Hutchmed (china) Limited · HKEX:13
Hutchmed (china) — Hutchison China MediTech (Chi-Med) — CLSA Investors' Forum 2019
115 slides from Hutchmed (china)'s conference presentation, September 2019
Slide 1: CLSA Investors' Forum
CLSA Investors’ Forum September 2019 AIM/Nasdaq: HCM
Slide 2: Safe harbor statement & disclaimer
Safe harbor statement & disclaimer The performance and results of operations of the Chi-Med 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 “safe
Slide 3: Agenda
Agenda 1 Company overview P4 2 Operating Highlights P7 3 Pipeline & Potential Upcoming Events P36 4 Financial Highlights, Cash & Guidance P39 5 Summary P42 6 Appendix P46 3
Slide 4: Company Overview
1 Company Overview
Slide 5: Building a global science-focused biopharma company from an established base in China
Building a global science-focused biopharma company from an established base in China… Global Innovation 5 clinical drug candidates in US/EU development Building global clinical development footprint World-class ~440-person scientific team China Oncology Major market potential driven by regu
Slide 6: Proven innovation & commercial operations
Proven innovation & commercial operations Industry / Chi-Med Management Team (years) Integrated Innovation Organization [1] Mr. CHRISTIAN HOGG, BSc, MBA US Office 30 / 19 Analytical 3% Medicinal Chief Executive Officer Chem. 11% Chem. 8% Dr. WEIGUO SU, PhD Pharmacology 4% 29 / 14 Process EVP, Chief
Slide 7: Operating Highlights – H1 2019
2 Operating Highlights – H1 2019
Slide 8: Main H1 2019 Operating Highlights
Main H1 2019 Operating Highlights Surufatinib Positive China Phase III – non-pancreatic NET – un-blinded a year ahead of schedule; Initiated Phase IIb/III – biliary tract cancer; & Phase I for PD-1 combos. Elunate® (fruquintinib capsules) Early progress on Elunate® – 3L colorectal cancer in Ch
Slide 9: Surufatinib: angio-immuno kinase inhibitor
Tumor-associated macrophages Mechanism of Action ` Anti-angiogenesis: cut off blood flow to tumor (VEGFR/FGFR). Immunotherapy: inhibit T-cells expression of tumor- associated macrophages which cloak cancer cells from T-cell attack (CSF-1R). Angiogenesis Surufatinib: angio-immuno kinase inhibitor 2
Slide 10: Surufatinib: Overview of NET
Surufatinib Overview of NET – ~140,000 patients in the U.S. [1][2] What are neuroendocrine tumors (“NET”)? U.S. NET epidemiology – highly fragmented Tumor begins in the specialized cells of the body’s 55~75% 10%~20% 25%~30% neuroendocrine system. Cells have traits of both Gastroentero Other/ Lun
Slide 11: Surufatinib: Existing U.S. NET treatment landscape
Surufatinib Existing U.S. NET treatment landscape – also highly fragmented Somatostatin Based Therapies Kinase Inhibitor Therapies Sandostatin® LAR Somatuline Depot® Lutathera® Afinitor® Sutent® Surufatinib (octreotide) (lanreotide) 177 ( Lu-Dotatate) (everolimus) (sunitinib) (preparing China NDA) 2
Slide 12: Surufatinib – China NET – Phase II data
Surufatinib – China NET – Phase II data [1] Broad spectrum NET efficacy incl. Sutent®/Afinitor® failure ptnts. Phase II: Pancreatic NET Phase II: Progression-Free Survival (PFS) PDs or Probability of Progression-Free Survival 20% 100% Median PFS Deaths 10% Best percent change from baseline (months)
Slide 13: Surufatinib – China NET
Surufatinib – China NET Non-Pancreatic NET estimated to represent ~80% of China NET Epidemiology – China NET & BTC patient populations Potential Annual Estimated NRDL Pricing First suru Incidence Prevalence mPFS References monotherapy China NET 100% 67,600 ~300,000 indication Non- (Est. China ratio[
Slide 14: Surufatinib – China NET competitive landscape
Surufatinib – China NET All NET est. ~$100-120m/yr. – currently under treated/diagnosed Competitive landscape – China NET treatments [1] Brand Indication/s Launched 2017 2018 Q1-2019 SUTENT® Pancr. NET 2007 Sales (US$ million) 27 24 7 (sunitinib – VEGFR) (& GIST/RCC) NRDL Pfizer List Price (US$/mont
Slide 15: Surufatinib: potentially first un-partnered oncology launch
