Ligand Pharmaceuticals Incorporated · NASDAQ:LGND
Ligand Pharmaceuticals — Investor Day (October 2020)
131 slides from Ligand Pharmaceuticals's investor day presentation, Oct 20, 2020
Slide 1: Investor & Analyst Day: Innovation Driving Value
Exhibit 99.1 INVESTOR & ANALYST DAY INNOVATION DRIVING VALUE OCTOBER 20, 2020 Nasdaq:1 LGND Copyright © 2020 Ligand. All Rights Reserved.
Slide 2: Safe Harbor Statement
2 SAFE HARBOR STATEMENT The following presentation contains forward-looking statements by Ligand and its partners that involve risks and uncertainties and reflect Ligand's and it’s partners’ judgment as of the date of this presentation. Words such as “plans,” “believes,” “expects,” “projects,” “coul
Slide 3: Agenda
3 AGENDA Eastern Time Business Overview 11:00 a.m. – 11:20 a.m. John Higgins, CEO Technologies, OmniAb and Internal R&D 11:20 a.m. – 11:35 a.m. Matt Foehr, President and COO Vince Antle, PhD, SVP Technical Captisol Updates 11:35 a.m. – 11:40 a.m. Operations and Quality Assurance Monica Tijerina, PhD
Slide 4: Business Overview
BUSINESS OVERVIEW John Higgins CEO 4 Copyright © 2020 Ligand. All Rights Reserved.
Slide 5: About Ligand
5 ABOUT LIGAND Medical research and technology Robust platform of company discovering medicines, discovery tools and improving safety and reducing technologies needed to manufacturing costs solve industry challenges PEOPLE & TECHNOLOGY INNOVATION INNOVATION DRIVING VALUE Superior support and High gr
Slide 6: Ligand Adds Value: Just Ask Our Partners
6 LIGAND ADDS VALUE . . . . . . JUST ASK OUR 130 PARTNERS Our research and technology help partners… Discover medicines Ligand’s technology and R&D support entitles us to share Improve safety in revenue of partners through Reduce costs royalties
Slide 7: Select Partners: Valuable License Agreements and Partnerships
7 SELECT PARTNERS VALUABLE LICENSE AGREEMENTS AND PARTNERSHIPS Kyprolis JZP-458 Sparsentan Parempanel IV IMVT-1401 Teriparatide Ensifentrine Teclistamab Evomela Veklury Pevonedistat Zimberelimab PTX-022 Sugemalimab V114 Pneumosil
Slide 8: Ligand's Operations
8 LIGAND’S OPERATIONS Company headquarters Recent R&D expansion 158 employees 4 U.S. sites where major changing to Bay Area to support the OmniAb 58 with PhDs R&D platforms operate (Emeryville) in 2021 and Captisol businesses OmniAb Captisol Protein Ion Channel Expression Company footprint has evolv
Slide 9: Ligand's Core Technologies Platforms Drive Value
9 LIGAND’S CORE TECHNOLOGIES PLATFORMS DRIVE VALUE FROM DISCOVERY THROUGH MANUFACTURING Discovery Development Manufacturing Commercialization OmniAb Ion Channels Partners Manage Captisol All Elements of Commercializing Protein Expression Internal R&D Investment
Slide 10: Accelerating Growth
10 ACCELERATING GROWTH
Slide 11: Three-Year Outlook for the Year 2023
11 THREE-YEAR OUTLOOK FOR THE YEAR 2023 • Three core segments of revenue • All projected to grow meaningfully over next few years on modest cost structure • Forecast for significantly increasing operating cash flow 2020 2023
Slide 12: Strong Growth Driven by Royalty Revenue
12 STRONG GROWTH DRIVEN BY ROYALTY REVENUE
Slide 13: Financial Outlook: Royalty Revenue
13 FINANCIAL OUTLOOK: ROYALTY REVENUE LIGAND FORECASTS ROYALTY REVENUE WILL TRIPLE OVER NEXT THREE YEARS ~$33M $95M Pfenex ~1/3 from products Pfenex ~$17M New ~$12M approvals Existing $33M products ~2/3 Core Ligand Royalties 2020 2023 Does not assume any sparsentan royalties or TE rating for teripar
Slide 14: Strongest Pipeline in Company's History
14 STRONGEST PIPELINE IN COMPANY’S HISTORY
Slide 15: Partnered Pipeline
15 PARTNERED PIPELINE BROAD PORTFOLIO WITH OVER 130 DIFFERENT PARTNERS PROTEIN EXPRESSION PROPRIETARY Acquired platform October 2020 COMPOUNDS / OTHER More deals this year than any other First approvals expected in 2021
Slide 16: Most Substantial Calendar of Late-Stage Events
16 MOST SUBSTANTIAL CALENDAR OF LATE-STAGE EVENTS IN LIGAND’S HISTORY Q4 2020 2021 5 Potential Approvals for Major Programs PTX-022 Erwinia asparaginase V114 Sparsentan Pivotal data Approval Approval Phase 3 data Pevonedistat Zimberelimab Teriparatide Ensifentrine Phase 3 data NMPA approval TE appro
Slide 17: Investing in Our Future to Drive Growth
17 INVESTING IN OUR FUTURE TO DRIVE GROWTH - Internal R&D investment - Technology acquisitions - Tuck-in M&A - Transformative M&A
Slide 18: Over $2 Billion Deployed
18 OVER $2 BILLION DEPLOYED - Return of capital to shareholders - M&A
Slide 19: Growing ESG Initiatives
19 GROWING ESG INITIATIVES • At Ligand we strive to be good citizens of the communities where we do business and we take our Environmental, Social and Governance responsibilities seriously ‒ Committed to regular ESG reporting and disclosure; annual report and additional materials available on corpor
Slide 20: Ligand Independent Directors
20 LIGAND INDEPENDENT DIRECTORS John Kozarich, PhD John LaMattina, PhD Sunil Patel Sarah Boyce Chairman Former President of Public & Private Biotech Executive CEO, Avidity Biosciences Merck Research Executive Research, Pfizer, Inc. Past companies include: Abgenix, Past companies include: CEO, ActivX
Slide 21: Focus and Strategy for Next Three Years
21 FOCUS AND STRATEGY FOR NEXT THREE YEARS Innovation and Technology Mergers and Acquisitions Financial Growth • Continued investment in R&D • Use increasing cash flow to • At least 8 new products to drive our innovation acquire innovation and P&L expected to be approved • Develop new technologies c
Slide 22: Technologies, OmniAb, and Internal R&D
TECHNOLOGIES, OMNIAB, AND INTERNAL R&D Matt Foehr President and COO 22 Copyright © 2020 Ligand. All Rights Reserved.
