London: Monday, December 31, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) announces the following blocklisting six monthly return:
| 1. | Name of applicant: | Hutchison China MediTech Limited | |
| 2. | Name of scheme: | (a) | Share Option Scheme conditionally adopted by Hutchison China MediTech Limited in 2005 (“2005 HCML Share Option Scheme”) |
| (b) | Share Option Scheme conditionally adopted by Hutchison China MediTech Limited in 2015 (“2015 HCML Share Option Scheme”) | ||
| 3. | Period of return: | From June 29, 2018 to December 28, 2018 | |
| 4. | Balance under scheme from previous return: | (a) | 2005 HCML Share Option Scheme: 219,353 ordinary shares of US$1 each |
| (b) | 2015 HCML Share Option Scheme: 2,425,597 ordinary shares of US$1 each | ||
| 5. | The amount by which the block scheme has been increased, if the scheme has been increased since the date of the last return: | (a) | 2005 HCML Share Option Scheme: Nil |
| (b) | 2015 HCML Share Option Scheme: Nil | ||
| 6. | Number of securities issued/allotted under scheme during period: | (a) | 2005 HCML Share Option Scheme: 12,562 ordinary shares of US$1 each |
| (b) | 2015 HCML Share Option Scheme: 112,500 ordinary shares of US$1 each | ||
| 7. | Balance under scheme not yet issued/allotted at end of the period: | (a) | 2005 HCML Share Option Scheme: 206,791 ordinary shares of US$1 each |
| (b) | 2015 HCML Share Option Scheme: 2,313,097 ordinary shares of US$1 each | ||
| 8. | Number and class of securities originally listed and the date of admission: | (i) | 2,560,606 ordinary shares of US$1 each admitted on June 26, 2007 |
| (ii) | 1,000,000 ordinary shares of US$1 each admitted on June 20, 2016 | ||
| (iii) | 1,425,597 ordinary shares of US$1 each admitted on April 27, 2018 | ||
| 9. | Total number of securities in issue at the end of the period: | 66,657,745 ordinary shares of US$1 each | |
| Name of contact: | Christian Hogg | ||
| Address of contact: | Level 18, The Metropolis Tower, 10 Metropolis Drive, Hung Hom, Kowloon, Hong Kong | ||
| Telephone number of contact: | +852 2121 8200 | ||
Chi-Med (AIM/Nasdaq: HCM) is an innovative biopharmaceutical company which researches, develops, manufactures and markets pharmaceutical products. Its Innovation Platform, Hutchison MediPharma, has about 400 scientists and staff focusing on discovering, developing and commercializing targeted therapeutics in oncology and autoimmune diseases. It has a portfolio of eight cancer drug candidates currently in clinical studies around the world. Chi-Med’s Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products, covering an extensive network of hospitals across China.
Dual-listed on the AIM market of the London Stock Exchange and the Nasdaq Global Select Market, Chi-Med is headquartered in Hong Kong and majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.
Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200
David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com
Xuan Yang, Solebury Trout
+1 (415) 971 9412 (Mobile)
UK & Europe – Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk
Americas – Brad Miles, Solebury Trout
+1 (917) 570 7340 (Mobile)
Hong Kong & Asia ex-China – Joseph Chi Lo, Brunswick
+852 9850 5033 (Mobile)
Hong Kong & Asia ex-China – Zhou Yi, Brunswick
+852 9783 6894 (Mobile)
Mainland China – Sam Shen, Edelman
+86 1367 179 1029 (Mobile)
Richard Gray / Andrew Potts, Panmure Gordon (UK) Limited
+44 (20) 7886 2500
London: Monday, December 31, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) hereby notifies the market that as at December 31, 2018, the issued share capital of Chi-Med consisted of 66,657,745 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 66,657,745 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 66,657,745 ordinary shares would be equivalent to 66,657,745 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 133,315,490 American depositary shares (each equating to one-half of one ordinary share) which are traded on Nasdaq.
