London: Wednesday, November 30, 2016: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) has received notification that Dr Weiguo Su, Executive Vice President and Chief Scientific Officer (being a Person Discharging Managerial Responsibilities), has exercised 25,535 share options (granted in 2007 and which are soon due to expire in May 2017) over ordinary shares of US$1.00 each in Chi-Med (the “Ordinary Shares”) at an exercise price of GBP1.535 per share on November 25, 2016. Such Ordinary Shares will be held in the form of American Depositary Shares (“ADSs”) each representing one half of one Ordinary Share.
Following the above exercise of options and subject to the completion of allotment, the holding of Dr Su is 25,535 Ordinary Shares, representing approximately 0.04% of the current issued share capital of Chi-Med, which he intends to hold as a long term investment. Additionally Dr Su holds a further 300,000 unexercised options which would represent a further 0.49% of the issued share capital of Chi-Med.
The notification set out below is provided in accordance with the requirements of the EU Market Abuse Regulation.
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Details of the person discharging managerial responsibilities/person closely associated | |||||||||
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a) |
Name | Dr Weiguo Su | ||||||||
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Reason for the notification | |||||||||
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a) |
Position/status | Executive Vice President and Chief Scientific Officer of Chi-Med | ||||||||
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b) |
Initial notification/Amendment | Initial notification | ||||||||
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Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor | |||||||||
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a) |
Name | Hutchison China MediTech Limited | ||||||||
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b) |
LEI | N/A | ||||||||
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4 |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted | |||||||||
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a) |
Description of the financial instrument, type of instrument Identification code |
Ordinary Shares of US$1.00 each in the form of ADSs each representing one half of one Ordinary Share of US$1.00 DI ISIN: KYG4672N1016 |
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b) |
Nature of the transaction | Exercise of share options on November 25, 2016 at a price of GBP1.535 per share. Such Ordinary Shares will be held in the form of ADSs. | ||||||||
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c) |
Price(s) and volume(s) |
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Aggregated information — Aggregate volume — Price |
Aggregated volume: 25,535 Price information: GBP1.535 |
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e) |
Date of the transaction | 2016-11-25 | ||||||||
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f) |
Place of the transaction | Outside a trading venue | ||||||||
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson |
+44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
|
David Dible, Citigate Dewe Rogerson |
+44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Wednesday, November 30, 2016: For information purposes, Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) hereby notifies the market that as at November 30, 2016, the issued share capital of Chi-Med consisted of 60,703,323 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 60,703,323 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.
For illustrative purposes only, the 60,703,323 ordinary shares would be equivalent to 60,703,323 CREST depositary interests (each equating to one ordinary share) which are traded on AIM or, if the CREST depositary interests were converted in their entirety, equivalent to 121,406,646 American depositary shares (each equating to one-half of one ordinary share) which are traded on Nasdaq.
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson |
+44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
|
David Dible, Citigate Dewe Rogerson |
+44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Wednesday, November 23, 2016: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) has received notification that Mr Michael Howell, Independent Non-executive Director, sold 10,000 ordinary shares of US$1.00 each in Chi-Med (the “Ordinary Shares”) at an average price of GBP18.83 per share on November 18, 2016 and November 21, 2016 under a personal share trading plan (the “Plan”). Pursuant to the Plan, a total of 20,000 Ordinary Shares have now been sold. Previously under the Plan 10,000 Ordinary Shares were sold between October 24, 2016 and October 28, 2016 and announced on November 1, 2016. The Plan was put in place by Mr Howell to facilitate a financial settlement arising from a marital separation agreement.
Following the above sale of 10,000 Ordinary Shares, the holding of Mr Howell is 118,600 Ordinary Shares, representing approximately 0.20% of the current issued share capital of Chi-Med.
The notification set out below is provided in accordance with the requirements of the EU Market Abuse Regulation.
