Venue: The 13^th International Conference of the Asian Clinical Oncology Society in Chiang Mai, Thailand

Abstract #: ABS093

Authors: Jin Li, Shukui Qin, Yuxian Bai, Yanhong Deng, Lei Yang, Zhendong Chen, Haijun Zhong, Rui-hua Xu, Hongming Pan, Weijian Guo, Yongqian Shu, Ying Yuan, Jianfeng Zhou, Nong Xu, Tianshu Liu, Dong Ma, Changping Wu, Ying Cheng, Jianming Xu, Donghui Chen, Wei Li, Sanyuan Sun, Zhuang Yu, Peiguo Cao, Lin Shen, Haihui Chen, Jiejun Wang, Shubin Wang, Hongbing Wang, Rubing Han, Songhua Fan, Xin Wang, Ye Hua, Hongyan Li, Xiaojun Guo

Presenter: Dr. Lei Yang (Nantong Tumor Hospital, Nantong, China)

Session: Abstract Session 2: Colorectal Cancer, Lung

Date: Saturday, 24 February, 2018

Location: Empress Grand Hall

A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Savolitinib in Patients with Metastatic Renal Cell Carcinoma

S Vari¹, B Szabados¹, A GomezdeLiano¹, K Mousa², L Rammazzo², A Prendergast², T Powles¹

Background:

Anti-PD-L1 and CTLA-4 antibodies are associated with clinical benefit in mRCC. MET dysregulation plays an important role in papillary RCC pathogenesis and is a mechanism of resistance against TKIs in ccRCC. Pre-clinical data suggests benefit in dual MET plus PD-L1 inhibition. The phase Ib part of this trial was designed to determine the RP2D of savolitinib (c-Met kinase inhibitor) and durvalumab (PD-L1 mAb) when given in combination (NCT028195996).

Methods:

International, investigator led phase Ib/IIa study with a dose de-escalation (3+3) part in patients with metastatic renal cell cancer (irrespective of PD-L1 and MET alteration status). Dose level 0 (600mg OD savolitinib and 1500mg Q4wk durvalumab) and -1A (400mg OD savolitinib and 1500mg Q4wk durvalumab) were investigated. Patients received a 28 day cycle of savolitinib before commencing durvalumab treatment on day 1 of cycle 2. Treatment given until PD (RECIST v1.1) or intolerable toxicity. Primary endpoint was DLTs over a 2 month period. Secondary endpoints included PK and safety (CTCAE v4.03).

Results:

6 evaluable patients enrolled at dose level 0 with no reported DLTs. Median age 46 years (25-59), median ECOG 1. ccRCC (n=4), papillary cell (n=2). All 6 patients had Intermediate Heng risk score. 3 ccRCC patients had 3 previous lines of therapy and 1 ccRCC received 1 prior therapy. 1 papillary cell patient entered with no prior lines of therapy and 1 received 4 prior lines. Worst reported toxicity related to IMP was fatigue G2-3 (n=2). Other toxicities: G1-2 pain (n=3), G2 Caugh (n=1), G2 diarrhoea (n=1), G1 gastritis (n=1), G1 nausea (n=2), G2 Peripheral edema (n=2), Rash G2 (n=1), G1 transaminitis (n=1), PPE G2 (n=1). Two AESIs were reported, gastritis G1 and G3 numbness. At 12 weeks best response by RECIST v1.1 was SD (n=4).

Conclusions:

Based on DLTs and cumulative toxicity, dose level 0 was selected as the RP2D for the expansion phase. Dose level -1A was not investigated. Adverse events were in keeping with established single agent safety profiles. The expansion phase is open to recruitment in the UK and Spain and is investigating two cohort populations. mccRCC or sarcomatoid RCC patients (n=156) randomised (1:1:1:1) to savolitinib alone, durvalumab alone, savolitinib plus durvalumab or tremelimumab and durvalumab followed by durvalumab alone. Metastatic papillary patients (n=39) receive durvalumab plus savolitinib. A biomarker enrichment phase in tumours positive for MET or PD-L1 alterations may be investigated.

London: Tuesday, February 13, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) has completed patient enrollment of FALUCA, its Phase III pivotal trial of fruquintinib in advanced, third-line, non-small cell lung cancer (“NSCLC”) patients in China. Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”) 1, 2 and 3, that has met its primary endpoint in several Phase II and III clinical trials in China for the treatment of lung, colorectal and gastric cancers. Top-line FALUCA data is expected to be reported in late 2018 when the overall survival (“OS”) data is mature and, subject to a positive outcome, would be followed by a second New Drug Application (“NDA”) submission thereafter. Fruquintinib’s first NDA, for the treatment of colorectal cancer, was submitted to the China Food and Drug Administration (“CFDA”) in June 2017.

