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1 Carnegie Nordic Healthcare Seminar Stockholm Wednesday 24 March 2010 Presented by Bertil Samuelsson, VP Discovery & Research Rein Piir, CFO / IR.

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Presentation on theme: "1 Carnegie Nordic Healthcare Seminar Stockholm Wednesday 24 March 2010 Presented by Bertil Samuelsson, VP Discovery & Research Rein Piir, CFO / IR."— Presentation transcript:

1 1 Carnegie Nordic Healthcare Seminar Stockholm Wednesday 24 March 2010 Presented by Bertil Samuelsson, VP Discovery & Research Rein Piir, CFO / IR

2 2 One focused pipeline March 2010

3 3

4 4 Our first product have seen the light of the market - launched as Rx in Sweden and Finland

5 5 Xerese™ – Xerclear™ strategy NORDIC Launched Xerclear™ Rx in SE on March 15 and in FIN March 22. OTC to follow during EU European partner discussion for Xerclear™ ongoing in parallel with preparation of product launch by late H Initially, legal status is OTC and Rx, with an overall switch to OTC over time. US MEDA is the US partner for Xerese™. They are preparing for product launch by Q3/Q Like other cold sore pharmaceuticals, Xerese™ will be a prescription (Rx) product ROW Discussions ongoing 5

6 6 US market for topical cold sore products 6 Topical cold sore cream market is approximately USD MUSD/year Prescription status for all antiviral treatments (acyclovir, penciclovir) Main competitors are Zovirax cream, Denavir cream and Abreva Market

7 7 EU Market for topical cold sore products 7 Topical cold sore treatment value of the main European markets is approximately 200 MUSD/year EU is a scattered and competitive market dominated by OTC products The market value for SE and FIN is 7 MUSD/year Market

8 8 Medivir R&D A project pipeline with major focus on anti infective Strong preclinical delivery Validated discovery process & technology platforms generating quality development candidates –HCV PI; less then 3 years from lead series (LI phase) to start of Phase IIa clinical trials (in collaboration with Tibotec/J&J) One of the largest compound libraries in the industry –~4 500 nucleoside analogue –~ protease inhibitors Proprietary and specialized protease technologies: –X-RAPiD, a combinatorial library of ~ compounds for screening any protease –e-FOCUS software provide a map of the protease subsites, generating exquisite structure activity relationships (SAR) for inhibitor development X-ray crystallography & high field NMR –Tools for structure based drug design Early and extensive in vitro and in vivo DMPKT profiling –Focus on once daily, low dosage and orally bioavailable drugs Large network of preclinical and clinical specialist collaborators and CROs complementing internal drug discovery and development

9 9 One focused pipeline March 2010

10 10 Valomaciclovir - licensed to Epiphany Biosciences Agreement –Equity in Epiphany –Milestone payments to USD 24.5 M –Royalty from world wide sales –Medivir has the marketing rights for the Nordic countries –Epiphany responsible for the clinical development Valomaciclovir (EPB-348) A broad-spectrum herpes antiviral with high commercial prospects Lead indication: Varicella Zoster (Shingles). Shingles sales in the major markets exceeded 0.8 billion USD in 2008 Develoment status: –Completed Phase IIb trial, met primary endpoint, time to complete crusting, at once daily dosing Randomized, double-blind, active-controlled, multi-center, parallel-group (non-inferiority with Valtrex as comparator) at 46 U.S. clinical centers including 373 patients –Phase 2b data show reduction in incidence of PHN –Data suggestive of wider treatment window –Targeting 2012 regulatory submissions and 2013 launch in US and EU EBV (infectious mononucleosis) – Phase IIa complete, met primary endpoint

11 11 MIV-210 (lagociclovir valactate) licensed to Daewoong Agreement –China, South Korea, Japan and Taiwan territories for HBV –Daewoong responsible for the clinical development –Medivir has the marketing rights for the rest of the world Lagociclovir valactate: –Potent inhibitor of HBV in vitro and in animal models –Active against all tested HBV mutants, e.g. to lamivudine, adefovir, and entecavir –Is synergistic with lamivudine and adefovir in vitro Dose in HBV patients expected to be mg q.d. News flow and events in the upcoming 12 months –Start of Phase 2a in HBV patients