Surufatinib Potentially our first un-partnered oncology drug launch 2 Phase III NET registration studies... 25 China sites. SANET-ep • SANET-ep Interim Analysis June 2019 – study early Surufatinib Non-pancreatic NET termination – already met mPFS endpoint; 1° endpoint: (Planned N=273) R Placeb
Slide 16: Surufatinib: Other ongoing trials
Surufatinib Other ongoing trials Phase IIb/III study in 2L BTC First patient dosed in March 2019; Nearly all planned sites now activated; Interim analysis mid-2020, based on first 80 patients; Total enrollment ~300 patients. PD-1 collaborations With Junshi (Tuoyi®): dose escalation near co
Slide 17: Elunate (fruquintinib capsules)
2b Elunate® (fruquintinib capsules)
Slide 18: 3rd-line colorectal cancer
3rd-line colorectal cancer (“CRC”) Epidemiology Launch pricing [3] Shanghai PRDL – effective June 10, 2019 China Annual Incidence Launch pricing (OOP [4]) Population covered by Shanghai PRDL [7] 380,000 patients [1] ~US$ 3,260 per cycle 15.0 million or 62% of total 24.2 million population [8] (RMB 2
Slide 19: H1 2019 performance
H1 2019 performance Elunate® Performance Sales (millions) [1] Total Cycles (OOP&PAP) [2] Chi-Med Revenue (US$ million) 12 8,000 H2-2018 H1-2019 10 $11.4 Manufacturing [3] $3.3m $3.0m (RMB 77.1) 6,000 ~6,850 Royalty 0.3 1.7 8 Total HCM Revenue 3.6 4.7 6 4,000 4 2,000 2 $1.7 ~680 (RMB 12.0) 0 0 H2-201
Slide 20: China VEGFR landscape
China VEGFR landscape Competitive landscape – small molecule VEGFR TKIs Brand Indication/s Launch 2011 2012 2013 2014 2015 2016 2017 2018 Q1-2019 STIVARGA® 3L CRC /2L GIST May 2017 Sales (US$ million) [1] 5 21 20 (regorafenib) 2L HCC Mar 2018 NRDL List Price (US$/mo.) 4,368 2,352 Bayer AG Oct-18 NEX
Slide 21: NRDL reimbursement status
NRDL reimbursement status 2019 China NRDL update – High-level process Jan - Mar Apr - Aug Aug - Sept Sept - Nov Normal NRDL Set-Up stage Review stage Announcement Products [1] • NHSA[3] Draft policy • KOL[3] consultation • Publish drug list for (updated every • KOL[3] Network • Select new drugs Norm
Slide 22: Elunate 3rd-line CRC efficacy advantage
Elunate® 3rd-line CRC efficacy advantage FRESCO [1] CONCUR CONCUR CORRECT Third-Line Metastatic Colorectal cancer Chinese Patients (Mainland China, Mainland China, Hong Kong, Mainland China Global Hong Kong, Taiwan) [2] Taiwan, Vietnam, South Korea Treatment arms Elunate® Placebo Stivarga® Placebo S
Slide 23: Elunate: Toxicity limitations of Stivarga
Elunate® Toxicity limitations of Stivarga® BIOCHEMICAL ACTIVITY IC50 (nmol/L) IC50 (nmol/L) FRESCO Study CONCUR Study On-Target Kinases: 3rd-Line Metastatic Colorectal cancer Mainland China [1] (Mainland China, HK, Taiwan) [2] VEGFR1 VEGFR2 33 35 13 4.2 Treatment arms Elunate® Placebo Stivarga® Plac
Slide 24: Ongoing trials
Ongoing trials Phase III in 2L gastric cancer (FRUTIGA) Passed first interim analysis by IDMC, trials continuing per IDMC recommendation; On track to complete enrollment Q2 2020. PD-1 collaborations With Innovent (Tyvyt®): dose/regimen finding ongoing; With Genor (genolimzumab): dose escalat
Slide 25: AstraZeneca and Chi-Med: Savolitinib
AstraZeneca and Chi-Med Harnessing the power of Chinese Innovation Savolitinib 2c
Slide 26: Savolitinib: Biggest opportunity is MET+ NSCLC
Savolitinib Biggest opportunity is MET+ NSCLC Primary NSCLC Resistance-driven EGFRm+ NSCLC All Iressa/Tarceva patients relapse Median PFS 9-10 months. 1.8 million NSCLC patients per year MET+ MET+ ~6% Other ~10% Other (T790M-) MET+ / EGFRm T790M+ MET+ ~30% SCLC/ ~6% ~30% Unknown Unknown Unknown 1st
Slide 27: Savolitinib – China's lead MET inhibitor
Savolitinib – MET Exon 14 deletion NSCLC China’s lead MET inhibitor 1. Competitive landscape outside China: Treatment Line N BICR [1] ORR 95% CI Capmatinib ASCO 2019 #9004 2/3L 69 40.6% (28/69) 28.9%, 53.1% selective MET (Novartis/ Incyte) ASCO 2019 #9004 1L 28 67.9% (19/28) 47.6%, 84.1% Tepotinib s
Slide 28: Savolitinib – MET Exon 14 deletion NSCLC