Chi-Med (AIM/Nasdaq: HCM) is an innovative biopharmaceutical company which researches, develops, manufactures and markets pharmaceutical products. Its Innovation Platform, Hutchison MediPharma, has about 400 scientists and staff focusing on discovering, developing and commercializing targeted therapeutics in oncology and autoimmune diseases. It has a portfolio of eight cancer drug candidates currently in clinical studies around the world. Chi-Med’s Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products, covering an extensive network of hospitals across China.
Dual-listed on the AIM market of the London Stock Exchange and the Nasdaq Global Select Market, Chi-Med is headquartered in Hong Kong and majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.
Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200
David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com
Xuan Yang, Solebury Trout
+1 (415) 971 9412 (Mobile)
UK & Europe – Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk
Americas – Brad Miles, Solebury Trout
+1 (917) 570 7340 (Mobile)
Hong Kong & Asia ex-China – Joseph Chi Lo, Brunswick
+852 9850 5033 (Mobile)
Hong Kong & Asia ex-China – Zhou Yi, Brunswick
+852 9783 6894 (Mobile)
Mainland China – Sam Shen, Edelman
+86 1367 179 1029 (Mobile)
Richard Gray / Andrew Potts, Panmure Gordon (UK) Limited
+44 (20) 7886 2500
Handlery Union Square, San Francisco, CA
– Chi-Med acquires right to determine & conduct all future life cycle indication development of fruquintinib monotherapy as well as innovative combinations in China –
– Chi-Med to assume all development costs of life cycle indications in China in return for an increase in both milestone and royalty payments from Lilly –
– Chi-Med acquires potential future co-promotion rights for fruquintinib in China –
London: Thursday, December 20, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces certain amendments (“2018 Amendment”) to the 2013 License and Collaboration Agreement (“2013 Agreement”) on fruquintinib with Lilly Shanghai an affiliate of Eli Lilly and Company (“Lilly”). The 2018 Amendment covers adjustments in the respective roles and responsibilities of Chi-Med and Lilly, in China, for the development and commercialization of fruquintinib in the areas of future life cycle planning and development, collaborations for co-development of fruquintinib with other third-party anti-cancer agents as well as promotion and distribution rights of fruquintinib.
“Through this amendment, Chi-Med is stepping forward to take on greater responsibility in return for a broader role and a larger share of the future economic interest on fruquintinib,” commented Simon To, Chairman of Chi-Med. “Lilly has been and will continue to be a most important partner for Chi-Med in bringing fruquintinib to as broad a patient population as possible and we share a common goal to maximize the commercial success of fruquintinib in China.” He added, “The recent approval and launch of fruquintinib for colorectal cancer in China is an important first step on this journey.”
Under the terms of the 2013 Agreement, decision making on LCI development beyond the initial indications of third-line colorectal cancer (“CRC”), third-line non-small cell lung cancer (“NSCLC”) and second-line gastric cancer was controlled by Lilly. The majority of development costs for LCIs were to be paid by Lilly, with the minority by Chi-Med.
The 2018 Amendment now gives Chi-Med all planning, execution and decision making responsibilities for LCI development on fruquintinib in China. Chi-Med will pay all of the costs associated with fruquintinib LCI development in China. In return for this investment of capital and resources, Lilly will pay Chi-Med a $20 million milestone upon approval of each fruquintinib LCI in China, for up to three LCIs, totaling up to $60 million in LCI approval milestone payments. Furthermore, upon the launch of the first LCI, the tiered royalty structure, payable by Lilly to Chi-Med on total molecule sales in China, has been raised from the range of 15-20% in the 2013 Agreement to a new level of 15-29% under the 2018 Amendment.
Under the terms of the 2013 Agreement, Lilly held full commercialization rights to fruquintinib in China.
