— NDA supported by data from global Phase III FRESCO-2 study in the U.S., Europe, Japan and Australia along with data from Phase III FRESCO study conducted in China —

— FRESCO-2 showed fruquintinib treatment reduced the risk of death by 34% in refractory metastatic colorectal cancer (0.66 HR), consistent with the 35% reduction in the risk of death seen in FRESCO  —

— Marketing authorization submissions in Europe and Japan on track to complete in 2023 —

Hong Kong, Shanghai & Florham Park, NJ  —   Friday   March 31, 2023: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that it completed the rolling submission of a New Drug Application (“NDA”) to the U.S. Food and Drug Administration (“FDA”) for fruquintinib, its highly selective and potent oral inhibitor of VEGFR-1, -2 and -3, for the treatment of refractory metastatic colorectal cancer (“CRC”).

“This FDA submission is a significant milestone for patients in the U.S. with metastatic CRC, one of the most common and deadly cancers in the U.S. and worldwide. Fruquintinib is an important treatment option for patients with metastatic CRC in China, where it has been available to patients since 2018. We look forward to working with our partner Takeda to commercialize fruquintinib outside China, and we remain on track to submit regulatory filings in Europe and Japan later this year,” said Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED.

The NDA is supported by the global Phase III multi-regional clinical trial (“MRCT”) FRESCO-2 study conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care (“BSC”) vs placebo plus BSC in patients with refractory metastatic CRC, along with data from the FRESCO study conducted in China. Filing of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and an NDA to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) are planned in 2023.

In March 2023, HUTCHMED and Takeda Pharmaceutical Company Limited (TSE:4502, NYSE:TAK) closed an exclusive license agreement to further the global development, commercialization and manufacture of fruquintinib outside China. In China, fruquintinib is approved under the brand name ELUNATE^® and is included in the China National Reimbursement Drug List (“NRDL”). HUTCHMED markets fruquintinib in China in partnership with Eli Lilly and Company.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.[i] In the U.S., an estimated 153,000 patients were diagnosed with CRC and there were 53,000 deaths from the disease in 2023.[ii] In Europe, CRC was the second most common cancer in 2020, with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC is the most common cancer, with an estimated 148,000 new cases and 60,000 deaths in 2020.¹ Although early stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options.

About Fruquintinib

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 with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date, and is being investigated in combinations with other anti-cancer therapies.

About Fruquintinib Approval in 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 November 2018 under the brand name ELUNATE^®.  It has been included in the 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-epidermal growth factor receptor (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 (NCT02314819).  The primary endpoint of the study, overall survival (“OS”), was achieved with a hazard ratio (“HR”) of 0.65 (95% confidence interval [“CI”] 0.51–0.83; p<0.001)

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.

About the FRESCO-2 Phase III Trial in CRC Outside China

The FRESCO-2 study is a MRCT conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus BSC vs placebo plus BSC in patients with refractory metastatic CRC (NCT04322539). The results were presented at European Society for Medical Oncology (ESMO) congress in September 2022.[iv] The MRCT FRESCO-2 study demonstrated that treatment with fruquintinib resulted in a statistically significant and clinically meaningful increase in the primary OS endpoint and key secondary progression free survival (“PFS”) endpoint compared to treatment with placebo.

Specifically, the median OS was 7.4 months for the 461 patients treated with fruquintinib compared to 4.8 months for the 230 patients in the placebo group (HR 0.66; 95% CI 0.55–0.80; p<0.001). The median PFS was 3.7 months for patients treated with fruquintinib compared to 1.8 months for patients in the placebo group (HR 0.32; 95% CI 0.27–0.39; p<0.001). The disease control rate (“DCR”) was 55.5% in the fruquintinib group compared to 16.1% for patients in the placebo group. Median duration of follow-up was approximately 11 months for patients in both groups.

The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported fruquintinib studies. Grade 3 or above adverse events occurred in 62.7% of patients who received fruquintinib, compared to 50.4% of patients who received placebo. Grade 3 or above adverse events that occurred in more than 5% of patients who received fruquintinib were hypertension (13.6% vs 0.9% in the placebo group), asthenia (7.7% vs 3.9% in the placebo group) and hand-foot syndrome (6.4% vs 0% in the placebo group). Treatment related adverse events leading to discontinuation occurred in 20.4% of patients who received fruquintinib, compared to 21.1% of patients who received placebo.

About Other Fruquintinib Developments

Gastric Cancer in China: The FRUTIGA study is a randomized, double-blind, Phase III study in China to evaluate fruquintinib combined with paclitaxel compared with paclitaxel monotherapy, for second-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma (NCT03223376). Topline results were announced in November 2022. The trial met one of the primary endpoints of statistically significant improvement in PFS, which is clinically meaningful. The other primary endpoint of OS was not statistically significant per the pre-specified statistical plan, although there was a numerical improvement in median OS. Fruquintinib also demonstrated a statistically significant improvement in secondary endpoints including objective response rate (ORR), DCR, and improved duration of response (DoR). The safety profile of fruquintinib in FRUTIGA was consistent with previously reported studies. Results are expected to be disclosed at an upcoming scientific meeting.

