| NOTIFICATION OF MAJOR HOLDINGS (to be sent to the relevant issuer and to the FCA in Microsoft Word format if possible) i | |||||||||||||||
| 1a. Identity of the issuer or the underlying issuer of existing shares to which voting rights are attached ii: | HUTCHMED (China) Limited | ||||||||||||||
| 1b. Please indicate if the issuer is a non-UK issuer (please mark with an “X” if appropriate) | |||||||||||||||
| Non-UK issuer | X | ||||||||||||||
| 2. Reason for the notification (please mark the appropriate box or boxes with an “X”) | |||||||||||||||
| An acquisition or disposal of voting rights | X | ||||||||||||||
| An acquisition or disposal of financial instruments | |||||||||||||||
| An event changing the breakdown of voting rights | |||||||||||||||
| Other (please specify) iii: | |||||||||||||||
| 3. Details of person subject to the notification obligation iv | |||||||||||||||
| Name | Jean Eric Salata | ||||||||||||||
| City and country of registered office (if applicable) | N/A | ||||||||||||||
| 4. Full name of shareholder(s) (if different from 3.) v | |||||||||||||||
| Name | |||||||||||||||
| City and country of registered office (if applicable) | |||||||||||||||
| 5. Date on which the threshold was crossed or reached vi: | 18 August 2022 | ||||||||||||||
| 6. Date on which issuer notified (DD/MM/YYYY): | 23 August 2022 | ||||||||||||||
| 7. Total positions of person(s) subject to the notification obligation | |||||||||||||||
| % of voting rights attached to shares (total of 8. A) | % of voting rights through financial instruments (total of 8.B 1 + 8.B 2) |
Total of both in % (8.A + 8.B) | Total number of voting rights held in issuer (8.A + 8.B) vii | ||||||||||||
| Resulting situation on the date on which threshold was crossed or reached | 2.91% | 2.91% | 25,173,775 | ||||||||||||
| Position of previous notification (if applicable) | 3.06% | 3.06% | |||||||||||||
| 8. Notified details of the resulting situation on the date on which the threshold was crossed or reached viii | |||||||||||||||
| A: Voting rights attached to shares | |||||||||||||||
| Class/type of sharesISIN code (if possible) |
Number of voting rights ix | % of voting rights | |||||||||||||
|
Direct (DTR5.1) |
Indirect (DTR5.2.1) |
Direct (DTR5.1) |
Indirect (DTR5.2.1) |
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| Ordinary Shares KYG4672N1198 | 25,173,775 | 2.91% | |||||||||||||
| SUBTOTAL 8. A | 25,173,775 | 2.91% | |||||||||||||
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| B 1: Financial Instruments according to DTR5.3.1R (1) (a) | |||||||||||||||
| Type of financial instrument | Expiration date x |
Exercise/ Conversion Period xi |
Number of voting rights that may be acquired if the instrument is exercised/converted. | % of voting rights | |||||||||||
| SUBTOTAL 8. B 1 | |||||||||||||||
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| B 2: Financial Instruments with similar economic effect according to DTR5.3.1R (1) (b) | |||||||||||||||
| Type of financial instrument | Expiration date x |
Exercise/ Conversion Period xi |
Physical or cash Settlement xii |
Number of voting rights | % of voting rights | ||||||||||
| SUBTOTAL 8.B.2 | |||||||||||||||
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— Trial met primary endpoint of overall survival and all secondary endpoints —
— Selected as a late-breaker presentation —
— Conference call and webcast to be held on Monday, September 12 at 2:00 pm Paris time to review the presentation at the Congress —
Hong Kong, Shanghai & Florham Park, NJ — Tuesday, August 23, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) today announces that initial results of the multi-regional clinical trial (“MRCT”) of fruquintinib, FRESCO-2, will be presented at the upcoming European Society for Medical Oncology (“ESMO”) Congress 2022, taking place on September 9-13, 2022. The meeting will be held at the Paris Expo Porte de Versailles, in Paris, France.
Further details of the presentation are as follows:
| Title: | FRESCO-2: A global Phase 3 multi-regional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer |
| Presenter: | Arvind Dasari, MD, MS, Associate Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX |
| Session: | Proffered Paper session 2: GI, lower digestive |
| Abstract No.: | LBA25 |
| Date & Time: | Monday, September 12, 2022, 10:55 – 11:15 am Paris time |
| Location: | 7.2.F – Fécamp Auditorium |
Investor audio webcast and conference call is scheduled on Monday, September 12 at 2:00 pm Paris Time (1:00 pm London time, 8:00 am New York time, and 8:00 pm Hong Kong time).
Participating on the webcast will be members of the HUTCHMED management team as well as co-Principal Investigators from the study: Dr. Arvind Dasari and Professor Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology and Co-Leader, Gastrointestinal Cancer Research Program, at the Vanderbilt-Ingram Cancer Center.
Details of the conference call dial-in and the webcast link will be provided on the company website at www.hutch-med.com/event/. The presentation will be available for downloading before the conference call begins. A replay will also be available on the website shortly after the event.
The FRESCO-2 study was a MRCT conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care (“BSC”) vs placebo plus BSC in patients with advanced, refractory metastatic colorectal cancer (“CRC”). As previously disclosed, the study met its primary endpoint of overall survival (“OS”) in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in progression-free survival (“PFS”), a key secondary endpoint, was observed. The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported studies.
CRC is a cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, estimated to have caused more than 915,000 deaths in 2020.[1] In the U.S., an estimated 151,000 people will have been diagnosed with CRC and 53,000 people will have died from CRC in 2022.[2] In Europe, CRC is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020.1 In Japan, CRC is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020.1
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Metastatic CRC in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE®. It has been included in the China National Reimbursement Drug List (NRDL) since January 2020. ELUNATE® is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study[3], a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:
Gastric Cancer (“GC”) in China: The FRUTIGA study is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for the treatment of patients with advanced gastric or esophagogastric junction (“GEJ”) adenocarcinoma who did not respond to first-line standard chemotherapy. Approximately 700 patients have received either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. The co-primary efficacy endpoints are OS and PFS (clinicaltrials.gov identifier: NCT03223376).