The 2018 Amendment provides Chi-Med the right to promote fruquintinib in provinces that represent 30% of the sales of fruquintinib in China (“Chi-Med Territory”) upon the occurrence of certain commercial milestones. The Chi-Med Territory will expand to provinces that represent 40% of the sales of fruquintinib in China subject to additional criteria being met. Lilly will pay Chi-Med a fee for service to conduct all promotional activities in the Chi-Med Territory.
Lilly has provided consent, and freedom to operate, for Chi-Med to enter into joint development collaborations with certain third-party pharmaceutical companies to explore combination treatments of fruquintinib and various immunotherapy agents. The first such collaborations with Innovent Biologics (Suzhou) Co. Ltd. (“Innovent”) and Genor Biopharma Co. Ltd. (“Genor”) will explore the combination of fruquintinib and their respective programmed cell death protein-1 (“PD-1”) antibodies, sintilimab (IBI308) and genolimzumab (GB226), in several solid tumor settings.
Our updated guidance for 2018, compared to the most recent guidance in our 2018 Interim Results announcement for the period ended June 30, 2018 dated July 27, 2018, includes a $12 million increase in expected full year Innovation Platform R&D expense to $142-152 million. This increase reflects the 2018 Amendment of the fruquintinib collaboration with Lilly; our recent co-development collaborations with multiple partners to explore immunotherapy (PD-1) combinations with our vascular endothelial growth factor receptor (VEGFR) inhibitors; as well as a general rise in clinical trial spending on our eight clinical drug candidates and discovery programs including a one-time non-cash adjustment relating to one of our joint ventures. Further, while progress has been made towards realizing the one-time property compensation gain under the Commercial Platform, it is not expected to occur in 2018. We make no other changes to the full year 2018 financial guidance as detailed below:
| 2018 Previous Guidance | 2018 Current Guidance | Adjustment | |
| Group Level: | |||
| · Consolidated revenue | $155-175m | $155-175m | None |
| · Admin., interest & tax | $(16)-(18)m | $(16)-(18)m | None |
| · Net loss[1] | $(39)-(72)m | $(71)-(84)m | $(12)-(32)m increase |
| Innovation Platform: | |||
| · Consolidated revenue | $40-50m | $40-50m | None |
| · Adjusted (non-GAAP) R&D expenses | $(130)-(140)m | $(142)-(152)m | $(12)m increase |
| · Net loss[1] | $(80)-(100)m | $(92)-(112)m | $(12)m increase |
| Commercial Platform: | |||
| · Sales (consolidated) | $115-125m | $115-125m | None |
| · Sales of non-consolidated JVs[2] | $460-480m | $460-480m | None |
| · Net income on an adjusted (non-GAAP) basis excl. one-time gains[1] | $41-43m | $41-43m | None |
| · One-time gains[1] | $0-20m[3] | $0m | $0-(20)m decrease |
| · Net income[1] | $41-63m | $41-43m | $0-(20)m decrease |
Notes: [1] Attributable to Chi-Med; [2] Joint ventures; [3] One-time property compensation, timing of which is dependent on Guangzhou government policy.
All dollars are expressed in US dollar currency unless otherwise stated.
Fruquintinib (brand name: Elunate®) is a small molecule, selective and highly potent inhibitor of VEGFR 1, 2 and 3. VEGFR inhibitors play a pivotal role in tumor-related angiogenesis, cutting off the blood supply that a tumor needs to grow rapidly. The global market for anti-angiogenesis therapies was estimated at over $18 billion in 2017, including both monoclonal antibodies and small molecules approved in around 30 tumor settings. During the discovery research process, which began at Chi-Med in 2007, fruquintinib was successfully designed to be differentiated by improving kinase selectivity in comparison to other approved small molecule tyrosine kinase inhibitors (TKIs), to minimize off-target toxicities, improve tolerability and provide more consistent target coverage, resulting in better clinical efficacy.
The superior tolerability, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may be highly suitable for innovative combinations with other anti-cancer therapies. The most common adverse reactions included hypertension, hand-foot syndrome and proteinuria. Clinically effective management of these adverse effects is feasible. For important safety information about fruquintinib, please see www.chi-med.com.
