TopoTarget - Kapitalmarkedsdag marts 2012


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TopoTarget - Kapitalmarkedsdag marts 2012

  1. 1. ProInvestor Life Science Seminar Anders Vadsholt (CFO) and Lars Damstrup (Medical Director) Topotarget A/S – March 27, 2012
  2. 2. Safe harbor statementThis presentation may contain forward-looking statements, including statements about our expectations of theprogression of our pre-clinical and clinical pipeline including the timing for commencement and completion ofclinical trials and with respect to cash burn guidance. Such statements are based on managements currentexpectations and are subject to a number of risks and uncertainties that could cause actual results to differmaterially from those described in the forward-looking statements. Topotarget cautions investors that therecan be no assurance that actual results or business conditions will not differ materially from those projected orsuggested in such forward-looking statements as a result of various factors, including, but not limited to, thefollowing: The risk that any one or more of the drug development programs of Topotarget A/S will not proceedas planned for technical, scientific, or commercial reasons or due to patient enrollment issues or based on newinformation from non-clinical or clinical studies or from other sources; the success of competing products andtechnologies; technological uncertainty and product development risks; uncertainty of additional funding;Topotargets history of incurring losses and the uncertainty of achieving profitability; Topotargets stage ofdevelopment as a biopharmaceutical company; government regulation; patent infringement claims againstTopotargets products, processes, and technologies; the ability to protect Topotargets patents and proprietaryrights; uncertainties relating to commercialization rights; and product liability exposure. We disclaim anyintention or obligation to update or revise any forward-looking statements, whether as a result of newinformation, future events, or otherwise, unless required by law. 2
  3. 3. Topotarget corporate presentation• Executive summary• Belinostat supercharging chemotherapy• Financial overview 3
  4. 4. Topotarget at a glance (1) An international Scandinavian-based biopharmaceutical company dedicated to develop and market cancer therapies• Headquartered in Copenhagen, Denmark (Medicon Valley Alliance) with ~24 employees with a lean cost structure pursued• Focused on development and commercialization of belinostat, a molecular targeted cancer therapy• Divestment of Topotarget USA, Inc. and Totect to Apricus Biosciences, Inc. closed on December 30, 2011 Listing NASDAQ OMX Copenhagen Symbol TOPO Market capitalization DKK 400m (as of March 22, 2012) No. of shares 132,652,050 (as of March 22, 2012) 4
  5. 5. Topotarget at a glance (2) • In collaboration with Spectrum Pharmaceuticals, Inc. (SPPI) and the NCI we are developing and commercializing belinostat in the US • Based on current plans and without taking potential SPPI milestones into account, cash resources will take us into 2013 Shareholder Ownership Geographic split of shareholders*The 10 largest shareholders Other + 30%combined 20%HealthCap funds + 13% DenmarkAvanza Pension + 6% 40% UK 8%* Estimated Switzerland 10% Sweden 22% 5
  6. 6. Topotarget is making a difference to cancer patients … Creating shareholder value Lead Strong Unmet Track record development TOPOTARGET Partnerships – STRONG INVESTMENT CASE belinostat market need candidate profile Proven track Novel cancer drug Strong Solid tumor Promising record only 7 target: partnerships: preliminary years from idea to Hematological clinical efficacy launch: HDACi Spectrum diseases Pharmaceuticals, I Robust safety Totect® nc. Solid commercial Savene® potential Strong IP National Cancer Institute Large database Rigshospitalet (DK) Mono- and combination therapy 6
