 Investor and
Analyst Day June 23, 2011
Nasdaq: LGND
Exhibit 99.1 |
 Investor
and Analyst Day John Higgins
President and Chief Executive Officer
2 |
 3
Safe Harbor Statement
•
The following presentation contains forward-looking statements regarding Ligand’s
prospects, plans and strategies, drug development programs and collaborations.
Forward- looking statements include financial projections, expectations regarding
research and development programs, and other statements including words such as
“will,” “should,”
“could,”
“plan,”
etc. Actual events or results may differ from Ligand’s expectations. For
example, expense reductions and drug development programs may not be realized. In
addition there can be no assurance that Ligand will achieve its guidance in
2011. •
The forward-looking statements made in the presentation are subject to several risk
factors, including, but not limited to, Ligand’s reliance on collaborative
partners for milestone and royalty payments, regulatory hurdles facing Ligand's,
CyDex's and partner's product candidates, uncertainty regarding Ligand's, CyDex's and
partner's product development costs, the possibility that Ligand's, CyDex's and
partner's drug candidates might not be proved to be safe and efficacious and
commercial performance of Ligand's and/or its partner's products. Additional
risks may apply to forward-looking statements made in this presentation.
•
The risk factors facing Ligand are explained in greater detail in Ligand’s filings with
the SEC, including the most recently filed annual reports on Form 10-K and
quarterly reports on Form 10-Q, as well as other public filings.
•
While forward-looking statements reflect our good faith beliefs (or those of the
indicated third parties), they are not guarantees of future performance. We disclaim
any obligation to update or revise any forward-looking statements, whether as a
result of new information, future events or otherwise. |
 4
Investor and Analyst Day Agenda
Welcome and Company Overview
John Higgins
Captisol
®
Technology
Matt Foehr
Melphalan Program
Rick White
Promacta Highlights
Rob McKay
Thrombocytopenia in Hep C
Nezam H. Afdhal, M.D.
Chief of Hepatology, Director of Liver Center,
Beth Israel Deaconess Medical Center
Financial Highlights
John Sharp
Small Group Workshops
•
Captisol –
Powerful Enabling Technology
•
“Shots on Goal”
Portfolio
Questions and Answers / Reception |
 5
Small-Group Workshops
1.
Captisol
®
–
Powerful Enabling Technology
Matt
Foehr
–
Executive
Vice
President,
Chief
Operating
Officer
JD Pipkin –
Senior Director, New Product Development
Vince Antle –
Senior Director, Technical Operations and Quality Assurance
2.
“Shots-on-Goal”
Portfolio
Rob McKay
–
Senior Director, Business Development and Investor Relations
Syed Kazmi
–
VP, Business Development and Strategic Planning
Rick White
–
VP, Business Development and Marketing
Room
3
2 |
 6
Ligand’s Business Model
Ligand's focus is to build a large portfolio of high
quality pharmaceutical assets that can drive
substantial cash flow and profitability. We operate
the
business with an emphasis on focused drug
development
and
partnerships,
with
a
disciplined
and
highly selective cost structure. |
 7
Revenue Outlook
Robust Pipeline
Captisol
®
–
Enabling Technology
High Quality Partners
The Foundation of the Ligand Opportunity |
 8
Ligand is Doing Great
•
Significant expansion (doubling of portfolio to over 60 programs) in
past 6 months as a result of Cydex acquisition
•
A number of positive news events by partners in 2011
•
Important new additions to senior management and Board of Directors
•
Most revenue generating assets ever on lowest cost structure
•
Positive clinical data announced in the past three months
•
Promacta
®
is a “now”
story
•
Directors have personally purchased over $1.2 million of Ligand stock
(131,125 shares) over the past 6 months. Directors now own 10% of
Ligand.
