Transcript Diapositive 1

AMYLIN
Février 2008
ACCADEBLED Sophie – DAUSQUE Guy – VLEMINCKX Camille
1
Company Overview
Locations and Subsidiaries
• Amylin Pharmaceuticals, Inc.
9360 Towne Centre Drive
San Diego
California 92121
• Amylin Europe Ltd.
Mendelstraße 11
D-48149 Münster
Germany
2
Company Overview
Business Description
• Total employees : 1900
• R&D investment +++
• Focus on new peptide hormone candidates
• Two marketed products (first-in-class medicines)
BYETTA® and SYMLIN®  Diabetes
Create a sustainable growth for Amylin
3
Company Overview
Biopharmaceutical company
Biotech, Drug Discovery
Discovery
Development
Commercialization
DIABETES
CARDIOVASCULAR
DISEASE
OBESITY
4
The beginning …
Amylin: The Second -Cell Hormone
- First reported in 1987
- 37-amino acid neuroendocrine hormone
- Important regulator of glucose influx into bloodstream
- Co-located and co-secreted with insulin from pancreatic
-cells
- Equivalently deficient in type 1 and type 2 diabetes as
insulin
5
Amylin
Insulin
Unger. Williams Textbook of Endocrinology. 1992.
Interest in Neurohormones
LEPTIN
Regulation of
(1) Energy homeostasis
(2) Fat metabolism
GLP-1
(3) Glc metabolism AMYLIN
(1) InducesofGlc-dep
PYY insulin secretion
(4) Body weight Regulation
(2)(1)
Inhibites
Glc-dep glucagon secretion
Appetite
(1) Induces satiety
(3) ↓ food intake and body weight
(2) Food
intake
(4) Stimulates
β cell proliferation
(3) Postprandial [glucose]
GIP
(1) Induces Glc-dep insulin secretion
(2) Stimulates β cell proliferation
GIP
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1987
• Amylin discovered by researchers at Oxford University
 Foundation of the company
1995
• Pramlintide (SYMLIN®) Amylin analog
1996
• Exenatide (BYETTA®) GLP-1 mimetic
Licensed from researcher John Eng
2002
• Continuous-infusion version of GLP-1
 Acquired rights from Restoragen Inc.
2005
• Chemical Ligation technology
 Acquired rights from Gryphon
2006
• Leptin
 Licensed from Amgen
Feb
2006
March
• GIP Receptor agonists
 Licensed from Diabetica
7
Pipeline
88
DIABETES
9
Diabetes market
15M diagnosed in US
Incidence +++
90-95% are type 2
Medical treatment based on the level of Hemoglobin A1C
→ < 7% : no medical treatment
→ 7-9% : oral diabetes agents
→ > 9% : insulin
1010
Traditional consensus
Discrimination in the 2nd
and 3rd line based on :
– Efficacity : glucose level
– Safety : hypoglycemia risk
– Others benefits :
• Cardiovascular
• Modalities of use
• Weight loss
• Cost
11
PRESCRIPTIONS
SALES
12
Source : Non-insulin therapies for type 2 diabetes, mona Ashiya and Richard E.T. Smith, News and Analysis, volume 6, October 2007, Nature Publishing group
MARKETED PRODUCTS
• BYETTA® Exenatide
• SYMLIN® Pramlintide
13
MECHANISM BYETTA®
Incretin mimetic
Ingestion
of food
GI tract
Pancreas
Release of
active incretins
GLP-1 and GIP
DPP-4
enzyme
Exenatide
Glucose
dependent
 Insulin
(GLP-1and
GIP)
Beta cells
Inactive
GIP
 Blood glucose
in fasting and
postprandial
states
Alpha cells
Glucosedependent
 Glucagon
(GLP-1)
Inactive
GLP-1
 Glucose
uptake by
peripheral
tissue
 Hepatic
glucose
production
GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide
14 14
MECHANISM of SYMLIN®
Amylin analog
Ingestion
of food
