Immunity for Life TM. Sven Rohmann, MD, PhD

Transcription

1 Immunity for Life TM Sven Rohmann, MD, PhD

2 Disclaimer This Presentation includes and is based, inter alia, on forward-looking information and statements that are subject to risks and uncertainties that could cause actual results to differ. These statements and this Presentation are based on current expectations, estimates and projections, which generally are identifiable by statements containing words such as expects, believes, estimates or similar expressions. Important factors that could cause actual results to differ materially from those expectations include, among others, general economic and industry conditions in markets which are expected to be major markets for Biotec Pharmacon ASA s products, as well as risks and uncertainties related to product development, regulatory approvals, commercial partnerships, the outcome of intellectual property rights litigation and the competitive situation. Although Biotec Pharmacon ASA believes that its expectations and the Presentation are based upon reasonable assumptions, it can give no assurance that those expectations will be achieved or that the actual results will be as set out in the Presentation. Biotec Pharmacon ASA is making no representation or warranty, expressed or implied, as to the accuracy, reliability or completeness of the Presentation, and neither Biotec Pharmacon ASA nor any of its directors, officers or employees will have any liability to you or any other persons resulting from your use of the information contained herein. This presentation was prepared for the 4 th Annual International Partnering Conference Bio-Europe Spring in Barcelona, on March 8-10, 2009, and the information contained within will not be updated in this presentation. The following slides should be read and considered in connection with other information provided by the company. No shares of Biotec Pharmacon ASA are being offered in connection with this presentation and no such shares have been registered under the U.S. Securities Act of 1933, as amended (the "Act"), and such shares may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Act. 2

3 What happened with SBG in Phase III? >>> SBG failed to show activity in DU AND OM! Diabetic ulcers Oral mucositis Preclinical Phase I Phase II Phase III NDA Failed Failed Immunotherapy of cancer IBD "We are not overly surprised by the results from the oral mucositis study, given the outcome of the diabetic ulcer studies in November last year. As with the diabetic ulcer studies, there was no statistically significant difference between the two treatment groups, although a marginal advantage of SBG over placebo was seen for the primary endpoint", says CEO Lars Viksmoen. 3

4 What happened with SBG in Phase III? Re-analysis of study medication (drug substance and drug product) Substance Drug substance (Active Product Ingredient) Drug product (Polyethylene-ampules) Drug product (Polyethylene-ampules) Storage place Quality laboratorium Tromsø Production factory Tromsø (from Holopack) Returned from study centers (UK og Europa) Compared with samples of drug substance/product also from phase I and II, where available Basket of tests, with main focus on biological activity, both for SBG and placebo 4

5 What happened with SBG in Phase III? Possible root causes and conclusions Possible root causes : Study design flaws Technical study flaws Product flaws SBG Placebo Conclusions: Systemic failure no flaws found in manufacturing process or in study design and/or study conduct Early evidence of unexpected interaction between the polyethylene product container and SBG, rendering SBG inactive over time 5

6 No alteration in molecular structure Molecular weight distribution (SEC-MALS-RI) (drug substance vs drug product) 6

7 Fragmentation of the gel structure Re-analysis of study medication (drug substance vs drug product) Active Drug Substance Phase III batch Inactive Drug Product Phase III batch

8 Consequences of fragmented gel structure MoA depends on intact 3-D conformity SBG binds to multiple receptors on macrophages CR3 (CD11b/CD18)-receptor SBG Dectin-1 Human b-glucan receptor A B C Toll like receptor 2/6 8

9 Biological activity Reduction of biological activity Re-analysis of study medication Biological activity in Drug Substance vs Drug Product SBG Drug substance A SBG drug Substance B SBG Phase III product in PE-ampules Concentration 9

10 The Polyethylene Issue Root cause findings 3rd party assessment It is highly likely that a root cause for the current form of SBG failing has been identified Based on considerable experience the suspected inactivation of SBG in polyethylene ampoules would not have been normally expected as an issue during the selection of ampoules as the primary container for SBG Ashley Hankinson, Global Compliance International 10