•
Over past year, daily trading volume has increased by ~30% |
 9
Ligand’s Potential Downside
Individual project set-backs
Slower growth
Partners drop programs
Risk
Reward
The Investment Proposition: Risk vs. Reward
Ligand’s Potential Upside
Potential blockbuster product
approved/
in-development
Near-term profitability
Well funded/financially disciplined
More
royalty
partnerships
than
any
peer
co
Attractive fully-owned
pipeline
Substantial calendar of news flow
Large NOLs
We believe the upside reward is substantially greater than the downside risk
|
 10
Ligand’s Potential Upside
List presented last summer (2010)
Updated Outlook
Potential blockbuster product approved/
in development
Data
for
Promacta
®
expected
over
next
6
months
Near-term profitability
Projected to turn profitable by year-end 2011
Well funded/financially disciplined
Lowest cost structure in company’s history
More royalty partnerships than any peer co
Large portfolio of assets, doubled in over last 12 months
Attractive fully-owned pipeline
SARM, diabetes, JAK 3, and melphalan programs
Substantial calendar of news flow
Continued news flow
Large NOLs
Continue to be ready to use following profitability |
     11
Potential Significant Revenue Expansion Over Next Several Years
*Plus license fees
Illustrative Growth
2015
2012
"Shots on Goal"
Vision
Turning into Reality
Promacta
Avinza
Conbriza
Promacta
Nexterone
Avinza
Carfilzomib
Conbriza
Aprela
Nexterone
CXCR2
Carfilzomib
Clopidogrel
>$30 million revenue*
Melphalan
Carbamazepine
Merck Captisol
®
Program
>$200 million revenue* |
 12
Worldwide Quarterly Promacta
®
Revenue Growth
$0.0
$2.0
$4.0
$6.0
$8.0
$10.0
$12.0
$14.0
$16.0
$18.0
$20.0
4Q08
1Q09
2Q09
3Q09
4Q09
1Q10
2Q10
3Q10
4Q10
1Q11
New markets and
new indications
should help
accelerate
revenue growth
Ligand and GSK reports
Ligand expects to
receive royalties
for another
14 years |
 13
Over 50 Partnered Programs
17%
9%
30%
39%
5%
•
Over half of the partnered portfolio is Phase II or later
•
Portfolio is highly diversified across many partners, stages of development and
therapeutic areas
•
Merck,
GSK
and
Pfizer
are
our
partners
with
the
most
programs
Marketed /
Approved
Phase III / NDA
Phase II
Phase I
PreClin
Ligand Portfolio: Partnered Programs
|
 14
19%
12%
7%
26%
35%
•
Programs are highly diversified across more than 10 therapeutic areas
•
The therapeutic areas most represented in the portfolio are oncology,
inflammation, neurology and metabolic disease
Ligand Portfolio: Total Portfolio Snapshot
Total Portfolio (Over 60 programs)
Marketed /
Approved
Phase III / NDA
Phase II
Phase I
PreClin |
 15
Ligand's Internal Pipeline Focus |
 16
Timing*
Projected Event
3Q11
Carfilzomib NDA filing
Platform Captisol Partnership
4Q11
Promacta Phase III HepC Results
Aprela NDA filing
SARM program update
1Q12
Initiate pivotal Melphalan study
Top Line IL-9 Phase II Results
Clopidogrel 505(b)(2) study initiation
2Q12
Merck CXCR2/COPD Study Completion
Carfilzomib NDA Approval
Promacta sNDA filing for HepC
*Ligand internal estimates
Ligand Portfolio:
Potential Upcoming News Flow |
 |
 18
•
High return late-stage
internal development
programs
•
New opportunities
New
Shots
•
High quality
relationships
•
Significant
expansion of “shots
on goal”
Deals
•
Powerful
enabling
technology
meeting key
needs
Captisol
Captisol
®
®
CyDex Acquisition:
What has it brought to Ligand? |
 19
Captisol
®
:
The Need |
 20
Patented, chemically-modified cyclodextrin
Increase drug solubility, reduce site reactions
Versatile across molecule families and sizes
Safe, inactive, inert
Over 100 clinical studies
Type V Drug Master File
Captisol
®
:
Enabling New Drugs |
 21
•
Strong manufacturing technology and IP estate
•
Hovione Partnership
50 metric ton capacity for Captisol
®
, ability to double
Exclusive relationship with built-in site redundancy
•
Intellectual Property
8 patent families covering technology, 12 patent families for products
Formulation and process-based patent portfolio providing protection
through 2029
Trade secrets, Drug Master File
Continuing internal innovation
Captisol
®
:
Enabling New Drugs |
 22
Captisol
®
:
The Value |
 23
Approved or
pending
products
Broader
platform
relationships
with partners
who can
leverage
Captisol
®
in
more ways
Internal
Captisol-
enabled
®
development
programs
with potential
for high
returns
Captisol
®
:
The Value |
 24
•
Reformulation can bring meaningful innovation to
established medicines
•
Late-stage internal development can create significant
value in exchange for relatively modest investment