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1 |
Details of the person discharging managerial responsibilities/person closely associated | |||||||||||
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a) |
Name | Mr Michael Howell | ||||||||||
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2 |
Reason for the notification | |||||||||||
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a) |
Position/status | Independent Non-executive Director of Chi-Med | ||||||||||
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b) |
Initial notification/Amendment | Initial notification | ||||||||||
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3 |
Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor | |||||||||||
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a) |
Name | Hutchison China MediTech Limited | ||||||||||
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b) |
LEI | N/A | ||||||||||
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4 |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted | |||||||||||
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a) |
Description of the financial instrument, type of instrument Identification code | Ordinary Shares of US$1.00 each DI ISIN: KYG4672N1016 ADS ISIN: US44842L1035 |
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b) |
Nature of the transaction | Sale of 5,000 Ordinary Shares on November 18, 2016 and 5,000 Ordinary Shares on November 21, 2016 at an average price of GBP18.83 | ||||||||||
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c) |
Price(s) and volume(s) |
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d) |
Aggregated information — Aggregate volume — Price |
Aggregated volume: 10,000 Price information: GBP18.83 |
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e) |
Date of the transaction |
2016-11-18 – disposal of 5,000 Ordinary Shares 2016-11-21 – disposal of 5,000 Ordinary Shares |
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f) |
Place of the transaction | London Stock Exchange (XLON) | ||||||||||
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson |
+44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
|
David Dible, Citigate Dewe Rogerson |
+44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
Press Release
London: Wednesday, November 23, 2016: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces that results from two non-small cell lung cancer (“NSCLC”) clinical studies will be presented at WCLC in Vienna, Austria, from December 4 to 7, 2016. Results from the positive Phase II third-line NSCLC clinical trial of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”), will be detailed in an oral presentation. Results from the ongoing Phase Ib first-line NSCLC clinical trial of epitinib, a highly selective inhibitor of the epidermal growth factor receptor (“EGFR”) designed to optimize brain penetration, will also be presented.
In September 2015, Chi-Med announced that the fruquintinib Phase II NSCLC clinical trial had successfully achieved its primary endpoint. The oral and poster presentations will include more mature data than those included in the following fruquintinib and epitinib study abstracts.
The results of the two studies will be presented in detail at WCLC as follows:
| Type: | Oral Presentation |
| Title: | A Randomized, Multi-Center, Double-Blind Phase II Study of Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer |
| Presenter: | Shun Lu |
| Abstract: | #4571 |
| Session: | OA11 – Angiogenesis in Advanced Lung Cancer, Oral Session |
| Date & Time: | Tuesday, December 6, 2016 (11:00 AM – 12:30 PM) |
| Type: | Poster Presentations |
| Title: | A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis |
| Authors: | Qing Zhou, et al. |
| Abstract: | #4253 |
| 1st Session: | JCES01 Joint IASLC–Chinese Society for Clinical Oncology / Chinese Alliance Against Lung Cancer Session (ID 413) |
| Date & Time: | Sunday, December 4, 2016 (10:30 AM – 11:30 AM) |
| 2nd Session: | 07. Advanced NSCLC P2.03b – Poster Session with Presenters Present (ID 465) |
| Date & Time: | Tuesday, December 6, 2016 (2:30 PM – 3:45 PM) |
The WCLC presentations will be made available for download at www.chi-med.com/news on the following day.
Organized by the International Association for the Study of Lung Cancer (IASLC) and held annually, WCLC is a global, multidisciplinary scientific forum for sharing current knowledge and research progress in lung cancer. For more information, please visit: wclc2016.iaslc.com.
Shun Lu, Jianhua Chang, XiaoQing Liu, Jianhua Shi, You Lu, Wei Li, Jinji Yang, Jianying Zhou, Jie Wang, Lei Yang, Zhiwei Chen, Xiangdong Zhou, Zhe Liu, Ye Hua, Weiguo Su.
Background
Targeting the tumor microenvironment, such as tumor angiogenesis, has led to the successful development and approval of a number of targeted therapies thereby changing the standard of care for many types of cancer. However, treatment options are limited in third-line non-small cell lung cancer (“NSCLC”) patients. Fruquintinib is a potent and highly selective oral kinase inhibitor targeting vascular endothelial growth factor receptors and is currently in late stage development for multiple cancers. This Phase II study was designed to evaluate the efficacy and safety of fruquintinib in third-line NSCLC patients (NCT02590965).
