On March 11, 2019 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported its audited financial results for the year ended December 31, 2018 and provides updates on key clinical programs (Press release, Hutchison China MediTech, MAR 11, 2019, https://www.chi-med.com/fy2018-results-and-programs-update/ [SID1234534188]).
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Fruquintinib (Elunate)
Received New Drug Application ("NDA") approval for fruquintinib and launched in late November 2018 for colorectal cancer ("CRC"), the first ever China-discovered novel oncology drug to receive full NDA approval in China; and
Completed an agreement with Eli Lilly and Company ("Lilly") to amend the original 2013 license and collaboration agreement for fruquintinib enabling both parties to maximize its long-term commercial potential in China.
Savolitinib
Initiated two studies with potential for registration in lung cancer:
(1) China Phase II in mesenchymal epithelial transition receptor ("MET") exon 14 mutation/deletion non-small cell lung cancer ("NSCLC"); and
(2) Global Tagrisso/savolitinib combination Phase II in MET-positive Tagrisso refractory NSCLC.
Presented Phase II data of Imfinzi/savolitinib combination in papillary renal cell carcinoma ("PRCC"), a tolerable combination with immature but encouraging efficacy.
Hematological malignancies: Expanded Phase I/Ib dataset in Australia and China in lymphoma for HMPL-523 targeting spleen tyrosine kinase ("Syk") and HMPL-689 targeting phosphoinositide 3-kinase delta ("PI3Kδ"). Cleared U.S. Investigational New Drug ("IND") applications on both assets with U.S. and E.U. clinical development set to start in H1 2019.
Immunotherapy combinations: Signed four co-development collaborations for fruquintinib and surufatinib in combination with various programmed cell death protein-1 ("PD-1") monoclonal antibodies.
Global clinical development: Expansion of U.S. and international clinical and regulatory operations firmly underway with five Chi-Med drug candidates either in or about to start global clinical development.
"With the launch of Elunate underway and doing well, and with its financial prospects enhanced by the recent Lilly amendment, we are focused on our broader late-stage clinical development program with multiple important opportunities being pursued in parallel," said Simon To, Chairman, Chi-Med. "We took a big step in 2018 to expand our U.S. development capability in order that we can take full advantage of the global potential of our assets. We also entered the immuno oncology arena through multiple development collaborations combining PD-1 antibodies with our highly selective small molecules. The increased investment in all these activities is partially offset by robust income from our commercial operation in China, which also serves as a very powerful platform for future product launches."
"Looking ahead, we target multiple NDAs in the coming two or three years, covering savolitinib, surufatinib and fruquintinib, as well as registration studies with our hematological cancer assets. We believe that these activities will address a broad range of unmet medical needs and benefit a large number of patients."
Financial Highlights
The items below are selected financial data for the year ended December 31, 2018. All dollars are expressed in US dollar currency unless otherwise stated. For more details, please refer to "Financial Review", "Operations Review" and "Audited Consolidated Financial Statements" below.
OVERALL GROUP: in-line with our most recent guidance
Group revenue of $214.1 million (2017: $241.2m).
Net loss attributable to Chi‑Med of $74.8 million (2017: net loss $26.7m).
Adjusted Group net cash flow (non-GAAP) was -$57.3 million in 2018. Cash from our Commercial Platform, as well as payments received from our multi-national partners, offset more than half of our research and development ("R&D") expenses.
Cash resources of $420.3 million at Group level as of December 31, 2018 ($479.6m as of December 31, 2017), including cash and cash equivalents, short-term investments and unutilized bank facilities.
INNOVATION PLATFORM: increased investment in R&D driven by expansion of our operations and progress on our clinical development pipeline
Consolidated revenue was $41.2 million (2017: $36.0m) mainly from service fee payments from AstraZeneca AB (publ) ("AstraZeneca"), Lilly and Nutrition Science Partners Limited ("NSP"), our 50/50 joint venture with Nestlé Health Science S.A., and $13.5m in milestone payments from Lilly following fruquintinib approval. Following fruquintinib’s launch, under the brand name Elunate, we recorded revenue of $3.3m and royalty income of $0.3m during the last five weeks of 2018.