•
505(b)(2) pathway leverages existing data
Lower development costs
Shorter timelines
Smaller infrastructure requirements
Captisol-enabled
®
Internal Development Programs |
 25
•
High dose conditioning treatment prior to
hematopoietic progenitor (stem) cell transplantation
for multiple myeloma
•
Orphan Drug Status
Market exclusivity, PDUFA fee waiver
•
Phase II dosing now completed
Interim results presented at ASCO
•
Pivotal trial projected to begin early 2012
Captisol-enabled
®
PG-Free Melphalan |
 |
 27
Continuing need for new
and innovative therapies
Multiple Myeloma
Second most common
hematologic cancer
50,000 patients
in the U.S., 20,000
diagnosed annually
Area of growing
industry interest
Transplant remains
a centerpiece in
managing disease
progression |
 28
Multiple
Myeloma:
Disease
Treatment
and
Progression |
 29
Deep Freeze
Thawing and infusion of
patient stem cells
Autologous
Stem
Cells
Autologous
Stem
Cells
Autologous
Stem
Cells
High Dose
Chemotherapy
Cryopreservation of
patient stem cells
Mobilization and
leukapheresis of
patient stem cells
Multiple Myeloma:
Stem Cell Transplantation |
 30
Captisol-enabled
®
Melphalan for
Injection
Ligand
Internal Development Asset
One vial system
Propylene glycol-free
24-hr infusion window
Treatment Flexibility
Alkeran
®
Launched in 1993
GlaxoSmithKline
Two vial system
Propylene glycol diluent
60-min infusion window
Per label limitations
Melphalan Product Comparison |
 31
Captisol-enabled
®
Melphalan for
Injection
Ligand
Internal Development Asset
One vial system
Propylene glycol-free
24-hr infusion window
Treatment Flexibility
Product Advantages:
•
Improved stability and use time in an all
aqueous formulation
•
Longer administration durations, slower
infusion rates
•
Elimination of two-vial system
Physicians expected to:
•
Safely achieve higher dose intensity
•
Easily deliver concomitant meds in high-
dose regimens
•
Modulate dose to patient tolerability
•
Higher dosage
potential for improved
response rates
Melphalan Product Comparison |
 32
•
IMS Reports Sales of $85MM for Rolling 12 Month Period
•
Majority of the Current Usage as a High Dose Conditioning Agent Prior to
Autologous Stem Cell Transplant in Multiple Myeloma Patients (currently off
label)
•
Potential Label, and Orphan Designation, for Captisol-enabled
®
Propylene
Glycol-Free Melphalan Addresses this Market
•
Unmet Medical Need with the Current Standard of Care:
Stability following reconstitution (60 minutes)
Limits on Absolute Daily Dosing
Limits on Duration of Infusion
Potential Adverse Reactions Due to Co-Solvent (propylene glycol)
Melphalan Market |
 33
A Marketing and Sales effort could be relatively lean and efficient
•
Melphalan therapy is well understood and entrenched, with few
influential bone-marrow-transplant hospitals
“Ultra-niche”
call universe
•
Benefits of Captisol-enabled
®
Melphalan formulation are easily
positioned
•
Effective promotion with lean sales organization achievable
•
Orphan Indication has favorable payer landscape (public and private)
Compass/Defined Health survey, 2009
Captisol-enabled
®
Melphalan: Opportunity |
 34
Captisol-enabled
®
Melphalan: Projected Timeline |
 |
 36
The Shots on Goal Model
8 Assets Currently
Generating Commercial
Revenue
Over 50
Partnered Programs
Over 60
Total Programs
Over 25
Different Partners
Over 10
Therapeutic Areas
Minimizing Risk Through Portfolio Size and Diversification
10 Potential New
Approvals in
the Next 4 Years
-
- |
 37
The Value Pyramid For Ligand Assets
The Top of the Value Pyramid for Ligand is Promacta
Avinza
Carfilzomib
Aprela Nexterone
CXCR2 Viviant
Over 50 Additional Programs
from Preclinical to PIII
•
There are numerous programs in
the Ligand portfolio today which
add significant value to the
business
•
But, Ligand’s royalty interest in the
Promacta franchise at GSK is the
most valuable single asset Ligand
owns |
 38
Promacta Background
•
What is Promacta
Promacta is a once-daily oral medicine that activates the thrombopoietin
(TPO) receptor
Activation of the TPO receptor causes platelets to increase, relieving
conditions of low platelets known as thrombocytopenia
•
History
Ligand and GSK jointly discovered Promacta as part of a thrombopoietin
(TPO) receptor agonist research collaboration started in 1995
GSK later licensed from Ligand the follow-on TPO receptor agonist LGD-4665
in 2008 |
 39
Approved for ITP
Marketed by GSK
PIII HepC Data Release in 3Q/4Q11
Promacta Follow-On : GSK-5921
5-10%, blended 9% on $1B in Sales
An Approved Drug in All Major Markets