Immunotherapy combinations: HUTCHMED has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd) and sintilimab (IBI308, developed by Innovent Biologics, Inc. and marketed as TYVYT® in China).
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with advanced CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with advanced CRC or other indications in the U.S., Europe, Japan, Australia or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the safety profile of fruquintinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug products such as paclitaxel, tislelizumab and sintilimab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
[1] The Global Cancer Observatory. Accessed September 21, 2021.
[2] SEER. Cancer Stat Facts: Colorectal Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed June 27, 2022.
[3] Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855.
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe – Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie / Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
| Corporate Information | |
| Chairman’s Statement | 4 |
| 2021 Interim Results & Business Updates | 5 |
| Interim 2022 Financial Results | 11 |
| Financial Summary | 13 |
| Operations Review | |
|
Oncology/Immunology |
16 28 |
| Use of Non-GAAP Financial Measures and Reconciliation | 29 |
| Group Capital Resources | 31 |
| Other Information | 36 |
| Disclosure of Interests | 40 |
| Long Term Incentive Plan | 47 |
| Corporate Governance | 50 |
| Changes in Information of Directors | 51 |
| Interim Unaudited Condensed Consolidated Financial Statements | 52 |
| References and Abbreviations | 78 |
| Information for Shareholders | |
San Diego, Shanghai and Hong Kong — Tuesday, August 9, 2022: Inmagene Biopharmaceuticals (“Inmagene“) and HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) announce today that the first participant, based in the United States, was dosed in a global Phase I trial of IMG-004, a non-covalent, reversible, third-generation Bruton Tyrosine Kinase (“BTK”) inhibitor. Inmagene is developing the drug candidate to potentially treat immunological diseases.
The Phase I study is a double-blind, randomized, placebo-controlled, single and multiple dose escalation study in healthy subjects. The study aims to explore IMG-004’s safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects. Additional details can be found at clinicaltrials.gov, using identifier NCT05349097.
“IMG-004 is the second novel drug candidate under the collaboration with HUTCHMED which Inmagene has successfully advanced into clinical studies this year,” said Dr Jonathan Wang, Inmagene’s Chairman and Chief Executive Officer. “Inmagene also expects to submit another investigational new drug (“IND”) application for a third novel drug candidate in 2022. Such results have demonstrated the Inmagene team’s innovative and execution capabilities.”
Dr Jean-Louis Saillot, Chief Development Officer of Inmagene, said, “IMG-004 was designed specifically for inflammatory and autoimmune diseases, and in preclinical models, it has shown improved activity, selectivity, and pharmacokinetic profile. We welcome the start of the IMG-004 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with immunological diseases.”
IMG-004 is a non-covalent, reversible small molecule inhibitor targeting BTK. Designed specifically for inflammatory and autoimmune diseases that usually require long-term treatment, IMG-004 is potent, highly selective and brain permeable. It was originally discovered by HUTCHMED, with Inmagene assuming development responsibility at the candidate stage. Inmagene has an exclusive option to in-license IMG-004’s global rights for the treatment of immunological diseases.
BTK is a non-receptor tyrosine kinase in the Tec family of protein tyrosine kinases. It is involved in innate and adaptive immune responses related to certain immune-mediated diseases. Given the central role of BTK in immunity pathways, BTK inhibitors may offer a potential therapeutic approach for the treatment of a wide range of inflammatory and autoimmune diseases.
Inmagene is a global clinical-stage biotechnology company focused on developing novel therapeutics for immunology-related diseases. The company is building a robust pipeline of nearly twenty drug development programs.
Inmagene’s most advanced drug candidate is IMG-020 (izokibep), which has successfully met the endpoints in global phase II studies for both psoriasis and psoriatic arthritis (“PsA”). It has received the IND approval from the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for phase III studies in plaque psoriasis. Inmagene is working with its partners to conduct global phase II studies for multiple autoimmune diseases, including PsA, ankylosing spondylitis (AS) and uveitis. In addition, IMG-004 and IMG-007, both of which with options on global rights, are in global phase I studies.
Believing in “Borderless Innovation”, the Inmagene team strives to integrate efficient resources worldwide to develop novel therapeutics for global patients. Based on its proprietary QuadraTek™ drug discovery platform, Inmagene is operating 12 “Smart Innovation” programs to create and develop drug candidates with global rights. Inmagene also in-licenses drug candidates and, together with its partners, carries out global development activities, including global multi-center clinical trials. Inmagene has formed strategic partnerships with multiple partners, such as HUTCHMED and Affibody AB, to develop highly innovative drug candidates. For more information, please visit: www.inmagenebio.com.
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Inmagene’s and/or HUTCHMED’s current expectations regarding future events, including expectations regarding the therapeutic potential of IMG-004 for the treatment of patients with immunological diseases, the further clinical development of IMG-004, expectations as to whether clinical studies of IMG-004 would meet their primary or secondary endpoints, and expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of IMG-004 to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of IMG-004 for a targeted indication; the sufficiency of funding; and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of various risks applicable to HUTCHMED, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. Neither Inmagene nor HUTCHMED undertakes to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Investor Enquiries |
|
| Aaron Liu | aaronliu@inmagenebio.com |
Media Enquiries |
|
| Sinara Zhang | zhangy@inmagenebio.com |
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe – Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie / Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
— Trial met primary endpoint of overall survival and all secondary endpoints —
— Overall safety consistent with fruquintinib known profile —
— Plans for regulatory submissions underway in the U.S., Europe and Japan —
— Results to be submitted to an upcoming medical meeting —
Hong Kong, Shanghai & Florham Park, NJ — Monday, August 8, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM, HKEX: 13) today announces that the pivotal global Phase 3 FRESCO-2 trial evaluating the investigational use of fruquintinib met its primary endpoint of overall survival (“OS”) in patients with advanced, refractory metastatic colorectal cancer (“CRC”).
