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Carnegie Nordic Healthcare SeminarStockholm

Wednesday 24 March 2010

Presented by

Bertil Samuelsson, VP Discovery & Research Rein Piir, CFO / IR

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One focused pipeline March 2010

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

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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 H2-2010. 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 Q3/Q4 2010. Like other cold sore pharmaceuticals, Xerese™ will be a prescription (Rx) product

ROW

Discussions ongoing

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US market for topical cold sore products

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Topical cold sore cream market is approximately USD 150-180 MUSD/year

Prescription status for all antiviral treatments (acyclovir, penciclovir)

Main competitors are Zovirax cream, Denavir cream and Abreva

Market

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EU Market for topical cold sore products

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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

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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– ~25 000 protease inhibitors

• Proprietary and specialized protease technologies:– X-RAPiD, a combinatorial library of ~120 000 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

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One focused pipeline March 2010

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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

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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 2a in HBV patients

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Main partner – three programs:

HCV PI, TMC435 HCV-Pol HIV-PI

Profile Profile ProfileA potent second generation protease inhibitor, QD dosing A nucleoside NS5B inhibitor Highly competitive CD target profile protease HIV inhibitor

Status Status StatusPhase IIb-trials in treatment naive patients ongoing In preclinical development (IND) phase In preclinical lead optimization Phase IIb-trials in treatment experienced patients ongoing

Next step Next step Next stepStart of phase III-trials in treatment naive patients Initiation of phase I trials Selection of CD

Summary of the licensing agreementsAll development costs covered by Tibotec / J&JRemaining milestone payments for these programs of € 200mRoyalties on global salesNordic marketing and sales rights retained by Medivir

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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)

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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;3:211-220 Schmitz U, Tan SL. Recent Pat Antiinfect Drug Discov 2008;3:77-92

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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

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MK-0608

R-1626

R-7128

Biocryst

Biota/BI

Development stage of HCV nucleosides

Tibotec/Medivir

Firs

t ge

nera

tion

TMC651755TMC619688& prodrugs

NM-283

Idenix (IDX-184)

Pharmasset PSI-7851

Seco

nd

gene

ratio

n

Inhibitex

Roche

PSI-938PSI-879

Pre-clin Ph I Ph Ib/IIa Ph IIb Ph III

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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

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Cathepsin K inhibitors – for the treatment of osteoporosis, osteoarthritis and metastatic bone disease (MBD)

Cathepsin K inhibitors intervene in disease states where there is excessivebone 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 2008. Deutsche Bank projects a denosumab SRE market of 2.1 billion USD in peak sales

Osteoclast

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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

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Medivir Cathepsin K Inhibitor CDs MIV-710 & MIV-711 High efficacy predicted from biomarkers of osteoporosis

0 4 8 12 16 20 24

0

20

40

60

80

100

120

140

Vehicle (n=10)

MIV-701 (n=5)

MIV-710 (n=7)

MIV-711 (n=4)

Time (h)

% of baseline CTX-I

Treatment Max inhibition (%)

Inhibition at 24h (%)

Vehicle 56 2

MIV-701 64 22

MIV-710 75 51

MIV-711 95 75

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

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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

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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

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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.

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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 deathSynaptic degeneration

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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 nM against BACE and IC50 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

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Main partner – three programs:

HCV PI, TMC435 HCV-Pol HIV-PI

Profile Profile ProfileA potent second generation protease inhibitor, QD dosing A nucleoside NS5B inhibitor Highly competitive CD target profile protease HIV inhibitor

Status Status StatusPhase IIb-trials in treatment naive patients ongoing In preclinical development (IND) phase In preclinical lead optimization Phase IIb-trials in treatment experienced patients ongoing

Next step Next step Next stepStart of phase III-trials in treatment naive patients Initiation of phase I trials Selection of CD

Summary of the licensing agreementsAll development costs covered by Tibotec / J&JRemaining milestone payments for these programs of € 200mRoyalties on global salesNordic marketing and sales rights retained by Medivir

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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

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Telaprevir J&J/Vertex

Boceprevir Merck

Pre-clin Ph I Ph Ib/IIa Ph IIb Ph III

ITMN-191/R7227Roche/ITMN

BI 201335

Pro

tea

se

In

hib

ito

rs

HCV PI – the competitive landscape

TMC435J&J/ Medivir

VaniprevirMK7009

ABT-450

PHX-1766

MerckSCH900518

Vertex-813

BMS650032

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

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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

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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

C205: A global phase 2b study in treatment-naïve HCV patients;

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PEG-IFN + RBV Post therapy FU

24 48128

Triple PEG-IFN + RBV

Post therapy FU

TriplePEG-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 1000-1200 mg BID + pegIFNalpha-2A 180 g weekly

12W Triple + 12W SoC

24W Triple

48W SoC

N = 400

Study Start Date: May 2009 - Once daily (QD), 75mg and 150 mg, of TMC435 + SoC:- 12-week triple therapy followed by SOC alone up to week 24- 24-week triple therapy

PEG-IFN + RBV

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Triple Therapy Post therapy FU

24 4812

PEG-IFN + RBV

Weeks

Triple Therapy

Triple Therapy

Triple Therapy

Post therapy FU

Post therapy FU

Post therapy FU

PEG-IFN + RBV

PEG-IFN + RBV Post therapy FUTriple Therapy

1

2

3

4

6Post therapy FU7

Triple Therapy Post therapy FU5

PEG-IFN + RBV

TMC435 100 mg q.d. TMC435 150 mg q.d.

Primary endpoint: Proportion of patients with undetectable virus levels 24 weeks after planned end-of-treatment (SVR24)SoC: Ribavirin 1000-1200 mg BID + pegIFNalpha-2A 180 g weekly

TMC435 100 mg, 12WTMC435 150 mg, 12W

TMC435 100 mg, 24WTMC435 150 mg, 24W

TMC435 100 mg, 48WTMC435 150 mg, 48W

SoC, 48W

N = 455

C206: A global phase 2b study in treatment-experienced HCV patients

Study Start Date: September 2009

- 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

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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

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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 IIIStart 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 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 TMC435 and other DAA agents

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• Appendix

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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

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- 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

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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)”

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Regulatory status in EU

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2g tube OTC 2g 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