On July 28, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13), the innovative, commercial-stage biopharmaceutical company, reported its unaudited financial results for the six months ended June 30, 2021 and provides updates on key clinical and commercial developments since the start of the year (Press release, Hutchison China MediTech, JUL 28, 2021, View Source [SID1234585339]).
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2021 INTERIM RESULTS & BUSINESS UPDATES
"HUTCHMED’s progress has been truly exceptional," said Mr. Simon To, Chairman of HUTCHMED. "Our novel drug discovery and development engine keeps powering ahead. Not only have we secured our third and fourth oncology drug NDA4 approvals in China, but also our first U.S. FDA5 and EMA6 applications for market approval have been accepted."
"Ten registrational studies are set to start this year on our five lead global assets. These are based on exciting data from proof-of-concept studies of both monotherapies and immunotherapy/TKI7 combinations. In addition, our early-stage portfolio is also progressing with our IDH1/28, ERK9 and third generation BTK10 inhibitors all starting development this year."
"In parallel, our commercial oncology operations are rapidly progressing."
"In China, our oncology team is now about 540 people on the ground marketing ELUNATE and SULANDA, recording in-market sales11 of $48.1 million in the first half of 2021. In the U.S., our oncology commercial team is building to support potential launches of surufatinib in 2022 and fruquintinib in 2023. On ORPATHYS, our partner AstraZeneca12 will leverage its great commercial capabilities in lung cancer to market this important first-in-class drug."
"On the corporate-level we took several important steps during the first half to support our global plans. We changed our name to HUTCHMED, consolidating several legacy group and operating names into a single ubiquitous global corporate identity. We also built a balance of about $1.2 billion in cash and resources through our homecoming IPO13 on HKEX as well as through divestment of our non-core OTC14 drug business."
"Over the next three years, we will continue to rapidly build our global R&D15 and commercial organizations, supporting the anticipated global launches of our oncology drugs."
I. COMMERCIAL OPERATIONS
Total revenues increased 47% to $157.4 million in the first half of 2021 (H1-20: $106.8m);
Oncology/Immunology consolidated revenues increased 161% to $42.9 million (H1-20: $16.4m). Our China oncology commercial organization expanded to about 540 personnel (end 2020: ~390) covering over 2,500 oncology hospitals and over 29,000 oncology physicians;
ELUNATE (fruquintinib in China) in-market sales increased 186% to $40.1 million (H1-20: $14.0m), reflecting enhanced detailing, promotion and local & regional marketing in China through our organization;
SULANDA (surufatinib in China) launched for both extra-pancreatic NET16 (mid-January 2021) and pancreatic NET (June 2021), with sales of $8.0 million (H1-20: nil);
ORPATHYS (savolitinib) launched in July 2021, just three weeks after approval, through AstraZeneca’s extensive, market-leading oncology commercial organization. HUTCHMED will receive a fixed royalty of 30% on all sales in China; and
U.S. commercial organization continued to build for the potential surufatinib U.S. approval in the first half of 2022. The team is fully engaged on all aspects of launch readiness including supply chain, market access, marketing, sales and commercial operations.
II. REGULATORY ACHIEVEMENTS
China
Received China NMPA17 NDA approval for ORPATHYS (savolitinib) as a treatment for patients with MET18 exon 14 skipping alteration NSCLC19 in June 2021, making savolitinib the first-in-class selective MET inhibitor in China; and
Received second China NMPA NDA approval for SULANDA in June 2021 as a treatment for patients with advanced pancreatic NET.
United States & Europe
Completed submission of U.S. FDA NDA for surufatinib, which was accepted in June 2021, for the treatment of both pancreatic and extra-pancreatic NET. The assigned PDUFA20 goal date is April 30, 2022; and
Fully submitted EMA MAA21 for surufatinib, which was validated and accepted in July 2021, for the treatment of both pancreatic and non-pancreatic NET.