Savolitinib – MET Exon 14 deletion NSCLC [1] Potential China NDA submission in 2020 [2] 4. Encouraging MET Exon14d NSCLC Brain MRI …8 weeks later …32 weeks later study China data at AACR 2019 [3] before treatment… on savolitinib… on savolitinib… 41 pts; 31 pts efficacy evaluable. Promising antitumor
Slide 29: Savolitinib – 2L NSCLC combo with TATTON B
Savolitinib – 2L NSCLC[1] combo w/ TATTON B Study at AACR 2019 …TATTON B [2] – ...promising efficacy in MET+ T790M- Iressa/Tarceva failure patients % Enrolled % Efficacy Evaluable 2L post Iressa®/ Tarceva® Best response after treatment with savolitinib and Tagrisso # pts (n=46) (n=43) Complete or pa
Slide 30: Savolitinib – 2L/3L NSCLC combo with TATTON B
Savolitinib – 2L/3L NSCLC[1] combo w/ TATTON B Study at AACR 2019 …TATTON B [2] – ...promising efficacy in MET+ Tagrisso failure patients... % Enrolled % Efficacy Evaluable 2L/3L post Tagrisso® Best response after treatment with savolitinib and Tagrisso # pts (n=48) (n=39) Complete or partial respon
Slide 31: SAVANNAH Study
SAVANNAH Study Encouraging TATTON data – led to the initiation of SAVANNAH Addressing resistance with combinations SAVANNAH (NCT03778229) 1st Line Metastatic 2nd Line+ Metastatic Phase II single-arm study: Global – N. & S. America, Eur., & Asia. AURA3 Primary endpoint ORR. IPASS T790M+ SAVANNA
Slide 32: Savolitinib + Imfinzi combination
Savolitinib + Imfinzi® combination 1. Could MET + PD-L1 inhibition be synergistic? 3. PD-1/PD-L1s important in non-ccRCC but need to see mature mPFS/mOS & further biomarker analysis [1] Synergistic benefit TT + IO Savo mono. Survival (%) MET+ All lines: (n=44) Additive benefit TT + IO ORR 18.2% Papi
Slide 33: Other Operating Highlights – H1 2019
Other Operating Highlights – H1 2019 2d
Slide 34: Other H1 2019 Operating Highlights
Other H1 2019 Operating Highlights B-cell malignancies / non-Hodgkin’s lymphoma HMPL-523 (Syk) – >150 patients dosed in China/Australia Phase I/Ib; to guide registration strategy in late 2019; HMPL-689 (PI3Kδ) – Phase II dose selected in China & expansion underway; US/EU Phase I sites open & s
Slide 35: What is next from discovery?
What is next from discovery? Differentiated assets against multiple targets Priming & activations Anti-angiogenesis aOX40 VEGFR (fruquintinib) VEGFR/FGFR (surufatinib) 4-1BB FGFR (HMPL-453) Antigen release Negative regulators Treg (HMPL-689) MET (savolitinib) CSF-1R (surufatinib) E
Slide 36: Pipeline & Potential Upcoming Events
3 Pipeline & Potential Upcoming Events
Slide 37: Portfolio summary
Portfolio summary Multiple waves of innovation – progressing rapidly Dose Finding / Proof-of-Concept Registration Intent Marketed Safety Run-In Fruquintinib + Tyvyt (PD-1) Savolitinib Savo + Tagrisso (SAVANNAH) Elunate (Fruquintinib capsules) Solid Tumors [1] MET Exon 14 deletion NSCLC 2L/3L Tagriss
Slide 38: Potential upcoming events
Potential upcoming events H1-19 H2-19 H1-20 Savo + Imfinzi® Papillary RCC (CALYPSO) HMPL-523 (Syk) Indolent NHL Savo + Imfinzi® Papillary RCC (CALYPSO) Savo + Tagrisso® NSCLC (SAVANNAH) Ph. II Interim Data Ph. I Start (US/EU) Ph. II Interim Data Ph.II Interim Savo + Tagrisso® NSCLC (TATTON) Ph. Ib
Slide 39: H1 2019 Financial Results, Cash & Guidance
4 H1 2019 Financial Results, Cash & Guidance
Slide 40: H1 2019 Financial results
H1 2019 Financial results R&D expense accelerated to $74.5m in first 6 months at CER [2] 2018 H1-18 H1-19 Growth (Non-GAAP) GROUP REVENUES 214.1 102.2 102.2 - +5% Global Unconsolidated JV Revenues 491.5 271.7 276.9 +2% +8% Innovation SEGMENT NET INCOME/(LOSS) [1] INNOVATION PLATFORM (102.4) (52.9) (
Slide 41: Cash position & 2019 Guidance
Cash position & 2019 Guidance $384 million in available cash resources [1] Cash Position 2019 Previous 2019 Current (at end June 2019) (US$ millions) Guidance Guidance $237 million cash / Research & (160) - (200) (130) – (170) cash equiv. / Short Global Development Expenses term inv. [2] Innovatio
Slide 42: Summary
-_—| inne Pio Crt rey aor CH By im ry
Slide 43: Objectives for existing assets 2019-2021