Methods
A total of 91 patients were randomized to receive best supportive care (“BSC”) plus fruquintinib or BSC plus placebo in a 2:1 ratio from 12 Chinese clinical centers. Fruquintinib initial dose was 5 mg once daily and treatment was given in every 4-week cycle (3 weeks treatment followed by 1 week off). The primary objective was to compare progression free survival (“PFS”) between the two treatment groups. Secondary efficacy parameters included objective response rate (“ORR”), disease control rate (“DCR”), overall survival (“OS”). Tumor response was assessed per RECIST 1.1.
Results
As of August 7, 2015, median PFS was 3.8 months for the fruquintinib group comparing with 1.2 months for the placebo group (hazard ratio=0.27, p<0.001). The ORR was 16.4% for the fruquintinib group comparing with 0% for the placebo group (p=0.02). The DCR of the fruquintinib group was significantly higher than that of the placebo group with a difference of 53.8% (36.3, 71.4; 95% CI, p<0.001). OS was not mature and initial analysis revealed 3- and 6-month OS rates of 90.2% and 68.3% for the fruquintinib group, and 73.3% and 58.2% for the placebo group, respectively. Adverse event was reported in 68.9% and 60.0% patients in fruquintinib and placebo group, respectively. The incidence of serious adverse events was 3.3% in the fruquintinib group and 6.7% in the placebo group.
Conclusion
Fruquintinib in third-line NSCLC met the primary efficacy endpoint of PFS and demonstrated superiority in the secondary endpoints of ORR and DCR as compared with placebo. OS has yet to mature. Fruquintinib was generally well tolerated and safety profile consistent with previously reported. These results support further development of fruquintinib in third-line NSCLC patients. A randomized, double-blind, multi-center Phase III registration study was initiated in December 2015 (NCT02691299). Clinical trial information: NCT02590965.
Qing Zhou, Bin Gan, Qunying Hong, Mengzhao Wang, Xiaoqing Liu, Yi-Long Wu.
Background
A significant portion of patients with NSCLC develop brain metastasis. Patients with brain metastasis suffer from poor prognosis with a median survival of less than 6 months and low quality of life with limited treatment options. First generation EGFR tyrosine kinase inhibitors (EGFR TKIs) have demonstrated significant clinical benefit for patients with EGFR-mutant NSCLC. However, their effect on brain metastasis is limited due to poor drug penetration into the brain. Epitinib is an EGFR TKI designed to improve brain penetration. A Phase I dose escalation study on epitinib has been completed and the recommended Phase 2 dose (RP2D) determined. This Phase I dose expansion study was designed to evaluate the efficacy and safety of epitinib in EGFR-mutant NSCLC patients with brain metastasis.
Methods
This is an ongoing open label, multi-center Phase I dose expansion study. EGFR-mutant NSCLC patients with confirmed brain metastasis, either prior EGFR TKI treated or EGFR TKI treatment naïve, were enrolled to receive oral epitinib 160 mg once daily. Patients with extra-cranial disease progression while on treatment with an EGFR TKI were excluded. Tumor response was assessed per RECIST 1.1.
Results
As of May 31, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR TKI treatment naïve) have been enrolled and treated with epitinib. The most frequent adverse events (“AEs”) were skin rash (89%), elevated ALT (41%)/AST (37%), hyper-pigmentation (41%) and diarrhea (30%). The most frequent Grade 3/4 AEs were elevations in ALT (19%), gamma-GGT (11%), AST (7%), and hyperbilirubinemia (7%) and skin rash (n=1, 4%). There have been no Grade 5 AEs to date. Among the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI naïve), 7 (7/24, 29%) achieved a partial response (“PR”), including 1 unconfirmed PR. All PRs occurred in EGFR TKI treatment naïve patients (7/13, 53.8%). Of the 24 evaluable patients, 8 (5 EGFR treatment naïve, 3 EGFR TKI pretreated) had measurable brain metastasis (lesion diameter>10 mm per RECIST 1.1) with 2 PRs (both EGFR TKI treatment naïve patients, 2/5, 40%).
Conclusion
Epitinib 160mg once daily treatment in EGFR-mutant NSCLC patients with brain metastasis demonstrated clinical activity both extra- and intra-cranial. Epitinib was well tolerated. The data to data appears encouraging and warrants further development of epitinib.
