Ligand Pharmaceuticals Incorporated · NASDAQ:LGND
Ligand Pharmaceuticals — Investor Day (November 2013)
180 slides from Ligand Pharmaceuticals's investor day presentation, Nov 14, 2013
Slide 1: 2014 and Beyond Analyst Day
2014 and Beyond Analyst Day Chicago - November 14, 2013 NASDAQ: LGND
Slide 2: Forward-looking statements
2 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
Slide 3: Agenda
3 Agenda 1) Business Overview • Events Transforming Ligand • 2014 Growth and Beyond John Higgins President & CEO 2) “Shots-on-Goal” Portfolio Select Program Updates Nishan de Silva, M.D., VP, Corporate Development 3) Research & Technology Platform Highlights of Key Assets Matt Foehr Chief Operating
Slide 4: Ligand . . . 2014 and Beyond
4 Ligand . . . 2014 and Beyond • 2013 was a break-out year for Ligand turning sustainably profitable and realizing major portfolio events • Today, Ligand is transforming into a high-growth financial company with economic rights to some of the world’s most important medicines • Our “Shots-on-Goal” bu
Slide 5: Excellent Productivity from Main Pillars of the Business
5 Excellent Productivity Recently from 3 Main Pillars of the Business • Outlook: Continued strong performance among all three projected for 2014 Largest Assets Financial Performance Portfolio Promacta 38% Kyprolis 261 % Captisol sales New data, regulatory and commercial events Extraordinary P&L effi
Slide 6: What's Happened Over Past Months
6 What’s Happened Over Past 12 Months Approvals for Major New Markets and Drugs New Licenses Adding >$100 m of Potential Fees and Royalties Late Stage Clinical Advances Acquisition that Substantially Increased Assets Financials Promacta-HCV Duavee Spectrum CURx Ethicor Azure Others BACE CE-Melphalan
Slide 7: Ligand By the Numbers
Ligand _ By the Numbers
Slide 8: Fully funded Shots-on-Goal
90 Over 8 Fully funded Shots-on-Goal
Slide 9: New partnered products expected to launch in 2014
4 9 New partnered products expected to launch in 2014
Slide 10: Partnered products by 2020
20 Partnered products by 2020 10
Slide 11: $700 Million in potential milestone payments
$700 Million 11 In potential milestone payments from existing deals Over
Slide 12: $800 Million projected partner R&D investment
$800 Million 12 Projected R&D investment by our partners on our programs in the next year Over
Slide 13: Clinical trials run by partners in 2014
80 Over 13 Clinical trials run by our partners in 2014
Slide 14: 77% increase in Captisol sample requests
77% 14 Increase in requests for Captisol samples since we acquired the technology
Slide 15: $800 Million in gross tax assets
$800 Million 15 In gross tax assets Over
Slide 16: 85% net income CAGR projected
85% 16 Net income compounded annual growth rate projected for next three years Over
Slide 17: Ligand . . . By the Numbers
17 • Over 90 fully funded Shots-on-Goal • 4 partnered new drugs expected to launch in 2014 • 20 partnered products by 2020 • Over $700 million in potential milestone payments from existing deals • Over $800 million projected R&D investment by our partners on our programs in the next year • Over 80 c
Slide 18: Why is Ligand a Compelling Company?
18 Pharmaceutical Royalties Economic rights to some of the industry's most exciting programs Why is Ligand a Compelling Company?
Slide 19: Why is Ligand a Compelling Company?
19 Why is Ligand a Compelling Company? Driving • Novel and pioneering research for significant programs • Cutting-edge formulation technology that is making major drugs possible • Investor-oriented business model with a uniquely qualified team for executing the plan Beyond an extraordinary portfolio
Slide 20: Shots-on-Goal Business Model
“Shots-on-Goal” Business Model
Slide 21: Shots-on-Goal Business Model
21 • Ligand’s business model is premised on these basic principals: — The more programs in development the more likely you will have success — A company does not need to retain full program rights to generate significant revenue and cash flow “Shots-on-Goal” Business Model
Slide 22: Shots-on-Goal Business Model
22 • Ligand has two primary business objectives: — Drive R&D to earliest inflection point for partnering — Acquire assets efficiently to further build portfolio • The Goal: Above average returns, below average risk — Economic rights to major pharma programs — High-margin, high-growth, recurring reve
Slide 23: Ligand's Business Model is Thriving
23 0 20 40 60 80 100 2007 2013 9 90 + In six years… 10x increase in fully-funded programs 6x increase in royalty bearing products What does this tell us? 1. We are executing well to expand our portfolio 2. Our partners are doing their job getting new products to the market Partnered Programs Ligand’
Slide 24: Ligand's Business Model is Thriving
• We estimate our partners will spend over $800 million next year in R&D to advance our programs — 14 Phase 3 trials — 23 Phase 2 trials — 42 Phase 1 trials — 2 Phase 4 trials — 19 preclinical programs — Manufacturing scale-up — Regulatory filing fees Ligand’s Business Model is Thriving Fully-funded
Slide 25: Strong Execution Continues to Define Ligand
25 Research Technology Deal Making Strong Execution Continues to Define Ligand Driving Largest Portfolio of Royalty Assets Ever for Ligand
Slide 26: Timeline of Ligand's Recent Acquisitions
26 • Intense period of deal-making since late 2008 • Consistent strategy and business focus over past 5 years • Investors now beginning to realize the quality and value of what we've assembled Timeline of Ligand’s Recent Acquisitions December `08 – Pharmacopeia December `09 – Neurogen January `10 –
Slide 27: Ligand . . . 2014 and Beyond
27 Ligand is uniquely positioned to generate significant cash flow per share – High-quality revenue – High gross margins – Low operating costs – Significant tax assets – Low share count Ligand . . . 2014 and Beyond
Slide 28: Revenue Outlook for Two Blockbusters
28 $ billi o n s $ billi o n s High Low Average Sales figures converted from GBP to USD Conversion rate = 1.60 9 GSK covering analysts reports as of 10/23/13 19 AMGN covering analysts reports as of 10/22/13 Revenue Outlook for Two Blockbusters Sell-Side Analyst Projections
Slide 29: Projected Total Revenues Underlying Ligand's Royalties
29 Projected Total Revenues Underlying Ligand’s Royalties $ Bi lli o n s $0.0 $0.5 $1.0 $1.5 $2.0 $2.5 2013 2014 2015 2016 Total revenue for all of Ligand’s royalty generating assets projected to exceed $2.2 billion in 2016 By end of the decade underlying revenue for Ligand royalty-based products co
Slide 30: Illustrative 2018 Ligand Revenue Potential
30 Royalties > $165 million Deal Fees, Material Sales >$35 million • Fablyn • Dela IV • Nexterone • Carb IV • Conbriza • RE - 021 • CE - Topi • More than quadrupling of revenue in 5 years • No increase in operating expense required to produce this growth • Does not assume any royalty contributions f
Slide 31: Three-Year Financial Outlook
31 • High annual revenue growth projected for next three years — 2014: $62 - $64 million — 2015: > $81 million — 2016: > $106 million • Low annual cash expenses of approximately $20 million per year • Significant earnings per share growth projected next three years — 2014: $1.40 - $1.45 — 2015: > $2
Slide 32: What Does Ligand Plan To Do with Its Excess Cash?