III. CLINICAL DEVELOPMENT ACTIVITIES
Surufatinib (SULANDA in China), a small molecule inhibitor of VEGFR22, FGFR23 and CSF-1R24 designed to inhibit tumor angiogenesis and promote the body’s immune response against tumor cells via tumor associated macrophage regulation; approved and launched in China
Initiated an international Phase Ib/II study of surufatinib combined with tislelizumab (NCT04579757), BeiGene’s25 PD-126 antibody, in the U.S. and Europe, in March 2021;
Presented NEC27 cohort preliminary data from the China Phase II study of surufatinib plus TUOYI, Junshi’s28 anti-PD-1 antibody, (NCT04169672) at the 2021 ASCO (Free ASCO Whitepaper)29 Annual Meeting. The combination demonstrated good preliminary efficacy and manageable tolerability. There are currently no standard second-line treatments available to NEC patients;
Presented preliminary data from the gastric and gastroesophageal junction cancers cohort of the China Phase II study of surufatinib plus TUOYI (NCT04169672) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, which also demonstrated good preliminary efficacy and manageable tolerability in this patient population. Registration design for gastric cancer is under discussion;
Completed enrollment of a further four China Phase II cohorts for surufatinib plus TUOYI (NCT04169672) including biliary tract, esophageal, small cell lung cancers and sarcoma, with further thyroid, NSCLC and endometrial cancer cohorts continuing to enroll;
Presented updated results from U.S. Phase Ib monotherapy NET cohorts (NCT02549937) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. In heavily pretreated patients with NET, surufatinib demonstrated encouraging efficacy in patients refractory or intolerant to AFINITOR and SUTENT, with a manageable safety profile consistent with the completed Phase III trials SANET‑p and SANET‑ep;
Presented a subgroup analysis by Ki-67 and baseline CgA30 of the Phase III monotherapy study in pancreatic NET (SANET-p) (NCT02589821) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. SANET-p had shown that surufatinib demonstrated statistically significant and clinically meaningful improvement in PFS31, and this exploratory analysis showed that surufatinib demonstrated benefit irrespective of Ki-67 expression levels or baseline CgA; and
Presented Phase II data for surufatinib monotherapy in BTC32 patients (NCT02966821) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting in U.S. patients after first-line chemotherapy. This data highlights surufatinib’s potential in BTC. Emerging data from our Phase II cohort of the surufatinib combination plus TUOYI, however, means we will prioritize development of the combination over the monotherapy.
Potential upcoming clinical and regulatory milestones for surufatinib:
Initiate the first Phase III pivotal study for the SULANDA plus TUOYI combination in late 2021, in NEC patients in China;
Submit for presentation further Phase II data for the SULANDA plus TUOYI combination in select indications in the second half of 2021, such as potentially biliary tract, esophageal, small cell lung cancers and sarcoma and updated NET/NEC cohort data; and
Initiate pivotal study in NET patients in Japan in late 2021.
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; approved and launched in China
Completed enrollment in four cohorts of the Phase II study of fruquintinib combined with TYVYT (NCT03903705), Innovent’s33 PD-1 antibody – in CRC34, HCC35, endometrial cancer and RCC36. Also initiated additional cohorts in gastric cancer, cervical cancer and NSCLC;
Presented preliminary CRC cohorts data from the Phase Ib/II studies of fruquintinib combined with TYVYT and of fruquintinib combined with geptanolimab, Genor’s37 PD-1 antibody, at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (NCT04179084 and NCT03977090, respectively). Both combination studies showed encouraging, durable benefit in advanced CRC patients with manageable safety profiles. A registration strategy for CRC is under discussion, as well as for additional indications; and
Initiated a Phase II study in China and Korea for fruquintinib in combination with tislelizumab (NCT04716634, led by BeiGene) with advanced or metastatic, unresectable gastric cancer, CRC or NSCLC.
Potential upcoming clinical and regulatory milestones for fruquintinib:
Submit Phase Ib U.S. monotherapy expansion data in metastatic CRC (NCT03251378) in the second half of 2021 for publication in early 2022;
Submit for presentation additional cohorts’ data from the studies of fruquintinib combined with an anti-PD-1 antibody in the second half of 2021, such as HCC, endometrial cancer and RCC;
Initiate a Phase Ib/II study in the U.S. for fruquintinib in combination with tislelizumab (NCT04577963) in patients with advanced, refractory triple negative breast cancer in the second half of 2021;
Initiate a registrational study in China of fruquintinib combined with an anti-PD-1 antibody in endometrial cancer patients, in the second half of 2021, the first of several potential pivotal studies with this combination;
Complete enrollment of the FRESCO-2 global Phase III registration study (NCT04322539) in refractory metastatic CRC in late 2021, which is expected to enroll over 680 patients from over 150 sites in 14 countries; and
Complete enrollment of the FRUTIGA China Phase III registration study (NCT03223376) in advanced gastric cancer in late 2021, which is expected to enroll approximately 700 patients from approximately 35 sites in China.
