Ipsen Sa · EURONEXT:IPN
Ipsen Sa — Investor Day (May 2019)
138 slides from Ipsen Sa's investor day presentation, May 14, 2019
Slide 1: Investor Day
Investor Day May 14, 2019 Paris Marin Living with fibrodysplasia ossificans progressiva Hamilton, Canada
Slide 2: Disclaimer & Safe Harbor
Disclaimer & Safe Harbor This presentation includes only summary information and does not purport to be comprehensive. Forward-looking statements, targets and estimates contained herein are for illustrative purposes only and are based on management’s current views and assumptions. Such statements in
Slide 3: Agenda
Agenda 1:00pm 01 Vision & Strategy David Meek 1:10pm 02 Financials Aymeric Le Chatelier 1:20pm 03 R&D strategy/ External innovation strategy Alexandre LeBeaut/ Ivana Magovčević-Liebisch 1:35pm Q&A 1:55pm 04 Rare Diseases Harout Semerjian/ Clarissa Desjardins 2:20pm 05 Neuroscience Harout Semerjian/
Slide 4: Vision and Strategy
Vision and Strategy David Meek Chief Executive Officer
Slide 5: Vision
VISION Being a leading global biopharmaceutical company focused on Innovation and Specialty Care 5
Slide 6: Ipsen at a glance
Ipsen at a glance Industry leading top Specialty Care Advancing R&D pipeline and bottom-line growth 89% of sales 5 NCEs and multiple LCM programs #1 or #2 in key markets High-performing Top 14 Oncology Well-diversified executive management company globally geographically z team 2018 sales >€1.5bn Pr
Slide 7: Delivering on our strategy
Delivering on our strategy Objectives from 2017 Investor Day Execution ✓ Industry-leading 20%+ sales growth in 2017 and 2018 driven by Deliver double-digit growth and improving profitability Specialty Care ✓ COI margin improvement of 6.7pt 2016-2018 Implement R&D transformation with focus on innovat
Slide 8: Strengthening leadership position in three therapeutic areas
Strengthening leadership position in three therapeutic areas Ronny Janice Wade Living with neuroendocrine tumors Living with cervical dystonia Living with acromegaly Ringwood, UK Tennessee, USA Utah, USA Oncology Neuroscience Rare Diseases • Differentiated, best-in-class products in • Expertise in r
Slide 9: Roadmap and priorities
Roadmap and priorities Growth Pipeline Culture • Maximize growth and market share • Increase value of the pipeline by • Drive further transformation and worldwide for differentiated best-in-class accelerating key R&D programs ambition through leadership and people Specialty Care products • Identify,
Slide 10: Multiple value-driving and differentiated pipeline opportunities
Multiple value-driving and differentiated pipeline opportunities Five new chemical entities in the clinic; Nine regulatory submissions from 2019 to 2022 Preclinical Phase I Phase II Phase III Registration 177Lu-IPN-01072 68Ga-IPN-01070 Longer-acting toxin (Satoreotide Tetraxetan) (Satoreotide Trizox
Slide 11: Execution on growth strategy through external innovation
Execution on growth strategy through external innovation Continued investment in R&D pipeline for long-term growth Active business development Driven by To build an innovative and efforts strong balance sheet sustainable pipeline • Strengthened and agile global • Quickly replenishing firepower • Exe
Slide 12: Transformative company culture with focus on social responsibility
Transformative company culture with focus on social responsibility Employees Patients & Society Environment Caring for and developing employees, Providing innovative solutions for the Protecting the environment, minimizing the encouraging diversity and inclusion, and benefit of patients & society ba
Slide 13: Objectives of the day
Objectives of the day Provide commercial highlights and Provide financial outlook and capital Update on R&D and deep dive in R&D pipeline allocation strategy External Innovation strategy by therapeutic area Create and deliver long-term value by executing on growth strategy 13
Slide 14: Financial update
Financial update Aymeric Le Chatelier Chief Financial Officer
Slide 15: Top-tier consistent financial performance
Top-tier consistent financial performance Significant top-line growth and margin enhancement Strong cash flow generation while investing in business development On track to deliver 2020 guidance1 one year early 2016 2019 CAGR CAGR 41% Sales €1.58bn >€2.5bn2 +17% Core Operating Income €364mn >€750mn2
Slide 16: Financial outlook 2022
Financial outlook 2022 Group Net Sales ~€3.2bn Core Operating Margin >32.0% (assuming current level of exchange rates) (as % of net sales) 2019 2020 2021 2022 • Existing portfolio, including palovarotene for FOP indications1, assumes no approvals of additional meaningful products or indications • As
Slide 17: Strong growth from key Specialty Care products
Strong growth from key Specialty Care products Brand/ asset Geographies Major indications Growth / Peak sales Neuroendocrine Tumors (NET) Global Double-digit growth until potential impact of generic Acromegaly Ex-US and Japan Prostate Cancer High to mid single-digit growth in all territories Renal C
Slide 18: Somatuline – Potential SSA competitive environment
Somatuline® – Potential SSA competitive environment Market Intelligence Somatuline® outlook • Short-acting generic formulations of octreotide and • Long-acting formulations remain standard of care in growing lanreotide available for many years with no impact market • Number of companies identified w
