Hutchmed (china) Limited · HKEX:13
Hutchmed (china) — Hutchmed — Investor Presentation (June 2021)
126 slides from Hutchmed (china)'s investor presentation, June 2021
Slide 1: Corporate Presentation June 2021
CORPORATE PRESENTATION JUNE 2021 Nasdaq / AIM: HCM
Slide 2: Safe Harbor Statement & Disclaimer
Safe Harbor Statement & Disclaimer The performance and results of operations of the HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results. This presentation contains forward-looking statements within the meaning of the “saf
Slide 3: 1. Overview
1. OVERVIEW
Slide 4: Building a global science-focused biopharma
Building a global science-focused biopharma Global novel oncology drug discovery & manufacturing operations based in China Clinical development and regulatory operations in all major markets In-house commercial in China & U.S. – self-determination in about half of global pharma market Commercial par
Slide 5: Our Strengths
Our Strengths Fully integrated 1,300+ person R&D and commercialization platform built over 20 years 1 2 3 4 WORLD CLASS HIGHLY DIFFERENTIATED DEEP PAN-CHINA SEASONED MNC MGMT. DISCOVERY & NME PORTFOLIO & MARKET ACCESS TEAM – STRONG DEVELOPMENT GLOBAL PIPELINE CAPABILITY GOVERNANCE CAPABILITY First g
Slide 6: Differentiated portfolio
Differentiated portfolio 2 HIGHLY DIFFERENTIATED NME PORTFOLIO AND GLOBAL PIPELINE All discovered in-house & designed for global differentiation PRODUCT MOA DISCOVERY[1] INDICATIONS PARTNER RIGHTS CHINA[2] GLOBAL[2] VEGFR 1/2/3, Neuroendocrine tumors (NET), Surufatinib In-house Marketed (non-pNET) U
Slide 7: 2. Oncology Commercial Operations
2. ONCOLOGY COMMERCIAL OPERATIONS
Slide 8: 3 novel drugs launched / in review
3 novel drugs launched / in review 2021 Oncology consolidated revenues guidance $110-$130 million (vs. 2020 $30.2m actual) Fruquintinib China commercial Surufatinib launched in China Savolitinib potential approval responsibility assumed Oct 2020 Jan 2021 as early as Q2 2021 Receiving 70-80% of in-ma
Slide 9: 500+ person oncology commercial team
500+ person oncology commercial team Expanding rapidly to support ELUNATE® and SULANDA® launches Broad drug marketing and distribution capabilities 2,500+ oncology hospitals and with long-standing operational track record 20,000+ oncology physicians covered • Fully in-place since mid-2020; in traini
Slide 10: ELUNATE coverage and key opportunities
ELUNATE® coverage and key opportunities Sales benefitting from deeper coverage… Increased on-the-ground activities HUTCHMED Oncology team May 31, 2021 vs. Sept 30, 2020 involved since Q4 2020 Hospital pharmacy ~380 +95% listings FY 2019 FY 2020 Q1-Q3 2020 Q4 2020 Q1 2021[3] Commerical ~520 on-the-gr
Slide 11: SULANDA launch
SULANDA® launch Executed within 3 weeks of NDA approval…just beginning Dec 30, 2020 Jan 14, 2021 Jan 19, 2021 Jan 29, 2021 Mar 31, 2021 NDA Approved First order shipped First Prescribed Prescription in 30 provinces $5.5 million[1] in 1st quarter on market Patient access Eligible to negotiate for N
Slide 12: US Commercial Team Taking Shape
US Commercial Team Taking Shape Commercial Leadership positions filled 2021 Critical Deliverables • Insights framework, Brand Plan, Launch Plan VP, Sales and Training VP, Marketing 25+ Years of Pharma 25+ Years of Pharma • Development of Global Experience Experience Value Dossier, Pricing 20+ Oncolo
Slide 13: 3. Clinical Development Updates
3. CLINICAL DEVELOPMENT UPDATES
Slide 14: Surufatinib recap: Unique MOA differentiation
Surufatinib recap: Unique MOA differentiation Potentially enhance immune-mediated anti-tumor effect in addition to anti-angiogenesis Inhibits VEGFR1/2/3 & FGFR1 – blocking Synergistic effect with PD-1 inhibitors in vascular cell growth and angiogenesis NET/NEC, which had showed limited activity to d
Slide 15: Surufatinib: Monotherapy efficacy across NETs
Surufatinib: Monotherapy efficacy across NETs • >800 patients in clinical trials to date • Proven single-agent efficacy: SANET-ep & SANET-p Phase IIIs met endpoints at interim • China approved for non-pancreatic NET; NDA in review for pancreatic NET • US NDA submitted Non-Pancreatic[1] (SANET-ep, n=
Slide 16: Surufatinib: NET registration update
Surufatinib: NET registration update CHINA GLOBAL Extra-pancreatic (non-pancreatic) NET US FDA NDA submitted April 2021 • NDA approved Dec 2020 • Fast Track Designations for both pNET & non-pNET • Launched Jan 2021 • Orphan Drug designation granted for pNET • Preparing for NRDL discussion • FDA deci
