Transcript nektar - Moodle Lille 2

NEKTAR
Marion REUMAUX, Camille SAUVAGE, Cécile TARNUS
Faculty of Pharmacy, Lille2,
March 2010
Biopharmaceutical company developing a robust
pipeline of novel therapeutics based on its
advanced polymer conjugate chemistry
technology platform.
Objective: create value by advancing our lead drug
candidates through early to mid-stage clinical
development.
Corporate statut :
Founded in 1990 in California under the name of Inhale
therapeutic system
Chief Executive Officer : Howard W. Robin
Publicly-traded (NASDQ: NKTR) since 1994
 350 employees
Localisation:
strategy
reduce risks and time associated with drug
development
– Drugs approved
– Pharmacologic target known and approved
=the known safety and efficacy.
=approval in indications for which the parent drugs
have not been studied or approved
Partners
Strategy of development :
Partnerships and co-development agreements with
pharmaceutical companies
partnering strategy
• to fund further clinical development
• manage the global regulatory filing process
• manage the marketing
• sell the approved drugs
• depend on factors:
• the cost
• complexity of development,
• marketing
• commercialization needs
Advantages of these partnering
for Nektar
• few needs of cash to fund the end of
developpment and others part of drug life.
• Royalties function of sales in the different
countries.
• payment for licence exploitation.
Conditions of partnering
Obligation of
partner:
Obligation of
Nektar:
Responsible for:
- future clinical development
- commercialization costs
- worldwide regulatory filings
Possible Responsibility for:
- raw material manufacturing
- medical device manufacturing
Termination of Agreements
• 10 years after first commercialization in a country
• upon the expiration of their last relevant patent
containing a valid claim
• if marketing authorization is withdrawn
• If marketing is no longer feasible due to certain
circumstances
9 approved products for partners
Different therapeutic area of R&D
MAP0004
NKTR-102
NKTR-118
NKTR-125
Cipro
Factor
inhale
VIII
-Préclinical
-Phase
II
III
modified
CNS/ Pain
Immunology
/
Oncology
Inflammation
Therapeutics
areas
Antiinfectives
Others
Hemophilia
--MAP
-AstraZeneca
-No
-Bayer
4 different
partner
-Preclinical
indications
NKTR-119
Cimzia
NKTR-061
Hematide
-Baxter
--Phase
No
--Preclinical
newpartner
indication
II
III
-AstraZeneca
-UCB
-Bayer
-Affymax
NKTR-105
NKTR-181,NKTRNKTR-063
CDP791
-Phase
-Phase
194 IIII
-No
partner
-UCB
NKTR-171
NKTR-140
-Preclinical
-Preclinical
-No partner
-No partner
From inhale therapeutics system
to nektar therapeutics
1990
The begining of the story…
Creation of INHALE THERAPEUTICS SYSTEMS
advantages of pulmonary
delivery
• greater patient compliance (vs injection)
• rapid onset of action
• more efficient and targeted treatment of lung
disorders
• for systemic and local drug administration
Inhale therapeutic products
products
Indication
Phase
Partners
Cipro inhal
Cystic Fibrosis
Infection
Phase II
Bayer
NKTR-061
(inahled
amikacin)
Gram-negative
pneumonia
Phase II
Bayer
NKTR-063
(inhaled
vancomycin)
MAP004
Gram-positive
pneumonia
Phase I
Migraine
Phase III
MAP
Exubera
diabetes
AMM 2006
Pfizer
1990
1995
Neulasta ® :
- stimulates the production
of neutrophils
- neutropenia treatment
Exubera ® :inhaled insulin
diabetic treatment
Nektar and Pfizer : inhaled
insulin
An important market (2007)
• 2.5 millions in France
• 246 millions in the world
Almost 8 % of the European and
north American population
• In 2025 : estimate to 300 millions by OMS
Medical need
• Discovery of insulin 90 years ago converted
insulin-dependent diabetes from a fatal to a
treatable disease
• At that time, scientists were already looking
for a more pleasant and less damaging way to
administer the hormone.
• Admittedly, today's throwaway syringes with
ultra-thin are a huge improvement. And the
insulin itself produces far fewer side effects than
the impure animal insulins available then.