Slide 19: 2022 Core Operating Income growth drivers
2022 Core Operating Income growth drivers Core Operating Margin >32.0% COGS Sales & Marketing R&D G&A Slight increase Significant reduction as Increase as a % of sales Slight decrease as % of sales % of sales to reach 14%-15% of sales • Higher Cabometyx royalties and • Streamlining of operations and
Slide 20: Capital allocation principles
Capital allocation principles • Significant financing capacity to leverage balance sheet up to 2.0x Net Debt to EBITDA • >€1bn business development fire power by end of 2020 Business development • Strict financial discipline based on IRR, value creation > cost of capital and risk adjusted analysis a
Slide 21: Priorities to deliver strong shareholder return
Priorities to deliver strong shareholder return • Maintain ambition of double-digit top-line growth • Maximize key product growth Sales • Build leadership position in attractive Specialty Care markets growth • Utilize multiple levers to optimize resource allocation Margin • Increase synergies throug
Slide 22: R&D / External Innovation Strategy
R&D / External 03 Innovation Strategy
Slide 23: R&D Strategy and Portfolio
R&D Strategy and Portfolio Alexandre LeBeaut, MD Chief Scientific Officer
Slide 24: Growing our Pipeline: R&D Strategy
Growing our Pipeline: R&D Strategy Aiming for first/ Focus on Oncology, Neuroscience best-in-class assets drives Be a leading external innovation- and Be a development powerhouse differentiation sourcing organization Rare Diseases of the pipeline • Addressing unmet medical • Innovative programs: Sys
Slide 25: Accomplishments since Investor Day 2017
Accomplishments since Investor Day 2017 Oncology Neuroscience Rare Diseases Decapeptyl® Xermelo® Dysport® Dysport® Breast cancer (EU) Carcinoid syndrome ALL spasticity (U.S.) PLL spasticity (EU) 9 Somatuline® New delivery system (EU) Somatuline® GEP NET Japan Major indications Somatuline® Autogel® C
Slide 26: Being a Development Powerhouse
Being a Development Powerhouse • Seasoned experts leading innovation platforms • Integrated digital solutions (site selection, in silico clinical trials) • Regulatory science to support innovative study design (e.g. basket trials) Acceleration of Execution • Integrated pharmaceutical development Pat
Slide 27: Leading a risk-balanced early and late stage innovative proprietary pipeline
Leading a risk-balanced early and late stage innovative proprietary pipeline Preclinical Phase 1 Phase 2 Phase 3 Palovarotene (FOP chronic) Palovarotene (FOP episodic) Palovarotene (MO) First-in-class Palovarotene (dry eye) NTSR1 177Lu-IPN01087 (solid tumors) Long-acting toxin mrBoNT/A Long-acting t
Slide 28: Targeted regulatory submissions
Targeted regulatory submissions Delivering >1 NCE / significant new indication per year 2019 2020 2021 2022 2023 Somatuline® Cabometyx® Cabometyx® IPN01070* Onivyde® GEP-NET (China) 1L RCC combo with nivolumab 1L HCC combo with atezolizumab GEP-NET imaging (U.S., EU) SCLC (U.S.) Dysport® Decapeptyl
Slide 29: R&D strategy: Creating value with advancing pipeline
R&D strategy: Creating value with advancing pipeline • Strongest pipeline in Ipsen’s history risk-balanced across three therapeutics areas and phases development • 5 New Chemical Entities progressing in clinical development • Innovative programs with potential to expand into additional indications –
Slide 30: External Innovation Strategy
External Innovation Strategy Ivana Magovčević-Liebisch, Ph.D., J.D. Chief Business Officer
Slide 31: External innovation-focused organization actively searching for new assets
External innovation-focused organization actively searching for new assets • Dedicated team – ~30 scientific and business professionals based across global hubs • Integrative & collaborative organization – Ability to move quickly and effectively from opportunity identification through decision makin
Slide 32: Areas of Focus
Areas of Focus • Focus on rare or niche solid tumors Oncology • All stages of development candidates and marketed products • All modalities excluding vaccines, oncolytic viruses, cell therapies, gene therapies • Rare bone and musculoskeletal diseases and their adjacencies Rare Diseases • All stages
Slide 33: Track Record of Success Through Diverse Partnerships & Transactions
Track Record of Success Through Diverse Partnerships & Transactions Early Innovation Partnerships Academic Alliances Partnerships/ Licensing Asset & Company Acquisitions New venture capital fund Cambridge, MA (U.S.) 33
Slide 34: Clementia: Successful Execution of External Innovation Strategy
Clementia: Successful Execution of External Innovation Strategy Proactively identified Agility in moving Collaborative and Focused on seamless Clementia as quickly to initiate and integrated teamwork integration to bring transformative drive the process internally and with palovarotene to opportunit
Slide 35: Q&A
Q&A
Slide 36: Rare Diseases
Rare Diseases SIPSEN
Slide 37: Rare Diseases
Marin Living with fibrodysplasia ossificans progressiva Hamilton, Canada Rare Diseases Harout Semerjian Chief Commercial Officer
Slide 38: Rare Diseases background