Slide 17: Surufatinib: Promising PD-1 combos
Surufatinib: Promising PD-1 combos Planning first Phase III in China in ≥2L NEC with Junshi; additional registration studies under discussion ASCO Surufatinib PD-1 Studies Summary 2021 Surufatinib + Surufatinib + Lenvatinib + ABSTRACT toripalimab [1] toripalimab [2] pembrolizumab [3] PD-1 Patient fo
Slide 18: Surufatinib PD-1 combos global aspirations
Surufatinib PD-1 combos global aspirations Surufatinib + Tislelizumab (PD-1 mAb) first patient enrolled in March 2021 Part 1 – Dose Finding Part 2 – Expansion Cohorts all-comers indication-specific cohorts A: 4L Colorectal Cancer Rationale Dose Level 2 • Global aspirations SURU 300mg QD B: 2L Neuroe
Slide 19: Fruquintinib recap: Highly selective to VEGFR
Fruquintinib recap: Highly selective to VEGFR Efficacy with limit off-target toxicity • Potent against VEGFR1,2,3, resulting in consistent VEGFR 1 VEGFR 2 VEGFR 3 clinical benefit for patients who failed bevacizumab • Highly selective vs. other kinases with good safety profile with readily manageabl
Slide 20: FRESCO-2 to support 3L+ mCRC US/EU/JP NDA
FRESCO-2 to support 3L+ mCRC US/EU/JP NDA Regulatory alignment on fruquintinib across all major markets FRESCO PHASE III (≥3L CRC): Basis for US, EU, Japan filings OVERALL SURVIVAL FRESCO US FRESCO-2 FDA NDA 9.30 months vs. 6.57 months China Ph Ib Global & Stratified HR (95% CI): 0.65 (0.51–0.83) Ph
Slide 21: Fruquintinib: PD-1 inhibitor combinations
Fruquintinib: PD-1 inhibitor combinations Durable benefit seen in advanced colorectal cancer ASCO ASCO 2021 2021 Fruquintinib PD-1 studies Summary Fruq mono Lenvatinib + PD-1 Patient focus Status/ plan Fruq + ABSTRACT Ph. III Fruq + pembro- geptano- TYVYT® CRC CN Phase II ongoing (FRESCO) sintilimab
Slide 22: Fruquintinib: Development summary
Fruquintinib: Development summary Current development status and next steps CHINA GLOBAL FRUTIGA: Phase III in 2L gastric cancer ongoing Colorectal cancer • Expect fully enrolled around YE 2021 • FRESCO-2 Phase III initiated in U.S., EU & Japan • Top-line data expected H2 2022 • U.S. Phase Ib/II com
Slide 23: Savolitinib recap: MoA and data summary
Savolitinib recap: MoA and data summary Designed to avoid known renal toxicity while retaining potency Quinolinone metabolite in 1st-gen MET compounds has low solubility in Evidence of clinical differentiation humans and when metabolized by the kidneys, appeared to crystallize, resulting in obstruct
Slide 24: Savolitinib: MET Exon14 skipping alterations
Savolitinib: MET Exon14 skipping alterations Encouraging anti-tumor activity across multiple settings in NSCLC NSCLC with MET Exon14 skipping alterations Phase II in NSCLC harboring MET Exon 14 skipping alterations (data by IRC) • 2-3% of NSCLC, up to 22% in PSC • Most common in elderly patients Chi
Slide 25: EGFR TKI refract. NSCLC w/ MET amplification
EGFR TKI refract. NSCLC w/ MET amplification Phase III registration studies are being planned in combinations with TAGRISSO® (osimertinib) SAVANNAH: Broadest TAGRISSO® refractory TATTON D population – FISH+ and/or IHC+ line agnostic TATTON B Savo 300mg Savo 600mg [1] + TAGRISSO® + TAGRISSO® 2L/3L EG
Slide 26: Savolitinib: Promising in MET-driven PRCC
Savolitinib: Promising in MET-driven PRCC Global Phase III trial in planning in combination with IMFINZI® (durvalumab) SAVOIR: Single agent anti-tumor activity in MET-driven PRCC CALYPSO: IMFINZI® (PD-L1i) combination activity[2] All 9 savo responders remained in response at data cut-off Highly corr
Slide 27: Savolitinib recap: MET ampl. in gastric cancer
Savolitinib recap: MET ampl. in gastric cancer Initiating Phase II trial in China VIKTORY: Best tumor response (savolitinib arm) VIKTORY: Duration of response (savolitinib arm) 100 80 Partial Response 60 Stable Disease Progressive Disease / Not Evaluable maximum tumor reduction (%) 40 20 0 ≥10 copy
Slide 28: Savolitinib development summary
Savolitinib development summary CHINA GLOBAL MET Exon14 skipping NSCLC MET-driven PRCC • NDA under review • Phase III registration study • On track for mid-2021 approval • Savolitinib + IMFINZI® vs. sunitinib in MET-driven PRCC 2L EGFR TKI refractory NSCLC with MET amplification • Expected study ini
Slide 29: Next wave of innovation
Next wave of innovation Current development status summary HMPL-689 & HMPL-523 HMPL-453 HMPL-306 HMPL-295 • China Ph.Ib dose • Ph.II initiated in IHCC in • Addresses mutant IDH • 10th in-house discovered expansions underway; China; switching, from IDH1 to asset (ERK, MAPK • U.S. & EU Ph.I multiple •
