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 Press Release

London: Friday, 30 October 2015: Hutchison China MediTech Limited (“Chi‑Med”) (AIM: HCM) today announces that Hutchison MediPharma Limited (“HMP”), its drug R&D subsidiary, will present further scientific data on sulfatinib (HMPL‑012), fruquintinib (HMPL‑013) and savolitinib (AZD6094, HMPL‑504) at the International Conference on Molecular Targets and Cancer Therapeutics, which will be held in Boston, Massachusetts, USA from 5 to 9 November 2015.  Sulfatinib, fruquintinib and savolitinib were all discovered by HMP and are currently being evaluated in clinical trials for the treatment of various cancers.

Sulfatinib is an oral drug candidate that selectively inhibits the tyrosine kinase activity associated with the vascular endothelial growth factor receptor (“VEGFR”) and fibroblast growth receptor (“FGFR”), a receptor for a protein which also plays a role in tumour growth.  HMP will present clinical data from its Phase I trial in China, focusing on neuroendocrine tumour (“NET”) patients.  In this study, sulfatinib’s objective response rate among the 18 efficacy-evaluable NET patients was 44.4% and disease control rate was 100%.  By comparison, sunitinib and everolimus, the two approved single agent therapies for neuroendocrine tumours, achieve objective response rates of less than 10% in their pivotal clinical trials.  Furthermore, neuroendocrine tumour responses to sulfatinib have been observed to improve gradually with time.

Savolitinib is an inhibitor of the c-Met receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumours, and fruquintinib is a highly selective inhibitor of VEGFR1, 2 and 3.  In clear cell renal cell carcinoma (“ccRCC”), c-Met activation has emerged as one of the mechanisms for resistance to anti-VEGF/VEGFR therapies, implying that inhibition of the c-Met and VEGFR pathways in a combination therapy could produce additional clinical benefit.  HMP will present data from a preclinical study to assess the effect of savolitinib and fruquintinib combined in ccRCC xenograft models.  In this study, while single-agent treatment at clinically relevant doses only exhibited mild to moderate tumour growth inhibition, a significantly increased anti-tumour effect was observed for the group receiving combination therapy.

Preclinical data will also be presented regarding savolitinib in non-small cell lung cancer (“NSCLC”) and mechanisms of acquired savolitinib resistance.

The following posters will be made available at www.chi‑med.com/news/ after they are presented at the conference:

 

1st Presentation Title:	First-in-human phase I study of a selective VEGFR/FGFR dual inhibitor sulfatinib in patients with advanced solid tumours
Authors:	Jian-Ming Xu, et al.
Session:	Poster Session A – Angiogenesis and Antiangiogenesis Agents
Date & Time:	Friday 6 November 2015, 12:15 PM – 3:15 PM

 

2nd Presentation Title:	Synergistic effect of c-Met inhibitor Savolitinib in combination with a VEGFR inhibitor Fruquintinib in clear cell renal cell carcinoma xenograft models
Authors:	Yongxin Ren, et al.
Session:	Poster Session B –Therapeutic Agents: Small Molecule Kinase Inhibitors
Date & Time:	Saturday 7 November 2015, 12:30 PM – 3:30 PM

 

3rd Presentation Title:	Acquired resistance to the cMET inhibitor savolitinib in lung cancer models through EGFR/mTOR/MYC deregulation and adoption of PIM signalling
Authors:	Ryan Henry, et al.
Session:	Late-Breaking Poster Session – Drug Resistance and Modifiers
Date & Time:	Sunday 8 November 2015, 12:30 PM – 3:30 PM

 

Hosted by the American Association for Cancer Research (“AACR”), the National Cancer Institute (“NCI”), and the European Organisation for Research and Treatment of Cancer (“EORTC”), the 2015 Molecular Targets and Cancer Therapeutics conference will bring together an estimated 3,000 academics, scientists, and pharmaceutical industry representatives from across the globe to discuss innovations in drug development, target selection, and the impact of new discoveries in molecular biology.

 

Ends

 

Enquiries

Chi-Med
Telephone:      +852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon (UK) Limited
Telephone:      +44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone:      +44 20 7638 9571
Anthony Carlisle, Mobile: +44 7973 611 888
David Dible, Mobile: +44 7967 566 919

 

Notes to Editors

Abstracts

Title:    First-in-human phase I study of a selective VEGFR/FGFR dual inhibitor sulfatinib in patients with advanced solid tumours

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.

 

Title:   Synergistic effect of c-Met inhibitor Savolitinib in combination with a VEGFR inhibitor Fruquintinib in clear cell renal cell carcinoma xenograft models

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.

 

Title:   Acquired resistance to the cMET inhibitor savolitinib in lung cancer models through EGFR/mTOR/MYC deregulation and adoption of PIM signalling

Authors: Ryan E. Henry, Evan R. Barry, Brendon Ladd, Aleksandra Markovets, Garry J. Beran, Yongxin Ren, Feng Zhou, Lillian Castriotta, Ammar Adam, Weiguo Qing, Weiguo Su, Edwin Clark, Celina M. D’Cruz, Alwin Schuller.

Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments.  Aberrant receptor tyrosine kinase (RTK) signalling is a well-documented driver of disease onset and progression in multiple cancer types, including NSCLC, where the cMET RTK contributes to tumour progression, maintenance and resistance to targeted therapies.  Here, we explore the therapeutic potential of the potent and selective cMET inhibitor savolitinib (volitinib, AZD6094, HMPL‑504) in NSCLC and begin to elucidate mechanisms of acquired savolitinib resistance in preclinical models.  Using in vitro proliferation assays and immunoblot analysis, we determine that savolitinib rapidly inhibits cMET auto-phosphorylation/activation and reduces the viability of NSCLC cell lines NCI-H1993 and EBC-1 with a GI₅₀ of 4.20 nM and 2.14 nM, respectively.  In vivo, once daily treatment of NCI-H1993 xenografts with 3.0 mg/kg savolitinib significantly slows tumour growth, whereas treatment of EBC-1 xenografts with 30.0 mg/kg results in tumour stasis.  Importantly, we observe tumour regressions in a patient-derived xenograft model of a NSCLC lymph node metastasis, HLXF‑036LN, dosed with savolitinib 50.0 mg/kg once daily.  Pharmacodynamic analysis of in vitro and in vivo models shows that savolitinib sensitivity correlates with blockade of PI3K/AKT and MAPK signalling, and interestingly, with cMYC (MYC) protein down-regulation.  To elucidate mechanisms of acquired resistance in NSCLC, we generated savolitinib resistance in vitro using the NCI‑H1993 and EBC-1 cell lines and further sub-cloned resistant NCI‑H1993 cells to study the heterogeneity of resistance mechanisms.  Using small-molecule screening, phospho-protein arrays and interrogation of signalling pathway activity by immunoblot, we identify 1) deregulated mTORC1/2 signalling and 2) the uncoupling of MYC expression from cMET activation as commonly contributing to resistance in all clones tested.  RNA interference (siRNA) and MYC over-expression experiments confirm the novel finding that sustained MYC expression can partially drive resistance to a tyrosine kinase inhibitor such as savolitinib.  Additionally, we identify clone-specific resistance mechanisms arising via a previously-described switch to EGFR dependence or by our novel finding of a de novo requirement for PIM signalling.  Taken together, this work demonstrates the preclinical efficacy of savolitinib in NSCLC and provides an initial characterization of potential resistance mechanisms, identifying core resistance targets and clone-specific vulnerabilities that could be exploited to counter acquired savolitinib resistance that may emerge in the clinic.

 

About sulfatinib

Sulfatinib is an oral drug candidate that selectively inhibits the tyrosine kinase activity associated with VEGFR and FGFR.  Angiogenesis is an important mechanism in tumour pathogenesis, and inhibition of VEGF-mediated angiogenesis has been important in the treatment of a variety of cancers.  FGFR is a receptor for a protein which also plays a role in tumour growth.  HMP is conducting, or in the process of initiating, two Phase III and two Phase Ib clinical trials in China, and one Phase I clinical trial in the United States.  These trials are intended to assess the effectiveness of sulfatinib for the treatment of neuroendocrine cancer and thyroid cancer patients.

 

About fruquintinib

Fruquintinib is designed as a highly selective and potent oral inhibitor of VEGFR, namely VEGFR1, VEGFR2, and VEGFR3.  In March and September 2015, Chi-Med announced that the first proof-of-concept studies of fruquintinib in China in patients with third-line metastatic colorectal cancer and non-small cell lung cancer clearly met their primary endpoints of progression free survival by demonstrating superiority compared with placebo.  Fruquintinib was well tolerated in both studies, showing no major unexpected safety issues.  HMP is conducting or in the process of initiating two Phase III clinical trials in these indications.  HMP is also conducting a Phase Ib dose-finding study of fruquintinib, in combination with paclitaxel, in second line gastric cancer patients in China.

In October 2013, HMP entered into a licensing, co-development and commercialisation agreement with Eli Lilly for fruquintinib.

 

About savolitinib

Savolitinib is a potential global first-in-class inhibitor of c-Met, receptor tyrosine kinase, an enzyme which exhibits aberrant behaviour (e.g. gene amplification, over-expression and mutation) in many types of solid tumours.  Savolitinib was developed as a potent and highly selective oral c-Met inhibitor that was designed to address renal toxicity, the primary issue that has to-date prevented other selective c-Met inhibitors from gaining regulatory approval.  In Phase I/Ib clinical studies in Australia and China, savolitinib has shown promising signs of clinical efficacy, causing tumour size reduction, in c-Met aberrant patients in papillary renal cell carcinoma, non-small cell lung cancer, colorectal cancer and gastric cancer.

Currently, HMP and AstraZeneca AB, its partner on savolitinib, are conducting nine clinical studies of savolitinib monotherapy treatment as well as savolitinib in combination treatments with other tyrosine kinase inhibitors and chemotherapy in kidney, lung and gastric cancers.  Furthermore, by the end of 2015, HMP and AstraZeneca AB expect to initiate three further proof-of-concept studies for savolitinib, two of which will involve combinations with immunotherapies.

 

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.

 

Forward-Looking Statements

This announcement contains forward-looking statements that reflect Chi-Med’s current expectations regarding future events, including its plans to initiate clinical studies for its drug candidates in the targeted indications, 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 enrolment 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 a drug candidate to meet the primary or secondary endpoint of a study, the ability of a drug candidate to obtain regulatory approval in different jurisdictions, the ability of a drug candidate to gain commercial acceptance after obtaining regulatory approval 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. 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.

London: Friday, 30 October 2015: For information purposes, Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) hereby notifies the market that as at 30 October 2015, the issued share capital of Chi-Med consisted of 56,533,118 ordinary shares of US$1.00 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 56,533,118 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, Chi-Med under the Financial Conduct Authority’s Disclosure Rules and Transparency Rules.

 

Ends

Enquiries

Chi-Med
Telephone:      +852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon (UK) Limited
Telephone:      +44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone:      +44 20 7638 9571
Anthony Carlisle
Mobile:            +44 7973 611 888
David Dible
Mobile:            +44 7967 566 919

 

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:  Friday, 30 October 2015:  Hutchison China MediTech Limited (“Chi‑Med”) (AIM: HCM) today announces that Hutchison MediPharma Limited (“HMP”), its drug R&D subsidiary, has successfully completed its first-in-human Phase I clinical trial of HMPL‑523.  HMPL‑523 is a novel, highly selective and potent small molecule inhibitor targeting spleen tyrosine kinase, also known as Syk, a key component in B-cell receptor signalling.