  7. 7. … with a clear-cut focus on belinostat 2010 2012  Belinostat Early-stage acquisitions • Optimized organization • PTCL*** • Prioritized late-stage pipeline • Cancer of unknown primary Savene®/Totect® • Experienced development team • MDS/AML*** Unfocused early-stage pipeline • US partner • Non-small cell lung cancer • Research facility closed down • Bladder cancer Discovery platform • Enhancement of BoD and • Hepatocellular cancerHigh burn rate, 100+ employees management team • Ovarian cancer • Establishment of GOAB* and Several cancer targets disease-specific advisory boards *) Global Oncology Advisory Board **) Clinical Study Report • Completion of CSRs** ***) Peripheral T-cell lymphoma, myelodys- Belinostat plastic syndromes, acute myeloid leukemia Take-off 2011 7
  8. 8. Partnerships are key to a successful commercialization of belinostat North Asia Canada Europe USA China Mexico India Africa South America AustraliaChina: First right of negotiationto Spectrum Pharmaceuticals, Inc. 8
  9. 9. Belinostat partner agreement withDeal terms• Agreement, February 2, 2010• Total deal value USD 350 million, USD 30 million cash upfront, double-digit royalties• Milestone includes 1 million SPPI shares and cash milestone at acceptance of PTCL NDA filing• SPPI funds PTCL BELIEF trial and Topotarget funds randomized phase II CUP study• Co-development in additional indications, cost split 70/30 (SPPI/Topotarget)• Joint development and commercialization committees set-up• Territory: North Ameri-ca and India, with a first right of negotiation to China• SPPI is responsible for submitting an NDA on belinostat for PTCL 9
  10. 10. Overall strategy for 2012 and beyond (1) belinostatContinue to establish belinostat as one of the mostsuccessful HDAC inhibitors in selected indications by:– Analyzing late-stage PTCL and CUP study results– Submitting NDA to the FDA in PTCL through US partner Spectrum Pharmaceuticals (SPPI)– Exploring commercial opportunities outside the US to maximize commercial value– Unlocking full potential by initiating further clinical studies in the most promising indications within hematology and solid tumors 10
  11. 11. Strategy for 2012 and beyond (2)• Pre-market and launch PTCL in ex-US countries – Timely and complete submission of NDA (led by SPPI) – Leverage FDA approval for launches in Latin America, Eastern Europe (non-EMA), and Asia/Pacific (led by Topotarget A/S)• Identify partners and/or distributors for ex-US markets• Develop life-cycle plan and prepare markets for future indications – Liquid tumors – pursue at least one hematology indication – Solid tumors – leverage CUP data into randomized trials, e.g. bladder cancer – Initiate investigator-driven clinical trials• Develop aggressive communication plan to drive customer value and differentiation vs. competition• Strengthen customer collaborations and engagements – KOLs, oncology organizations, and advocacy groups 11
  12. 12. Topotarget corporate presentation• Executive summary• Belinostat supercharging chemotherapy• Financial overview 12
  13. 13. Histone DeACetylase inhibitors (HDACi) Bypassing natural apoptosis is a hallmark of the cancer diseaseMain characteristics of belinostat• ”Turns on” suppressor genes ‒ Inhibiting HDACs activate silenced genes ‒ Some of these are apoptotic (cell death) genes ‒ Activation causes selective cancer cell death• ”Turns off” oncogenes ‒ Results in inhibitions of cancer cell growthOther mechanisms of action• Inhibition of the growth and development of new blood vessels, in effect starving cancer cells• Induction of immune system to target cancer cells• Interacts with for example tubulin, thus synergizing with various chemotherapies and potentially overcoming drug resistance, which is the main reason for failure of cancer treatment 13
  14. 14. Belinostat is supercharging chemotherapy Cancer cells can over time develop resistance to the given chemotherapy – a resistance that HDACi’s may overcome HDACi’s work in synergy with chemotherapy by supercharging the effects of cytostatics Belinostat is a novel pan-HDACi with the ability of regulation of multiple class I and II HDAC’sBelinostat in combination with chemotherapy increases efficacy with only a minor or moderate increase in toxicity 14 14