11 The Polyethylene Issue First Clinical Evidence in DU? Sub-analysis of clinical data*- batch-to-batch performance Product (DP) % healed Comparator product % healed p-value SBG Nottingham 1 st batch (N=46) 21.7% Placebo (N=34) 32.4% 0.29 SBG Nottingham 2 nd batch (N=21) 52.4% Placebo (N=21) 33.3% 0.22 SBG Nottingham 1 st batch (N=46) 21.7% SBG Nottingham 2 nd batch (N=21) 52.4% *Ad-hoc, non pre-specified analysis 11

12 The Polyethylene Issue: Unexpected interaction between SBG and polyethylene in the product container Problem: Interaction with polyethylene of the product container destroys treatment efficacy of SBG during prolonged storage Solution: Change the product container away from polyethylene (e.g. to carboethylene) Initiate accelerated stability studies - as part of a follow-up program 12

13 Proof of Concept Clinical phase II SBG in treatment of diabetic foot ulcers SBG Control 13

14 Proof of Concept clinical phase II SBG for prevention and treatment of oral mucositis Patients developing severe Oral Mucositis (%) Placebo SBG Source: Sook Bin Woo, emedicine, Chemotherapy-induced Oral Mucositis Duration of therapy (days) n=36 14

15 + SBG Proof of concept Cancer SBG and monoclonal antibodies in cancer Significant (p<0.05) effect of mab+sbg versus mab alone mab alone Methodology: Inoculation of mice with human neuroblastoma cancer cells, leading to development of tumors Treatment with the mab 3F8 in active and control group SBG in addition to mab (3F8) in the active group Primary end point: Tumor size (% increase) mab + SBG 15

16 + SBG Clinical Proof of Concept Phase Ib/IIa Clinical phase Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Phase I/II, Sloan Kettering Blue area = periods of patient inclusion, black areas = periods of study completion and reporting Before After Patient populations First study; n=45 Patient enrolment completed Primary endpoint Assess the clinical toxicity of SBG in combination with anti-gd2 antibody 3F8 in stage 4 juvenile neuroblastoma patients. Secondary endpoints Assess the biologic effects of SBG in combination with anti-cd2 antibody 3F8 Marked decrease in neuroblastoma disease burden 123I-MIBG scan of patient treated with one cycle of 3F8+SBG (80mg/kg/day)

17 Proof of concept IBD SBG in the treatment of ulcerative colitis SBG protects against DSS-induced colitis, and has effect on epithelial proliferation and intestinal restitution Oral SBG treatment stimulates expansion of Peyer s patches and mesenteric lymph nodes (not shown) *P<0.05, **P<0.01, ***P<0.001, 2-way ANOVA Sandvik et al submitted 17

18 SBG Partnering Opportunities Diabetic ulcers Oral mucositis Preclinical Phase I Phase II Phase III NDA Immunotherapy of cancer IBD Open for partnering discussions with both global and regional partners Open for partnering opportunities for SBG for all disease indications 18

19 Summary Disappointing phase III results SBG did not show superiority over placebo in diabetic foot ulcer and oral mucositis Interaction with polyethylene in product containers may have rendered SBG clinically inactive Phase III failures asks for re-alignments of R&D activities; cost base and workforce match the new activity level Maintained and continuing discussions with potential partners and investment groups Continued strong growth in Biotec Marine Biochemicals AS Divested Immunocorp Consumer Health AS for 31.5 M NOK. 19

20 Contact: Sven Rohmann, MD, PhD Mobile: Biotec Pharmacon ASA, Strandgata 3 N-9008 Tromso, Norway, or Biotec Pharmacon ASA, Drammensveien 149 N-0277 Oslo, Norway 20

21 Back-up s & Financials

22 Financial Highlights (NOKm) Q409 Q Marine Biochemicals Pharmaceutical development Revenues Marine Biochemicals Pharmaceutical development Corporate and unallocated EBITDA Profit before tax Net profit, continued business Net profit consumer health, discontinued Net profit animal health, discontinued Net profit Split into new segments and restated for the divestments of Animal Health in 2008 and Consumer Health in