Slide 30: HMPL-689 Recap: Highly selective PI3Kδ inhibitor
HMPL-689 Recap: Highly selective PI3Kδ inhibitor First in our next wave of innovation B-cell signaling is critical in hematological cancer Designed to be a global best-in-class inhibitor of PI3Kδ B-Cell Receptor RITUXAN® TNFα IL-6 Receptor • Improved isoform selectivity CD79 TNFα Receptor (sparing P
Slide 31: HMPL-689 recap: Dose escalation data (ASH)
HMPL-689 recap: Dose escalation data (ASH) Promising clinical activity in multiple tumor types Best Response of Target Lesions in Dose Escalation Stage (ITT N=56) CLL/SLL DLBCL FL HL MCL MZL +80% +60% Best change from baseline +40% +20% 0% -20% -40% PR -60% -80% -100% Overall Response Rate 48% (35-6
Slide 32: HMPL-689 recap: Dose escalation data (ASH)
HMPL-689 recap: Dose escalation data (ASH) Well tolerated with a favorable safety profile Incidence of select treatment emergent adverse events – all AEs / grade ≥3 AEs HMPL-689[1] Zydelig® Aliqopa® Copiktra® Ukoniq® Parsaclisib Parsaclisib Zandelisib Zandelisib (idelalisib)[2] (copanlisib)[2] (duve
Slide 33: HMPL-689: Development summary and registration pathway
HMPL-689: Development summary and registration pathway CHINA GLOBAL Monotherapy U.S. & EU Ph.I multiple dose cohorts complete • FL / MZL registration study ongoing ‒ NDA submission potentially late 2022 / early 2023 Next steps • Additional indications will be planned • Evaluate efficacy signals usin
Slide 34: 2021: Another busy year for HUTCHMED
2021: Another busy year for HUTCHMED • 2L EGFR TKI refractory NSCLC, China; 2L EGFR TKI refractory Savolitinib: 5 NSCLC, global; 1L EGFRm+ with MET overexpression, China; MET driven PRCC, global; MET amplified GC 10 new Surufatinib: 1 • 2L NEC, in combination with toripalimab registration Fruquintin
Slide 35: 4. Estimated Incidence in Main Target Indications
4. ESTIMATED INCIDENCE IN MAIN TARGET INDICATIONS
Slide 36: Savolitinib market potential
Savolitinib market potential Potential first-in-class selective METi in China – global studies planned in NSCLC & PRCC Est. Annual Incidence (’000) [1, 2, 3] Median DOT [4] China U.S. EU5 Japan Total Colorectal 4 3 3 1 11 TBD MET+ EGFR ref. Esophageal 16 1 1 1 20 TBD MET Gene Ampl. Gastric 8.0 mo. 2
Slide 37: Fruquintinib market potential
Fruquintinib market potential Best-in-class selective VEGFRi – global monotherapy in 3rd line CRC; expand through chemo/PD-1 combinations in earlier line settings Est. Annual Incidence (’000) [1, 2, 3] Median China U.S. EU5 Japan Total DOT [4] Endometrial TNBC, RCC, HCC, NSCLC TBD TBD TBD TBD TBD TB
Slide 38: Surufatinib market potential
Surufatinib market potential Best-in-class VEGFRi with synergistic activity – global monotherapy in Advanced Grade 1/2 NET; expand through PD-1 combinations in earlier line settings Est. Annual Incidence (’000) [1, 2, 3] Median China U.S. EU5 Japan Total DOT [4] Esophageal, Biliary Tract, SCLC, Gast
Slide 39: HMPL-689 market potential
HMPL-689 market potential Emerging hematological malignancies asset – global and China development moving now in parallel in multiple indolent NHL indications Est. Annual Incidence (’000) [1, 2, 3] Median China U.S. EU5 Japan Total DOT [4] iNHL: Diffuse Large B-cell Lymphoma 11 9 8 4 32 TBD 2nd Line
Slide 40: HMPL-523 market potential
HMPL-523 market potential Emerging immunology and hematological malignancies asset – first approval opportunity in ITP – global opportunity in BTKi refractory indolent NHL Est. Annual Incidence (’000) [1, 2, 3] Median China U.S. EU5 Japan Total DOT [4] Indolent NHL (MCL, MZL, CLL/SLL, WM) 1 13 10 5
Slide 41: 5. Potential Upcoming Clinical & Regulatory Milestones
5. POTENTIAL UPCOMING CLINICAL & REGULATORY MILESTONES
Slide 42: Potential upcoming events
Potential upcoming events Clinical & regulatory milestones in US, EU & Japan Early ’21 Mid ’21 Late ’21 2022 NETs mono. NDA US NDA submission Surufatinib Solid tumors Ph. Ib/IIs Tislelizumab PD-1 combo start (VEGFR 1/2/3; FGFR1; & NETs mono. MAA EU MAA submission** ⍟ CSF-1R inhibitor) NETs mono.
Slide 43: Potential upcoming events
Potential upcoming events Clinical & regulatory milestones in China Early ’21 Mid ’21 Late ’21 2022 non-pNET Market Approval & launch Surufatinib NEC & GC PD-1 combo Ph. Ib/II TUOYI® PD-1 combo data (ASCO) (VEGFR 1/2/3; FGFR1; & pNET Market Approval & launch** ⍟ CSF-1R inhibitor) PD-1 combo Ph.
