Transcript Medivir

Medivir September 2007
Lunch presentation at SHB
CEO Lars Adlersson
VP Research Bertil Samuelsson
CFO / IR Rein Piir
Business model
Structure:
Research & development
of protease inhibitors
Sales & marketing of
proprietary products
Quids
(e.g. JNJ)
Own products
(e.g. HIV Franchise, HCV PI)
Revenue streams:
Upfronts & milestones
Royalties
Pharmaceutical
sales revenues
Acquired products
Co marketing
2
Key projects and recent events
LABIAL HERPES
HEPATITIS C
(TMC-435350)
Lipsovir®, all patients enrolled in the phase III
programme
Phase I trials ongoing
Pre-clinical data presented on TMC-435350
MIV-701, Phase Ib trial ongoing
OSTEOPOROSIS
Sales &
marketing
VP Sales and Marketing starts in October
3
All patients now enrolled in phase III program
Number of patients enrolled
Pivotal
study
2400 (2400)
Immuno
compromised
200 (200)
Children/
Adolescents
240 (240)
Started treatment
1316 (1400)
105 (105)
130 (130)
Lipsovir
Acyclovir
Placebo
Lipsovir
Acyclovir
Lipsovir
Prevention
Safety/Healing time
Safety
Q1 2008
Q1 2008
Q1 2008
Treatment arms
Endpoint
Results
Partner strategy - Sign partner/s after completion of phase III
4
4
Time line
Timeline and prognosis at program start (July 2006)
Start of
pivotal trial
(PS)
Q3 06
Q3 06
Results
IC & AC
Start of 2
supportive
phase III
trials
(IC & AC)
Q4 06
Q1 07
94% treated
in PS
Approval
Results in
PS
Q2 07
Q3 07
Q4 07
Q1 08
Results from
All patients
all studies
included in the
phase III program
Q2 08
Q3 08
Q4 08
Q1 09
Approva
l
Filing
Marketing
Partner(s)
Timeline and new prognosis September 2007
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Hepatitis C –opportunities to improve current therapy
• Efficacy – SVR superior to Pegasus/RBV
– G1 treatment naïve: currently achieves ~45% SVR (of HCV infected
in the US >70% has G1)
– Non-responders
– Genotype 2-6
• Decrease treatment duration
– Currently 48 weeks for most common and difficult-to-treat
genotype 1 (G1)
• Safety – no added AE’s compared with Pegasus/RBV
– Standard-of-care associated with severe side effects (flu-like
symptoms, fatigue, depression, hemolytic anemia)
– Contraindicated in patients with decompensated liver failure
• Dosing – once daily (q.d.)
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Hepatitis C – Medivir/J&J program
Process
• Partnership with Tibotec / Johnson &
Johnson since November 2004
• Phase I trials initiated February 2007
• Pre-clinical data on TMC435350 presented
in Glasgow at “14th International
Symposium on Hepatitis C Virus and
Related Viruses” September 9-13
• Clinical phase Ia data on safety,
tolerability and pharmacokinetics will be
presented at the AASLD Liver Meeting in
Boston 2-6th November.
Patents
• Extensive and non-limiting IP published
July 2005
Licensing agreement
• Rights to receive pharmaceutical product
for Nordic countries from JNJ at predefined point in development
• Nordic rights retained by Medivir
NS3/4A:
Key protease for
virus replication
Enzyme inhibiting compound
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HCV Direct Antivirals in Development
PROTEASE
INHIBITORS
Pre-clin
Ph I
Ph IIa
Ph IIb
Ph III
J&J/Vertex VX-950
Medivir/Tibotec
ITMN-191
Roche/ITMN
SGP Sch503034
Gilead GS9132
Abbott/Enanta
BMS?
Phenomix
Boehringer
?
NS5A
INHIBITORS
POLYMERASE
INHIBITORS
Biocryst
Biota/BI
Tibotec
Multiple
GNLB
Merck MK-0608
Novartis
Idenix NM-283
Roche/Pharmasset
R-7128 (RO5024048)
?
Gilead GS9190
Roche R-1626
XTL-2125
BILB-1941
GSK pyrrolidine
HCV-796
VPHM/Wyeth
Arrow A-831
nucleoside
Non-nucleoside
Combination with PEG-IFN
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Medivir/Tibotec HCV PI Series
•
Several series of highly potent NS3/4A
inhibitors with strong IP developed
1
R
2
R
L
H
N
O
M
O
Enzymatic activity on genotype 1b/1b (Ki, nM)
0.3 nM
Replicon activity on genotype 1b
[IC50, nM]
7.8 nM
O
3
R
( )n
•
Data on TMC435350
In vivo rat PK, Oral dose: 40 mg/kg
T 1/2 (h)
F (%)
2.6
45
Fine tuning of these inhibitors in
collaboration with Tibotec
Pharmaceuticals Ltd, J&J, has resulted
in the selection of a Clinical Candidate,
TMC435350
From presentations at the 1st International Workshop on Hepatitis C Resistance and New Compounds, Boston 25-26 October 2006
and the 3rd Anglo-Swedish Medicinal Chemistry Meeting, 11-14 March 2007, Åre, Sweden
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Rat exposure of TMC435350
Fig 6.