Promacta
®
: The Foundation of the Ligand Growth Story
Aspects Of The Promacta Franchise Make It An Ideal
Foundation For Ligand’s Financial Growth Story
Significant Royalty Interest
Major Upcoming Catalyst Events
Long Patent Protection
Major Potential for Label Expansion
Marketed by a Premier Pharma Company
Life-Cycle Management Opportunity
ITP
HepC
Oncology
Others
Patented until July 2025 |
 40
Promacta Program Recent Developments (1 of 2)
•
New ITP Launches Around the World
EU, Japan, South America
•
Increased ITP Sales
World-wide ITP sales in 1Q2011 increased 109% over 1Q2010
The Promacta ITP Franchise Has Continued To
Generate Positive News In The Past Year |
 41
Promacta Program Recent Developments (2 of 2)
•
Full ITP Approval Granted by FDA
GSK completed post-approval commitment of generating long-term safety
data
Label now includes efficacy and safety data from RAISE, 6-month ITP
study Since 2008, GSK has been working with FDA. Studies submitted:
•
6-month efficacy and safety data
•
2-year safety data in chronic ITP
•
Updates from chronic liver disease (ELEVATE) trial
The Promacta ITP Franchise Has Continued To
Generate Positive News In The Past Year |
 42
Idiopathic Thrombocytopenia Purpura (ITP)
Phase I
Phase II
Phase III
Approved
Hepatitis C-Related Thrombocytopenia
Oncology-Related
Thrombocytopenia
Clinical Studies
2 P-III Studies
GSK Is Investing Significantly In The
Growth Of The Promacta Franchise
11 PI and PII Studies
Approved
(Label Expansion
Studies Ongoing)
GSK Investment in Promacta Franchise Expansion |
 43
Patients
needed
to potentially
reach
$1B
in sales
Thrombocytopenia Is Comprised Of Multiple Sub-Markets of
Thrombocytopenia-Inducing Diseases, Similar to Anemia and Neutropenia
Wall Street Research on GSK published Nov. 21, 2005
Thrombocytopenia: A Multibillion Dollar Platelet Potential
|
 44
Significant Revenue Growth Potential for Ligand
Territory Expansion
Indication Expansion
•
HepC
•
Oncology
•
Others
+
+
Long IP Protection
2025
Expansion of the Promacta Franchise
Translates Into Significant Revenue Growth for Ligand
Promacta Royalty
Illustrative Ligand Revenue
Annual Sales
Royalty
<$100M
4.70%
$100M-$200M
6.60%
$200M-$400M
7.5%
$400M-$1.5B
9.40%
>1.5B
9.30%
Annual
Sales
Blended
Royalty
Ligand
Revenue
$500M
7.1%
$36M
$1B
8.3%
$83M
$1.5B
8.6%
$130M |
 45
45
The Role for Eltrombopag (Promacta) in the
Treatment of HepC-Related Thrombocytopenia
N. Afdhal M.D
Beth Israel Deaconess Liver Center
Harvard Medical School |
 46
46
Agenda
Eltrombopag and thrombocytopenia
Current status of HCV therapy
The ENABLE 1 and ENABLE 2 P-III Studies
ELEVATE Study –
conclusions on Eltrombopag safety |
 47
47
The Unmet Medical Need for Thrombocytopenia
Thrombocytopenia is a major factor in patients being unable to
achieve a desired clinical outcome in dozens of diseases
Currently estimated to be nearly two million patients annually in the
US who need to be treated for thrombocytopenia
Current non-drug techniques used to increase platelets (i.e. platelet
transfusion, splenectomy) are costly, risky, and inconvenient.
The need for a more convenient and effective method for combating
thrombocytopenia is clear |
 48
48
Liver Disease–Associated
Thrombocytopenia Platelet counts may be as low as
20,000–40,000/
L
Prevalence of thrombocytopenia
increases with severity of liver disease
Degree of thrombocytopenia correlated
with severity of liver disease
Thrombocytopenia predictive of
reduced 5-year survival
Thrombocytopenia may develop or
worsen with interferon-based therapy
4% in recent DAA trials
Degree of Liver
Damage
Thrombocytopenia
Prevalence
Normal liver
2.3%
Fatty liver
5.1%
Chronic hepatitis
20.3%
Advanced liver
disease
31.8% |
 49
49
Eltrombopag
Thrombopoietin receptor agonist
Oral, once-daily tablet
Induces megakaryocyte
proliferation and differentiation
Increases platelet counts in
patients with HCV¹
1. McHutchison J, et al.N Engl J Med.
2007;357:2227–2236. |
 50
50
Current Status of HCV therapy
and the Role for Eltrombopag |
 51
Thrombocytopenia, HepC, and Eltrombopag
Nearly 10% of HepC
patients in the US suffer from treatment-limiting
thrombocytopenia
These patients have significantly worse outcomes due to their
underlying liver disease and inability to complete antiviral therapies
Eltrombopag
PII data demonstrates that this drug may be useful for
these patients to overcome thrombocytopenia limitations and
complete antiviral therapy
Key
question
arising
around
the
eltrombopag
HepC
opportunity
How will new HepC
therapies impact the need for eltrombopag?