Objectives for existing assets 2019-2021 Global China Existing China Innovation Oncology Business NDA submission for savolitinib Establish Elunate® as Cash generative China combo with Tagrisso® best-in-class VEGFR TKI in Commercial Platform >$5bn market by 2026 [1] Expand savo. Exon14 deleti
Slide 44: Chi-Med in short
Chi-Med in short 19-year track record of achievement & discipline In-house discovery excellence – world-class scientific talent & strategy – discovery platform that has created all clinical assets internally; Proven development – the first China company to bring home-grown asset to market[1];
Slide 45: Thank you
CHI- HUTCHISON CHINA MEDITECH Thank you
Slide 46: Appendix
Appendix A1 Strategies Global Innovation P47 China Oncology P55 Existing China Business P61 A2 Product Candidate Details P67 A3 Further Corporate Information P105 46
Slide 47: Strategies – Global Innovation
Strategies – Global Innovation A1a Pushing the envelope on our most valuable assets
Slide 48: One of China's largest discovery platforms in oncology
One of China’s largest & most established discovery platforms in oncology Global step-change innovation Aiming for multiple potential first-in-class assets Kinase selectivity – enable combos Limit off-target toxicity & address TKI resistance Discovery of broad range of assets against novel targe
Slide 49: Attack cancer from multiple angles at same time
Attack cancer from multiple angles at same time Immune Desert Excluded Infiltrate Insufficient T cell response Inadequate T cell homing Chemotherapies Anti-angiogenics Vaccines Stromal targets CAR-T (pro-inflammatory Chemokines strategies) Vaccines TCB’s Antigen Release Inflamed Aber
Slide 50: Advanced medicinal chemistry provides superior selectivity & safety
Our advanced medicinal chemistry provides superior selectivity & safety profiles… C-MET (Wild-type & mutants) VEGFR 1/2/3 PAK3 Savolitinib ~1,000 times ~250 times more selective to c-MET more selective to than next kinase (PAK3) [5] VEGFR3 than next non- VEGFR kinase (Ret) [6] Screening at >90% inhi
Slide 51: Global clinical drug portfolio (1/2)
Global clinical drug portfolio (1/2) Savolitinib Fruquintinib Potential First-in-class small molecule selective MET inhibitor Potential Best-in-class small molecule selective VEGFR 1/2/3 inhibitor Indications: MET-driven NSCLC; RCC; Gastric; Prostate cancer Indications: Colorectal; NSCLC; Gastric ca
Slide 52: Global clinical drug portfolio (2/2)
Global clinical drug portfolio (2/2) Surufatinib HMPL-523 HMPL-689 Potential First-in-class small molecule Potential Best-in-class small molecule Unique small molecule VEGFR 1/2/3, FGFR1 & CSF-1R inhibitor selective Syk inhibitor selective PI3Kδ inhibitor Neuroendocrine tumors (pNET/ep-NET); Indolen
Slide 53: 5 assets in global development
5 assets in global development …US/EU clinical & regulatory team fully operational Program Treatment Indication Target patient Study name Sites Dose finding / safety run-in Proof-of-concept Registration ® ® Savolitinib + Tagrisso NSCLC 2L/3L EGFRm; Tagrisso ref.; MET+ SAVANNAH Global Oxnard/Ahn – DF
Slide 54: Global Innovation: Main targets for 2019-2021
Global Innovation Main targets for 2019-2021 Aim for Savolitinib / Tagrisso® combo NDA submission Build out US/EU development operation US/EU C&R operation set up in Florham Park, NJ Accelerate development of 4 un-partnered global assets Fruq (ex-China) & suru registration studies & explor
Slide 55: Strategies – China Oncology
Strategies – China Oncology A1b Next-gen oncology drugs to meet major needs in China
Slide 56: China oncology – ~24% of world's cancer patients
China oncology – ~24% of world’s cancer patients[1] Industry’s attention turning to unmet medical need in China oncology Regulatory reforms in China – addressing low SoC [2] Major investment inflow Chi-Med is a first mover Elunate® launch in 3L mCRC; First ever in China [3] Deep pipeline – 8
Slide 57: China now world's 2nd largest pharma market
China now world’s 2nd largest pharma market …investment, approvals & access all accelerating rapidly Per Capita Healthcare Spending PRC Pharmaceutical Market Size Medical Insurance Coverage [1] (US$ billions) 7% CAGR Million people (2018-2023E) 317 Urban employees with 8% CAGR 328 USA 287 307 Full a
