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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 systemChief Executive Officer : Howard W. RobinPublicly-traded (NASDQ: NKTR) since 1994
350 employees
Localisation:
strategyreduce 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
PartnersStrategy of development : Partnerships and co-development agreements with pharmaceutical companies
partnering strategy •t
o fund further clinical development
•manage the global regulatory filing process
•manage the marketing
•sell the approved drugs
•depend on factors:•the cost •complex
ity 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:
Possible Responsibility for:- raw material manufacturing - medical device manufacturing
Responsible for:- future clinical development- commercialization costs- worldwide regulatory filings
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•if marketing authorization is withdrawn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
Therapeutics areas
CNS/ Pain
Immunology/
Inflammation
Anti-infectivesHemophilia
Others
Oncology
Different therapeutic area of R&D
Therapeutics areas
CNS/ Pain
Immunology/
Inflammation
Anti-infectivesHemophilia
Others
Oncology
Therapeutics areas
CNS/ Pain
Immunology/
Inflammation
Anti-infectivesHemophilia
Others
Oncology
Therapeutics areas
CNS/ Pain
Immunology/
Inflammation
Anti-infectivesHemophilia
Others
Oncology
Therapeutics areas
CNS/ Pain
Immunology/ Inflammation
Anti-infectives
Hemophilia
Others
Oncology
Therapeutics areas
CNS/ Pain
Immunology/ Inflammation
Anti-infectives
Hemophilia
Others
Oncology
NKTR-102-Phase II- 4 different indications- No partner
NKTR-105-Phase I-No partner
NKTR-118-Phase II-AstraZenecaNKTR-119-Preclinical-AstraZenecaNKTR-181,NKTR-194NKTR-171-Preclinical-No partner
NKTR-125-Préclinical-No partnerCimzia- new indication-UCB
Cipro inhale-Phase II-BayerNKTR-061-Phase II-BayerNKTR-063-Phase I-No partnerNKTR-140-Preclinical-No partner
Factor VIII modified-Preclinical-Baxter
MAP0004-Phase III-MAPHematide-Phase III-AffymaxCDP791-Phase II-UCB
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 productsproducts 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)
Gram-positive pneumonia
Phase I
MAP004 Migraine Phase III MAP
Exubera diabetes AMM 2006 Pfizer
1990
1995
Exubera ® :inhaled insulindiabetic treatment
Neulasta ® : - stimulates the production
of neutrophils- neutropenia treatment
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
January 1995Inhale and Pfizer announced their
collaboration
June 1998 Trials (IIb) indicate
their inhaled-insulin 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, co-develop and co-promote
Liability of Inhale : -supplying the delivery devices-And insulin powderAchievement receive a share of the royalties on sales
janvier 2006Pfizer buys exubera
part to Sanofi Aventis (for 1.3
milliard $)
AMM
Novembre 2007payment of $135
million from Pfizer in satisfaction of all
remaining obligations
janvier 2006pfizer rachete les parts d’exubéra a
sanofi aventis (pour 1.3 milliard de
dollars)
AMM
Novembre 2007payment of $135
million from Pfizer in satisfaction of all
remaining obligations
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• unwieldy and not very discreet• Exubera caused a slight decline in lung
function.• Problematic delivery• the need for spirometry (before and periodically)
• Lack of long-term safety data.Scott Joy, associate professor of medicine at Duke University Medical Center said, “I have not prescribed Exubera to a single patient yet, with the reason being that I don’t have a spirometer here in the office.”
Some insurance companies are refusing to pay
Impact to nektar
- total revenue from Pfizer: in % of nektar total revenue
- 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.
2006 2007 200864% 67% 0%
• 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
Micera®:- a continuous erythropoietin receptor
activator- treatment of anemia associated with
chronic kidney disease
1990
2000
1995
2001
1997
Acquisition of
Somavert ® : - human growth hormon receptor antagonist- treatment of acromegaly
Cimzia®: - at the moment 2 indications -crohn desease- rheumatoid arthritis
PEG-Intron®:-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 interestsCreat new drugs with optimized
properties
Reposition approves products for new indications
Rescue non-viable drug candidates
Multiple therapeutics areas
PEGylation limitationsReactions 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
The active parent molecule is cleaved from the prodrug through pH or enzymatic hydrolysis
Above all for oncolytics drugs
NKTR-102 and NKTR-105
Large Molecule Polymer Conjugates
• 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
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.
Antibody Fragment Conjugates• Branched PEG conjugated to antibody fragment => become the Fc fragment• Stable or degradable linkage
AVANTAGESImprove toxicity profileExtend half-lifeReduce glomerular filtration rateReduce antigenicity
1990
2000
2002
1995
2001
1997
Acquisition of Macugen ®: in treating age-related
macular degeneration
1990
2000
2002
2005
1995
2001
1997
Acquisition of
2003
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.
2007Collaboration with Bayer HealthCare
• NKTR-061 ( inhaled amikacin) • Indication: Gram-negative pneumonias,
• used: with conventional mechanical ventilators or as a hand-held ‘off-vent’.
result of complications of other
patient conditions or surgeries
2008sale and transfer part of research to Novartis
Pharma AGOn 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
NKTR-118 and NKTR-119 as study case
Deal between Nektar and AstraZenaca for NKTR-118 andNKTR-119 developmentInitial payment: $125 millionTotal payement: $1.4 billion
?20092007 2010
NKTR-118: a novel PEGylated naloxol conjugate for the treatement of opioid-bowel dysfunction (OBD)
Traditional constipation treatment • not so effective
PEGylated naloxol • Direct action on opiod-receptor
Commercial opportunity for prevention and treatment > $1 billion
OBD 40% of patients taking opioid
naloxol
NKTR-118: a novel PEGylated naloxol conjugate for the treatement of opioid-bowel dysfunction (OBD)
Central μ-opioid receptors
=> analgesia
peripheral μ-opioid receptors => inibits bowel
fonctionPeripheral antagonists
disloge opiod
No adverse GI effects
No crossing of the blood-brain barrier
Opioid agonists still
activating receptors
No reversal analgesia
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-119NKTR-118 NKTR-119
• Co-formulation: NKTR-118 and opioid
• Indication: Analgesic for pain
• Clinical programme to demonstrate proo-of-principle in humans initiated in 2009
• Indication: Opiod bowel dysfunction
• Phase 2 complete
2006 2007 2008 20090
50
100
150
200
250
300
collaboration and other
product sales and royal-ties
Total revenue (millions)
$71,931
$217,718
$273,027
$90,185
Bayer24%
UCB16%
Novartis15%
Roche14%
Others31%
Different collaboration deals (2008)
Revenue
2006 2007 20080%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Revenue by geographic area
other countriesUSEU
R&D expenses (millions)
2006 2007 2008 20090
20
40
60
80
100
120
140
160
180
$149,381
$95,109
$154,417$153,575
• Possibility of repurchase ?
• many partnering with big pharma
• Desire to lead their product from research to commercialization.
Futur for Nektar
STRENGTH•Strong and strategic alliance•Innovating technological platform
•Blockbusters
•diverse sectors of applications
•Various pipeline
WEAKNESSES• Financially dependant on its partnerships• R&D budget too high• few products on the market•Since the pulmonary sector sale => only one technological platform
OPPORTUNITIES• Short term: to strengthen the partners network
• Long term: develop its own molecule to commercialization
THREATS• Competitors•Fail of NKTR-118 and 119
SWOT analysis