The first-in-human Phase I study of HMPL‑523 was a dose-escalating study conducted to assess the safety, tolerability and pharmacokinetics of both single and repeat doses of HMPL‑523 in healthy volunteers in Australia.  The study began in June 2014, and completed ten single dose cohorts, with eight patients per cohort, from 5mg single dose through 800mg single dose.  In April 2015, the multiple ascending dose section of the Phase I study commenced in which HMPL‑523 was administered once daily for 14 consecutive days.  Four dose cohorts have now completed this section of the study, again with eight patients per cohort, from 200mg multiple dose through to 400mg multiple dose.  At 400mg daily, HMPL‑523 drug exposures are believed to be well above the predicted efficacious dose level and, consequently, there is no intention to escalate further in healthy volunteers.

The preliminary safety profile of HMPL‑523 was in-line with our expectations.  No material off-target toxicities such as hypertension and severe diarrhoea were observed with HMPL‑523 in this study.  Furthermore, HMPL‑523 exhibited a linear pharmacokinetic profile and a dose dependent suppression of B-cell activation.  Full results of the Phase I study will be published in due course.

Christian Hogg, CEO of Chi‑Med, said, “We have now established what we believe is a dose range for the further development of HMPL‑523.  This will now allow Chi-Med to move this important, potentially first-in-class compound into global Phase II proof-of-concept studies against multiple indications both in autoimmune diseases and oncology.”

 

 

Ends

 

Enquiries

Chi-Med
Telephone:      +852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon (UK) Limited
Telephone:      +44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone:      +44 20 7638 9571
Anthony Carlisle, Mobile: +44 7973 611 888
David Dible, Mobile: +44 7967 566 919

 

Notes to Editors

About HMPL‑523

As one of the major cellular components of the immune system, B-cells play pivotal roles in several immune system related diseases, such as autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and allergy, as well as haematological cancers (i.e. B-cell malignancies) including lymphoma and leukaemia.  Targeted B-cell receptor signalling therapies, including monoclonal antibodies (“mAb”) and small molecules, have been proven to be clinically effective for the treatment of rheumatoid arthritis (“RA”) as well as B-cell malignancies, leading to scientific and commercial success.

HMPL‑523 is an oral small molecule therapy targeting Syk, a major component in the B-cell signalling pathway.  If proven safe and effective, we believe HMPL‑523 will be an attractive therapy due to its convenience of use as compared to the intravenous B-cell receptor blocking mAb rituximab (Roche) and the TNFα blocking mAb drugs like infliximab (Janssen), adalimumab (AbbVie) and etanercept (Amgen/Pfizer).  Furthermore, oral small molecules such as HMPL‑523 are generally cleared more quickly from the body as compared to mAbs, thereby reducing the risk of infections which result from sustained suppression of the immune system.

The total global market for RA drugs is predicted to grow from approximately US$34 billion in 2014 to US$45 billion by 2020, according to Frost & Sullivan.

 

About small molecule B-cell signalling pathway inhibitors in immunology

Clinical efficacy in RA has been established by a first generation small molecule Syk inhibitor, fostamatinib (Rigel/AstraZeneca).  Unfortunately, poor kinase selectivity linked to critical off-target side effects such as hypertension, severe diarrhoea, and neutropenia limited fostamatinib’s dose and led to failure in Phase III studies and ultimately discontinuation in RA.

We designed HMPL‑523 to be highly selective to eliminate these off-target toxicities thereby creating the opportunity for safe combination with other therapies to maximise efficacy.  Furthermore, the pharmacokinetic properties of HMPL‑523 are unique, with pre-clinical studies indicating extensive tissue distribution.  We believe high tissue distribution is important, particularly in tissue-oriented autoimmune diseases, and research on HMPL‑523 has confirmed this by demonstrating strong efficacy in RA and lupus pre-clinical models with relatively low plasma concentrations.  Consequently, in addition to our planned global Phase II development in RA, we intend to evaluate HMPL‑523 as a treatment for lupus.

 

About small molecule B-cell signalling pathway inhibitors in haematological cancer

The advantages of small molecule B-cell receptor signalling therapy has driven research and development by major pharmaceutical companies.  Notable success has been achieved in B-cell malignancies in oncology, such as lymphoma and leukaemia, where small molecule inhibitors are now being used to target kinases down-stream from Syk in the B-cell signalling pathway, namely Bruton’s tyrosine kinase (“BTK”) and PI3Kδ.  In 2013 and 2014, ibrutinib (BTK/AbbVie) and idelalisib (PI3Kδ/Gilead) both received Breakthrough Therapy designation and accelerated approval from the FDA in the U.S. in haematological cancer indications.  Given the important role of B-cell receptor signalling in haematological cancer, we intend to initiate a Phase I study in Australia in haematological cancer patients in late 2015.

In early clinical studies in haematological cancer, where off-target toxicities are less limiting, several small molecule Syk inhibitors have begun to show promise.  Fostamatinib, entospletinib (Gilead) and TAK-659 (Takeda) have all exhibited efficacy against various sub-types of non-Hodgkin’s lymphoma, in either a single agent or combination setting, thereby indicating that Syk is a relevant target for these diseases.

 

About HMP

HMP is a novel drug R&D company focusing on discovering, developing and commercialising innovative therapeutics in oncology and autoimmune diseases.  With a team of around 250 scientists and staff, its pipeline is comprised of novel oral compounds for cancer and inflammation in development in North America, Europe, Australia and Greater China.  HMP is a subsidiary of Chi-Med.  For more information, please visit: www.hmplglobal.com.

 

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.

 

Forward-Looking Statements

This announcement contains forward-looking statements that reflect Chi‑Med’s current expectations regarding future events, including its plans to initiate clinical studies for its drug candidates in the targeted indications, 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 enrolment 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 a drug candidate to meet the primary or secondary endpoint of a study, the ability of a drug candidate to obtain regulatory approval in different jurisdictions, the ability of a drug candidate to gain commercial acceptance after obtaining regulatory approval 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.  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.

London: Friday, 23 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) today announces that Hutchison MediPharma Limited (“HMP”), its drug R&D subsidiary, is set to receive a US$10 million milestone payment, in the fourth quarter of 2015, from its partner Eli Lilly and Company (“Lilly”).

