The following includes the text of the Announcement, excluding the appendix. For the complete Announcement, please download the PDF.
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NOT FOR DISTRIBUTION, DIRECTLY OR INDIRECTLY, TO U.S. NEWSWIRE SERVICES OR FOR RELEASE, PUBLICATION OR DISSEMINATION IN OR INTO OR FROM THE UNITED STATES, CANADA, AUSTRALIA, JAPAN OR SOUTH AFRICA OR ANY OTHER JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OF SUCH JURISDICTION

London: Friday, 13 November 2015: Further to its announcement on 16 October 2015, Hutchison China MediTech Limited (“Chi‑Med”) (AIM: HCM) announces that it has publicly filed today a second draft of the registration statement on Form F-1 (the “Form F-1 Registration Statement”) with the United States Securities and Exchange Commission (the “SEC”) in relation to a potential listing of American depositary shares (“ADSs”) representing its ordinary shares on the Nasdaq Stock Market (the “Offering”).  As of the date of this announcement, Chi-Med has not yet set a definite timetable or decided on further details of the potential Offering and there can be no assurance that the potential Offering will be completed. Accordingly, the number of ADSs which may be offered and the offering price of the potential Offering have not yet been determined. The directors of Chi-Med will assess various factors, including market conditions, in considering whether formally to launch the transaction.

Bank of America Merrill Lynch and Deutsche Bank Securities (in alphabetical order) are acting as joint global coordinators and joint bookrunners for the potential Offering.

The second draft of the Form F-1 Registration Statement relating to the ADSs has been filed with the SEC but has not yet become effective. The ADSs may not be sold, nor may offers to buy be accepted, prior to the time the Form F-1 Registration Statement becomes effective. The Form F-1 Registration Statement and all subsequent amendments may be accessed through the SEC’s website at www.sec.gov.

This announcement does not constitute an offer to sell or the solicitation of an offer to buy ADSs or any other securities, nor shall there be any sale of ADSs in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Shareholders and potential investors should note that the potential Offering may or may not proceed, and accordingly are advised to exercise caution when dealing in the securities of Chi-Med.

Presentation of Financial Information

As announced by Chi-Med on 16 October 2015, the consolidated financial statements of Chi-Med included in the Form F‑1 Registration Statement have been prepared in accordance with U.S. GAAP, while the historical consolidated financial statements of Chi-Med published prior to the potential Offering were prepared in accordance with IFRS. The second draft of the Form F-1 Registration Statement filed with the SEC today supplementally contains the unaudited condensed consolidated financial statements of Chi-Med as of and for the nine months ended 30 September 2015 and 30 September 2014.  In addition, the second draft of the Form F-1 Registration Statement filed today supplementally contains unaudited condensed consolidated accounts for the three non-consolidated joint ventures of Chi-Med, namely, Shanghai Hutchison Pharmaceuticals Limited, Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited and Nutrition Science Partners Limited, as of and for the nine months ended 30 September 2015 and 30 September 2014, which are prepared in accordance with IFRS.  Such unaudited condensed consolidated financial statements are set out in the Appendix to this announcement.

Ends

Enquiries

Christian Hogg, CEO

Richard Gray
Andrew Potts

About Chi‑Med

Chi‑Med is a China‑based, globally‑focused healthcare group which researches, develops, manufactures and sells pharmaceuticals and health‑related consumer products.  Its Innovation Platform 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: 0001). For more information, please visit: www.chi‑med.com.

Important information

This announcement, which includes the appendix to it, does not constitute a Form F‑1 Registration Statement and does not constitute or form, and will not form, part of any offer or invitation to sell or issue, or the solicitation of an offer to purchase or acquire, any of the Ordinary Shares or ADSs or any other securities in the United States or in any other jurisdiction. Securities may not be offered or sold in the United States absent registration or an exemption from registration under the United States Securities Act of 1933, as amended (“U.S. Securities Act”).  Any public offering of securities to be made in the United States will be made by means of a Form F‑1 Registration Statement. Such Form F‑1 Registration Statement will contain detailed information about the issuer and its management and financial statements. This announcement is being issued pursuant to and in accordance with Rule 135e under the U.S. Securities Act.

