Скачать презентацию Handelsbanken lunch meeting Monday 29 March 2010 Presented Скачать презентацию Handelsbanken lunch meeting Monday 29 March 2010 Presented

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Handelsbanken lunch meeting Monday 29 March 2010 Presented by Ron Long, CEO Bertil Samuelsson, Handelsbanken lunch meeting Monday 29 March 2010 Presented by Ron Long, CEO Bertil Samuelsson, VP Discovery & Research Rein Piir, CFO / IR 1

The proceeds of the Rights Offering will enable us to: • Develop its projects The proceeds of the Rights Offering will enable us to: • Develop its projects further under its own management in order to create value for shareholders • Strengthen the Company’s commercial organization and capabilities • Invest in additional research projects targeting infectious diseases • Create operational and financial flexibility 2

One focused pipeline March 2010 3 One focused pipeline March 2010 3

4 4

Xerese™ – Xerclear™ strategy NORDIC Launched Xerclear™ Rx in SE on March 15 and Xerese™ – Xerclear™ strategy NORDIC Launched Xerclear™ Rx in SE on March 15 and in FIN March 22. OTC to follow during 2010. EU European partner discussion for Xerclear™ ongoing in parallel with preparation of product launch by late H 2 -2010. 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 Q 3/Q 4 2010. Like other cold sore pharmaceuticals, Xerese™ will be a prescription (Rx) product ROW Discussions ongoing 5

One focused pipeline March 2010 6 One focused pipeline March 2010 6

Valomaciclovir - licensed to Epiphany Biosciences Agreement – Equity in Epiphany – Milestone payments 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 2 b 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 7

MIV-210 (lagociclovir valactate) licensed to Daewoong • Agreement – China, South Korea, Japan and 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 10 -20 mg q. d. • News flow and events in the upcoming 12 months – Start of Phase 2 a in HBV patients 8

Main partner – three programs: 9 Main partner – three programs: 9

Hepatitis C (HCV) - background Disease & market • ~180 million worldwide infected with 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 So. C 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) 10

HCV- Future of new DAA agents; New treatments evolving Programs in collaboration with Tibotec/JNJ HCV- Future of new DAA agents; New treatments evolving Programs in collaboration with Tibotec/JNJ 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 TMC 435 as a front runner of this new wave, is strongly positioned to become part of these future DAA combination treatments Kwong A, et al. Drug Discovery Today: Therapeutic Strategies 2006; 3: 211 -220 Schmitz U, Tan SL. Recent Pat Antiinfect Drug Discov 2008; 3: 77 -92 In-house HCV programs 11

Hepatitis C - Nucleoside NS 5 B Polymerase Inhibitors Status • Partnership entered with Hepatitis C - Nucleoside NS 5 B 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 € 137 m + royalties on sales for one product reaching market. • Additional € 130 m for second compound and indication reaching market + royalties on sales. • All development costs covered by JNJ • Nordic rights retained by Medivir 12

Development stage of HCV nucleosides Ph I Pre-clin Ph Ib/IIa Ph IIb Ph III Development stage of HCV nucleosides Ph I Pre-clin Ph Ib/IIa Ph IIb Ph III NM-283 MK-0608 First generation Biocryst R-1626 Biota/BI Tibotec/Medivir R-7128 Inhibitex Idenix (IDX-184) Roche Second generation TMC 619688 TMC 651755 & prodrugs PSI-938 PSI-879 Pharmasset PSI-7851 13

HCV Nucleoside program News flow and events in the upcoming 12 months • Start 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 14

Cathepsin K inhibitors – for the treatment of osteoporosis, osteoarthritis and metastatic bone disease 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 Osteoclast 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 2008. Deutsche Bank projects a denosumab SRE market of 2. 1 billion USD in peak sales 15

Medivir Cathepsin K inhibitor program • Two Candidate Drugs selected in 2009 (MIV-710 and 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 16