At an advanced stage, tumors secrete large amounts of vascular endothelial growth factors (“VEGF”), a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor in order to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play a pivotal role in tumor-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 tumors to grow and invade.
Every year, it is estimated that approximately 1.7 million new patients around the world are diagnosed with NSCLC, according to Frost & Sullivan. Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, and more than breast, prostate and colorectal cancers combined. TKIs are used in many cancer therapies and act by blocking the cell signaling pathways that drive the growth of tumor cells. 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. To date, several anti-VEGF/VEGFR agents have shown clinical efficacy against a number of tumor 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.
Patients who have the EGFRm+ form of NSCLC, which occurs in an estimated 10-15% of NSCLC patients in Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs. However, tumors almost always develop resistance to treatment leading to disease progression.
Brain metastasis has been identified in 10-30% EGFRm+ NSCLC patients at initial diagnosis and is one of the most devastating complications of lung cancer with poor life expectancy around 5-10 months. However, currently marketed EGFR-TKIs are unable to penetrate the blood-brain barrier with sufficient concentrations to provide clinical benefit in the brain, leaving the majority of patients with brain metastasis without an effective targeted therapy.
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, without known off-target toxicities. It is currently under the joint development in China by Chi-Med and its partner Eli Lilly and Company. Two late stage, pivotal Phase III registration studies are ongoing in lung cancer and colorectal cancer. In addition, fruquintinib is also in clinical development for gastric cancer.
Lung: The FALUCA trial is a randomized, double-blind, placebo-controlled, multi-center, Phase III registration study targeted at treating patients with advanced non-squamous NSCLC, who have failed two lines of systemic chemotherapy. Enrollment began in December 2015. Patients are randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, ORR, DCR and duration of response. Chi-Med plans to enroll approximately 520 patients in about 45 centers across China. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02691299.
Colorectal: The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic colorectal cancer who have failed at least two prior systemic antineoplastic therapies, including fluoropyrimidine, oxaliplatin and irinotecan. Enrollment was completed in May 2016. 416 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, objective response rate, disease control rate and duration of response. Once a pre-specified number of OS events (deaths) have occurred, data analysis will commence. Additional details of the FRESCO study may be found at clinicaltrials.gov, using identifier NCT02314819.
Gastric: Chi-Med completed a Phase Ib dose finding study of fruquintinib in combination with paclitaxel, which established a combination regimen that was well tolerated. Chi-Med continues to enroll patients in this Phase Ib to expand the data-set. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02415023.
EGFR inhibitors have revolutionized the treatment of NSCLC with EGFR activating mutations. However, existing EGFR inhibitors cannot penetrate the blood-brain barrier effectively, leaving the majority of patients with brain metastasis without an effective therapy. In contrast, epitinib (HMPL-813) is a potent and highly selective oral EGFR inhibitor designed to optimize brain penetration and has demonstrated brain penetration and efficacy in pre-clinical studies. Should epitinib be able to provide clinical benefit to NSCLC patients with brain metastasis, subject to regulatory approval, it may be well positioned to address a major global unmet medical need. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02590952.
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of fruquintinib or epitinib, plans to initiate clinical studies for fruquintinib or epitinib, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidates fruquintinib or epitinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of fruquintinib or epitinib for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Investor Enquiries
Christian Hogg, CEO
+852 2121 8200
International Media Enquiries
Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk
U.S. Based Media Enquiries
Brad Miles, BMC Communications
+1 (917) 570 7340 (Mobile)
bmiles@bmccommunications.com
Susan Duffy, BMC Communications
+1 (917) 499 8887 (Mobile)
sduffy@bmccommunications.com
Investor Relations
Matt Beck, The Trout Group
+1 (917) 415 1750 (Mobile)
mbeck@troutgroup.com
David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedr.co.uk
Panmure Gordon (UK) Limited
Richard Gray / Andrew Potts
+44 (20) 7886 2500
Background: Syk plays a pivotal role in the regulation of downstream signals in immune receptors, including BCRs, which play a key role in autoimmune diseases such as RA. This abstract reports the results of the first-in-human study of HMPL-523, a highly selective, potent, and orally available inhibitor of Syk.