No money, securities or other consideration is being solicited, and, if sent in response to the information contained in this announcement, will not be accepted.

Members of the public outside the United States will not be eligible to take part in the potential Offering described above.

This announcement is not directed to, or intended for distribution or use by, any person or entity that is a citizen or resident or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction.

The distribution of this announcement into jurisdictions other than the United Kingdom may be restricted by law.  Persons into whose possession this announcement come should inform themselves about and observe any such restrictions.

For readers in the European Economic Area

In any EEA Member State that has implemented the Prospectus Directive, this announcement, which includes the appendices to it, is only addressed to and directed at qualified investors in that Member State within the meaning of the Prospectus Directive.  The term “Prospectus Directive” means Directive 2003/71/EC (and amendments thereto, including Directive 2010/73/EU, to the extent implemented in each relevant Member State), together with any relevant implementing measure in the relevant Member State.

For readers in the United Kingdom

This announcement, which includes the appendix to it, insofar as it constitutes an invitation or inducement to enter into investment activity (within the meaning of section 21 of the Financial Services and Markets Act 2000, as amended) in connection with the securities which are the subject of the potential Offering described in this announcement or otherwise, is being directed only at (i) persons who are outside the United Kingdom or (ii) persons who have professional experience in matters relating to investments who fall within Article 19(5) (investment professionals) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (“Order”) or (iii) certain high value persons and entities who fall within Article 49(2)(a) to (d) (high net worth companies, unincorporated associations etc) of the Order; or (iv) any other person to whom it may lawfully be communicated (all such persons in (i) to (iv) together being referred to as “relevant persons”). The ADSs are only available to, and any invitation, offer or agreement to subscribe for, purchase or otherwise acquire such ADSs will be engaged in only with, relevant persons. Any person who is not a relevant person should not act or rely on this announcement or any of its contents.

Forward‑looking statements

This announcement, which includes the appendix to it, may contain forward‑looking statements that reflect Chi‑Med’s current expectations regarding future events, including the launch and completion of the potential Offering. A further list and description of risks, uncertainties and other risks associated with an investment in Chi‑Med can be found in Chi‑Med’s filings with the United States Securities and Exchange Commission, including the Form F‑1 Registration Statement. Existing and prospective investors are cautioned not to place undue reliance on these forward‑looking statements, which speak only as of the date hereof. Chi‑Med 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.

Appendix
Unaudited Condensed Consolidated Financial Statements of Chi-Med prepared in accordance with U.S. GAAP
and
Unaudited Condensed Consolidated Accounts of Non‑Consolidated Joint Ventures
prepared in accordance with IFRS

Please download the PDF for the full text of the Announcement including the Appendix.

London: Tuesday, 10 November 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) today announces that the ordinary resolution and the special resolution put to its Extraordinary General Meeting held on 10 November 2015 (“EGM”) were duly passed.

The EGM follows the announcement by Chi-Med on 16 October 2015 of a potential issuance of new ordinary shares (the “Equity Raise”) in connection with a potential listing of American depositary shares on the Nasdaq Stock Market. The resolutions passed at the EGM were required to be approved by the shareholders in order to enable Chi-Med to proceed with the Equity Raise and these authorities will expire at the next Annual General Meeting of Chi-Med.

The poll results of the resolutions were as follows:

*  Percentages rounded to 5 decimal places
^#  A vote withheld is not a vote in law and is not counted in the calculation of the proportion of the votes for and against a resolution.

As at the date of the EGM, the number of issued ordinary shares of Chi-Med was 56,533,118, which was the total number of ordinary shares entitling the holders to attend and vote on the ordinary resolution and special resolution proposed at the EGM.

