Chi-Med Reports 2020 Interim Results and Provides Updates on Key Clinical Programs

– Strong global pipeline progress – three U.S. FDA¹ Fast Track Designations; surufatinib U.S. NDA² preparations underway; and initiation of global Phase III for fruquintinib –

– Two further NDAs submitted in China – savolitinib in MET³ Exon 14 skipping mutation NSCLC⁴, and surufatinib in pancreatic NET⁵ – 

– Expansion of commercial activities in oncology – Chi-Med to be responsible for medical detailing and marketing for Elunate^® throughout Mainland China starting October 2020 –

– Company to Host Results Call & Webcast Today at 1 p.m. BST / 8 a.m. EDT / 8 p.m. HKT –

HONG KONG and SHANGHAI and FLORHAM PARK, N.J., July 30, 2020 (GLOBE NEWSWIRE) -- Hutchison China MediTech Limited (“”) (Nasdaq/AIM: HCM), an innovation-driven, commercial-stage biopharmaceutical company, today announces its unaudited financial results for the six months ended June 30, 2020 and provides updates on key clinical and commercial developments.

“During the first half of 2020, we continued to build our fully integrated business in China, from research and development to manufacturing and commercialization and sales, with a focus on oncology,” said Mr. Simon To, Chairman of Chi-Med.  “NDAs for surufatinib and savolitinib are currently under review by the China NMPA⁶ and we are now preparing for multiple potential launches employing our newly-established commercial organization in oncology, covering all provinces in Mainland China.” 

“We are also one of a few China-based biotech companies working to realize the global potential of our home-grown innovative drug candidates,” he added.  “We currently have nine novel drug candidates in clinical trials, many with global potential, and an additional five drug candidates at the IND⁷-enabling stage.”

“Over the past three years, we have significantly expanded our international development footprint and, in the first half of 2020, locked in global registration strategies for surufatinib and fruquintinib, while our global partnership with AstraZeneca⁸ is approaching the same for savolitinib. A deep pipeline of unpartnered earlier-stage oncology assets follows, with most notably, global development of our Syk⁹ and PI3Kδ¹⁰ assets progressing well and our IDH 1/2¹¹ inhibitor expected to start Phase I in the United States this year.”

“We believe that the anticipated launches of multiple innovative oncology drugs over the next twelve to eighteen months will address a broad range of unmet medical needs and benefit a large number of patients globally, propelling Chi-Med into a new phase of growth.”

FIRST HALF 2020 OPERATING HIGHLIGHTS

Set out below are some of Chi-Med’s operating highlights so far this year.  For more details, please refer to “Operations Review” below.

I.     PREPARING TO LAUNCH MULTIPLE ONCOLOGY DRUGS IN CHINA

Savolitinib – NDA submitted for potential first-in-class selective MET TKI¹² in China:

• NDA accepted by NMPA in MET Exon 14 skipping mutation NSCLC:  presented positive results at ASCO¹³ from a registration study in MET Exon 14 skipping mutation NSCLC demonstrating 49.2% ORR¹⁴, 93.4% DCR¹⁵ and 9.6 months DoR¹⁶ in efficacy evaluable patients, underpinning the NDA acceptance in May 2020 and subsequent grant of Priority Review status in July 2020.

Surufatinib – Two NDAs with first China launch in NET planned for late 2020:

• Progressed non-pancreatic NET NDA:  Supported by the positive SANET-ep Phase III and submitted in late 2019, the NMPA NDA review process is on-track, and we continue to plan for launch in late 2020;
  
  
  
  
• Submitted Pancreatic NET NDA:  Following positive interim analysis and early termination of SANET-p Phase III, an NDA for pancreatic NET has been submitted in China, which we anticipate may be accepted in the near term;
  
  
  
  
• Progressed to Phase II for Tuoyi^® combination:  Initiated a Phase II in early 2020 in eight solid tumor indications for surufatinib plus Tuoyi^®, a China-approved PD-1¹⁷ antibody from Junshi¹⁸.  Data presented at AACR¹⁹, shows the combination is well tolerated with encouraging activity, ORR 64% and DCR 100% in efficacy evaluable patients at the RP2D²⁰; and
  
  
  
  
• Initiated Tyvyt^® PD-1 combination:  In July 2020, Innovent²¹ initiated a Phase I combining surufatinib with their China-approved PD-1 monoclonal antibody, Tyvyt^®.