R&D expenses on an as adjusted (non-GAAP) basis increased to $142.2 million (2017: $88.0m), primarily driven by the progress in the development of our eight clinical drug candidates, five of which are now in development outside China; investment in the establishment of small molecule manufacturing operations in China; and expansion of U.S. and international clinical and regulatory operations.
Net loss from our Innovation Platform attributable to Chi-Med of $102.4 million (2017: net loss of $51.9m).
COMMERCIAL PLATFORM: continued solid net income growth amid shift in revenue model and over-the-counter ("OTC") logistics divestment
Total consolidated sales fell 16% to $172.9 million (2017: $205.2m) because of the implementation of the Two-Invoice System in China, a new government policy that led to a shift in our revenue recognition for certain third-party drugs from gross sales consolidation to a fee-for-service revenue model. This new Two-Invoice System policy did not affect our total consolidated net income in 2018.
Total sales of non-consolidated joint ventures, on an as adjusted (non-GAAP) basis excluding the effects of the divestment of certain non-core operations, up 13% to $491.5 million (2017: $433.3m) driven by strong growth across major product categories.
Total consolidated net income from our Commercial Platform attributable to Chi-Med up 10% to $41.4 million (2017: $37.5m), on an as adjusted (non-GAAP) basis excluding one-time gains in 2017.
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U.K. Analysts Meeting and Webcast Scheduled Today at 9:00 a.m. GMT (5:00 p.m. HKT) – at Citigate Dewe Rogerson, 3 London Wall Buildings, London, EC2M 5SY, U.K. Investors may participate in the call at +44 20 3003 2666 (800 900 476 toll free in Hong Kong), or access a live video webcast of the call via Chi-Med’s website at www.chi-med.com/investors/event-information/.
U.S. Conference Call Scheduled Today at 9:00 a.m. EDT – to participate in the call from the U.S., please dial 1 866 966 5335.
Additional dial-in numbers are also available at Chi-Med’s website. For both calls please use conference ID "Chi-Med."
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Innovation Platform — Operating HIGHLIGHTS
The points below summarize some of the pipeline development highlights during 2018 and to-date in 2019. For more details, please refer to "Operations Review – Innovation Platform" below.
FRUQUINTINIB – Highly selective tyrosine kinase inhibitor ("TKI") of vascular endothelial growth factor receptor ("VEGFR") 1/2/3 – focus on maximizing commercial potential of our first approved drug:
FRESCO China Phase III in third-line CRC, potentially best-in-class in terms of both efficacy and safety.
China NDA – approval and launch: received full approval for launch of fruquintinib (under the brand name Elunate) in CRC in September 2018, including Good Manufacturing Practice ("GMP") certification of our manufacturing facility in Suzhou. In partnership with Lilly, we launched fruquintinib in China in late November 2018 in a series of national launch meetings across China;
Material financial impact: during 2018 Chi-Med recognized revenue from Lilly totaling $26.9 million including $14.0 million in milestone and upfront payments, $9.3 million service fees and costs, and $3.6 million in revenue from product purchases and royalties since the late-November 2018 launch;
JAMA publication: in June 2018, the full FRESCO results were published in the Journal of the American Medical Association ("JAMA"), which we believe to be the first China-based novel oncology therapy Phase III trial to be published in the JAMA, a landmark achievement; and
Two further analyses of FRESCO data presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") in June 2018: (1) a subgroup analysis by prior anti-VEGF or anti-epidermal growth factor receptor ("EGFR") target therapy showed that fruquintinib had clinically meaningful benefits regardless of prior targeted therapy (PTT) without observed cumulative toxicity; and (2) an ad-hoc analysis of quality-adjusted time without symptoms or toxicity ("Q-TWiST") showed relative improvement of Q-TWiST with fruquintinib, representing a potentially clinically important quality-of-life benefit for patients;
2018 Lilly Amendment: an important amendment to the original 2013 agreement that we believe secures the long-term commercial potential fruquintinib. Chi-Med will pay the full cost of any future clinical development in China. In return, Chi-Med gains:
Full freedom to operate in selecting and pursuing any future indications in China;
Materially higher milestones and royalties;
Freedom to collaborate with any third-party in clinical development; and
Possible promotion rights in 30-40% of China for fruquintinib, based on territorial sales. This transition is not expected before 2021. Until then, Lilly is responsible for all costs associated with the launch and commercialization of fruquintinib in China. If Chi-Med assumes fruquintinib promotion in the 30-40% of China, we will receive service fees, which we expect to be net income accretive to Chi-Med.