Methods: We conducted a 3-part study to investigate the safety, tolerability, and PK of HMPL-523 as well as its PD measured by CD63+ as the biomarker, and the effect of food on PK in healthy adult male subjects. The study design is summarized in the table below.
Study Design
| Endpoints | Part A (Single Ascending Dose): PK |
Part B (Multiple Ascending Dose): PK/PD |
Part C: Effect of Food on PK |
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| General design | A randomized, double- blind, placebo-controlled design | Cross over | |||||||||||||||
| Dose | Single dose | Once daily for 14 days | Once on Day 1 and Day 8, respectively | ||||||||||||||
| Meal condition | Fasted | Fed | Fed |
Fasted on Day 1; wash-out for 7 days; after the consumption of a high-calorie meal on Day 8 |
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| Dosage (mg, N) | 5, N=6 | 20, N=6 | 50, N=6 | 100, N=6 | 200, N=6 | 300, N=6 | Pbo, N=12 | 300, N=6 | 400, N=6 | 600, N=6 | 800, N=6 | Pbo, N=8 | 200, N=12 | 300, N=6 | 400, N=6 | Pbo, N=8 | 100, N=6 |
Pbo = Placebo
Results: A total of 118 adult male healthy subjects were enrolled at baseline. 114 (96.6%) subjects completed the study. A total of 83 treatment emergent adverse events (“TEAEs”) were reported as the following: 38.9% in the HMPL-523 groups, and 32.1% in the placebo groups, respectively. The majority of TEAEs were mild (63/83 or 75.9%) with 18/83 (21.7%) moderate events. Two serious adverse events (SAEs) were reported due to elevated lipase (HMPL-523 200mg) and febrile illness (HMPL-523 400mg) in Part B (multiple ascending doses [“MAD”]). As a result, HMPL-523 was discontinued in the two subjects. All of the TEAEs and SAEs were resolved.
Part A (single ascending dose [SAD]) PK results revealed that HMPL-523 was rapidly absorbed with median time to maximum plasma concentration (Tmax) between 3 and 6 hours under both fasted and fed conditions. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of HMPL-523 increased proportionally with dose increased up to 800mg. The terminal half-life (t1/2) ranged between 9.808 hours and 13.488 hours across HMPL-523 doses of 100 to 800mg.
Part B (MAD) PK results showed that steady state was achieved within 48 hours of daily administration and accumulation of 1.3 to 1.5 folds was observed over 14 days of dosing. In an ex vivo human whole blood PD assay, HMPL-523 inhibited anti-IgE-induced basophil activation (CD63+) in a concentration-dependent manner with an estimated half maximal effective concentration (EC50) of 47.70ng/mL. The human PK exposures at 200mg once daily and above can be expected to provide the target coverage required for clinical efficacy based on the preclinical PK/PD analysis.
In Part C, systemic exposure of HMPL-523 was increased up to 1.5 folds when administered in the fed condition compared to the fasted condition, indicating that food consumption increases the relative bioavailability of HMPL-523.
Conclusions: Overall, the safety and laboratory data suggests that the single and multiple doses of HPML-523 were generally well tolerated. A multiple-dose regimen of 300mg or less of HMPL-523, administered once daily, is recommended for future Phase II clinical trials for autoimmune diseases.
Press Release
London: Monday, November 14, 2016: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces that data from a recent Phase I, first-in-human, dose escalating study of the safety, tolerability and pharmacokinetics (“PK”) and pharmacodynamics (“PD”) of single and multiple doses of HMPL-523, will be presented at the Annual Meeting of the American College of rheumatology/Association of Rheumatology Health Professionals (the “ACR/ARHP Annual Meeting”), being held in Washington DC, USA from November 11 to November 16, 2016. The presentation will include additional data on HMPL-523, a highly selective, potent and orally available inhibitor of Spleen Tyrosine Kinase (“Syk”).