Slide 23: Platform Technologies
PLATFORM TECHNOLOGIES 23 Copyright © 2020 Ligand. All Rights Reserved.
Slide 24: Three Primary Technology Platforms
24 THREE PRIMARY TECHNOLOGY PLATFORMS CUTTING-EDGE, ROYALTY-BEARING TECHNOLOGIES THAT MAKE MAJOR LIFE- SAVING GLOBAL DRUGS POSSIBLE Antibody Discovery Formulation Manufacturing/CMC Protein Expression Technology Delivering fully human antibodies Enabling the creation of new products Making production
Slide 25: Partnered Pipeline Snapshot
25 PARTNERED PIPELINE SNAPSHOT Partner Program Therapy Area Technology Preclinical Phase 1 Phase 2 Phase 3 Marketed Kyprolis® Oncology Captisol EVOMELA® Oncology Captisol Veklury® Infection Captisol Emergency Use Authorization by FDA in US Teriparatide Osteoporosis Expression Multiple Multiple Multi
Slide 26: OmniAb Updates
OMNIAB UPDATES 26 Copyright © 2020 Ligand. All Rights Reserved.
Slide 27: Antibodies and Industry Demand
27 ANTIBODIES AND INDUSTRY DEMAND HIGHER SUCCESS RATES FOR ANTIBODY MEDICINES DRIVE OUR INDUSTRY’S NEED FOR DISCOVERY TECHNOLOGY First Approvals of Therapeutic Antibodies in U.S. or EU 80 Industry Success Rates Historical Cancer Likelihood of Approval at success rates Non-cancer for antibody classes
Slide 28: The OmniAb Technology Suite
28 THE OMNIAB TECHNOLOGY SUITE CONTINUING OUR BEST-IN-CLASS STATUS WITH INNOVATION AND TECHNOLOGY OFFERING EXPANSION The only three- species platform High demand for bispecific antibodies Industry-first ultralong CDR-H3s Bispecific platforms Industry-leading broadest offering Antigen generation for
Slide 29: OmniAb Performance: Partner and Program Growth
29 OMNIAB PERFORMANCE Partner and Program Growth Ligand has more than tripled number of OmniAb 100 80 agreements since 2012, driving substantial Partners 60 program growth Programs 40 Novel Antibody Patents 20 filed by our Partners 0 Approaching 40 patent filings 40 by our partners claiming an 30 Om
Slide 30: OmniAb Performance: Clinical Trials and Partner Progression
30 OMNIAB PERFORMANCE CLINICAL TRIALS AND PARTNER PROGRESSION Clinical Trial Starts by Year 60 Substantial growth in clinical Phase 1 programs in 2020 Phase 2 Over 8,500 clinical Phase 3 patients have been or are 40 planned to be treated Upcoming new clinical starts from J&J with OmniAb and Merck an
Slide 31: OmniAb Performance: Clinical Successes by Our Partners
31 OMNIAB PERFORMANCE CLINICAL SUCCESSES BY OUR PARTNERS OmniAb programs have progressed faster than anticipated IMVT-1401/Batoclimab (anti-FcRn) Teclistamab (JNJ64007957) ‒ Anti-FcRn mAb discovered in OmniRat® ‒ Janssen developing teclistamab, anti-BCMAxCD3 bispecific discovered with OmniAb platfor
Slide 32: OmniAb Performance: Clinical Successes by Our Partners
32 OMNIAB PERFORMANCE CLINICAL SUCCESSES BY OUR PARTNERS Major commercial deals centered on OmniAb antibodies, first two approvals expected in 2021 Sugemalimab (anti-PD-L1) Zimberelimab (anti-PD-1) ‒ mAb targeting PD-L1 discovered in OmniRat ‒ anti-PD-1 mAb discovered using OmniRat ‒ Positive result
Slide 33: OmniAb Technology
33 OMNIAB TECHNOLOGY Best-in-Class technology for antibody discovery meeting a growing need in the industry Partners continue to have success with OmniAb- derived antibodies First OmniAb-derived commercial products now projected in 2021
Slide 34: Internal R&D Programs
INTERNAL R&D PROGRAMS 34 Copyright © 2020 Ligand. All Rights Reserved.
