Transcript alkermes - Moodle Lille 2

David Michel
Tarik Rihani
Simon Mayer
14 mars 2013
Alkermes Inc

Pennsylvania corporation formed on July 13, 1987

Headquartered in Waltham, Massachusetts.
WHY WORK WITH ALKERMES ?
11/03/2013
Product challenge solved
11/03/2013
Principal Parteners
The Merger
Elan Drug Technologie

1969 in Irland

667 people

CRO


Develop technologies to unsolved drug formulation
challenges
NanoCrystal technology; SODAS® Technology…
MERGER TRANSACTION
Cost of transaction : 950 M$
• 500 $ million in cash
• 25% of Newco
• 460 $ million in stock worth
Alkermes, Inc.
Elan Drug
Technologies
Reasons for the Merger

Alkermes.Inc
 be less reliant on its Risperdal Consta
risperidone
 diversifing portfolio of products
 valuable late-stage pipeline
 Robust cashflows to invest in its proprietary
drug candidates
 create a larger, faster-growing
biopharmaceutical company
11/03/2013
Elan Drug Technologie
 No commercial products
 No commercial organisation
 Not profitable : Indebtedness
Reasons for the Merger
be less reliant on its Risperdal Consta risperidone
Reasons for the Merger
Five Key Products Drive Revenue Growth
Reasons for the Merger
Financial engine to grow revenue and expand margins
Reasons for the Merger
Lates stage pipeline drives a long terme growth.
Risks Related to New Alkermes
1. Plan of integration may encounter unexpected difficulties or incur unexpected
costs.
2. New Alkermes shares will be highly volatile and may decline if the merging is
unsuccessful
3. keeping existing customers and obtaining new customers
4. With the approval of Invega, many people on Wall Street were having a
problem rationalizing if Invega was going to compete with Risperdal
Alkermes' localisation
Ireland Facility
Ohio Facility
Massachusetts
Facility
Georgia Facility
Headquarters
(Dublin)
Financial analysis
Alkermes' revenues
Research and development revenue
Développement of BYDUREON
Pay for sales in Europe
Manufacturing and royalty revenues
New drugs on the market
Product sales , net
rising price of VIVITROL
authorized sales VIVITROL in Russia
Alkermes' expenses
Cost of goods manufactured and sold
The merger adding the EDT portfolio valued at
approximately 70 millions
Research and development
ALKS 37 et ALKS 9070
Clinical studies remaining old Alkermes
Collaboration with Acceleron
Alkermes R&D expenses
MERGER IMPACT
Emergence of long-term debt following the merger with Elan
($441,360 millions)
Alkermes‘ technologies
Nanotechnology in drug delivery, is being embraced particularly as a
means of improving or enhancing the delivery of drugs,
It’s considered by many as key to optimising drug delivery.
• long-acting injectable technologies enables the gradual release into the body of
small molecules at a controlled rate over a specific period of time.
• By enabling patients to take medications less frequently, it can be especially
beneficial in treating CNS diseases such as psychiatric disorders, in which
medication compliance is closely correlated with improved outcomes.
• Ex : Medisorb®, LinkeRx® and NanoCrystal®.
NanoCrystal technology : (ELAN)
allowed for a stable, low viscosity, high drug-loaded formulation in a small
injection volume, to be developed.
enabling the formulation of poorly water soluble compounds.
maintain a drug in its original crystalline form until biologically activated
It is Elan’s most successful delivery technology which generated US $1.9 billion
in 2010.
• customize drug-release profiles and dosage forms
– oral delayed release
-extended release
– pulsatile release
-immediate release
– and chrono-timed delivery
• The OCR technology platform can bring one or more of the following
benefits for new and existing drug products:
– Highly flexible release profiles
– Reduced gastrointestinal irritancy
– Tableting technology within a capsule
– Hydrophilic matrix-controlled diffusion and erosion
– Bilayer technology.
• SODAS® Technology (ELAN) (Spheroidal Oral Drug Absorption System )
• is a multiparticulate system for controlling the release of drugs taken orally .
• coating of uniform spherical sugar beads of 1-2 mm in diameter with drug and
excipients.
• then coated with controlled release polymers to form a release rate controlling
membrane
• Depending on the coating polymers chosen, different release profiles
• PRODAS® Technology (Programmable Oral Drug Absorption System)
• Multiparticulate minitablet technology system, which combines the
benefits of tableting technology within a capsule.
• it is possible to combine mini-tablets with different release profiles or sizes
within the one capsule in order to achieve high drug loading and constant
release profile throughout the GI tract.
MXDAS® Technology (MatriXDrug Absorption System)
-drug in a hydrophilic polymer matrix, which controls the drug’s rate of release
through a process of diffusion and erosion in the gastrointestinal tractDrug.