32 1) Acquire assets to continue building “Shots-on-Goal” portfolio 2) Return capital to shareholders: — Dividends — Share repurchases What Does Ligand Plan To Do with Its Excess Cash?
Slide 33: Portfolio Overview
33 Portfolio Overview Nishan de Silva
Slide 34: Ligand's Business Model: Shots-on-Goal
• Large and diverse portfolio of opportunities maximizes odds of business success • Ligand has a robust portfolio of partnered programs • Portfolio has grown by more than 20 programs net in the last year through acquisitions and licensing deals Ligand’s Business Model: “Shots-on-Goal” 34
Slide 35: Over 90 Shots-on-Goal
12% 8% 20% 41% 20% 35 Preclinical Marketed + NDA Phase 3 / Pivotal Phase II Phase I Key programs include: • Promacta (GSK) • Kyprolis (Amgen) • Duavee (Pfizer) • CE-Melphalan (Spectrum) • Noxafil IV (Merck) • Carbamazepine IV (Lundbeck) • BACE (Merck) • RE-021 (Retrophin) 90+ Partnered Programs Liga
Slide 36: Portfolio By Partner Type
Biotech, 37% Big Pharma, 40% Spec Pharma, 10% Generic, 13% 36 55 Different Partners Select Big Pharma Select Biotech Strong Diversity Among Pharma Industry Companies Select Spec Pharma Select Generic Ligand’s Portfolio: By Partner Type
Slide 37: Portfolio By Indication
Oncology 43% CNS 8% Inflammation 13% Blood Disorder 8% Metabolic Disease 7% Anti-microbial 5% Anti-viral 4% Cardiology 4%Opthamology 3% Other 4% 37 Valuable distribution among almost all major disease categories Ligand’s Portfolio: By Indication
Slide 38: Significant Growth Potential from New Products
38 • Realistically, not all 90 programs will make it to market considering standard pharma success rates • But, given current program status, here is how new products could enter the market through 2020 Year 2014 2015 2016 2017 2018 2019 2020 Potential New Commercial Products 4 3 2 1 14 17 29 Cumula
Slide 39: 20 Products by 2020
39 • Drug development success rates have been tracked and published through the years • In 2010 Nature Reviews Drug Discovery published average rates of success by stage of development as follows: ― 91% probability of success for compounds with a submitted NDA ― 64% probability of success for Phase
Slide 40: Ripening of the Late-stage Portfolio
Ripening of the Late-stage Portfolio Strong partners - investing and creating forward momentum Partner Asset Therapy Area 2014 2015 2016 DUAVEE™ Women’s Health √ Noxafil IV Anti-microbial √ Undisclosed Undisclosed √ Carbamazepine IV Neurology √ CE-Melphalan Oncology √ Delafloxacin IV Anti-infective
Slide 41: Selexis Acquisition Highlights
• April 2013 acquired royalty rights to over 15 biotech programs • Selexis technology increases yields for biologic manufacturing • Royalty assets an excellent fit with Ligand’s business model • Expands Ligand’s royalty portfolio beyond small molecules into biologics • $4.5 million acquisition price
Slide 42: Selexis Portfolio Acquisition
45% 55% 42 Novel Biologics with: • Merrimack • Baxter • Aveo • CSL • Glenmark • Others Biosimilars with: • Coherus • Biocad • Others Selexis deal includes royalties on novel and biosimilar biologics Selexis Portfolio Acquisition
Slide 43: Selexis Portfolio: Novel Biologics
• Partners pursuing monoclonal antibodies for large market opportunities in oncology and inflammatory diseases: ― Inflammatory disease targets include lupus and rheumatoid arthritis ― Cancer targets include lung, ovarian, breast, gastric and colorectal tumors • All biologics are first-in-class, nove
Slide 44: Selexis: Biosimilar Biologics
• Biosimilars market projected to potentially exceed $20 billion worldwide in 2020 • Biosimilars for blockbuster novel biologics in the acquired Selexis portfolio include: ― Rituxan ― Enbrel ― Remicaid • Hot area - multiple recent deals with hundreds of millions of dollars in milestones and royaltie
Slide 45: Spectrum: Captisol-Enabled Melphalan
• Captisol formulation of chemotherapy drug used predominantly for stem cell transplant conditioning in Multiple Myeloma patients • Partnership signed with Spectrum Pharmaceuticals March 2013 ― Over $50 million in potential milestones ― Significant double-digit royalty on potential net sales • Pivot
Slide 46: Retrophin RE-021
• Dual-acting Endothelin Receptor Antagonist (ERA) and Angiotensin Receptor Blocker (ARB) being developed for Focal Segmental Glomerulosclerosis (FSGS) • Significant previous clinical development in hypertension • Retrophin is pursuing novel development and regulatory pathway ― Targeting FSGS, rare
Slide 47: CURx: Captisol-Enabled Topiramate
• Captisol formulation of anti-epileptic drug otherwise available only orally — Captisol allows IV formulation for first time — Targeted at seizures in hospitalized epilepsy patients who are unable to take oral topiramate • Ligand obtained Orphan Drug Designation and published Phase I results while
Slide 48: Carbamazepine IV
48 • Captisol-enabled formulation of widely used oral antiepileptic drug • Lundbeck completed Phase 3 trial and secured Orphan Designation in 2013 • 2.7 million adults in US have epilepsy, making it the third most common neurological disorder after Alzheimer's and stroke1 • Phase 3 data presentation
Slide 49: NOXAFIL IV
49 • Captisol-enabled IV formulation of global anti-fungal, leveraging existing NOXAFIL® franchise • Merck presented positive Phase 3 study of patients at risk of invasive fungal infection at ICAAC in September • Noxafil, marketed globally by Merck, currently only available as an oral suspension • L
Slide 50: Pradefovir and MB07133