Slide 35: Internal R&D
35 INTERNAL R&D LIGAND SELECTIVELY INVESTS IN INTERNAL R&D TO DRIVE PARTNERING EVENTS WITH UPSIZED LICENSING TERMS • Current internal R&D investments are focused on three initiatives OmniChicken Antibody Programs PF810 Initiating potentially Five antibody programs Recently-acquired next pivotal tria
Slide 36: Planned Pivotal Trial
36 PLANNED PIVOTAL TRIAL DIFFERENTIATED LABEL-ENABLING CLINICAL STUDY • Trial to demonstrate reduction in incidence of contrast-induced acute kidney injury (CI-AKI) and equivalence of image quality following administration of CE-Iohexol compared to GE’s Omnipaque® ‒ ~540-subject clinical trial, proj
Slide 37: Recent Market Research
37 RECENT MARKET RESEARCH PRIMARY MARKET RESEARCH WITH U.S.-BASED HOSPITAL PAYERS FURTHER DEMONSTRATES THE NEED AND OPPORTUNITY FOR CE-IOHEXOL • Gained perspective from hospital payers on key issues Select Payer Feedback associated with CI-AKI including clinical approaches, the cost burden, and curr
Slide 38: OmniChicken Antibody Programs
38 OMNICHICKEN ANTIBODY PROGRAMS FIVE PROGRAMS NOW PRIMED FOR FUTURE PARTNERING EVENTS ANTIBODY PROGRAM STATUS Initial Biochem and Patent Target Discovery Cellular Assays* Filings Differentiating competitive benchmark data now generated B7-H3 ✔️ ✔️ June 2020 CD38 ✔️ ✔️ June 2020 Three programs curre
Slide 39: PF810 Recently-Acquired Program
39 PF810 RECENTLY-ACQUIRED PROGRAM • PF810 program recently acquired with Pfenex • Next-generation peptide therapeutic program focused on endocrinology ‒ Leverages extensive CMC and clinical know-how • Proof-of-concept established in two species, including non-human primates • Significant near-term
Slide 40: Captisol Updates
CAPTISOL UPDATES Vince Antle, PhD SVP Technical Operations and Quality Assurance 40 Copyright © 2020 Ligand. All Rights Reserved.
Slide 41: Captisol Technology
41 CAPTISOL TECHNOLOGY Addresses consistent and enduring industry need: formulation solubility and stability ‒ An estimated 40% of small molecule drug candidates have low solubility Clinical and regulatory success, combined with vast safety database have significantly increased awareness, visibility
Slide 42: Captisol Key Technology Features
42 CAPTISOL KEY TECHNOLOGY FEATURES Manufacturing, Global Reach Intellectual Property Drug Master Files Quality & Scale Captisol-enabled drugs are Substantial know-how Type 4 and 5 DMFs in U.S. with Manufacturing is conducted marketed in >70 countries >20,000 pages containing in cGMP plants via vali
Slide 43: Captisol New Agreements in 2020
43 CAPTISOL NEW AGREEMENTS IN 2020 • Increased visibility for the platform has New New Research Use Clinical/Commercial driven new agreements to highest levels Agreements Agreements ever for the technology 135 12 120 10 105 90 8 75 6 60 45 4 30 2 15 0 0 2018 2019 2020 2018 2019 2020
Slide 44: Captisol in 2020: Delivery Routes
44 CAPTISOL IN 2020 DELIVERY ROUTES EXPANSION OF SAFETY DATA IN DMF’S HAS DIVERSIFIED THE DELIVERY ROUTES THAT CAPTISOL PARTNERS PURSUE Delivery Route Used by • While all currently approved Captisol-enabled products are IV, a Clinical/Commercial Partners growing number of partners are using the tech
Slide 45: Captisol Operational Developments
45 CAPTISOL OPERATIONAL DEVELOPMENTS Now have cGMP manufacturing operations at four sites, including one in the U.S. Over the past 6 months, Ligand has completed work to Increased efficiency of processing, testing and batch release significantly increase efficiencies and Captisol output Currently le
Slide 46: Captisol Technology
46 CAPTISOL TECHNOLOGY Enabling new life-saving drugs Meeting significant industry needs Positioned for substantial growth
Slide 47: Monica Tijerina biography
Monica Tijerina is an Executive Director in Formulation and Process Development at Gilead Sciences where she leads a team managing clinical drug product outsource manufacturing, clinical supplies chain management, and drug product pilot plant and GMP warehouse. Prior to joining Gilead, Monica held p
Slide 48: Remdesivir for the Treatment of Covid-19 and the Role of Captisol
Remdesivir for the Treatment of Covid-19 and the Role of Captisol® Monica Tijerina, PhD Executive Director, Formulation and Process Development October 20, 2020 48
Slide 49: Remdesivir Is a Broad-spectrum Antiviral Agent
Remdesivir Is a Broad-spectrum Antiviral Agent • Warren TK, et al. Nature 2016;531:381-5. • Lo MK, et al. Sci Reports 20177:43395. • Sheahan TP, et al. Sci Transl Med 2017; 9:eaal3653. • Agostini ML, et al. Mbio 2018;9(2):e00221-18. 49
Slide 50: Captisol Increases Solubility of Remdesivir
Captisol® Increases Solubility of Remdesivir free API goes to site of action free Captisol eliminated remdesivir Simulation of complexation Captisol Pipkin, et al., Drug Development and Delivery, June 2020, Vol. 20, No. 5, p 42-47 50
Slide 51: Expansion of Veklury for Treatment of COVID-19
Expansion of Veklury for Treatment of COVID-19 May 1: October 8 : Remdesivir receives August 7: Gilead signs joint FDA emergency use July 21: Gilead Submits NDA procurement authorization (EUA) Initiate pediatric for Veklury agreement with clinical trials with European Commission July 8: August 28: M
Slide 52: Manufacturing Projections
Manufacturing Projections Cumulative Treatment Courses Powder for concentrate for 50-fold increase in production solution for infusion > 100 MT of Captisol >2,000,000 • Room-temperature storage Expect enough supply to meet 190,000 global demand by 30,000 end of October 5,000 JAN APRIL JUNE OCT DEC 2
Slide 53: COVID-19 Therapeutic Approaches
COVID-19 THERAPEUTIC APPROACHES INTRODUCTION TO DR. MATT DAVIS, PHARMD 53 Copyright © 2020 Ligand. All Rights Reserved.