FALUCA China Phase III in third-line NSCLC: completed enrollment of 527 patients and in November 2018 we read-out top-line results in which fruquintinib demonstrated tolerable safety and strong anti-tumor efficacy in NSCLC, meeting all secondary endpoints, however it did not achieve its primary overall survival ("OS") endpoint;
Global clinical development: Chi-Med retains all rights to fruquintinib outside of China. In 2018, the U.S. recommended Phase II dose for fruquintinib was determined to be the same as the dose in China. Planning is ongoing for a Phase II/III registration study in CRC in the U.S. / Europe in addition to multiple exploratory studies of fruquintinib in the U.S.; and
PD-1 collaborations: in late 2018 we entered into collaboration agreements with Innovent Biologics (Suzhou) Co. Ltd. ("Innovent") globally and Genor Biopharma Co. Ltd. ("Genor") in China to explore fruquintinib in combination with their respective PD-1 monoclonal antibodies Tyvyt (sintilimab) and genolimzumab. Safety run-in studies are now underway/being planned.
SAVOLITINIB – Highly selective TKI of MET:
Lung cancer – MET is an increasingly important target in NSCLC both in first-line and as a major resistance mechanism in EGFR TKI-refractory patients
In EGFR-TKI refractory NSCLC: following ongoing encouraging data in the TATTON Phase Ib/II studies in late 2018, AstraZeneca proceeded with initiation of SAVANNAH, a Phase II study of the Tagrisso / savolitinib combination therapy in MET-positive, third-generation EGFR TKI-refractory NSCLC (principally second-line and third-line after Tagrisso). SAVANNAH is a global study in North and South America, Europe and Asia which, subject to positive clinical outcome, is designed to support potential NDA submission. Primary data completion is anticipated in 2021;
In MET Exon 14 mutation/deletion NSCLC: China Phase II registration intent study is ongoing with primary data completion anticipated in 2020 and potential to be the first NDA for savolitinib.
Kidney cancer – immunotherapy combinations rapidly changing the treatment landscape in RCC
CALYPSO Phase II combination of savolitinib with Imfinzi programmed death-ligand 1 ("PD-L1") inhibitor: interim data for the PRCC cohort of the CALYPSO Phase II study were presented last month at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Symposium ("ASCO GU") reporting an objective response rate ("ORR") of 27% (11/41). For previously untreated patients ORR was 32% (9/28). The savolitinib / Imfinzi combination was tolerable. Investigators concluded that the combination is associated with durable responses in PRCC and that both progression free survival ("PFS") and OS data were immature but encouraging. This compares to savolitinib monotherapy which reported a 7% ORR in PRCC patients (18% ORR in MET-positive; and 0% ORR in MET-negative) in a previously reported Phase II study; and
SAVOIR Phase III in MET-positive PRCC: AstraZeneca and Chi-Med decided to suspend enrollment in the SAVOIR study due to multiple factors. These included our molecular epidemiology study which as well as emerging favorable data in PRCC for immunotherapies. We intend to reassess PRCC strategy in favor of potential combinations of savolitinib and immunotherapy.
SURUFATINIB (HMPL-012 or sulfatinib) – unique angio-immuno kinase inhibitor of VEGFR, fibroblast growth factor receptor ("FGFR") 1, and colony stimulating factor-1 receptor ("CSF-1R"):
China Phase IIIs in neuroendocrine tumor ("NET"): enrollment continued in the two Phase III registration studies in pancreatic-NET patients (SANET-p) as well as the broader non-pancreatic-NET population (SANET-ep). Interim analyses are expected for 2019; if results are positive and support NDA submission in early 2020, surufatinib could potentially be Chi-Med’s first novel drug candidate to be launched by our own commercial team;
China Phase II/III in biliary tract cancer ("BTC"): based on our Phase Ib study, planning is close to complete for a randomized, open-label Phase II/III study to evaluate efficacy and safety of surufatinib in second line BTC patients in comparison to capecitabine. Study initiation is expected imminently;
U.S. Phase Ib expansion: our U.S. dose escalation study completed in 2018 and a Phase Ib dose expansion study in NET and BTC patients is ongoing;
PD-1 collaborations: in late 2018 we signed collaboration agreements with Shanghai Junshi Biosciences Co. Ltd. ("Junshi") globally and Taizhou Hanzhong Pharmaceuticals, Inc. ("Hanzhong") in China to explore surufatinib in combination with their respective PD-1 monoclonal antibodies Tuoyi (toripalimab) and HX008. The safety run-in study of surufatinib plus Tuoyi is now underway.