50 • Two drug candidates developed from HepDirect platform — Pradefovir for Hepatitis B- IND approved — MB07133 for liver cancer- IND submitted • Chiva developing both for Chinese market • Large market opportunities — ~100M patients in China with Hepatitis B — >40% of all cases of liver cancer are i
Slide 51: Driving Future Growth: Technology and R&D
Driving Future Growth: Technology and R&D Matt Foehr
Slide 52: Three Ways to Drive New Deals
52 • Ligand’s technologies, research, and acquired unpartnered assets position us to do more deals and create future growth opportunities Three Ways to Drive New Deals Technology • Captisol® • HepDirect™ Research • Oral GCSF • IRAK-4 • SARMs Acquired Assets • Glucagon Receptor Antagonist • Captisol-
Slide 53: Ligand's R&D Model
53 • Partnering-driven, backed by strong science ― Drive R&D to earliest inflection point for partnering • Focus on de-risking, through internal or external milestones, with a goal of partnering ― Leverage ripening science and landscape evolution ― External milestones - allowing others’ investments
Slide 54: Translating R&D Investment into Future Profits
54 Translating R&D Investment into Future Profits Carefully designed R&D investment to drive partnering Ligand’s Added Value Regulatory Path Initiate Pivotal Trial Orphan Designation Melphalan Topiramate Intellectual Property Licensing Package RE-021 Program
Slide 55: Translating R&D Investment into Future Profits
55 Translating R&D Investment into Future Profits Carefully designed R&D investment to drive partnering Ligand’s Added Value Regulatory Path Initiate Pivotal Trial Orphan Designation Melphalan Topiramate Intellectual Property Licensing Package RE-021 Program Partner Up-Front Milestones Royalties $3
Slide 56: Translating R&D Investment into Future Profits
56 Translating R&D Investment into Future Profits Carefully designed R&D investment to drive partnering Ligand’s Added Value Regulatory Path Initiate Pivotal Trial Orphan Designation Melphalan Topiramate Intellectual Property Licensing Package RE-021 Program Partner Up-Front Milestones Royalties $3
Slide 57: Captisol Platform for Continued Growth
57 • Addresses continued and growing industry need → formulation solubility and stability ― Makes major drugs possible: Kyprolis™ ― Makes existing drugs better: Nexterone®, CE-Melphalan, Noxafil® IV • The right technology at the right time ― Combinatorial chemistry/screening advances have greatly in
Slide 58: Captisol: Creating Partnerships
58 New Sample Requests 0 100 200 300 • Almost doubling of new sample requests since Ligand acquisition • “Partnership process flow” follows the progression and timing of a new drug through early development Acquired Technology Creating Partnerships with
Slide 59: Captisol-to-API Proportional Quantity
59 Illustrative Proportional Quantity: Captisol-to-API in a finished drug dose 60 mg 3,000 mg Captisol API
Slide 60: HepDirect Partnering Platform
60 • Patented prodrug technology designed to deliver drugs directly to the liver ― Proven efficient and selective in prodrug conversion ― Reduces extra-hepatic exposure through intracellular metabolism and biliary excretion HepDirect™ Partnering Platform - Targeted Drug Delivery • An ideal delivery
Slide 61: Highlights of Key Assets
Highlights of Key Assets
Slide 62: Promacta
62 • Oral medicine that boosts platelets to treat thrombocytopenia • Marketed by GSK • Long patent protection through 2027 • Potential for major label expansion — Over 25 active clinical trials — Recent/upcoming data presented in: MDS, AML, CLL and Aplastic Anemia • Royalty rates of 4.7% to 9.4% 6.6
Slide 63: Promacta: Pillars of Growth
• Thrombocytopenia (low platelet) market represents a major global commercial opportunity • Similar to anemia and neutropenia, thrombocytopenia is made up of a number of “sub-markets” of thrombocytopenia-inducing diseases in which medical need is real, life threatening and unmet • Three different ar
Slide 64: Promacta: ITP
64 • Steroids, platelet transfusion, splenectomy all create significant treatment challenges • Pediatrics account for half of new diagnoses per year • Initially launched for ITP indication in 2009, now marketed in 94 countries • Continued market share growth quarterly 6.6% 9.4% Promacta: ITP • Idiop
Slide 65: Promacta: Thrombocytopenia in HCV
65 Worldwide HCV prevalence Worldwide HCV with low platelets Patients required for ~$2B annual sales 150+ million • Thrombocytopenia exhibited in sickest sub-set of HCV patients • 100,000 patients represents ~2% of worldwide patients with low platelets • While significant evolution of HCV treatment
Slide 66: Platelets and the Evolving Hepatitis C Space
66 • Recent Advisory Committee Panel recommends a drug approved for: — Genotype 2 and 3 in combination with Ribavirin — Genotype 1 and 4 in combination with Ribavirin and interferon • Revolutionary new drugs are poised to profoundly alter Hepatitis C treatment • For mild, moderate and even severe pa
Slide 67: Platelets and the Evolving Hepatitis C Space
67 • Despite dramatic landscape shifts, there is a necessary role for platelet generation in the sickest Hepatitis C patients — End-stage Hepatitis C patients are cirrhotic → liver so diseased it produces low platelets and supportive care necessary to reduce bleeding risks — While US poised for appr
Slide 68: Promacta: Regional Quarterly Revenue
$ m ill ion s Sales figures converted from GBP to USD Note: “EMAP” = Emerging Markets Asia Pacific 68 2011 ROW 17% EMAP 80% EU 64% US 25% TOTAL 38% Promacta: Regional Quarterly Revenue $0.0 $10.0 $20.0 $30.0 $40.0 $50.0 $60.0 $70.0 $80.0 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 ROW EMAP EU US 2012 2013 Expe