Fruquintinib – Commercial progress on Elunate^® (fruquintinib capsules):

• 174% overall increase in Elunate^® prescriptions²² during the first half of 2020:  Inclusion in the 2020 National Reimbursement Drug List (“NRDL”) has led to a major increase in access.  In-market sales, as provided by Lilly²³, were $14.0 million²⁴ (H1-19: $11.4m) during the first half of 2020;
  
  
  
  
• Chi-Med to commercialize Elunate^® in China beginning in October 2020:  In July 2020, an agreement was reached with Lilly that Chi-Med will commence medical detailing and marketing activities for Elunate^® across all of China effective October 1, 2020;
  
  
  
  
• Phase III interim analysis in second-line gastric cancer:  In June 2020, following the second and final interim analysis for futility of the FRUTIGA study in China the IDMC²⁵ recommended to continue the study.  FRUTIGA is expected to complete enrollment in late 2020 or early 2021; and
  
  
  
  
• Expanded Tyvyt^® PD-1 combination: Phase I dose escalation for the fruquintinib and Tyvyt^® combination completed in July 2020.  A Phase Ib expansion study at the RP2D is underway in China targeting five solid tumor indications.

Established in-house oncology commercial organization – Team now in place for imminent launches:

• An in-house oncology commercial organization has now been established with over 320 staff, versus about 90 at the start of 2020, in order to support the potential launch of surufatinib in China and commercialization of Elunate^®.

II.    REALIZING THE GLOBAL POTENTIAL OF OUR LATE STAGE ONCOLOGY ASSETS

Surufatinib – U.S. NDA under preparation:

• Secured FDA Fast Track Designations:  FDA granted Fast Track Designations for both pancreatic NET and non-pancreatic NET in April 2020;
  
  
  
  
• Positive U.S. NET bridging study:  Presented results at ASCO from the U.S. Phase Ib NET study in June 2020, reporting 100% DCR in heavily pre-treated pancreatic-NET and non-pancreatic NET patients;
  
  
  
  
• Agreed U.S. NDA submission pathway:  In May 2020, agreed with FDA that the two pivotal NET studies in China, along with existing data from the U.S. bridging study, could support an NDA submission.  Now planning a U.S. NDA rolling submission from late 2020 into early 2021;
  
  
  
  
• U.S. commercial launch strategy:  Work underway to establish U.S. launch readiness for late 2021;
  
  
  
  
• Progressed European regulatory discussions:  Engaging extensively with European regulatory authorities, targeting MAA²⁶ submission for NET during 2021; and
  
  
  
  
• BeiGene²⁷ global PD-1 collaboration:  Entered into a clinical collaboration in May 2020 to explore the combination of surufatinib with BeiGene’s PD-1 antibody, tislelizumab, in the U.S..

Fruquintinib – global Phase III registration study in CRC²⁸ underway:

• Secured FDA Fast Track Designation:  Granted in June 2020 for patients with metastatic CRC;
  
  
  
  
• Initiated FRESCO-2 global Phase III registration study in CRC:  Following study design endorsement by the FDA, EMA²⁹ and PMDA³⁰, we initiated the global Phase III registration study in metastatic CRC.  Enrollment of over 500 patients in ~130 sites in 10 countries targeted to complete in late 2021; and
  
  
  
  
• BeiGene and Innovent global PD-1 collaborations:  Entered into a clinical collaboration with BeiGene in the U.S., Europe, China and Australia in May 2020 to explore the combination of fruquintinib and tislelizumab.  Our work with Innovent has now established the RP2D for the fruquintinib and Tyvyt^® combination and a U.S. IND is planned for late 2020.