Rare Diseases background Affecting fewer than 1 in 2,000 people ~7000 ~5% >560 Rare Diseases have therapeutic medicines in development for Rare Most are genetic or have treatment available Diseases a genetic component Relatively quicker regulatory pathway and limited competition Significant unmet me
Slide 39: Ipsen's Rare Diseases capabilities
Ipsen’s Rare Diseases capabilities Mission: To develop and bring innovative solutions to people living with debilitating or life- threatening conditions as quickly as possible • Established legacy of Rare Disease assets in Endocrinology (Nutropin®, Increlex®, Somatuline® in acromegaly); Oncology (So
Slide 40: Acquisition of Clementia Pharmaceuticals: A Rare Disease company
Acquisition of Clementia Pharmaceuticals: A Rare Disease company Acquisition Announced 25 February and closed 17 April Key asset Palovarotene, an investigational retinoic acid receptor gamma (RARγ) selective agonist, for the treatment of fibrodysplasia ossificans progressiva (FOP), multiple osteocho
Slide 41: FOP is a severely disabling bone disorder
FOP is a severely disabling bone disorder Skeleton of Harry Eastlack • Harry passed away 6 days before his 40th birthday • Fused skeleton exemplifies harsh reality of FOP • Reminder of how much work remains to help FOP patients • On display at the Mutter Museum of The College of Physicians in Philad
Slide 42: High unmet medical need for FOP
High unmet medical need for FOP Currently no approved therapies to prevent or treat the formation of heterotopic ossifications (HO, new bone) in FOP High-dose corticosteroids started Surgical intervention not Activities that trigger flare-ups within the first 24 hours of a flare- recommended – risks
Slide 43: FOP patients treated by specialists in centers of excellence
FOP patients treated by specialists in centers of excellence Centers of excellence identified in Patients managed by variety of major markets specialists • Pediatricians • Endocrinologists specializing in bone/ mineral disorders • Orthopedic surgeons • Medical geneticists Very active and engaged glo
Slide 44: Significant commercial opportunity for FOP
Significant commercial opportunity for FOP Well-defined patient population Limited commercial investments • Prevalence: 1.3/ 1 million lives1: ~9,000 patients • Focused commercial investments required for U.S. and ex-US launch based on existing • >800 identified addressable patients in U.S. and capa
Slide 45: Favorable FOP launch dynamics expected
Favorable FOP launch dynamics expected Ultra-rare disease pricing expected Well-characterized disease Favorable product profile based on • Genetic mutation • Strong clinical efficacy • Serious unmet need • Characteristic big toe malformation at • Daily oral therapy • Compelling clinical profile birt
Slide 46: Multiple Osteochondromas (MO) – Significant upside opportunity
Multiple Osteochondromas (MO) – Significant upside opportunity Another disabling bone disorder with no therapeutic treatment options • Ultra-rare, debilitating, bone disorder in which multiple benign bone tumors, also known as osteochondromas (OCs), develop on bones • Diagnosed prevalence1,2,3: 1 in
Slide 47: Palovarotene R&D
Janice Living with cervical dystonia Tennessee, USA Palovarotene R&D Clarissa Desjardins, PhD Chief Executive Officer, Clementia
Slide 48: Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP)
Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP) • Disease of uncontrolled new bone formation • Symptoms start ~2-4 years of age • Progressive, irreversible, cumulative • Immobility by mid-twenties • Median age at death 40 years • No available therapies: steroids and NSAIDs are used for
Slide 49: Palovarotene acts on the BMP Signalling Pathway
Palovarotene acts on the BMP Signalling Pathway • FOP is caused by mutations in the ACVR1 gene. Mutant ACVR1 is believed to be overactive on its own, and in the presence of BMP ligands, which induces the BMP signalling pathway. • This leads to muscles, ligaments and tendons progressively turning to
Slide 50: Palovarotene Phase 2 and extension study
Palovarotene Phase 2 and extension study -201 Study -202 Study Part A & Part B 10 mg, 5 mg, or Placebo 5 mg, 2.5 mg, or Placebo No Treatment 14 days 28 days Imaging endpoints Functional endpoints Symptom and other measures • X-ray • FOP Patient Reported • NRS pain and swelling • CT scan Outcome (PRO
Slide 51: Natural history study of 114 patients
Natural history study of 114 patients 3-year non-interventional study to gain insight Baseline data from first 101 patients into FOP disease progression1 • Annual in-clinic visits, telephone interviews between • All but one subject (99%) had great toe visits, in-clinic visits to study new flare ups
Slide 52: Phase 2 study: 12-week flare-up data
Phase 2 study: 12-week flare-up data 72–75% reduction in new bone growth (HO volumes) at 12 weeks for patients receiving palovarotene at the time of flare- up relative to placebo/untreated flare-ups1,2 • The reduction with the episodic 20/10 mg regimen was statistically significant (p=0.02)1,2 HO: h
Slide 53: Palovarotene has established safety profile with manageable tolerability
Palovarotene has established safety profile with manageable tolerability Phase 2 studies Established safety profile in earlier studies • Dose-related increases in adverse events (AEs); most • Palovarotene was previously investigated in 800 mild or moderate in severity individuals as a possible thera