Slide 58: Cancer is a major unmet need in China
Cancer is a major unmet need in China …investments in launches/access starting to have an impact Cancer Incidence in China (2018) Novel drugs post NRDL inclusion China 4,285 U.S. 1,735 (Bar Chart US$ millions) India 1,157 Japan 883 Germany 609 Price per cycle: US$4,505 -66% US$1,538 (RMB10,364) Braz
Slide 59: Assets in China development
8 assets in China development …fruq launched – savo/suru NDAs & Syk/PI3Kδ PoC ahead Program Treatment Indication Target patient Study name Sites Dose find / safety run-in Proof-of-concept Registration Enrolled Savolitinib NSCLC MET Exon 14 deletion China Lu Shun – SH Chest Hosp. n >60 Savolitinib Sa
Slide 60: China Oncology: Main targets for 2019-2021
China Oncology Main targets for 2019-2021 Establish Elunate® as the best-in-class VEGFR TKI in China market Work with Lilly to maximize penetration & sales performance; Aggressively expand PD-1 combination collaborations & broader LCI program Launch our un-partnered oncology drugs Target s
Slide 61: Strategies – Existing China Business
Strategies – Existing China Business A1c Cash generation & China commercial know-how / infrastructure
Slide 62: Existing China business
Existing China business Chi-Med spent 17 years building China commercial presence Valuable know-how in operating within the complex medical system in China Clear operating synergies with our novel oncology assets China operations/JVs have generated >$210 million dividends since inception China
Slide 63: Chi-Med's Commercial Platform in China
Chi-Med’s Commercial Platform in China Integrated platform built from ground up 2 National House- Major Commercial Leadership JVs with 3 Major Hold Name Brands & Production Scale Market Shares China Pharmas >2,400 Rx & ~900 OTC sales Market leader in the sub- people in over 330 [1] cities & categori
Slide 64: Established Rx Commercial Platform in Mainland China
Established Rx Commercial Platform in Mainland China… Chi-Med management run all day-to-day operations National Coverage: Over 330 cities & towns. NORTH ~24,400 hospitals. ~88,400 doctors. >2,400 Rx Pop’n: 320m (23%) CV Medical Reps: 585 (25%) Medical reps. covering Sales People 585 HSP Sales st
Slide 65: Chi-Med's Commercial Platform in China
Chi-Med’s Commercial Platform in China Proven track record, ~$300 million in net income since inception Revenues (Non-GAAP) [1][2] Net Income/(Loss) attrib. to Chi-Med (US$ millions) (US$ millions) 70 664 Total NI [3] NI to Chi- 2007-2018 Med CAGR 639 Prescription Drugs 342 171 +38% 582 Consumer Hea
Slide 66: Existing China Business: Plans for 2019-2021
Existing China Business Plans for 2019-2021 Continue organic growth Focus on proprietary prescription drug products Build out synergies with China Oncology Organization Strategically evaluate potential for M&A Focus on cash generation 66
Slide 67: Product Candidate Details
Product Candidate Details A2 Further details on each drug candidate
Slide 68: Superior safety allows for combinations
Superior safety allows for combinations TKI + TKI combos to address acquired resistance RESULTS:CANDIDATE RESULTS: CANDIDATEACQUIRED ACQUIREDRESISTANCE RESISTANCEMECHANISMS MECHANISMSWITH WITH OSIMERTINIB (n=91)* R OSIMERTINIB (n=91)* • No • Noevidence ofacquired evidence of acquired EGFR EGFR T790M
Slide 69: Savolitinib (AZD6094)
Savolitinib (AZD6094) A2a Potential first-in-class selective MET inhibitor
Slide 70: Savolitinib: Potential first-in-class selective MET inhibitor
Savolitinib (AZD6094) Potential first-in-class selective MET inhibitor 1. Strong potential to become first selective MET 2. MET is aberrant in many tumor settings. [7] MET New Cases (2018) inhibitor approved in certain indications. Over- Clear clinical efficacy observed in non-small cell lung Indi
Slide 71: Savolitinib – 2L EGFRm NSCLC