Slide 44: 6. Financial Results, Guidance and Summary
6. FINANCIAL RESULTS, GUIDANCE AND SUMMARY
Slide 45: Condensed Consolidated Balance Sheet
Condensed Consolidated Balance Sheet (in $’000) As of Dec 31, As of Mar 31, Cash Position 2019 2020 2021 (at end March 2021) Assets Cash, cash equivalents & short-term investments 396,072 • $396m cash / cash eq. / ST inv. [1] 217,168 435,176 Accounts receivable 43,254 47,870 53,822 • $69m unutilized
Slide 46: Condensed Consolidated Statement of Operations
Condensed Consolidated Statement of Operations (in $’000, except share and per share data) Year Ended Dec 31, Quarter Ended Mar 31, 2021 Guidance 2019 2020 2020 2021 Revenues: • $110-130m in consolidated Oncology/Immunology – Mktd Prod. 10,766 19,953 2,884 18,840 Oncology/Immunology Oncology/Immunol
Slide 47: Summary
Summary Leveraging powerful China commercial expertise, ~600 person oncology team end 2021 Oncology Commercial 2021 Oncology consolidated revenues guidance $110-130 million US org. preparing for 1st US launches – potentially suru early 2022 & fruq 2023 Starting multiple global & China registration s
Slide 48: Thank you
Thank you www.hutch-med.com
Slide 49: Appendix
APPENDIX A1 Strategies Realizing global potential of novel oncology assets Building a fully integrated oncology business in China & US A2 Product Candidate Details A3 Manufacturing Expertise A4 Further Corporate Information
Slide 50: A1 HUTCHMED Strategy
HUTCHMED Al HUTCHMED STRATEGY
Slide 51: World class discovery engine
World class discovery engine 1 WORLD-CLASS DISCOVERY & DEVELOPMENT CAPABILITY Most prolific & validated in China biotech Focus on Global Quality Innovation HUTCHMED’s Advanced Chemistry Approach Provides Proven & Validated at All Levels Superior Selectivity Profiles 53 year track record in oncology,
Slide 52: Established global C&R infrastructure
Established global C&R infrastructure 1 WORLD-CLASS DISCOVERY & DEVELOPMENT CAPABILITY Track record of breakthroughs 2 HIGHLY DIFFERENTIATED NME PORTFOLIO AND GLOBAL PIPELINE Integrated development team of 120+ C&R & ~200 Fruquintinib (ELUNATE® in China) CMC staff located in Shanghai, Suzhou & Florh
Slide 53: 6 assets in global development
6 assets in global development 2 HIGHLY DIFFERENTIATED NME PORTFOLIO AND GLOBAL PIPELINE Rapid expansion of our US/EU clinical & regulatory team Program Treatment Indication Target patient Study name Sites Dose finding / safety run-in Proof-of-concept Registration Savolitinib + TAGRISSO® NSCLC 2L/3L
Slide 54: 9 assets in China development
9 assets in China development 2 HIGHLY DIFFERENTIATED NME PORTFOLIO AND GLOBAL PIPELINE …8-10 registration studies planned to start in 2021 Program Treatment Indication Target patient Study name Sites Dose find / safety run-in Proof-of-concept Registration Savolitinib NSCLC MET Exon 14 skipping Chin
Slide 55: China Commercial operations infrastructure
China Commercial operations infrastructure 3 CAPABILITY DEEP PAN-CHINA MARKET ACCESS HUTCHMED leverages strong scale and capabilities from two organizations Nationwide distribution Oncology focus, deep disease Third-party distribution & promotion expertise & logistics 2,200+ sales reps 520+ (and
Slide 56: Seasoned executives – MNC veterans
Seasoned executives – MNC veterans 4 SEASONED MGMT TEAM & STRONG GOVERNANCE Global standards – Reputation & transparency Management Team Selected Shareholders Christian Hogg Weiguo Su Johnny Cheng Junjie Zhou Chief Executive Chief Scientific Chief Financial General Officer Officer Officer Manager, S
Slide 57: A1a Realizing Global Potential of Novel Oncology Assets
A1a REALIZING GLOBAL POTENTIAL OF NOVEL ONCOLOGY ASSETS
Slide 58: Attack cancer from multiple angles at same time
Attack cancer from multiple angles at same time Need combinations of potent, yet tolerable drugs against specific targets Immune Desert Excluded Infiltrate Insufficient T cell response Inadequate T cell homing Chemotherapies Anti-angiogenics Vaccines Stromal targets CAR-T (pro-inflammatory
Slide 59: Immunotherapy combinations
Immunotherapy combinations assets potentially ideal TKI combo partners for immunotherapy 1L Clear Cell Renal Cell Carcinoma [1] INLYTA® LENVIMA® Fruquintinib Surufatinib Selective angio- Relatively Objective Response Rate 59% Selectivity selective Relatively selective Highly selective immuno kinase
Slide 60: Maximizing the value of our lead assets
Maximizing the value of our lead assets 2 marketed products, 3 NDAs under review & 8-10 reg. studies by mid-2021 Dose Finding / Proof-of-Concept Registration Intent NDA Filed / Marketed Safety Run-In TAGRISSO® ref. MET+ NSCLC MET Exon 14 skipping NSCLC TAGRISSO ref. MET+ NSCLC TAGRISSO® combo (SAVAN
Slide 61: Deep NME early pipeline
Deep NME early pipeline Multiple further waves of innovation progressing Dose Finding/ IND preparation Proof-of Concept Registration Intent Safety Run-In HMPL-689 iNHL (CBCL, CLL, FL, MCL, MZL, 6 iNHL settings (FL, MZL, MCL, DLBCL, iNHL – Ph.II (multiple iNHL studies) (Registration) PI3Kδ inhibitor
Slide 62: Early programs summary
Early programs summary • Phase II in iHCC with FGFR2 fusion enrolling HMPL-453 • Early signs of clinical activity (FGFR1/2/3) • Combinations study IND planned mid-2021: 1L chemo & IO combos • Potent IDH1/2 inhibitor with brain penetration • Designed to overcome resistance due to isoform conversion H
Slide 63: Three new INDs planned for 2021