Slide 54: FOP Phase 2 data supports NDA submission
FOP Phase 2 data supports NDA submission Extensive Phase 2 clinical development program • FDA has agreed that Phase 2 flare-up data supports NDA submission for the episodic dosing regimen of palovarotene in FOP in children and adults • NDA submission targeted for H2 2019 • Fast-track, breakthrough t
Slide 55: Evaluating a new dosing regimen for FOP: Phase 3 MOVE Trial
Evaluating a new dosing regimen for FOP: Phase 3 MOVE Trial Efficacy and safety study of chronic oral palovarotene for the treatment of FOP Global Study 15 sites, 11 countries, using natural history study as external control HO Primary Endpoint annualized volume of new HO measured by whole body CT s
Slide 56: Palovarotene for Multiple Osteochondromas (MO)
Palovarotene for Multiple Osteochondromas (MO) • MO, also known as HME, is the most common inherited musculoskeletal condition • MO is characterized by the development of multiple, benign, cartilage- capped bone tumors (osteochondromas) • Development of osteochondromas (OCs) results in functional li
Slide 57: Multiple osteochondromas (MO): Excess BMP signaling plays a role
Multiple osteochondromas (MO): Excess BMP signaling plays a role • The majority of patients with MO carry loss-of-function mutations in the EXT1 or EXT2 gene, which encode proteins essential for biosynthesis of heparan sulfate (HS) chains on specific proteoglycans (HSPGs) • Decreases in or absence o
Slide 58: Phase 2 trial of palovarotene in MO
Phase 2 trial of palovarotene in MO Excess BMP signaling plays a role • Double-blind, randomized, placebo-controlled trial • Palovarotene 2.5 mg daily vs 5 mg daily vs placebo for 2 years Palovarotene 2.5 mg daily • 240 patients age 2–14 years with symptomatic MO • Primary endpoint: Annualized rate
Slide 59: Advancing palovarotene clinical trial pipeline
Advancing palovarotene clinical trial pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Next Milestone FOP NDA submission Flare-up episodic treatment (registrational trial) H2 2019 FOP Chronic treatment Interim analyses (registrational trial) 2019 Multiple Osteochondromas (MO) Complete enrolme
Slide 60: Neuroscience
05 Neuroscience
Slide 61: Dysport
Dysport® Harout Semerjian Chief Commercial Officer
Slide 62: Dynamic and attractive neurotoxin market
Dynamic and attractive neurotoxin market Attractive botulinum toxin market • Market split between Therapeutics (~55%) and Aesthetics (~45%) Botulinum toxin market (in $bn) • Market split between U.S. (~58%) and ex-U.S. (~42%) CAGR: 8% 6.5 6.0 • Market growth rate expected to continue for the foresee
Slide 63: Dysport: A unique neurotoxin to manufacture
Dysport®: A unique neurotoxin to manufacture Cornerstone product to Ipsen’s Neurotoxin franchise, ~30 years of manufacturing expertise • Highly complex production processes difficult to replicate and executed by staff with substantial and unique expertise in toxin manufacturing • State-of-the-art dr
Slide 64: Strong commercial execution
Strong commercial execution Ipsen Dysport® sales 2014-2018 €mn 400 CAGR: 8.1% • Ipsen’s Dysport® 2018 sales up 12.6% at CER 348 • Solid volume growth in therapeutics 328 • Strong performance of Galderma in aesthetics 300 280 285 255 Global in-market sales under Dysport brand: 200 >€500 million 100 0
Slide 65: Aesthetics: Well-positioned in attractive growing market
Aesthetics: Well-positioned in attractive growing market Drivers of continued growth Successful Galderma partnership • Growth driven by the U.S. and emerging markets • Commercial partner in all geographies except Russia (China) and Middle East • Favorable market dynamics1: • Global leader in aesthet
Slide 66: Significant opportunity remains in Therapeutics
Significant opportunity remains in Therapeutics Dysport addressing >40% of therapeutics market 2018 Global therapeutic neurotoxin sales per indication1 Performance by geography • #2 in EU markets (UK, Germany, Italy) Other • Market leader in Brazil and Russia Blepharospasm • Limited but growing mark
Slide 67: Lifecycle management: Hallux valgus (bunions)
Lifecycle management: Hallux valgus (bunions) Disease characterization Phase 2 clinical development • High prevalence worldwide: 23%1 • Multiple-dose, double-blind, randomized, placebo- →15% consult specialist controlled study of ~165 patients →10%2 moderate to severe patients • Primary endpoint: Ch
Slide 68: Lifecycle management: Vulvodynia
Lifecycle management: Vulvodynia Disease characterization • Underestimated prevalence worldwide: 6.5%1 of female population → 69%2 consult specialist → 40% vulvodynia diagnosis → 60%3 provoked vulvodynia • Vulvar pain for at least 3 months, without a clear identifiable cause often associated with se
Slide 69: Next-generation neurotoxins
Next-generation neurotoxins John Chaddock, PhD VP, Head of Neuroscience Area Operations
Slide 70: Pioneering research in next-generation toxins
Pioneering research in next-generation toxins From experts in natural neurotoxins ~30 years of expertise in: • Pharmacology • Preclinical/ clinical development • Manufacturing/ scale up To leaders in recombinant toxins • Enhanced, well-characterized, high quality molecules • High level of understand
Slide 71: Recombinant Technology: Why it is important?