Slide 54: COVID-19 Therapeutic Development Categories
54 COVID-19 THERAPEUTIC APPROACHES COVID-19 THERAPEUTIC DEVELOPMENT CAN BE BROADLY CLASSIFIED INTO 3 CATEGORIES • Immune modulators ‒ Drugs that primary alter the immune system to reduce the viral spread or reduce the cytokine storm (e.g., dexamethasone) • Antibodies ‒ Antibodies designed to block t
Slide 55: COVID-19 Treatment Landscape and Guidelines
COVID-19 Treatment Landscape and Guidelines R e m d e s i v i r Matt Davis, PharmD Infectious Disease Clinical Pharmacy Specialist UCLA Ronald Reagan Medical Center Mrdavis@mednet.ucla.edu @Mattdavis138 55
Slide 56: Transparency Declaration
Transparency Declaration • No disclosures related to Ligand or Gilead 56
Slide 57: Outline
Outline Pre-Clinical Data Clinical Data Pharmacology Randomized Trial Data Structure-Activity Relationship Guideline Recommendations In vitro Data Place in Therapy/Future Directions 57
Slide 58: Remdesivir Pharmacology
Remdesivir Pharmacology Mechanisms: 1. Interference with RNA-dependent RNA polymerase → delayed termination of RNA transcription 2. Template incorporation inhibiting complementary base addition/replication Status: COVID-19 clinical trials ongoing; multiple phase III trials completed EUA granted 5/1/
Slide 59: Remdesivir Structure Activity Relationship
Remdesivir Structure Activity Relationship Monophosphoramidate 1’Cyano C- adenosine Nucleoside Analog Siegel; ACS 2017. DOI: 10.1021/acs.jmedchem.6b01594 59
Slide 60: Remdesivir Structure Activity Relationship
Remdesivir Structure Activity Relationship C-Adenosine Analog Monophosphate Form Remdesivir Rate limiting Charge reduces Neutral charge, bypasses phosphorylation permeability rate limiting step Siegel; ACS 2017. DOI: 10.1021/acs.jmedchem.6b01594 60
Slide 61: Remdesivir Structure Activity Relationship
Remdesivir Structure Activity Relationship Monophosphoramidate 1’Cyano C- adenosine Nucleoside Analog Siegel; ACS 2017. DOI: 10.1021/acs.jmedchem.6b01594 61
Slide 62: Remdesivir Structure Activity Relationship
Remdesivir Structure Activity Relationship C-Adenosine Analog Remdesivir Poor selectivity, highly cytotoxic 1’Cyano modification confers selectivity Siegel; ACS 2017. DOI: 10.1021/acs.jmedchem.6b01594 62
Slide 63: Safety – Phase I
Safety – Phase I • Multiple-dose, 5-14 days • Any TEAE - 56-72%; All Grade 1-2 • ALT/AST increase • Onset 5-25 days; resolution 3-47 days • Phlebitis • Extremity pain • Nausea • Constipation • Dyspepsia • Headache 63
Slide 64: In vitro Activity
In vitro Activity Filoviridae Paramyxoviridae Pneumoviridae Orthocoronaviridae ● Ebola ● Measles ● Respiratory ● HCoV-NL63 ● Marburg ● Mumps Syncytial Virus ● HCoV-OC43 ● Nipah ● Human ● HCoV-229E ● Hendra Metapneumovirus ● HCoV-HKU1 ● MERS ● SARS-CoV-1 HCoV = Human Coronavirus; MERS = Middle East R
Slide 65: In vitro Activity
In vitro Activity Virus EC50 (cells) CC50 (cells) Selectivity Index SARS-CoV-2 0.01 µM (HAE) >100 µM (HAE) >1000 SARS-CoV-1 0.069 µM (HAE) > 10 µM (HAE) >144 MERS 0.074 µM (HAE) > 10 µM (HAE) >135 Ebola 0.086 µM (MCr) 6.1 (Hep-2) N/A EC50 = 50% effective concentration; CC50 = 50% cytotoxic concentra
Slide 66: In vitro Activity
In vitro Activity Virus EC50 (cells) CC50 (cells) Selectivity Index SARS-CoV-2 0.01 µM (HAE) >100 µM (HAE) >1000 SARS-CoV-1 0.069SARS- CoVµM -(HAE)2 EC50 > 10 µM (HAE) >144 Ribavirin 109.5 µM MERS 0.074 µM (HAE) > 10 µM (HAE) >135 Penciclovir 95.96 µM Favipiravir 61.9 µM Ebola 0.086 µM (MCr) 6.1 (He
Slide 67: Coronaviruses and Proofreading
Coronaviruses and Proofreading Removed by proofreading Ribavirin Penciclovir Favipiravir Maintains activity; high fitness cost Remdesivir Agostini; Am Soc Micro 2018. DOI: 10.1128/mBio.00221-18 Smith; PLoS Pathog 2013. DOI: 10.1371/journal.ppat.1003565 Wang; Cell Res 2020. DOI: 10.1038/s41422-020-02
Slide 68: Coronaviruses and Proofreading
Coronaviruses and Proofreading Modest activity change w/o ExoN Modest activity change w/o ExoN Agostini; Am Soc Micro 2018. DOI: 10.1128/mBio.00221-18 68
Slide 69: ACTT-1 Trial
ACTT-1 Trial • N = 1062; Randomized, double-blind, placebo-controlled • Severe COVID-19 (SpO2 < 94%) or oxygen supplementation • Comparators: 10 days of remdesivir vs. placebo • Baseline severity: Low-flow (41.0%), MV/ECMO (26.8%); well-matched Primary Outcome Mortality Safety Time to Recovery 10d v