But many diabetics still yearn for an alternative to
injection
Challenges to Alternate of Insulin Delivery
• Oral administration: limited bioavailability
• Transdermal: delivery and efficacy insufficient so
far
• Intranasal: limited bioavailability, enhancers
needed
• Pulmonary: provides alternative route
Liability of Inhale :
-supplying the delivery devices
-And insulin powder
Achievement
receive a share of the royalties on sales
June 1998
January 1995
Inhale and Pfizer
announced their
collaboration
Trials (IIb) indicate
their inhaledinsulin product is
as effective as
insulin shots
November 1998
Pfizer and
Hoechst Marion
Roussel (Sanofi
aventis) go into
partnership
to help foot the bill
-for the clinical development programme
- building the Frankfurt production plant
-Aggreement : jointy manufacture, codevelop and co-promote
Novembre 2007
janvier 2006
Pfizer buys
exubera part to
Sanofi Aventis (for
1.3 milliard $)
AMM
payment of $135
million from Pfizer
in satisfaction of
all remaining
obligations
Marketing
janvier 2006
Novembre 2007
pfizer rachete les
parts d’exubéra a
sanofi aventis
(pour 1.3 milliard
de dollars)
payment of $135
million from Pfizer
in satisfaction of
all remaining
obligations
AMM
on October Pfizer made a jolting
turnabout, announcing it was pulling
the plug on Exubera, returning all
rights to Nektar.
Failure of Exubera
• higher prices for a product that offered no
medical advantage over injected drugs
Some insurance companies are refusing to pay
• unwieldy and not very discreet
• Exubera caused a slight decline in lung
function.
• Problematic delivery
• the need for spirometry (before and periodically)
Scott Joy, associate professor of medicine at Duke University Medical
•Center
Lack
of“I long-term
safety
data.
said,
have not prescribed
Exubera
to a single patient yet,
with the reason being that I don’t have a spirometer here in the
office.”
Coup de grace in 2007
occurrence of lung cancer
Impact to nektar
- total revenue from Pfizer:
in % of nektar total revenue
2006
2007
2008
64%
67%
0%
- For the termination agreement they
received$135.0 million from Pfizer.
- For manufacturing termination agreement with
Bespak and Tech Group they paid $39.9 million.
• Until april 2008, nektar search a new partner to
fund exubera commercial program.
• They kept maintenance agreement with both
Pfizer and Tech Group to preserve key personnel
and manufacturing capacity.
• But lung cancer increased and they decide to stop
all collaboration with potentiel partner for
exubera
1990
1997
1995
Pegasys ® : treatment of Hepatitis C
1990
1995
1997
2001
2000
Somavert
®:
Micera®:
Cimzia®:
- -human
growtherythropoietin
hormon
a-continuous
at the moment 2 indications
receptor
antagonist
receptor
activator
-crohn desease
- treatment
ofofacromegaly
- treatment
anemia
associated with
rheumatoid
arthritis
PEG-Intron®:Acquisition
chronic kidney disease
of
-a pegylated recombinan human interferon-alpha
-treatment of Hepatitis C
PEGylation technology
• Significant business: in 2005, sales for Pegyleted
proteins amounted to more than $5 billion
• PEGylation create blockbusters products, such as
PEG-Intron® and Pegasys®
• Improve the pharmacological property of a drug, but
it has also has to be considered as a life cycle
extention
PEGylation interests
• Non-toxic, non-antigenic, non-immunogenic
• Improve safety
• Different PD and PK properties but the same
target
INCREASE STABILITY /
HALF-TIME
Reduced
dosing
frequency
PEGylation interests
Creat new drugs with optimized
properties
Reposition approves products for
new indications
Rescue non-viable drug candidates
Multiple therapeutics areas
PEGylation limitations
Reactions are not hightly specific, Pegylation can
be incomplete
Traditional PEG systems are polydisperse
=> problem for Quality Control
Now => monodisperse Pegylation
Can accumulated in the liver
Loss of biological activity but it is compensated
by the prolonged body half time
Small Molecule Polymer
Conjugates
• Can pass trough intestinal
gate to act on a cell surface
target receptor
• Or, reduced transport
across specific membrane
barriers in the body, such as
the blood-brain barrier
( => depend on the type of polymer
used)
The drug can also be
engineered to cross cell
membranes to reach an
intracellular target
Increase oral
bioavailability
NKTR-118, NKTR-140
and NKTR-171
Pro-Drug Conjugates
Several drug molecules
attached to a large
molecular weight polymer
in a multi-arm
architecture
Programmable
releasable linkers
Above all for oncolytics drugs
NKTR-102 and NKTR-105
The active parent
molecule is cleaved
from the prodrug
through pH or
enzymatic hydrolysis
Large Molecule Polymer
Conjugates
The linkage allows for a
programmed and
complete release of the
therapeutic to optimize its
bioactivity and allow it to
bind to this receptor in its
natural state.