HUTCHMED is also developing fruquintinib for the treatment of multiple solid tumor cancers in combination with PD-1 monoclonal antibodies for the treatment of endometrial and other solid tumors.

About HUTCHMED

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 approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients 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.

Forward-Looking Statements

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 submission of an NDA for fruquintinib for the treatment of CRC with the FDA and the timing of such submission, the therapeutic potential of fruquintinib for the treatment of patients with 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 CRC or other indications in the U.S. or other jurisdictions such as Europe or Japan, its potential to gain approvals from regulatory authorities on an expedited basis or at all; the efficacy and 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; each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; Takeda’s ability to successfully develop and commercialize fruquintinib; 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 as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Such forward-looking statements include, without limitation, statements regarding the plan to develop and commercialize fruquintinib under the license agreement; potential payments under the license agreement, including the upfront payment and any milestone or royalty payments; potential benefits of the license agreement; and HUTCHMED’s strategy, goals and anticipated milestones, business plans and focus. 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.

[i] The Global Cancer Observatory. Accessed December 12, 2022.

[ii] SEER. Cancer Stat Facts: Colorectal Cancer. National Cancer Institute.  https://seer.cancer.gov/statfacts/html/colorect.html. Accessed December 12, 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.

[iv] Dasari NA, Lonardi S, et al. LBA25 – FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7): S808-S869. 10.1016/annonc/annonc1089.

Contacts

The outcome for patients in Japan from the FRESCO-2 multi-regional clinical trial of fruquintinib, an oral inhibitor of VEGFR-1, -2 and -3, are being presented at the 2023 Japanese Society of Medical Oncology Annual Meeting, taking place March 16-18 in Fukuoka, Japan.

Background & Methods

FRESCO-2 is a global, Phase III, multi-regional, double-blind, placebo-controlled clinical trial (NCT04322539) conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care (“BSC”) vs placebo plus BSC in patients with refractory metastatic colorectal cancer (“CRC”), randomized 2:1.  In total, 691 patients were enrolled in the study, of which 56 (8%) were from Japan.

In FRESCO-2, fruquintinib significantly improved the primary endpoint of overall survival (“OS”) (hazard ratio [“HR”] 0.66, 95% confidence interval [“CI”] 0.55-0.80; p<0.001) and secondary endpoints including progression free survival (“PFS”) (HR 0.32, 95% CI 0.27-0.39; p<0.001), disease control rate (“DCR”) and objective response rate (“ORR”), with a favorable toxicity profile. Fruquintinib or placebo was given 5 mg orally once a day on 3 weeks on, 1 week off, 28-day cycles. Key patient inclusion criteria included prior chemotherapy, prior anti-VEGF therapy, and if RAS wild type, prior anti-EGFR therapy; if BRAFV600E mutant or MSI-high, at least one prior targeted regimen; and prior exposure to trifluridine/tipiracil and/or regorafenib. These results were initially presented at the European Society for Medical Oncology Congress 2022 in September 2022.

Results

Among Japanese patients in the FRESCO-2 study, median OS was 6.9 months for the 40 patients treated with fruquintinib compared to 5.6 months for the 16 patients in the placebo group (HR 0.42; 95% CI 0.19–0.92; p=0.055). Median PFS was 3.6 months for patients treated with fruquintinib compared to 1.8 months for patients in the placebo group (HR 0.27; 95% CI 0.13–0.56; p=0.004). The DCR was 62.5% in the fruquintinib group compared to 25.0% for patients in the placebo group. The ORR was 2.5% in the fruquintinib group compared to 0% for patients in the placebo group. Median duration of follow-up was approximately 9 months for patients in both groups.

The incidence of treatment emergent adverse events for fruquintinib in Japanese patients from the FRESCO-2 study was higher compared to the entire study patient population.  These events were typically managed with dose interruptions or reductions. Grade 3 or above adverse events occurred in 71.8% of patients who received fruquintinib, compared to 29.4% of patients who received placebo. Grade 3 or above adverse events that occurred in three or more patients (≥ 5%) who received fruquintinib were hypertension (nine [23.1%] vs none in the placebo group), hand-foot syndrome (seven [17.9%] vs none in the placebo group), and proteinuria (three [7.7%] vs. none in the placebo group).

Conclusion

In refractory metastatic CRC patients in Japan, fruquintinib demonstrated a clinically meaningful improvement in OS and PFS, and a safety profile that is consistent with FRESCO-2 results in the overall population. These results are expected to support fruquintinib as a potential new treatment option for Japanese patients with refractory metastatic CRC.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.[i] In the U.S., an estimated 153,000 patients were diagnosed with CRC and there were 53,000 deaths from the disease in 2023.[ii] In Europe, CRC was the second most common cancer in 2020, with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC is the most common cancer, with an estimated 148,000 new cases and 60,000 deaths in 2020.¹ Although early stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options.

Reference:

[i] The Global Cancer Observatory. Accessed December 12, 2022.

[ii] Siegel RL, Wagle NS, Cercek A, et al. Colorectal cancer statistics, 2023 [published online ahead of print, 2023 Mar 1]. CA Cancer J Clin. 2023;10.3322/caac.21772. doi:10.3322/caac.21772

Hong Kong, Shanghai & Florham Park, NJ — Tuesday, March 14, 2023: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that, further to its announcement on January 23, 2023 and following the completion of customary closing conditions including antitrust regulatory reviews, the exclusive license agreement with a subsidiary of Takeda Pharmaceutical Company Limited (TSE:​4502, NYSE:​TAK) to further the global development, commercialization and manufacture of fruquintinib outside China has closed.

With a strong preclinical and clinical profile, fruquintinib offers a potential new treatment option for patients with refractory metastatic colorectal cancer (“CRC”), supporting the shared goal of Takeda and HUTCHMED to improve the lives of those living with cancer worldwide. Takeda is now responsible for the development, commercialization and manufacture of fruquintinib in all included territories worldwide excluding mainland China, Hong Kong and Macau, where it is marketed by HUTCHMED.

Following the closing of the exclusive license agreement, HUTCHMED Limited will receive US$400 million shortly, and is eligible to receive up to US$730 million in additional potential payments relating to regulatory, development and commercial sales milestones, as well as royalties on net sales. Marketing authorization submissions in the U.S., Europe and Japan are planned to complete in 2023, with the rolling submission to the U.S. Food and Drug Administration (“FDA”) initiated in December 2022.

About Fruquintinib

Fruquintinib is a highly selective and potent inhibitor of vascular endothelial growth factor receptors (“VEGFR”) -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date, and is being investigated in combinations with other anti-cancer therapies.

About HUTCHMED

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 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients 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.

Takeda’s Commitment to Oncology

At Takeda Oncology, we are united by our aspiration to cure cancer and motivated every day to work harder for patients with limited or ineffective treatment options. Our agile structure and deep in-house expertise are complemented by a network of partnerships that optimize our ability to research, develop and deliver transformative medicines to people living with cancer. Building on decades of leadership in oncology and a portfolio of approved medicines for hematologic cancers and solid tumors, we are advancing a cutting-edge pipeline focused on the power of innate immunity. With inspiration from patients and innovation from everywhere, our goal is to introduce new classes of immunotherapies that can lead to deep, durable responses so that more patients can benefit from – and have access to – innovative medicines.

For more information, visit www.takedaoncology.com.

Forward-Looking Statements

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 submission of a New Drug Application (“NDA”) for fruquintinib for the treatment of CRC with the FDA and the timing of such submission, the therapeutic potential of fruquintinib for the treatment of patients with 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 CRC or other indications in the U.S. or other jurisdictions such as Europe or Japan, its potential to gain approvals from regulatory authorities on an expedited basis or at all; the efficacy and 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; each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; Takeda’s ability to successfully develop and commercialize fruquintinib; 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 as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Such forward-looking statements include, without limitation, statements regarding the plan to develop and commercialize fruquintinib under the license agreement; potential payments under the license agreement, including the upfront payment and any milestone or royalty payments; potential benefits of the license agreement; and HUTCHMED’s strategy, goals and anticipated milestones, business plans and focus. 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.

Contacts

Hong Kong, Shanghai & Florham Park, NJ — Monday, March 13, 2023: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:HCM, HKEX:13) today confirms that it does not have any exposure to Silicon Valley Bank (“SVB”) or Silicon Valley Bank UK Limited (“SVBUK”). The Company does not hold any cash deposits or securities with SVB or SVBUK.

About HUTCHMED

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 approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients 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.

Contacts

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, March 8, 2023: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM: HCM; SEHK:13) has received notifications that Mr Johnny Cheng, Executive Director and Chief Financial Officer, sold a total of 1,300,000 Ordinary Shares of US$0.10 each of the Company at an average price of HK$27.073 per Ordinary Shares on March 3, 2023  and March 6, 2023.

Following the above sale of 1,300,000 Ordinary Shares, the holding of Mr Cheng is 1,261,460 Ordinary Shares and 274,493 ADSs ^Note, representing approximately 0.3% of the current issued share capital of the Company.

Note: 274,493 ADSs included (i) 41,552 ADSs currently held by Mr Cheng, (ii) 217,800 ADSs granted under Share Option Scheme and (iii) 15,141 ADSs as beneficiary of a trust under long term incentive plan.

Please download the full announcement for the notification as provided in accordance with the requirements of the EU Market Abuse Regulation.

Hong Kong, Shanghai & Florham Park, NJ — Monday, March 6, 2023: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; SEHK:13) announces that following the announcement of the 2022 annual results of HUTCHMED on February 28, 2023, the following awards granted under the Long Term Incentive Plan (“LTIP”) on April 20, 2020 to Dr Weiguo Su and Mr Johnny Cheng were vested on March 3, 2023:-

The notifications set out below are provided in accordance with the requirements of the EU Market Abuse Regulation.

• Dr Weiguo Su

• Mr Johnny Cheng

About HUTCHMED

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 about 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception HUTCHMED has been focused on bringing cancer drug candidates from in-house discovery to patients 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.