Three new INDs planned for 2021 • Reversible, non-covalent, potent against both wild type & C481S mutant enzymes HMPL-760 • Improved potency in in vivo models vs. ibrutinib and ARQ-531 (3rd gen BTK) • Potential for combinations with HMPL-689 (PI3Kδ), HMPL-A83 (CD47) • IND submission mid-2021 in both
Slide 64: Discovery Project Overview
Discovery Project Overview 01 02 03 Small molecules Large molecules New technology Six ongoing projects Multiple mAb and Initiating bsAb projects ongoing Apoptosis CD47-based PROTAC Cell signaling antibody platform Antibody-Drug Epigenetics Conjugate Protein translation 64
Slide 65: A1b Building a Fully Integrated Oncology Business in China & US
A1b BUILDING A FULLY INTEGRATED ONCOLOGY BUSINESS IN CHINA & US
Slide 66: China and US are key oncology markets
China and US are key oncology markets CHINA US ~25% of world cancer patients [1] ~40% of global oncology medicine spending [4] [5] Industry’s attention turning to unmet medical need Innovation is being rewarded in China oncology Oncology medicine spending grew to $72 billion in 2020 from $45 billi
Slide 67: HUTCHMED competence in China operations
HUTCHMED competence in China operations A 17-year track record of 19% CAGR net income growth in our Other Ventures businesses 73 [3] 70 [3] Net Income/(Loss) NI to 2007-2020 attrib. to HUTCHMED [1] Total NI [2] HUTCHMED CAGR Other Ventures Base Operations 675 312 +19% One-time Gains 158 72 44 41 42
Slide 68: International development
International development Rapid expansion of our US/EU clinical & regulatory team, progressing a broad clinical portfolio of trials and regulatory engagements H1 2021 H2 2021 Suru Suru NET (US) NET (EU) Completed rolling NDA Sub MAA Submission* Suru + Tislelizumab PD-1 combo Ph. Ib/IIs Start F
Slide 69: A2a Savolitinib
A2a SAVOLITINIB A highly selective small molecule inhibitor of MET being developed broadly across MET-driven patient populations in lung cancer, gastric cancer and renal cell carcinoma
Slide 70: NSCLC by driver aberration
NSCLC by driver aberration Biggest opportunity is MET+ (mutant / gene amplified) NSCLC Primary NSCLC Resistance-driven EGFRm+ NSCLC 1.8 million NSCLC TAGRISSO® patients relapse patients per year 1L Median PFS 19 months. MET+ MET+ Other Other ~6% EGFRm ~10% MET+ / Unknown (T790M-) ~30% T790M+ MET+ SC
Slide 71: Savolitinib – MET Exon 14 skipping NSCLC
Savolitinib – MET Exon 14 skipping NSCLC China’s lead selective MET inhibitor Competitive landscape outside China: MET mDoR Treatment Line aberration N BICR[1] ORR (%) DCR (%) (months) mPFS (months) Capmatinib [2] [3] 1L (cohort 5b) Ex14 skipping 28 68 [48, 84] 96 [82, 100] 12.6 [5.6, NE] 12.4 [8.2,
Slide 72: TATTON B & D data – PFS
TATTON B & D data – PFS TAGRISSO® + savolitinib in EGFR TKI refractory NSCLC Median (range) 1.0 Median PFS, duration of response, 0.9 months [95% CI] months 0.8 progression-free survival Part B1 0.7 Prior third-generation EGFR-TKI; 5.5 [4.1, 7.7] 9.5 [4.2, 14.7] Probability of 0.6 (600 mg [1] ; n=69
Slide 73: TATTON B & D data – AEs & tolerability
+ savo in EGFR TKI refractory NSCLC TATTON B & D data – AEs & tolerability Event, n (%) All Part B (n=138) Part D (n=42) osimertinib 80 mg osimertinib 80 mg + savolitinib 600 mg [1] + savolitinib 300 mg [1] Any AE 138 (100) 41 (98) Any AE possibly related to savolitinib 124 (90) 32 (76) AE grade ≥3
Slide 74: TATTON B & D data – AEs & SAEs
TATTON B & D data – AEs & SAEs Most common AEs[1] independent of causality & SAEs (≥3%)[2] All Part B (n=138) Part D (n=42) All Part B (n=138) Part D (n=42) AE*, n (%) AE*, n (%) All Grade All Grade All grades Grade ≥3 All grades Grade ≥3 grades ≥3 grades ≥3 Rash 26 (19%) 3 (2%) 8 (19%) 0 Nausea 67
Slide 75: Savolitinib – MET+ gastric cancer
Savolitinib – MET+ gastric cancer A major problem in east Asia – Japan, Korea & China 1. Gastric (stomach) cancer is the 4th most common cancer 2. MET+ disease is more aggressive [1] globally – 768,000 deaths/year 1.0 MET amp. -ve mOS: 68.7 mo 0.9 MET amp. +ve mOS: 28.6 mo 0.8 Survival probability 1
Slide 76: A2b Surufatinib (SULANDA in China)
A2b SURUFATINIB (SULANDA® IN CHINA) A small molecule inhibitor of VEGFR, FGFR & CSF-1R designed to inhibit tumor angiogenesis and promote the body’s immune response against tumor cells via tumor associated macrophage regulation
Slide 77: Surufatinib: Overview of NET
Surufatinib Overview of NET – 140,000~170,000 patients in the U.S. [1][2][3] NET growth – better diagnosis [4] What are neuroendocrine tumors (“NET”)? Incidence per 100 000 for Neuroendocrine Tumors Incidence per 100 000 for All Malignant Neoplasms • ~2% of all malignancies • Tumor begins in the spe
Slide 78: High-level NET landscape
High-level NET landscape Long-term disease – rapid deterioration in later stages [1][2][3] Grade 1 (G1) NET G1/2 – Advanced NET G3 – NET/NEC Localized / Regional Regional / Distant Distant ~8-35% NET patients Somatostatin Analogue ~60% NET patients – first No approved – Functional NET – Treatment –
Slide 79: G1/2 Advanced NET
G1/2 Advanced NET [1] (Ki-67 Index 0-20) Global China Global opportunity in lung/other NETs & China wide-open Octreotide Lanreotide Site est. % 177Lu-Dotatate Streptozocin Sunitinib Everolimus Surufatinib LAR autogel Progressed in past Progressed in past Progressed in past Disease status Treatment n
Slide 80: 140,000~170,000 NET patients in U.S.