23 Marine Biochemicals 2009 revenue at NOK 17.6 million, well above the 15 MNOK target Q4 09 revenue increase of 28% and 47% for the full year 2009 NOKm Q4 09 Q Revenue Other operating expenses (net) EBITDA Depreciation EBIT Strong full year growth for both SAP (+34%) and Cod- UNG (+107 %) Strong positive contribution; EBITDA-margin of 36% in Q4 09 and 47% for the full year Remains committed to longerterm target to double revenue over the next three years 23

24 Pharmaceutical Development Overall costs in line with fullyear guiding Not fully comparable after restating and new segment reporting structure NOKm Q4 09 Q Revenue Other operating expenses (net) EBITDA Depreciation EBIT Clinical development costs amounted to NOK 35.2 million in 2009 (NOK 34.6) Significantly lower in 2010, although with some costs related to phase III wrap-up in Q1 10 Lower in-house costs From 35 to 14 employees in the parent company 24

25 Cash Flow NOK ( 000) Q4 09 Q Cash Flow from operating activities Cash Flow from investing activities Cash Flow from financing activities Cash flow in the period

26 Consolidated Balance Sheet Condensed figures (NOK 000) Non-current assets Cash and cash eq Other current assets Total current assets Assets Equity Liabilities Equity & Liabilities Equity Ratio 65% 85% Non-current assets reduced by NOK 30.7 million due to valuation allowance of deferred tax after failed phase III studies Equity reduction to NOK 60.2 million (65%) reflects losses in the period Cash position of NOK 50 million, including approximately NOK 20 million from divestment of Immunocorp Consumer Health Payment of remaining sales price of NOK 31.5 million due in Q

27 Summary (I) Priority action plan for Pharma Development Confirm root cause behind disappointing phase III results Address reasons and make sure that SBG will not fail again Re-establish the pharmaceutical strategy platform Sufficient funding for planned activities no need for further asset sales High cash burn in Q1 10 due to wrap up clinical studies Significantly lower cost base from Q2 10 Decide on level of partner and/or industrial investor involvement and collaboration alternatives and ensure funding for future R&D activities Full-year cash burn depending on program/project activity, strategic choices and partnering activity 27

28 Summary (II) Growing the Marine Biochemicals business Continuing expansion in the molecular biology and diagnostics markets Grow: Existing products Existing customers Expand: Customer base Use in new applications Product portfolio with new products Profitable doubling of revenue expected over the next 3 years (mainly from existing products) 28

29 Thank You! 29

30 Non-pharmaceutical business Biotec Marine Biochemicals Immunocorp Consumer Health

31 Biotec Marine Biochemicals Enzymes for R&D and diagnostics markets Strong revenue growth - exceeded the 2009 revenue target Strong growth for both SAP and Cod-UNG New product pipe line High margin business Longer-term target to double revenue over the next three years Molecular structure of cod Uracil-DNA N-glycosylase (Leiros, et al. 2003) 31

32 Biotec Marine Biochemicals Market development Market growth: >10% CAGR Increased customer focus: New customer focused organization in place Customer input into product development Typical presentation of qpcr data (own data) New applications/use: New PCR kits from major research & diagnostic kit companies w/bmb enzymes 32

33 Biotec Marine Biochemicals R&D and product development New enzyme products: HL-dsDNase and SAN in extensive trials - very well received by key opinion leaders New products in pipeline R&D: Bio-prospecting activities in Tromsø (Sfi-MABCENT) Increasing customer needs input into R&D process In house molecular engineering expertise Specialty; cold adapted/heat labile Proteins in SDS-PAGE gel (own data) 33

34 Immunocorp Consumer Health Non-core business - divested at the end of Q4 Good strategic match with the buyer Sana Pharma AS 5-year supply agreement Sales price NOK 31.5 million Cash effect of ~NOK 20 million in 2009, with the remainder due in Q Strengthening the focus and financial platform for the BP core businesses - allowing ICH to pursue growth opportunities 34