Savolitinib – AstraZeneca collaboration making progress in lung and kidney cancer:

• SAVANNAH interim analysis – In late July 2020, AstraZeneca and Chi-Med conducted a first internal interim analysis for the SAVANNAH global Phase II study of the savolitinib plus Tagrisso combination in EGFR mutation positive TKI refractory NSCLC patients.  Early interim efficacy and safety data is now under review.  The enrollment of the SAVANNAH study continues apace in 13 countries;
  
  
  
  
• Encouraging efficacy in MET-driven PRCC³¹:  In June 2020, we presented data at ASCO for SAVOIR, a Phase III study of savolitinib versus sunitinib.  Savolitinib demonstrated encouraging efficacy compared to sunitinib with a 27% versus 7% ORR, a trend toward benefit in PFS³² and an improvement in OS³³ with tolerability advantages; and
  
  
  
  
• Preliminary signal for savolitinib/Imfinzi^® (PD-L1³⁴) combination in all PRCC:  In February 2020, we presented data from the CALYPSO Phase II study at ASCO GU³⁵ showing the combination was tolerable and associated with durable efficacy, with a 12.3 month median OS. 

III.   INVESTING IN THE FUTURE – EARLY PIPELINE

• Non-Hodgkin’s lymphoma (“NHL”):  Advanced Phase Ib expansion of both of our NHL assets, HMPL-523 (Syk) and HMPL-689 (PI3Kδ) in China.  We expect these studies to inform our China registration study decisions in 2020.  In the U.S. and Europe, we continued to expand development of HMPL-523 and HMPL-689, with over twenty Phase I sites now enrolling;
  
  
  
  
• HMPL-453 – selective FGFR³⁶ 1/2/3 inhibitor:  We initiated a Phase II study in advanced malignant mesothelioma in China in March 2020, with a second Phase II, in Cholangiocarcinoma, in planning;
  
  
  
  
• HMPL-306 – IDH 1/2 dual inhibitor:  In late July 2020, we dosed our first patient in a Phase I study in China with our ninth in-house discovered asset, HMPL-306; and
  
  
  
  
• Five additional novel drug candidates in oncology are currently progressing through IND-enabling studies and are anticipated to reach the clinic over the next twelve to eighteen months.

IV.   UPDATE ON THE IMPACT OF COVID-19

• Working to effectively manage COVID-19 challenges:  The COVID-19 outbreak initially posed some challenges to our operations resulting from restrictions in travel.  Our teams adapted quickly and have been able to minimize the effect across our businesses thus far.  We will continue to closely monitor the evolving situation.  At this stage, we are unable to assess the long-term effect of the outbreak, if any.

KEY EVENTS PLANNED FOR BALANCE 2020 & EARLY 2021

FINANCIAL HIGHLIGHTS

The items below are selected financial data for the six months ended June 30, 2020.  All dollars are expressed in U.S. dollar currency unless otherwise stated. For more details, please refer to “Financial Review”, “Operations Review” and “Interim Unaudited Condensed Consolidated Financial Statements” below. 

OVERALL GROUP:

• Group revenue of $106.8 million (H1-19: $102.2m);
  
  
  
  
• Net loss attributable to Chi‑Med of $49.7 million (H1-19: net loss of $45.4m);
  
  
  
  
• Adjusted Group (non-GAAP) net cash flows excluding financing activities was -$32.5 million (H1-19: -$34.2m).  Cash from our Commercial Platform, as well as cash received from our multi-national partners, continued to offset a substantial portion of our R&D⁴¹ expenses;
  
  
  
  
• Recent financing activity strengthens cash position.  We held cash, cash equivalents and short-term investments of $281.0 million as of June 30, 2020 (December 31, 2019: $217.2m).  In early July 2020, we completed a private placement to General Atlantic⁴², raising an additional $100.0 million in gross proceeds, to further strengthen our cash position; and
  
  
  
  
• Additional unutilized bank facilities of $119.3 million (December 31, 2019: $119.3m) and bank borrowings of $26.8 million (December 31, 2019: $26.8m).