Slide 70: ACTT-1 Trial: Time to Recovery
ACTT-1 Trial Time to Recovery Ambient Air Low-flow Remdesivir 10 d vs. Placebo 15 d RR 1.29 (95%CI 1.12-1.49; P<0.001) High-flow MV/ECMO Beigel; NEJM 2020. DOI: 10.1056/NEJMoa2007764 70
Slide 71: ACTT-1 Trial: Clinical Worsening
ACTT-1 Trial Day 15 Clinical Worsening – Remdesivir vs. Placebo Ambient Air High-flow 8.3% vs. 15.7% 30.5% vs. 36.7% Low-flow MV/ECMO 10.4% vs. 23.6% 10.7% vs. 13.6% Beigel; NEJM 2020. DOI: 10.1056/NEJMoa2007764 71
Slide 72: ACTT-1 Trial: Mortality
ACTT-1 Trial Mortality – Day 15 KM Estimate 6.7% vs. 11.9% All Patients HR 0.55 (95%CI 0.36-0.83) Mortality – Day 29 KM Estimate 11.4% vs. 15.2% HR 0.73 (95%CI 0.52-1.03) KM = Kaplan-Meier Low-flow Beigel; NEJM 2020. DOI: 10.1056/NEJMoa2007764 72
Slide 73: ACTT-1 Trial Adverse Events
ACTT-1 Trial Adverse Events Remdesivir (n = 541) Placebo (n = 522) Generally well tolerated overall Serious – n (%) 131 (25) 163 (32) Acute kidney injury 9 (1.7) 17 (3.3) Higher rates of adverse events in Resp failure/distress 64 (12) 100 (19.4) placebo arm than remdesivir; High Hypotension/shock 9
Slide 74: SIMPLE-1 Severe Trial
SIMPLE-1 Severe Trial • N = 397; Randomized, open-label, no placebo • Severe COVID-19 (SpO2 < 94%); Excluded MV/ECMO • Comparators: 5 vs. 10 days of remdesivir • 10-day group significantly sicker at baseline (P = 0.02) Primary Outcome Secondary Outcomes Serious AEs 14-Day Clinical Status Time to Rec
Slide 75: SIMPLE-1 Severe Trial
SIMPLE-1 Severe Trial Caution: • Post-hoc analysis • Small subgroups • Inconsistent trends Goldman; NEJM 2020. DOI: 10.1056/NEJMoa2015301 75
Slide 76: SIMPLE-2 Moderate Trial
SIMPLE-2 Moderate Trial • N = 596; Randomized, open-label, controlled • Moderate COVID-19 (SpO2 > 94%); ≥ 80% on room air • Comparators: 5 vs. 10 days of remdesivir vs. standard care (insufficient placebo) • Patients well-matched on baseline severity and comorbidities Primary Outcome Secondary Outco
Slide 77: SIMPLE-2 Moderate Trial
SIMPLE-2 Moderate Trial RDV pts. – 6% RDV pts. – 3-4% less progression less progression Spinner; JAMA 2020. DOI:10.1001/jama.2020.16349 77
Slide 78: Clinical Summary
Clinical Summary • Remdesivir significantly reduces time to clinical recovery • Benefit most apparent in low-flow patients; modest benefit for moderate disease • Minimal/no benefit observed in high-flow, mechanically ventilated, ECMO • Clinically, but not statistically significant mortality reductio
Slide 79: Guideline Recommendations: IDSA
Guideline Recommendations Infectious Diseases Society of America • The panel suggests against remdesivir for routine treatment of moderate COVID-19 (oxygen saturation >94% and no supplemental oxygen); strongly urges continued recruitment into trials. • The panel suggests remdesivir for severe COVID-
Slide 80: Guideline Recommendations: NIH
Guideline Recommendations National Institutes of Health • Outpatient or inpatient ambient air (moderate): No specific antiviral recommended; The panel recommends against dexamethasone • Low-flow (severe): Remdesivir plus dexamethasone; dexamethasone alone if remdesivir unavailable • High-flow (sever
Slide 81: Role in Therapeutic Landscape
Role in Therapeutic Landscape remdesivir, plasma, immune globulins remdesivir, dexamethasone, baracitinib Clinical trials Adapted from: Siddiqi; JHLT 2020. DOI: 10.1016/j.healun.2020.03.012 81
Slide 82: Severity Spectrum
Severity Spectrum Severity (n = 44,415) Mild/Mod 81% Severe 14% remdesivir Critical 5% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% Wu; JAMA 2020. DOI:10.1001/jama.2020.2648 82
Slide 83: Current Investigations
Current Investigations Trial Sponsor Population Intervention ACTT-3 NIAID SpO2 ≤ 94% RDV + IFN ß-1a vs. RDV + PCB DisCoVeRy Inserm SpO2 < 94% RDV vs. HCQ vs. IFN-ß vs. LPV/r vs. SOC Solidarity WHO Hospitalized RDV vs. HCQ vs. LPV/r vs. IFN-ß1a REMDACTA Roche/Gil > 6L NC RDV + tocilizumab vs. RDV + P
Slide 84: Questions
Questions Matt Davis, PharmD MRDavis@mednet.ucla.edu @Mattdavis138 84
Slide 85: Business Overview: Protein Expression Business
BUSINESS OVERVIEW Patrick Lucy SVP and CBO Protein Expression Business 85 Copyright © 2020 Ligand. All Rights Reserved.