Savolitinib – 2L EGFRm NSCLC Very strong preclinical rationale for combination w/ EGFR-TKIs 1. 2nd Line NSCLC is a fast and attractive indication 2. Potential in EGFR-TKI resistant NSCLC: for savolitinib to go after. Also important unmet Must shut down both EGFRm & MET signaling pathways; medical
Slide 72: Savolitinib – 2L NSCLC combo: MET+ & T790M+
Savolitinib – 2L NSCLC[1] combo w/ Encouraging in MET+ / T790M-, next step under discussion Savo / Iressa® combo in 1st gen. EGFRm-TKI refractory ...Iressa® combo – ~6mo. Duration of patients[2]...outstanding response in MET+ / T790M- Response in MET+ / T790M- patients MET+ / T790M+ MET+ (T790M-) ME
Slide 73: Savolitinib – 2L/3L NSCLC – resistant
Savolitinib – 2L/3L NSCLC[1] – resistant MET+ driven resistance in ~30% of patients Tagrisso® resistant tissue & ctDNA analysis [2] Other EGFR # Prior Prior 3rd gen Pt TISSUE (NGS, FISH) PLASMA ctDNA (NGS) MET+ mutation Therapies TKI Unknown ~30% 1 L858R 1 MET amp, T790 WT MET amp, T790M ND 3rd Line
Slide 74: Safety & tolerability
Safety & tolerability Tagrisso® & savo both highly selective/tolerable monotherapies Efficacy Discontinuations as % Enrolled US FDA Median PFS Due to Withdrawn Approval Treatment Disease setting n ORR (mo.) AE / Other Total [5] Monotherapy – Tagrisso® / savolitinib 30-Mar-17 Tagrisso® (osimertinib)
Slide 75: PRCC – unmet medical need
PRCC – unmet medical need Lower response rates to treatments 1. Limited treatment options for non-ccRCC 2. RCC est. ~$13.0 bn. 3. Unmet medical need: market by 2030 [1] Several approved therapies in ccRCC [3] Immunotherapy setting new treatment paradigm FIRST LINE – clear-cell RCC [4] ORR mPFS mOS M
Slide 76: Savolitinib – PRCC Phase II
Savolitinib – PRCC Phase II Clear efficacy & durable response in MET+ PRCC patients 1. Savolitinib clear ORR benefit in MET+ patients. 3. Disease Control Rate (“DCR”) – big advantage in MET+ 80 with DCR 73.2% vs. MET- 28.2%.^ Best Tumor measurement changes from baseline (%) 60 Objective Response Rat
Slide 77: Savolitinib – gastric cancer
Savolitinib – gastric cancer A major problem in east Asia – Japan, South Korea & China 1. Gastric (stomach) cancer is the 5th most common TSC1/2 Null Ph II SMC Genomic 12 vistusertib cancer globally – 782,700 deaths/year Screening RICTOR Ph II USA 26 Program 11 amplification vistusertib New Cases (‘
Slide 78: Savo potential not only in NSCLC
Savo potential not only in NSCLC… …highly promising efficacy in MET+ gastric cancer (…& kidney) Strong preclinical efficacy. 3. VIKTORY trial – 34-year old male; surgery ruled-out; failed 4-cycles XELOX. Gastric cancer Hs746T xenograft model Vehicle Savolitinib – 0.3mg/kg, p.o.,qd Baseline … after S
Slide 79: Fruquintinib – 24hr full target coverage
Fruquintinib – 24hr full target coverage The most selective VEGFR inhibitor in clinical trials globally [1] VEGF Production Blood vessel growth 1. Only inhibits VEGFR – limits off-target toxicity & Tumor allows for full & sustained target inhibition. Tumor growth 600 VEGF 500 Day=14, 6mg QD Plasma C
Slide 80: Elunate (fruquintinib capsules)
Elunate® (fruquintinib capsules) A2b Highly selective anti-angiogenesis inhibitor
Slide 81: Fruquintinib – 3L/4L colorectal cancer
Fruquintinib – 3L/4L colorectal cancer Develop in US/EU for rego/TAS-102 ref./intol. patients[1] [1] ASCO = American Society of Clinical Oncology Annual Meeting. 81
Slide 82: Many Firsts for China biotech
Many “Firsts” for China biotech 2017 2018 Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Oral Presentation Presentation of further analyses JAMA Publication SHFDA Review Granted FRESCO Priority Positive NIFDC Review PAI Specs review & validation; Sample Reado
Slide 83: Launched – Nov. 25, 2018
Launched – Nov. 25, 2018 First ever oncology drug discovered & launched in China [1] [1] unconditional/Full approval 83
Slide 84: FALUCA – Third-line NSCLC Monotherapy
FALUCA – Third-line NSCLC Monotherapy Presented at WCLC 2019 FALUCA Phase III (enrolled Dec. 2015 Efficacy Endpoints (Intent-to-Treat) [2] Good safety; most Grade ≥3 TEAEs target-related & clinically manageable. to Feb. 2018) Fruq. Placebo Patient (%) Fruq (N=354) Pbo (N=173) p-value TEAE ≥ Grade 3