Phase I monotherapy in the U.S.: In December 2017, Chi-Med initiated a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier NCT03251378). This study is almost complete, and proof-of-concept (“POC”) studies are expected to begin in 2019.
PD-1 checkpoint inhibitor combination: It is an important part of Chi-Med’s strategy to explore the potential synergies of its drug candidates in combination with other anti-cancer treatments in several solid tumor settings. In November 2018, Chi-Med entered into a global collaboration agreement to evaluate the safety, tolerability and efficacy of fruquintinib in combination with sintilimab (IBI308), a PD-1 inhibitor being developed by Innovent.
CRC in China: The National Medical Products Administration (NMPA) approved the first New Drug Application (“NDA”) for fruquintinib for the treatment of patients with advanced CRC in September 2018. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with CRC in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology Annual Meeting held on June 5, 2017 and was published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier NCT02314819).
Gastric cancer in China: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol® (paclitaxel), known as the FRUTIGA study, in approximately 500 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier NCT03223376). An interim analysis on FRUTIGA, to establish POC, is anticipated during the first half of 2019 and if successful could trigger a POC milestone payment from Lilly. The FRUTIGA study followed a Phase I/II clinical trial in 34 patients with gastric cancer that demonstrated that combination therapy of fruquintinib and Taxol® was generally well-tolerated with promising tumor response (clinicaltrials.gov identifier NCT02415023).
Lung cancer in China: 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. 527 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 best supportive care (“BSC”); or placebo plus BSC. On November 16, 2018, Chi-Med announced that FALUCA did not meet the primary endpoint to demonstrate a statistically significant increase in overall survival (OS) compared to placebo, however the data did show statistically significant improvement in all secondary endpoints including progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) as compared to the placebo. The safety profile of the trial was in line with that observed in prior clinical studies. Full detailed results are expected to be disclosed at an upcoming scientific meeting. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02691299.
Along with FALUCA, fruquintinib is concurrently being studied in a Phase II study in combination with Iressa® (gefitinib) in patients with untreated advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Preliminary results were highlighted in an oral presentation at the 18th World Conference on Lung Cancer on October 16, 2017.
PD-1 checkpoint inhibitor combination: In October 2018, Chi-Med entered into a further collaboration in China to evaluate the combination of fruquintinib with genolimzumab (GB226), a PD-1 inhibitor being developed by Genor.
Chi-Med (AIM/Nasdaq: HCM) is an innovative biopharmaceutical company which researches, develops, manufactures and markets pharmaceutical products. Its Innovation Platform, Hutchison MediPharma, has about 400 scientists and staff focusing on discovering, developing and commercializing targeted therapeutics in oncology and autoimmune diseases. It has a portfolio of eight cancer drug candidates currently in clinical studies around the world. Chi-Med’s Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products, covering an extensive network of hospitals across China.
Dual-listed on the AIM market of the London Stock Exchange and the Nasdaq Global Select Market, Chi-Med is headquartered in Hong Kong and majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.
This announcement 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 ability of fruquintinib to gain commercial acceptance in China, the potential market of fruquintinib for patients with metastatic CRC who have failed two prior treatments in China, the ability for Chi-Med to quickly provide fruquintinib to patients by year end, and the clinical development of fruquintinib in other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding Chi-Med’s ability to obtain regulatory approval in different jurisdictions, to commercialize fruquintinib, that the benefits obtained from fruquintinib during clinical trials will be the same for all patients who are prescribed fruquintinib, that no unidentified side effects will occur which could result in the NMPA pulling fruquintinib from the market and the sufficiency of funding to support commercialization of fruquintinib in metastatic CRC and the development of fruquintinib in other indications. In addition, as certain studies rely on the use of Iressa® (gefitinib), Taxol® (paclitaxel), sintilimab or genolimzumab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of Iressa®, Taxol®, sintilimab and genolimzumab. 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 announcement, whether as a result of new information, future events or circumstances or otherwise.
In addition to financial information prepared in accordance with U.S. GAAP, this announcement also contains certain non-GAAP financial measures.
Adjusted R&D expenses: We exclude the expected impact of the revenue received from external customers of our Innovation Platform, which is reinvested into our clinical trials, to derive our adjusted R&D expense. Revenue received from external customers of our Innovation Platform consists of milestone and other payments from our collaboration partners. The variability of such payments makes the identification of trends in our ongoing R&D activities more difficult. We believe the presentation of adjusted R&D expenses guidance provides useful and meaningful information about our ongoing R&D activities by enhancing investors’ understanding of the scope of our normal, recurring operating R&D expenses.
Adjusted consolidated net income attributable to Chi-Med from our Commercial Platform: We exclude the impact of one-time gains which could be triggered by the payment of land compensation from the Guangzhou government to a non-consolidated JV, dependent on Guangzhou government policy.
Management uses such measures internally for planning and forecasting purposes and to measure the Chi-Med Group’s overall performance. We believe these adjusted financial measures provide useful and meaningful information to us and investors because they enhance investors’ understanding of the continuing operating performance of our business and facilitate the comparison of performance between past and future periods. These adjusted financial measures are non-GAAP measures and should be considered in addition to, but not as a substitute for, the information prepared in accordance with U.S. GAAP. Other companies may define these measures in different ways.
| Reconciliation of GAAP to adjusted R&D expenses | 2018 Previous Guidance | 2018 Current Guidance |
| Segment operating loss — Innovation Platform | $(80)-(100)m | $(92)-(112)m |
| Less: Segment revenue from external customers — Innovation Platform | $(40)-(50)m | $(40)-(50)m |
| Adjusted R&D expenses | $(130)-(140)m | $(142)-(152)m |
| Reconciliation of GAAP to adjusted consolidated net income attributable to Chi-Med from our Commercial Platform | 2018 Previous Guidance | 2018 Current Guidance |
| Consolidated net income attributable to Chi-Med — Commercial Platform | $41-63m | $41-43m |
| Less: One-time gains from land compensation | $0-(20)m | $0m |
| Adjusted consolidated net income attributable to Chi-Med — Commercial Platform | $41-43m | $41-43m |
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014.
Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200
David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com
Xuan Yang, Solebury Trout
+1 (415) 971 9412 (Mobile)
xyang@troutgroup.com
UK & Europe – Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk
Americas – Brad Miles, Solebury Trout
+1 (917) 570 7340 (Mobile)
bmiles@troutgroup.com
Hong Kong & Asia ex-China – Joseph Chi Lo, Brunswick
+852 9850 5033 (Mobile)
jlo@brunswickgroup.com
Zhou Yi, Brunswick
+852 9783 6894 (Mobile)
yzhou@brunswickgroup.com
Mainland China – Sam Shen, Edelman
+86 1367 179 1029 (Mobile)
sam.shen@edelman.com
Richard Gray / Andrew Potts, Panmure Gordon (UK) Limited
+44 (20) 7886 2500
– Global SAVANNAH study of savolitinib / Tagrisso®combination in MET+ EGFRm NSCLC underway. Data presented at ESMO 2018 showedMET-amplification among the most frequent mechanisms of acquired resistance to AstraZeneca’s Tagrisso® –
– China registration study of savolitinib monotherapy in MET Exon 14 deletion NSCLC patients set to complete enrollment mid-late 2019. First potential savolitinib NDA targeted in 2020 –
– The outcome of a molecular epidemiology study, along with rapidly changing treatment landscape, leading to change in savolitinib kidney cancer strategy –
London: Thursday, December 20, 2018: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today provides a full update on the savolitinib development programs in both lung cancer and kidney cancer.