Slide 86: Solving Our Industry's Protein Production Challenges
86 SOLVING OUR INDUSTRY’S PROTEIN PRODUCTION CHALLENGES Our Expression Technology Platform uniquely enables complex protein drug production with quality and efficiency • The global therapeutic protein market is estimated to be $100B+ and is growing • Clinical and commercial success achieved with pro
Slide 87: Our Expression Technology Platform
87 OUR EXPRESSION TECHNOLOGY PLATFORM One of the most comprehensive prokaryotic protein production platforms in the biopharmaceutical industry Applies to broad range of protein types, differentiated in state-of-the-art binding modalities Approved products from platforms expected to drive expanded us
Slide 88: A Unique Value-Driving Platform
88 A UNIQUE VALUE-DRIVING PLATFORM • Industrial legacy in the labs of Mycogen Corp and The Dow Chemical Company Expression Platform has given rise to approved products and has maintained a success rate of over 80% in expressing a variety of “lead” protein candidates • Platform delivers significant c
Slide 89: The Industry's Deepest Prokaryotic Protein Production Platform
89 THE INDUSTRY'S DEEPEST PROKARYOTIC PROTEIN PRODUCTION PLATFORM P. fluorescens: A GRAM-NEGATIVE, NON-PATHOGENIC, METABOLICALLY VERSATILE ORGANISM ‒ Genome sequenced, leveraged to engineer host strains and design expression plasmids ‒ Animal origin and used with antibiotic-free processes ‒ High-thr
Slide 90: Expression Technology Platform: Our Extensive Toolbox
90 EXPRESSION TECHNOLOGY PLATFORM OUR EXTENSIVE TOOLBOX • Enables parallel, high-throughput, Codon Optimized Genes combinatorial assessment of protein Plasmids expression based on thousands of Elements plasmid/host strain combinations combined to Transcriptional Promoters generate >100 rapid cloning
Slide 91: Expression Technology Platform: Automation
91 EXPRESSION TECHNOLOGY PLATFORM AUTOMATION • Automation allows high throughput parallel construction and screening of thousands of expression strains ‒ Lead strain engineering: All strains are expressing the same gene/protein ‒ Discovery mode: A subset of strains are expressing putative lead prote
Slide 92: Expression Technology Platform: Our Strain Screening Approach
92 EXPRESSION TECHNOLOGY PLATFORM OUR STRAIN SCREENING APPROACH • Combinatorial screening approach can assess thousands of unique expression strains in parallel • Speed, Quality and Yield create significant advantages and minimization of time and cost Automation-enabled HTP Strain Construction, Expr
Slide 93: Expression Technology Platform: Intellectual Property
93 EXPRESSION TECHNOLOGY PLATFORM INTELLECTUAL PROPERTY Protein Expression & Recovery Platform supported by 27 issued U.S. patents 3 Patent Families (last expiry 2030) Substantial know-how also supports the Tools for Protein Expression platform 6 Patent Families (last expiry 2036) High-Throughput Sc
Slide 94: Expression Technology Platform: Vast Experience
94 EXPRESSION TECHNOLOGY PLATFORM VAST EXPERIENCE DEMONSTRATES PLATFORM VERSATILITY AND SUCCESS Protein Type Our Improvements Alternative Host Yeast: Fab 10-20x yield improvement, high quality at 1L scale Quality issues Low yield Microbial Outer E. coli: Soluble active expression 20 g/L Completely i
Slide 95: Case Study: Jazz Pharmaceuticals Partnership
95 CASE STUDY: JAZZ PHARMACEUTICALS PARTNERSHIP POSITIONED TO MAINTAIN STRONG ASPARAGINASE LEADERSHIP Challenges for Jazz Our Solution Successful Results • PBL, the owner and sole • Experience in protein expression of • PF743 (JZP-458) – successfully manufacturer of Erwinaze, continues enzymes made
Slide 96: Concept to Pivotal Phase 2/3 Study in ~2.5 Years
96 CONCEPT TO PIVOTAL PHASE 2/3 STUDY IN ~2.5 YEARS JZP-458: DRIVEN BY PATIENT NEED FOR RELIABLE, LIFE-SAVING THERAPY Significant need for reliable, Global expansion opportunities — Treatment population consistent, high-quality supply Europe and Japan expansion OBJECTIVE: Agreement with Pivotal laun
Slide 97: Teriparatide Injection Partnership
97 TERIPARATIDE INJECTION PARTNERSHIP • First FDA approved 505(b)(2) therapeutic equivalent candidate to Forteo® ‒ Approved for treatment of osteoporosis in certain patients at high risk for fracture ‒ $1.8B global anabolic market • Launched in June 2020 in U.S. ‒ EU approval August 2020, ROW in-pro
Slide 98: Expression Technology Partnerships: CRM197 Opportunity
98 EXPRESSION TECHNOLOGY PARTNERSHIPS HIGHLIGHTING OUR CRM197 OPPORTUNITY CRM197 is a non-toxic mutant of diptheria toxin, used as a carrier protein in vaccines Platform rights to use CRM197 in up to 4 Commercial license exclusive to a production vaccine products strain for CRM197 for use in any SII
Slide 99: Expression Technology Platform: Competitive Advantage
99 EXPRESSION TECHNOLOGY PLATFORM COMPETITIVE ADVANTAGE Pfenex Expression Technology Platform Has a Legacy of Success and Value Creation Platform has long history of successful production strain identification with unprecedented speed, while maintaining a success rate of >80% with complex proteins E
Slide 100: Financial Overview & Outlook
FINANCIAL OVERVIEW & OUTLOOK Matt Korenberg CFO 100 Copyright © 2020 Ligand. All Rights Reserved.