Medivir Cathepsin K Inhibitor CDs MIV-710 & MIV-711 % of baseline CTX-I High efficacy Medivir Cathepsin K Inhibitor CDs MIV-710 & MIV-711 % of baseline CTX-I High efficacy predicted from biomarkers of osteoporosis Reduction in plasma CTx-I, a biomarker of bone breakdown, in cynomolgus monkeys after: - Oral administration - Single low dose 100 80 Vehicle 56 2 64 22 75 51 MIV-711 Almost 100% suppression of osteoporosis bone breakdown over 8 h Inhibition at 24 h (%) MIV-710 120 Max inhibition (%) MIV-701 140 Treatment 95 75 Vehicle (n=10) MIV-701 (n=5) 60 MIV-710 (n=7) MIV-711 (n=4) MIV-701 40 MIV-710 20 MIV-711 0 0 4 8 12 16 20 24 • Highly advantageous plasma exposure for MIV-711 (128 fold higher compared with MIV-7 • Almost complete inhibition of bone erosion w extended effect duration (8 h) after a single or • 75% of effect maintained after 24 h Time (h) A clinical efficacious once daily dose of ~50 mg – low cost of gods 17

PPI-801/802 (MIV-410): For the treatment of HIV – licensed to Presidio Pharmaceuticals • Agreement PPI-801/802 (MIV-410): For the treatment of HIV – licensed to Presidio Pharmaceuticals • Agreement – – • Milestone payments of maximally USD 41. 75 m 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 c. DNA 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 18

HIV-PI Program Disease & market • An estimated 35 M people worldwide were infected 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 19

Cathepsin S Inhibitors - for Neuropathic pain and RA • Strong link to neuropathic Cathepsin S Inhibitors - for Neuropathic pain and RA • Strong link to neuropathic pain – – • Strong link to RA – – – • upregulated in DRG infiltrating macrophages and near site of peripheral injury in rodent models secreted by activated microglial cells in CNS in rodent models 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. 20

BACE Inhibitors for the treatment of Alzheimer’s disease (AD) Disease and market • Around 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 Reduced brain volume Neuronal cell death Synaptic degeneration Plaque (Amyloid β-peptid Drugs available today 4 No available drugs cures/prevents the disease 4 A few drugs cause transient symptomatic relief – Acetylcholine esterase inhibitors – Glutamate antagonist 21

BACE Inhibitors - The leading hypothesis for next generation AD drugs • Project status: 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 Ki values <1 n. M against BACE and IC 50 values < 1 n. M in cell-based assays measuring Aβ 40 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 22

Main partner – three programs: 23 Main partner – three programs: 23

Lead HCV compound TMC 435 in phase IIb A leading, second generation protease inhibitor Lead HCV compound TMC 435 in phase IIb A leading, second generation protease inhibitor • > potency than 1 st 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 So. C Licensing agreement • Remaining milestones of EUR 47 m • Royalties on market sales • All development costs covered by Tibotec • Nordic rights retained by Medivir 24

HCV PI – the competitive landscape Pre-clin Ph Ib/IIa TMC 435 J&J/ Medivir Protease HCV PI – the competitive landscape Pre-clin Ph Ib/IIa TMC 435 J&J/ Medivir Protease Inhibitors VBY 376 ABT-450 ACH-1625 Ph III Telaprevir J&J/Vertex ITMN-191/R 7227 Roche/ITMN Vertex-813 PHX-1766 Ph IIb BI 201335 Boceprevir Merck BMS 650032 Vaniprevir MK 7009 Merck SCH 900518 TMC 435 - the leading second generation HCV PI: 1) potent 2) well tolerated 3) low dose 4) one pill and 5) once daily 25

TMC 435 C 201: A phase 2 a study in G 1 treatment-naïve and TMC 435 C 201: A phase 2 a study in G 1 treatment-naïve and treatment-experienced patients (2008/09) • • A once daily (QD) treatment of TMC 435 in doses from 25 to 200 mg + So. C 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/m. L (undetectable) • In treatment-experienced patients potent antiviral activity was achieved at week 4 (RVR) – 7/9 patients levels below LLQ (<25 IU/m. L) at 150 mg and 8/10 for 200 mg at day 28 26 26