Savolitinib (ORPATHYS), a highly selective small molecule inhibitor of MET being developed broadly across MET-driven patient populations in lung and gastric cancer and renal cell carcinoma
Presented CALYPSO Phase II study data in MET-driven patients (NCT02819596) for savolitinib in combination with IMFINZI, AstraZeneca’s PD-L138 antibody at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. In MET-driven PRCC39 patients, the combination demonstrated encouraging synergy in efficacy and tolerability in line with single agent safety profiles;
Published in The Lancet Respiratory Medicine updated data from the Phase II study (NCT02897479), which were the results reviewed by the NMPA when it approved savolitinib for the treatment of patients with MET exon 14 skipping alteration NSCLC;
Presented final Phase II data for TATTON (NCT02143466) at WCLC40 2020 (held in January 2021), a global exploratory study in NSCLC aiming to recruit patients with MET amplification who had progressed after prior treatment with EGFR41 inhibitors. TATTON clearly confirmed the importance of the savolitinib plus TAGRISSO combination; and
Initiated Phase II study with potential for registration (NCT04923932) for savolitinib in metastatic gastric cancer in China in mid-2021.
Potential upcoming clinical and regulatory milestones for savolitinib:
Initiate a confirmatory China Phase IIIb post-approval study (NCT04923945) of savolitinib monotherapy in MET exon 14 skipping alteration patients in mid-2021 following its market launch, which is expected to enroll approximately 160 patients from approximately 40 sites;
Initiate SAMETA, a global Phase III pivotal study of the savolitinib plus IMFINZI combination in MET-driven, unresectable and locally advanced or metastatic PRCC, based on the encouraging results of SAVOIR and CALYPSO studies, in the second half of 2021;
Initiate SANOVO, a pivotal Phase III study in China for the savolitinib plus TAGRISSO combination in treatment naïve patients with EGFR mutant positive NSCLC with MET aberration in the second half of 2021;
Initiate SACHI, a pivotal Phase III study in China for the savolitinib plus TAGRISSO combination in patients with NSCLC who have progressed following EGFR TKI treatment due to MET amplification in the second half of 2021; and
Conclude the SAVANNAH Phase II study (NCT03778229) for the savolitinib plus TAGRISSO combination in NSCLC patients harboring EGFR mutation and MET amplification or overexpression. SAVANNAH will inform final regulatory, biomarker and dose regimen strategy for the initiation of global Phase III development in late 2021.
HMPL-689, an investigative and highly selective small molecule inhibitor of PI3Kδ42 designed to address the gastrointestinal and hepatotoxicity associated with currently approved and clinical-stage PI3Kδ inhibitors
Initiated Phase II studies with potential for registration intent in China for the treatment of patients with follicular lymphoma and patients with marginal zone lymphoma in April 2021.
Potential upcoming clinical and regulatory milestones for HMPL-689:
Complete Phase Ib dose expansion study (NCT03128164) and submit interim data for presentation in the second half of 2021. Over 95 patients have enrolled at the RP2D43 in six non-Hodgkin’s lymphoma sub-type cohorts;
Complete Phase I dose escalation in the U.S. and Europe (NCT03786926) in mid-2021 and initiate Phase Ib expansion studies in multiple non-Hodgkin’s lymphoma indications;
Complete U.S. FDA regulatory discussions in the second half of 2021 followed by the initiation of registration intent studies in indolent non-Hodgkin’s lymphoma by the end of 2021;
Initiate additional Phase II studies with potential for registration intent in China in additional relapsed/refractory non-Hodgkin’s lymphoma indications in late 2021 or early 2022; and
Initiate studies in combination with other anti-cancer therapies in China in early 2022.
HMPL-523, an investigative and highly selective small molecule inhibitor of Syk44, an important component of the B-cell receptor signaling pathway, for the treatment of hematological cancers and immune disease
Completed Phase Ib ITP45 dose expansion study (NCT03951623) in China with all patients having completed eight weeks treatment.
Potential upcoming clinical and regulatory milestones for HMPL-523:
Initiate dose expansion of the Phase I study (NCT03779113) in the U.S. and Europe, following completion of dose escalation, in the second half of 2021;
Initiate a Phase III study in ITP in China in late 2021, after engagement with the CDE46;
Initiate a Phase II study in AIHA47 in China in late 2021; and
Submit for presentation Phase Ib study preliminary data in ITP (NCT03951623) in late 2021.
HMPL-453, an investigative and highly selective small molecule inhibitor of FGFR 1/2/3
Potential upcoming clinical and regulatory milestones for HMPL-453:
Initiate studies in combination with other anti-cancer therapies in China in late 2021 or early 2022, based on the response to the late June 2021 submission of an IND48 to the NMPA.