The FRESCO-2 study was a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care (“BSC”) vs placebo plus BSC in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically-significant improvement in progression-free survival (“PFS”), a key secondary endpoint, was observed. The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported studies. Full results will be submitted for presentation at an upcoming medical meeting.
HUTCHMED has been in communication with regulatory agencies globally regarding the FRESCO-2 trial design and conduct and will discuss these data with the agencies in the U.S., Europe and Japan with the intent to submit marketing authorization applications as soon as possible. The U.S. FDA granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020.
“We are very happy to see the positive outcomes of the FRESCO-2 study which offers a potential new treatment for patients with advanced metastatic colorectal cancer, where the unmet need is very high and patients have limited treatment options,” said Dr Marek Kania, Executive Vice President, Managing Director and Chief Medical Officer of HUTCHMED International. “Results from the global FRESCO-2 study supplement findings from the original FRESCO study that led to the marketing approval and commercialization of fruquintinib in China. We would like to thank the patients, their families, and the healthcare professionals who participated in this study and helped achieve this important milestone.”
Professor Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology and Co-Leader, Gastrointestinal Cancer Research Program, at the Vanderbilt-Ingram Cancer Center, who served as the FRESCO2 co-PI and Steering Committee member said: “Completion of the international FRESCO-2 phase III trial in a timely fashion during the era of COVID-19 isolation demonstrates the unmet need for new therapeutic agents in metastatic colorectal cancer. By meeting the primary endpoint of OS with a secondary endpoint of PFS, fruquintinib provides a significant potential new option for our refractory colorectal cancer patients. As an oral agent, fruquintinib also provides added convenience for our patients. Based on fruquintinib’s profile, we will likely see further exploration in future clinical trials in different settings. This is extremely encouraging, and I look forward to seeing the final results.”
Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “We are pleased to have successfully completed our first multi-regional clinical trial, FRESCO-2, to support the global registration of fruquintinib. It has already benefited patients with advanced CRC in China since its launch in 2018. It is also being evaluated alone and in combination with other agents in various tumor types in ongoing studies around the world.”
HUTCHMED retains all commercial rights to fruquintinib outside of China. In China, where fruquintinib is marketed under the brand name ELUNATE®, HUTCHMED is partnered with Eli Lilly and Company and is responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing. Fruquintinib is not approved for use outside of China.
CRC is a cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, estimated to have caused more than 915,000 deaths in 2020.[i] In the U.S., an estimated 151,000 people will have been diagnosed with CRC and 53,000 people will have died from CRC in 2022.[ii] In Europe, CRC is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020.1 In Japan, CRC is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020.1
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Metastatic CRC in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE®. It has been included in the China National Reimbursement Drug List (NRDL) since January 2020. ELUNATE® is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study[iii], a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:
Gastric Cancer (“GC”) in China: The FRUTIGA study is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for the treatment of patients with advanced gastric or esophagogastric junction (“GEJ”) adenocarcinoma who did not respond to first-line standard chemotherapy. Approximately 700 patients have received either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. The co-primary efficacy endpoints are OS and PFS (clinicaltrials.gov identifier: NCT03223376).
Immunotherapy combinations: HUTCHMED has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd) and sintilimab (IBI308, developed by Innovent Biologics, Inc. and marketed as TYVYT® in China).
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.
This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with advanced CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with advanced CRC or other indications in the U.S., Europe, Japan, Australia or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the safety profile of fruquintinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug products such as paclitaxel, tislelizumab and sintilimab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).
[i] The Global Cancer Observatory. Accessed September 21, 2021.
[ii] SEER. Cancer Stat Facts: Colorectal Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed June 27, 2022.
[iii] Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855.
— MET is the most common biomarker in patients with EGFR-mutated lung cancer who develop resistance to targeted therapy —
— Global SAFFRON Phase III trial evaluating this combination is underway —
Hong Kong, Shanghai & Florham Park, NJ — Monday, August 8, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM, HKEX: 13) and AstraZeneca PLC (“AstraZeneca”) (LON/STO/Nasdaq: AZN) today announce that preliminary results from the SAVANNAH Phase II trial showed that TAGRISSO® (osimertinib) plus savolitinib demonstrated an objective response rate (“ORR”) of 49% (95% confidence interval [“CI”], 39-59%) in patients with epidermal growth factor receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”) with high levels of mesenchymal epithelial transition (“MET”) overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO®.
The highest ORR was observed in patients with high levels of MET who were not treated with prior chemotherapy (52% [95% CI, 41-63%]). In patients whose tumors did not show high levels of MET, the ORR was 9% (95% CI, 4-18%). These results are being shared at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), taking place on August 6-9, 2022 in Vienna, Austria.
Savolitinib, marketed in China under the brand name ORPATHYS®, is an oral, potent and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed and commercialized by AstraZeneca and HUTCHMED.
While EGFR-targeted therapy can provide a durable survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being the most common resistance biomarker.1 Among patients screened for enrolment in SAVANNAH, all of whom experienced disease progression on TAGRISSO®, 62% had tumors with MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.
Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and Principal Investigator in the SAVANNAH Phase II trial, said: “Acquired resistance to targeted therapy and disease progression are difficult realities for most patients with EGFR-mutated NSCLC. These preliminary SAVANNAH results potentially support a novel approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, like savolitinib. They also suggest that with the right biomarker testing strategy, MET may be a more prevalent target among resistant patients than previously understood, supporting further investigation of the osimertinib plus savolitinib regimen.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca said: “The current standard of care for patients with EGFR-mutated lung cancer who progress on targeted treatment is chemotherapy. The results from SAVANNAH suggest savolitinib added to TAGRISSO® at the time of disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option. We look forward to better understanding the potential of the TAGRISSO® plus savolitinib regimen in this trial and in the SAFFRON Phase III trial.”
Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: “It is encouraging to see the savolitinib and TAGRISSO® combination regimen progress into a global Phase III study, SAFFRON, with a well-supported patient selection strategy that could benefit more patients than previously recognized. The preliminary results of the SAVANNAH study also affirm the role of molecular testing prior to initiating subsequent treatment for NSCLC patients who experience disease progression on an EGFR-targeted therapy. We are aligned in pursuing a selective, patient-centric approach in development efforts for savolitinib in this setting.”
In this analysis, patients’ MET overexpression and/or amplification levels were determined by two tests: immunohistochemistry (“IHC”), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridization (“FISH”), which detects a specific DNA sequence from cancer cells. All patients in this analysis (n=193) had at least IHC50+ and/or FISH5+, and were treated with savolitinib 300mg once daily added to TAGRISSO® 80mg once daily following disease progression on TAGRISSO® alone.
Summary of efficacy resultsi:
| Endpoint | All patients (IHC50+ and/or FISH5+; n=193) |
Patients with high levels of METii (IHC90+ and/or FISH10+) |
Patients with lower levels of METii (n=77) | |
| All (n=108) |
No prior chemo (n=87) |
|||
| ORR, % (95% CI) | 32 (26, 39) | 49 (39, 59) | 52 (41, 63) | 9 (4, 18) |
| Median DoRiii, months (95% CI) | 8.3 (6.9, 9.7) | 9.3 (7.6, 10.6) | 9.6 (7.6, 14.9) | 6.9 (4.1, 16.9) |
|
Median PFSiv, months (95% CI) |
5.3 (4.2, 5.8) | 7.1 (5.3, 8.0) | 7.2 (4.7, 9.2) | 2.8 (2.6, 4.3) |
| DCRv, % (95% CI) | 61 (53, 68) | 74 (65, 82) | 75 (64, 83) | 43 (32, 55) |
The safety profile of TAGRISSO® plus savolitinib was consistent with the known profiles of the combination and each treatment alone. No new safety signals were identified. Less than half (45%) of patients in this analysis experienced Grade 3 or higher adverse events (“AEs”), with those most frequently reported including pulmonary embolism, dyspnea, decreased neutrophil count and pneumonia. AEs attributable to savolitinib and leading to discontinuation occurred in 13% of patients.
The global SAFFRON Phase III trial will further assess the TAGRISSO® plus savolitinib combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.3 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease and approximately 10-15% of NSCLC patients in the U.S. and Europe and 30-40% of patients in Asia have EGFRm NSCLC.4,5,6,7
MET is a tyrosine kinase receptor that has an essential role in normal cell development.8 MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is the primary mechanism of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. 8,9 The prevalence of MET depends on the sample type, detection method and assay cut-off used.10
SAVANNAH is an ongoing global, randomized, single-arm Phase II trial studying the efficacy of savolitinib added to TAGRISSO® in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO®. Patients were treated with savolitinib 300 or 600 mg once-daily (QD) or 300 mg twice-daily, in combination with oral osimertinib 80 mg QD.
The trial has enrolled 294 patients to date in more than 80 centers globally, including centers in the U.S., Canada, Europe, South America and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS, DoR and safety.
TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO® (40mg and 80mg once-daily oral tablets) has been used to treat approximately 575,000 patients across indications worldwide and AstraZeneca continues to explore TAGRISSO® as a treatment for patients across multiple stages of EGFRm NSCLC.
In Phase III trials, TAGRISSO® is being investigated in the neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), in the Stage III locally advanced unresectable setting following chemoradiation therapy (LAURA), and in combination with chemotherapy in the advanced setting (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO® given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.
Savolitinib is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.
Savolitinib is marketed in China under the brand name ORPATHYS® for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.
In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including TAGRISSO® (osimertinib) and IRESSA® (gefitinib); IMFINZI® (durvalumab) and tremelimumab; ENHERTU® (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; ORPATHYS® (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.
References
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of savolitinib for the treatment of patients with NSCLC, the further clinical development of savolitinib in this and other indications, its expectations as to whether clinical studies of savolitinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of HUTCHMED’s data to support New Drug Application approval of savolitinib for the treatment of patients with NSCLC in China, the U.S., E.U., Japan or other jurisdictions, the safety profile of savolitinib, the potential for savolitinib to become a new standard of care for patients with NSCLC and other types of cancer, its ability to implement and complete its further clinical development plans for savolitinib, the potential commercial launch of savolitinib in the U.S., E.U., Japan, China and other jurisdictions, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of TAGRISSO® and IMFINZI® as combination therapeutics with savolitinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of TAGRISSO® and IMFINZI®. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe – Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie / Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Oncology/Immunology revenues up 113% to $91.1 million, due to ELUNATE®, SULANDA® and ORPATHYS® growth
First presentation of SAVANNAH data showing 52% response rate and 9.6 month duration of response in 2L+ post-TAGRISSO® NSCLC1 patients with high MET2 levels and no prior chemotherapy
Initiated six new trials thus far in 2022 with a further six starting, including with five new drug candidates
FRESCO-2 Phase III, our first global multi-regional clinical trial, on track to read out in August 2022
Company to Host Interim Results Call & Webcast Today at 8 p.m. HKT / 1 p.m. BST / 8 a.m. EDT
Hong Kong, Shanghai & Florham Park, NJ — Monday, August 1, 2022: HUTCHMED (China) Limited (“HUTCHMED”, the “Company” or “we”) (Nasdaq/AIM:HCM; HKEX:13), the innovative, commercial-stage biopharmaceutical company, today reports its unaudited financial results and provides updates on key clinical and commercial developments for the six months ended June 30, 2022.