Slide 85: Fruquintinib – 1L NSCLC combo
Fruquintinib – 1L NSCLC combo w/ Two small molecule TKIs allow for better management of tox. 1. Promising efficacy in first line – 76% ORR (13/17). [1,2,3] 3. Combination of highly selective TKIs vs. mAbs: daily dose Disease control rate (DCR)[ 1][2] 100% (17/17) flexibility improves tolerability. T
Slide 86: Fruquintinib – Gastric combo with paclitaxel
Fruquintinib – Gastric combo with paclitaxel Phase III initiated Oct 2017 – Interim analysis early 2019 1. Dose proportional increase of fruquintinib AUC at steady 3. Encouragingly low level of dose reduction/interruption. state. Over 30% increase in paclitaxel drug exposure (mean Actual mean admini
Slide 87: VEGFR / immunotherapy (PD-1s) combinations
VEGFR / immunotherapy (PD-1s) combinations Pembrolizumab (PD-1) + axitinib (VEGFR) Axitinib (VEGFR) Pembrolizumab (PD-1) versus sunitinib (VEGFR) monotherapy monotherapy in 1L ccRCC monotherapy in 1L ccRCC in 1L ccRCC Complete Response: 0% Complete Response: 3% Objective Response Rate: 34% Objective
Slide 88: Fruquintinib & surufatinib both unique VEGFR TKIs
Fruquintinib & surufatinib both unique VEGFR TKIs …potentially ideal VEGFR combo partners for immunotherapy st nd TKI 1 Generation 2 Generation Next Generation Selective angio-immuno Selectivity Multiple targets Relatively selective Highly selective kinase inhibitor ® ® ® ® ® ® [1] Inhibitors Sutent
Slide 89: Assets potentially ideal TKI combo partners for immunotherapy
Immunotherapy combinations… assets potentially ideal TKI combo partners for immunotherapy ® 1L Clear Cell Renal Cell Carcinoma [1] Inlyta Fruquintinib Surufatinib Selective angio-immuno Objective Response Rate 59% Selectivity Relatively selective Highly selective kinase inhibitor Complete Response S
Slide 90: Chi-Med immunotherapy collaborations
Chi-Med immunotherapy collaborations Global Development China only Managed by AstraZeneca Jointly managed by Chi-Med & partners Managed by partners savolitinib + Imfinzi® (PD-L1) fruquintinib + Tyvyt® (PD-1) fruquintinib + GB226 (PD-1) ccRCC/PRCC Solid tumors Solid tumors Taizhou Hanzhong Junshi Bio
Slide 91: Lilly amendment – Dec 2018
Lilly amendment – Dec 2018 Secures long-term commercial potential Chi-Med will pay full cost of any future development in China. In return, Chi-Med gains: Freedom to operate in selecting & pursuing any future indications in China; Materially higher milestones & royalties upon launch in new LCI
Slide 92: Surufatinib
Surufatinib A2c Highly active TKI with unique angio-immuno activity
Slide 93: Surufatinib – China NET – Phase II (ENETS 2017)
Surufatinib – China NET – Phase II (ENETS 2017 [1]) Tumor devascularization & central necrosis Duodenum NET G2 w/ multiple liver & retroperitoneal Baseline Week 52 lymph node metastases Patient 1 Baseline Week 56 w/ multiple liver metastases Rectum NET G2 Patient 2 [1] ENETS = European Neuroendocrin
Slide 94: HMPL-523 (Syk) & HMPL-689 (PI3Kδ)
HMPL-523 (Syk) & HMPL-689 (PI3Kδ) A2d Potential first-in-class (Syk) & best-in-class (PI3Kδ) assets
Slide 95: HMPL-523 – hematological malignancies
HMPL-523 – hematological malignancies Syk exciting target emerging – Lymphoma PoC ongoing 1. The B-cell signaling is critical in hematological cancer with three 2. Entospletinib – 65% Nodal Response Rate CLL & SLL [4] [5]. breakthrough therapies recently approved. Best Change in SPD from Baseline (%
Slide 96: HMPL-523 (Syk) in hematological cancer
HMPL-523 (Syk) in hematological cancer Australia & China – large Ph.Ib expansion. US/EU Ph.I imminent 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 • Australia:
Slide 97: HMPL-689 – Phase I Australia & China ongoing
HMPL-689 – Phase I Australia & China ongoing Designed to be a best-in-class inhibitor of PI3Kδ 1. PI3Kδ now a proven target. 2. PI3Kδ inhibitors being developed in a very broad range of indications. PI3Kδ activation associated with allergy, Compound Indication Status Issue inflammation & oncology.