  15. 15. Belinostat has a compelling clinical profile FLEXIBLE ADMINISTRATION Option of multiple administration and formulation modes (IV, CIV, and oral) ABILITY TO COMBINE Combined with main established chemotherapies will lead to a maximized commercial potential ENCOURAGING SAFETY PROFILEShown to be well tolerated in the clinical use (≈900 pts.), with an excellent safety including cardiac toxicity profile and minimal bone marrow toxicity PROMISING EFFICACY DATA Preliminary clinical efficacy in solid and hematological malignancies Synergistic pre-clinical effect with established therapies 15
  16. 16. Preliminary safety data confirms belinostat’s differentiation potential Belinostat preliminary safety data shows lower incidence of grade 3-4 Adverse Events within most common related AEs (nausea, fatigue, diarrhea, vomiting) when compared to marketed drugs within same class and within same primary pursued PTCL indication Istodax® Zolinza® Folotyn® 1) 2) 3) 4) Belinostat Romidepsin Vorinostat Pralatrexate # of patients: 68 363 74 111 % of patients with grade 3-4 related Adverse Events: % % % % Nausea 1 4 4 4 Fatigue 3 11 5 6 Diarrhea 0 2 0 2 Vomiting 0 5 0 2 Please note that for this slide, the comparison data is not generated in a head-to-head study. The analysis is carried out based on available published study data on the respective marketed drugs approved for CTCL and PTCL.1) Source: Safety population from belinostat clinical studies: TT-30 and CLN-6, I.V.2) Source: Prescribing information Romidepsin, FDA label 2011-09-30, approved for CTCL and PTCL, I.V.3) Source: Olsen et al., Phase IIb Multicenter Trial of Vorinostat …, Journal of Clinical Oncology 2007; 25 (21), approved in CTCL, Oral4) Source: Prescribing information Pralatrexate, FDA label 2011-07-01, approved for PTCL , I.V. 16
  17. 17. Overview of belinostat clinical trials 2012 Randomized Target Enrollment TimeIndication Study Sponsor Phase I Phase II phase II or Milestone # status frame pivotal BELIEF 100- Top-line resultsPTCL SPPI Completed 2012 (CLN-19) 120 NDA filing H1CUP CLN-17 TT 88 Completed Top-line results 2012Solid Scientific CLN-9 TT 92 Completed 2012tumors publication Results stage I Phase I completed H1Solid + STS CLN-14 TT 55 LPFV stage I in Phase II 2012 phase II recruitingDrug-Drug CLN-20 SPPI/TT 39 Recruiting Top-line results 2012interaction SPI-1014 RecruitmentNSCLC SPPI/TT 35 Recruiting n/a Bel completed 17
  18. 18. PTCL is an orphan indication with a high unmet medical need ... Key facts for PTCL PTCL characteristics• Incidence: 15,500 new cases per annum • Peripheral T-cell lymphoma (PTCL) is a (US, Japan, and EU27) subtype of non-Hodgkin’s lymphoma• Prevalence: 41,000 patients (US, EU) • 10-15% of non-Hodgkin’s lymphoma patients are PTCL patients• Niche market: World-wide market size • Aggressive, high-grade cancer estimated to be USD 100-130 million • Generally with a poor prognosis and limited treatment options • Average age of patients with PTCL: 65 years 18
  19. 19. ... and there are promising data from initial PTCL clinical trial Pre- LeftStudy CLN-6 axillary Case report PTCL (monotherapy) node• Phase IIa trial with patients who had refractory CTCL (28) or PTCL (25)• Efficacy in 19 evaluable PTCL patients ‒ CR: 2, PR: 4, SD: 4 ‒ Response rate: carinal node Pre-treatment On treatment 6/19 = 32% [CI: 16-45%] - ‒ Duration of a) Response: +268 days • 61- • b) Stable disease: +133 days 19
  20. 20. Pivotal PTCL study BELIEF successfully enrolled FDA Interactions Study facts BELIEFSpecial Protocol Assessment (SPA) • BELinostat In patients with relapsed or• Pivotal trial BELIEF in place with an rEFractory peripheral T-cell lymphoma ORR of at least 20% Protocol designOrphan drug • Open-labelled, multi-center,• Designation granted prospective, phase IIb pivotal trial • Enrollment of 129 patients completedFast track • Dosing• Designation granted – I.V., 1000mg/m2, days 1-5 every three weeksNDA submission• Planned for 2012 DMC outcome • Positive interim analysis in March 2011 – Safety and futility – based on <5 responses in 45 evaluable patients 20