Further progress in early/proof-of-concept clinical trials, including:
HMPL-523 – highly selective Syk TKI:
Non-Hodgkin’s lymphoma: a Phase Ib dose expansion study is ongoing in both China and Australia in multiple sub-types of non-Hodgkin’s lymphoma including chronic lymphocytic leukemia; small lymphocytic lymphoma; follicular lymphoma; marginal zone lymphoma; diffuse large B-cell lymphoma; and mantle cell lymphoma;
Gained U.S. clearance for IND application; and
Initiated a Phase I study in combination with azacitidine, an approved hypo methylation agent, in elderly patients with acute myeloid leukemia in China. Dose escalation is now ongoing.
HMPL-689 a highly selective PI3Kδ TKI: a Phase I dose escalation study is approaching completion in China in non-Hodgkin’s lymphoma patients; and our U.S. IND application has also been cleared.
Epitinib Phase Ib/II in EGFR gene amplified glioblastoma, a type of primary brain cancer: a dose escalation study was initiated in China in the first quarter of 2018 with epitinib.
Expansion of U.S. and international operations, and recruitment of key personnel: established new office in New Jersey to support our multiple unpartnered compounds through proof-of-concept and registration trials outside of Asia.
Innovation Platform — KEY EVENTS IN 2019
Early 2019:
Savolitinib – Phase Ib/II data (CALYPSO) – PRCC cohort dataset for the Imfinzi / savolitinib combination presented at ASCO (Free ASCO Whitepaper) GU (February 2019);
Surufatinib – Phase I start – PD-1 combinations – initiate China safety run-in study for surufatinib combination with Tuoyi;
Savolitinib – Phase Ib/II data (TATTON) – presentation of Tagrisso / savolitinib combination updated interim dataset in MET positive EGFR TKI refractory NSCLC at the 2019 American Association of Cancer Research ("AACR") conference in March 29 to April 3, 2019;
Savolitinib – Phase II data – MET Exon 14 NSCLC – preliminary China Phase II data to be presented at the 2019 AACR (Free AACR Whitepaper) conference;
Fruquintinib – Phase III interim analysis (FRUTIGA) – interim analysis for futility in second-line gastric cancer Phase III in China of fruquintinib / Taxol (paclitaxel) combination;
Surufatinib – Phase II/III start – expected start of China Phase II/III study in biliary tract cancer;
HMPL-523 (Syk) – Phase I start – expected start of U.S. / E.U. Phase I/Ib study in indolent non-Hodgkin’s lymphoma;
Fruquintinib – Phase I start – PD-1 combinations – initiate China safety run-in studies for fruquintinib combinations with Tyvyt and genolimzumab; and
HMPL-689 (PI3Kδ) – Phase I start – expected start of U.S. / E.U. Phase I/Ib study in indolent non-Hodgkin’s lymphoma.
Mid-2019:
Savolitinib – Phase II data (VIKTORY) – publication of the results of Phase II umbrella trial in metastatic gastric cancer based on tumor molecular profiling with MET-positive patients represented in three out of twelve VIKTORY treatment arms;
Surufatinib – Phase III interim analysis (SANET-ep) – planned interim analysis in non-pancreatic NET Phase III in China of surufatinib monotherapy; and
Fruquintinib – Phase III data (FALUCA) – intend to submit full analysis of third-line NSCLC registration study for presentation at a scientific conference.