12 12 Main partner – three programs:

13 13 Hepatitis C (HCV) - background Disease & market ~180 million worldwide infected with hepatitis C virus ~12 million infected in the US, Europe and Japan Immense medical need: only 40-50% of patients with genotype 1 respond to current SoC therapy (48 weeks of PEG-IFN/ribavirin) Estimated market value of 10.5 billion USD in 2015 The need for new drugs Increased SVR rates (cure rates) Improved safety and side effect profile Shorter duration of treatment Higher compliance –lower drug burden and simplified dosing (once daily, no food interaction and large “forgiveness” factor)

14 14 HCV- Future of new DAA agents; New treatments evolving Directly Acting Antiviral (DAA) Agents New oral agents will dramatically increase SVR and shorten treatment duration Initially as “add-on” therapy but in combination eventually displace one or both of ribavirin and Peg-IFN New anti viral agents with different MOA will be used in combination with each other, similar to HIV, to improve efficacy, shorten treatment duration and minimize development of resistance - Combinations of Protease Inhibitors with other direct antivirals will drive the future market Medivir, with TMC435 as a front runner of this new wave, is strongly positioned to become part of these future DAA combination treatments Programs in collaboration with Tibotec/JNJ In-house HCV programs Kwong A, et al. Drug Discovery Today: Therapeutic Strategies 2006;3: Schmitz U, Tan SL. Recent Pat Antiinfect Drug Discov 2008;3:77-92

15 15 Hepatitis C - Nucleoside NS5B Polymerase Inhibitors Status Partnership entered with Tibotec/J&J May 2008 Presently in late preclinical development phase towards phase I clinical trials Next step Start of phase I Licensing agreement Remaining milestones of €137m + royalties on sales for one product reaching market. Additional €130m for second compound and indication reaching market + royalties on sales. All development costs covered by JNJ Nordic rights retained by Medivir

16 16 MK-0608 R-1626 R-7128 Biocryst Biota/BI Development stage of HCV nucleosides Tibotec/Medivir First generation TMC TMC & prodrugs NM-283 Idenix (IDX-184) Pharmasset PSI-7851 Second generation Inhibitex Roche PSI-938 PSI-879 Pre-clin Ph I Ph Ib/IIa Ph IIb Ph III

17 17 HCV Nucleoside program - News flow and events in the upcoming 12 months Start of Phase I clinical trials Presentation of Phase I clinical trial data Presentation on antiviral potency, mechanism of action and DAA synergy data

18 18 Cathepsin K inhibitors – for the treatment of osteoporosis, osteoarthritis and metastatic bone disease (MBD) Cathepsin K inhibitors intervene in disease states where there is excessive bone loss, e.g. osteoporosis, osteoarthritis and metastatic bone disease Market value estimates: Osteoporosis: Global sales for 2010 estimated at 7.9 billion USD Osteoarthritis: Global sales for 2010 estimated at 4.4 billion USD MBD: Global bone metastasis market was 1.3 billion USD in Deutsche Bank projects a denosumab SRE market of 2.1 billion USD in peak sales Osteoclast

19 19 Medivir Cathepsin K inhibitor program Two Candidate Drugs selected in 2009 (MIV-710 and MIV-711) MIV-710 and MIV-711: –display superior pharmacokinetic properties compared with MIV-701 (discontinued) which showed “proof-of-principle” in phase I clinical trials during 2007 –exhibit potent and reversible anti-resorptive activity on bone –does not suppress the beneficial bone formation, as other anti-resorptives –furnish long duration of activity Dose in human –An efficacious dose of ~50 mg once daily anticipated Strong IP position A broad program targeting multiple indications of great unmet medical need –osteoporosis, OP –osteoarthritis, OA –metastatic bone disease News flow and events in the upcoming 12 months –Upscale of CD and completion of preclinical development phase –Partnering discussions