Recombinant Technology: Why it is important? Creating recombinant toxins Expected benefits of recombinant toxins Ability to modify aspects of neurotoxin function to • Enhanced characteristics – potency, stability, duration, enhance therapeutic applications spread, onset of action, immunogenicity • S
Slide 72: Modified recombinant neurotoxins: Modify catalytic site for new intracellular targets
Modified recombinant neurotoxins: Modify catalytic site for new intracellular targets Identification and Characterization of Botulium Neurotoxin A Detailed knowledge of the structure Substrate Binding Pockets and Their Re-Engineering for Human of BoNT + collaboration with experts SNAP-23 in the fiel
Slide 73: Modified recombinant neurotoxins: Optimize receptor binding to increase potency
Modified recombinant neurotoxins: Optimize receptor binding to increase potency Detailed knowledge of the structure of BoNT + collaboration with experts in the field + recombinant BoNT platform = • Engineered BoNT/B binding domain with improved affinity for the human motor neuron • Establishes the p
Slide 74: Clinical translation: Paving the way for a new treatment paradigm
Clinical translation: Paving the way for a new treatment paradigm Developing a unique portfolio of existing and new neurotoxins with different pharmacodynamics profiles, allowing physicians to choose the neurotoxin that will fit patients’ unique medical needs Fast-acting recombinant Natural Abobotul
Slide 75: Discovering a New Class of Biopharmaceuticals: Targeted Secretion Inhibitors (TSIs)
Discovering a New Class of Biopharmaceuticals: Targeted Secretion Inhibitors (TSIs) Developing a new class of proteins by incorporating toxin/ non-toxin domains: Targeted secretion inhibitors (TSI)1 with the ability to not only target neurons but also other types of cells in the body leading to a wi
Slide 76: Extending neurotoxin leadership with next-generation toxins
Extending neurotoxin leadership with next-generation toxins • Pioneers in cutting-edge innovation leveraging long legacy and expertise in neurotoxin field • Uniquely broad portfolio to serve patient needs across the treatment spectrum • Fast and long-acting neurotoxin programs advancing in the clini
Slide 77: Q&A
Q&A
Slide 78: Oncology
06 Oncology
Slide 79: Oncology Commercial Highlights
Oncology Commercial Highlights Richard Paulson Executive Vice-President and Chief Executive Officer of North America
Slide 80: Global Oncology Strategy
Global Oncology Strategy To be a leader in solid tumors with high unmet needs in well-defined patient populations Maximize leadership position in Neuroendocrine Specialty Oncology markets Tumors (NET) GLOBAL • Leading #1 or #2 market share against formidable oncology players Prostate Cancer EX-US AN
Slide 81: Ipsen Oncology sales double 2015-2018
Ipsen Oncology sales double 2015-2018 €mn 2000 • Oncology sales reach €1.5bn in 2018, +30% at CER CAGR: 26% 1503 1500 • Franchise accounts for 68% of Ipsen sales vs. 52% in 2015 1186 • Ipsen #14 in global Oncology rankings 1000 905 • Decapyptyl® mid to high-single digit growth 753 • Encouraging laun
Slide 82: Decapeptyl
Decapeptyl Mid to high single-digit growth expected to continue Strengthened commercial Attractive market dynamics 6-month formulation organization • Androgen deprivation • 30+ years of experience • Cost and time efficient with therapy (ADT) is the no loss of prostate-specific • Launched in >70 mark
Slide 83: Cabometyx
Cabometyx®
Slide 84: TKI of choice in 2L RCC
TKI of choice in 2L RCC Unique mechanism of action, strong clinical profile • Oral, small molecule that targets MET and AXL beyond TKI market share in 2L aRCC2 – Q1 2019 VEGF receptors1, with the potential to overcome the resistance induced by prior antiangiogenic therapies • Consistent results acro
Slide 85: Cabometyx securing solid position along RCC treatment paradigm
Cabometyx® securing solid position along RCC treatment paradigm Evolving RCC market dynamics Support for Cabometyx® use post-IO therapy1 • Evolving RCC market dynamics • Retrospective multicenter analysis • First IO combination approved in Europe January 2019 • Cabometyx: clinical efficacy post-IO i
Slide 86: Expected sequencing of evolving RCC market
Expected sequencing of evolving RCC market 1L 2L Other targeted therapies IO combinations Cabometyx Other targeted therapies IO monotherapy Cabometyx New treatments that have demonstrated superiority over standard of care Significant 2L market share gains expected for Cabometyx® as IO combinations m
Slide 87: Cabometyx in Hepatocellular Carcinoma (HCC) market
Cabometyx® in Hepatocellular Carcinoma (HCC) market Strong clinical profile HCC market opportunity • Approval in EU in November 2018 based on Phase 3 • High unmet medical need with numerous negative CELESTIAL trial: Phase 3 trials in recent years • Efficacy benefit vs. placebo (OS: 10.2 mo vs 8.0) •
Slide 88: Expansion of Cabometyx opportunity
Expansion of Cabometyx opportunity ® IO combination 2L HCC • Approved November Peak year sales: 2018 in EU • €300mn RCC 1L RCC • Launched in • €100mn 2L HCC • Approved May 2018 in 5 countries • Upside opportunity from ongoing IO combo EU trials • Launched in 8 countries >40 ongoing Investigator Spon
Slide 89: Onivyde
Innovator patent core
Slide 90: Significant U.S. opportunity in metastatic pancreatic cancer
Significant U.S. opportunity in metastatic pancreatic cancer Half of patients diagnosed in metastatic Metastatic Pancreatic Cancer Patients1: ~37,000 setting Resectable? 20%2 • Accounting for <5% of all new cancer cases but is the Resectable? Yes -- Surgery #3 cancer in number of deaths • 5-year sur