The milestone payment was triggered by the positive proof-of-concept (“POC”) Phase II study of fruquintinib in the treatment of patients with advanced non-squamous non-small cell lung cancer (“NSCLC”) in China. Last month, top line results of this POC Phase II study were reported showing fruquintinib met the primary endpoint of progression free survival (“PFS”). The adverse events demonstrated in the POC study are consistent with the known safety profile for fruquintinib. Full details of the NSCLC Phase II POC results will be presented at a global medical conference in 2016.

Pursuant to the fruquintinib licensing, co-development, and commercialisation agreement entered into by HMP and Lilly in October 2013, HMP will receive reimbursements for costs associated with further clinical development in China for NSCLC according to a pre-specified cost-sharing rate. We now intend to initiate a pivotal Phase III study of fruquintinib in non-squamous NSCLC in China.

Including this US$10 million NSCLC POC milestone payment, HMP will have received a total of US$31.7 million from Lilly so far this year.

 

Ends

Enquiries

Chi-Med
Telephone: ​+852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon (UK) Limited
Telephone: ​+44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone:​ +44 20 7638 9571
Anthony Carlisle, Mobile: ​+44 7973 611 888
David Dible, Mobile: ​+44 7967 566 919

 

Notes to Editors

About fruquintinib

Fruquintinib is designed as a highly selective and potent oral inhibitor of vascular endothelial growth factor (“VEGF”) receptors (“VEGFR”), namely VEGFR1, VEGFR2, and VEGFR3. Angiogenesis is an important mechanism in tumour pathogenesis, and inhibition of VEGF-mediated angiogenesis has been important in the treatment of a variety of cancers.

In addition to the planned pivotal Phase III study in NSCLC, fruquintinib is being developed in metastatic colorectal cancer and gastric cancer:

Metastatic colorectal cancer fruquintinib monotherapy – HMP reported full results of the first POC Phase II study of fruquintinib in a randomised, double-blind, placebo-controlled, multi-centre Phase II clinical trial in patients with third-line metastatic colorectal cancer. This Phase II study showed fruquintinib had met the primary endpoint of PFS. The adverse events demonstrated in this POC study are consistent with the known safety profile for fruquintinib. 71 patients were enrolled in the trial, and median PFS was 4.73 months in the fruquintinib arm compared with 0.99 month in the placebo arm, with a hazard ratio of 0.30 (p<0.001).

As a result, HMP initiated FRESCO, a Phase III registration study in patients with metastatic colorectal cancer, who have failed at least two prior systemic cancer therapies, including flouropyrimidine, oxaliplatin and irinotecan. HMP plans to enrol more than 400 patients in about 25 centres across China for this study, with top-line results expected in 2016.

Gastric cancer fruquintinib combination with paclitaxel – HMP is nearing completion of a Phase Ib dose-finding study of fruquintinib, in combination with paclitaxel, in second-line gastric cancer patients and plans to initiate a Phase II POC study in early 2016.

 

About VEGF and NSCLC in China

At an advanced stage, tumours secrete large amounts of VEGF, a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumour in order to provide greater blood flow, oxygen, and nutrients to the tumour. VEGF and VEGF receptors play a pivotal role in tumour-related angiogenesis, and inhibition of the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumours to grow and invade.

Lung cancer is one of the leading malignant causes of death in the world, and there were an estimated 1.9 million new cases of lung cancer diagnosed worldwide in 2014, of which approximately 36% were from China. The very high prevalence of lung cancer in China as compared to the rest of the world is thought to be linked in part to the high incidence of cigarette smoking in the country. The number of new cases annually is expected to grow and reach an estimated 2.3 million globally by 2020. There are two major types of lung cancer: small cell lung cancer and NSCLC. NSCLC is a disease in which malignant cancer cells form in the tissues of the lung, and can be further classified based on cancer cell types with the most common ones including squamous cell carcinoma, large cell carcinoma and adenocarcinoma.

To date, several anti-VEGF/VEGFR agents have shown clinical efficacy against a number of tumour types. Given the scale and growth in the China oncology market, the market for VEGF/VEGFR inhibitors in China is expected to develop quickly in the next few years.

 

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: 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.

Following the above transactions, the combined holding of Mr Nash and his spouse is 36,442 Shares, representing approximately 0.06% of the current issued share capital of Chi-Med.

 

Ends

 

Enquiries

 

Chi-Med
Telephone: ​+852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon (UK) Limited
Telephone: ​+44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone: ​+44 20 7638 9571
Anthony Carlisle, Mobile: ​+44 7973 611 888
David Dible, Mobile: ​+44 7967 566 919

 

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, 19 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) announces that the Remuneration Committee of Chi-Med today granted conditional awards (the “LTIP Awards”) under the Long Term Incentive Plan (the “LTIP”) of Chi-Med adopted at its Annual General Meeting on 24 April 2015.

The LTIP Awards grant participating directors or employees a conditional right to receive ordinary shares in Chi-Med (the “Ordinary Shares”), to be purchased on-market by an independent third party trustee (the “Trustee”) up to a maximum cash amount depending upon the achievement of annual performance targets (which will be aligned with the strategic objectives of Chi-Med as determined by the Remuneration Committee) for each financial year of Chi-Med stipulated in the LTIP Awards.

The Ordinary Shares, to be purchased by the Trustee following determination of the cash amount based on actual achievement of each annual performance target, will then be held by the Trustee until they are vested. Vesting will occur one business day after the publication date of the annual report of Chi-Med for the financial year falling two years after the financial year to which the LTIP Award relates.  Vesting will also depend upon the continued employment of the award holder with the Chi-Med group and will otherwise be at the discretion of the Board of Directors of Chi-Med. The initial LTIP Awards will cover a three-year period from 2014 to 2016 (the “LTIP Period”).