20 20 Medivir Cathepsin K Inhibitor CDs MIV-710 & MIV-711 High efficacy predicted from biomarkers of osteoporosis Vehicle (n=10) MIV-701 (n=5) MIV-710 (n=7) MIV-711 (n=4) Time (h) % of baseline CTX-I TreatmentMax inhibition (%) Inhibition at 24h (%) Vehicle562 MIV MIV MIV Reduction in plasma CTx-I, a biomarker of bone breakdown, in cynomolgus monkeys after: - Oral administration - Single low dose Almost 100% suppression of osteoporosis bone breakdown over 8h A clinical efficacious once daily dose of ~50 mg – low cost of gods Highly advantageous plasma exposure for MIV-711 (128 fold higher compared with MIV-701) Almost complete inhibition of bone erosion with extended effect duration (8h) after a single oral dose 75% of effect maintained after 24h MIV-710 MIV-711 MIV-701

21 21 PPI-801/802 (MIV-410): For the treatment of HIV – licensed to Presidio Pharmaceuticals Agreement –Milestone payments of maximally USD 41.75m –Royalty from world wide sales –Presidio responsible for the preclinical & clinical development –Medivir has the marketing rights for the Nordic countries PPI-801/802 (formerly called MIV-410): –Nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action. PPI-801 is a non-obligate chain terminator being incorporated into the nascent cDNA chain and terminates at a penultimate position following the addition of at least one additional nucleoside –Broad-spectrum activity: is effective at inhibiting a wide variety of NRTI resistant mutants Indication –Treatment failures from HAART –First-line therapy for newly infected individuals News flow and events in the upcoming 12 months –Completion of preclinical development phase

22 22 HIV-PI Program Disease & market An estimated 35 M people worldwide were infected by HIV, of which a total of approximately 2 M people in Western Europe and North America In an increasing number of patients, HIV is developing resistance There is no cure Estimated market value for HIV/AIDS: 12.7 Bn USD in 2010 R&D collaboration with Tibotec/J&J Collaboration Agreement entered in June 2006 Research funding at Medivir up to December 2008 Development milestones & royalties similar to HCV PI license agreement Highly competitive CD target profile Extensive non-limiting patent portfolio News flow and events in the upcoming 12 months Selection of candidate drug (CD) and start of preclinical development

23 23 Cathepsin S Inhibitors - for Neuropathic pain and RA Strong link to neuropathic pain –upregulated in DRG infiltrating macrophages and near site of peripheral injury in rodent models –secreted by activated microglial cells in CNS in rodent models Strong link to RA –crucial role in MHC Class II antigen presentation –performs final step in processing of invariant chain –antigen presentation is key to establishing an immune response Medivir Cathepsin S program –Strong IP (patent) position –Potent, selective and orally bioavailable inhibitors developed –Proof-of-principle has been demonstrated for Medivir lead inhibitor in a preclinical rodent model of neuropathic pain News flow and events in the upcoming 12 months –Candidate Drug Selection –Start licensing discussions A cathepsin S inhibitor acting by reducing microglial activation leads to decrease in the pain signal transduction and eleviate neuropathic pain.

24 24 BACE Inhibitors for the treatment of Alzheimer’s disease (AD) Disease and market Around 35 million AD cases world-wide today with a three fold increase to 105 million AD cases expected by 2050 Life expectancy from diagnosis: Approx. 10 years The annual costs for AD is estimated to 148 billion USD Drugs available today  No available drugs cures/prevents the disease  A few drugs cause transient symptomatic relief –Acetylcholine esterase inhibitors –Glutamate antagonist Plaque (Amyloid β-peptide) Reduced brain volume Neuronal cell death Synaptic degeneration