140,000~170,000 NET patients in U.S. [1][2] U.S. NET treatment landscape – highly fragmented Somatostatin Based Therapies Kinase Inhibitor Therapies Sandostatin® LAR Somatuline Depot® Lutathera® Afinitor® Sutent® Surufatinib (octreotide) (lanreotide) (177Lu-Dotatate) (everolimus) (sunitinib) (Approv
Slide 81: Surufatinib: US NET Market Landscape
Surufatinib: US NET Market Landscape A rare heterogeneous tumor that presents in the metastatic stage in 40-50% of patients NETs are relatively rare and heterogeneous tumor type, PERCENT OF NETS CASES BY LOCATION1 comprising ~2% of all malignancies1,2 ~15% ~7% US 2021 estimates: 1,3 Pancreatic • 140
Slide 82: Surufatinib: US extrapancreatic NET Prescriber Level Data
Surufatinib: US extrapancreatic NET Prescriber Level Data < 10% of eligible patients are prescribed everolimus or sunitinib in 2018 IQVIA’s medical claims and prescription data longitudinal databases track patients over time and not dependent on insurance carrier, pharmacy, or employer. • 1.0 billio
Slide 83: US NET Phase Ib bridging study
US NET Phase Ib bridging study Encouraging surufatinib efficacy in everolimus & sunitinib refractory/intolerant patients 8 12 33X10 PR Confirmed PR (n=3) surufatinib 24 2 15 X uPR Unconfirmed PR (n=1) 12 8 X Treatment ongoing (n=5) everolimus 3 11 2 4 15 PR X Rx stop – AE (n=1) sunitinib 2 3 10 6 2
Slide 84: G1/2 Advanced extra-pancreatic NET
G1/2 Advanced extra-pancreatic NET Investigator assessed median PFS SANET-ep [1] (n=198) RADIANT-4 [2] (n=302) Surufatinib: 9.2 months (95% CI 7.4, 11.1) Everolimus: 14.0 months (95% CI, 11.24-17.71) 1.0 Placebo: 3.8 months (95% CI 3.7, 5.7) 1.0 Placebo: 5.5 months (95% CI, 3.71-7.39) 0.9 HR = 0.334
Slide 85: G1/2 Advanced pancreatic NET
G1/2 Advanced pancreatic NET Investigator assessed median PFS (primary endpoints) SANET-p [1] (n=172) RADIANT-3 (everolimus) [2] (n=410) 100 Everolimus: 11.0 mths (95% CI, 8.4-13.9) Surufatinib: 10.9 months (95% CI 7.5, 13.8) Probability of Progression- 80 Placebo: 4.6 mths (95% CI, 3. 1-5.4) Placeb
Slide 86: Surufatinib vs. everolimus and sunitinib
Surufatinib vs. everolimus and sunitinib Broader range of tumor origins & later-stage patients Asia/China SANET-ep [1] U.S. RADIANT-4 [2] SANET-ep Extra- (n=198) Extra- (n=302) Enrolled more pts with poor prognosis. Pancreatic (surufatinib vs Pancreatic (everolimus vs NET placebo) NET placebo) Survi
Slide 87: A2c Fruquintinib (ELUNATE in China)
A2c FRUQUINTINIB (ELUNATE® IN CHINA) A highly selective small molecule inhibitor of VEGFR 1/2/3 designed to improve kinase selectivity to minimize off-target toxicity and thereby improve tolerability
Slide 88: Fruquintinib & surufatinib both unique VEGFR TKIs
Fruquintinib & surufatinib both unique VEGFR TKIs …potentially ideal VEGFR combos for immunotherapy TKI 1st Generation 2nd Generation Next Generation Selective angio-immuno Selectivity Multiple targets Relatively selective Highly selective kinase inhibitor Inhibitors Sutent® Nexavar® Focus V® Fotivd
Slide 89: Efficacy advantage
Efficacy advantage FRESCO [1] CONCUR CONCUR CORRECT Third-Line Chinese Patients Mainland China, Hong Metastatic Colorectal cancer Mainland China (Mainland China, Hong Kong, Taiwan, Vietnam, Global Kong, Taiwan) [2] South Korea Treatment arms ELUNATE® Placebo STIVARGA® Placebo STIVARGA® Placebo STIVA
Slide 90: Stivarga tox limitations
Stivarga® tox limitations BIOCHEMICAL ACTIVITY IC50 (nmol/L) IC50 (nmol/L) FRESCO Study CONCUR Study 3rd-Line Metastatic Colorectal cancer Mainland China [1] (Mainland China, HK, Taiwan) [2] On-Target Kinases: VEGFR1 33 13 Treatment arms ELUNATE® Placebo STIVARGA® Placebo VEGFR2 35 4.2 Patients (n)
Slide 91: NRDL
NRDL 2020 accessible pricing Epidemiology National Reimbursement Drug List (NRDL) China Annual Incidence Effective Jan 1, 2020: 550,000 patients [1] ● 8 newly listed oncology drugs, including ELUNATE® ● NRDL reimburses 50-70% of patient costs under urban scheme Surgery 1 st-line treated ~15% [2] Wit
Slide 92: Fruquintinib: US CRC Landscape Overview
Fruquintinib: US CRC Landscape Overview [1] Approved Stivarga (rego) & Lonsurf (TAS-102) used 20% to 30% in 3L+ patients Unmet need remains high in refractory setting CRC Current and Future Market Situation Percent of Cases by Stage at Diagnosis [3] • Total value of CRC market expected to increase f
Slide 93: US data supporting FRESCO-2 initiation