Chi-Med has granted the following LTIP Awards to the Executive Directors:

 

Award Holder	Maximum US$ amount per annum for the LTIP Period stipulated in the LTIP Awards
Mr Christian Hogg (Chief Executive Officer)	329,385
Mr Johnny Cheng (Chief Financial Officer)	101,619

 

An additional 41 senior managers and executives employed by Chi-Med and its subsidiaries have simultaneously been granted LTIP Awards for the LTIP Period.

Further announcements will be made in due course at the time the LTIP Awards are vested, when the number of the Ordinary Shares to which each Executive Director is entitled will be known.

 

Ends

 

Enquiries

Chi-Med Christian Hogg, CEO	Telephone:      +852 2121 8200
Panmure Gordon (UK) Limited Richard Gray Andrew Potts	Telephone:      +44 20 7886 2500
Citigate Dewe Rogerson Anthony Carlisle David Dible	Telephone:      +44 20 7638 9571 Mobile:            +44 7973 611 888 Mobile:            +44 7967 566 919

 

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.

For determining the entitlement to attend and vote at the Extraordinary General Meeting.

An explanatory circular, incorporating a letter from the Chairman and a Notice of Extraordinary General Meeting, and a form of proxy have been posted to shareholders.

Press Release

London: Friday, 16 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) announces that it has publicly filed today a registration statement on Form F-1 (the “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 press release, 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 to formally 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 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 Registration Statement becomes effective. The Registration Statement and all subsequent amendments may be accessed through the SEC’s website at www.sec.gov.

The Offering, if it does proceed, will be made only by means of a prospectus that will form part of the effective Registration Statement. Copies of the preliminary prospectus, when available, may be obtained from (in alphabetical order) (i) Bank of America Merrill Lynch, Attn: Prospectus Department, 222 Broadway, New York, NY 10038, or by email at dg.prospectus_requests@baml.com, or (ii) Deutsche Bank Securities Inc., Attn: Prospectus Group, 60 Wall Street, New York, NY 10005, or by email at prospectus.cpdg@db.com.

This press release 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.

 

Ends

 

Enquiries

Chi-Med Christian Hogg, CEO	Telephone: +852 2121 8200
Panmure Gordon (UK) Limited Richard Gray Andrew Potts	Telephone: +44 20 7886 2500
Citigate Dewe Rogerson Anthony Carlisle David Dible	Telephone: +44 20 7638 9571 Mobile: +44 7973 611 888 Mobile: +44 7967 566 919

 

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.

 

Forward-looking statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties, including statements regarding the proposed Offering.  Actual results may differ materially from those projected or implied. More information about potential factors that could affect Chi-Med’s business and financial results is contained in the Registration Statement filed with the SEC. Any forward-looking statement made by Chi-Med herein, or elsewhere, speaks only as of the date on which such statement is made. Chi-Med does not intend, and undertakes no duty, to update any forward-looking statements after the date hereof to reflect future events or circumstances.

London: Friday, 16 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) today announces that, following the announcement that it had publicly filed a registration statement on Form F-1 (“Form F-1 Registration Statement”) with the United States Securities and Exchange Commission for a potential offering of American depositary shares on the Nasdaq Stock Market (“Offering”), an explanatory circular and a form of proxy have been posted to shareholders. The circular incorporates a letter from the Chairman and a Notice of Extraordinary General Meeting convening an Extraordinary General Meeting to be held at 4th Floor, Hutchison House, 5 Hester Road, Battersea, London SW11 4AN on Tuesday, 10 November 2015 at 10:00 a.m. in order for shareholders to vote upon the resolutions required to enable the directors of Chi-Med to issue new ordinary shares in connection with the potential Offering.

The circular, which has today been posted to shareholders, is also available on the website of Chi-Med at www.chi-med.com.

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.

Ends

Enquiries:

Chi-Med Christian Hogg, CEO	Telephone: +852 2121 8200
Panmure Gordon (UK) Limited Richard Gray Andrew Potts	Telephone: +44 20 7886 2500
Citigate Dewe Rogerson Anthony Carlisle David Dible	Telephone: +44 20 7638 9571 Mobile: +44 7973 611 888 Mobile: +44 7967 566 919

 

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 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 American depositary shares 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 (the “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.

 

Forward-Looking Statements

This announcement may contain forward-looking statements that reflect Chi-Med’s current expectations regarding future events, including its intention to complete the potential Offering. Forward looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, the possibility that the potential Offering will not be completed within a particular time frame or at a particular amount, or at all, including as a result of regulatory, market or other factors.  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.

The following includes the text of the Announcement but excludes the appendix. For the complete release, please download the PDF.
—

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, 16 October 2015: Hutchison China MediTech Limited (“Chi‑Med”) (AIM: HCM) today announces that it is evaluating the feasibility of a potential issuance of new Ordinary Shares (the “Equity Raise”) in connection with a potential listing of American depositary shares (“ADSs”) representing such Ordinary Shares on the Nasdaq Stock Market (the “Offering”).  Chi‑Med has publicly filed today a registration statement on Form F‑1 (“Form F‑1 Registration Statement”) with the United States Securities and Exchange Commission (the “SEC”) in relation to the potential Offering.  The Offering will be made only by means of an effective Form F‑1 Registration Statement. As at 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. The number of offering shares and offering price of the potential Offering have not yet been determined. The directors of Chi‑Med (“Directors”) will assess various factors, including market conditions, in considering whether to formally launch the transaction.

Any equity securities of Chi‑Med listed on Nasdaq as part of the potential Offering will be in the form of ADSs. ADSs are negotiable instruments issued by a depositary bank that represent ownership of Ordinary Shares. They are designed to facilitate the purchase, holding and sale of Ordinary Shares by investors who wish to trade on Nasdaq. ADSs are similar to Depositary Interests in that each ADS will represent a fixed number of Ordinary Shares (the exact ratio of ADSs to Ordinary Shares will be determined during the Offering process), save that ADSs will be denominated in US dollars.

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.