Slide 69: Promacta: Label Expansion
Promacta: Label Expansion • GSK investing significantly to expand indications for Promacta, over 25 active clinical trials ITP (94 Markets) Hepatitis C (37 Markets) Potential Future Indications Aplastic Anemia MDS AML CIT Others • Data at recent and upcoming medical meetings raises visibility and po
Slide 70: Promacta: Oncology Related Thrombocytopenia
Oncology Related Thrombocytopenia Chemotherapy -induced (CIT) Cancers of the Blood Myelodysplastic Syndrome (MDS) Acute Myeloid Leukemia (AML) Bone Marrow Suppression Broad set of significant global unmet medical needs Chronic Lymphocytic Leukemia (CLL) Cancer Treatment Attacking Platelets 70 Promac
Slide 71: MDS, AML and CLL
Myelodysplastic Syndromes (MDS) Acute Myeloid Leukemia (AML) Chronic Lymphocytic Leukemia (CLL) Cancers of the Blood Patients have severe cytopenia, need frequent transfusions Fast-progressing cancer of the blood Slow-progressing cancer Excess bleeding results in major complications or death for nea
Slide 72: Promacta: Development in Aplastic Anemia
• Disease where bone marrow does not produce enough new cells • Patients have pan-cytopenia, or low red cells, low white cells and low platelets • ~7,000 new cases of AA diagnosed each year1 72 Promacta: Development in Aplastic Anemia 1American Cancer Society, 2013 and Marrow Forums, 2013 • Suggesti
Slide 73: Promacta Projections: GSK Sell-Side Analysts
$0 $200 $400 $600 $800 $1,000 $1,200 2015 2016 2017 2018 2019 2020 73 Promacta Projections: GSK Sell-Side Analysts Annual Revenue Projections $ mi lli on s High Low Average Sales figures converted from GBP to USD Conversion rate : £1 = $1.60 9 GSK covering analysts reporting as of 10/23/13
Slide 74: Kyprolis
74 • Amgen acquired Onyx October 1, 2013 — Amgen - true pioneer in treatment of serious illness with a global presence in over 50 countries • Established agent in 3rd Line+ multiple myeloma • Major investment by Amgen, focused on expanding label and geographies — Front-Line: Phase 3 (CLARION) — Rela
Slide 75: Kyprolis: Upcoming Events
75 • Amgen projects primary analysis of FOCUS trial in relapsed/ refractory MM to occur in 1H 2014 • Independent Data Monitoring committee review of interim analysis of ASPIRE in relapsed MM projected in 1H 2014 • Upcoming data and presentations at ASH 9.4% Kyprolis: Upcoming Events 1Amgen Q3 2013 p
Slide 76: Accelerating Royalty Revenue
Accelerating Royalty Revenue Year-over-Year performance of Ligand’s royalty-bearing assets Product Therapy Areas Total # of Markets Q3 2012 Sales Q3 2013 Sales % Increase ITP Hepatitis C 95 37 $55 m $76 m 38% Multiple Myeloma 1 $18 m $65 m 261% Emergency Medicine 1 Pain 1 $37 m $40 m 8% Women’s Heal
Slide 77: MK-8931: BACE1 Inhibitor
MK-8931: BACE1 Inhibitor • Merck is developing MK-8931, an oral beta-secretase (BACE1) inhibitor, for potential treatment of Alzheimer's disease (AD) • MK-8931 is first BACE1 inhibitor demonstrated to lower β- amyloid in the cerebral spinal fluid of people with AD • Merck has the leading position in
Slide 78: BACE1 and the Amyloid Hypothesis
BACE1 and the Amyloid Hypothesis • The presence of β-amyloid plaques in the brain is a well-known manifestation of Alzheimer's disease (AD) • The amyloid hypothesis asserts that formation of amyloid β peptides that lead to β-amyloid plaques in the brain is a primary contributor to the underlying cau
Slide 79: MK-8931 Clinical Trials
MK-8931 Clinical Trials • Merck’s EPOCH trial began in late 2012 – Phase 2/3, 78-week, randomized, placebo-controlled, parallel-group, double- blind trial in patients with mild to moderate AD – 200 patient Phase 2 safety portion of the study; anticipated to enroll up to 1,700 patients in the main Ph
Slide 80: DUAVEE
DUAVEE™
Slide 81: DUAVEE
81 • Combo of Bazedoxifene (SERM) and Premarin®, partnered globally with Pfizer • Received FDA approval in October for treatment of moderate-to-severe vasomotor symptoms (“hot flashes”) associated with menopause and the prevention of postmenopausal osteoporosis • US launch planned Q1 2014, European
Slide 82: Hormone replacement therapy market
82 • Hormone replacement therapy for menopausal symptoms was once a 4 billion dollar category — 22 million prescriptions written for Prempro® in the US in 2001, with revenue greater than $2 billion — Safety concerns raised by Women’s Health Initiative (WHI) led to sharp declines in use and decreased
Slide 83: Pfizer Preparing for DUAVEE Launch
83 Pfizer Preparing for DUAVEE™ Launch
Slide 84: Dr. Cynthia A. Stuenkel
Dr. Cynthia A. Stuenkel
Slide 85: Introducing Dr. Cynthia Stuenkel
• Clinical Professor of Medicine, UCSD • Established one of the first Menopause Clinics in 1988 • Expert in: — Management of post-menopausal symptoms — Hormone therapy — Osteoporosis — Breast cancer prevention • Past-President of the North American Menopause Society • National spokesperson for Endoc
Slide 86: Managing Menopause Symptoms: Yesterday, Today, and Tomorrow
Managing Menopause Symptoms: Yesterday, Today, and Tomorrow Cynthia A. Stuenkel, MD University of California, San Diego Ligand Pharmaceuticals, Inc. Analyst Day November 14, 2013
Slide 87: A Contemporary Approach to Menopause
A Contemporary Approach to Menopause The menopause experience Brief history of hormone therapy Expanding role of available therapies
Slide 88: 1542-1587
1542-1587
Slide 89: The Contemporary Woman...