Ends

Enquiries

Christian Hogg, CEO

Richard Gray
Andrew Potts

About Chi-Med

Chi-Med is a China-based, globally-focused healthcare group which researches, develops, manufactures and sells pharmaceuticals and health-related consumer products.  Its Innovation Platform 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: 0001).  For more information, please visit: www.chi-med.com.

London: Monday, 9 November 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) hereby makes the following amendments to the “Director’s Share Dealing” announcement released on 20 October 2015 subsequent to the notification received from Mr Christopher Nash on 5 November 2015.

The announcement has been corrected to reflect that following the dealings on 19 October 2015, the combined shareholding of Mr Nash and his spouse is 36,434, not the previously reported 36,442, due to the inadvertent sale of 8 shares by Mr Nash’s broker to cover dealing commission in the transaction below.

The full amended announcement is shown below:-

“London: Tuesday, 20 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) received notification on 19 October 2015 that Mr Christopher Nash, Independent Non-executive Director, has:

• purchased jointly with his spouse 4,512 ordinary shares of US$1.00 each in Chi-Med (the “Shares”) at a price of GBP21.95 per Share on 19 October 2015; and

• transferred 5,626 Shares at GBP21.65 per Share from one of his investment funds to his another investment fund (jointly held with his spouse) on 19 October 2015; 8 shares were sold in the transaction to cover dealing commission, leaving 5,618 shares in the receiving fund.

Following the above transactions, the combined shareholding of Mr Nash and his spouse is 36,434 Shares, representing approximately 0.06% of the current issued share capital of Chi-Med.”

Ends

Enquiries

Christian Hogg, CEO

Richard Gray
Andrew Potts

About Chi-Med

Chi-Med is a China-based, globally-focused healthcare group which researches, develops, manufactures and sells pharmaceuticals and health-related consumer products.  Its Innovation Platform 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: 0001).  For more information, please visit: www.chi-med.com.

Abstract (please download the poster for full details):

Authors: Yongxin Ren, Shiming Fan, Yunxin Chen, Renxiang Tang, Wei Zhang, Jianxing Tang, Linfang Wang, Dongxia Shi, Hongbo Chen, Min Cheng, Weiguo Qing, Weiguo Su

Renal cell carcinoma (RCC) is the most common type of kidney tumour in human.  Approximately 80~85% of RCC is clear cell renal cell carcinoma (ccRCC).  Although VEGF/VEGFR targeted therapies bring significant advances in the treatment of RCC, ultimate resistance occurs in most cases following a transient period of clinical benefit.  The hepatocyte growth factor (HGF) receptor c-Met activation emerges as one of the mechanisms for resistance to anti-VEGF/VEGFR therapies in ccRCC, implying that a combinational inhibition of c-Met and VEGFR pathways may induce a synergistic anti-tumour effect and could produce additional clinical benefit. The aim of this study was to assess the effect of a combination strategy targeting the VEGFR and c-MET pathways in ccRCC xenograft models.

Savolitinib (AZD6094, HMPL‑504) is a highly selective inhibitor against c-Met.  Fruquintinib (HMPL-013) strongly inhibits VEGFR1, 2 and 3.  Both of them were discovered by HMP and are currently being evaluated in clinical trials for the treatment of various cancers.  Several subcutaneous xenograft models were established in nude mice with human ccRCC cell lines or patient derived tumours (PDX) to investigate the anti-tumour effect of combination of savolitinib with fruquintinib.  Treatment with savolitinib or fruquintinib at clinically relevant dose only exhibited mild to moderate tumour growth inhibition as a single agent in all of tested models, but significantly increased anti-tumour effect was observed in all of tested models for the combination group.  It seemed that the enhanced anti-tumour effect was associated with c-Met inhibition.  In a ccRCC PDX model KIN1T1342, the increased anti-tumour effect was correlated with dose increment of savolitinib.  Immunohistochemistry (IHC) analysis revealed that combination treatment produced stronger inhibition on tumour proliferation marker Ki67 and angiogenesis marker CD31, compared to either savolitinib or fruquintinib alone, indicating that the observed synergistic effect might be attributed to the dual inhibition on tumour signalling and tumour microenvironment.  C-Met expression was observed in all tested models, and treatment with savolitinib effectively suppressed phospho-MET.

