Ligand Pharmaceuticals Incorporated · NASDAQ:LGND
Ligand Pharmaceuticals — Investor Day (June 2010)
103 slides from Ligand Pharmaceuticals's investor day presentation, Jun 24, 2010
Slide 1: Investor and Analyst Day
Investor and Analyst Day June 24, 2010 Nasdaq: LGND Exhibit 99.1
Slide 2: Ligand Pharmaceuticals, Inc. Investor and Analyst Day
Ligand Pharmaceuticals, Inc. Investor and Analyst Day John Higgins President and Chief Executive Officer June 24, 2010 - New York
Slide 3: Safe Harbor Statement
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,
Slide 4: Investor and Analyst Day Agenda
Investor and Analyst Day Agenda Welcome and Company Overview John Higgins Financial Highlights John Sharp Ligand Partnered Asset Portfolio Rob McKay Promacta Nezam H. Afdhal, MD Expanding the Partnership Pipeline Syed Kazmi, PhD SARM Program Shalender Bhasin, MD Questions & Answers / Reception
Slide 5: Investor Day
Investor Day • Ligand’s Directors own ~9% of the company • Other top holders – Wellington – Biotech Value Fund – BlackRock – UBS – Vanguard – Pennant – Chesapeake Partners – DWS Investment GmbH – RA Capital
Slide 6: We Have Delivered
We Have Delivered • We have fully restructured and rebuilt Ligand • We have cut costs while building our asset base • We have met our financial guidance • We have advanced our pipeline • We have completed three valuable acquisitions
Slide 7: Our Business Philosophy
Our Business Philosophy • Run a business that is oriented toward being a financial growth story – Our belief is we should not build a business around “biotech promises,” instead we should build a business that generates cash flow and makes investors (shareholders) money • Buy or develop a large port
Slide 8: Ligand: A Business Model Built on Today's Reality
Perception Reality Ligand: A Business Model Built on Today’s Reality • The rewards from discovering, developing, and commercializing a biotech drug can be enormous • True, but the vast majority of programs fail to ever reach that payoff • A biotech company should retain late-stage and/or commercial
Slide 9: Why the Ligand Royalty Model is So Compelling
Why the Ligand Royalty Model is So Compelling Ligand Today “Yesterday’s” Royalty Model “Yesterday’s” FIPCO Model • Integrate most functional expertise into the company • Short remaining patent life • Own products through late-stage development or commercialization Vast portfolio of royalty partnersh
Slide 10: Why the Ligand Royalty Model is So Compelling
Why the Ligand Royalty Model is So Compelling Ligand Today “Yesterday’s” Royalty Model “Yesterday’s” FIPCO Model • Integrate most functional expertise into the company • Short remaining patent life • Own products through late-stage development or commercialization Vast portfolio of royalty partnersh
Slide 11: Why the Ligand Royalty Model is So Compelling Ligand Today
Why the Ligand Royalty Model is So Compelling Ligand Today Vast portfolio of royalty partnerships Research and partnering engine Result • Large revenue & ER potential • Substantially lower costs and risks • Over 30 programs • Long patent lives • Some high royalties that approach a profit split • Eff
Slide 12: The Investment Proposition: Risk vs. Reward
The Investment Proposition: Risk vs. Reward We believe the upside reward is substantially greater than the downside risk Ligand’s Potential Downside Individual project set-backs Slower growth Partners drop programs Ligand’s Potential Upside Blockbuster product approved/in-development Near-term profi
Slide 13: Illustrative Sum of the Parts
Illustrative Sum of the Parts • Cash $30 million • Over $500 million in NOLs with estimated ~$100 million net present value • Avinza – up to $25 million in net present value - royalty annuity through 2017 • Promacta Currently marketed and in development for five other indications 12 years remaining
Slide 14: Sum of the Parts Illustration
Sum of the Parts Illustration Avinza • Promacta • SERMs • 30 other funded programs • Fully owned pipeline Nols Cash $180 million Current Market Capitalization “Biotech” Value How much more will this grow over the next few years? ~$25 ~$100 ~$30 $155 million
Slide 15: Ligand…Why Now?