The Contemporary Woman...
Slide 90: The Contemporary Woman
The Contemporary Woman… 51 year old CFO, executive coach, who sits on multiple Fortune 100 boards, presents with the chief complaint: “I don‟t know what‟s happening to me!”
Slide 91: The Contemporary Woman
The Contemporary Woman… 51 year old CFO, executive coach, who sits on multiple Fortune 100 boards, presents with the chief complaint: “I don‟t know what‟s happening to me!” She awakens at night feeling incredibly hot, then sweaty, followed by a chill. Her last period was 6 months ago. She admits to
Slide 92: The Contemporary Woman
The Contemporary Woman… 51 year old CFO, executive coach, who sits on multiple Fortune 100 boards, presents with the chief complaint: “I don‟t know what‟s happening to me!” She awakens at night feeling incredibly hot, then sweaty, followed by a chill. Her last period was 6 months ago. She admits to
Slide 93: The Menopausal Transition
The Menopausal Transition 20s 30s 40s 50s 60s 70s 80s+ Reproductive Menopause transition Postmenopause
Slide 94: The Menopausal Transition
The Menopausal Transition 20s 30s 40s 50s 60s 70s 80s+ Reproductive Menopause transition Postmenopause Menopause
Slide 95: The Menopausal Transition
The Menopausal Transition 20s 30s 40s 50s 60s 70s 80s+ Reproductive Menopause transition Postmenopause The final menstrual period— diagnosed retrospectively after 12 months amenorrhea Menopause
Slide 96: Consequences of Menopause: The Good News
Consequences of Menopause The Good News Liberates women from: Inconvenience and discomfort of monthly menstrual cycles Associated mood swings Concerns with contraception and potential for unintended pregnancy
Slide 97: Consequences of Menopause: The Bad News
Consequences of Menopause The Bad News Decline in estrogen associated with: Vasomotor symptoms Depressive and anxiety symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 98: The Menopausal Landscape Today
The Menopausal Landscape Today In 2000, there were an estimated 45.6 million postmenopausal women in the US www.menopause.org; www.hormone.org
Slide 99: The Menopausal Landscape Today
The Menopausal Landscape Today In 2000, there were an estimated 45.6 million postmenopausal women in the US By 2020, the number is expected to be > 50 million www.menopause.org; www.hormone.org
Slide 100: The Menopausal Landscape Today
The Menopausal Landscape Today In 2000, there were an estimated 45.6 million postmenopausal women in the US By 2020, the number is expected to be > 50 million In a 2012 survey by the Endocrine Society 70% of women not treated for menopause symptoms 62% had never discussed symptoms with pro
Slide 101: Approach to Symptom Relief in the Postmenopausal Woman
Approach to Symptom Relief in the Postmenopausal Woman Her subjective experience How bothered is she? Her desires regarding therapeutic options What does she want? Her medical history, age, time since menopause Will therapy be safe?
Slide 102: The Hormone Health Network
The Hormone Health Network www.hormone.org
Slide 103: www.menopause.org
www.menopause.org
Slide 104: Benefits of Estrogen Therapy
Benefits of Estrogen Therapy Estrogen therapy improves: Vasomotor symptoms Depressive symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 105: Benefits of Estrogen Therapy
Benefits of Estrogen Therapy Estrogen therapy improves: Vasomotor symptoms Depressive symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 106: Benefits of Estrogen Therapy
Benefits of Estrogen Therapy Estrogen therapy improves: Vasomotor symptoms Depressive symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 107: Benefits of Estrogen Therapy
Benefits of Estrogen Therapy Estrogen therapy improves: Vasomotor symptoms Depressive symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 108: Benefits of Estrogen Therapy
Benefits of Estrogen Therapy Estrogen therapy improves: Vasomotor symptoms Depressive symptoms, sleep disorders, memory complaints Urogenital atrophy Osteoporosis
Slide 109: A Brief History...
A Brief History...
Slide 110: The Beginning: Premarin introduced in 1942
The Beginning… Premarin introduced in 1942 • Distributed by Wyeth Ayerst • Conjugated equine estrogens (CEE) • Prepared from urine collected from pregnant mares
Slide 111: The 60's: Feminine Forever
The 60’s “Feminine Forever” Robert A. Wilson, MD 1966
Slide 112: Feminine Forever, Robert Wilson, MD, 1966
Feminine Forever Robert Wilson, MD, 1966 “At age 50, there are no ova, no follicles, no theca, no estrogen---truly a galloping catastrophe.”
Slide 113: Feminine Forever, Robert Wilson, MD, 1966
Feminine Forever Robert Wilson, MD, 1966 But with estrogen… “Breasts and genital organs will not shrivel. Such women will be more pleasant to live with and will not become dull and unattractive.”
Slide 114: Feminine Forever, Robert Wilson, MD, 1966
Feminine Forever Robert Wilson, MD, 1966 But with estrogen… “Breasts and genital organs will not shrivel. Such women will be more pleasant to live with and will not become dull and unattractive.”
Slide 115: The 70's: Unopposed estrogen and endometrial cancer
The 70’s Unopposed estrogen therapy increases the risk of endometrial (uterine) cancer New England Journal of Medicine, 1976
Slide 116: The 70's: Progestogen therapy
The 70’s Progestogen therapy, when combined with estrogen, reduces uterine risk Medroxyprogesterone acetate (MPA) Provera
Slide 117: The 90's
“Despite the absence of clinical trial data, by the mid-1990s it was almost dogma that hormone therapy would prevent coronary heart disease in postmenopausal women.” The 90’s
Slide 118: The 90's
“Documentation that all postmenopausal patients had been offered estrogen was one of the criteria used to evaluate the quality of medical practice. Not to recommend estrogen therapy was thought to be unethical.” The 90’s Elizabeth Barrett-Connor, MD J Clin Endocrinol Metab, 2003
Slide 119: The 90's
Premarin, conjugated equine estrogen (CEE), was the most widely dispensed prescription drug in the U.S. The 90’s
Slide 120: 1992-2002...