All amounts are expressed in U.S. dollars unless otherwise stated.
“HUTCHMED has continued to make good progress in the last six months,” said Mr Simon To, Chairman of HUTCHMED.
“We have driven revenue growth in our innovative portfolio of marketed drugs. With ELUNATE® for CRC3 and following last year’s successful launches of ORPATHYS® for MET-driven NSCLC and SULANDA® for epNETs4 and pNETs5, this will be the first full year of product sales from three novel, in-house discovered oncology products in China, with strong sales momentum. We have also significantly expanded our in-house commercial team to drive growth. On top of this, in June we announced that TAZVERIK® was approved for use in the Hainan Pilot Zone, bringing the clinical benefits of a fourth product to patients in China.”
“Our experienced clinical team has also made progress in the first half of this year. We have initiated a number of key early-stage trials and our later-stage pipeline of on-going studies are also moving at a steady pace, with promising new data from the SAVANNAH study of savolitinib combined with osimertinib being presented in more detail in August. We believe that the achievement of these milestones demonstrates the depth and potential of our R&D6 pipeline, which is the core of our business and the foundation for our growth in the years ahead.”
“HUTCHMED continues to be well-financed, which positions us well to continue delivering on our strategic objectives. We are a global biopharmaceutical company developing high quality, novel oncology and immunology drug candidates for patients across the world and under the leadership of Dr Weiguo Su, our new Chief Executive Officer, I have great hope for the future.”
Dr Weiguo Su said, “In HUTCHMED, I see a company with exciting science and a first-in-class or differentiated, best-in-class pipeline of clinical-stage candidates, each with substantial prospects for additional indications and combinations, which is exceptional, particularly in the China biopharma industry.”
“After driving our innovation as Head of Research and Chief Scientific Officer for the last 16 years, I was delighted to become the Chief Executive Officer earlier this year and am very excited about the next chapter of our growth.”
“There are several reasons which underline the opportunity in our future. These include our expected ongoing growth of ORPATHYS®, SULANDA® and ELUNATE® revenues in China, and FRESCO-2, our first global, multi-regional clinical trial, which is due to read out later this month. While receiving a Complete Response Letter for surufatinib from the U.S. FDA7 earlier this year and our decision today to withdraw the EMA8 MAA9 are a disappointment, it has no impact on our global development strategy. We will continue to leverage our solid balance sheet, strong commercial capability with extensive China coverage that generates cash, pipeline of innovative products and world-class people, as we work towards our goal of being a leading global biopharmaceutical company.”
| $’millions | In-market Sales* | Consolidated Revenues** | ||||||
| H1 2022 | H1 2021 | % Change | H1 2022 | H1 2021 | % Change | |||
| Unaudited | Unaudited | |||||||
| ELUNATE® | $50.4 | $40.1 | 26% | $36.0 | $29.8 | 21% | ||
| SULANDA® | $13.6 | $8.0 | 69% | $13.6 | $8.0 | 69% | ||
| ORPATHYS® | $23.3 | – | – | $13.8 | – | – | ||
| TAZVERIK® | $0.1 | – | – | $0.1 | – | – | ||
| Product Sales | $87.4 | $48.1 | 82% | $63.5 | $37.8 | 68% | ||
| Other R&D services income | $12.6 | $5.1 | 149% | |||||
| Milestone payment | $15.0 | – | – | |||||
| Total Oncology/Immunology | $91.1 | $42.9 | 113% | |||||
|
* = For ELUNATE® and ORPATHYS®, represents total sales to third parties as provided by Lilly12 and AstraZeneca, respectively; |
||||||||
Major milestones and data presentations for savolitinib in 2022:
Potential upcoming clinical and regulatory milestones for savolitinib:
Major milestones and data presentations for fruquintinib in 2022:
Potential upcoming clinical and regulatory milestones for fruquintinib:
Major data presentation for surufatinib in 2022:
Potential upcoming clinical and regulatory milestones for surufatinib:
Potential upcoming clinical and regulatory milestones for amdizalisib:
Potential upcoming clinical milestones for sovleplenib:
Major milestones and data presentations for tazemetostat in 2022:
Potential upcoming clinical and regulatory milestones for tazemetostat:
Potential upcoming clinical and regulatory milestones for HMPL-306:
COVID-19 had some impact on our research, clinical studies and our commercial activities in the first half of 2022, particularly with respect to hospital lockdowns, travel restrictions, and shipping difficulties. Sites in Shanghai were particularly impacted during April and May. Measures were put in place to minimize the impact of such restrictions to the extent possible, including online patient follow-up and the retention of core research teams on-site to maintain critical activities, with business returning to normal in June. We will continue to closely monitor the evolving situation.
The Group is committed to the long-term sustainability of its businesses and the communities in which we conduct business. In the first half of 2022, we published 2021 Sustainability Report of HUTCHMED, detailing our environmental, social and governance performance of HUTCHMED during 2021, including our sustainability governance, stakeholder engagement and materiality analysis, business ethics, environmental performance, research and development, responsible commercialization, and human capital management.
Five new sustainability-related policies and statements – Sustainability Policy, Environmental Policy, Health and Safety Policy, Human Rights Policy and Modern Slavery and Human Trafficking Statement – were published along with the 2021 Sustainability Report, serving to demonstrate our commitment in sustainability, enriched and more transparent disclosures, as well as acting as an important gateway to communicate with our stakeholders in all sustainability matters.
In the second half of 2022, we will continue our efforts in facilitating discussions regarding relevant sustainability issues and opportunities, including climate-related issues, and actively looking to set our own sustainability targets and goals.