Ligand…Why Now? • Given reduced expenses and revenue outlook, we project turning profitable on an operating basis next year • Promacta is a “now” story – New trials have initiated recently – New territories are launching for ITP – HepC P-III trials are winding down with data expected in about a year
Slide 16: A View of the Future
A View of the Future • 2 marketed products : Avinza and Promacta • 2 approved products pending launch: Conbriza and Fablyn • 2 products announced to have NDA filings by end of 2012: Aprela and Acadesine • 9 drug candidates could launch between 2014 and 2018 CXCR2 BACE P-38 JNK2 CDK LXR IL-9 FXR Hepa
Slide 17: Potential Significant Revenue Expansion Over Next Several Years
Potential Significant Revenue Expansion Over Next Several Years Illustrative Growth Promacta Avinza Promacta Conbriza Avinza Aprela Conbriza Fablyn Aprela Acadesine Fablyn CDK >$20 million royalties CXCR2 Plus license fees P-38 IL- >$200 million royalties Plus license fees
Slide 18: Potential Significant Revenue Expansion Over Next Several Years
Potential Significant Revenue Expansion Over Next Several Years >$20 Mil. >$200 Mil. • 10 fold increase in royalties. Growth due to: – New product launches – New territories – New indications – Increasing royalty rates upon sales growth • Potential for nearly $100 million in milestones over the same
Slide 19: Ligand Pharmaceuticals, Inc. Financial Update
Ligand Pharmaceuticals, Inc. Financial Update Delivering Good Performance John Sharp Vice President, Finance and Chief Financial Officer
Slide 20: Highlights
Highlights • Operating Expenses • Overview of Net Operating Losses • Financial Guidance • Reverse Stock Split
Slide 21: Operating Expense Trend
Operating Expense Trend $0.0 $10.0 $20.0 $30.0 $40.0 $50.0 $60.0 $70.0 $80.0 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 3 acquisitions while significantly expanding its asset
Slide 22: Value of Net Operating Loss Carryforwards (NOL)
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, 2009 = $514 million • Due to tax code, NOL’
Slide 23: Financial Guidance
Financial Guidance 2010 Guidance: • Revenue approximately $25 million Combination of royalty, contract payments and milestones • Operating expenses approximately $30 million One-third G&A, two-thirds R&D • Cash at year end projected to be greater than $30 million 2011 Guidance: • Operating expenses
Slide 24: Reverse Split
Reverse Split • Over Ligand's history, company raised money through a series of highly dilutive financings • Company initiated restructuring about three years ago but never addressed its bloated share base • Now is an appropriate time given the progress of the company and our outlook for the busines
Slide 25: Illustrative Income Statement Assuming Reverse Split
Illustrative Income Statement Assuming Reverse Split ($ in millions) Pre-split Post-split Revenue 40.0 $ 40.0 $ Expenses 20.0 20.0 EBIT 20.0 20.0 Interest & other 1.0 1.0 Taxes (0.4) (0.4) Net income 20.6 $ 20.6 $ EPS 0.18 $ 1.31 $ Shares outstanding 117.6 15.7 * * assumes midpoint of split range;1-
Slide 26: Ligand Partnered Asset Portfolio
Ligand Pharmaceuticals, Inc. Ligand Partnered Asset Portfolio Value Through Shots on Goal Rob McKay Associate Director, Business Development
Slide 27: Ligand's Partnered Asset Portfolio
Ligand’s Partnered Asset Portfolio Ligand has a very large portfolio of partnered programs which are the core of Ligand's financial growth model
Slide 28: Ligand's Partnered Asset Portfolio
Ligand’s Partnered Asset Portfolio The Ligand partnered portfolio consists of 33 fully funded programs that have the potential to generate over $500M in milestones and royalties on future sales
Slide 29: Ligand's Partnered Asset Portfolio
Ligand’s Partnered Asset Portfolio Significant potential for new product launches and expanded indications the next several years * *
Slide 30: Ligand's Partnered Asset Portfolio
Ligand’s Partnered Asset Portfolio Over half of the partnered portfolio is in mid-late stage clinical trials
Slide 31: Ligand's Partnered Asset Portfolio
Ligand’s Partnered Asset Portfolio Significant news flow over the next 18 months • Aprela NDA Filing • Promacta-Japan ITP Approval • Promacta HepC PIII Data • SARM PI Data •BACE PII Initiation • IL-9 PII Completion • Conbriza EU Launch • Oral EPO Clinical Candidate • Glucagon Clinical Candidate • TR
Slide 32: Quality Partnerships and Portfolio Value
Quality Partnerships and Portfolio Value • Ligand's promising long-term growth is firmly based on finding partners who can deliver our assets into the hands of patients • Ligand’s ideal partners have the following qualities: – The expertise to bring each unique asset through development into the mar
Slide 33: Examples of Value Through Quality Partnerships