1992-2002...
Slide 121: Women's Health Initiative Clinical Trial Design
Women’s Health Initiative (WHI) Ages 50-79 Hormone Therapy Clinical Trial Design Women with a uterus Women who had no uterus Conjugated equine estrogen (CEE) 0.625 mg/d Placebo CEE 0.625 mg/d + medroxyprogesterone acetate (MPA) 2.5 mg/d Placebo N= 16,608 N= 10,739
Slide 122: Long-Term Administration of HT
Long-Term Administration of HT Benefits Risks Fractures Colorectal CHD Cancer Stroke Breast Cancer Venous thrombo- embolism Global Index > 1
Slide 123: Trends in Menopausal Hormone Therapy Use, 2000-2009
Trends in Menopausal Hormone Therapy Use, 2000-2009 • Tsai SA, et al. Menopause 2011; 18:385
Slide 124: Trends in Menopausal Hormone Therapy Use, 2000-2009
Trends in Menopausal Hormone Therapy Use, 2000-2009 • Tsai SA, et al. Menopause 2011; 18:385
Slide 125: Trends in Menopausal Hormone Therapy Use, 2000-2009
Trends in Menopausal Hormone Therapy Use, 2000-2009 • Tsai SA, et al. Menopause 2011; 18:385 76%
Slide 126: Treatments of Menopause-Associated Vasomotor Symptoms
Nonprescription Remedies Prescription Rx Estrogen Mind-Body and Behavior Lifestyle Modification Treatments of Menopause- Associated Vasomotor Symptoms Stuenkel CA. in Women & Health, Elsevier, 2013.
Slide 127: Lessons learned...
WOMEN’S HEALTH NEALE Lessons learned...
Slide 128: Lesson 1: No primary prevention indication
1. Neither estrogen nor combined therapy is indicated for primary prevention of chronic conditions. AHA 2011; NAMS 2012, ACOG 2013; USPSTF 2013
Slide 129: Lesson 2: Risks return to baseline after discontinuation
2. When hormone therapy is discontinued, the rates of most risks (and benefits) return to baseline. Manson JE, et al. JAMA 2013; 310:1353
Slide 130: Lesson 3: Age and years since menopause
3. A woman’s age and years since menopause at the time of initiation of hormone therapy affect clinical cardiovascular outcomes. Rossouw JE, et al. JAMA 2007;297:1465.
Slide 131: A Decade after the WHI: The Experts Do Agree
A Decade after the WHI— The Experts Do Agree Goal: acknowledge benefits and risks of hormone therapy for relief of menopausal symptoms Stuenkel CA., et al. Menopause. 2012 Aug;19(8):846-847; J Clin Endocrinol Metab 2012; Aug;97(8):2617-8; Fertil Steril. 2012 Aug;98(2):313-4.
Slide 132: The Experts Do Agree: Endorsements
A Decade after the WHI— The Experts Do Agree: Endorsements • Academy of Women’s Health • American Academy of Family Physicians • American Academy of Physician Assistants • American Association of Clinical Endocrinologists • American Medical Women’s Association • Asociacion Mexicana para el Estudio d
Slide 133: Lesson 4: Unopposed vs combined estrogen effects
4. The effects of unopposed estrogen differ from combined estrogen and progestogen therapy. Manson JE, et al. JAMA 2013; 310:1353
Slide 134: Divergence of Benefit-Risk Profile in the WHI
Divergence of Benefit-Risk Profile in the WHI Women Age 50 to 59 Years CE Placebo CE/MPA CHD Endpoints Breast Cancer *CHD endpoints: myocardial infarction and CHD death LaCroix AZ, et al. JAMA 2011; Rossouw JE et al. JAMA, 2007; Heiss G et al, JAMA, 2008; by CA Stuenkel, 2013. MORE BENEFIT MORE HARM
Slide 135: Concerns with Progestogen Therapy
Concerns with Progestogen Therapy Tolerability issues -Vaginal bleeding -Breast tenderness -Mood effects -Breast density Diverging safety profile of E versus E+P Alternative progestogen regimens are unproven regarding safety and efficacy Another method is needed to protect the uterus
Slide 136: The SERM Landscape...
The SERM Landscape...
Slide 137: SERM Nomenclature
SERM Nomenclature Selective Estrogen Receptor Modulator Abbreviated as „SERM‟ FDA preferred terminology Estrogen Agonist/ Antagonist with Tissue-Selective Effects
Slide 138: Model of Estrogen Receptor Pharmacology
Model of Estrogen Receptor Pharmacology Nelson ER Wardell SE, McDonnell DP Bone 2013; 53:42-50.