Stomach
Pramlintide
GI tract
AMYLIN
 GLUCAGON
Pancreas
Blood
sugar
INSULIN
TISSUE
15
15
Brand name / Generic name
SYMLIN / pramlintide
BYETTA / exenatide
Manufacturer
Amylin Pharmaceuticals
Amylin/Eli Lilly
FDA approval date
March 17, 2005
April 28, 2005
Market availablity
June 2005 (USA)
June 2005 (USA)
April 2007 (Europe)
Therapeutic class
Anti-diabetic, Amylin analog
Anti-diabetic, Incretin mimetic
Adjunctive therapy to
mealtime Insulin
Adjunctive therapy
Type I and II Diabetes
Type II Diabetes
(for patient who have failed to
achieve desired Glc control despite
optimal insulin therapy)
(for patients who have inadequate
control despite treatment with oral
agents Metformine+ SFUand/or TZD)
Approval clinical indications
None
Unapproved/ Off-label uses
but Symlin has completed phase II
studies for weight loss
None
Drugs in the same class
None
None
16
Market Niche
Cost for 30 day
supply
Dosage
/
Administration
Most common
side Effects
 For diabetics the most difficult to treat
 Requires extra injection in addition to
Insulin
 Provides a bridge to
insulin therapy
 Induces weight loss
$99,40 - $397,60
$201,94
15 µg - 120 µg prior to major meals
5 µg - 10 µg
twice daily prior to meals
Depending :
(1) Type I or II
(2) response to therapy
Nausea, vomiting, abdominal pain, headache,
fatigue and dizziness
Nausea, vomiting, diarrhea,
jitteriness, dizziness,
headache 17
Pancreatitis
BYETTA®
Positive results
(3 pivotal studies)
180
Late 2003
Submitted
NDA
FDA accepted
for review
FDA
Approval
EU
Approval
NDA Room T°
usage
June 2004
Sept 2004
April 2005
Nov 2006
Feb 2007
Launch in
Europe
April 2007
160
• Europe : Agreement with EliLilly
- Global development and commercialization of Byetta
120
- Launched in 30 countries during 2007
Sales
M$(M$)
140
100
• USA : Effective execution in the market place
-80High adoption by the diabetes specialists > 85%
-60Growth in use among Primary Care Physicians (PCPs)
40
•20 > 700 000 patients since its introduction
0
• Net
product
sales1Q06
2Q05
3Q05 4Q05
2Q06 3Q06 4Q06 1Q07 2Q07 3Q07 4Q07
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SYMLIN®
20
Approvable letter
!Additionnal trials!
Consultation FDA
 Clinical trials
2nd A. letter
!Additionnal data!
Submit
response
FDA Approval
NDA
Sympen
18
Oct 2001
Dec 2001
Dec 2003
Sept 2004
March 2005
Oct 2007
16
14
SalesM$(M$)
• Strategy
12
• > 80 000 patients
10
• Net product sales
8
6
4
2
0
2Q05
3Q05
4Q05
1Q06
2Q06
3Q06
4Q06
1Q07
2Q07
3Q07
4Q07
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Type II Diabetes Market
2020
EXENATIDE LAR
Collaboration pipeline
21
Exenatide LAR Project
•
First once-weekly injection for type 2 diabetes
 52 doses a year vs. 730 or greater
• Based on Alkermes’ proprietary technology for long-acting
medications
-Gradual, controlled release
(24 hours a day and 7 days a week)
-Consistent concentration of
exenatide provided
Anticipates
Better efficacy and
tolerability
than BYETTA
Improves
Patient compliance
and outcomes
22
Exenatide LAR
Phase II Study
HbA1C Change (%)
Weight Loss (kg)
Placebo LAR
Exenatide LAR
0,8 mg
Exenatide LAR
2 mg
Maggs D, et al. Presented at EASD Annual Meeting, Copenhagen-Malmö, Denmark-Sweden, September 14–17, 2006.