Slide 101: Overview
101 OVERVIEW Q3 Captisol M&A and Results; Outlook to Capital Updated 2020 2023 Allocation and 2021 Guidance
Slide 102: Q3 Captisol Revenue & Updated 2020 Outlook
102 Q3 CAPTISOL REVENUE & UPDATED 2020 OUTLOOK • Booked $23 million of Captisol revenue in Q3 • 2020 full-year Captisol sales guidance: $92 million, increased from $90 million; implies $23 million for Q4 2020 • Royalty outlook for 2020 of $33 million, increased from $32 million ‒ Stable outlook for
Slide 103: 2020 Updated Guidance
103 2020 UPDATED GUIDANCE INCLUDING IMPACT OF PFENEX, ICAGEN, TAURUS, XCELLA ACQUISITIONS AND VERNALIS DIVESTITURE $170 All revenue lines contributing to million increased guidance Total Revenue Gross margin in-line with 80% - 85% previous guidance 55%+ Gross Margin 2020 revenue and adjusted $73 - $
Slide 104: 2021 Revenue Guidance
104 2021 REVENUE GUIDANCE $285 MILLION TOTAL REVENUE Royalties Kyprolis Evomela Core Revenue of $130 Million Growth of Kyprolis and Teriparatide Evomela with addition Other of Pfenex portfolio $40 Contract Material Sales Commercial Strong outlook with Clinical $45 sales driven by existing Royalties
Slide 105: 2021 P&L Guidance
105 2021 P&L GUIDANCE 2021 TOTAL REVENUE AN ALL-TIME HIGH FOR LIGAND 2020G 2021G • 68% revenue growth over 2020 Revenue $170 $285 • Royalty growth in core assets and addition of four new royalty streams Gross Margin 80% - 85% 75% - 80% ‒ 2021 launches for JZP-458 and Merck V114 Cash R&D $43 to $45 $
Slide 106: 2021 P&L Guidance: Margins
106 2021 P&L GUIDANCE MARGINS STRONG EVEN WITH IMPACT OF MIX SHIFT 2020G 2021G • Royalty and Contract lines 100% gross Revenue $170 $285 margins Gross Margin 80% - 85% 75% - 80% • Captisol is a more significant portion of Cash R&D $43 to $45 $45 to $50 revenue in 2021 driving increased dollar value
Slide 107: 2021 P&L Guidance: Cash Operating Expenses
107 2021 P&L GUIDANCE CASH OPERATING EXPENSES ADJUSTED FOR M&A 2020G 2021G • Addition of full year of Pfenex team and Revenue $170 $285 spend in 2021 Gross Margin 80% - 85% 75% - 80% • CE-Iohexol trial costs impact 2021 Cash R&D $43 to $45 $45 to $50 • Vernalis costs removed from 2021 Cash G&A $30 t
Slide 108: 2021 P&L Guidance: EPS Growth
108 2021 P&L GUIDANCE EPS GROWTH SIGNIFICANT OVER 2020 2020G 2021G • 52% adjusted EPS growth over 2020 Revenue $170 $285 Gross Margin 80% - 85% 75% - 80% • Share count not currently assuming any share repurchase in 2021 Cash R&D $43 to $45 $45 to $50 Cash G&A $30 to $32 $35 to $40 Cash Expenses $73
Slide 109: Three-Year Outlook: Total Revenue
109 THREE-YEAR OUTLOOK TOTAL REVENUE ~$62M $220M Royalty outlook does not include contribution $170M* Royalty ~$35M ~3X Royalty from Sparsentan or Increase Teriparatide TE approval Contract ~$10M $113M Captisol ~2X Contract Increase 2023 does not include ~30% Captisol any contribution from Growth re
Slide 110: Three-Year Outlook: Royalties
110 THREE-YEAR OUTLOOK ROYALTIES ~$33 M $95M V114 Teriparatide Pfenex products Erwinia Pneumosil Asparaginase ~$17M New PTX-022 Zimberelimab ~$12M approvals Existing Pevonedistat Sugemalimab $33M products Kyprolis Duavee/Conbriza Evomela Nexterone/Others 2020 2023 Does not assume any sparsentan roya
Slide 111: Three-Year Outlook: Captisol
111 THREE-YEAR OUTLOOK CAPTISOL Approved commercial product growth driven by Kyprolis and Nexterone Steady growth with significant potential Clinical trials and pipeline approvals upside from high add incrementally in near-term use programs like CE-Iohexol if Research partners and new license approv
Slide 112: Three-Year Outlook: Contract
112 THREE-YEAR OUTLOOK CONTRACT PROPRIETARY COMPOUNDS / OTHER Total Potential Contractual Payments in excess of PROTEIN $4.5 Billion EXPRESSION
Slide 113: Three-Year Outlook: Contract
113 THREE-YEAR OUTLOOK CONTRACT $200 million of contract revenue booked in past 5 years and >$400 million risk-adjusted contract payments over next 5 years >$4.5 billion potential contract payments >$1 billion risk- adjusted contract payments 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 20
Slide 114: Portfolio Information Management System
114 PORTFOLIO INFORMATION MANAGEMENT SYSTEM FACILITATING THE MANAGEMENT AND TRACKING OF OVER 1500 COMPANIES AND EVENTS Lead Science Database Reporting Review Collaboration and Partner reports and Dedicated Science lead data share through contracts linked to for each program cloud-based technology pr
Slide 115: Captisol and the COVID-19 Pandemic
115 CAPTISOL AND THE COVID-19 PANDEMIC Three stages of world need may drive demand for supply of Captisol Ligand’s View Ligand forecasts Large Captisol Urgent demand now as pandemic continues higher Captisol quantities supplied needs for in 2020 as 5 to 30 countries might stockpile manufacturing man
Slide 116: Captisol and the COVID-19 Pandemic
116 CAPTISOL AND THE COVID-19 PANDEMIC • In 2004, the U.S. and other countries began stockpiling antiviral medications, namely Tamiflu® (Roche) and Relenza® (GSK) ‒ Roche supplied ~350 million treatment courses (3.5 billion doses) of Tamiflu to governments between 2004 and 20091 • Typically each yea
Slide 117: Capital Deployment: Track Record
117 CAPITAL DEPLOYMENT TRACK RECORD OF SUCCESSFULLY DEPLOYING CAPITAL • Ligand is a company devoted to science and patient care that has exhibited an outstanding track record of deploying capital ‒ High-growth financial business ‒ Lean operating model ‒ Disciplined financial managers • Over the past
Slide 118: Over $2 Billion of Capital Deployment
118 OVER $2 BILLION OF CAPITAL DEPLOYMENT ~$1.25 Billion for Return of Capital - 8 million shares repurchased (33% of outstanding) - Quarter billion of dividends $204M bond buyback at $253M special $68M share discount; $73M dividend; repurchase share repurchase $41M share repurchase $575M share repu
Slide 119: Capital Deployment Strategy Remains Unchanged
119 CAPITAL DEPLOYMENT CAPITAL-DEPLOYMENT STRATEGY REMAINS UNCHANGED • M&A is a primary focus of our capital- Capital deployment deployment strategy allocation over time • Funding cycles and our business model create ample M&A opportunities M&A 50% • Share buybacks and bond repurchases have been pri
Slide 120: Questions
QUESTIONS 120 Copyright © 2020 Ligand. All Rights Reserved.