INNOVATION PLATFORM (our R&D operations):

• Consolidated revenue was $7.8 million (H1-19: $7.3m) mainly from service fee payments from AstraZeneca and Lilly; and
  
  
  
  
• Net loss from our Innovation Platform attributable to Chi-Med of $73.6 million (H1-19: net loss of $67.1m) resulting from expansion in the development of our nine novel drug candidates, with five now in global development, and establishment of scaled international clinical and regulatory operations.

COMMERCIAL PLATFORM (our commercial operations):

• Total consolidated sales up 4% (9% at CER⁴³) to $99.0 million (H1-19: $94.9m) mainly due to continued progress on our Prescription Drugs subsidiary Hutchison Sinopharm⁴⁴ as well as manufacturing revenues and royalties from Elunate^®;
  
  
  
  
• Total consolidated net income from our Commercial Platform attributable to Chi-Med up 14% (19% at CER) to $35.5 million (H1-19: $31.0m), strong performance despite the limitations posed by COVID-19 underpinned by the growing profits of our Prescription Drugs operations in China; and
  
  
  
  
• Guangzhou land compensation:  In June 2020, our 50/50 joint venture, HBYS⁴⁵, entered into an agreement with the Guangzhou government for the return of an unused piece of land in return for cash compensation of up to $95 million.  HBYS will receive compensation in stages over a period of approximately one year.  The first $24.1 million payment was received by HBYS in late June 2020 and the return will be recorded in Chi-Med’s statement of operations in H2 2020.

FINANCIAL GUIDANCE

During the first half of 2020, we performed in-line with published guidance, with dividends from our Commercial Platform offsetting a material portion of our R&D expenses as expected. 

Over the balance of 2020, cash investments will rise in a number of areas including:  several major global clinical and regulatory activities such as the global FRESCO-2 Phase III for fruquintinib and the submission of the U.S. NDA for surufatinib; the first phase of construction of our new large-scale oncology manufacturing facility in Shanghai; and expansion of our commercial activities in oncology in China, specifically our new commercial role on Elunate^® and preparation for the surufatinib launch.

We assume at this stage that the financial impact of the COVID-19 outbreak will not be material to the Group.  Since we cannot predict how the situation will evolve, we will monitor and adjust if needed, as new material information emerges.  We therefore provide unchanged Financial Guidance for 2020 below.

Use of Non-GAAP Financial Measures and Reconciliation – References in this announcement to adjusted Innovation Platform segment operating loss, adjusted Group net cash flows excluding financing activities and financial measures reported at CER are based on non-GAAP financial measures.  Please see the “Use of Non-GAAP Financial Measures and Reconciliation” below for further information relevant to the interpretation of these financial measures and reconciliations of these financial measures to the most comparable GAAP measures, respectively. 

Conference Call and Audio Webcast Presentation Scheduled Today at 1 p.m. BST / 8 a.m. EDT / 8 p.m. HKT –  Investors may participate in the call as follows: +44 20 3194 0569 (U.K.) / +1 646 722 4977 (U.S.) /  6500 (Hong Kong), or access a live audio webcast of the call via Chi-Med’s website at .

Additional dial-in numbers are also available at . Please use participant access code “54962123#.”

About Chi-Med

Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases.  It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China.  For more information, please visit: .

CONTACTS

References

Unless the context requires otherwise, references in this announcement to the “Group,” the “Company,” “Chi-Med,” “Chi-Med Group,” “we,” “us,” and “our,” mean Hutchison China MediTech Limited and its consolidated subsidiaries and joint ventures unless otherwise stated or indicated by context.