Is
there
a
long-term
safety
concern
for
eltrombopag
because of
the ELEVATE study results? |
 52
HCV Pipeline* by MOA and Stage of Development
3/2/2010 –
selected
compounds only.
*Publicly available information via press release, corporate
presentations, and assumptions based on patent filings.
|
 53
Target “Regimen”
Outcomes
Today’s Regimen
2015+
Target
IFN + Ribavirin
(R)
G1-Naive
•
SVR = 40%
•
Duration = 48 weeks
G2-3 Naïve
•
SVR = 75%
•
Duration = 24 weeks
G1-Experienced
•
No meaningful option
•
Frequent dosing and
poor tolerability
New Triple / Quad
Combo Regimens
•
Highest possible SVR
•
No / low resistance
•
Better tolerability
•
Shorter durations
•
Simplified delivery
1.
IFN + R + DAA
2.
IFN + DAA + DAA
3.
IFN + R + DAA + DAA
4.
DAA + DAA (+ DAA)
IFN = Interferon
R = Ribavirin
DAA = Novel Direct Acting Antiviral agents
Regimen 4. High risk / low probability / far away / no PoC
|
 54
SVR Rates in Telaprevir-Treated Patients Compared with
Peginterferon/Ribavirin
Alone
Jacobson IM et al. Hepatology.
2010;52(Suppl 1):Abstract 211.
Telaprevier
12 weeks +
Peg/Riba
48 weeks
Telaprevier
8 weeks +
Peg/Riba
48 weeks
Peg/Riba
48 weeks |
 55
The Impact of New HepC
Therapies on the Use
of Eltrombopag
in HepC
Underlying thrombocytopenia is still an issue for many HepC
patients
The new protease inhibitors do not change that fact
•
New protease inhibitor therapies slightly increase the rate of
thrombocytopenia
Due to increased SVR seen with new cocktails, the need for
eltrombopag
should actually increase
•
Higher SVR rates may encourage doctors to treat more
aggressively those patients with thrombocytopenia |
 56
56
Eltrombopag
Clinical Studies
HepC
Studies |
 57
Eltrombopag
PII HepC
Study Design
4 wk
12 wk
PEG-IFN + ribavirin
+ eltrombopag
Pre-antiviral
Eltrombopag
4 wk
4 wk
4 wk
12 wk +
Eltrombopag
12 wk +
Eltrombopag
12 wk +
Eltrombopag
INITIATE
antiviral Rx if platelets
>70–100 K/µL
30 mg
50 mg
75 mg
PART
1 PART
2 4 wk
4 wk
4 wk
4 wk
Follow-up |
 PLACEBO
30 mg
50 mg
75 mg
0.0007
0.0003
< 0.0001
0%
74%
75%
95%
0%
20%
40%
60%
80%
100%
McHutchison, NEJM 2007
58
Phase II: Primary Efficacy Endpoint
Platelet count
100,000/uL at Week 4 |
 59
59
PLACEBO
30 mg
50 mg
75 mg
6%
53%
36%
65%
0%
20%
40%
60%
80%
100%
Phase II:
Subjects Completing 12 Weeks of PEG-IFN Therapy
|
 Phase
II: Median Platelet Count > 200K without thrombotic events
0
50
100
150
200
250
0
14
28
42
56
70
84
98
112
Placebo
30 mg
50 mg
75 mg
INITIATION
MAINTENANCE
Study Day
McHutchison, AASLD 2006
60 |
 61
Treatment Group, n (%)
PBO
N=18
30mg
N=14
50mg
N=19
75mg
N=23
Any AE
10 (56)
11 (79)
10 (53)
13 (57)
Headache
3 (17)
5 (36)
3 (16)
4 (17)
Dry mouth
1 (6)
2 (14)
2 (11)
2 (9)
Pruritus
0
0
0
2 (9)
Nausea
0
1 (7)
2 (11)
1 (4)
Fatigue
0
0
2 (11)
1 (4)
Upper abdominal pain
0
2 (14)
2 (11)
0
Insomnia
0
0
2 (11)
0
Arthralgia
0
2 (14)
1 (5)
0
No thromboembolic
or elevated LFT events of concern
Phase
II:
Adverse
Events
–
Pre-Antiviral
Phase |
 62
62
Phase II: Conclusions
Eltrombopag increased platelet counts in subjects in all dose groups
A significant number of subjects achieved the primary endpoint (Week 4)
in all dose groups compared to placebo
Eltrombopag enabled 45/56 subjects to initiate IFN therapy
–
31 subjects completed 12 weeks of IFN therapy
Preliminary PK findings in general indicate exposure increases with dose
with wide variability
No safety signals of concern in this initial short term study
Safety and efficacy data supports further investigation of eltrombopag in
this patient population |
 Two parallel global Phase III studies
ENABLE 1 and 2
63
peginterferon
alfa-2a
(PEGASYS)
plus
ribavirin
–
ENABLE 1
peginterferon
alfa-2b
(PEG-Intron)
plus
ribavirin
–
ENABLE 2
ltrombopag
to
INitiate
and
Maintain
Interferon
ntiviral
Treatment
to Benefit Subjects with Hepatitis C related Liver DiseasE
E
A |
 Pre-Antiviral Phase
Open-label eltrombopag
(2 –
9 weeks)
Antiviral Phase
Randomized
(up to 48 weeks)
platelets
>90,000/uL (E1)
or
100,000/uL (E2)
25mg>50mg>75mg>100mg
•
2:1 randomization eltrombopag:placebo
•
Dose titration of eltrombopag allowed throughout
•
Primary endpoint = proportion of patients achieving SVR (6M off –Tx)
•
N=750 dosed/675 randomized study
•
3 regions, 26 countries, >250 centres
SVR
SVR
6 months
off-Tx
Randomized Withdrawal Design
open label
eltrombopag
Eltrombopag
+ PEG-IFN/Rib
Placebo
+ PEG-IFN/Rib
64 |
 65
65
Screening
45
Days
Platelets
<75K/µL
Pre-Antiviral Treatment Phase
Open-label eltrombopag dosed for
up to 9wks until platelet count
increases to enable initiation of
antiviral therapy.