Slide 98: Epitinib
Epitinib A2e EGFR inhibitor with blood-brain-barrier penetration
Slide 99: Epitinib – 70% response in NSCLC with brain mets
Epitinib – 70% response in NSCLC w/ brain mets[1] Unmet medical need. Investment case under review. 1. Phase Ib [1] – epitinib monotherapy in EGFRm+ NSCLC 2. Phase Ib [1] – solid/durable efficacy in brain in EGFRm+ patients – efficacy in lung in-line with Iressa®/Tarceva®. NSCLC patients with measur
Slide 100: Epitinib – Strong PoC efficacy – 160mg QD dose
Epitinib – Strong PoC efficacy – 160mg QD dose 62-year-old female Lung Baseline +28 days Brain Baseline +28 days 57-year-old male Lung Baseline +28 days Brain Baseline +28 days 52-year-old male Lung Baseline +28 days Brain Baseline +28 days 100
Slide 101: Epitinib – Safe & well tolerated
Epitinib – Safe & well tolerated 3. Epitinib well tolerated by patients[1] w/advanced CASE STUDY – EGFR-TKI naïve patient solid tumors. Safety profile is consistent with that of Male, 46, diagnosed with Stage IV NSCLC adenocarcinoma (Exon21) Metastases in the approved EGFR-TKIs (e.g. Iressa®/ Ta
Slide 102: Theliatinib (EGFRwt) & HMPL-453 (FGFR)
Theliatinib (EGFRwt) & HMPL-453 (FGFR) A2f Potential best-in-class assets
Slide 103: Theliatinib
Theliatinib Potent & highly selective TKI – strong affinity to EGFRwt kinase 1. Major unmet medical need for wild-type EGFR CASE STUDY – EGFR protein over expression activation tumors. May 4, 2016: Man, 62, stage IV esophageal squamous cell cancer EGFR TKIs are less effective in solid tumors wit
Slide 104: HMPL-453 – Phase I in China ongoing
HMPL-453 – Phase I in China ongoing Designed as best-in-class FGFR1/2/3 inhibitor 1. FGFR genetic alterations are oncogenic drivers. 2. FGFR – diverse & complicated genetic changes with FGF/FGFR signaling normally involved in multiple tumor types harboring low incidence. embryonic development, tis
Slide 105: Further Corporate Information
Further Corporate Information A3
Slide 106: Important milestones in Chi-Med's evolution
Important milestones in Chi-Med’s evolution Innovation Discovery China Registr. & China Launches & Start-up & M&A Platform Global Early Dev. Expanding Global Registration 2000 - 2005 2006 - 2010 2011 - 2016 2017 - 2018 2019 2017 NSCLC PoC data WCLC Savo + Tagrisso® Global license deal savo. + Tagris
Slide 107: Chi-Med Group Structure - Major Entities
Chi-Med Group Structure - Major Entities Non-Consolidated Joint Ventures Chi-Med Group Level Revenues – H1 2019: $102.2m (H1 2018: $102.2m) Chi-Med Subsidiaries Net Loss Attributable to Chi-Med – H1 2019: -$45.4m (H1 2018: -$32.7m) Innovation Platform Commercial Platform Revenue – H1 2019: $12.0m (H
Slide 108: FY2019 H1 Inter-group cash flow
FY2019 H1 Inter-group cash flow $237.3m cash (Jun 30, 2019); $146.3m in undrawn bank facilities Capital Markets ESOP & Bank Loans (at Jun 30, 2019) Pharma Partners AIM (~$75m – May 2006) Treasury Drawn down: $0m AstraZeneca; Eli Lilly; Nestlé Nasdaq (~$96m – Mar 2016) Nasdaq (~$293m – Oct 2017) Shar
Slide 109: Non-GAAP Financial Measures and Reconciliation (1/3)
Non-GAAP Financial Measures and Reconciliation (1/3) Reconciliation of Adjusted Group net cash flows and Adjusted Group net Reconciliation of Adjusted Research and Development Expenses: cash flows excluding financing activities: Jun 30, 2019 Current 2019 Previous 2019 Guidance Guidance H1 2018 H1 20
Slide 110: Non-GAAP Financial Measures and Reconciliation (2/3)
Non-GAAP Financial Measures and Reconciliation (2/3) Reconciliation of GAAP growth to CER growth Six Months Ended Growth Amount Growth % $’Million (except %) June 30, June 30, Exchange Actual Exchange Actual at CER CER growth % 2019 2018 effects growth % effect % Consolidated sales 102.2 102.2 - 5.1
Slide 111: Non-GAAP Financial Measures and Reconciliation (3/3)
Non-GAAP Financial Measures and Reconciliation (3/3) Reconciliation of Non-GAAP Sales and Non-GAAP Net (loss)/income after tax [1] Prescription Drugs: includes our Consolidated subsidiary (Hutchison Sinopharm) and Non-consolidated joint venture (SHPL); Consumer Health: includes our Consolidated
Slide 112: China Commercial Platform has substantial value
China Commercial Platform has substantial value Chi-Med’s Commercial Platform continues to perform well relative to our peer group. The market value, based on China Pharma median PE multiples is approximately $1.8 billion.[1] Given our share in the JVs, Chi-Med’s share of this value is approxima
Slide 113: National Reimbursement Drug List Pricing (July 2017)
National Reimbursement Drug List Pricing (“NRDL”) July’17 update – 15 new drugs in oncology[1] added to NRDL Unit Pricing (US$) [3] Approximate Monthly Pricing (US$) [3] Brand (generic) Company Dosage Avg. Tender Reimbursed ∆% Dosage Avg. Tender Reimbursed Indication coverage Herceptin® Breast: 4mg/
Slide 114: National Reimbursement Drug List Pricing (Oct 2018)
National Reimbursement Drug List Pricing (“NRDL”) Oct’18 update – 17 new drugs in oncology added to NRDL Unit Pricing (US$) [2] Approximate Monthly Pricing (US$) [2] Brand (generic) Company Dosage Avg. Tender Reimbursed ∆% Dosage [1] Avg. Tender Reimbursed Indication coverage ® Focus V (anlotinib) S
Slide 115: Thank you
CHI- HUTCHISON CHINA MEDITECH Thank you
Hutchison China MediTech (Chi-Med) — CLSA Investors' Forum 2019 on 6ix