• Peptides => smaller in size than biologics
•Nektar has designed a novel hydrolyzable
linker
•Half life extended
•Also for proteins and larger molecules
•No drug candidate yet in there pipeline
Antibody Fragment Conjugates
• Branched PEG conjugated to antibody
fragment => become the Fc fragment
• Stable or degradable linkage
AVANTAGES
Improve toxicity profile
Extend half-life
Reduce glomerular filtration rate
Reduce antigenicity
1990
1995
1997
2001
2000
2002
Acquisition
of
Macugen ®: in treating age-related
macular degeneration
1990
1995
1997
2001
2000
2005
2002
2003
Acquisition
of
Inhale Therapeutics Systems
change to NEKTAR THERAPEUTIC
Acquisition of AEROGEN
• Aerogen is a specialty medical device
company
• Nektar Therapeutics buy drug delivery
specialist Aerogen for $32 million
boost its position in
respiratory technologies.
1990
1995
1997
2001
2000
2005
2002
Acquisitio
n of
2007
2007
Collaboration with Bayer HealthCare
• NKTR-061 ( inhaled amikacin)
• Indication: Gram-negative pneumonias,
result of complications of other
patient conditions or surgeries
•
used: with conventional mechanical ventilators
or as a hand-held ‘off-vent’.
1990
1995
1997
2001
2000
2005
2002
Acquisition of
2008
2007
2008
sale and transfer part of research to Novartis
Pharma AG
On December 31, 2008
Pulmonary area acquisition
• To 115 millions $
• Assignment concerned:
–
–
–
–
–
Research
Development
Formulation and manufacturing technology
Equipement,140 personnel
Intellectuel propreties
• retained all rights to BAY41-6551, partnered with Bayer
Healthcare + royalty rights for the Cipro Inhale
1990
1995
1997
2001
2000
2005
2002
Acquisition
of
2008
2007
2009
NKTR-118 and NKTR-119 as study
case
Deal between Nektar and AstraZenaca for
NKTR-118 andNKTR-119 development
Initial payment: $125 million
Total payement: $1.4 billion
?
2007
2009
2010
NKTR-118: a novel PEGylated
naloxol conjugate for the treatement of
opioid-bowel dysfunction (OBD)
naloxol
OBD 40% of patients taking opioid
Traditional
constipation
treatment
PEGylated naloxol
• not so effective
• Direct action on opiod-receptor
Commercial opportunity for prevention
and treatment > $1 billion
NKTR-118: a novel PEGylated naloxol conjugate
for the treatement of opioid-bowel dysfunction
(OBD)
Central μ-opioid
receptors
=> analgesia
peripheral μopioid receptors
=> inibits bowel
fonction
Opioid
agonists still
No reversal
activating
analgesia
receptors
No crossing of the bloodbrain barrier
No adverse GI
effects
Peripheral antagonists
disloge opiod
Study design
Results
Conclusion
• Oral NKTR-118 restores GI function by increasing the
frequency of SBMs
• No reversal or no reduction of opioid-mediated analgesia
• Well tolerated, side effects being dose dependent
NKTR-118 => NKTR-119
NKTR-118
• Indication: Opiod bowel
dysfunction
• Phase 2 complete
NKTR-119
• Co-formulation: NKTR-118
and opioid
• Indication: Analgesic for
pain
• Clinical programme to
demonstrate proo-ofprinciple in humans
initiated in 2009
Total revenue (millions)
300
$273,027
250
$217,718
collaboration and
other
product sales and
royalties
200
150
$90,185
100
$71,931
50
0
2006
2007
2008
2009
Revenue
Different collaboration deals
(2008)
Others
31%
Roche
14%
Revenue by geographic area
Bayer
24%
Novartis
15%
100%
90%
UCB
16%
80%
70%
60%
other
countries
50%
US
40%
EU
30%
20%
10%
0%
2006
2007
2008
R&D expenses
(millions)
180
160
$149,381
$153,575
$154,417
140
120
$95,109
100
80
60
40
20
0
2006
2007
2008
2009
Futur for Nektar
• Possibility of repurchase ?
• many partnering with big pharma
• Desire to lead their product from research to
commercialization.
SWOT analysis
STRENGTH
WEAKNESSES
•Strong and strategic alliance
• Financially dependant on its partnerships
•Innovating technological platform
• R&D budget too high
•Blockbusters
• few products on the market
•diverse sectors of applications
•Since the pulmonary sector sale => only one
technological platform
•Various pipeline
OPPORTUNITIES
• Short term: to strengthen the partners
network
• Long term: develop its own molecule to
commercialization
THREATS
• Competitors
•Fail of NKTR-118 and 119
Thanks for your attention