxics used in treatment Orphan disease : Target-population in mtnbc after failure of 1 st line = 10,900 in the US and 24,900 in EU Market potential EU + US = 1.7 bn as of today and up to 2.3 bn by 2035 Recurrent ovarian cancer High unmet need DNA damaging cytotoxics used in treatment Orphan disease: Target-population = 7,000 in the US and 9,000 in EU-5 Market potential EU + US = 1.9 bn as of today and up to 2.7 bn by 2035 Clinical development will be implemented after first optimizing the manufacturing process, set to start as soon as the deal closes 24

25 Key elements of acquisition Deal structure: No cash expenditure for Onxeo 1.7 million in Onxeo shares at closing 1 million in Onxeo shares when product enters phase 2 trial for systemic use Historic shareholder of DNA Therapeutics to bring 1 million at closing Earn out: 25 million per indication ( based on royalties on sales) Calendar 29 February: signing of the binding term sheet End of March: expected closing of transaction, Onxeo to become 100% owner of DNA Therapeutics 25

26 Perspectives

27 ONXEO: Building a diversified product portfolio in orphan oncology 27

28 Significant near / mid-term catalysts to drive value DNA Therapeutics Deal closing March/April 2016 Livatag Combinations preclinical results 1H 2016 and onwards Phase III trial: Next DSMB April 2016 Phase III trial: Preliminary results 2017 Beleodaq 1 st line Phase III initiation 2016 Beleodaq combinations preclinical results 1H 2016 and onwards Validive Phase III trial initiation Subject to partnership 28

29 Wrapping Up : Why Invest in Onxeo Emerging global leader in a highly dynamic market : Orphan Oncology therapeutics Strong track record from preclinical to registration Ambitious M&A strategy to build a deep and promising pipeline Recently reinforced product portfolio, that includes promising idna technology Well balanced pipeline from preclinical programs to advanced clinical stage triggering short to mid terms value catalysts A well experienced team dedicated to best develop our projects 29

30 Q&A

31 Thank you for your attention!

32 Appendix

33 BELEODAQ, a breakthrough technology A pan-hdac inhibitor Increases acetylation of histone, epigenetic modification Turns on tumor suppressor genes Turns off oncogenes Mechanism of action provides broad potential Potent anticancer compound; Strong synergy in combination with classical chemotherapies; Ideal combination product with emerging immunooncology agents 33 Olaff, Witt et al., Cancer Letters 277 (2009) 8-21

34 LIVATAG Mechanism of action ideally suited to address liver cancer Nanoparticle formulation of Doxorubicin Proprietary Transdrug nanotechnology platform Nanoformulation designed to accumulate in the liver and evade tumor cell resistance mediated by MDR efflux pumps Mechanism of action Absorption to the cell surface Release of doxorubicin close the cell membrane as ion pair doxo/pihca Ion pair protects doxorubicin - reduced drug efflux through MDR-related protein Nuclear delivery of free doxorubicin with subsequent cytotoxic effect 34

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