Examples of Value Through Quality Partnerships Assessing the value of Ligand’s partnered portfolio by examining two premier partnerships
Slide 34: The Merck-Ligand Collaboration
The Merck-Ligand Collaboration • A pipeline of innovative products in established or emerging Merck franchises • The potential for milestone and royalty revenue in the near and long-term • Regular news flow from a variety of programs Phase III CABG Phase II COPD Phase II Oncology Phase I Alzheimer’s
Slide 35: SCH 527123 (CXCR2 Antagonist)
SCH 527123 (CXCR2 Antagonist) • What does SCH 527123 do? Antagonist of chemokine receptor 2, blocking the activation of neutrophils. Reduces airway damage and mucous build up seen in diseases like COPD • What stage of development is SCH 527123 at? Phase II study for COPD. Expected to be completed in
Slide 36: Dinaciclib (CDK Inhibitor)
Dinaciclib (CDK Inhibitor) • What does Dinaciclib do? Inhibitor of cyclin dependent kinase (CDK) Inhibiting CDK should block cell-cycle progression and promote apoptosis • What stage of development is Dinaciclib at? Multiple Phase II studies for cancer. The studies will complete in late 2010 through
Slide 37: BACE Inhibitor Program
BACE Inhibitor Program • What does a BACE Inhibitor do? BACE inhibitors block the activity beta-secretase (BACE) Inhibiting beta-secretase should lower the amount of beta- amyloid protein produced in the brain, limiting the plaque formation that is thought to be a cause of Alzheimer’s disease • What
Slide 38: Merck Collaboration Summary
Merck Collaboration Summary The Merck collection of assets has the potential to produce one of the next blockbuster drugs in the Ligand asset portfolio Phase III CABG Phase II COPD Phase II Oncology Phase I Alzheimer’s Pre-clinical The opportunity is for any one (or several) of these assets to becom
Slide 39: The GSK-Ligand Collaboration
The GSK-Ligand Collaboration • Increasing royalty revenue over time from expanded indications • Regular news flow of filings and approvals • Regular news flow from a variety of programs • 2nd Generation TPO Receptor Agonist licensed to GSK as a follow-on molecule to Promacta Approved ITP Phase III H
Slide 40: Promacta Facts
Promacta Facts • What does Promacta do? Promacta is a once daily oral medicine that activates the thrombopoietin (TPO) receptor Activation of the TPO receptor causes an increase in the production of platelets • What is Promacta approved for? Promacta is approved for ITP in multiple countries • What
Slide 41: Promacta and HepC-Related Thrombocytopenia
Promacta and HepC-Related Thrombocytopenia • GSK is currently running two potentially large Phase III studies in HepC patients Study 1 (PEGASYS/Ribavirin) Study 2 (PEGINTRON/Ribavirin) • Both studies are randomized, double blind, placebo controlled in patients currently on peginterferon/ribavirin •
Slide 42: Promacta: Reasons for Excitement
Promacta: Reasons for Excitement • The platelet segment is the next frontier in the multi-billion dollar hematology market • Promacta and its backup compound will build a long-term platelet franchise for GSK/Ligand • GSK is expending large amounts of resources and money to expand Promacta markets an
Slide 43: What Promacta Means to Ligand
What Promacta Means to Ligand Independent Analyst Projected Sales for Promacta* Potential royalty revenues from Promacta are the basis for transformative growth at Ligand Year Yearly Revenue Projections for Ligand from Promacta Sales** *Projected sales figures are the average projections from 6 inde
Slide 44: Promacta and its Role in Treating HepC-Related Thrombocytopenia
Ligand Pharmaceuticals, Inc. Promacta and its Role in Treating HepC-Related Thrombocytopenia Nezam Afdhal, M.D. Gastroenterology Chief of Hepatology, Beth Israel Deaconess Medical Center
Slide 45: The Role for Eltrombopag in the Treatment of HepC-Related Thrombocytopenia
The Role for Eltrombopag in the Treatment of HepC-Related Thrombocytopenia N. Afdhal M.D Beth Israel Deaconess Liver Center Harvard Medical School
Slide 46: Agenda
Agenda Eltrombopag Background Conclusions from the ELEVATE Study Eltrombopag PII HepC Study Results The ENABLE 1 and ENABLE 2 PIII Studies
Slide 47: The Unmet Medical Need for Thrombocytopenia
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 te
Slide 48: Liver Disease – Associated Thrombocytopenia
Liver Disease – Associated Thrombocytopenia Platelet counts may be as low as 20,000–40,000/µL 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 Thrombocyt
Slide 49: Eltrombopag
Eltrombopag Thrombopoietin receptor agonist Oral, once-daily tablet Induces megakaryocyte proliferation and differentiation Increases platelet counts in patients with HCV 1. McHutchison J, et al.N Engl J Med. 2007;357:2227–2236.
Slide 50: Eltrombopag – Mechanism of Action
Eltrombopag – Mechanism of Action Cytoplasm STAT RAS/RAF MAPKK p42/44 SOS SOS GRB2 SHC Cell membrane thrombopoietin receptor inactive receptor active receptor Signal Transduction eltrombopag Increased platelet production
Slide 51: Eltrombopag Clinical Studies
Eltrombopag Clinical Studies Conclusions from the ELEVATE Study
Slide 52: Eltrombopag in Chronic Liver Disease Patients: ELEVATE
Eltrombopag in Chronic Liver Disease Patients with Thrombocytopenia Undergoing an Elective Invasive Procedure: Results from ELEVATE, a Randomised Clinical Trial N. Afdhal, E. Giannini, G.N. Tayyab, A. Mohsin, J-W. Lee, A. Andriulli, L. Jeffers, J. McHutchison, F. Campbell, N. Blackman, D. Hyde, A. B
Slide 53: Median Platelet Count from ELEVATE
Median Platelet Count from ELEVATE Placebo Eltrombopag n = n = Number with available data: Eltrombopag Placebo Screening Day Day Day Day 16–19 DFU DFU DFU DFU Median (interquartile range) Treatment Period Procedure
Slide 54: Primary Endpoint: Avoiding Platelet Transfusions with Elective Invasive Procedure
Primary Endpoint: Avoiding Platelet Transfusions with Elective Invasive Procedure Difference 53% (95% CI: 43, 62) p < 0.0001 Placebo (N = 147) Eltrombopag (N = 145) 72% 19% n = 28 n = 104
Slide 55: Selected Adverse Events
Selected Adverse Events 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) * Basal cell carcinoma (Grade 2) reported for one patient receiving placebo a
Slide 56: Summary of Thrombotic Events
Summary of Thrombotic Events Thrombotic event Temporal relationship to last dose Temporal relationship to procedure Platelet count at event (Gi/L) Procedure PV / SMV thrombosis +1 –6 days Brain tumour resection PV thrombosis +5 +4 days Oesophageal variceal ligation SMV thrombosis +8 +7 days Dental e
Slide 57: Thrombotic Events and Platelet Count
Thrombotic Events and Platelet Count Platelet count >200,000/ µ L 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
Slide 58: Conclusions
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 a
Slide 59: Eltrombopag Clinical Studies: HepC Studies
Eltrombopag Clinical Studies HepC Studies
Slide 60: Eltrombopag PII HepC Study Design
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 same here 12 wk same here INITIATE antiviral Rx if platelets >70–100 K/ µ L 30 mg 50 mg 75 mg PART 1 PART 4 wk 4 wk 4 wk 4 wk Follow-up
Slide 61: Primary Efficacy Endpoint Platelet count at Week 4
Primary Efficacy Endpoint Platelet count 100,000/uL at Week 4 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
Slide 62: Subjects Initiating PEG-IFN Therapy
Subjects Initiating PEG-IFN Therapy at Week 4 PLACEBO 30 mg 50 mg 75 mg 22% 74% 71% 91% 0% 20% 40% 60% 80% 100%
Slide 63: Subjects Completing Weeks of PEG-IFN Therapy
Subjects Completing 12 Weeks of PEG-IFN Therapy PLACEBO 30 mg 50 mg 75 mg 6% 53% 36% 65% 0% 20% 40% 60% 80% 100%
Slide 64: HCV Phase II Study Median Platelet Count
HCV Phase II Study Median Platelet Count Study Day Placebo 30 mg 50 mg 75 mg INITIATION MAINTENANCE McHutchison, AASLD 2006
Slide 65: Adverse Events – Pre-Antiviral Phase
Adverse Events – Pre-Antiviral Phase 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 2 (9) Nausea 1 (7) 2 (11) 1 (4) Fatigue 2 (11) 1 (4) Upper abdominal pain 2 (14)
Slide 66: Conclusions
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 P
Slide 67: ENABLE 1 & ENABLE 2
ENABLE 1 & 2 parallel global Phase III studies E ltrombopag to I N itiate and Maintain Interferon A ntiviral Treatment to B enefit Subjects with Hepatitis C related L iver Diseas E peginterferon alfa-2a (PEGASYS) plus ribavirin – ENABLE peginterferon alfa-2b (PEG-Intron) plus ribavirin – ENABLE
Slide 68: Randomised Withdrawal Design
Randomised Withdrawal Design open label eltrombopag Eltrombopag + PEG-IFN/Rib Pre-Antiviral Phase Open-label eltrombopag (2 – 9 weeks) Antiviral Phase Randomised (up to 48 weeks) Placebo + PEG-IFN/Rib platelets >90,000/uL (E1) or 100,000/uL (E2) 25mg>50mg>75mg>100mg • 2:1 randomisation eltrombopag:p
Slide 69: ENABLE 1 & 2 Study Design
ENABLE 1 & 2 Study Design Screening Days Platelets <75K/µL 25mg 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 2 Weeks Platelets 90K/µL* Platelets 90K/µL* Platelets 90K/µL
Slide 70: Endpoints
Endpoints 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
Slide 71: Eltrombopag Summary
Eltrombopag Summary Eltrombopag is an effective platelet stimulator in CLD Eltrombopag can reduce need for platelet transfusion in CLD patients but final dose and safety concerns must be addressed ENABLE studies will confirm role of eltrombopag in HCV therapy in
Slide 72: Ligand Business Development: Expanding the Partnership Pipeline
Ligand Pharmaceuticals, Inc. Ligand Business Development Expanding the Partnership Pipeline Syed Kazmi, Ph.D. Vice President, Business Development and Strategic Planning
Slide 73: The Business Model at Ligand
The Business Model at Ligand • Conduct only early-stage research Do what we are good at • Very successful track record of discovery and IND generation – Over 40 clinical candidates, 22 INDs, 5 drugs approved and 3 on the market Proven and productive technology platform • Strong research capabilities
Slide 74: Ligand Unpartnered Assets
Ligand Unpartnered Assets SARM TR ß Agonist Glucagon H3 EPO Androgen Receptor Modulator Thyroid Receptor-beta Agonist Glucagon Receptor Antagonist Histamine H3 Receptor Antagonist Oral EPO Receptor Agonist Muscle Wasting Dyslipidemia Diabetes Cognitive Disorders Anemia Phase Ib Pre-Clinical Pre-Clin
Slide 75: Ligand Unpartnered Assets
Ligand Unpartnered Assets SARM TR ß Agonist Glucagon H3 EPO Androgen Receptor Modulator Thyroid Receptor-beta Agonist Glucagon Receptor Antagonist Histamine H3 Receptor Antagonist Oral EPO Receptor Agonist Muscle Wasting Dyslipidemia Diabetes Cognitive Disorders Anemia Phase Ib Pre-Clinical Pre-Clin
Slide 76: The Ligand TR-beta Program
The Ligand TR-beta Program • Metabasis acquisition brings a robust IP portfolio and industry-leading experience in liver-targeted drug delivery using proprietary HepDirect Technology • Ligand brings deep experience in nuclear hormone receptor chemistry and pharmacology for discovering novel liver-ta
Slide 77: Thyroid Receptor Overview
Thyroid Receptor Overview • Target validation: TR activation in liver affects the expression of several genes, leading to reductions in LDL, triglycerides,Lp(a), and ApoB TR ß is the major isoform expressed in liver for tissue-specific effects • TR activation in extra-hepatic tissues result in dose-
Slide 78: Dyslipidemia – Unmet Medical Need
Dyslipidemia – Unmet Medical Need Low Cardio Risk Med Cardio Risk High Cardio Risk Statin Intolerant 26M US Dyslipidemic Patients Largely Meeting LDL Goals on Existing Therapies 20% 15% Approximately 9M Patients in need of Add-On Therapies Add-on treatments for patients still not reaching LDL goals
Slide 79: Thyroid Receptor Program Status
Thyroid Receptor Program Status MB07811 - First generation liver-targeted prodrug • Phase Ib study completed in 56 subjects Clinical proof of concept with dose-dependent decrease in LDL (15- 41%), Apo B, TGs, and Lp(a) Modest dose-related side effects including thyroid axis suppression in a small co
Slide 80: TR Partnering Opportunity
TR Partnering Opportunity • Robust Partnering Package Extensive clinical package with first generation drug candidate to help drive SARs generation lead candidates representing novel chemistry platforms Strong IP for a well validated target Potential for first-in-class NME in a growing area of unmet
Slide 81: SARM Overview
SARM Overview • LGD-4033, a Selective Androgen Receptor Modulator (SARM), for the treatment of muscle wasting disorders • LGD-4033 has desirable tissue-selective properties A potent, full agonist on bone with anabolic and anti- resorptive effects A potent, full agonist on skeletal muscle with anabol
Slide 82: SARM Program Status
SARM Program Status • Phase I Single Ascending Dose study completed late 2009 LGD-4033 is safe and well tolerated at single doses up to 22mg Suitable for once-daily dosing No SAEs or dose-related clinical significant adverse events reported • Phase I Multiple Ascending Dose study ongoing LGD-4033 do
Slide 83: Competitive Pipeline – Relevant to LGD-4033 Development
Competitive Pipeline – Relevant to LGD-4033 Development The pipeline snapshot below is based upon the developmental agents listed for treatment of cachexia (various disease states) and sarcopenia. Muscle Wasting Disease Development in the US Preclinical Preclinical Phase II Phase I Phase III Ostarin
Slide 84: LGD-4033 Partnering Opportunity
LGD-4033 Partnering Opportunity • Robust Partnering Package • New NME with clinical POC data for a well validated target • A large library of novel SARM back-up candidates • Blockbuster drug potential in a high unmet medical need area • Partnership Landscape Multiple commercial markets allow for bot
Slide 85: Selective Androgen Receptor Modulator LGD-4033
Ligand Pharmaceuticals, Inc. Selective Androgen Receptor Modulator LGD-4033 Shalendar Bhasin, M.D. Professor of Medicine, Boston University School of Medicine Chief, Section of Endocrinology, Diabetes, and Nutrition Director, Boston Claude D. Pepper Older Americans Independence Center for Function P
Slide 86: The Unmet Medical Need for a SARM Therapeutic
Shalender Bhasin, MD Professor of Medicine, Boston University School of Medicine Chief, Section of Endocrinology, Diabetes, and Nutrition Director, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies Boston Medical Center The Unment Medical Need for a SARM Th
Slide 87: Aged Population as a Share of Total U.S. Population
Aged Population as a Share of Total U.S. Population Continues to Grow
Slide 88: Age-Related Decline in Lean Mass and Muscle Strength
Age-Related Decline in Lean Mass and Muscle Strength (BLSA; Roy et al 2002) Age (years) Leg and Arm Lean Mass (kg) Quadriceps and Biceps Strength (N) Age (years)
Slide 89: Growth in Disability Among Older Adults
Aging baby boomers: 65+ will grow from 35 million in 2000 to over 70 million in 2030. Recent rate of disability —40% (ACS, 2004). The oldest old: the fastest growing segment Grow from 3.0 to 6.2 million in the next decade Social Security Disability Program and the Supplemental Security Program pay $
Slide 90: The Unmet Medical Need – Frailty & Sarcopenia
The Unmet Medical Need – Frailty & Sarcopenia • Age-related loss of muscle mass, strength and functionality • Estimated 10 million Americans over the age of 65 suffer from sarcopenia • Currently no FDA-approved treatment options available
Slide 91: Rationale for Function Promoting Anabolic Therapies
Rationale for Function Promoting Anabolic Therapies Androgen Therapy Alterations in Gene Expression Stem Cell Commitment Increased Muscle Mass Increased Muscle Strength and Performance Improved Physical Function Decreased Physical Dependence, Improved Health Perceptions and Health-Related Outcomes
Slide 92: Testosterone Dose Response in Young and Older Men
-2 -1 Young Men (18-34) Older Men (60-75) T Dose (mg) Change in FFM (kg) T Dose Effect P <0.0001 Age Effect P = 0.22 Change in T X age P = 0.46 Bhasin et al , JCEM Testosterone Dose Response in Young and Older Men: Testosterone Dose Response in Young and Older Men: Change in Fat Free Mass Change in
Slide 93: The Need for a SARM Therapeutic
The Need for a SARM Therapeutic 80 years of empiric, clinical, epidemiological, and clinical trials data provide 80 years of empiric, clinical, epidemiological, and clinical trials data provide unequivocal evidence that androgens increase skeletal muscle mass and unequivocal evidence that androgens
Slide 94: Clinical Trial of Ostarine: Increased Total Lean Mass
Clinical Trial of Ostarine: Increased Total Lean Mass and Decreased Total Fat Mass J Dalton. Data presented at 2007 Endo Meeting, Toronto. We Need More Potent SARMs with Greater Tissue Selectivity Total Lean Mass (all subjects) -500 Placebo 0.1 mg 0.3 mg 1 mg 3 mg Dose # p<0.001 compared to placebo,
Slide 95: LGD-4033 Overview
LGD-4033 retains the beneficial properties of natural androgens, while mitigating the toxic actions and side effects of steroidal androgens • Ligand is developing LGD-4033, a Selective Androgen Receptor Modulator (SARM), for the treatment of muscle wasting disorders • LGD-4033 has desirable tissue-s
Slide 96: Tissue selectivity of LGD-4033
Tissue selectivity of LGD-4033 for skeletal muscle vs. prostate LGD-4033 Prostate Muscle >500x Dose (mg/kg/day, po) Ostarine >390x Comparison of LGD-4033 and Ostarine in the rat model for male hypogonadism
Slide 97: LGD-4033 Increases Muscle Mass Throughout the Body
LGD-4033 Increases Muscle Mass Throughout the Body * * * Effect of LGD-4033 on the weight of skeletal muscle in female rats treated once daily with 3 mg/kg LGD-4033 for 4 weeks
Slide 98: LGD-4033: Similar Potency on Muscle and Bone
LGD-4033: Similar Potency on Muscle and Bone Indicates Potential for Treating Osteoporosis Dose (mg/kg/day, po) -4 -2 Lumbar Spine DEXA Analysis in Female Rats Skeletal Muscle Weight in Male Rats Dose (mg/kg p.o.)
Slide 99: LGD-4033 Phase I Development - Overview
Study Objective Key Observations SAD — Single dose safety and tolerability / Pharmacokinetics 0.1-22 mg Well tolerated at all doses; Dose proportional AUC; T : ~26-38 hrs No SAE’s reported MAD — Multiple dose safety and tolerability / Pharmacokinetics Study ongoing LGD-4033 Phase I Development - Ove
Slide 100: Summary of Single Ascending Dose Study
• Drug exposure was high and dose-proportional after a single oral dose suggesting that a low dose will give sufficient systemic exposure to be therapeutically effective • Elimination half-life (t 31 hours) consistent with once- a-day oral dosing • No serious adverse events occurred • A total of 5 m
Slide 101: L4033-02 Multiple Ascending Dose Study
L4033-02 Multiple Ascending Dose Study 3 mg Dose Cohort 4 (N=8) * 1 mg Dose Cohort 3 (N=20) 0.3 mg Dose Cohort 2 (N=20) 0.1 mg Dose Cohort 1 (N=8) Biomarkers: DEXA for Lean Body Mass, 1-RM for strength, FSR for muscle protein synthesis Healthy Males: 21-50 years Doses: 0.1, 0.3, 1 & 3 mg Treatment D
Slide 102: Regulatory Pathway for SARM Drugs
Regulatory Pathway for SARM Drugs • Demonstrating improvements in: – Physical function – Health outcomes, such as quality of life, reduction in falls • FDA feedback on required primary end points for Phase IIb as disclosed by GTx – Total lean body mass – Performance measure (e.g.Stair climb) – Weigh
Slide 103: LIGAND
LIGAND