US data supporting FRESCO-2 initiation AACR, ASCO & ESMO presentations demonstrate compelling preliminary monotherapy efficacy and safety in heavily pre-treated US CRC patients US Ph. Ib: 81% stable disease in evaluable pts (ESMO’20) Global FRESCO-2 initiated September 2020 Eligibility Median Durati
Slide 94: Gastric combo with paclitaxel
Gastric combo with paclitaxel Phase 2 results supports ongoing Phase III FRUTIGA 1.1 Dose proportional increase of fruquintinib AUC at steady state. 3.3 Encouragingly low level of dose reduction/interruption. Actual 30%+ increase in paclitaxel exposure (mean AUC0-8) after multiple mean administered
Slide 95: FRUTIGA – 2L gastric combo with paclitaxel
FRUTIGA – 2L gastric combo with paclitaxel Ongoing – interim futility analysis Jun 2020 (~200 OS events) Gastric (stomach) cancer is the 5th most common FRUTIGA study design cancer globally –769,000 deaths/year 1,089 New cases ('000) Patient eligibility Fruquintinib 4mg QD 3/1 + 470 • Gastroesophage
Slide 96: FALUCA – Third-line NSCLC Monotherapy
FALUCA – Third-line NSCLC Monotherapy Presented at WCLC 2019 FALUCA Phase III Efficacy Endpoints (Intent-to-Treat) [2] Good safety; most Grade ≥3 TEAEs target- related & clinically manageable. (enrolled Dec 2015 to Feb 2018) Patient (%) Fruq. (N=354) Pbo (N=173) • Met all secondary endpoints: mPFS;
Slide 97: A2d HMPL-689 & HMPL-523
A2d HMPL-689 & HMPL-523 Targeting B-cell signaling for hematological cancers and immunology
Slide 98: HMPL-689 – finding major room for improvement
HMPL-689 – finding major room for improvement Safety profiles of current PI3Kδ inhibitors are not good PI3Kδ inhibitors being developed in a broad range of indications. Compound Company Indication Status Issue BOXED WARNING: FATAL AND SERIOUS TOXICITIES: Zydelig® Gilead Relapsed CLL/SLL, FL Approved
Slide 99: HMPL-689 – designed to be better
HMPL-689 – designed to be better Intent to improve safety… HMPL-689 – Advantages Manageable toxicity profile [1] Improved isoform selectivity – sparing PI3Kγ & PI3Kα. Treatment-emergent AEs All doses (N=56) All Grade Improved potency at whole blood level – over five-fold more occurred in ≥ 5% of
Slide 100: HMPL-689: Clinical profile being confirmed
HMPL-689: Clinical profile being confirmed China-based Phase Ib dose expansion cohorts enrolling to inform registration studies Dose expansion 30~40 pts for each cohort A: 2L+ MZL • Expansion completed – registration intent Phase II initiated B: 3L+ CLL/SLL • Expansion continuing to enroll C: 3L+ FL
Slide 101: HMPL-689: China registration intent Phase II
HMPL-689: China registration intent Phase II First patient enrolled April 2021 TWO STAGE DESIGN: HMPL-689 30mg QD, 28 days/cycle Cohort 1: R/R MZL • ≥2L after ≥1L CD20i tx STAGE I: Efficacy evaluation STAGE II: ~33 patients ≥15 CR/PR ~48 patients • N~80 Tumor evaluations (TE) • No prior PI3Ki/BTKi C
Slide 102: HMPL-689: US/EU Lymphoma Phase Ib
HMPL-689: US/EU Lymphoma Phase Ib Intl to build on China data, and engage FDA in H2 2021 Next step: Complete dose escalation in Q3 2021 Dose expansion • Dose expansion to focus on FL and MZL • End of Phase I meeting with US FDA H2 2021 to confirm registration path FL MZL Dose escalation Relapsed/ref
Slide 103: HMPL-523 (Syk) in hematological cancer
HMPL-523 (Syk) in hematological cancer Phase I/Ib ongoing in Australia, China, US & EU • Extensive Ph.I dose escalation Australia & China Phase I/Ib studies study now complete in Australia & China (total n>60); • RP2D [1] determined & large Ph. Ib Stage I: dose escalation “3 + 3” each dose cohort Co
Slide 104: HMPL-523 Global NHL Development Overview
HMPL-523 Global NHL Development Overview International to build on China data, and explore additional subgroups Next step: Complete dose escalation in Q3 2021 Dose expansion Lymphoma study: • Establish RP2D for international development n = 10 for each cohort • International expansion cohorts to sta
Slide 105: HMPL-523: Immune thrombocytopenia (ITP)
HMPL-523: Immune thrombocytopenia (ITP) Current treatments target Treg, magakaryocyte and B cells HMPL-523 • Moderate efficacy • All patients become refractory Phagocytosis / SYK degradation SYK is a validated target for ITP • Fostamatinib approved in the US • Moderate efficacy, dose limited by tox
Slide 106: A2e Next Wave of Innovations
HUTCHMED A2e NEXT WAVE OF INNOVATIONS
Slide 107: What is next from discovery?