The Holding Foreign Companies Accountable Act, or the Act, was signed into law in December 2020. It provides that if the U.S. Securities and Exchange Commission (SEC) determines that a U.S.-listed company has filed audit reports issued by a registered public accounting firm that has not been subject to inspection by the Public Company Accounting Oversight Board (PCAOB) for three consecutive years beginning in 2021, the SEC shall prohibit such company’s shares or ADSs40 from being traded on a national securities exchange or in the over-the-counter trading market in the U.S.
As had been expected, following its adoption of implementing rules pursuant to the Act, the SEC named over 150 companies, including HUTCHMED, to its conclusive list of issuers identified under these rules. Under the current terms of the Act, the Company’s ADSs will be delisted from the Nasdaq Stock Market in early 2024, unless the Act is amended to exclude the Company or the PCAOB is able to conduct a full inspection of the Company’s auditor during the required timeframe. In addition, legislation is being considered in the U.S. to shorten the number of non-inspection years from three years to two. In the case that such legislation becomes law, it will reduce the time period before our ADSs could be delisted from the Nasdaq Stock Market and prohibited from over-the-counter trading in the U.S. from 2024 to 2023.
This has had no impact on the Company’s business operations. We continue to monitor market developments and evaluate all strategic options, with the appropriate counsel and guidance.
The Company’s ADSs, each of which represents five ordinary shares, continue to trade uninterrupted on the Nasdaq Global Select Market. Its ordinary shares are also admitted for trading in London on the AIM market, and are primary listed on HKEX41. The shares listed on HKEX and AIM are fully fungible with the shares represented by the Company’s ADSs.
ELUNATE® revenues increased 21% to $36.0 million (H1-21: $29.8m) in manufacturing revenues, promotion and marketing service revenues and royalties, as our in-house sales team increased in-market sales 26% to $50.4 million (H1-21: $40.1m), as provided by Lilly;
SULANDA® revenues increased 69% to $13.6 million (H1-21: $8.0m), after inclusion on the NRDL starting in January 2022;
ORPATHYS® revenues of $13.8 million (H1-21: nil), in manufacturing revenues and royalties. AstraZeneca reported $23.3 million in-market sales (H1-21: nil) of ORPATHYS® in first half of 2022;
TAZVERIK® revenues of $0.1 million following its successful launch in Hainan in June 2022;
Milestone payment of $15.0 million (H1-21: nil), to us by AstraZeneca, was triggered in February 2022 upon initiation of start-up activities for SAFFRON; and
Other R&D services income of $12.6 million (H1-21: $5.1m), which were primarily fees from AstraZeneca and Lilly for the management of development activities in China.
Condensed Consolidated Balance Sheets Data
(in $’000)
| As of June 30, | As of December 31, | |||
| 2022 | 2021 | |||
| (Unaudited) | ||||
| Assets | ||||
| Cash and cash equivalents and short-term investments | 826,200 | 1,011,700 | ||
| Accounts receivable | 77,078 | 83,580 | ||
| Other current assets | 118,959 | 116,796 | ||
| Property, plant and equipment | 44,059 | 41,275 | ||
| Investments in equity investees | 82,999 | 76,479 | ||
| Other non-current assets | 45,038 | 42,831 | ||
| Total assets | 1,194,333 | 1,372,661 | ||
| Liabilities and shareholders’ equity | ||||
| Accounts payable | 51,005 | 41,177 | ||
| Other payables, accruals and advance receipts | 233,606 | 210,839 | ||
| Bank borrowings | 418 | 26,905 | ||
| Other liabilities | 57,455 | 54,226 | ||
| Total liabilities | 342,484 | 333,147 | ||
| Company’s shareholders’ equity | 799,728 | 986,893 | ||
| Non-controlling interests | 52,121 | 52,621 | ||
| Total liabilities and shareholders’ equity | 1,194,333 | 1,372,661 |
Condensed Consolidated Statements of Operations Data
(Unaudited, in $’000, except share and per share data)
| Six Months Ended June 30, | |||
| 2022 | 2021 | ||
| Revenues: | |||
| Oncology/Immunology – Marketed Products | 63,517 | 37,795 | |
| Oncology/Immunology – R&D | 27,552 | 5,056 | |
| Oncology/Immunology consolidated revenues | 91,069 | 42,851 | |
| Other Ventures | 110,978 | 114,511 | |
| Total revenues | 202,047 | 157,362 | |
| Operating expenses: | |||
| Costs of revenues | (137,318) | (123,249) | |
| Research and development expenses | (181,741) | (123,050) | |
| Selling and general administrative expenses | (79,742) | (54,797) | |
| Total operating expenses | (398,801) | (301,096) | |
|
|
(196,754) | (143,734) | |
| Other (expense)/income, net | (3,882) | 3,287 | |
| Loss before income taxes and equity in earnings of equity investees | (200,636) | (140,447) | |
| Income tax benefit/(expense) | 4,215 | (1,859) | |
| Equity in earnings of equity investees, net of tax | 33,549 | 42,966 | |
| Net loss | (162,872) | (99,340) | |
| Less: Net loss/(income) attributable to non-controlling interests | 11 | (3,057) | |
| Net loss attributable to HUTCHMED | (162,861) | (102,397) | |
|
Losses per share attributable to HUTCHMED – basic and diluted |
(0.19) | (0.14) | |
| Number of shares used in per share calculation – basic and diluted | 849,283,553 | 729,239,181 | |
|
Losses per ADS attributable to HUTCHMED – basic and diluted |
(0.96) | (0.70) | |
| Number of ADSs used in per share calculation – basic and diluted | 169,856,711 | 145,847,836 | |
We provide financial guidance for 2022 below reflecting expected revenue growth of ELUNATE®, SULANDA® and ORPATHYS® in China. We believe that we remain on track to meet the 2022 guidance for Oncology/Immunology revenues provided in the announcement of our 2021 full year results on March 3, 2022.
| H1 2022 Actual |
2022 Current Guidance |
Adjustments vs. Previous Guidance | |
| Oncology/Immunology consolidated revenues | $91.1 million | $160 – 190 million | nil |
Shareholders and investors should note that:
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.