Slide 139: Clinical Indications for SERM Rx
Menopause Management Clinical Indications for SERM Rx Prevention and Treatment Breast cancer Osteoporosis Symptom Relief Dyspareunia Vasomotor symptoms
Slide 140: Clinical Indications for SERM Rx
Menopause Management Clinical Indications for SERM Rx Prevention and Treatment Breast cancer Osteoporosis Symptom Relief Dyspareunia Vasomotor symptoms
Slide 141: Clinical Indications for SERM Rx
Menopause Management Clinical Indications for SERM Rx Prevention and Treatment Breast cancer Osteoporosis Symptom Relief Dyspareunia Vasomotor symptoms
Slide 142: Ospemifene: Treatment of Dyspareunia
Ospemifene: Treatment of Dyspareunia FDA approval February 26, 2013 Oral 60 mg tablet taken once daily with food Indication: • Treatment of moderate to severe dyspareunia • A symptom of vulvar and vaginal atrophy due to menopause www.fda.gov/NewsEvents
Slide 143: Clinical Indications for SERM Rx
Menopause Management Clinical Indications for SERM Rx Prevention and Treatment Breast cancer Osteoporosis Symptom Relief Dyspareunia Vasomotor symptoms
Slide 144: TSEC: Tissue Selective Estrogen Complex
TSEC: Tissue Selective Estrogen Complex Pairs SERM bazedoxifene 20 mg Conjugated estrogens 0.45 mg New paradigm (FDA approved October 3, 2013) Treatment of vasomotor symptoms Osteoporosis prevention Provides endometrial protection without progestogens Karode Y. Endocrinology 2008;149:6084-
Slide 145: TSEC: Tissue Selective Estrogen Complex
TSEC: Tissue Selective Estrogen Complex Bazedoxifene (20 mg) with CE (0.625 mg or 0.45 mg) Relieves vasomotor symptoms1,2 Improves vaginal symptoms1,3 Improves sleep and quality of life4 Decreases bone turnover and bone loss 5 Effects breast tenderness,1 vaginal bleeding,6 and rates of end
Slide 146: Breast Density Effects of Bazedoxifene-Conjugated Estrogens
Breast Density Effects of Bazedoxifene-Conjugated Estrogens Pinkerton JV et al. Obstet Gynecol 2013; 121:959-68.; 1 year trial
Slide 147: TSEC: Additional Safety Data
TSEC: Additional Safety Data For bazedoxifene 20 mg with CE 0.625 mg or 0.45mg: VTE rates not additive Rates for MI and CVA were not increased compared to placebo Longer follow-up and larger study populations are needed to clarify risks and potential benefits Taylor HS and Ohleth K. Menopause 201
Slide 148: Menopause Management Summary and Conclusions
Menopause Management Summary and Conclusions Although estrogen has been known for over 70 years to be the most effective agent to relieve symptoms of menopause, unique challenges remain for managing signs and symptoms of the menopause transition and maintaining postmenopausal health
Slide 149: Menopause Management Summary and Conclusions
Menopause Management Summary and Conclusions For women with a uterus, combined estrogen and progestogen therapy increases risks and decreases patient tolerability of postmenopausal hormone therapy SERM (Selective Estrogen Receptor Modulator) or TSEC (Tissue Selective Estrogen Complex) therapy ha
Slide 150: Menopause Management Summary and Conclusions
Menopause Management Summary and Conclusions The menopause transition, when viewed as a portal to the second half of life, becomes a critical window to reassess lifestyle, recognize ongoing and potential health concerns, and take a proactive approach to future wellbeing
Slide 151: Managing Menopause Symptoms: Yesterday, Today, and Tomorrow
Managing Menopause Symptoms: Yesterday, Today, and Tomorrow Cynthia A. Stuenkel, MD University of California, San Diego Ligand Pharmaceuticals, Inc. Analyst Day November 14, 2013
Slide 152: Keith Marschke, Ph.D.
Keith Marschke, Ph.D.
Slide 153: Introducing Keith Marschke, Ph.D.
Introducing Keith Marschke, Ph.D. • Vice President of Biology • Joined Ligand in 1994 • Held leadership roles in some of Ligand’s most successful discovery programs — TPO, EPO, GCSF — SARM and SERMs • Ph.D. in Molecular and Cellular Pathobiology from the Bowman Gray School of Medicine- Wake Forest U
Slide 154: Glucagon Receptor Antagonist Program
Glucagon Receptor Antagonist Program
Slide 155: Diabetes: A Growing Global Epidemic
Diabetes: A Growing Global Epidemic 155 • Currently affects over 350 million people worldwide — 26 million in U.S. (11% of adult population) — 2 million Americans diagnosed every year • By 2050, 1 in 3 adults in U.S. will have diabetes if trend continues 2013 Non-Diabetics Diabetics Source: American
Slide 156: Major Global Market for Diabetes Drugs
Major Global Market for Diabetes Drugs $33 B $60+ B Sources: Brinson Patrick report 12/3/12; SunTrust report 6/25/13 • One of the largest drug categories • Global market projected to double to over $60 billion by 2020 • Combination therapy highly prevalent and necessary to optimize management of the
Slide 157: Glucagon: A Long History
• Glucagon - essential regulator of glucose and recognized as a pharmacological target for over 30 years — Glucagon increases glucose levels, opposing insulin — Glucagon antagonism reduces plasma glucose in diabetics • Significant ripening of science during last 3 years 1923 1953 1982 Insulin discov
Slide 158: GCGR Antagonists Role in Type 2 Diabetes
• Expected effective across broad population of patients — Lean/Obese: Elevated hepatic glucose production determinant of hyperglycemia in early and late disease — Advanced patients: Glucagon-to-insulin ratio increases • Efficacious in both fed and fasted states • Expect to be prescribed in combinat
Slide 159: Significant Opportunity for GCGR Antagonists
Class Estimated Peak Sales Potential Potential Drugs in 2020 DPP-IV Inhibitors $12 Billion 5 GLP-1 Agonists $7 Billion 5 SGLT-2 Inhibitors $2 Billion 4 GCGR Antagonists ++++ 2 Source: Thompson Reuters, Annual Reports • Branded treatments have multi-billion dollar sales potential • By 2020, existing
Slide 160: Advantages of Potent GCGR Antagonist
Existing Class Product Profile GCGR Advantage DPP-IV Inhibitors Modest reduction of plasma glucose Higher glucose reduction GLP-1 Agonists Only available as injectables Oral SGLT-2 Inhibitors Contraindicated for renally impaired patients Spares kidney • Product profile and recent clinical data sugge
Slide 161: Global Diabetes Dance Card