23
Exenatide LAR
Comparator Trial
Results
• A1C reduction from baseline of ~1.9% compared to
~1.5%
• Average weight reduction of ~8 pounds in both groups
• No major or severe hypoglycemia
30-week, open-label, noninferiority study
• Improved tolerability ~30% less nausea
Type 2 diabetes : 295 subjects
Open-ended extension ongoing
24
Exenatide LAR
Submission Timing
FUTURE STUDIES
3 superiority trials underway to support commercialization
- Once-weekly vs. TZD vs. DPP-4
 Added to metformin background therapy
- Once-weekly vs. insulin glargine
 Added to background Met+SU therapy
- Monotherapy study vs. Metformin
25
Exenatide LAR
Type II Diabetes Market
26
DIABETES
OBESITY
OBESITY
The increasing burden of
obesity
27
Obesity Market
Sales of main
(US$m)
Sales ofdrugs/classes
main drugs/classes (US$m)
2000
2000
2005
β3-adrenoceptor agonists
2010
β3-adrenoceptor agonists
2010
2005
of main drugs/classes (US$m)
Other novel centrally acting
β3-adrenoceptor agonists
appetitesupressants
2000
Other novel centrally acting
appetitesupressants
Leptin-related compounds
Noradrenergic anorectic agents
Pancreatic-lipase inhibitors
Xenical
Leptin-related compounds
Serotonin- and noradrenalinereuptake inhibitors
Other
novel
Noradrenergic
anorectic
agentscentrally acting
Acomplia$ 426 m
(antagonist CB1)
appetitesupressants
$ 723 mPancreatic-lipase inhibitors
Leptin-related compounds
S$m)
$ 1.366 m
Serotonin- and noradrenalinereuptake inhibitors
Sibutramine
β3-adrenoceptoragonists
agonists
β3-adrenoceptor
Noradrenergic anorectic agents
Other novel
novel centrally
centrallyacting
acting
Other
appetitesupressants
appetitesupressants
Pancreatic-lipase inhibitors
Leptin-relatedcompounds
compounds
Leptin-related
Serotonin- and noradrenalinereuptake inhibitors
28
Noradrenergicanorectic
anorecticagents
agents
Noradrenergic
PIPELINE PRODUCTS
In-house pipeline
29
INTO Program
Integrated Neurohormonal Therapy for Obesity Program
Key role of neurohormones in regulating appetite and energy balance
 Studies of the interaction among these hormones within the brain
 Uncover their full therapeutic potential
PROTAGONISTS
Amylin  Pramlintide or Amylinomimetics
PYY 3-36
Leptin  Metreleptin
30
Pramlintide + Leptin
Proof of concept (synergy) – Phase II
24-week Clinical Obestity study :
Phase IIA, randomized, double-blind, active-drug-controlled, multicenter study
177 overweight and obese patients (BMI 27-35 and weight average ~205 pounds) 31
31
Pramlintide + Leptin
Study results
Metreleptin
(r-metHuLeptin)
Pramlintide
Pramlintide +
Metreleptin
No report of weight loss
8,4% of weight loss
weight loss leveled off
toward the end
Lost average :
17 pounds
12,7% (p<0,001)
continuous weight loss
till the end
Lost average :
25 pounds
Most common side effects : (1) injection site adverse events
(2) nausea - mild to moderate and transient nature
32
SWOT ANALYSIS
33
STRENGHTS
WEAKNESSES
Byetta
New management team
Strategic alliances
OPPORTUNITIES
THREATS
34
Alliance Eli Lilly / Amylin
Agreement for the global developement and commercialization of exenatide
Byetta + Byetta LAR
Operating profits
Developement and
Commercialization
cost
In US
shared equally between Amylin and
Lilly
In US
shared equally between Amylin and
Lilly
Outside US
80% Lilly / 20% Amylin
 Royalties
Outside US
100 % Lilly
Advantages :
 International
 Commercial
35
Alliance Alkermes / Amylin
Developement and manufacturing of exenatide LAR
Medisorb injectable sustained
release drug delivery technology
ALKERMES = Biotechnology company
• Targets : CNS disorders, addiction and diabetes
• Extended-release injectable, pulmonary, and oral products
• Two commercial products :
- Risperdal consta® (Risperidone LAR)
First and only atypical antipsychotic medication LAR (Janssen-Cilag)
- Vivitrol® (Naltrexone)
Once-mounthly injectable medication  treatment of alcohol dependence (Cephalon)
3636
STRENGHTS
Byetta
New management team
Strategic alliances
OPPORTUNITIES
WEAKNESSES
Narrow customer concentration
Narrow Market difficult to extend
Pancreatitis risk
Reliance on third party manufacturers
THREATS
37
Reliance on third party manufacturers
NO MANUFACTURING CAPABILITIES
BYETTA®
Reliance on Bachem and Mallinckrodt
 To manufacture its long-term
commercial supply of bulk exenatide
Reliance on single-source manufacturers
 For some of the raw materials used by
Bachem and Mallinckrodt
Reliance on Wockhard and Baxer
 Manufacture the dosage form of
Byetta in cartbridges
SYMLIN®
Bachem and Lonza
 commercial supply of bulk pramlintide
acetate
Baxter
 dosage form of Symlin in vials
Wockhardt
 dosage form of Symlin in cartridges
Ypsomed
 components for the Symlin disposable pen
Hollister-Stier  assembly of the pen
38
STRENGHTS
Byetta
New management team
Strategic alliances
OPPORTUNITIES
WEAKNESSES
Narrow customer concentration
Narrow Market difficult to extend
Pancreatitis risk
Reliance on third party manufacturers
THREATS
Exenatide LAR
INTO Obesity program
Symlin indication expansion
Manufacturing facilities
TZD decline
39
STRENGHTS
Byetta
New management team
Strategic alliances
OPPORTUNITIES
Exenatide LAR
INTO Obesity program
Symlin indication expansion
Manufacturing facilities
TZD decline
WEAKNESSES
Narrow customer concentration
Narrow Market difficult to extend
Pancreatitis risk
Reliance on third party manufacturers
THREATS
Regulations
Industry consolidation
Competition
40
Competition
DIABETES AND
METABOLIC
DISORDERS
•
•
•
•
•
•
•
•
•
•
AstraZeneca
Bristol-Myers Squibb
GlaxoSmithKline
Lilly
Merck
Novartis
Novo Nordisk
Pfizer
Sanofi-Aventis
Takeda
Pharmaceuticals
OBESITY : Few products…
• Sanofi-Aventis : Acomplia
• Roche : Xenical
• Abbott : Meridia
… But a lot of failures!!!
41
COMPANY FINANCIAL
42
Financial statements
• Sources of revenues :
– Products:
• Byetta : direct / indirect
• Symlin : Direct, only in the US
– Collaborative agreement :
• Eli Lilly ( sept 2002)
43
Financial statements
Source of expenses
300 000
cost of goods sold
costs ($)
250 000
200 000
selling, general and
administrative
150 000
100 000
research and
development
50 000
0
2002
2003
2004
2005
2006
year
44
Financial statements
45
Forecast
• Consensus
2005
2006
2007 E
2008 E
2009 E
2010 E
75,3
430,3
704,8
900,0
1202,0
1500,6
0,0
0,0
26,8
49,4
66,8
80,1
11,5
43,8
53,3
79,4
99,9
119,0
86,8
474,1
784,9
1028,7
1368,7
1699,8
53,8
36,8
60,0
50,0
35,0
35,0
Total Revenues
140,6
510,9
844,9
1078,7
1403,7
1734,8
Cost of sales
14,8
50,1
76,9
102,9
136,9
170,0
Gross profit
125,8
460,9
768,0
975,9
1266,8
1564,8
R&D
132,1
222,1
270,0
290,0
300,0
305,0
SG&A
171,5
282,0
395,0
415,0
425,0
430,0
31,4
194,2
324,9
414,9
554,1
675,3
-209,2
-237,3
-221,9
-144,0
-12,3
154,5
Other income
2,5
18,5
15,0
22,0
30,0
43,2
Pretax Incomes
-206,7
-218,8
-206,9
-122,0
17,7
197,7
0,0
0,0
0,0
0,0
0,0
49,4
-206,7
-218,8
-206,9
-122,0
17,7
148,3
Average Shares Fully Diluted (millions)
105,5
122,6
131,5
133,0
134,8
Earnings Per Share before Extraord. Charges
-1,96
-1,78
-1,57
-0,92
0,13
136,0
46
1,09
Exenatide / LAR (US sales)
Exenatide / LAR (Ex-US sales)
Symlin
Net product Revenue
Revenue under collaboration agreements
Co-promotion expense (Exenatide / LAR US)
Operating Income
Income Taxes
Net Income before Extraord. Charges
Forecast
• Consensus could be modified by recent results :
– The FDA approved its pen device for delivering its diabetes drug
SYMLIN, but rejected its application to increase SYMLIN's label to
include patients using basal insulin.
→ no label expansion
→ impact on amylin’s plans to develop the active ingredient in Symlin
as weight-loss drug : program INTO
– Deception by the results of a 30-week comparator study of onceweekly exenatide long-acting release (LAR) injection and
BYETTA® (exenatide) injection taken twice daily in patients with
type 2 diabetes
→ positive results but not sufficient
47
Consequences on the market
48
48
Conclusion
• Sources of revenues threatened
– Small markets for the two products
– No label expansion in a near period
– Growth of number of competitor on the byetta’s market
• Sources of depenses in growth
– Early-stage and late-stage programs (proof of efficacy
and safety, launch of exenatide LAR)
– Construction of manufacturing facility for exenatide LAR
• Weak pipeline
– Few products
– Strong links between the products
49
Conclusion
« The Amylin story is tied to the success or
failure of his potential blockbuster
Exenatide LAR »
50
Thank you for your attention
Questions ?
51