“This important progress on the savolitinib / Tagrisso® combination in lung cancer is a product of the close collaboration that Chi-Med has with AstraZeneca,” commented Christian Hogg, Chief Executive Officer of Chi-Med. He added, “We are also making rapid progress in China on MET Exon 14 deletion lung cancer where we now expect to complete enrollment of our registration intent study in 2019. In addition, we continue to believe that there is a role for a selective MET inhibitor in kidney cancer, and will use the deep body of clinical and epidemiological data that we have amassed to adapt our savolitinib strategy to the fast changing treatment landscape.”
Mene Pangalos, Executive Vice-President of AstraZeneca’s Innovative Medicines and Early Development Biotech Unit, commented that, “Recent data in lung cancer has further confirmed the importance of MET as both a resistance mechanism to EGFR inhibitors and as a target in its own right. Savolitinib has the potential to provide benefit for cancer patients who have MET-driven tumors, including those with the Exon 14 deletion. The initiation of the SAVANNAH study is an important step in our goal of bringing novel targeted therapies forward which selectively inhibit key oncogenic drivers. I am delighted to see the successful collaboration with Chi-Med deliver more important data that has the potential to redefine the way in which MET-driven disease is treated.”
TAGRISSO – Tagrisso® (osimertinib). Since its first approval in 2015, Tagrisso® has been established as a new standard of care in the treatment of Epidermal Growth Factor Receptor mutation (“EGFRm”) non-small cell lung cancer (“NSCLC”), and has now been approved in over 80 countries. AstraZeneca recently announced that Tagrisso® would be added to China’s national drug reimbursement program as second-line treatment for NSCLC patients in 2019;
TATTON – The combination of Tagrisso® / savolitinib is being explored as a treatment option for MET+ EGFRm NSCLC.
SAVANNAH – Based on these encouraging results, Chi-Med and AstraZeneca have initiated SAVANNAH, a global Phase II study of Tagrisso® / savolitinib combination in patients with MET+ EGFRm NSCLC who have progressed following Tagrisso®.
Further opportunities identified in EGFRm NSCLC:
MET Exon 14 deletion first-line NSCLC:
MET Exon 14 deletion first-line NSCLC is present in 2-3% of NSCLC patients. The China Phase II study of savolitinib monotherapy is currently enrolling in NSCLC patients with MET Exon 14 deletion who have failed prior systemic therapy, or are unwilling or unable to receive chemotherapy:
We believe MET Exon 14 deletion NSCLC has the potential to be the first savolitinib approval world-wide.
Kidney cancer treatment landscape. The treatment landscape of renal cell carcinoma (“RCC”) has evolved rapidly in recent years. Monotherapy treatment with second generation vascular endothelial growth factor receptor (“VEGFR”) TKIs as well as programmed cell death protein-1 (“PD-1”) monoclonal antibodies (“mAb”) are improving patient outcomes with ORRs increasing to >30% and in first-line clear cell RCC (“ccRCC”). Lately, VEGFR TKI / PD-1 mAb combinations have been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) driven by their ORRs of >70% in first-line ccRCC patients.
Papillary renal cell carcinoma (“PRCC”) continues to be a difficult sub-type of RCC to treat and has been shown to harbor MET-driven disease in between 40-70% of patients. As a result, while PRCC does favor the introduction of a MET TKI, enthusiasm for VEGFR TKI / PD-1 mAb monotherapy and combinations in PRCC is high.
Molecular Epidemiology (“MES”) update – We have recently completed the largest MES study conducted on PRCC patients, which was aimed at developing a more comprehensive understanding of the role of MET-driven disease in PRCC. Archived tissue samples from over 200 PRCC patients in the US, Canada, France and Asia (Korea) were screened using our companion diagnostic to identify MET-driven disease. Historical medical records from these patients were then used to determine if MET-driven disease is predictive of worse outcome for patients treated with sunitinib, in terms of progression free survival (“PFS”), time to treatment failure (TTF) and overall survival (OS). Preliminary MES findings are as follows:
CALYPSO study in PRCC – An independently sponsored Phase II study of savolitinib monotherapy and in combination with Imfinzi® (durvalumab), AstraZeneca’s anti Programmed death-ligand 1 (“PD-L1”) mAb, is underway in both PRCC and ccRCC patients (NCT02819596; U.K./Spain; sponsor: Queen Mary’s University, London).
SAVOIR Phase III study – SAVOIR (NCT03091192) is a global Phase III registration study of savolitinib versus Sutent® in MET-driven metastatic PRCC patients. The study was initiated in June 2017 with a primary endpoint for efficacy of PFS. The SAVOIR protocol was designed, with regulatory endorsement, to include an adjustment at the time of MES readout to enable rebalancing the ratio of first-line vs. second-line and above MET positive PRCC patients.
MES implications on SAVOIR study:
As a result, the savolitinib registration strategy for PRCC is being reassessed, to take into account these findings as well as the rapidly changing RCC treatment landscape. Enrollment in the SAVOIR study has been suspended.
Savolitinib is a potential first-in-class inhibitor of c-MET, an enzyme which has been shown to function abnormally in many types of solid tumors. Chi-Med designed savolitinib to be a potent and highly selective oral inhibitor, which, through chemical structure modification, addresses human metabolite-related renal toxicity, the primary issue that halted development of several other selective c-MET inhibitors. In clinical studies to date, involving over 700 patients, savolitinib has shown promising signs of clinical efficacy in patients with c-MET gene alterations in PRCC, NSCLC, colorectal cancer (CRC) and gastric cancer with an acceptable safety profile. Chi-Med is currently testing savolitinib in partnership with AstraZeneca in Phase Ib/II studies, in multiple solid tumor indications, both as a monotherapy and in combinations.
Chi-Med (AIM/Nasdaq: HCM) is an innovative biopharmaceutical company which researches, develops, manufactures and markets pharmaceutical products. Its Innovation Platform, Hutchison MediPharma, has about 400 scientists and staff focusing on discovering, developing and commercializing targeted therapeutics in oncology and autoimmune diseases. It has a portfolio of eight cancer drug candidates currently in clinical studies around the world. Chi-Med’s Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products, covering an extensive network of hospitals across China.
Dual-listed on the AIM market of the London Stock Exchange and the Nasdaq Global Select Market, Chi-Med is headquartered in Hong Kong and majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.
This announcement 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 savolitinib, plans to initiate clinical studies for savolitinib, 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 savolitinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval, the potential market of savolitinib for a targeted indication and the sufficiency of funding. In addition, as certain studies rely on the use of Tagrisso®, Iressa® and Imfinzi® as combination therapeutics with savolitinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of Tagrisso®, Iressa® and Imfinzi®. 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 announcement, whether as a result of new information, future events or circumstances or otherwise.
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014.
Mark Lee, Senior Vice President, Corporate Finance & Development
+852 2121 8200
David Dible, Citigate Dewe Rogerson
+44 7967 566 919 (Mobile)
david.dible@citigatedewerogerson.com
Xuan Yang, Solebury Trout
+1 (415) 971 9412 (Mobile)
xyang@troutgroup.com
UK & Europe – Anthony Carlisle, Citigate Dewe Rogerson
+44 7973 611 888 (Mobile)
anthony.carlisle@cdrconsultancy.co.uk
Americas – Brad Miles, Solebury Trout
+1 (917) 570 7340 (Mobile)
bmiles@troutgroup.com
Hong Kong & Asia ex-China – Joseph Chi Lo, Brunswick
+852 9850 5033 (Mobile)
jlo@brunswickgroup.com
Zhou Yi, Brunswick
+852 9783 6894 (Mobile)
yzhou@brunswickgroup.com
Mainland China – Sam Shen, Edelman
+86 1367 179 1029 (Mobile)
sam.shen@edelman.com
Richard Gray / Andrew Potts, Panmure Gordon (UK) Limited
+44 (20) 7886 2500