Mr Simon To, Executive Director and Chairman of Chi‑Med, said, “We believe the United States not only represents one of the world’s most important pharmaceutical markets for the development of our drug candidates but also the largest healthcare investment community. We consider that Chi‑Med should take this important step to increase its profile amongst U.S. investors and seek to benefit from the additional liquidity that we believe a listing on Nasdaq should provide. The potential U.S. listing and financing will importantly, if successful, enable Chi‑Med to accelerate and broaden investment in its product pipeline and expand its manufacturing facilities to support the potential future commercialisation of its products.”

A copy of the Form F‑1 Registration Statement can be accessed through the website of the United States Securities and Exchange Commission at www.sec.gov.

 

Background to the potential Equity Raise and Offering

The potential Equity Raise and Offering are intended to support the implementation of Chi‑Med’s current drug development plans. It is the belief of the Directors that the United States represents one of the most important markets for the development of Chi‑Med’s drug candidates, and the United States also has a large number of specialist healthcare investors. The Directors believe that Chi‑Med should obtain exposure to the United States capital markets to increase its profile amongst United States investors and seek to benefit from the additional liquidity that the Directors believe a listing on Nasdaq should provide. In summary, given the nature of the business of Chi‑Med and its subsidiaries (the “Group”), the Directors believe that the potential Equity Raise and Offering together comprise an appropriate and beneficial route for Chi‑Med to take.

Although the final size of the potential Equity Raise is yet to be determined, if the potential Equity Raise and Offering do proceed, Chi‑Med intends to use the net proceeds of the potential Equity Raise, together with the cash generated by its operations, primarily to advance the clinical development of its multiple drug candidates. In particular, Chi‑Med expects to apply these net proceeds as follows:

a) to accelerate and broaden clinical development of the drug candidates for which it retains all worldwide rights, specifically to advance:

i. HMPL 523 through Phase I and Proof of Concept studies, expected to be conducted in Australia, the United States and China, in rheumatoid arthritis, lupus and haematological cancer;

ii. sulfatinib through NDA submission in China and through Phase I and Proof of Concept studies, expected to be conducted in the United States, in neuroendocrine tumours, and through Phase I and Proof of Concept studies, expected to be conducted in China, in thyroid cancer;

iii. epitinib through NDA submission in China and Phase I and Proof of Concept studies, expected to be conducted in the United States, in non small cell lung cancer with brain metastasis; and

iv. theliatinib through Phase I and Proof of Concept studies, expected to be conducted in China and the United States, in head and neck cancer and oesophageal cancer;

b) to support its share of the development costs of its partnered clinical drug candidates, including to advance:

i. savolitinib through NDA submission globally in papillary renal cell carcinoma and EGFR tyrosine kinase inhibitor refractory non small cell lung cancer and through Proof of Concept studies globally in gastric cancer and VEGFR tyrosine kinase inhibitor refractory clear cell renal cell carcinoma;

ii. fruquintinib through NDA submission in colorectal cancer and non small cell lung cancer in China and through Proof of Concept in gastric cancer in China and to advance fruquintinib through Proof of Concept in non small cell lung cancer in the United States either independently or in partnership with Eli Lilly subject to the exercise of its global option; and

iii. HMPL 004 through an interim analysis in a global Phase III study in mild to moderate ulcerative colitis;

c) to progress pre clinical drug candidates, specifically to advance:

i. HMPL 689 through Phase I and Proof of Concept studies, expected to be conducted in Australia, the United States and China, in haematological cancer;

ii. HMPL 453 through Phase I and Proof of Concept studies, expected to be conducted in Australia, the United States and China, in bladder cancer; and

iii. other drug candidates through pre clinical studies and into Phase I clinical trials;

d) to build production facilities to produce both clinical and commercial supply of its drug candidates; and

e) to repay certain of its existing term loan from Scotiabank (Hong Kong) Limited.

Although Chi‑Med expects that the majority of the net proceeds from the potential Equity Raise, if the potential Equity Raise and Offering do proceed, would be used to advance the clinical development of its multiple drug candidates, the precise amounts allocated to each of the expenditure items listed above will only be determined once the final size of the potential Equity Raise is known.

Chi‑Med expects to use the remainder of the net proceeds (if any) to provide funding for working capital and other general corporate purposes, such as acquiring the commercial rights to other drug products and expanding its research organisation and infrastructure.

If the potential Equity Raise and Offering do proceed, the expected usage of the potential Equity Raise net proceeds represents the Directors’ intentions based upon their current plans and Chi‑Med’s business conditions. Due to the many variables inherent in the development of its drug candidates at this time, such as the timing of patient enrolment and evolving regulatory requirements, the Directors cannot currently predict the stage of development they expect to achieve for Chi‑Med’s pre‑clinical and clinical trial and drug candidates with the net proceeds of the potential Equity Raise. The amounts and timings of the actual expenditure to be incurred by Chi‑Med may vary significantly depending on numerous factors, including the results of the pre‑clinical and clinical trial of its drug candidates, its operating costs and expenditures and the amount of cash generated by its operations. Accordingly, the Directors will have broad discretion over the usage of the net proceeds and investors will be relying on the judgment of the Directors regarding the application of the net proceeds. Pending such usage, the Directors intend to invest these net proceeds in high‑quality, investment‑grade, short‑term fixed income instruments.

Pending the execution of the potential Offering, Chi-Med has sufficient resources and support to pursue the current research and development of its drug candidates.

Chi‑Med will be seeking shareholders’ approval to authorise the Directors to issue new Ordinary Shares in connection with the potential Offering at an extraordinary general meeting of Chi‑Med which is expected to take place on Tuesday, 10 November 2015. An explanatory circular will shortly be posted to shareholders to provide further information in relation to the potential Offering. A further announcement will be published if Chi‑Med decides to proceed with the potential Offering.