C 201: Conclusions from the phase 2 a study In both treatment-naïve and treatment-experienced C 201: Conclusions from the phase 2 a study In both treatment-naïve and treatment-experienced patients infected with HCV genotype-1, TMC 435 once daily in combination with So. C 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 2 b studies is 150 mg. The mechanism of action has been determined and will be presented at an upcoming conference • No evidence of any drug-related hepatotoxicity 27

C 205: A global phase 2 b study in treatment-naïve HCV patients; Study Start C 205: A global phase 2 b study in treatment-naïve HCV patients; Study Start Date: May 2009 - Once daily (QD), 75 mg and 150 mg, of TMC 435 + So. C: - 12 -week triple therapy followed by SOC alone up to week 24 - 24 -week triple therapy Time (weeks) 8 12 48 24 72 Weeks TMC 75 mg, 12 W Triple PEG-IFN + RBV Post therapy FU TMC 150 mg, 12 W Triple PEG-IFN + RBV Post therapy FU TMC 75 mg, 24 W Triple Therapy Post therapy FU TMC 150 mg, 24 W Triple Therapy Post therapy FU 12 W Triple + 12 W So. C 24 W Triple So. C PEG-IFN + RBV Post therapy FU 48 W So. C N = 400 Primary endpoint: Proportion of patients with undetectable virus levels 24 weeks after planned end-of-treatment (SVR 24) So. C: Ribavirin 1000 -1200 mg BID + peg. IFNalpha-2 A 180 g weekly 1

C 206: A global phase 2 b study in treatment-experienced HCV patients Study Start C 206: A global phase 2 b study in treatment-experienced HCV patients Study Start Date: September 2009 - Once daily (QD), 100 mg and 150 mg, of TMC 435 + So. C: - triple therapy for 24 -weeks followed by 24 -weeks SOC - triple therapy for 48 -weeks 12 TMC 435 100 mg, 12 W TMC 435 150 mg, 12 W TMC 435 100 mg, 24 W TMC 435 150 mg, 24 W TMC 435 100 mg, 48 W TMC 435 150 mg, 48 W So. C, 48 W 48 24 72 1 Triple Therapy PEG-IFN + RBV Post therapy FU 2 Triple Therapy PEG-IFN + RBV Weeks Post therapy FU 3 Triple Therapy PEG-IFN + RBV Post therapy FU 4 Triple Therapy PEG-IFN + RBV Post therapy FU 5 Triple Therapy Post therapy FU 6 Triple Therapy Post therapy FU 7 PEG-IFN + RBV Post therapy FU TMC 435 100 mg q. d. TMC 435 150 mg q. d. N = 455 Primary endpoint: Proportion of patients with undetectable virus levels 24 weeks after planned end-of-treatment (SVR 24) So. C: Ribavirin 1000 -1200 mg BID + peg. IFNalpha-2 A 180 g weekly 1

TMC 435 – other phase 2 clinical trials • C 215: a phase IIb TMC 435 – other phase 2 clinical trials • C 215: a phase IIb study in Japan in treatment naïve genotype-1 HCV patients – Study Start Date: June 2009 – Patients will receive TMC 435 (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 TMC 435 once daily plus So. C followed by 12 weeks of treatment with So. C. – In treatment arms 3 and 4, patients will receive 24 weeks of triple therapy with TMC 435 once daily plus So. C. – In treatment arm 5 (control group), patients will be treated with So. C treatment for 48 weeks • C 202: in treatment naïve genotype 2 to 6 HCV patients – Study Start Date: February 2009 – Study Completion Date: November 2009 – Patients will receive TMC 435 during 7 days, once daily dosing at 200 mg, as monotherapy. Subsequently, they can continue with So. C treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor 30

TMC 435: News flow and events in the upcoming 12 months • C 205: TMC 435: News flow and events in the upcoming 12 months • C 205: 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 • C 206: EOT data from the phase IIb study in treatment experienced genotype-1 HCV patients • C 215: Presentation of data from the phase IIb study in treatment naïve Japanese genotype-1 HCV patients • C 202: Presentation of data from the phase IIa study in treatment naïve genotype 2 - 6 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 TMC 435 and other DAA agents 31