Exposure of TMC435350
1000000
100000
Liver
TMC435350 (nM)
10000
1000
Plasma
100
EC99
EC90
10
EC50
1
0
4
8
12
16
20
24
time (h)
Good systemic oral bioavailability
Plasma exposure : C8h-plasma>EC99; liver exposure C24h-liver >EC99
Contains CONFIDENTIAL data on TMC435.
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TMC435350
Safety pharmacology
• Agar Ames assay: negative
• Mouse lymphoma assay: negative
• Mouse micronucleus screening assay: negative
• No effect on autonomic and behavioral parameters in
mice up to 300 mg/kg (oral) and in rats up to 10
mg/kg in a Pharmascreen®
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TMC435350 - Combination with IFNα in vitro
 Displays additive to synergistic effects with IFNa in cells
Log HCV RNA change vs non treated
control (normalized to RPL13A)
 combination with IFNa suppresses generation of TMC435350 resistance
 combination leads to >4 log10 reduction in HCV RNA (9 days) in cells
0
-0.5
TMC435350
(0.6x EC50)
-1
-1.5
IFNα (1XEC50)
-2
TMC435350
(0.6xEC50) + IFNα (1xEC50)
-2.5
IFNα (10xEC50)
-3
-3.5
TMC435350
(6xEC50)
-4
TMC435350
-4.5
(6xEC50) + IFNα (1xEC50)
-5
0
3
6
9
days
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Bone disorders (MIV-701)
• MIV-701 selectively inhibits the
bone and cartilage degrading
enzyme cathepsin K
• Osteoporosis, osteoarthritis and
bone metastases
Bone surface
• Target profile:
• Improved bone quality (c/f
bisphosphonates)
• Bone growth capability
Cath K
• Once-daily oral dosing
• Strong Follow-on program in
place with CD selection as next
step
Osteoclast
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Bone disorders (MIV-701)
Market
• Approx 100 million patients in major
growing markets (osteoporosis only)
• Strong interest in cathepsin K inhibition
from major pharma companies
Process
• Clinical phase Ia trials commenced
March 2007
• Phase Ib trials ongoing
• Results from the phase I trial late 2007
Patent/generic competition
• Patent applications being processed
• Expected patent protection until 2025
Partner strategy
• Establish industrial partnership after
completion of phase I (2008)
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MIV-701 Phase I
Study initiated March 2007 Completion during Q4 2007
Objective: Safety, tolerability, PK and biomarkers for efficacy
Part 1
 Groups A and B
Single dose male
Fed and fasted
 Group C
Single dose female (PMW)
Part 2
 Group D and E
Multiple dosing male 7 days
 Group F
Multiple dose male 14 days
Part 3
Group G
Multiple dose PMW 14 days
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“The Protease Discovery Engine” A reliable repeat innovator
HIV – PI
–Collaboration project with Tibotec / Johnson & Johnson
MMP- COPD
–Excellent results in pre-clinical disease model
–Next step: selection of Candidate Drug
Renin - Hypertension
–IP compiled for three distinct and highly potent inhibitor series
–Next step: studies in a pre-clinical hypertensive efficacy model
Cathepsin S – RA, MS and pain
–Potent and selective inhibitors
–Efficacious in preclinical disease models
–Fine-tuning of PK properties
BACE – Alzheimer’s disease
–High potency and selective inhibitor series identified
–Optimization ongoing
–IP filed
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Key Events Going Forward
LIPSOVIR
HEPATITIS C
(TMS-435350)
MIV-701
Sales &
marketing
• Phase III data, Q1 2008
• Partnership agreement(s)
• Market approval, 2008/09
• Phase Ia data in November 2007
• Start phase II trials
• Possibility to receive “approved drug”from Johnson & Johnson
• Phase I data late 2007
• Partnership post phase I
• Product acquisitions, quids and co marketing 2008/09
• MIV-606 start of phase IIb trials
HIV FRANCHISE
• New clinical trials and new data in other outlicensed projects
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Next step in company transformation
A profitable pharmaceutical company
with its own research and sales