—–
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 “55793362#.”
—–
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe – Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie / Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Unless the context requires otherwise, references in this announcement to the “Group,” the “Company,” “HUTCHMED,” “HUTCHMED Group,” “we,” “us,” and “our,” mean HUTCHMED (China) Limited and its consolidated subsidiaries and joint ventures unless otherwise stated or indicated by context.
The performance and results of operations of the Group contained within this announcement are historical in nature, and past performance is no guarantee of future results of the Group. This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by words like “will,” “expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,” “pipeline,” “could,” “potential,” “first-in-class,” “best-in-class,” “designed to,” “objective,” “guidance,” “pursue,” or similar terms, or by express or implied discussions regarding potential drug candidates, potential indications for drug candidates or by discussions of strategy, plans, expectations or intentions. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that any of our drug candidates will be approved for sale in any market, that any approvals which are obtained will be obtained at any particular time, or that the sales of products marketed or otherwise commercialized by HUTCHMED and/or its collaboration partners (collectively, “HUTCHMED’s Products”) will achieve any particular revenue or net income levels. In particular, management’s expectations could be affected by, among other things: unexpected regulatory actions or delays or government regulation generally, including, among others, the risk that HUTCHMED’s ADSs could be barred from trading in the United States as a result of the Holding Foreign Companies Accountable Act and the rules promulgated thereunder; the uncertainties inherent in research and development, including the inability to meet our key study assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria and funding requirements, changes to clinical protocols, unexpected adverse events or safety, quality or manufacturing issues; the inability of a drug candidate to meet the primary or secondary endpoint of a study; the inability of a drug candidate to obtain regulatory approval in different jurisdictions or the utilization, market acceptance and commercial success of HUTCHMED’s Products after obtaining regulatory approval; competing drugs and product candidates that may be superior to, or more cost effective than HUTCHMED’s Products and drug candidates; the impact of studies (whether conducted by HUTCHMED or others and whether mandated or voluntary) or recommendations and guidelines from governmental authorities and other third parties on the commercial success of HUTCHMED’s Products and candidates in development; the ability of HUTCHMED to manufacture and manage supply chains for multiple products and product candidates; the availability and extent of reimbursement of HUTCHMED’s Products from third-party payers, including private payer healthcare and insurance programs and government insurance programs; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; the costs of developing, producing and selling HUTCHMED’s Products; the ability of HUTCHMED to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; global trends toward health care cost containment, including ongoing pricing pressures; uncertainties regarding actual or potential legal proceedings, including, among others, actual or potential product liability litigation, litigation and investigations regarding sales and marketing practices, intellectual property disputes, and government investigations generally; and general economic and industry conditions, including uncertainties regarding the effects of the persistently weak economic and financial environment in many countries, uncertainties regarding future global exchange rates and uncertainties regarding the impact of the COVID-19 pandemic. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on HKEX. HUTCHMED is providing the information in this announcement as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.
In addition, this announcement contains statistical data and estimates that HUTCHMED obtained from industry publications and reports generated by third-party market research firms. Although HUTCHMED believes that the publications, reports and surveys are reliable, HUTCHMED has not independently verified the data and cannot guarantee the accuracy or completeness of such data. You are cautioned not to give undue weight to this data. Such data involves risks and uncertainties and are subject to change based on various factors, including those discussed above.
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).
Ends
REFERENCES AND ABBREVIATIONS
1 NSCLC = Non-small cell lung cancer.
2 MET = Mesenchymal epithelial transition factor.
3 CRC = Colorectal cancer.
4 epNET = extra-pancreatic neuroendocrine tumor.
5 pNET= pancreatic neuroendocrine tumor.
6 R&D = Research and development.
7 FDA = Food and Drug Administration.
8 EMA = European Medicines Agency.
9 MAA = Marketing Authorization Application.
10 In-market sales = total sales to third parties provided by Eli Lilly (ELUNATE®), AstraZeneca (ORPATHYS®) and HUTCHMED (SULANDA® and TAZVERIK®).
11 NRDL = National Reimbursement Drug List.
12 Lilly = Eli Lilly and Company.
13 ITP = Immune thrombocytopenia purpura.
14 NMPA = National Medical Products Administration.
15 NDA = New Drug Application.
16 EU = European Union.
17 EGFR = Epidermal growth factor receptor.
18 WCLC = World Conference on Lung Cancer.
19 DoR = Duration of response.
20 PFS = Progression-free survival.
21 OS = Overall survival.
22 ELCC = European Lung Cancer Congress.
23 VEGFR = Vascular endothelial growth factor receptor.
24 ASCO GI = ASCO (American Society of Clinical Oncology) Gastrointestinal Cancers Symposium.
25 PMDA = Pharmaceuticals and Medical Devices Agency.
26 FGFR = Fibroblast growth factor receptor.
27 CSF-1R = Colony-stimulating factor 1 receptor.
28 ASCO = American Society of Clinical Oncology.
29 PI3Kδ = Phosphoinositide 3-kinase delta.
30 Syk = Spleen tyrosine kinase.
31 AIHA = autoimmune hemolytic anemia.
32 Epizyme = Epizyme Inc.
33 IDH = Isocitrate dehydrogenase.
34 BTK = Bruton’s tyrosine kinase.
35 MAPK pathway = RAS-RAF-MEK-ERK signaling cascade.
36 IND = Investigational New Drug (application).
37 We also report changes in performance at constant exchange rate (“CER”) which is a non-GAAP measure. Please refer to “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.