Slide 91: Onivyde strong clinical profile and differentiation
Onivyde® strong clinical profile and differentiation Differentiated product for metastatic pancreatic cancer Category 1 evidence in NCCN guidelines • First and only FDA-approved therapy for post-gemcitabine • Onivyde + 5-FU/LV significantly improved OS among patients pancreatic cancer previously tre
Slide 92: Global pancreatic cancer market could triple by 2024
Global pancreatic cancer market could triple by 2024 as treatment paradigm evolves to sequencing of therapies 2018-2024 projected market value 3,500 3,000 CAGR: 21% 893 2,500 Market Value ($M) 2,000 612 1,500 475 1,000 2,173 268 236 1,660 292 260 1,147 500 847 507 515 657 0 2018 2019 2020 2021 2022
Slide 93: Onivyde: Significant synergies from U.S. Oncology commercial team
Onivyde®: Significant synergies from U.S. Oncology commercial team • Dedicated and experienced team of ~180 professionals including sales, marketing, reimbursement, medical affairs, patient/ payor services • Extensive Oncology experience in pancreatic cancer • ~65% overlap with Somatuline® call poin
Slide 94: Expansion potential of Onivyde franchise
Expansion potential of Onivyde® franchise Other indications 2L SCLC Ph 2 trial readout H2 2019 1L PDAC • 35K new cases/yr in U.S. Ph 2 trial interim • 14K patients treated in 2L readout mid-2019 • Topotecan only FDA-approved 2L • 28K patients eligible for treatment: 2L PDAC treatment • OS: 7.8 month
Slide 95: Somatuline
Somatuline® Innovator patent core
Slide 96: Somatuline: Best-in-class product in attractive NET market
Somatuline®: Best-in-class product in attractive Neuroendocrine Tumor (NET) market SSA market growing Differentiated product Attractive NET market dynamics double digits profile • Somatostatin analog (SSA) market 2,500 • Best-in-class SSA with real-world CAGR: +11.3% evidence and more extensive labe
Slide 97: SSA competitive environment
SSA competitive environment Manufacturing unique depot IP position Constraints to entry formulation • Somatuline® Depot (U.S.) – March • Specialized peptide manufacturing • Unique formulation manufactured 2020 acromegaly, December 2021 process using advanced liquid crystal orphan drug designation in
Slide 98: Exceptional Somatuline performance driving Specialty Care business
Exceptional Somatuline® performance driving Specialty Care business 3-year sales growth Attractive financial profile €mn CAGR: 25% • Wholly-owned global asset 847 800 • Largest, fast-growing and most profitable product 703 • Achieved blockbuster status in 2018 600 • Market share increasing steadily
Slide 99: Expanding leadership in NET market
Expanding leadership in NET market Growth strategy in resilient NET market Momentum driven by continuing patients and growing new patient share2 • Strong growth market (11%) to continue • Expansion of SSA market to over $2bn since Somatuline NET launch in U.S. in early 2015 • Over 5x increase in NET
Slide 100: Somatuline momentum driven by real-world evidence, new delivery system
Somatuline® momentum driven by real-world evidence, new delivery system and continued investment Delivery systems matter • Delivery system important to HCPs • Patient experience matters • Real-world evidence demonstrates value of delivery system • 99% full dose delivery • Shorter injection prep time
Slide 101: Systemic Radiation Therapy
Systemic Radiation Therapy Sandy McEwan, MB, FRCPC, FSNMMI Vice President, Radiopharmaceuticals
Slide 102: Building Systemic Radiation Therapy (SRT) platform
Building Systemic Radiation Therapy (SRT) platform Ipsen’s commitment to SRT: Developing innovative radiolabeled diagnostics and therapeutics for enhanced care through precision medicine • Entered the field via OctreoPharm acquisition in 2015 • Strategic alignment with Ipsen’s NET/oncology franchise
Slide 103: Rationale of Systemic Radiation Therapy (SRT)
Rationale of Systemic Radiation Therapy (SRT) SRT: Precision targeted treatment strategy using radiolabelled peptides or other molecules to deliver therapeutic doses of radiation to cancer cells which overexpress specific receptors * Target Ligand Spacer Precision targeting of overexpressed receptor
Slide 104: Systemic Radiation Therapy Characteristics
Systemic Radiation Therapy Characteristics • Companion imaging diagnostic/imaging biomarker • Patient selection defined by image • Identification of tumor heterogeneity • Fractionated schedules are most effective • High clinical response rate • Stable disease is common • Low toxicity, high patient a
Slide 105: Theranostics: Companion diagnostic imaging agent defines treatment potential
Theranostics: Companion diagnostic imaging agent defines treatment potential for SRT https://breast-cancer.ca/histlgy/ Rx Dx TARGETED COMPANION THERAPEUTIC DIAGNOSTIC IMAGE Therapeutic strategy uses same Theranostics Companion Diagnostic may be IHC or targeting strategy as Dx but delivers an image -
Slide 106: Complex manufacturing/ supply chain management capabilities
Complex manufacturing/ supply chain management capabilities Lutetium-177 CMO Central Diagnostic Clinical Site Production Manufacturing Availability Precursor Irradiation Receive Required Gallium-68 in Reactor Lutetium-177 licenses Diagnostic Lutetium-177 Separation Manufacturing in Radiopharmacy Syn
Slide 107: Comparison of Satoreotide binding with DOTA-TATE
Comparison of Satoreotide binding with DOTA-TATE SSTR2 (Somatostatin Receptor type 2) antagonist Satoreotide has 3-4 more binding sites than the agonist Diagnostic: 68Ga-IPN-01070 Therapeutic: 177Lu-IPN-01072 177Lu-DOTA-TATE 177Lu-Satoreotide 177 177 L u -O P S 2 0 1 L u -D O T A -T A T E 0 .3 0 0 .