To evaluate c-Met expression in Chinese ccRCC patients, Formalin-Fixed and Paraffin-Embedded (FFPE) tumour sections were collected from sixty-two treatment-naive patients during surgical resection.  Positive c-Met expression was found in 69% (43/62) of ccRCC samples under IHC staining.

Overall our data demonstrated that c-Met was widely expressed in Chinese ccRCC patients and provided a rationale to test the combined HGF/c-Met and VEGF/VEGFR pathway blockade in the treatment of ccRCC in the clinical trials.

Abstract (download poster for full details):

Authors: Jian-Ming Xu, Lin Shen, Yan Wang, Yu-ling Chen, Ru Jia, Jian Wang, Ke Li, Yang Sai, Jing Li, Chuan Qi, Hua Ye, Su Weiguo

Background: Sulfatinib is a highly selective oral small molecule inhibitor targeting both vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR).  A phase I dose-escalation study was carried out to determine sulfatinib maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), pharmacokinetic (PK) profiles, and preliminary antitumor activity in patients with advanced solid tumours.

Methods: Sulfatinib was administered orally in 28-day treatment cycles until disease progression or unacceptable toxicity.  The study utilized 3+3 dose escalation method, with ascending dose cohorts from 50mg to 350mg daily.  During the study, a milled formulation was developed to reduce the inter-patient PK variations and optimize drug absorption.  The milled formulation was used in 200mg once daily (QD) to 350mg QD dose cohorts.

Results: As of July 6, 2015, a total of 77 patients had been enrolled.  Forty‑three of the 77 patients received original formulation in dose cohorts from 50mg to 300mg daily.  The data of patients treated with original formulation dosing from 50 to 300mg once daily, or 125mg and 150mg twice daily were reported in ASCO 2012(#3040).  Thirty-four of the 77 patients received milled formulation.  Among the 34 patients, 23 were enrolled in the dose-escalation phase, receiving sulfatinib 200mg to 350mg QD whereas 11 patients were enrolled in the dose-expansion phase receiving sulfatinib 300mg or 350 mg QD.  Among the 34 patients, there were 24 male patients (70.6%) and 10 female patients (29.4%).  The median age was 55.97 (23.35-73.17) years.  The most common adverse events of 34 patients were hypertension, proteinuria, diarrhoea, elevated AST/ALT and decreased blood albumin, mostly grade1/2.  One DLT (grade 3 ALT/AST increase) was observed in the 200 mg QD dose group.  MTD was not reached up to 350mg QD.  Among the 34 subjects treated with milled formulation, 22 subjects were diagnosed with neuroendocrine tumours (NETs).  Eight NET patients (5 in 300mg QD and 3 in 350mg QD cohort) had confirmed partial response (PR) with median duration of response (DoR) of 13.8 months.  The tumour origins of the 8 NET patients include pancreas (3 patients), duodenum (1 patient), rectum (1 patient), thymus (1 patient) and unknown origin (2 patients).  Objective response rate among the 18 efficacy evaluable NET patients was 44.4% and disease control rate was 100%.  Sulfatinib half-life (t_1/2) in plasma averaged 14-20 hours at the test dose levels, which supported sulfatinib QD dosing frequency.  Following QD multiple dosing, sulfatinib achieved steady state on Day 14.  The drug exposure increased when the dose increased from 200 mg to 300 mg, and then plateaued from 300 mg to 350 mg. Based on the clinical safety, efficacy, and PK data, the recommended Phase II dose is determined to be 300 mg QD.