 

The Existing Shareholders

The Directors recognise the importance of Chi‑Med’s existing shareholder base and plan to retain admission of the Ordinary Shares to trading on the AIM market of the London Stock Exchange (“AIM”) alongside the listing of the ADSs on Nasdaq. Notwithstanding the planned listing of the ADSs on Nasdaq, Chi‑Med will continue to be subject to the AIM Rules. Shareholders will continue to be able to deal in Depositary Interests and/or Ordinary Shares on AIM and following the listing of the ADSs on Nasdaq will, subject to certain restrictions that apply where such shareholders are affiliates of Chi‑Med, also be able to deal in ADSs on Nasdaq. Shareholders should consult their own legal advisers as to whether they are affiliates of Chi‑Med but, generally, shareholders should note that Directors, certain officers and shareholders holding more than 10 per cent. of the issued Ordinary Shares are considered to be affiliates for these purposes.

 

The Potential Offering

A document setting out certain information addressing questions concerning the potential Offering and trading of ADSs on Nasdaq, and explaining how to convert Ordinary Shares and Depositary Interests into ADSs (and vice versa), will be prepared for the benefit of shareholders (the “FAQs”). Shareholders are encouraged to review the FAQs, which will be available for viewing on Chi‑Med’s website at www.chi‑med.com following the listing of the ADSs on Nasdaq, and to consult their stockbroker, solicitor, accountant or other independent financial adviser in the event of any doubt.

In relation to the potential Offering, Chi‑Med has filed the Form F‑1 Registration Statement. The Form F‑1 Registration Statement, which has not yet become effective, anticipates an offer of new Ordinary Shares in the form of ADSs. A precise determination of the number of ADSs to be offered by Chi‑Med and the offering price has not yet been made.

Chi‑Med will also make an application for the new Ordinary Shares to be issued in connection with the potential Equity Raise to be admitted to trading on AIM.  As noted above, application has been made to Nasdaq for the ADSs representing such Ordinary Shares to be listed on the Nasdaq Stock Market upon effectiveness of the Form F‑1 Registration Statement. The new Ordinary Shares issued as a result of the potential Equity Raise will rank pari passu with the existing Ordinary Shares of Chi‑Med.

The potential Offering will be made only by means of an effective Form F‑1 Registration Statement.

The ADSs and the new Ordinary Shares to be issued as a result of the potential Equity Raise may not be subscribed for or sold, nor may offers to subscribe for or buy the ADSs or the new Ordinary Shares to be issued as a result of the potential Equity Raise be accepted, prior to the time the Form F‑1 Registration Statement becomes effective.

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

The consolidated financial statements of the Group included in the Form F‑1 Registration Statement (comprising the consolidated financial statements for the years ended 31 December 2014 and 31 December 2013 and the unaudited condensed consolidated financial statements for the six months ended 30 June 2015 and 30 June 2014, together the “Historical Financial Information”) have been prepared in accordance with U.S. GAAP, while the historical consolidated financial statements of the Group published prior to the potential Offering were prepared in accordance with IFRS. The Board wishes to change the accounting standards it adopts in the preparation of the consolidated financial statements of the Group from IFRS to U.S. GAAP following the completion of the potential Offering. In addition, Chi‑Med has three non‑consolidated joint ventures ‑ Shanghai Hutchison Pharmaceuticals Limited, Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited and Nutrition Science Partners Limited.  The consolidated financial data of each such joint venture (which are prepared under IFRS, as of and for the years ended 31 December 2014 and 31 December 2013 and as of and for the six months ended 30 June 2015 and 30 June 2014) and the Historical Financial Information, each as extracted from the Form F‑1 Registration Statement, are set out in the Appendix to this announcement.

 

Ends

Enquiries:

Chi‑Med Christian Hogg, CEO	Telephone: +852 2121 8200
Panmure Gordon (UK) Limited Richard Gray Andrew Potts	Telephone: +44 20 7886 2500
Citigate Dewe Rogerson Anthony Carlisle David Dible	Telephone: +44 20 7638 9571 Mobile:       +44 7973 611 888 Mobile:       +44 7967 566 919

 

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 appendices 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 appendices 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 appendices to it, may contain forward‑looking statements that reflect Chi‑Med’s current expectations regarding future events, including the commercialisation and regulatory clearance of Chi‑Med’s products, the Group’s liquidity and results of operations, as well as the Group’s future capital raising activities. Forward‑looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including the success of Chi‑Med’s research and development and commercialisation strategies, the uncertainties related to the regulatory process and the acceptance of Chi‑Med’s products by hospitals and other medical professionals. 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.

 

Defined Terms

For the purposes of this announcement:

“AIM Rules” means the rules and guidance for companies whose shares are admitted to trading on AIM entitled “AIM Rules for Companies” published by the London Stock Exchange, as amended from time to time;

“CREST” means an electronic settlement system for United Kingdom and Irish securities operated by Euroclear UK & Ireland Limited for the paperless settlement of securities in uncertificated form;

“Depositary Interests” means the dematerialised depositary interests each representing an entitlement to Ordinary Shares which may be traded through CREST in dematerialised form;

“EGFR”  means epidermal growth factor receptor;

“Group” means Chi‑Med and its subsidiaries;

“IFRS”  means the International Financial Reporting Standards as issued by the International Accounting Standards Board;

“Nasdaq” means the Nasdaq Stock Market;

“NDA submission” means a request for approval to market a drug containing evidence of safety and efficacy which is demonstrated by extensive pre‑clinical and clinical testing;

“Ordinary Shares” means the fully paid ordinary shares in the capital of Chi‑Med which have a nominal value of US$1 each, and “Ordinary Share” means any one of them;

“Phase I” means a preliminary clinical trial for clinical pharmacology and body safety, conducted to observe the human body tolerance for new medicine and pharmacokinetics, so as to provide a basis for determining the prescription plan;

“Phase III” means a clinical trial stage to verify the clinical effectiveness, the purpose of which is to test and determine the clinical effectiveness and safety of the medicine used on patients with targeted indication, to evaluate the benefits and risks thereof and, eventually, to provide sufficient basis for review of the medicine registration application;

“Proof‑of‑Concept” means a clinical trial conducted to establish the clinical effectiveness and safety of the new medicine used on patients with the targeted indication. Generally Proof‑of‑Concept trials are categorised as either Phase Ib or Phase II trials, which are clinical trials conducted in a larger patient population than for a Phase I trial, but in a smaller patient populations than Phase III registration application trials;

“U.S. GAAP” means the United States generally accepted accounting principles; and

“VEGFR” means vascular endothelial growth factor receptor.