  21. 21. Update on BELIEF study (pivotal PTCL) (1)• Registrational and pivotal phase IIb study – 129 patients enrolled• Sponsored, conducted, and finalized by SPPI (initiated by Topotarget A/S)• Top-line data expected to be announced by SPPI in H2 2012• NDA submission to the FDA expected by end 2012 with estimated approval in 2013• Expected milestone payments from SPPI: – Following FDA acceptance of NDA: 1 million shares of common stock in SPPI and a double- digit million USD cash payment – Upon FDA approval: Double-digit million USD cash payment 21
  22. 22. Update on BELIEF study (pivotal PTCL) (2)• Following US launch, Topotarget A/S will receive double-digit royalty payments from SPPI• Possibility of subsequent drug approval in emerging markets for PTCL indication (provided FDA approval) and led by Topotarget A/S• Topotarget A/S pursues partnership opportunities in Europe, Asia/Pacific, Latin America, and in the rest of the world• Potential value of belinostat may exist in other liquid tumor indications as well, e.g. MDS 22
  23. 23. Update on CUP clinical study• Randomized, controlled study with 89 patients enrolled• Fully conducted and sponsored by Topotarget A/S• Announcement of top-line phase II data expected by end of H1 2012• Based on the design and modest powering of the CUP study, the study will not serve as a registration study• However, an obtained PFS improvement rate of 20-40% will be viewed as a positive trend warranting further studies in this indication 23
  24. 24. Topotarget corporate presentation• Executive summary• Belinostat supercharging chemotherapy• Financial overview 24
  25. 25. Specific Action Plan to secure financial capability for 2012 and onwards• ‘Special Plan’ initiated in December 2011 to best secure financial capability for belinostat: – Direct investment efforts into finalization of PTCL pivotal study and subsequent NDA filing with SPPI – Finalize randomized phase II CUP study – Continue clinical development in solid tumors and hematological cancer – Topotarget USA, Inc. and all Totect® related activities divested to Apricus Biosciences, Inc. – Hiring freeze in place and a reduction of the number of employees in Denmark by around 40% – Reduction of cash burn rate by approx. 15% incl. cash preserving plan 25
  26. 26. Successful divestment of Totect and Topotarget USA, Inc.• Transaction completed in December 2011• Apricus Biosciences, Inc. acquired the rights to Totect in North and South America as well as Topotarget USA, Inc.• Improved financial implications: – Upfront: USD 2 million – Milestone: USD 2 million 26
  27. 27. Triggers expected to increase the value* – a data-driven process PTCL top-line data PTCL NDA filing CUP top-line Ovarian and CUP Potential orphan drug FDA approval of NDA filing data read-out designation for PTCL EU (SPPI milestone) H1 2012 H2 2012 H1 2013 Divestment of Initiation of new belinostat SPPI milestone upon Totect clinical trials** acceptance of NDA filing Partner Europe and Asia/Pac* Timelines are illustrative only** Preparation (i.e. contracts and regulatory) 27 27
  28. 28. Financial highlightsDKK 000 2011 2010Revenue 65.598 107.826Production costs (1.840) (5.442)Research and development costs (54.345) (71.608)Write down of research and development projects - (189.541)Administrative expenses (40.765) (38.778)Net loss from continued operations (29.012) (84.785)Net (loss)/profit from discontinued operations (3.999) 29.095Net loss for the year (33.011) (55.689)Basic and diluted EPS (DKK) continued and discontinued operations (0,25) (0,42) Dec 31, 2011 Dec 31, 2010Cash flow from operating activities (88.847) 40.101Cash flow from investing activities (1.919) 34.686Cash flow from financing activities - 138 28 28
  29. 29. Outlook• Topotarget A/S expects an estimated pre-tax loss in the range of DKK 75-95 million for the full year financial result of 2012• The expected net cash and cash equivalents will be around DKK 35-55 million at year-end 2012 29 29
  30. 30. Contact information Topotarget A/S Fruebjergvej 3 DK-2100 Copenhagen Tel: +45 39178392 Email: 30 30
  31. 31. Q&A 31 31