Past Performance and Forward-Looking Statements

The performance and results of operations of the Group contained within this announcement are historical in nature, and past performance is no guarantee of future results of the Group.  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 can be identified by words like “will,” “expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,” “pipeline,” “could,” “potential,” “first-in-class,” “designed to,” “objective,” “guidance,” “pursue,” or similar terms, or by express or implied discussions regarding potential drug candidates, potential indications for drug candidates or by discussions of strategy, plans, expectations or intentions. You should not place undue reliance on these statements.  Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements.  There can be no guarantee that any of our drug candidates will be approved for sale in any market, or that any approvals which are obtained will be obtained at any particular time, or that any such drug candidates will achieve any particular revenue or net income levels. In particular, management’s expectations could be affected by, among other things: unexpected regulatory actions or delays or government regulation generally; the uncertainties inherent in research and development, including the inability to meet our key study assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria and funding requirements, changes to clinical protocols, unexpected adverse events or safety, quality or manufacturing issues; the inability of a drug candidate to meet the primary or secondary endpoint of a study; the impact of the COVID-19 pandemic or other health crises in China or globally; the inability of a drug candidate to obtain regulatory approval in different jurisdictions or gain commercial acceptance after obtaining regulatory approval; global trends toward health care cost containment, including ongoing pricing pressures; uncertainties regarding actual or potential legal proceedings, including, among others, actual or potential product liability litigation, litigation and investigations regarding sales and marketing practices, intellectual property disputes, and government investigations generally; and general economic and industry conditions, including uncertainties regarding the effects of the persistently weak economic and financial environment in many countries and uncertainties regarding future global exchange rates. 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 is providing the information in this announcement as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.

In addition, this announcement contains statistical data and estimates that Chi-Med obtained from industry publications and reports generated by third-party market research firms.  Although Chi-Med believes that the publications, reports and surveys are reliable, Chi-Med has not independently verified the data and cannot guarantee the accuracy or completeness of such data.  You are cautioned not to give undue weight to this data.  Such data involves risks and uncertainties and are subject to change based on various factors, including those discussed above.

Inside Information

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014.

FINANCIAL REVIEW

Chi-Med Group revenue for the six months ended June 30, 2020 was $106.8 million (H1-19: $102.2m).  Revenue from the Commercial Platform increased to $99.0 million (H1-19: $94.9m) driven mainly by our Prescription Drugs business which included manufacturing revenue and royalties from the commercial sale of Elunate^® as well as increased sales by our Hutchison Sinopharm business.  Revenue from the Innovation Platform was $7.8 million in the first half of 2020 (H1-19: $7.3m).

Group revenues do not include the revenues of our two large-scale, 50/50 joint ventures in China, SHPL⁴⁶ (Prescription Drugs) and HBYS (Consumer Health), since these are accounted for using the equity method.

In the first half of 2020, our Commercial Platform, which is a material source of profit and cash flow for Chi-Med, recorded a segment operating profit of $37.3 million (H1-19: $34.1m).  Profit growth was primarily driven by the strong performance of SHPL, which effectively navigated challenges from COVID-19 and the discontinuation of distribution rights for Seroquel^® in May 2019.  Increased manufacturing revenue and royalties from Elunate^® also contributed, while the weakening of the RMB against the U.S. dollar in the first half of 2020 reduced the operating profit of our Commercial Platform in U.S. dollar terms by about 5%. 

The Innovation Platform incurred a segment operating loss of $73.4 million⁴⁷ (H1-19: operating loss of $67.2m) as a result of the expansion of discovery activities, clinical pipeline development and related organizational growth.

Net corporate unallocated operating loss, primarily Chi-Med Group overhead and operating costs, increased to $9.7 million (H1-19: $7.3m) mainly due to expanded administrative expenses and a lower level of interest income as a result of the decline in market interest rates. 

Consequently, Chi-Med Group’s operating loss was $45.7 million (H1-19: operating loss of $40.3m).

The aggregate of interest and income tax expenses of the Chi-Med Group, as well as net income attributable to non-controlling interests was $4.0 million (H1-19: $5.0m).

The resulting total Group net loss attributable to Chi-Med was $49.7 million (H1-19: net loss of $45.4m).

As a result, Group net loss attributable to Chi-Med in the first half of 2020 was $0.07 per ordinary share / $0.36 per American depositary share, which was unchanged from the first half of 2019.

Cash and Financing

Cash inflows from our Commercial Platform, as well as our R&D collaborations with AstraZeneca and Lilly, offset a material portion of our R&D expense.  As a result, total Chi-Med Adjusted (non-GAAP) Group net cash flows excluding financing activities was -$32.5 million (H1-19: -$34.2m) despite the aforementioned $73.4 million Innovation Platform segment operating loss.  

The Chi-Med Group held cash, cash equivalents and short-term investments of $281.0 million as of June 30, 2020 (December 31, 2019: $217.2m).  Subsequently, in early July 2020, we completed a private placement with General Atlantic raising an additional $100.0 million in gross proceeds, to further strengthen our cash position. 

Outstanding Chi-Med Group level bank loans as of June 30, 2020 amounted to $26.8 million (December 31, 2019: $26.8m) and additional unutilized bank facilities available to the Group totaled $119.3 million (December 31, 2019: $119.3m).

The primary source of cash to the Chi-Med Group from our Commercial Platform are dividends from our two non-consolidated Commercial Platform joint ventures, SHPL and HBYS.  During the first half of 2020, the Chi-Med Group received dividends of $35.3 million (H1-19: $18.2m) from SHPL and HBYS.  As of June 30, 2020, SHPL and HBYS held $103.3 million (December 31, 2019: $62.7m) in cash and cash equivalents with no outstanding bank loans. 

OPERATIONS REVIEW

We are an innovative, commercial-stage biopharmaceutical company based in China aiming to become a fully integrated global leader in the discovery, development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases.

Innovation Platform

Our Innovation Platform is a comprehensive drug discovery and development operation, with a large team of about 550 scientists and staff (December 31, 2019: ~500) in China and at our international operation in New Jersey.  Currently, we have nine self-discovered drug candidates in clinical trials, with five in global clinical development.

PRODUCT PIPELINE PROGRESS

SAVOLITINIB

Savolitinib is an oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase which has been shown to function abnormally in many types of solid tumors promoting tumor growth, angiogenesis, and metastasis.  In global partnership with AstraZeneca, savolitinib has been studied in over 1,000 patients to date, both as a monotherapy and in combinations.  In clinical studies it has shown promising clinical efficacy in patients with MET gene alterations in multiple tumor types with an acceptable safety profile.

Savolitinib – Lung cancer:

MET is a prime target in NSCLC.  The table below shows a summary of the clinical studies for savolitinib in lung cancer patients.

NDA accepted in MET Exon 14 skipping mutation NSCLC (NCT02897479) – It is estimated that 2-3% of NSCLC patients have MET Exon 14 skipping mutation, which leads to poor prognosis.  In late 2019, we completed a 70 patient Phase II registration study that formed the basis for NDA which was accepted by the China NMPA in May 2020.  

Results of the Phase II study were presented at ASCO in June 2020 and showed that as of the March 31, 2020 data cut off, ORR was 49.2% and DCR was 93.4% in 61 efficacy evaluable patients.  Median DoR was 9.6 months (95% confidence interval [“CI”] 5.5–not reached [“NR”]) with maturity of 40%.  Median PFS was 6.9 months (95% CI 4.2–19.3) with maturity of 50%.  Median OS was 14.0 months (95% CI: 9.7–NR) with maturity of 46%.  A total of 36% of patients in the Phase II study harbored pulmonary sarcomatoid carcinoma with Exon 14 skipping mutation, a particularly aggressive sub-type of NSCLC.  Treatment naïve patients accounted for 40% of the treated patients (mostly those unfit to receive first line chemotherapy) while the remainder had received prior treatments.  Clinical data demonstrated an acceptable safety profile with a low adverse event (“AE”) related discontinuations rate of 14.3%.

AstraZeneca and Chi-Med continue to explore the global development pathway for savolitinib in MET Exon 14 skipping mutation NSCLC.

EGFR⁴⁸ TKI-resistance in NSCLC – MET-amplification is a major mechanism for acquired resistance to both first generation EGFR TKIs, such as Iressa^® and Tarceva^®, as well as third-generation EGFR TKIs like Tagrisso^®, an EGFR TKI owned by AstraZeneca.  As many as 30% of EGFR mutation positive NSCLC patients develop MET amplification driven resistance to EGFR TKIs.  During the past three years, savolitinib has been studied extensively in these patients in the TATTON and SAVANNAH studies, and meeting their needs represents our major focus.

SAVANNAH Phase II study of combination with Tagrisso^® in patients who have progressed following Tagrisso^® due to MET amplification or overexpression (NCT03778229) – The SAVANNAH study is a single-arm, open-label study, with the potential for registration, enrolling in North and South America, Europe and Asia.  SAVANNAH followed the successful TATTON study, a Phase Ib/II expansion study of savolitinib in combination with Tagrisso^® in over 220 EGFR mutation positive TKI refractory NSCLC patients, with data presented at both AACR and ESMO Asia in 2019 and published in The Lancet Oncology this year. 

In late July 2020, AstraZeneca and Chi-Med conducted a first internal interim analysis for SAVANNAH, and review of early safety and efficacy data is ongoing. 

Savolitinib – Kidney cancer:

MET is a clear genetic driver in RCC⁴⁹.  The table below shows a summary of the clinical studies for savolitinib in kidney cancer patients.

MET+ Papillary Renal Cell Carcinoma (“PRCC”) – PRCC is the most common of the non-clear cell renal cell carcinomas, representing approximately 14% of kidney cancer.  Approximately 400,000 new cases of kidney cancer were diagnosed globally in 2018, equating to about 56,500 cases of PRCC, with approximately half harboring MET driven disease.  No targeted therapies have been approved specifically for PRCC.

SAVOIR Phase III in MET-positive PRCC (NCT03091192) – In late 2018, the SAVOIR study, a global Phase III study of savolitinib monotherapy compared with sunitinib in patients with MET-driven PRCC, was stopped due to confounding results from a separate, external, retrospective observational study. 

Results from 60 randomized patients (33 savolitinib, 27 sunitinib) were followed through August 19, 2019 with data presented at ASCO in May 2020.  Although patient numbers and follow-up were limited, trends in efficacy were promising.  In terms of OS, savolitinib patients had not reached median OS at data cut-off, compared to 13.2 months for sunitinib patients (HR⁵¹ 0.51; 95% CI: 0.21–1.17; p=0.110).  Median PFS was 7.0 months for savolitinib patients, compared to 5.6 for sunitinib patients (HR 0.71; 95% CI 0.37–1.36; p=0.313).  Responses were observed in 27% and 7% of savolitinib and sunitinib patients, respectively.  This difference did not reach statistical significance due to the small sample size.  None of the 9 responders on savolitinib treatment experienced disease progression as of data cut-off, compared to 1 of 2 responders on sunitinib treatment.  Sunitinib response rate was in range with previous studies.  In terms of safety, Grade ≥3 AEs were reported in 42% of savolitinib patients versus 81% of sunitinib patients, with AEs leading to dose modification in 30% and 74% of savolitinib and sunitinib patients, respectively.

Based on these data, Chi-Med and AstraZeneca are actively evaluating the opportunity to restart clinical work in PRCC for monotherapy savolitinib.

Savolitinib and Immunotherapy Combinations – Major evidence is emerging demonstrating that MET plays an important role in the tumor microenvironment, leading to reduced anti-tumor activity of immune cells in many solid tumors.  Therefore, combining immunotherapies with a MET inhibitor is hypothesized to enhance anti-tumor activity.  Chi-Med and AstraZeneca, as well as others, are currently conducting several clinical studies of anti-PD-1/PD-L1 antibodies in combination with MET inhibitors aimed at validating this hypothesis.

CALYPSO Phase II in combination with Imfinzi^® PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of savolitinib in combination with Imfinzi^®, an anti-PD-L1 antibody owned by AstraZeneca.  The study is evaluating the safety and efficacy of the savolitinib/Imfinzi^® combination in patients with PRCC and clear cell RCC at sites in the U.K. and Spain.

CALYPSO PRCC cohort – Interim data for the PRCC cohort of the CALYPSO Phase II study were presented at ASCO GU 2020 reporting an ORR of 27%, median PFS of 4.9 months (95% CI: 2.5, 12.0) and median OS of 12.3 months (95% CI: 5.8, 21.3).  Tolerability was in line with established single agent safety profiles.  Chi-Med and AstraZeneca continue to accumul