About Fruquintinib

Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Its tolerability, along with its clean drug-drug interaction profile demonstrated to date, may enable rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy. VEGFR plays a pivotal role in tumor-related angiogenesis.

About FALUCA

FALUCA is a randomized, double-blind, placebo-controlled, multi-center, Phase III registration study of fruquintinib targeted at treating patients with advanced non-squamous NSCLC, who have failed two lines of systemic chemotherapy. Patients were randomised at a 2:1 ratio to receive either 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus best supportive care (“BSC”); or placebo plus BSC.  Randomization was stratified by EGFR gene status and history of treatment by VEGF inhibitors. The primary endpoint is OS, with secondary endpoints including progression free survival (“PFS”), objective response rate (ORR), disease control rate (DCR) and duration of response (DoR). Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02691299.

It was initiated following a similar Phase II clinical trial in 91 third-line NSCLC patients that succeeded in meeting its primary efficacy endpoint of PFS, with no unexpected safety issues. Results were highlighted in an oral presentation at the 17^th World Conference on Lung Cancer on December 6, 2016 (clinicaltrials.gov identifier NCT02590965).

Other Fruquintinib Development Programs

Lung cancer in China: Along with FALUCA, fruquintinib is concurrently being studied in a Phase II study in combination with Iressa^® (gefitinib) in first-line setting for patients with advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Preliminary results were highlighted in an oral presentation at the 18^th World Conference on Lung Cancer on October 16, 2017.

Colorectal cancer in China: The CFDA acknowledged acceptance of the NDA for fruquintinib for the treatment of patients with advanced colorectal cancer (“CRC”) in June 2017. Fruquintinib was subsequently awarded priority review status in view of its significant clinical value, according to a CFDA announcement in September 2017. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with CRC in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology Annual Meeting held on June 5, 2017 (clinicaltrials.gov identifier NCT02314819). The FRESCO study followed an initial Phase I trial in 40 solid tumor patients, a Phase Ib study in 62 CRC patients, and a Phase II clinical trial in 71 CRC patients.

Gastric cancer in China: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol^® (paclitaxel), known as the FRUTIGA study, for the treatment of over 500 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier NCT03223376). The FRUTIGA study followed a Phase I/II clinical trial in 34 patients that demonstrated that combination therapy of fruquintinib and Taxol^® in such patients was generally well-tolerated with promising tumor response (clinicaltrials.gov identifier NCT02415023).

In China, fruquintinib is jointly developed with Eli Lilly and Company.

United States bridging trial: In December 2017, Chi-Med initiated a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03251378.

About Chi‑Med

Chi‑Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.

Chi‑Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi‑med.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 Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of fruquintinib, plans to initiate clinical studies for fruquintinib, its expectations as to whether such studies 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 enrollment rates, 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 drug candidate fruquintinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of fruquintinib for a targeted indication and the sufficiency of funding. 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 Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med 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

Investor Enquiries

Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200

U.K. & International Media Enquiries

Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk

U.S. Based Media Enquiries

Brad Miles, BMC Communications
+1 (917) 570 7340 (Mobile)
bmiles@bmccommunications.com

Susan Duffy, BMC Communications
+1 (917) 499 8887 (Mobile)
sduffy@bmccommunications.com

Investor Relations

Matt Beck, The Trout Group
+1 (917) 415 1750 (Mobile)
mbeck@troutgroup.com

David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com

Panmure Gordon (UK) Limited

Richard Gray / Andrew Potts
+44 (20) 7886 2500

London: Monday, February 5, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) will be announcing its final results for the year ended December 31, 2017 on Monday, March 12, 2018 at 7:00 am Greenwich Mean Time (GMT).

An analyst presentation will be held at 9:00 am GMT (5:00 pm Hong Kong Time) on the same day at Citigate Dewe Rogerson, 3 London Wall Buildings, London, EC2M 5SY, UK, which will be webcast via the company website at www.chi-med.com/investors/event-information/. The presentation will be available to download before the analyst presentation begins.

For North America based analysts and investors, Chi-Med will also host a conference call with Q&A at 9:00 am Eastern Daylight Time (1:00 pm GMT).

Details of the analyst presentation and conference call dial-in will be provided in the financial results announcement. A replay will also be available on the website shortly after each event.

About Chi-Med

Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.

Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.

CONTACTS

Investor Enquiries

Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200

U.K. & International Media Enquiries

Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk

U.S. Based Media Enquiries

Brad Miles, BMC Communications
+1 (917) 570 7340 (Mobile)
bmiles@bmccommunications.com

Susan Duffy, BMC Communications
+1 (917) 499 8887 (Mobile)
sduffy@bmccommunications.com

Investor Relations

Matt Beck, The Trout Group
+1 (917) 415 1750 (Mobile)
mbeck@troutgroup.com

David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com

Panmure Gordon (UK) Limited

Richard Gray / Andrew Potts
+44 (20) 7886 2500