What is next from discovery? Differentiated assets against multiple targets Priming & activations Anti-angiogenesis • VEGFR (fruquintinib) Multiple mAb • VEGFR/FGFR (surufatinib) Programs • FGFR (HMPL-453) • HMPL-A83 (CD47) Antigen release Negative regulators • Treg (HMPL-689) • MET (savolitinib) •
Slide 108: HMPL-453 – Phase II in China initiated
HMPL-453 – Phase II in China initiated Designed as best-in-class FGFR1/2/3 inhibitor 1. FGFR genetic alterations are oncogenic 2. FGFR – diverse & complicated genetic changes drivers. w/ multiple tumor types harboring low incidence. FGF/FGFR signaling normally involved in embryonic development, ti
Slide 109: Potential best-in-class IDH1/2 inhibitor
Potential best-in-class IDH1/2 inhibitor Potent IDH1/2 inhibitor with brain penetration HMPL-306 is a potent IDH1/2 dual inhibitor Unmet medical need & potential indications – • IDH1 & 2 mutations are validated targets in R&R AML IDH1/2 mutations are frequent genetic (IDH1i ivosidenib and IDH2i enas
Slide 110: MAPK pathway represents major unmet need
MAPK pathway represents major unmet need HMPL-295 – the first of several HUTCHMED assets targeting MAPK pathway The MAPK (RAS-RAF-MEK-ERK) signaling cascade • ERK (extracellular signal–regulated kinases) a key component • Pathway normal activation: ligand-dependent & tightly regulated by NF-1 and ne
Slide 111: Immunology partnership
Immunology partnership Accelerating four HUTCHMED drug candidates Overview • 4 novel preclinical drug candidates discovered by HUTCHMED for the potential treatment of multiple immunological diseases • Funded by Inmagene • Companies working together to move candidates to IND • Inmagene will pursue gl
Slide 112: A3 Manufacturing Expertise
HUTCHMED A3 MANUFACTURING EXPERTISE
Slide 113: Manufacturing strategy
Manufacturing strategy Some we control, some we outsource Small Molecule Manufacturing Large Molecule Manufacturing Global Manufacturing/ formulation (Suzhou / Shanghai) Collaborate with CDMOs • Formulation supported by HUTCHMED Suzhou • 2020-22: outsource mAb (≤$500m revenue) manufacturing to CDMOs
Slide 114: CMC Development & Manufacturing
CMC Development & Manufacturing Leadership Zhenping Wu, SVP • 13 years with HUTCHMED • 30 years in pharma manufacturing including Roche and Pfizer Analytical Drug Product Process Research Research & Manufacturing & Biologics CMC & Development Supply Chain Development • 9 years with HUTCHMED • 8 year
Slide 115: Outsourcing API manufacturing
Outsourcing API manufacturing Advancing clinical pipeline and produce commercial supplies • Work with leading CMOs in China for API manufacturing • Established strong relationships with CMOs from clinical manufacturing through commercialization • Plan to have two sites qualified for each product for
Slide 116: Drug Product and Biological Facilities
Drug Product and Biological Facilities New Shanghai factory to support production for China and global post 2025 SUZHOU FACTORY • Built to produce ELUNATE® and SULANDA® • Manufacturing talent developed • Suzhou is designed to U.S. GMP standards SHANGHAI FACTORY • Capex of $130 million over 5 years •
Slide 117: A4 Further Corporate Information
A4 FURTHER CORPORATE INFORMATION
Slide 118: Group Structure
Group Structure Main Entities / Offices Consolidated Hutchison China MediTech Non-Consolidated Group Level (Nasdaq/AIM: HCM) Oncology/Immunology Other Ventures[1] Discovery, development, manufacturing & commercialization Hutchison Sinopharm Rx Commercialization of novel oncology & immunology therape
Slide 119: Our Other Ventures have substantial value
Our Other Ventures have substantial value • HUTCHMED’s Other Ventures continue to perform well relative to our peer group. • Market value of our share of these JVs, based on China Pharma median PE multiples, approximately $0.9 billion.[1] • March 2021: agreed to divest smaller JV (OTC) for ~$169m ca
Slide 120: Non-GAAP Financial Measures & Reconciliation
Non-GAAP Financial Measures & Reconciliation Other Ventures - Reconciliation of Non-GAAP Sales and Non-GAAP Net (Loss)/Income After Tax [1] • Consolidated Subsidiaries: includes Hutchison Sinopharm and others • Non-consolidated joint venture: includes SHPL and HBYS Q1'20- IFRS US GAAP Q1'21 (US$ mil
Slide 121: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing July’17 – 15 new drugs in oncology[1] added to NRDL Unit Pricing (US$) [3] Approximate Monthly Pricing (US$) [3] Brand Avg. Avg. Company Dosage Reimbursed ∆% Dosage Reimbursed Indication coverage (generic) Tender Tender Herceptin® Breast: 4mg/kg wk 1, Roche 4
Slide 122: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing Oct’18 – 17 new drugs in oncology added to NRDL Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Avg. Avg. Brand (generic) Company Dosage Reimbursed ∆% Dosage [1] Reimbursed Indication coverage Tender Tender Focus V® (anlotinib) Sino Biopharm 12mg
Slide 123: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing Nov’19 update – 8 new drugs in oncology[1] Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Avg. Avg. Brand (generic) Company Dosage Reimbursed ∆% Dosage Reimbursed Indication coverage Tender Tender Elunate® HUTCHMED 5mg $161 $58 -64% 5mg QD 3wks/
Slide 124: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing Nov’19 update – 9 renewed drugs in oncology[1] Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Brand (generic) Company Dosage ’17 NRDL ’19 NRDL ∆% Dosage ’17 NRDL ’19 NRDL Indication coverage AiTan® Hengrui 425mg [3] $30 $27 -13% 850mg QD $1,823
Slide 125: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing Dec’20 update – 13 new oncology drugs through negotiation[1] Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Avg. Avg. Brand (generic) Company Dosage Reimbursed ∆% Dosage Reimbursed Indication coverage Tender Tender Lipusu® Luye Pharma 30mg $129
Slide 126: National Reimbursement Drug List Pricing
National Reimbursement Drug List Pricing Dec’20 update – 15 renewed drugs in oncology[1] Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Brand (generic) Company Dosage Avg. ∆% Dosage Avg. Indication coverage Reimbursed Reimbursed Tender Tender Focus V® (anlotinib) Sino Biopharm 12mg $75