-The tablets can be produced by direct compression or granulation and be enteric
coated if required
-It was used to develop a sustained release formulation of dalfampridine Ampyra®.
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inal.pdf
• DUREDAS™ Technology (DUal RElease Drug Absorption System)
• -Bilayer tablet which can provide immediate or sustained release of two drugs or
different release rates of the same drug in one dosage form.
• -initially developed for OTC controlled release analgesics. In this case one layer of
the tablets was formulated as an immediate release granulate to achieve rapid
onset of action, while the second released the drug slowly to provide sus-tained
pain relief.
NanoCrystal®
• The NanoCrystal technology :
 reducing the size of drug particles to increase their exposed
surface area,
 stabilizing the nanoparticles to maintain size.
 improved dissolution rate
 improved bioavailability,
 reduced dosage volume,
 increased maximum tolerated dose.
• → it is applicable to all routes of administration of
any dosage form.
Nanoparticle Technology
offer over competing technologies in the poorly water-soluble drug delivery space
include:
•
Rate and extent of drug release independent of pH
•
Improved bioavailability, rate of absorption and dose
•
delivery of drug to GI tract
•
Linearity Rapid dissolution
•
Excellent stability
•
High drug loading
• present opportunities for disease intervention in addiction, behavior and
mood modification, immunology, and pain
• understanding of opioid biology and how drug compounds can target
disease processes in the brain to treat CNS diseases to develop new drug
candidates that target opioid receptors.
• supported by a proprietary library of molecules designed to target different
types of opioid receptors.
• Medifusion.
 With traditionnal administration , the drug active must remain between a
maximum blood level value wich may represent a toxic level and a minimum
value below which the drug is no longer effective.
-With controlled administration the
blood level are constant between the
desired maximum and minimum for an
extented period of time
TECHNOLOGY IMPACT
Intangible assets:
Phenomen explained by four factors:
-collaboration
-NanoCrystal
-OCR technology
-IPR & D
Alkermes' products
Risperdal consta®
-Exclusively manufactured by Alkermes
-Marketed and sold by Janssen in
more than 90 countries.
Indication
Risperdal consta® is the first and only long-acting,
atypical antipsychotic approved by the FDA (2003) for
the treatment of schizophrenia.
For bipolar I disorder: the FDA approved Risperdal
consta® as both monotherapy and adjunctive therapy
to lithium or valproate in the maintenance treatment of
bipolar I disorder in May 2009.
What is schizophrenia?
 Schizophrenia is a chronic, severe and disabling brain disorder
 The disease is marked by:
→ positive symptoms: -hallucinations
-delusions
→ negative symptoms:-depression
-blunted emotions
-social withdrawal
 Worldwide, it is estimated that one person in every 100 develops schizophrenia.
 Studies have demonstrated that as many as 75% of patients with schizophrenia
have difficulty taking their oral medication.
What is bipolar I disorder?
Bipolar disorder is a brain disorder that causes unusual
shifts in a person's mood, energy and ability to function
→extreme highs: mania
→extreme lows: depression
Bipolar disorder affect approximately 5.7 million
American adults.
The median age of onset for bipolar disorder is 25
years.
Mechanism of action
Platform technology
uses polymer-based microsphere injectable
extended-release technology to deliver and
maintain therapeutic medication levels in the body
through just one injection every two weeks.
manufactured and commercialized by Janssen
Indication
INVEGA SUSTENNA/XEPLION is a once-monthly,
long-acting injectable atypical antipsychotic
approved by the FDA (2009) for the treatment of
schizophrenia in adults.
Platform technology
Uses nanoparticle injectable extended-release
technology to increase the rate of dissolution and
enable the formulation of an aqueous suspension
for once-monthly intramuscular administration.
Risperdal consta and Invega sustenna's
net sales
Patents :
Main competitor
• ZYPREXA®RELPREVV®
• Marketed and sold by Lilly
Vivitrol
•Alkermes develop, market
and sell, VIVITROL in the
U.S.
•Royalties revenues by Cilag
Indication
VIVITROL is the first and only once-monthly injectable
medication for the treatment of :
→alcohol dependence
→opioid detoxification
approved by the FDA :
-for the treatment of alcohol dependence in April 2006
-for opioid detoxification in October 2010.
Mechanism of action
Incidence of opioid and alcohol dependence
According to the 2010 U.S. National Survey on Drug
Use and Health, an estimated 1.5 million people aged
18 or older were dependent on pain relievers or
heroin
Approximately 18 million people in the U.S. are
dependent on or abuse alcohol