Part 1 (2-9 Wks)
Open-Label
Platelets
90K/µL*
Platelets
90K/µL*
Platelets
90K/µL*
*Platelets
<90K/µL
*Platelets
<90K/µL
*Platelets
<90K/µL
WD
START
*Platelets
<90K/µL
Platelets
90K/µL*
*90K/µL (ENABLE 1)
100K/µL (ENABLE 2)
2:1 Randomisation (Eltrombopag:Placebo)
Eltrombopag
plus
Antiviral Therapy
Antiviral Treatment Phase
Randomised either to
maintain dose of
eltrombopag from Part
1 or to matched
placebo.
Part 2 (
48 Wks)
Double-Blind
Placebo
plus
Antiviral Therapy
or
a
24 Week FU
Ocular/SVR
a
Post-last dose of
investigational
product.
ENABLE 1 and 2 Study Design
25mg
2 Weeks
50mg
1-2 Weeks
75mg
1-2 Weeks
100mg
1-3 Weeks |
 66
SVR rate defined as percentage of subjects with non-detectable
HCV-RNA at 24 weeks post-completion of the planned treatment
period
Platelet count
90-100,000/
L in Part 1
Dose modifications
Safety and tolerability
Platelet counts
PK
RVR,
EVR and ETR
Health-related quality of life
Safety
modified
to
include
risk
of
thrombotic
events
–
both
studies
completed without DSMB concerns
Endpoints |
 Eltrombopag Safety Summary
ELEVATE Study and Safety
67 |
 68
Eltrombopag in Chronic Liver Disease Patients
with Thrombocytopenia Undergoing an Elective
Invasive Procedure: Results from ELEVATE,
a Randomised Clinical Trial
N.
Afdhal,
E.
Giannini,²
G.N.
Tayyab,
A.
Mohsin,
4
J-W.
Lee,
5
A. Andriulli,
6
L. Jeffers,
7
J. McHutchison,
8
F. Campbell,
9
N. Blackman,
10
D. Hyde,
9
A. Brainsky,
11
D. Theodore
12
1. Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center,
Boston, MA, USA; 2. Gastroenterology Unit, Department of Internal
Medicine, University of Genoa, Genoa, Italy; 3. Department of Medicine,
Gastroenterology and Hepatology, Post Graduate Medical Institute, and Lahore
General Hospital, Lahore, Pakistan; 4. Department of Gastroenterology, Services
Hospital Lahore, Services Institute of Medical Sciences, Lahore,
Pakistan; 5. Department of Internal Medicine, Inha University Hospital
and School of Medicine, Incheon, Korea; 6. Department of Internal
Medicine, Division of Gastroenterology, Casa Sollievo Sofferenza
Hospital, San Giovanni Rotondo, Italy; 7. Center for Liver Diseases,
University of Miami, Miller School of Medicine, Miami, FL, USA; 8.
Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA; 9. Clinical Development,
GlaxoSmithKline, Stockley Park, Uxbridge, UK; 10. Biometrics and Epidemiology,
GlaxoSmithKline, Collegeville, PA, USA; 11. Clinical Development,
GlaxoSmithKline, Collegeville, PA, USA; 12. Clinical Development,
GlaxoSmithKline, Research Triangle Park, NC, USA 1
3 |
 Difference 53% (95%
CI: 43, 62) p
< 0.0001
0
10
20
30
40
50
60
80
100
Placebo
(N = 147)
Eltrombopag
(N = 145)
70
90
72%
19%
n = 28
n = 104
Primary Endpoint: Avoiding Platelet
Transfusions with Elective Invasive Procedure
69 |
 Placebo
(N = 145)
Eltrombopag
(N = 143)
n (%)
n (%)
Bleeding
25 (17)
19 (13)
Thrombotic event
2 (1)
6 (4)
Ocular (focus on cataracts / visual
acuity decrease)
6 (4)
6 (4)
Malignancies*
1 (<1)
1 (<1)
Selected Adverse Events
70
* Basal cell carcinoma (Grade 2) reported for one patient receiving placebo and B cell lymphoma (Grade
4) reported for one patient receiving eltrombopag; neither was considered to be related to
treatment by the investigator. |
 71
71
Thrombotic event
Temporal
relationship to last
dose
Temporal
relationship to
procedure
Platelet count at
event (Gi/L)
Procedure
PV / SMV thrombosis
+1
–6 days
417
Brain tumour
resection
PV thrombosis
+5
+4 days
288
Oesophageal
variceal
ligation
SMV thrombosis
+8
+7 days
235
Dental extraction
SMV / mesenteric
thrombosis
+9
+7 days
289
HCC ablation
SPV thrombosis
+14
+13 days
241
TACE
PV thrombosis
+38
+34 days
33
Oesophageal
variceal
ligation
Acute MI
+20
+19 days
83
Colon resection
Non-occlusive PV and
mesenteric thrombosis
+128
+128 days
Unknown
Oesophagoduo-
denoscopy
PV, portal vein; SMV, superior mesenteric vein; SPV, spleno-portal vein; MI,
myocardial infarction Eltrombopag
Placebo
Summary of Thrombotic Events |
 72
72
Platelet count
>200,000/µL
YES
NO
47 patients
(16%)
241 patients
(84%)
YES = 5 (10.6%)
NO = 42 (89.4%)
YES = 3 (1.2%)
NO = 238 (98.8%)
TEs
Thrombotic Events and Platelet Count |
 73
73
ELEVATE Conclusions
Eltrombopag 75 mg for 14 days
–
Reduced the need for platelet transfusions in CLD patients
with thrombocytopenia undergoing elective invasive
procedures
–
Increased platelets during treatment period and up to 2
weeks following treatment
–
Similar incidence of adverse events and serious adverse
events
–
More thrombotic events in the eltrombopag group
Relationship demonstrated for elevation of platelets
Procedure with endovascular inflammation essential feature
|
 74
74
ENABLE studies are expected to confirm role of eltrombopag in HCV
therapy in 2011
Eltrombopag
is
expected
to
be
more
widely
used
in
HCV
–
increased
SVR –
increased treatment
Long term safety of eltrombopag continues to be better understood
and continued expansion of the eltrombopag franchise is warranted
Eltrombopag Summary |
 75
Financial Highlights
John Sharp
Vice President, Finance
and Chief Financial Officer
Ligand
Pharmaceuticals
Incorporated |
 76
2011 Revenue Outlook
•
Total 2011 revenue currently projected to
be $22 -
$24 million
–
$11
-
$12
million
from
Captisol
sales
–
$8 million from royalties
–
$3 -
$4 million from license and other
•
Potential for additional sources of
revenue and cash in 2011 above these
projections based on new license
agreements
2011 Revenue Breakdown*
License And Other
Royalties
Material Sales
*Excludes revenue from new deals, if any
~15%
~35%
~50% |
 77
Financial Guidance
2011 Guidance:
•
Revenue of $22 -
$24 million
•
Operating expenses projected to be ~$20 million
•
Projecting turning profitable on an operating basis and
having positive cash flow from operations by the 4
th
quarter of 2011
•
Cash at year-end projected to be ~$20 million |
 78
Low Cost Structure
$0.0
$10.0
$20.0
$30.0
$40.0
$50.0
$60.0
$70.0
$80.0
2007
2008
2009
2010
2011*
G&A
R&D
* High end of expense guidance range
•
Ligand
has significantly reduced expenses over the last several years
•
During the same period, the company closed 5 acquisitions while
significantly expanding its asset base
Pharmacopeia Acquisition
Neurogen
Acquisition
Metabasis
Acquisition
CyDex
Acquisition
IL9 Account Acquisition |
 79
Multiple Future Revenue Sources
•
8 programs currently generating royalty revenues
•
Over 50 partnered programs
•
Numerous internal programs
•
Growing Captisol
business |
 80
Expected Revenue Growth
*Excludes revenue from new deals, if any
$0.0
$5.0
$10.0
$15.0
$20.0
$25.0
$30.0
$35.0
$40.0
$45.0
2011
Guidance*
2013 Illustrative
License & Other
Material Sales
Royalty
•
Revenue could potentially double within two years on similar cost structure
•
Recurring and high-growth royalty revenue projected to drive the majority of revenue in
2013 * |
 81
High Quality Revenue
Future revenue drivers:
–
Increased royalties from multiple commercial products
(Promacta,Conbriza, Carfilzomib, Nexterone, etc…)
–
Steadily
increasing
Captisol
sales
–
Less
dependence
on
“one-time”
license/milestone
events
•
Continued potential for additional sources of revenue and cash
from new license agreements |
 82
Value of Net Operating Loss Carryforwards
(NOL)
•
Ligand
has
accumulated
substantial
NOL’s
through
our
operating
history and acquisitions
•
NOL’s
should provide significant relief on taxable income if the
company turns profitable
•
NOL’s
as of December 31, 2010 = $438 million
•
Due
to
tax
code,
NOL’s
are
limited
in
the
quantity
and
the
timing
in
which
they
can
be
used,
so
we
do
not
expect
to
get
a
full
offset
on
taxable income immediately
•
Estimated
net
present
value
of
NOL’s
=
~$100M
•
In near-term, the NOL tax should reduce federal tax rate from 34%
down to 2% (AMT)
•
Additionally, Ligand
has ~$16 million of federal R&D Tax Credits |
 Ligand Pharmaceuticals Incorporated
83
83
83
83
“Shots on Goal”
Portfolio
2011 Ligand Analyst Day Workshop |
 The
“Shots on Goal” Model at Ligand
•
The low ROI for biopharma R&D suggests that sharing the cost and
risk of R&D through partnering is a preferred route to meaningful ROI
•
Ligand has assembled the largest portfolio of partnered assets of any
company in its biopharma peer group
–
Now over 50 assets fully funded by partners
•
A focus on assembling partnered assets allows Ligand to run a very
lean cost structure without significantly high R&D costs
•
Coupled with our cost structure,
this portfolio of assets gives
Ligand a reasonable probability of
becoming a sustainably profitable
biopharma business
84 |
 85
Industry Unique Partnered Asset Portfolio
•
Over 25 different partners
•
Over 10 different
therapeutic areas
•
Over half of the portfolio is
PII or later
•
Ligand estimates that
partners spend over
$150M per year on this
portfolio
•
Significant quarterly news
flow |
 86
Portfolio Asset Highlights
•
PIII/NDA
•
Captisol-enabled
proteasome
inhibitor for multiple
myeloma
•
Ligand eligible to
receive milestones,
royalties and
material sales
revenue
•
Potential 2012
launch
•
Beyond Promacta, there are multiple-late stage programs in the portfolio
that offer Ligand opportunities for substantial future revenue growth
Onyx
Carfilzomib
Merck
CXCR2
Pfizer
Aprela
Merck
Captisol Program
•
PII
•
Novel CXCR2
antagonist for
COPD
•
Ligand eligible to
receive milestones
and royalties
•
Potential 2015
launch
•
PIII
•
Combination of
Viviant and
Premarin for
menopausal
symptoms
•
Ligand eligible to
receive milestones
and royalties
•
Potential 2013
launch
•
PII
•
Captisol-enabled
undisclosed
program
•
Ligand eligible to
receive milestones
and material sales
revenue
•
Potential 2013
launch
Over 40 Other Programs from Preclinical to Phase III Represent
Another Potential Revenue Wave |
 87
Quality Portfolio News Flow
•
New Territory Launches
•
New Product Launches
•
NDA Approvals
•
NDA Filings
3Q11
4Q11
1Q12
2Q12
3Q12
4Q12
The
Size
of
the
Portfolio
Generates
Regular,
Meaningful,
Quarterly
News
Flow
•
PIII Data Releases
•
PIII Trial Initiations
•
PII Data Releases
Promacta
Nexterone
Viviant
Aprela
Carfilzomib
CXCR2
IL-9
CDK
Merck Captisol
Clopidogrel
Others |
 88
Deep Partner Relationships
•
PII CXCR2 (COPD)
•
PII CDK Inhibitor
(oncology)
•
PI BACE (Alzheimers)
•
Captisol Program
•
Promacta ITP
•
Promacta HepC
•
Promacta Oncology
•
LGD 4665/GSK 3521
•
Viviant
•
Aprela
•
Marketed Captisol
Products
Ligand has Multiple Broad and Diverse Relationships
With Premier Pharma Companies |
 89
Ligand Business Development
LIGAND
REVENUE DRIVERS
LIGAND
PROPRIETARY PIPELINE
LIGAND
BUSINESS
DEVELOPMENT
Ligand business development is the core engine that drives the shots on goal model
-Acquisitions –
Licensing –
Spin Offs -
Alliance Management- |