38 SHPL = Shanghai Hutchison Pharmaceuticals Limited.
39 HBYS = Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited.
40 ADS = American depositary share.
41 HKEX = The Main Board of The Stock Exchange of Hong Kong Limited.
42 GAAP = Generally Accepted Accounting Principles.
43 SG&A Expenses = selling, general and administrative expenses.
| Date: August 1, 2022 (Monday) |
| Announcement released: 7am EDT / 12pm noon BST / 7pm HKT |
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Hong Kong, Shanghai & Florham Park, NJ — Monday, August 1, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated a bridging study of tazemetostat in China. The first patient received their first dose on July 29, 2022.
The bridging study is a multicenter, open-label, Phase II study to evaluate the efficacy, safety and pharmacokinetics of tazemetostat for the treatment of patients with relapsed/refractory follicular lymphoma (“R/R FL”). The primary objective is to evaluate the efficacy of tazemetostat for treatment of patients with R/R FL who have mutations in EZH2[1] (Cohort 1). The secondary objectives are to evaluate the efficacy of tazemetostat for treatment of patients with R/R FL who have EZH2 wild-type (Cohort 2) and to evaluate the safety and the pharmacokinetics of tazemetostat for treatment of patients with R/R FL. The lead principal investigator is Dr Junning Cao of Shanghai Fudan University Cancer Center. Additional details may be found at clinicaltrials.gov, using identifier NCT05467943.
Tazemetostat is a methyltransferase inhibitor of EZH2 developed by Epizyme, Inc. (“Epizyme”). It is approved by the U.S. Food and Drug Administration (“FDA”) for the treatment of certain patients with advanced epithelioid sarcoma (“ES”) and certain patients with R/R FL under the FDA accelerated approval granted in January and June 2020, respectively.
In August 2021, HUTCHMED entered into a strategic collaboration with Epizyme to research, develop, manufacture and commercialize tazemetostat in China, Hong Kong, Macau and Taiwan.
In May 2022, tazemetostat was approved by the Health Commission and Medical Products Administration of Hainan Province of China to be used in the Hainan Boao Lecheng International Medical Tourism Pilot Zone (“Hainan Pilot Zone”), under the Clinically Urgently Needed Imported Drugs scheme, for the treatment of certain patients with ES and FL consistent with the label as approved by the FDA.
FL is a subtype of non-Hodgkin’s lymphoma (“NHL”). FL accounts for approximately 17% of NHL. In 2020, there were an estimated 16,000 and 13,000 new cases of FL in China and the U.S., respectively. [2],[3],[4]
ES is a rare, slow-growing type of soft tissue cancer. Radical tumor resection is the primary treatment for patients with ES. However, ES is known for its high propensity for locoregional recurrence and distant metastases. The survival of patients with ES is often unsatisfactory with very limited treatment options.[5]
TAZVERIK® is a methyltransferase inhibitor indicated in the United States for the treatment of:
These indications are approved under accelerated approval by the U.S. FDA based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.
View the U.S. Full Prescribing Information here: www.tazverik.com
TAZVERIK® is a registered trademark of Epizyme, Inc.
HUTCHMED and Epizyme are developing tazemetostat in various hematological and solid tumors in Greater China, with HUTCHMED leading the China portion of Epizyme’s SYMPHONY-1 study. HUTCHMED and Epizyme also intend to conduct additional global studies jointly.
SYMPHONY-1 (EZH-302) is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase 1b/3 study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with R2 in patients with relapsed or refractory FL after at least one prior line of therapy (clinicaltrials.gov identifier: NCT04224493).
We intend to initiate several combination studies of tazemetostat with HUTCHMED assets.
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of TAZVERIK® for the treatment of patients with ES or FL, the further clinical development of TAZVERIK® in this and other indications, risks associated with the use of TAZVERIK® in the Hainan Pilot Zone, including that it could be discontinued in the future for a variety of reasons, the risk that ongoing or future clinical trials conducted by HUTCHMED for TAZVERIK® may not meet their primary or secondary endpoints or will warrant meetings with regulatory authorities, submissions for regulatory approval or review by governmental authorities under the accelerated approval process and expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding regulatory approvals, including accelerated approval, to conduct trials or to market products (including to continue offering TAZVERIK® in the Hainan Pilot Zone or elsewhere in China, Hong Kong, Macau and Taiwan), its expectations that preclinical studies or earlier clinical studies are predictive of the results of future trials, such as the ongoing confirmatory trials, the safety profile of TAZVERIK®, the potential for TAZVERIK® to become a new standard of care for ES or FL patients, HUTCHMED’s and Epizyme’s ability to implement and complete its further clinical development plans for TAZVERIK®, the potential commercial launch of TAZVERIK® in China and other jurisdictions in the approved indications, the sufficiency of each company’s cash resources to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the timing of these events, and the impact of the COVID-19 pandemic on HUTCHMED’s business, results of operations and financial condition and on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug candidates as combination therapeutics with TAZVERIK®, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and regulatory approval of such drug candidates. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. HUTCHMED anticipates that subsequent events and developments may cause its views to change; however, HUTCHMED does not undertake any obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. For a further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited.
[1] EZH2 = Enhancer of Zeste Homolog 2
[2] Source: NCCN® – https://www.nccn.org
[3] Source: SEER – https://seer.cancer.gov/statfacts/html/follicular.html
[4] Source: GLOBOCAN https://gco.iarc.fr/
[5] Sobanko JF, Meijer L, Nigra TP. Epithelioid sarcoma: a review and update. J Clin Aesthet Dermatol. 2009;2(5):49-54.
Investor Enquiries |
|
| Mark Lee, Senior Vice President | +852 2121 8200 |
| Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
| Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
| Europe – Ben Atwell / Alex Shaw, FTI Consulting |
+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) HUTCHMED@fticonsulting.com |
| Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile) HUTCHMED@brunswickgroup.com |
Nominated Advisor |
|
| Atholl Tweedie / Freddy Crossley, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |