Hutchison Pharma announced that it has entered into a license agreement with Takeda Pharmaceutical for the development and commercialization of fruquintinib outside of China

On January 23, 2023, Hutchison announced that its subsidiary, Hutchison Whampoa Pharmaceutical (Shanghai) Co., Ltd., has entered into an exclusive license agreement with a subsidiary of Takeda Pharmaceutical Company Limited ("Takeda Pharmaceutical"). Further advance the development, commercialization and production of fruquintinib worldwide except Chinese mainland, Hong Kong and Macau. Fruquintinib is marketed in Chinese mainland, Hong Kong and Macau by Hutchison Pharmaceutical. Hutchison Whampoa Pharma (Shanghai) Limited will receive payments totaling up to US$1.13 billion, including an upfront payment of US$400 million upon completion of the agreement, as well as potential regulatory registration, development and commercial sales milestone payments, plus royalties based on net sales.

– Upon completion of the agreement, Hutchison will receive an upfront payment of US$400 million and potential future milestone payments of up to US$730 million, totaling up to US$1.13 billion, plus royalties based on net sales

– Completion of marketing authorization submissions in the United States, Europe and Japan is scheduled for 2023

– This collaboration is in line with Hutchison's strategic plan to establish a path to profitability and provide innovative medicines to patients around the world

– Hutchison will host a conference call and webcast today, 23 January 2023 (Monday) at 9:30 p.m. Hong Kong Time (8:30 a.m. EST / 1:30 p.m. GMT).

Fruquintinib is a highly selective and potent vascular endothelial growth factor receptor ("VEGFR")-1, -2, and -3 inhibitor. Fruquintinib can be administered orally and has the potential to be used in various subtypes of metastatic colorectal cancer regardless of biomarker status. The FRESCO-2 international multicenter phase III clinical trial of fruquintinib for the treatment of patients with refractory metastatic colorectal cancer has yielded positive results and was presented at the annual meeting of the European Society for Medical Oncology ("ESMO") in September 2022. The FRESCO-2 study met the primary endpoint of improved overall survival ("OS") in patients with metastatic colorectal cancer and was generally well tolerated.

Fruquintinib has the potential to change the treatment landscape for patients with refractory metastatic colorectal cancer, who require more treatment options. We look forward to bringing this innovative drug to patients outside of China through our strength in development and commercialization." Takeda Pharmaceutical has worked with partners to bring innovative drugs to patients in need around the world, and has a rich experience in related cooperation. The partnership with Hutchison Pharma further expands our anti-tumor portfolio and brings us one step closer to realizing our desire to cure cancer."

Teresa Bitetti, President, Global Anti-Oncology Business Unit at Takeda Pharmaceutical:

Under the terms of the agreement, Takeda will obtain from HMP Pharmaceuticals (Shanghai) Co., Ltd. an exclusive license to develop and commercialize fruquintinib for all indications worldwide except Chinese mainland, Hong Kong and Macau. Under the terms of the agreement, Hutchison Whampoa Pharmaceutical (Shanghai) Limited will receive payments of up to US$1.13 billion, including an upfront payment of US$400 million at closing and potentially additional regulatory registration, development and commercial sales milestone payments of up to US$730 million, as well as royalties based on net sales.

The effective nature of the transaction is subject to a number of customary closing conditions, including the completion of an antitrust regulatory review. Subject to the satisfaction of these conditions, Takeda will be solely responsible for the development and commercialization of fruquintinib in all regions worldwide except Chinese mainland, Hong Kong and Macau. As announced earlier, marketing authorization submissions in the US, Europe and Japan are scheduled to complete in 2023, with rolling submissions to the U.S. Food and Drug Administration ("FDA") scheduled to be completed in the first half of 2023.

Hutchison will continue to work with Eli Lilly to focus on advancing the late-stage clinical trial and commercialization of fruquintinib in Chinese mainland. Fruquintinib is approved in Chinese mainland and marketed under the trade name Ayote ® for the treatment of patients with metastatic colorectal cancer who have previously been treated with fluoropyrimidine, oxaliplatin, and irinotecan, including those who have previously received anti-vascular endothelial growth factor ("VEGF") and/or anti-epidermal growth factor receptor ("EGFR") therapy (RAS wild-type). Since January 2020, iYoute ® has been included in China's national medical insurance drug list.

Hutchison's management team will hold an investor and analyst conference call and webcast on Monday, January 23, 2023 at 8:30 a.m. New York time (1:30 p.m. London time / 9:30 p.m. Hong Kong time). Dial-in numbers and webcast details of the conference call will be posted www.hutch-med.com/event/ the Company's website. The recording of the meeting will also be uploaded to the Company's website for replay after the end.

Evercore Group LLC acted as exclusive financial advisor to Hutchison Pharmaceutical, with Ropes & Gray LLP acting as legal counsel.

About colorectal cancer

Colorectal cancer is cancer that begins in the colon or rectum. According to the International Agency for Research on Cancer (IARC), colorectal cancer is the third most common cancer worldwide. More than 935,000 deaths were estimated in 2020. [1] In the United States, an estimated 155,000 new cases of colorectal cancer and 54,000 deaths will occur in 2022. [2] In Europe, colorectal cancer is the second most common cancer, with about 520,000 new cases and 245,000 deaths. In Japan, colorectal cancer is the most common cancer, with an estimated 148,000 new cases and 60,000 deaths in 2020. [1] Although early-stage colorectal cancer can be removed surgically, there is still a large unmet medical need for metastatic colorectal cancer that is currently poorly treated and treatment options are limited.

About fruquintinib

Fruquintinib is a highly selective and potent oral VEGFR-1, -2, and -3 inhibitor. VEGFR inhibitors play a crucial role in inhibiting angiogenesis in tumors. The unique design of fruquintinib makes it more selective for kinases designed to minimize off-target toxicity, improve tolerability, and provide more stable coverage of targets. To date, fruquintinib has been generally well tolerated in patients, and studies of its combination with other antitumor therapies are ongoing.

About fruquintinib approved in China

Used to treat colorectal cancer

Fruquintinib was approved for sale in China by the National Medical Products Administration of China in September 2018 and commercially launched under the trade name Ayote ® in November 2018. It has been included in China's national medical insurance drug list since January 2020. Ayote ® is suitable for patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan, including patients who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). The results of the pivotal phase III registration study of fruquintinib FRESCO [3] in 416 patients with metastatic colorectal cancer in China were published in the Journal of the American Medical Association (JAMA) in June 2018 (NCT02314819).

The safety and efficacy of fruquintinib for the following research uses is not clear, and there is no guarantee that it will be approved by health authorities or commercially available for research use in any country or region.

About being carried out outside China

FRESCO-2 phase III study

The FRESCO-2 study is a global, multicenter clinical trial conducted in the United States, Europe, Japan and Australia to explore fruquintinib plus optimal supportive care versus placebo plus optimal supportive care in patients with advanced refractory metastatic colorectal cancer (NCT04322539). The results were announced at the ESMO Annual Meeting in September 2022. [4] The FRESCO-2 international multicenter clinical trial showed that fruquintinib therapy achieved statistically significant and clinically significant lengthening of progression-free survival ("PFS") at both the primary endpoint OS and the key secondary endpoint compared with placebo.

Specifically, the median OS of 461 patients treated with fruquintinib was 7.4 months, compared with 4.8 months for 230 patients in the placebo group (hazard ratio ["HR"] 0.66; 95% CI ["CI"] 0.55–0.80; p<0.001) 。 The median PFS was 3.7 months in patients treated with fruquintinib compared with 1.8 months 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% in the placebo group. The median follow-up for both groups was approximately 11 months.

The safety profile of fruquintinib in the FRESCO-2 study is consistent with those known in previously published fruquintinib clinical trials. Grade 3 or higher occurred in 62.7% of patients treated with fruquintinib, compared with 50.4% of patients treated with placebo. Grade 3 or above adverse events occurring in more than 5% were hypertension (13.6% versus 0.9% in the placebo group), fatigue (7.7% versus 3.9% in the placebo group), and hand-foot syndrome (6.4% versus 0% in the placebo group). Among patients receiving fruquintinib, 20.4% experienced treatment-related adverse events leading to discontinuation, compared with 21.1% in the placebo group.

Other development projects regarding fruquintinib

Chinese Gastric Cancer Study: The FRUTIGA study is a randomized, double-blind phase III clinical trial to evaluate combination therapy with fruquintinib and paclitaxel versus paclitaxel monotherapy in patients with second-line advanced gastric cancer or adenocarcinoma of the gastroesophageal junction (NCT03223376). The top-line results of the FRUTIGA study were published in November 2022. The study met one of the primary endpoints, a statistically significant improvement in PFS, which is clinically significant. The other primary endpoint, OS, although improvements were observed on median OS, were not statistically significant according to the preset statistical plan. In addition, fruquintinib observed statistically significant improvements in secondary endpoints including objective response rate (ORR), DCR, and prolonged duration of response (DoR). The safety profile of fruquintinib in FRUTIGA studies is also consistent with those observed in previously published studies. The full detailed results of the study are subject to further analysis and are expected to be presented at an upcoming academic conference.

Hutchison is also developing combination therapies with fruquintinib and PD-1 monoclonal antibodies for the treatment of endometrial cancer and other solid tumors.