Slide 108: Satoreotide background and strategy
Satoreotide background and strategy • Ipsen’s commitment to NET patient population • Provide solutions along the treatment journey and extend leadership position in the market • Commitment to improving lives of patients • Antagonist, potential first- and best-in-class systemic radiation therapeutic
Slide 109: Satoreotide development program
Satoreotide development program Therapeutic: 177Lu-IPN-01072 • Mass dose, administered dose selected • Treatment regimen selected • Trial design underway • Phase 2/3 trial to start Q1 2020 Satoreotide post-therapy image 109
Slide 110: Satoreotide development program
Satoreotide development program Diagnostic: 68Ga-IPN-01070 • Potential best-in-class asset: non-inferiority study vs. approved competitor • Showed superior detection capability • Positive indicator of treatment success • Next steps: Phase 2/3 trial to start Q4 2019/ Q1 2020 • Europe and North Americ
Slide 111: IPN01087 - First-in-class asset targeting tumours expressing NTSR1
IPN01087 - First-in-class asset targeting tumours expressing NTSR1 • Diagnostic: 111In-IPN01087 • Therapeutic: 177Lu-IPN01087 • Platform applicable to multiple possible indications: • Lead indication: PDAC in which 40-75% of patients overexpress NTSR-1 → Possibility of combining with Ipsen and other
Slide 112: NTSR-1 overexpressed in multiple cancers
NTSR-1 overexpressed in multiple cancers NTSR-1 Background Literature Evidence for NTSR-1 Expression1 • NTSR-1 Background Literature Evidence for NTSR-1 Expression • NTSR-1mediates multiple functions of PDAC: 61 – 80% (IHC) neurotensin CRC: 93 – 100% (IHC, mRNA) • Overexpressed in many cancers Gastr
Slide 113: Screening images in mCRC support high therapeutic index
Screening images in mCRC support high therapeutic index Subject 25000100002 - Screening Screening Images - Patient with CRC metastatic to liver High tumour : Background ratio = High therapeutic index 2-4h pi 16/24h pi Keosys 2019 – CONFIDENTIAL mCRC: Metastatic Colorectal Cancer 113
Slide 114: IPN01087 clinical development strategy
IPN01087 clinical development strategy Phase 1 study: • Open-label Phase 1/2 study to evaluate the safety, tolerability, biodistribution and antitumor activity of 177Lu-IPN-01087 for the treatment of subjects with solid tumors expressing NTSR-1 • Companion imaging biomarker in clinic Q4 2019 Partner
Slide 115: Conclusion
Conclusion Building world-class Systemic Radiation Therapy platform with potential first/best-in-class assets Providing solutions across the treatment paradigm and expanding Ipsen’s presence in markets with unmet needs (NET, PDAC) Rationale to expand into other tumor types and to combine with other
Slide 116: Oncology R&D
Ronny Living with neuroendocrine tumors Ringwood, UK Oncology R&D Yan Moore, MD SVP, Global Head of Oncology R&D
Slide 117: Strategic Vision for Oncology R&D
Strategic Vision for Oncology R&D Strategy Vision • Build streamlined and innovative oncology • Become global leader in well-characterized “development powerhouse” rare/selected cancers with defined patient • Maximize data-driven lifecycle populations management • Become partner of choice for other
Slide 118: Ipsen in Oncology: Current landscape
Ipsen in Oncology: Current landscape Neuroendocrine Prostate Renal Cell Carcinoma Pancreatic Hepatocellular Tumors (NET) Cancer (RCC) Cancer Carcinoma (HCC) Ongoing EU Somatostatin Differentiated Ongoing EU Established and launch in 1L & analog with product with OS launch in 2L HCC growing product 2
Slide 119: Cabometyx (cabozantinib)
Cabometyx® (cabozantinib) SIPSEN
Slide 120: Expanding Clinical Benefit of Cabometyx
Expanding Clinical Benefit of Cabometyx® • Establish Cabometyx® as standard of care in advanced renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC) • Expand monotherapy into additional indications beyond RCC and HCC • Become TKI of choice for IO combinations • Focus on China as a
Slide 121: Rationale For Cabozantinib/ IO Combinations
Rationale For Cabozantinib/ IO Combinations Cabozantinib Inhibits targets that promote Promotes an immune-permissive tumor immune-suppression environment e.g. VEGFRs, MET, AXL, MER, TYRO3 Increases Decreases Increases Decreases • Tumor MHC class 1 Number and/or function of • CD8 + T-cells Tregs + CD
Slide 122: Become TKI of choice across indications, monotherapy or combination
Become TKI of choice across indications, monotherapy or combination >100 ISTs in >25 tumors 2022 2L HCC 1L RCC 2L RCC 2018 Various Combinations in 2017 2016 Development with Immunotherapies March 2016 • RCC 1L Phase 3 CheckMate 9ER (cabozantinib + nivolumab) • HCC 1L Phase 3 Cosmic-312 (cabozantinib