25 25 BACE Inhibitors - The leading hypothesis for next generation AD drugs Project status: lead optimization stage Novel and patentable lead series developed Focus on two validated lead series Strong IP (patent) position Potent and selective BACE inhibitors Lead inhibitors display robust potencies K i values <1 nM against BACE and IC 50 values < 1 nM in cell-based assays measuring Aβ40 release orally bioavailable and displaying drug-like properties News flow and events in the upcoming 12 months Demonstration of high central exposure after oral administration in rodents Afford substantial efficacy in AD disease models after oral administration Start licensing discussions

26 26 Main partner – three programs:

27 27 Lead HCV compound TMC435 in phase IIb A leading, second generation protease inhibitor > potency than 1st generation PIs (telaprevir, boceprevir) Potent anti-viral activity shown in Phase IIa clinical trials Low pill burden: convenient one pill, once daily No food interactions No significant adverse events over current SoC Licensing agreement Remaining milestones of EUR 47m Royalties on market sales All development costs covered by Tibotec Nordic rights retained by Medivir

28 28 Telaprevir J&J/Vertex Boceprevir Merck Pre-clin Ph I Ph Ib/IIa Ph IIb Ph III ITMN-191/R7227 Roche/ITMN BI Protease Inhibitors HCV PI – the competitive landscape TMC435 J&J/ Medivir Vaniprevir MK7009 ABT-450 PHX-1766 Merck SCH Vertex-813 BMS VBY 376 TMC435 - the leading second generation HCV PI: 1) potent 2) well tolerated 3) low dose 4) one pill and 5) once daily ACH-1625

29 29 TMC435 C201: A phase 2a study in G1 treatment-naïve and treatment-experienced patients (2008/09) A once daily (QD) treatment of TMC435 in doses from 25 to 200 mg + SoC A four-week triple therapy (RVR), then followed by SOC alone up to week 24 or 48 Approximately 130 patients included In treatment-naïve patients, potent antiviral activity was achieved at week 4 (RVR) and at week 12 (EVR) –At week four 8/9 and 7/10 patients were undetectable in the 75 and 200 mg groups respectively (Panel B) –At week 12 all of the patients in the once daily 75 mg and 200 mg arms (Panel B) had HCV RNA <10 IU/mL (undetectable) In treatment-experienced patients potent antiviral activity was achieved at week 4 (RVR) –7/9 patients levels below LLQ (<25 IU/mL) at 150 mg and 8/10 for 200 mg at day 28

30 30 C201: Conclusions from the phase 2a study In both treatment-naïve and treatment-experienced patients infected with HCV genotype-1, TMC435 once daily in combination with SoC over 4 weeks of treatment. Demonstrated potent antiviral activity Was generally safe and well tolerated Was not associated with AE-related treatment discontinuations. Mild and reversible increases in bilirubin was observed. This was mainly observed in the highest dose groups (200 mg), whereas the highest dose in the ongoing phase 2b studies is 150mg. The mechanism of action has been determined and will be presented at an upcoming conference No evidence of any drug-related hepatotoxicity

31 C205: A global phase 2b study in treatment-naïve HCV patients; 72 PEG-IFN + RBV Post therapy FU Triple PEG-IFN + RBV Post therapy FU Triple PEG-IFN + RBV Post therapy FU Triple Therapy Post therapy FU Triple Therapy Post therapy FU Weeks Time ( weeks ) TMC 75 mg, 12W TMC 150 mg, 12 W TMC 75 mg, 24W TMC150 mg, 24W SoC Primary endpoint: Proportion of patients with undetectable virus levels 24 weeks after planned end-of-treatment (SVR24) SoC: Ribavirin mg BID + pegIFNalpha-2A 180  g weekly 12W Triple + 12W SoC 24W Triple 48W SoC N = 400 Study Start Date: May Once daily (QD), 75mg and 150 mg, of TMC435 + SoC: - 12-week triple therapy followed by SOC alone up to week week triple therapy