Platform technology
•uses polymer-based microsphere injectable
extended-release technology to deliver and
maintain therapeutic medication levels in the body
through just one injection every four weeks.
Vivitrol's net sales
Patents :
Competitors
• In the treatment of alcohol dependence:
-CAMPRAL ® (acamprosate calcium) sold by Forest
Laboratories
-ANTABUSE® (disulfirame) sold by Odyssey
-SELINCRO®(nalméfène) sold by Biotie therapies
• In the treatment of opioid dependence:
-methadone,
-oral naltrexone
-SUBOXONE®
-SUBUTEX ®
Each of which is marketed and sold by Reckitt Benckiser Pharmaceuticals, Inc. in the U.S.
Ampyra®/Fampyra®
•marketed and sold in the U.S. under the trade name
AMPYRA by Acorda
•marketed and sold outside the U.S. under the trade
name FAMPYRA by Biogen Idec
•Incorporates our Oral Controlled Release ("OCR")
technology.
Indication
-AMPYRA was approved by the FDA in
January 2010 as a treatment to improve
walking in patients with Multiple Sclerosis
(MS).
-FAMPYRA received conditional marketing approval in the EU in
July 2011 and is currently being sold by Biogen Idec in select
European countries, as well as Australia.
What is multiple sclerosis?
MS is a chronic, progressive disease in which the immune system attacks
and degrades the myelin sheath. People with MS may suffer
impairments in any number of neurological functions (often include
difficulty walking).
Mechanism of action
Ampyra's net sales
Bydureon®
uses our polymer-based microsphere injectable
extended-release technology
Exenatide is a GLP-1 agonist
Indication
-In June 2011, the European Commission granted marketing authorization
for the treatment of type 2 diabetes in adult patients in combination
with:
-metformin
-sulfonylurea
-thiazolidinedione
-metformin+ a sulfonylurea
-metformin+ a thiazolidinedione
-A once-weekly formulation of exenatide.
-In January 2012, the FDA approved BYDUREON® as an adjunct to diet and
exercise to improve glycemic control in adults with type 2 diabetes.
Pipeline
ALKS 3831
ALKS 3831
•Combinaison of ALKS 33 and olanzapine (ZYPREXA) designed to have
efficacy of olanzapine with attenued weight gain
•Olanzapine show to have highest efficacy, but also highest incidence of
weight gain among atypical antipsychotics
What is ALKS 33?
ALKS 33 is an oral opioid modulator characterized by limited
hepatic metabolism and durable pharmacologic activity in
modulating brain opioid receptors.
57% of olanzapine
patients
experience >7%
weight gain at one
year
• Randomized, double-blind
placebo-controlled trial to
evaluate safety and efficacy of
ALKS 3831 in attenuationinduced weight gain in 106
healthy volunteers
• Daily oral ALKS 3831
significantly attenued
olanzapine-induced weight gain
over three weeks
• Safety and tolerability of ALKS
3831 similar to olanzapine
• Phase 2 study begin mid CY’13.
ALKS 5461
A novel therapie for major depressive disorder
What is a major depression?
•
•
•
•
•
Fatigue or loss of energy almost every day.
Feelings of worthlessness or guilt almost every day.
Impaired concentration, indecisiveness.
Insomnia or hypersomnia (excessive sleeping) almost every day.
diminished interest or pleasure in almost all activities nearly
every day
• Restlessness or feeling slowed down.
• Recurring thoughts of death or suicide.
• Significant weight loss or gain
ALKS 5461 novel therapie for major
depressive disorder (MDD)
•Co-formulation of ALKS 33 and buprenorphine to form novel opioid receptor
modulator
•For patient who have inadequate response to standard antidepressant
therapies
•Positive phase 1: -multi-center, placebo-controlled, multi-dose study in
32 patients
-Well tolerated and significantly improved
depression scores on 7 days
•Phase 2: 130 patients enrolled in december 2012 (data expected H1 CY’13)
Aripiprazole lauroxil
(ALKS 9070)
A once-Monthly Prodrug of Aripiprazole
Platform technology
•ALKS 9070 is the first Alkermes’ product candidate
to leverage our proprietary LinkeRx TM product
platform
• A once-monthly injectable atypical antipsychotic in
development for the treatment of schizophrenia.
• Once in the body, aripiprazole lauroxil converts to
aripiprazole.
•In December 2011, initiation of a phase 3 clinical trial of aripiprazole lauroxil for the
treatment of schizophrenia:
-12-weeks, multicenter, double-blind, placebo-controlled study
-to assess the efficacy, safety and tolerability of aripiprazole lauroxil
-690 patients experiencing acute exacerbation of schizophrenia
•Data anticipated late 2013
•New agent to expand long acting treatment options
•Patent protection into late 2030
•interest to move from oral to an injectable form:
-> increase compliance
Manufacturing and royalty revenues
Financial year*
Conclusion
Strategy
• Capitalize on growth from our five key commercial
products
• Continue to advance our pipeline
• Grow revenues and manage our expenses to
expand our margins
Thanks for
your
attention
Any question ?