Class Company Lilly AZ BMS Merck BI Takeda Novartis Sanofi GSK Novo J&J DPP-IV Inhibitors √ √ √ √ √ √ √ GLP-1 Agonists √ √ √ √ √ √ SGLT-2 Inhibitors √ √ √ √ √ √ GCGR Antagonist √ Commercial or late-stage clinical assets Single region molecules not shown • Major diabetes players can fill a hole in th
Slide 162: Ligand's Glucagon Program: LGD-6972
Ligand’s Glucagon Program: LGD-6972 • Novel, highly potent, oral small molecule GCGR antagonist for treatment of type 2 diabetes • Clinical candidate with excellent properties — Highly potent and selective in vitro; superior potency to other compounds — Potent and efficacious in in vivo models of ty
Slide 163: Chronic Glucose Reduction in Diabetes Model
Treatment Lean Vehicle LGD-6972 Sitagliptin D P P IV A ct iv ity ( R F U /s e c) 0 5e+5 1e+6 2e+6 2e+6 * * Chronic Glucose Reduction in Diabetes Model • db/db mice: a model of advanced type 2 diabetes • Daily oral doses of LGD-6972 for 28-days American Diabetes Association (ADA) 72nd Scientific Sess
Slide 164: Glucose Reduction in Type 1 Diabetes Model
Glucose Reduction in Type 1 Diabetes Model • Mice injected with streptozotocin • LGD-6972 dosed orally after hyperglycemia established • Significant glucose reduction observed through 28 days 164 -S TZ + V eh ic le +S TZ + V eh ic le +S TZ + L G D -6 97 2 0 100 200 300 400 500 0.05 0.001 0.01 F a s
Slide 165: Phase I Clinical Trial Design
165 • Primary objective: Evaluate the safety and tolerability of single oral doses of LGD-6972 in healthy subjects and subjects with type 2 diabetes — Double-blind, placebo-controlled, randomized ascending dose study • Enrollment planned for 56 participants — Six groups of healthy subjects and one g
Slide 166: Financial Overview and Outlook
Financial Overview and Outlook John Sharp
Slide 167: Low Operating Costs
$0 $10 $20 $30 $40 $50 $60 $70 $80 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Low Operating Costs $ m il lio n s Combined R&D and G&A Cash Expense Do not need to increase costs to grow revenue from existing portfolio Focused spending discipline, elimination of costs not driving value 167
Slide 168: 2013 Cost Structure
45% 45% 10% Company Operations Facilities, insurance, taxes and administrative expenses 2013 Cost Structure • Annual cash costs of <$20 million • Efficient cost structure that supports activities to further expand the “Shots-on-Goal” portfolio Pipeline Costs Research & development, business developm
Slide 169: Projected Revenue Composition
Projected Revenue Composition 50% 53% 69% 78% $0 $20 $40 $60 $80 $100 2013 2014 2015 2016 License and other Material Sales Royalties > $106 $45-$46 $62-$64 > $81 By 2016, royalties projected to make up >75% of total revenues $ m il lio n s 169
Slide 170: 2014 – 2016 Revenue Buildup
2014 – 2016 Revenue Buildup • Royalty revenue: — Derived from sell-side research analysis and analyst projections for Promacta and Kyprolis • Captisol sales: — Projected to be between $15 and $20 million per year • License/milestones: — Projected to be between $5 and $10 million per year based on po
Slide 171: Gross Margins
Gross Margins • Royalties – 100% gross margin • License and Milestone payments – 100% gross margin • Captisol Material Sales – Projected 55% gross margin for 2014 - 2016 — Cost of goods % dependent on type of sale — Clinical: ~80% gross margin — Commercial: ~50% gross margin • For 2014 - 2016, major
Slide 172: Three-Year Financial Outlook
• High annual revenue growth projected for next three years — 2014: $62 - $64 million — 2015: > $81 million — 2016: > $106 million • Low annual cash expenses of approximately $20 million per year • Significant earnings per share growth projected next three years — 2014: $1.40 - $1.45 — 2015: > $2.13
Slide 173: Tax Assets
Tax Assets • Ligand has three types of tax assets — Net operating loss carryforwards (NOLs) — Tax credits — Future tax deductions • Based on continued tax analysis, Ligand’s projected gross tax assets have increased by $59 million over the past year, from $747 million to $806 million 173
Slide 174: Summary of Tax Assets
Summary of Tax Assets • NOLs: — $511 million of federal NOLs (~$464 million unrestricted) — $185 million of state NOLs • Tax credits: — $19.5 million of federal R&D tax credits — $17.5 million of state R&D tax credits • Future deductions: — $73 million of future federal NOLs (capitalized R&D) Based
Slide 175: Projected Tax Expense
Projected Tax Expense • Ligand currently has a full “valuation allowance” against its deferred $245 million tax assets – Until “valuation allowance” is released, annual book tax expense is equal to $0.5 million plus actual taxes paid • Upon reaching consistent, multi-year profitability, Ligand will
Slide 176: Long-term Cash Planning
Long-term Cash Planning Significant High-Quality Revenue Growth + Flat Cash Expenses + > $800 Million of Tax Assets = Accumulation of potentially large cash balance to be used for opportunistic acquisitions or returned to shareholders 176
Slide 177: 2013 Financial Guidance
2013 Financial Guidance ($ in millions) Revenue Royalties 6.8$ - 7.0$ 23.2$ - 23.4$ Material sales 3.7 - 4.0 15.9 - 16.2 License and other 0.5 - 1.0 5.9 - 6.4 11.0$ - 12.0$ 45.0$ - 46.0$ Cost of goods sold 45% 40% Combined R&D and G&A 5.9$ - 6.4$ 26.5$ - 27.0$ EPS - Non-GAAP 0.15$ - 0.17$ 0.49$ - 0.
Slide 178: Upcoming Milestones
Milestone Partner LGND Est. Timing CE-Carbamazapine NDA filing Lundbeck December RE-021 FONT-3 Phase 2 initiation Retrophin December ASH Conference (Promacta, Kyprolis, Oral GCSF) GSK, Onyx, LGND December AES Conference (CE-Carbamazepine) Lundbeck December Undisclosed (Captisol program) Phase 1 init
Slide 179: Upcoming Milestones
Milestone Partner LGND Est. Timing Melphalan NDA filing Spectrum 1H ‘14 MEI-143 Phase 2 initiation MEI Pharma 1H ‘14 MEI-344 Phase 1b initiation MEI Pharma 1H ‘14 CE-Delafoxacin Phase 3 completion Melinta Q3 ‘14 DUAVEE™ EU Approval Pfizer Q3 ‘14 EHA Conference (Promacta, Kyprolis) GSK, Onyx June ‘14
Slide 180: 2014 and Beyond Analyst Day
2014 and Beyond Analyst Day Chicago - November 14, 2013 NASDAQ: LGND
Ligand Pharmaceuticals — Investor Day (November 2013) on 6ix