32 PEG-IFN + RBV 72 Triple Therapy Post therapy FU PEG-IFN + RBV Weeks Triple Therapy Post therapy FU PEG-IFN + RBV Post therapy FU Triple Therapy Post therapy FU 7 Triple TherapyPost therapy FU 5 PEG-IFN + RBV TMC mg q.d.TMC mg q.d. Primary endpoint: Proportion of patients with undetectable virus levels 24 weeks after planned end-of-treatment (SVR24) SoC: Ribavirin mg BID + pegIFNalpha-2A 180  g weekly TMC mg, 12W TMC mg, 12W TMC mg, 24W TMC mg, 24W TMC mg, 48W TMC mg, 48W SoC, 48W N = 455 C206: A global phase 2b study in treatment-experienced HCV patients Study Start Date: September Once daily (QD), 100 mg and 150 mg, of TMC435 + SoC: - triple therapy for 24-weeks followed by 24-weeks SOC - triple therapy for 48-weeks

33 33 TMC435 – other phase 2 clinical trials C215: a phase IIb study in Japan in treatment naïve genotype-1 HCV patients –Study Start Date: June 2009 –Patients will receive TMC435 (50 or 100 mg) for a duration of 12 or 24 weeks. –In treatment arms 1 and 2, subjects will receive 12 weeks of triple therapy with TMC435 once daily plus SoC followed by 12 weeks of treatment with SoC. –In treatment arms 3 and 4, patients will receive 24 weeks of triple therapy with TMC435 once daily plus SoC. –In treatment arm 5 (control group), patients will be treated with SoC treatment for 48 weeks C202: in treatment naïve genotype 2 to 6 HCV patients –Study Start Date: February 2009 –Study Completion Date: November 2009 –Patients will receive TMC435 during 7 days, once daily dosing at 200mg, as monotherapy. Subsequently, they can continue with SoC treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor

34 34 TMC435: News flow and events in the upcoming 12 months C205: Presentation of data from the phase IIb study in treatment naïve genotype-1 HCV patients Phase III Start of phase III in treatment naïve genotype-1 HCV patients C206: EOT data from the phase IIb study in treatment experienced genotype-1 HCV patients C215: Presentation of data from the phase IIb study in treatment naïve Japanese genotype-1 HCV patients C202: Presentation of data from the phase IIa study in treatment naïve genotype HCV patients Presentation of mechanism of action (MOA) behind the transient reversible increases in bilirubin seen in some patients (mainly in the 200 mg dose arm) Presentation of in vitro data on synergy between TMC435 and other DAA agents

35 35 Appendix

36 36 Rationale HSV-1 Inflammatory response Xerclear The rationale for the use of a combination aciclovir and hydrocortisone in the treatment of recurrent mucocutaneous HSV is to enable control of both the viral replication and the inflammation

37 37 - a powerful package Prevents development of cold sores Decreases healing time of ulcerative cold sores The Xerclear™ vehicle improves dermal delivery Xerclear™ has a unique and compelling label text Granted patents: covering 1) composition-of-matter and 2) formulation 37

38 38 Xerese™ – Xerclear™ – a differentiating label First cold sore product with clinical data resulting in a unique and strong indication text – both in US and EU Indication text as approved in US “Xerese, a combination of acyclovir and hydrocortisone, is indicated for the early treatment of recurrent herpes labialis (cold sores) to reduce the likelihood of ulcerative cold sores and to shorten the lesion healing time in adults and adolescents (12 years of age and older)” Indication text as approved in EU ”Treatment of early signs and symptoms of recurrent herpes labialis (cold sores) to reduce the progression of cold sore episodes to ulcerative lesions in immunocompetent adults and adolescents (12 years of age and older)”

39 39 Regulatory status in EU 39 2g tube OTC2g tube Rx Regulatory Status in RMS/CMS Approved* (n=10) 6 (CZ, DK, IS, PT, SK, SE) 4 (AT, FI, FR,UK) Pending (n=4)4 (BE, ES, PL, DE) *Either direct or expected by a submission of a variation after the national approval


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