Late-2019:
Savolitinib – Enrollment completion – expect to complete enrollment of China Phase II registration study in MET Exon 14 NSCLC;
Fruquintinib – Phase II/III start – expected initiation of U.S. / E.U. Phase II/III study in metastatic CRC;
HMPL-523 – Registration study start – expected initiation of China registration study in indolent non-Hodgkin’s lymphoma;
Surufatinib – Phase Ib/II data – submit for publication of the results of Phase Ib/II study in biliary tract cancer in China; and
Surufatinib – Phase III interim analysis (SANET-p) – planned interim analysis in pancreatic NET Phase III in China of surufatinib monotherapy.
Commercial Platform — Operating Highlights
The points below summarize some of the operational and financial highlights of our Commercial Platform during 2018. For more details, please refer to "Operations Review — Commercial Platform" below.
Large-scale, high-performance drug marketing and distribution platform covering ~320 cities/towns in China with approximately 3,400 sales personnel. Targeting multiple indications with several household-name brands:
Sales of our non-consolidated Prescription Drugs joint venture, Shanghai Hutchison Pharmaceuticals Limited ("SHPL") grew by 13% to $275.7 million (2017: $244.6m). SHPL’s main product, She Xiang Bao Xin ("SXBX") pill, an oral vasodilator and pro-angiogenesis prescription therapy approved to treat coronary artery disease, saw sales increase by 11% to $233.1 million.
Our consolidated Prescription Drugs business, operated through Hutchison Whampoa Sinopharm Pharmaceuticals (Shanghai) Company Limited ("Hutchison Sinopharm"), saw sales decrease by 20% to $132.8 million (2017: $166.4m) as a result of the Chinese government’s phased implementation of the new Two-Invoice System, pursuant to which Hutchison Sinopharm had converted to earning service fees from the commercialization of certain third-party products instead of recognizing the gross sales; regardless of the Two-Invoice System change, sales performance on key third-party products, such as Seroquel, was strong resulting in 51% growth in service fees to $17.2 million (2017: $11.4m);
Sales of our non-consolidated Consumer Health joint venture, Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited ("HBYS"), grew by 14% to $215.8m (2017: $188.8m, excluding divested operations), driven by progress on certain secondary products.
Our consolidated Consumer Health sales increased by 3% to $40.1 million (2017: $38.8m).
FINANCIAL GUIDANCE
We provide streamlined Financial Guidance for 2019.
The ramp-up of manufacturing and royalty revenues from Lilly on Elunate is expected to significantly benefit the Company’s financial results in years to come, with a gradual start in 2019 – the product’s first full year on the market. On the broader Innovation Platform, we plan to continue to increase our investment in R&D particularly on clinical development of our main assets in the U.S. and Europe as well as in China (as discussed in the "Product pipeline progress" section below).
On the Commercial Platform, we expect to continue to generate cash flow directly through our subsidiaries and via dividends from our joint ventures. Two government reforms, the Two-Invoice System and the 4+7 Quality Consistency Evaluation ("QCE") System, could narrow growth rates this year before having a positive mid- to long-term impact for Chi-Med (both reforms are discussed in detail the "Commercial Platform," section below).
2019 Guidance
Research & Development Expenses $(160) – (200) million
Adjusted (non-GAAP) Group Net Cash Flow excluding financing activities $(120) – (150) million
2019 U.S. dollar guidance takes into account the weakening of the RMB, which is down 5% relative to the first half average last year due to global macroeconomic factors.
Use of Non-GAAP Financial Measures – References in this announcement to adjusted R&D expenses, adjusted consolidated net income attributable to Chi-Med from our Commercial Platform, adjusted consolidated operating profit from our Commercial Platform, adjusted consolidated net income attributable to Chi-Med from our Prescription Drugs business, adjusted revenues of HBYS and non-consolidated joint ventures, adjusted service fees for Seroquel, adjusted Group net cash flows and adjusted Group net cash flows excluding financing activities are based on non-GAAP financial measures. Please see the "Use of Non-GAAP Financial Measures and Reconciliation" below for further information relevant to the interpretation of these financial measures and reconciliations of these financial measures to the most comparable GAAP measures, respectively.
FINANCIAL STATEMENTS
Chi-Med will today file with the U.S. Securities and Exchange Commission its Annual Report on Form 20-F.
ANNUAL GENERAL MEETING
The Annual General Meeting of Chi-Med will be held at 4th Floor, Hutchison House, 5 Hester Road, Battersea, London SW11 4AN on Wednesday, April 24, 2019 at 11:00 a.m.