Slide 121: Appendix: Selected Partnered Program Highlights
APPENDIX Selected Partnered Program Highlights 121 Copyright © 2020 Ligand. All Rights Reserved.
Slide 122: Kyprolis: Amgen Product Utilizing Captisol
122 KYPROLIS AMGEN PRODUCT UTILIZING CAPTISOL Sales (in millions) ® US ROW • Kyprolis viewed as superior proteasome inhibitor for multiple Japan myeloma (MM) $325 $300 • Developed and marketed by Amgen, sold in Japan by Ono $275 Pharmaceuticals $250 $225 ‒ Utilizes Ligand’s Captisol technology $200
Slide 123: Selected Expression Technology Programs
123 SELECTED EXPRESSION TECHNOLOGYPROGRAMS IN CLINICAL AND PRECLINICAL DEVELOPMENT • JZP-458 • Soluble protein antigen-receptor X- ‒ Recombinant Erwinia asparaginase for linker (sparX) treatment of ALL ‒ Arcellx has developed ARC-T cells that are ‒ Providing reliable and consistent supply of readily
Slide 124: Selected OmniAb Programs in Clinical Development
124 SELECTED OMNIAB PROGRAMS IN CLINICAL DEVELOPMENT • APVO436 • GEN1046 (DuoBody®-PD-L1x4-1BB) ‒ Bispecific antibody targeting CD123 and ‒ Bispecific antibody, jointly owned by Genmab CD3 for the potential treatment of and BioNTech hematological malignancies ‒ Targets PD-L1 and 4-1BB, selected to b
Slide 125: Selected Captisol Programs in Late-Stage Development
125 SELECTED CAPTISOL PROGRAMS IN LATE-STAGE DEVELOPMENT • Pevonedistat (TAK-924) • IV Ganaxolone ‒ Captisol-enabled™ Nedd8-Activating ‒ Captisol-enabled, positive allosteric Enzyme Inhibitor for the IV treatment of modulator of GABAA receptor myelodysplastic syndromes (MDS) ‒ Phase 3 RAISE trial in
Slide 126: Selected Captisol Programs in Clinical Development
126 SELECTED CAPTISOL PROGRAMS IN CLINICAL DEVELOPMENT • Perampanel (E2007) • AMG 330 ‒ Eisai developing a Captiosl-enabled™ IV ‒ Bispecific T-cell engager (BiTE®) antibody formulation of perampanel (E2007) as an targeting CD33 and CD3 in development adjunctive therapy for epilepsy and for the treat
Slide 127: Selected Partner Pipeline Programs in Late-Stage Development
127 SELECTED PARTNER PIPELINE PROGRAMS IN LATE-STAGE DEVELOPMENT • Sparsentan • PTX-022 ‒ Novel, topical formulation of rapamycin ‒ Dual inhibitor of angiotensin and ™ endothelin receptors in development for (QTORIN 3.9% rapamycin anhydrous gel) severe kidney diseases in development to treat pachyon
Slide 128: Selected Partner Pipeline Programs in Clinical Development
128 SELECTED PARTNER PIPELINE PROGRAMS IN CLINICAL DEVELOPMENT • Ensifentrine (RPL554) • Lasofoxifene ‒ Dual PDE3 and PDE4 enzyme inhibitor for ‒ Nonsteroidal selective estrogen receptor the treatment of respiratory disease modulator (SERM) with novel activity in ER gene mutations, prevalent in pati
Slide 129: Selected Partner Pipeline Programs in Clinical Development
129 SELECTED PARTNER PIPELINE PROGRAMS IN CLINICAL DEVELOPMENT • VK-2809 • Pradefovir ‒ Selective, liver-targeted TRβ agonist, for ‒ HepDirect prodrug of the nucleoside the treatment of metabolic disorders, analog adefovir for the treatment of including non-alcoholic steatohepatitis hepatitis B viru
Slide 130: Selected Partner Pipeline Programs in Clinical Development
130 SELECTED PARTNER PIPELINE PROGRAMS IN CLINICAL DEVELOPMENT • Ciforadenant (CPI-444) • ECF843 ‒ Small molecule inhibitor of the ‒ Recombinant human lubricin for the adenosine A2A receptor treatment of dry eye and other ophthalmic indications ‒ Corvus reported positive results at ASCO 2020 from a
Slide 131: Other Commercial Captisol Assets
131 OTHER COMMERCIAL CAPTISOL ASSETS • Captisol-enabled formulation • Reported product sales of • Marketed by Acrotech in of melphalan approved for use $25.5 million in 2019 US and CASI in multiple myeloma Pharmaceuticals in China • Captisol-enabled IV product • EU/Asia partner, Menarini, • Marketed