HMPL-306, an investigative and highly selective small molecule inhibitor of IDH1/2 designed to address resistance to the currently marketed IDH inhibitors
Initiated dose escalation portion of a Phase I study (NCT04764474) in the U.S. in patients with relapsed or refractory hematological malignancies with an IDH1 and/or IDH2 mutation in the first half of 2021; and
Initiated dose escalation portion of a Phase I study (NCT04762602) in the U.S. in patients with solid tumors with an IDH1 and/or IDH2 mutation in the first half of 2021.
Potential upcoming clinical and regulatory milestones for HMPL-306:
Initiate dose expansion portion of the Phase I studies in China and the U.S. (NCT04272957, NCT04762602 and NCT04764474) in patients with relapsed or refractory hematological malignancies or solid tumors with an IDH1 and/or IDH2 mutation, after full enrollment of the dose escalation cohorts in late 2021 or early 2022.
HMPL-295, an investigative and highly selective small molecule inhibitor of ERK in the MAPK pathway 49 with the potential to address intrinsic or acquired resistance from upstream mechanisms such as RAS-RAF-MEK
Initiated Phase I trial (NCT04908046) in patients with advanced solid tumors in China in July 2021.
HMPL-760, an investigative, highly selective, third-generation small molecule inhibitor of BTK with improved potency versus first generation BTK inhibitors against both wild type & C481S mutant enzymes
Potential upcoming clinical and regulatory milestones for HMPL-760:
Initiate Phase I trial in the U.S. in patients with advanced hematological malignancies in late 2021, based on the IND submission in late June 2021 to the U.S. FDA to begin clinical trials; and
Initiate Phase I trial in China in patients with advanced hematological malignancies in late 2021 or early 2022, based on the IND submission in late June 2021 to the China NMPA.
Discovery, our in-house scientific team has been responsible for the discovery of all eleven of our clinical drug candidates including our three approved oncology drugs ELUNATE, SULANDA and ORPATHYS
Completed preclinical IND-enabling activities and submitted two INDs for HMPL-760 to the U.S. FDA and China NMPA.
Potential upcoming discovery milestones:
IND-enabling toxicity studies are underway for two additional in-house discovered oncology drug candidates, a potent and selective small molecule CSF-1R inhibitor (HMPL-653) and a CD47 antibody (HMPL-A83). If the outcomes of these studies are positive, we will follow with IND submissions in China and the U.S. in late 2021 and early 2022.
IV. MANUFACTURING
Rapid progress being made in building our new flagship Shanghai manufacturing facility, since breaking ground in December 2020. This facility is designed to increase our novel drug product manufacturing capacity by over five-fold and is on-track to commence production in 2024. In the first half of 2021 we obtained all necessary approvals and permits; completed vendor selection process for both the primary construction and specific equipment; completed site preparation and pilings; and initiated construction of the central utility building.
V. OTHER CORPORATE DEVELOPMENTS
Completed listing of ordinary shares and primary offering of 119,600,000 new ordinary shares50 on the Main Board of HKEX (the "Global Offering"), raising net proceeds of approximately $585 million, to advance our late-stage clinical programs as well as our pipeline of clinical-stage and preclinical drug candidates, further strengthening our oncology commercialization, clinical, regulatory and manufacturing capabilities and enabling funding of potential global business development and strategic acquisition opportunities and for general corporate purposes;
Announced a divestment agreement to sell our entire indirect interest in HBYS51, a non-core and non-consolidated over-the-counter drug joint venture business, to GL Capital52 with the aggregate amount attributable to HUTCHMED of approximately $169 million in cash. This cash amount represents about 22 times HBYS’s adjusted net profit attributable to HUTCHMED equity holders of $7.7 million in 202053. The transaction is subject to regulatory approval in China and is expected to close in the second half of 2021;
Changed our group company name to HUTCHMED in April 2021, and the names of several of our key subsidiaries. All remaining key subsidiaries’ names will change over the balance of 2021; and
Announced a strategic partnership with Inmagene54 in January 2021 to further develop four novel preclinical drug candidates discovered by HUTCHMED for the potential treatment of multiple immunological diseases.
VI. IMPACT OF COVID-19
COVID-19 has not impacted our clinical studies in any material manner to date in 2021. We will continue to closely monitor the evolving situation.
INTERIM 2021 FINANCIAL RESULTS
Cash, Cash Equivalents and Short-Term Investments were $950.4 million as of June 30, 2021 compared to $435.2 million as of December 31, 2020.