Conclusions: Sulfatinib was well tolerated with an acceptable safety profile.  Promising anti-tumour activity was observed in NET patients.  Further clinical studies with sulfatinib are warranted.

2015年11月6日：和黃醫藥今日宣布啟動索凡替尼（HMPL-012）在美國的I期臨床試驗。該藥的美國新藥臨床研究申請於今年遞交並通過，2015年11月4日首位受試者接受給藥治療。此外，和黃醫藥將於2015年末在中國啟動索凡替尼的兩項以神經內分泌瘤為適應症的III期臨床研究以及一項以甲狀腺癌為適應症的Ib 期臨床研究。

此次I期劑量遞增研究旨在評估索凡替尼在美國晚期實體瘤患者中的安全性和耐受性，研究結果將作為在美國啟動以神經內分泌瘤為適應症的II期臨床研究的依據。

索凡替尼是以血管細胞內皮生長因子受體（VEGFR）和成纖維細胞生長因子受體（FGFR）雙靶點的口服酪氨酸激酶抑製劑，能有效地抑制腫瘤血管生成。索凡替尼的中國I期臨床研究顯示，在18位可評估療效的神經內分泌瘤患者中，客觀緩解率達到44.4%。相較之下，舒尼替尼和依維莫司，這兩個已獲批的以胰腺神經內分泌瘤為適應症的靶向單藥，在各自的關鍵性臨床研究中客觀緩解率不足10%。此外，據觀察，索凡替尼對神經內分泌瘤的緩解隨著時間逐漸加強。中國I期臨床研究的結果將在2015年11月舉辦的AACR-NCI-EORTC國際分子靶點和癌症療法會議上進行公佈，屆時詳情也將見於 www.chi‑med.com/news/。

索凡替尼是和黃醫藥第一個獨立在中國完成概念驗證性臨床研究並赴美國進行臨床研究的腫瘤候選藥物。

索凡替尼臨床研究概覽

除了美國I期臨床研究，和黃醫藥正在進行或正在籌備啟動索凡替尼的四項中國臨床研究。

神經內分泌瘤

2014年10月，和黃醫藥在中國的廣譜神經內分泌瘤（包括胰腺、胃腸、肝臟、淋巴及肺等）患者中啟動了一項多中心、單臂、開放標籤的Ib / II期臨床研究，旨在進一步評估索凡替尼的療效、安全性、耐受性及藥代動力學特性。該研究計劃招募約80位受試者，現招募工作已接近尾聲。此次開放標籤的Ib 期臨床研究目前得到的結果大致與I期臨床研究的結果相一致，受此鼓舞，和黃醫藥現計劃於2015年末在中國同時啟動索凡替尼的兩項III期臨床研究，一項以胰腺神經內分泌瘤為適應症，另一項以晚期神經內分泌良性腫瘤（非胰腺）為適應症。

甲狀腺癌

和黃醫藥計劃於2015年末在中國啟動索凡替尼的Ib 期臨床研究以評估其治療甲狀腺髓樣癌及分化型甲狀腺癌的安全性、療效及藥代動力學特性。索凡替尼的VEGFR/FGFR1抑制特性在治療二線甲狀腺癌方面應該具有巨大的潛力，尤其是當前國內的患者群體尚無安全有效的治療方法。此次研究計劃招募50位局部晚期/放射性碘難治性轉移分化的甲狀腺癌或甲狀腺髓樣癌患者，每一種腫瘤類型分別招募約25位受試者。

關於神經內分泌瘤

神經內分泌腫瘤是起源於神經內分泌細胞的腫瘤，可以發生在體內很多部位，但最常見的是消化道及呼吸道的神經內分泌腫瘤。神經內分泌腫瘤因腫瘤小，患者症狀各異，導致診斷難度大。因此，每年神經內分泌腫瘤的病例數據也很難準確預測。2014年，美國大約有19,000例神經內分泌腫瘤新發病例，患者總數約為141,000例。