 

Appendix
Historical Financial Information prepared in accordance with U.S. GAAP
and
Historical Financial Information of Non‑Consolidated Joint Ventures
prepared in accordance with IFRS

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

Press Release

London: Tuesday, 13 October 2015: Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) today announces that Hutchison MediPharma Limited (“HMP”), its drug R&D subsidiary, and AstraZeneca AB (publ) (“AstraZeneca”) have completed enrolment in a global Phase II study of savolitinib (AZD6094), a potent and highly selective mesenchymal epithelial transition factor (“c-Met”) inhibitor.  This is a Phase II study to evaluate the efficacy and safety of savolitinib monotherapy (600 mg once daily) in papillary renal cell carcinoma (“PRCC”) in the United States, Canada and Europe.  PRCC represents about 14% of all new cases of kidney cancer.

Savolitinib is a potential global first-in-class inhibitor of c-Met, receptor tyrosine kinase, an enzyme which exhibits aberrant behaviour (e.g. gene amplification, over-expression and mutation) in many types of solid tumours.  Savolitinib was developed as a potent and highly selective oral c-Met inhibitor that was designed to address renal toxicity, the primary issue that has to-date prevented other selective c-Met inhibitors from gaining regulatory approval.  In Phase I/Ib clinical studies, savolitinib has shown promising signs of clinical efficacy, causing tumour size reduction, in c-Met aberrant patients in PRCC, non-small cell lung cancer, colorectal cancer and gastric cancer.

This Phase II study is an open-label, single-arm, multicentre study designed to evaluate the efficacy and safety of savolitinib in patients with locally advanced or metastatic PRCC.  A total of 90 patients have been enrolled in 22 centres, making it the largest prospective clinical study in PRCC ever conducted.  The primary objective of this study is to assess the anti-tumour activity of savolitinib in patients with PRCC, with secondary assessment objectives including progression free survival, duration of response, safety and tolerability and pharmacokinetics and pharmacodynamics.  Importantly, tumour samples from each patient are concurrently being subjected to molecular analysis to determine c-Met status in order to better understand the relationship between c-Met aberration and clinical outcome.

The interim data of the Phase II trial is expected to be published at the American Society of Clinical Oncology meeting in 2016.

 

Ends

 

Enquiries

Chi-Med
Telephone: +852 2121 8200
Christian Hogg, CEO

 

Panmure Gordon
Telephone: +44 20 7886 2500
Richard Gray
Andrew Potts

 

Citigate Dewe Rogerson
Telephone: +44 20 7638 9571
Anthony Carlisle – Mobile: +44 7973 611 888
David Dible – Mobile: +44 7967 566 919

 

Notes to Editors

About the c-Met signal pathway

C-Met, which is also known as hepatocyte growth factor receptor, or HGFR, is a signalling pathway that has specific roles in normal mammalian growth and development.  The aberrant activation of c-Met has been demonstrated to be highly correlated in many cancer indications, including kidney, lung, gastric, colorectal, oesophageal and brain cancer and plays a major role in cancer pathogenesis including tumour growth, survival, invasions, metastasis, the suppression of cell death as well as tumour angiogenesis.  To date, no selective c-Met inhibitors have received regulatory approval.

C-Met also plays a role in drug resistance in many tumour types.  For instance, c-Met gene amplification has been found in non-small cell lung cancer and colorectal cancer following epidermal growth factor receptor inhibition treatment, leading to drug resistance.  Furthermore, c-Met over-expression has been found to emerge in renal cell carcinoma following anti-VEGFR treatment.

 

About PRCC

In 2014, approximately 356,000 new cases of kidney cancer were observed globally, which is expected to grow to approximately 413,000 by 2020.  Renal cell carcinoma accounted for approximately 87% of all new cases of kidney cancer globally, including approximately 263,000 new cases of clear cell renal cell carcinoma and approximately 48,000 new cases of PRCC.

No targeted therapies for PRCC have been approved and there are no standard first-line treatments specifically for metastatic PRCC.  Anti-angiogenic drugs have shown limited activity against PRCC in retrospective studies, but very few prospective studies in pure papillary histology have been reported.  In a retrospective study, investigators collect data from past records without conducting follow-up with patients, as is the case with a prospective study.

 

About savolitinib for PRCC and other indications

During the Australian Phase I study of savolitinib, positive outcomes among PRCC patients had a strong correlation to c-Met gene status.  Three of eight PRCC patients treated achieved a partial response.  One of these patients has been on the drug for over 2 years and has had tumour measurement reduction of greater than 85%.  A further three of these eight PRCC patients achieved stable disease.  Importantly, the level of tumour response among these eight PRCC patients appeared to correlate with c-Met gene status.

Currently, we and AstraZeneca, our partners on savolitinib, are conducting nine clinical studies of savolitinib monotherapy treatment as well as savolitinib in combination treatments with other tyrosine kinase inhibitors and chemotherapy in kidney, lung and gastric cancers.  Furthermore, by the end of 2015, we expect to initiate three further proof-of-concept studies for savolitinib, two of which will involve combinations with immunotherapies.

 

About HMP

HMP is a novel drug R&D company focusing on discovering, developing and commercialising innovative therapeutics in oncology and autoimmune diseases.  With a team of around 250 scientists and staff, its pipeline is comprised of novel oral compounds for cancer and inflammation in development in North America, Europe, Australia and Greater China.

HMP is a subsidiary of Chi-Med.  For more information, please visit: www.hmplglobal.com.

 

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.

At the 2015 AIM Awards, Chi-Med was awarded the title of International Company of the Year.

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