Adjusted Group (non-GAAP55) net cash flows excluding financing activities in H1 2021 were -$63.1 million (H1-20: -$32.5m) mainly due to Oncology/Immunology R&D spending and partially offset by dividends received from our non-consolidated joint ventures totaling $42.1 million (H1-20: $35.3m); and
Net cash generated from financing activities in H1 2021 totaled $578.3 million (H1-20: $96.3m) mainly resulting from the Global Offering in June 2021 and a private placement in April 2021 to a fund affiliated with BPEA56.
Not included above is a further approximately $250 million from: $77 million in net proceeds in July 2021 from the exercise of the over-allotment option of the Global Offering; the $25 million milestone payment from AstraZeneca triggered by first commercial sales of ORPATHYS in July 2021; and the approximately $150 million in remaining net proceeds receivable under our agreed divestment of HBYS to GL Capital.
Revenues for the six months ended June 30, 2021 were $157.4 million compared to $106.8 million in the six months ended June 30, 2020.
Oncology/Immunology consolidated revenues increased 161% (152% at CER57) to $42.9 million (H1-20: $16.4m) comprised of:
ELUNATE revenues increased 244% to $29.8 million (H1-20: $8.6m) in manufacturing revenues, promotion and marketing service revenues and royalties, as our in-house sales team increased in-market sales 186% to $40.1 million (H1-20: $14.0m), as provided by Lilly58;
SULANDA sales revenues of $8.0 million since mid-January launch, initially to treat patients with advanced extra-pancreatic (non-pancreatic) NET, then also to treat patients with pancreatic NET in June 2021; and
R&D service fee revenues of $5.1 million (H1-20: $7.8m) primarily from AstraZeneca and Lilly.
ORPATHYS $25 million payment and fixed royalty of 30% on all China sales from AstraZeneca not included, as the milestone payment was recently triggered by its first sales in China in July 2021. AstraZeneca has launched ORPATHYS across China through its extensive, market-leading oncology commercial organization.
Other Ventures consolidated revenues increased 27% (18% at CER) to $114.5 million (H1-20: $90.4m) mainly due to continued sales growth of third-party prescription drug products.
Net Expenses for the six months ended June 30, 2021 were $259.8 million compared to $156.5 million in the six months ended June 30, 2020.
Cost of Revenues were $123.2 million (H1-20: $83.6m), the majority of which were the cost of third-party prescription drug products marketed through our profitable Other Ventures, as well as costs associated with promotion and marketing services to Lilly which commenced in October 2020;
R&D Expenses were $123.1 million (H1-20: $74.0m) mainly as a result of an expansion in the development of our eleven novel oncology drug candidates. With six now in global development, our rapidly scaling international clinical and regulatory operations in the U.S. and Europe incurred expenses of $59.3 million (H1-20: $19.9m) while R&D expenses in China were $63.8 million (H1-20: $54.1m);
SG&A59 Expenses were $54.8 million (H1-20: $27.4m) primarily due to increases in staff costs and share-based compensation to support expanding operations. This included the build-up of a large-scale national oncology commercial infrastructure in China to support our oncology products; and
Other Items60 generated net income of $41.3 million (H1-20: $28.5m) resulting primarily from an increase in our share of equity in the earnings from equity investees under our Other Ventures in China which delivered solid underlying net income growth of 19% (9% at CER) in the first half of 2021 and also benefited from a one-time land compensation of $5.1 million (H1-20: nil).
Net Loss attributable to HUTCHMED for the six months ended June 30, 2021 was $102.4 million compared to $49.7 million in the six months ended June 30, 2020.
As a result, the net loss attributable to HUTCHMED in the first half of 2021 was $0.14 per ordinary share / $0.70 per ADS61 compared to net loss attributable to HUTCHMED of $0.07 per ordinary share / $0.35 per ADS, in the six months ended June 30, 2020.
FINANCIAL GUIDANCE
During the first half of 2021, we performed as expected with commercial progress on ELUNATE, SULANDA and now ORPATHYS. While results are encouraging, we leave guidance unchanged.
Use of Non-GAAP Financial Measures and Reconciliation – References in this announcement to adjusted Group net cash flows excluding financing activities and financial measures reported at CER 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.
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Conference Call and Audio Webcast Presentation scheduled today at 8 p.m. HKT / 1 p.m. BST / 8 a.m. EDT – Investors may participate in the call as follows: +852 3027 6500 (Hong Kong) / +44 20 3194 0569 (U.K.) / +1 646 722 4977 (U.S.), or access a live audio webcast of the call via HUTCHMED’s website at www.hutch-med.com/event/.
Additional dial-in numbers are also available at HUTCHMED’s website. Please use participant access code "45675713#."