Syk plays a pivotal role in the regulation of downstream signaling in immune receptors, including B cell receptors (“BCRs”), which play a key role in autoimmune diseases such as rheumatoid arthritis (“RA”). A Phase I dose-escalating study to assess safety, tolerability and PK of HMPL-523 was completed in healthy volunteers in Australia in late 2015. HMPL-523 was administered at up to 800mg as a single dose and up to 400mg in multiple doses in 14 cohorts. The treatment was generally well tolerated without material off-target toxicities, including lower rates of diarrhea and hypertension compared to what had been observed in first-generation Syk inhibitors. Furthermore, HMPL-523 demonstrated a dose dependent suppression of B-cell activation. The Company plans to initiate a Phase II study in the U.S. in 2017.
HMPL-523 is also being studied in oncology indications. A Phase I dose escalation study was initiated in Australia in January 2016 and is expected to complete in the first half of 2017. This study is in patients with relapsed and/or refractory B-cell non-Hodgkin’s lymphoma or chronic lymphocytic leukemia for whom there is no standard therapy.
The ACR/ARHP Annual Meeting brings together more than 16,000 physicians, health professionals and industry partners from over 100 countries for six days of networking and educational events covering the latest cutting-edge research on clinical and basic science of rheumatologic care, as well as prevention, diagnosis, and treatment of rheumatic diseases.
ACR/ARHP 2016 Poster Presentation
Title: A Phase I, Randomized, Double Blind, Placebo-Controlled, Dose Escalating Study of the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of HMPL-523 in Australian Male Healthy Subjects
Abstract number: 1621
Track: Rheumatology
Date & Time: Monday, November 14, 2016, 9:00AM – 11.00AM EST
The presentation will be made available at http://chi-med.com/news/. Further information about the 2016 ACR/ARHP Annual Meeting and the abstracts are available at acrannualmeeting.org.
Background: Syk plays a pivotal role in the regulation of downstream signals in immune receptors, including BCRs, which play a key role in autoimmune diseases such as RA. This abstract reports the results of the first-in-human study of HMPL-523, a highly selective, potent, and orally available inhibitor of Syk.
Methods: We conducted a 3-part study to investigate the safety, tolerability, and PK of HMPL-523 as well as its PD measured by CD63+ as the biomarker, and the effect of food on PK in healthy adult male subjects. The study design is summarized in the table below.
Study Design
| Endpoints | Part A (Single Ascending Dose): PK |
Part B (Multiple Ascending Dose): PK/PD |
Part C: Effect of Food on PK |
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| General design | A randomized, double- blind, placebo-controlled design | Cross over | |||||||||||||||
| Dose | Single dose | Once daily for 14 days | Once on Day 1 and Day 8, respectively | ||||||||||||||
| Meal condition | Fasted | Fed | Fed |
Fasted on Day 1; wash-out for 7 days; after the consumption of a high-calorie meal on Day 8 |
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| Dosage (mg, N) | 5, N=6 | 20, N=6 | 50, N=6 | 100, N=6 | 200, N=6 | 300, N=6 | Pbo, N=12 | 300, N=6 | 400, N=6 | 600, N=6 | 800, N=6 | Pbo, N=8 | 200, N=12 | 300, N=6 | 400, N=6 | Pbo, N=8 | 100, N=6 |
Pbo = Placebo
Results: A total of 118 adult male healthy subjects were enrolled at baseline. 114 (96.6%) subjects completed the study. A total of 83 treatment emergent adverse events (“TEAEs”) were reported as the following: 38.9% in the HMPL-523 groups, and 32.1% in the placebo groups, respectively. The majority of TEAEs were mild (63/83 or 75.9%) with 18/83 (21.7%) moderate events. Two serious adverse events (SAEs) were reported due to elevated lipase (HMPL-523 200mg) and febrile illness (HMPL-523 400mg) in Part B (multiple ascending doses [“MAD”]). As a result, HMPL-523 was discontinued in the two subjects. All of the TEAEs and SAEs were resolved.
Part A (single ascending dose [SAD]) PK results revealed that HMPL-523 was rapidly absorbed with median time to maximum plasma concentration (Tmax) between 3 and 6 hours under both fasted and fed conditions. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of HMPL-523 increased proportionally with dose increased up to 800mg. The terminal half-life (t1/2) ranged between 9.808 hours and 13.488 hours across HMPL-523 doses of 100 to 800mg. Part B (MAD) PK results showed that steady state was achieved within 48 hours of daily administration and accumulation of 1.3 to 1.5 folds was observed over 14 days of dosing. In an ex vivo human whole blood PD assay, HMPL-523 inhibited anti-IgE-induced basophil activation (CD63+) in a concentration-dependent manner with an estimated half maximal effective concentration (EC50) of 47.70ng/mL. The human PK exposures at 200mg once daily and above can be expected to provide the target coverage required for clinical efficacy based on the preclinical PK/PD analysis.