Slide 123: COSMIC-312: Phase 3 Trial in 1L HCC in combination with IO
COSMIC-312: Phase 3 Trial in 1L HCC in combination with IO Sponsored by Exelixis/Roche COSMIC-312 Experimental arm A: Randomized, Open-Label Cabozantinib at 40 mg qd + in advanced 1L HCC (N = 640) Atezolizumab 1200 mg q3w • No prior systemic anticancer therapy • Child-Pugh Class A Randomization • EC
Slide 124: CheckMate 9ER: Phase 3 Cabometyx/IO combination in 1L RCC
CheckMate 9ER: Phase 3 Cabometyx®/IO combination in 1L RCC Sponsored by BMS/Exelixis Cabozantinib 40mg QD CheckMate 9ER Randomization + • Randomized, Open-Label, Ph3 Nivolumab 240mg Q2W • Cabozantinib + Nivolumab vs. N= ~650 1:1 sunitinib patients1 • All risk groups with previously- untreated advanc
Slide 125: Additional potential indications for Cabometyx
Additional potential indications for Cabometyx® COSMIC-021: Cabometyx® / atezolizumab in multiple tumors (sponsored by Exelixis/Roche) • 20 cohorts ongoing • Top-line results (from multiple cohorts) expected when cohort are fully enrolled and data has matured Cabometyx® monotherapy • Ewing sarcoma •
Slide 126: Onivyde (irinotecan liposomal injection)
Onivyde® (irinotecan liposomal injection)
Slide 127: 1L mPDAC Development: Phase 1/2 → Pivotal
1L mPDAC Development: Phase 1/2 → Pivotal Part 1: Single-arm study of previously untreated, Part 2: Planned Pivotal Study metastatic pancreatic cancer patients Phase 1 (dose finding): Completed; Phase 2 dose • Superiority design vs. Gem/Abx selection • Futility and Interim analyses included NAPOX =
Slide 128: 2L SCLC Development: Phase 2/3 Seamless Design
2L SCLC Development: Phase 2/3 Seamless Design Part 1: Phase 2a single arm study in 2L SCLC Part 2: Phase 3 randomized controlled trial patients who progressed from 1L platinum treatment • Enrollment completed (n=30) • Superiority design vs. Topotecan (SOC) • Part 1 results expected: H2 2019 • Prima
Slide 129: Phase 1 trial in Metastatic Breast Cancer (mBC)
Phase 1 trial in Metastatic Breast Cancer (mBC) Phase 1 study • Phase 1 study completed (n=30) • Results suggest Onivyde monotherapy has clinically meaningful anti-tumor activity, presented at 2019 AACR Meeting1 • HER2-, HR+ mBC patients: ORR 40% • TNBC patients: ORR 33% • Patients with active metas
Slide 130: Additional potential indications for Onivyde
Additional potential indications for Onivyde® Recurrent glioblastoma multiforme (rGBM) • Significant unmet medical need • Ongoing IST (UCSF): Promising signal of Onivyde intrathecal injection in recurrent GBM1 • 7 of 10 patients on study Pediatric Solid Tumors • Ongoing IST (South Plains Oncology Co
Slide 131: Evidence-based strategy working towards Onivyde as backbone therapy
Evidence-based strategy working towards Onivyde® as backbone therapy for multiple tumor types Combinations with Pediatric (Ewing sarcoma, pediatric Others indications novel agents (DDR, IO) brain tumors (glioblastoma, ovarian) 1L PDAC 2L SCLC Phase 2 ongoing mBC Phase 2/3 study ongoing Phase 2 inter
Slide 132: IPN60090
IPN60090
Slide 133: IPN60090: Novel potent oral selective GLS1 inhibitor
IPN60090: Novel potent oral selective GLS1 inhibitor Innovative approach Development strategy • Targeted therapy for unmet medical need in multiple Monotherapy (biomarker strategy) solid tumors Tumor Cells • Targeting tumor metabolism in biomarker-selected Blocks Glutamine Metabolism Nutrient Depriv
Slide 134: Phase 1 Trial Ongoing
Phase 1 Trial Ongoing Open-label, dose escalation/expansion study to investigate safety, PK, PD and anti-tumor activity Biomarker Selected Population Part 1 IPN60090 Monotherapy NSCLC With Undisclosed Biomarker Advanced solid tumor Potential to combine with Onivyde® Part 2 susceptible to: IPN60090 +
Slide 135: Combination interest
Multiple development opportunities Onivyde® PDAC, SCLC, BC, HGSOC Leveraging Ipsen portfolio Paclitaxel Endometrial cancer Combination interest HGSOC, endometrial PARP inhibitors cancer IPN60090 Expanding PI3K α or mTOR inhibitors Breast cancer through combinations CDK4/6 inhibitors Breast cancer EG
Slide 136: Oncology R&D
Oncology R&D Creating value with Oncology pipeline Continue to search for externally Develop innovative sourced assets Maximize benefits of assets with potential to existing portfolio synergize with existing Focus on rare/ niche pipeline cancers with unmet needs 136
Slide 137: Q&A
Q&A
Slide 138: Conclusion
Conclusion → Excellent business momentum across all major Specialty Care products and geographies → Maintain strong top-line growth and continued margin expansion → Strongest ever company R&D pipeline advancing first/best-in-class innovative assets → Mission to bring innovative, life-altering treatm