In Part C, systemic exposure of HMPL-523 was increased up to 1.5 folds when administered in the fed condition compared to the fasted condition, indicating that food consumption increases the relative bioavailability of HMPL-523.
Conclusions: Overall, the safety and laboratory data suggests that the single and multiple doses of HPML-523 were generally well tolerated. A multiple-dose regimen of 300mg or less of HMPL-523, administered once daily, is recommended for future Phase II clinical trials for autoimmune diseases.
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 hematological cancers (i.e. B-cell malignancies) including lymphoma and leukemia. Targeted B-cell receptor signaling therapies, including monoclonal antibodies and small molecules, have been proven to be clinically effective for the treatment of rheumatoid arthritis as well as B-cell malignancies, leading to scientific and commercial success.
Syk is a key protein involved in the B-cell signaling pathway.
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of HMPL-523, plans to initiate clinical studies for HMPL-523, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate HMPL-523 to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of HMPL-523 for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
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London: Tuesday, November 1, 2016: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) has received notification that Mr Michael Howell, Independent Non-executive Director, sold 10,000 ordinary shares of US$1.00 each in Chi-Med (the “Ordinary Shares”) at an average price of GBP18.453305 per share between October 24, 2016 and October 28, 2016 under a personal share trading plan (the “Plan”). Pursuant to the Plan, a total of 20,000 Ordinary Shares will be sold between October 24, 2016 and November 23, 2016 (inclusive). The Plan (and the previous sale of 15,000 Ordinary Shares made by Mr Howell on October 7, 2016) has been put in place to facilitate financial settlement arising from a marital separation agreement.
Following the above sale of 10,000 Ordinary Shares, the holding of Mr Howell is 128,600 Ordinary Shares, representing approximately 0.21% of the current issued share capital of Chi-Med.
The notification set out below is provided in accordance with the requirements of the EU Market Abuse Regulation.
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Details of the person discharging managerial responsibilities/person closely associated | |||||||||||||
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a) |
Name | Mr Michael Howell | ||||||||||||
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2 |
Reason for the notification | |||||||||||||
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a) |
Position/status | Independent Non-executive Director of Chi-Med | ||||||||||||
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b) |
Initial notification/Amendment | Initial notification | ||||||||||||
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3 |
Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor | |||||||||||||
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a) |
Name | Hutchison China MediTech Limited | ||||||||||||
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b) |
LEI | N/A | ||||||||||||
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4 |
Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted | |||||||||||||
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a) |
Description of the financial instrument, type of instrument Identification code | Ordinary Shares of US$1.00 each DI ISIN: KYG4672N1016 ADS ISIN: US44842L1035 |
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b) |
Nature of the transaction | Sale of 10,000 Ordinary Shares between October 24, 2016 and October 28, 2016 at an average price of GBP18.453305 | ||||||||||||
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c) |
Price(s) and volume(s) |
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d) |
Aggregated information — Aggregate volume — Price |
Aggregated volume: 10,000 Price information: GBP18.453305 |
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e) |
Date of the transaction | 2016-10-24; 14:07 – disposal of 339 Ordinary Shares 2016-10-25; 14:05 – disposal of 661 Ordinary Shares 2016-10-25; 14:44 – disposal of 2,000 Ordinary Shares 2016-10-25; 15:29 – disposal of 1,000 Ordinary Shares 2016-10-26; 13:57 – disposal of 3,000 Ordinary Shares 2016-10-28; 12:48 – disposal of 2,500 Ordinary Shares 2016-10-28; 14:09 – disposal of 500 Ordinary Shares |
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f) |
Place of the transaction | London Stock Exchange (XLON) | ||||||||||||
Chi-Med is an innovative China-based biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China. Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (646) 378 2933 | mbeck@troutgroup.com |
| David Dible,Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |