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1、Table of Contents UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington,D.C.20549 FORM 10-K (Mark One)Annual Report Pursuant to Section 13 or 15(d)of the Securities Exchange Act of 1934For the fiscal year ended:December 31,2020Or Transition Report Pursuant to Section 13 or 15(d)of the Securities

2、 Exchange Act of 1934Commission file number:001-38205 ZAI LAB LIMITED(Exact Name of Registrant as Specified in its Charter)Cayman Islands 98-1144595(State or other jurisdiction ofincorporation or organization)(I.R.S.EmployerIdentification No.)4560 Jinke RoadBldg.1,Fourth FloorPudongShanghai,China 20

3、1210(Address of principal executive offices)(Zip Code)+86 21 6163 2588(Registrants Telephone Number,Including Area Code)Securities registered pursuant to Section 12(b)of the Act:Title of each class Trading Symbol(s)Name of each exchange on which registeredAmerican Depositary Shares,each representing

4、 1Ordinary Share,par value$0.00006 per share ZLAB The Nasdaq Global Market Ordinary Shares,par value$0.00006 per share*9688 The Stock Exchange of Hong Kong Limited *Included in connection with the registration of the American Depositary Shares with the Securities and Exchange Commission.The ordinary

5、 shares are not registered or listed fortrading in the United States but are listed for trading on The Stock Exchange of Hong Kong Limited.Securities registered pursuant to Section 12(g)of the Act:NoneIndicate by check mark if the registrant is a well-known seasoned issuer,as defined in Rule 405 of

6、the Securities Act.Yes No Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d)of the Exchange Act.Yes No Indicate by check mark whether the registrant:(1)has filed all reports required to be filed by Section 13 or 15(d)of the Securities Exc

7、hange Act of 1934 during the preceding 12 months(orfor such shorter period that the registrant was required to file such reports),and(2)has been subject to such filing requirements for the past 90 days.Yes No Indicate by check mark whether the registrant has submitted electronically every Interactiv

8、e Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding12 months(or for such shorter period that the registrant was required to submit such files).Yes No Indicate by check mark whether the registrant is a large accelerated filer,an accelerated filer,a non-acc

9、elerated filer,a smaller reporting company,or an emerging growth company.See thedefinitions of“large accelerated filer,”“accelerated filer,”“smaller reporting company,”and“emerging growth company”in Rule 12b-2 of the Exchange Act.:Large accelerated filer Accelerated Filer Non-accelerated filer Small

10、er reporting company Emerging growth company If an emerging growth company,indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accountingstandards provided pursuant to Section 13(a)of the Exchange Act.Indicate

11、 by check mark whether the registrant has filed a report on and attestation to its managements assessment of the effectiveness of its internal control over financial reporting underSection 404(b)of the Sarbanes-Oxley Act(15 U.S.C.7262(b)by the registered public accounting firm that prepared or issue

12、d its audit report.Yes No Indicate by check mark whether the registrant is a shell company(as defined in Rule 12b-2 of the Exchange Act).Yes No As of June 30,2020,the last business day of the registrants most recently completed second fiscal quarter,the aggregate market value of the ordinary shares,

13、including in the form ofAmerican Depositary Shares(“ADSs”),each representing one ordinary share,held by non-affiliates of the registrant was approximately US$6.2 billion,based upon the closing price of theregistrants ADSs on the Nasdaq Global Market of US$82.13 on June 30,2020.As of February 26,2021

14、,88,592,343 ordinary shares,par value$0.00006 per share,were outstanding,of which 60,078,450 ordinary shares were held in the form of ADSs.DOCUMENTS INCORPORATED BY REFERENCEThe registrant intends to file a definitive proxy statement pursuant to Regulation 14A within 120 days of the end of the fisca

15、l year ended December 31,2020.Portions of such definitive proxystatement are incorporated by reference into Part III of this Annual Report on Form 10-K.Table of ContentsZai Lab LimitedAnnual Report on Form 10-KTABLE OF CONTENTS Page PART I 1 Item 1.Business 1 Item 1A.Risk Factors 61 Item 1B.Unresolv

16、ed Staff Comments 125 Item 2.Properties 125 Item 3.Legal Proceedings 125 Item 4.Mine Safety Disclosures 125 PART II 126 Item 5.Market for Registrants Common Equity,Related Stockholder Matters and Issuer Purchases of Equity Securities 126 Item 6.Selected Consolidated Financial Data 135 Item 7.Managem

17、ents Discussion and Analysis of Financial Condition and Results of Operations 135 Item 7A.Quantitative and Qualitative Disclosures About Market Risk 149 Item 8.Financial Statements and Supplementary Data 150 Item 9.Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

18、150 Item 9A.Controls and Procedures 150 Item 9B.Other Information 151 PART III 152 Item 10.Directors,Executive Officers and Corporate Governance 152 Item 11.Executive Compensation 152 Item 12.Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 152 Item 13.C

19、ertain Relationships and Related Transactions,and Director Independence 152 Item 14.Principal Accounting Fees and Services 152 PART IV 152 Item 15.Exhibits,Financial Statement Schedules 152 Item 16.Form 10-K Summary 152 -i-Table of ContentsForward-Looking StatementsThis Annual Report on Form 10-K co

20、ntains forward-looking statements.Forward-looking statements are neither historical facts nor assurances offuture performance.Instead,they are based on our current beliefs,expectations and assumptions regarding the future of our business,future plans andstrategies,our operational results and other f

21、uture conditions.Forward-looking statements can be identified by words such as“anticipate,”“believe,”“estimate,”“expect,”“intend,”“may,”“plan,”“predict,”“project,”“seek,”“target,”“potential,”“will,”“would,”“could,”“should,”“continue,”“contemplate”and other similar expressions,although not all forwar

22、d-looking statements contain these identifying words.These forward-lookingstatements include all matters that are not historical facts.They appear in a number of places throughout this Annual Report on Form 10-K and includestatements regarding our intentions,beliefs or current expectations concernin

23、g,among other things,our results of operations,financial condition,liquidity,prospects,growth,strategies and the industry in which we operate.By their nature,forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may ormay not occur

24、in the future.In the next section,we summarize some of those related risks.Although we base our forward-looking statements onassumptions that we believe are reasonable when made,we caution you that forward-looking statements are not guarantees of future performance andthat our actual results of oper

25、ations,financial condition and liquidity,and the development of the industry in which we operate may differ materiallyfrom those made in or suggested by the forward-looking statements contained in this Annual Report on Form 10-K.In addition,even if our results ofoperations,financial condition and li

26、quidity,and the development of the industry in which we operate,are consistent with the forward-lookingstatements contained in this Annual Report on Form 10-K,those results or developments may not be indicative of results or developments in subsequentperiods.Note on CompanyUsage of TermsUnless the c

27、ontext requires otherwise,references in this Annual Report to“Zai Lab,”the“Company,”“we,”“us,”and“our”refer to Zai LabLimited and its subsidiaries,on a consolidated basis;“Greater China”refers to mainland China,Hong Kong,Macau,and Taiwan;and“China”refersto mainland China.-ii-Table of ContentsSummary

28、 of Significant Risk FactorsThe following is a summary of significant risk factors and uncertainties that may affect our business which are discussed in more detail below in“Part IItem 1ARisk Factors”included in this Annual Report:our ability to successfully commercialize ZEJULA,Optune and any other

29、 products and product candidates that we may obtain regulatoryapproval for;the anticipated amount,timing and accounting of revenues;contingent,milestone,royalty and other payments under licensing,collaboration,and acquisition agreements;tax positions and contingencies;collectability of receivables;p

30、re-approval inventory;cost ofsales;research and development costs;compensation and other selling,general and administrative expenses;amortization of intangibleassets;foreign currency exchange risk;estimated fair value of assets and liabilities;and impairment assessments;expectations,plans and prospe

31、cts relating to sales,pricing,growth and launch of our marketed and pipeline products;the potential impact of increased product competition in the markets in which we compete,including increased competition from neworiginator therapies,generics,prodrugs and biosimilars of existing products and produ

32、cts approved under abbreviated regulatory pathways,including generic or biosimilar versions of our products;patent terms,patent term extensions,patent office actions and expected availability and any period of regulatory exclusivity;the timing,outcome and impact of administrative,regulatory,legal or

33、 other proceedings related to our patents and other proprietary andintellectual property rights,tax audits,assessments and settlements,pricing matters,sales and promotional practices,product liability andother matters;the drivers for growing our business,including our plans and intention to commit r

34、esources relating to discovery,research anddevelopment programs and business development opportunities as well as the potential benefits and results of certain businessdevelopment transactions;our ability to finance our operations and business initiatives and obtain funding for such activities;the e

35、xpectations,development plans and anticipated timelines,including costs and timing of potential clinical trials,filings and approvalsof our products,product candidates and pipeline programs,including collaborations with third-parties,as well as the potential therapeuticscope of the development and c

36、ommercialization of our and our collaborators pipeline products;reputational or financial harm to our business arising from adverse safety events,including product liability claims or lawsuits affectingour or any of our licensors marketed products,generic or biosimilar versions of our or any of our

37、licensors marketed products or anyother products from the same class as one of our or any of our licensors products;unexpected impacts on our business operations including sales,expenses,supply chain,manufacturing,cyber-attacks or other privacy ordata security incidents,research and development cost

38、s,clinical trials and employees;the potential impact of measures being taken worldwide designed to reduce healthcare costs and limit the overall level of governmentexpenditures,including the impact of pricing actions and reduced reimbursement for our products;our manufacturing capacity,use of third-

39、party contract manufacturing organizations,plans and timing relating to changes in ourmanufacturing capabilities or activities in new or existing manufacturing facilities;lease commitments,purchase obligations and the timing and satisfaction of other contractual obligations;-iii-Table of Contents th

40、e impact of new laws,regulatory requirements,judicial decisions and accounting standards;the disruption of our business relationships with our licensors;the direct and indirect impact of the COVID-19 pandemic on our business and operations,our and our partners ability to effectively travel,as needed

41、,during the COVID-19 pandemic,and the duration and impact of COVID-19 or any of its variants that may affect,precipitate orexacerbate one or more of any of the risks and uncertainties mentioned in this section;our ability to effectively manage our growth;the disruption in the capital or credit marke

42、ts which may adversely impact our ability to obtain necessary capital or credit marketfinancing;the geopolitical tensions that exist between China and the United States may adversely affect our business,our ability to grow,and ouraccess to necessary capital or credit markets;our ability to retain ke

43、y executives and to attract,retain and motivate personnel;and other risks and uncertainties,including those listed under“Part IItem 1ARisk Factors”.These factors should not be construed as exhaustive and should be read with the other cautionary statements and other information in this AnnualReport a

44、nd our other filings with the SEC.-iv-Table of ContentsPART IItem 1.BusinessOverviewWe are an innovative,research-based,commercial stage biopharmaceutical company with a substantial presence in both Greater China and theUnited States.We are focused on developing and commercializing therapies that ad

45、dress medical conditions with unmet needs in oncology,autoimmunedisorders and infectious disease.Our aim is to become a leading global biopharmaceutical company discovering,developing and commercializingproducts to extend and improve the lives of patients worldwide.Since 2014,we have taken steps to

46、execute our strategy to become a fully-integratedglobal biopharmaceutical company with substantial research and development,business development and commercialization capabilities.To date,wehave:received approval for and commercialized two products(ZEJULA and Optune);been granted Priority Review by

47、the China National Medical Products Administration(NMPA)for two New Drug Applications(NDA),forQINLOCK and NUZYRA;expanded our pipeline to increase our product candidates under development from four in 2015 to twenty-one today in oncology,autoimmune disorders and infectious diseases,including eleven

48、programs in late-stage clinical development;partnered with established biopharmaceutical and leading healthcare companies such as GlaxoSmithKline(GSK),Novocure,argenx,Turning Point,Deciphera and Incyte Corporation,through in-licensing product candidates to position ourselves as a partner of choice f

49、orthe development and commercialization of novel therapeutics in Greater China;achieved pricing reimbursement for ZEJULA in China through its inclusion on the National Reimbursement Drug List(NRDL);built a commercial organization of approximately 600 employees;increased our research and development

50、team to approximately 450 employees;assembled a leadership team of seasoned industry veterans with extensive pharmaceutical research,development and commercializationexperience in both global and Chinese biopharmaceutical companies;advanced our in-house discovery pipeline and capabilities targeting

51、global markets;built-out our facilities in China to support our regulatory,clinical,manufacturing and commercial infrastructure in eleven locations acrossGreater China and the United States;acquired land-use rights for 50,851 square meters of land in Suzhou for the purpose of constructing and operat

52、ing a research center;and expanded our U.S.footprint by opening a 20,000-square-foot research facility in the San Francisco Bay area and a new corporate office inCambridge,Massachusetts.We are committed to our goal of becoming a leading global biopharmaceutical company focused on discovering,develop

53、ing and commercializingproducts to extend and improve the lives of patients worldwide.We intend to continue to pursue a strategy of growth and development by:(i)expandingour product candidate pipeline through global collaborations and corporate development activities;(ii)capitalizing on commercial o

54、pportunities for ourapproved products;and(iii)investing in our global pipeline by advancing our internally discovered novel therapeutics.We also plan to expand ourcollaborations with leading academic institutions in both the United States and Greater China.We believe that this strategy,supported by

55、the aboveactions we have taken and will continue to take,will bring us closer to achieving our goal of becoming a leading global biopharmaceutical company.-1-Table of ContentsOur Approved Products and Product Candidates under Priority Review by the NMPAThe following table summarizes the status of ou

56、r commercial products,as well as the status of product candidates that are under Priority Reviewby the NMPA:Product Indications Regulatory Status Commercial Rights Partner 1st line ovarian cancer2nd line ovarian cancer Launched in China,Hong Kongand Macau China,Hong Kong and Macau Newly diagnosed an

57、d recurrentglioblastoma multiforme(GBM)Launched in China,Hong Kongand Macau China,Hong Kong,Macau andTaiwan 4th line gastrointestinal stromaltumors(GIST)Priority Review in China China,Hong Kong,Macau andTaiwan Acute bacterial skin and skinstructure infection(ABSSSI)Community-acquired bacterialpneumo

58、nia(CABP)Priority Review in China China,Hong Kong,Macau andTaiwan ZEJULA(Niraparib)ZEJULA is a once-daily small-molecule poly(ADP-ribose)polymerase 1/2,or PARP 1/2,inhibitor.A PARP inhibitor blocks the ability of cancercells to repair themselves after they have been damaged by radiation and certain

59、chemotherapies.This inhibition of DNA damage repair can result inboth the inability of cancer cells to replicate themselves and in programmed cell death.In September 2016,we entered into an exclusive license agreement with Tesaro Inc.(a company later acquired by GSK)to develop andcommercialize ZEJUL

60、A in China,Hong Kong and Macau.We have the exclusive right to develop and commercialize ZEJULA in the licensedterritories for all potential indications except prostate cancer.For further details of the exclusive license,see“Overview of Our Material License andStrategic Collaboration AgreementsGSK.”Z

61、EJULA was first approved in March 2017 by the United States Food and Drug Administration(FDA)for the maintenance treatment of adultpatients with recurrent epithelial ovarian,fallopian tube or primary peritoneal cancer who exhibit a complete or partial response to platinum-basedchemotherapy.Subsequen

62、tly,in 2019,the FDA approved ZEJULA for treatment of patients with advanced ovarian,fallopian tube or primary peritonealcancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency(HRD)-positive status,and in 2020 approved it a

63、s a monotherapy first-line maintenance treatment for women with advanced ovarian cancer who are in completeor partial response to first-line platinum-based chemotherapy regardless of biomarker status.The European Medicines Agency(EMA)approved ZEJULA in November 2017 as a monotherapy for the maintena

64、nce treatment of adult patientswith platinum-sensitive relapsed high grade serous epithelial ovarian,fallopian tube or primary peritoneal cancer who are in complete response or partialresponse to platinum-based chemotherapy.Additionally,ZEJULA was approved by the EMA in October 2020 as first-line mo

65、notherapy maintenancetreatment for adult patients with advanced epithelial(FIGO Stages III and IV)high-grade ovarian,fallopian tube or primary peritoneal cancer who are incomplete or partial response following platinum-based chemotherapy,platinum-responsive advanced ovarian cancer,regardless of biom

66、arker status.As maintenance therapy,ZEJULA is for women who have had prior chemotherapy treatment,but are expected to see their cancer return.ZEJULAis intended to avoid or slow a recurrence of the cancer if it is in-2-Table of Contentsremission after prior treatment.A platinum-sensitive cancer is on

67、e that responded to initial platinum-based chemotherapy and remained in remissionpost-chemotherapy for more than six months.Market Opportunity and CompetitionWe launched ZEJULA in Hong Kong in December 2018 for adult patients with platinum-sensitive relapsed high grade serous epithelial ovariancance

68、r who are in a complete response or partial response to platinum-based chemotherapy after approval by the Hong Kong Department of Health.ZEJULA was approved and launched in Macau in June 2019.We launched ZEJULA in China in January 2020 after approval in December 2019 by theNMPA as a second-line main

69、tenance treatment for women with recurrent platinum-sensitive ovarian cancer.In September 2020,ZEJULA was approvedby the NMPA as a maintenance treatment for adult patients with advanced epithelial ovarian,fallopian tube or primary peritoneal cancer who are in acomplete or partial response to first-l

70、ine platinum-based chemotherapy.ZEJULA is the only PARP inhibitor approved by the FDA,the EMA and theNMPA for first-and second-line maintenance treatment for women with platinum-responsive advanced ovarian cancer regardless of biomarker status,such as BRCA mutations.In May 2020,ZEJULA was recommende

71、d as a monotherapy first-line maintenance treatment for women with platinum-responsive advancedovarian cancer in the Ovarian Cancer PARP Inhibitor Clinical Guidelines published by Gynecological Oncology,Chinese Medical Association.InDecember 2020,ZEJULA was included in the updated National Reimburse

72、ment Drug List or the NRDL.As of January 31,2021,ZEJULA was listed in67 commercial health insurance plans and 44 supplemental insurance plans managed by municipal governments throughout China.Enrollment into thisregional reimbursement program has improved and will improve access to ZEJULA for many p

73、atients in need across China.We intend to pursue the approval and registration of ZEJULA for treatment across multiple solid tumor types in China,Hong Kong and Macau.We are also exploring the use of ZEJULA in multiple combination and monotherapy treatment options.In February 2020,we dosed the first

74、patient inChina in an open-label,single-arm,multicenter,Phase Ib dose escalation and expansion clinical study to assess the safety and antitumor activity oftebotelimab in combination with ZEJULA for the treatment of patients with advanced or metastatic gastric adenocarcinoma or gastroesophageal junc

75、tionadenocarcinoma(collectively as gastric cancer)who failed prior treatment.The primary endpoints of the study are to assess the safety of ZEJULA incombination with tebotelimab in patients with advanced gastric cancer and to determine the recommended Phase II dose.We expect to complete patientenrol

76、lment by the end of 2021.Optune(Tumor Treating Fields)Tumor Treating Fields(TTFields)therapy is a cancer treatment that uses electric fields tuned to specific frequencies to disrupt cancer cell division.TTFields therapy is delivered through a portable medical device.The complete delivery system,call

77、ed Optune or Optune Lua,includes a portableelectric field generator,arrays,rechargeable batteries and accessories.Sterile,single-use arrays are placed directly on the skin in the region surroundingthe tumor and connected to the electric field generator to deliver therapy.Arrays are changed when hair

78、 growth or the hydrogel reduces array adhesionto the skin.The therapy is designed to be delivered continuously throughout the day and night,and efficacy is strongly correlated to time on therapy.When the device is turned on,TTFields are continuously generated within the specific region of the body c

79、overed by the arrays.Healthy tissues locatedoutside of this region remain unaffected by the therapy.In 2015,Optune was approved by the FDA for the treatment of adult patients with newly diagnosed GBM in combination with temozolomide(TMZ),a chemotherapy drug,and for adult patients with GBM following

80、confirmed recurrence after chemotherapy as monotherapy treatment.Optune isalso approved or has a CE certificate for the treatment of GBM in the European Union,Japan and certain other countries.In September 2018,we entered into an exclusive license agreement with Novocure to develop and commercialize

81、 Optune in Greater China in allhuman therapeutic and preventative uses in the field of oncology.-3-Table of ContentsFor further details of the exclusive license,see“Overview of Our Material License and Strategic Collaboration AgreementsNovocure.”We launchedOptune in Hong Kong in 2018 and in China in

82、 June 2020 after the NMPA approved Optune in May 2020 in combination with temozolomide for thetreatment of patients with newly diagnosed GBM and also as a monotherapy for the treatment of patients with recurrent GBM.Market Opportunity and CompetitionGBM,a malignant form of astrocytoma,is the most ag

83、gressive form of brain cancer.In China,GBM represents about 47%of all newly diagnosedcases of brain cancer,with an estimated annual incidence of 53,600 patients in 2019.GBM is treated mainly by surgery,radiotherapy and temozolomide.Despite these treatments,prospects for long-term survival remains po

84、or.In China,the five-year survival rate of GBM patients is less than 5%.Optune isthe first treatment approved by the NMPA for GBM in China since 2007.In August 2020,in Hong Kong,we launched Optune Lua,a portable medical device that delivers TTFields for the treatment of unresectable,locally advanced

85、 or metastatic malignant pleural mesothelioma(MPM).MPM is a type of cancer that occurs in the thin layer of tissue in the torsocovering internal organs.In May 2019,Novocure received FDA approval for use of Optune Lua as a Humanitarian Use Device in combination withchemotherapy for the first-line tre

86、atment of adult patients with unresectable,locally advanced or metastatic MPM.For details about our clinicaldevelopment of Tumor Treating Fields,see the subsection“Our Oncology PipelineTumor Treating Fields.”QINLOCK(ripretinib)QINLOCK is an orally administered kinase switch control inhibitor.It is a

87、pproved by the FDA for use in the United States to treat fourth-lineadvanced gastrointestinal stromal tumors(GIST),where significant unmet medical need exists.In June 2019,we obtained an exclusive license from Deciphera to develop and commercialize QINLOCK in Greater China for the prevention,prophyl

88、axis,treatment,cure or amelioration of any disease or medical condition in humans.For further details of the exclusive license,see“Overviewof Our Material License and Strategic Collaboration AgreementsDeciphera.”In May 2020,the FDA approved QINLOCK for adult patients withGIST who have received prior

89、 treatment with three or more kinase inhibitors,including imatinib.Market OpportunityWe are exploring ripretinib for the treatment of GIST,the most common sarcomas of the gastrointestinal tract,which present most often in thestomach or small intestine.In July 2020,the NMPA accepted the NDA submissio

90、n of QINLOCK for fourth-line advanced GIST.That same month,QINLOCK wasapproved,pursuant to the special Named Patient Program(NPP),by the Health Commission and Medical Products Administration of Hainan Provinceas the first Urgently Needed Drug that can be taken from the Boao Pilot Zone by a designate

91、d patient.Under the NPP,patients may apply for permissionto purchase a small amount of legally imported drugs that are not yet registered domestically(either inside or outside the Boao Pilot Zone)and whichaddress urgent medical needs in the Boao Pilot Zone.In August 2020,the NMPA granted Priority Re

92、view to the NDA submission for QINLOCK for the treatment of adult patients with advancedGIST who have received priority treatment with three or more kinase inhibitors.We have also received Clinical Trial Authorization(CTA)approval forthe registrational study of QINLOCK in patients with second-line G

93、IST.This study is ongoing.NUZYRA(omadacycline)NUZYRA is a broad-spectrum antibiotic in a new class of tetracycline derivatives known as aminomethylcyclines.NUZYRA is primarily beingdeveloped by our partner Paratek Pharmaceuticals,Inc.,or-4-Table of ContentsParatek,for acute bacterial skin and skin s

94、tructure infections(ABSSSI),community-acquired bacterial pneumonia(CABP)and urinary tract infections(UTI)in both the hospital and community settings.In October 2018,NUZYRA was approved by the FDA for once-daily oral or intravenousadministration for the treatment of adults with CABP and ABSSSI.Our pa

95、rtner,Paratek,launched NUZYRA in the United States in February 2019.In April 2017,we obtained an exclusive license from Paratek to develop,manufacture and commercialize NUZYRA in Greater China in allhuman therapeutic and preventive uses other than biodefense.For further details of the exclusive lice

96、nse,see“Overview of Our Material License andStrategic Collaboration AgreementsParatek.”Market OpportunityThe World Health Organization has identified the development of worldwide resistance to currently available antibacterial agents as one of thegreatest threats to human health.We believe that NUZY

97、RAs potential use in multiple settings,including the emergency room,hospital and communitycare facilities,provides a significant benefit to patients as an empiric monotherapy.In 2015,the estimated incidence of ABSSSI and CABP in China was2.8 million patients and 16.5 million patients,respectively.We

98、 completed the technology transfer for NUZYRA in November 2017 to enable us to prepare for the manufacture of both oral tablets andintravenous injections of NUZYRA.In February 2020,the NMPA accepted our NDA for NUZYRA for the treatment of CABP and ABSSSI.In May 2020,the NMPA granted PriorityReview s

99、tatus for this NDA.-5-Table of ContentsOur Pipeline of Product CandidatesThe following table summarizes the status of our significant clinical pipeline assets as of February 28,2021:Note:*Greater China trial initiated,in preparation or currently being planned;(1)Phase Ib POC China-only trial,in comb

100、ination with tebotelimab(PD-1xLAG-3);(2)MAA being preparedfor submission in China;launched in Hong Kong;(3)Phase II pilot trial;(4)Global Phase III trial;registrational bridging trial ongoing in China;(5)Global Phase II potentially pivotal trial;(6)Registrational bridging trial on-going in China;(7)

101、Global Phase II/III trial and registration path in first-line gastric&GEJ cancer;in combination with retifanlimab(PD-1)andtebotelimab(PD-1xLAG-3),with or without chemotherapy,respectively;(8)Global Phase I/IIa trial;(9)Phase I POC China-only trial,in combination with brivanib;(10)Phase I/II POCChina

102、-only trial;(11)Phase Ib dose escalation trial completed;(12)BLA filed in December 2020 with FDA;and(13)Includes Greater China,South Korea,Vietnam,Thailand,Cambodia,Laos,Malaysia,Indonesia,Philippines,Singapore,Australia,New Zealand and Japan.This Table illustrates our clinical pipeline assets,inclu

103、ding their various stages of development,which are described more fully elsewhere in this Annual Report.For completeness,please read this Table in conjunction with the remainder of this Report.Abbreviations:Greater China=China,Hong Kong,Macau,and Taiwan;I/O=immuno-oncology;MPM=malignant pleural meso

104、thelioma;NSCLC=non-small cell lung cancer;GIST=gastrointestinal stromal tumors;B-NHL=B-cell non-Hodgkin lymphoma;GEJ=gastroesophageal junction;HCC=hepatocellular carcinoma;gMG=generalized myasthenia gravis;PV=pemphigus vulgaris;CIDP=chronic inflammatory demyelinating polyneuropathy;NMPA=National Med

105、ical Products Administration;POC=proof of concept;MAA=MarketingAuthorization Application;CTA=Clinical Trial Application;BLA=Biologics License Applications.Our Oncology PipelineZEJULAZEJULA is a once-daily small-molecule poly(ADP-ribose)polymerase 1/2,or PARP 1/2,inhibitor.-6-Table of ContentsAs disc

106、ussed above,we have the exclusive right to develop and commercialize ZEJULA in our licensed territories for all potential indicationsexcept prostate cancer pursuant to an exclusive license agreement with GSK.For further details of the exclusive license,see“Overview of Our MaterialLicense and Strateg

107、ic Collaboration AgreementsGSK.”We continue to explore ZEJULA for patients with breast cancer and non-small cell lung cancer in China.In February 2020,we dosed the firstpatient in a Phase I-b proof-of-concept China-only trial,in combination with tebotelimab(PD-1xLAG-3).We are also exploring the comb

108、inationpotential of ZEJULA with immuno-oncology therapy,targeted therapy and chemotherapy in the clinically relevant indications.Tumor Treating FieldsTTFields therapy is a cancer treatment that uses electric fields tuned to specific frequencies to disrupt cancer cell division.As discussed above,we h

109、ave an exclusive license from Novocure to develop and commercialize Optune in Greater China in all human therapeuticand preventative uses in the field of oncology.For further details of the exclusive license,see“Overview of Our Material License and StrategicCollaboration AgreementsNovocure.”Novocure

110、 continues to test TTFields against a broad range of solid tumor types.We intend to enroll patients in Greater China in the various globaltrials for TTFields.In January 2020,we enrolled the first patient in a Phase II pilot clinical trial evaluating the safety and efficacy of TTFields in combination

111、 withchemotherapy as a first-line treatment in patients with gastric adenocarcinoma,a type of gastric cancer.In 2015,gastric cancer was the second mostcommon cancer and the second-leading cause of death in China,with 679,100 newly diagnosed cases and 498,000 deaths.Gastric cancer is oftendiagnosed a

112、t an advanced stage and therefore has a very poor prognosis,with a five-year survival of only 35.9%.Current treatments of pancreatic cancerinclude surgical treatment,radiotherapy,chemotherapy,interventional therapy,endoscopic retrograde cholangiopancreatography-(ERCP-)relatedtreatment and traditiona

113、l Chinese medicine(TCM)treatments.We will also be participating in the PANOVA-3 Phase III pivotal trial of TTFields for pancreatic cancer.PANOVA-3 is a global,open-label,randomized Phase III trial evaluating the efficacy of TTFields administered concomitantly with gemcitabine and nab-paclitaxel as f

114、ront-line treatmentfor patients with unresectable,locally advanced pancreatic cancer.According to the World Health Organization,pancreatic cancer was the ninth leadingcancer type in China in 2020 with an estimated 124,994 newly diagnosed cases and 121,853 deaths.The current median survival of patien

115、ts withmetastatic pancreatic cancer is four to six months,and the five-year survival rate is 7.2%,making it the malignancy with the lowest survival rate inChina.Current treatments of pancreatic cancer include surgical treatment,radiotherapy,chemotherapy,interventional therapy,ERCP-related treatmenta

116、nd TCM treatment.We will also be participating in the Phase III pivotal LUNAR trial which is intended for patients who have recently been diagnosed withprogression of NSCLC during or after platinum-based therapy.Lung cancer consists of NSCLC in approximately 85%of cases and small cell lungcancer(SCL

117、C)in approximately 15%of cases.Lung cancer has the highest total incidence of any cancer in China.According to the World HealthOrganization,the incidence of lung cancer in China in 2020 was 815,563 cases,with 714,699 deaths.In China,the five-year survival rate of lung canceris estimated to be about

118、20%.We are preparing to submit to the NMPA a Marketing Authorization Application(MAA)for Optune Lua for MPM.We are also participating in a clinical trial of TTFields that includes ovarian cancer.Ovarian cancer is one of the most common gynecologiccancers in China.Since early symptoms of ovarian canc

119、er are not specific to-7-Table of Contentsthe disease and are difficult to detect,approximately 70%of women are diagnosed with ovarian cancer when the disease is at an advanced stage,whenprognosis is poor.Despite high response rates to platinum-based chemotherapy in the front-line setting,approximat

120、ely 85%of patients will experiencedisease recurrence.QINLOCK(ripretinib)QINLOCK is an orally administered kinase switch control inhibitor.We are developing QINLOCK for the treatment of GIST.In August 2020,theNMPA granted Priority Review of the NDA for QINLOCK for the treatment of adult patients with

121、 advanced GIST who have received prior treatmentwith three or more kinase inhibitors.We have also received the CTA approval for the registrational study of QINLOCK in patients with second-lineGIST.The study is ongoing.OdronextamabOdronextamab is an investigational bispecific monoclonal antibody desi

122、gned to trigger tumor killing by linking and activating a cytotoxic T-cell(binding to CD3)to a lymphoma cell(binding to CD20).Odronextamab has demonstrated clinical activity in heavily pre-treated patients with late stagesof follicular lymphoma(FL),diffuse large B-cell lymphoma(DLBCL)and other lymph

123、omas in a Phase I trial and is currently being investigated in apotentially registrational Phase II program.In April 2020,we entered into a collaboration agreement with Regeneron Ireland Designated Activity Company,an affiliate of RegeneronPharmaceuticals,Inc.,or Regeneron,pursuant to which we obtai

124、ned the development rights and exclusive commercialization rights to odronextamab foroncology in Greater China.For further details of this collaboration,see“Overview of Our Material License and Strategic Collaboration AgreementsRegeneron.”In December 2020,Regeneron has announced that it is pausing n

125、ew enrollment of patients with B-cell non-Hodgkin lymphomas in its trialsfor odronextamab in compliance with an FDA partial clinical hold requesting that Regeneron amend the trial protocols in order to further reduce theincidence of Grade 3 cytokine release syndrome(CRS)during step-up dosing.Current

126、ly enrolled patients who are deriving clinical benefit fromodronextamab may continue treatment following re-consent.We have received CTA approval in China for and plan to join the open-label,multi-center,global,potentially registrational Phase II programevaluating the efficacy and safety of odronext

127、amab in several disease-specific cohorts,including patients with R/R FL,DLBCL,mantle cell lymphoma(MCL),marginal zone lymphoma(MZL)and other B-NHL subtypes.RepotrectinibRepotrectinib is an investigational next-generation tyrosine kinase inhibitor(TKI)designed to effectively target ROS1 and TRK A/B/C

128、 inTKI-nave-or-pretreated cancer patients.The FDA has granted orphan drug designation for the development of repotrectinib in NSCLC withadenocarcinoma histology,Breakthrough Therapy designation for the treatment of patients with ROS1-positive metastatic NSCLC who have not beentreated with a ROS1 tyr

129、osine kinase inhibitor(TKI-nave)and three Fast Track designations.In July 2020,we entered into an exclusive license agreement with Turning Point Therapeutics or Turning Point,to develop and commercializerepotrectinib in Greater China in all human therapeutic indications.For further details of the ex

130、clusive license,see“Overview of Our Material Licenseand Strategic Collaboration AgreementsTurning Point.”Turning Point is currently evaluating repotrectinib in TRIDENT-1,an ongoing Phase I/II trial of repotrectinib in patients with ROS1+advancedNSCLC and patients with NTRK+advanced solid tumors.We h

131、ave submitted a Phase II registrational CTA and we anticipate opening additional sitesfor the TRIDENT-1 Phase II registrational clinical study of repotrectinib in China.We plan to recruit patients in Greater China in the Phase IITRIDENT-1 study in the first half of 2021.-8-Table of ContentsMARGENZA(

132、margetuximab-cmkb)Margetuximab is an investigational,immune-enhancing monoclonal antibody that targets HER2-expressing tumors,including certain types ofbreast and gastroesophageal cancers.On December 16,2020,the FDA approved MARGENZA for use in the United States,in combination withchemotherapy,for t

133、he treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2regimens,at least one of which was for metastatic disease.In June 2020,the FDA granted margetuximab an orphan drug designation for the treatment ofpatients with gastric and gastroe

134、sophageal junction(GEJ)cancer.In November 2018,we entered into an exclusive license agreement,the MacroGenics Agreement,with MacroGenics,Inc.,or MacroGenics,todevelop and commercialize MARGENZA in Greater China in all human fields of use.For further details of the exclusive license,see“Overview of O

135、urMaterial License and Strategic Collaboration AgreementsMacroGenics.”We are exploring regulatory approval pathways for MARGENZA in HER2-positive breast cancer in China.In February 2020,the first patient wasdosed in our registrational bridging study of MARGENZA in combination with chemotherapy for t

136、he treatment of patients with metastatic HER2-positive breast cancer.During 2020 in China,there were approximately 416,370 newly diagnosed cases and approximately 117,175 deaths related tobreast cancer.Approximately 20-25%of all breast cancer cases are HER2-positive breast cancer.In September 2020,w

137、e enrolled the first patient in Greater China in MAHOGANY,the MacroGenics-sponsored Phase II/III global study ofmargetuximab in combination with retifanlimab,a PD-1 antibody,or tebotelimab,a PD-1 x LAG-3 bispecific DART molecule,with or withoutchemotherapy,as a potential first-line treatment of HER2

138、-positive gastric cancer.BemarituzumabBemarituzumab is a humanized monoclonal antibody(IgG1 isotype)specific to the human FGFR2b receptor that is in clinical development as atargeted therapy for gastric and GEJ cancer patients whose tumors overexpress FGFR2b.In December 2017,we entered into an exclu

139、sive license agreement with Five Prime Therapeutics,or Five Prime,to develop and commercializebemarituzumab in Greater China for the treatment or prevention of any disease or condition in humans.For further details of the exclusive license,see“Overview of Our Material License and Strategic Collabora

140、tion AgreementsFive Prime.”In March 2020,Five Prime announced the publication of results from its Phase I escalation and expansion study of bemarituzumab monotherapyin patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma.No dose-limiting toxicities were reported.We

141、 enrolled Chinese patients into Five Primes Phase II FIGHT trial to evaluate bemarituzumab plus mFOLFOX6 chemotherapy in patients withfibroblast growth factor receptor 2b-positive(FGFR2b+),non HER2 positive(non HER2+)advanced gastric and GEJ cancer.In November 2020,FivePrime reported that the full P

142、hase II data for bemarituzumab met all three efficacy endpoints and demonstrated statistically significant and clinicallymeaningful improvements in the primary endpoint of progression-free survival and secondary endpoints of overall survival and overall response rate.InJanuary 2021,Five Prime announ

143、ced its plan to launch a Phase III trial for gastric cancer.CLN-081CLN-081 is an orally available small molecule designed as a next-generation,irreversible EGFR inhibitor in development by Cullinan Pearl forthe treatment of patients with EGFR exon 20 insertion NSCLC.-9-Table of ContentsIn December 2

144、020,we entered into an exclusive license agreement with Cullinan Pearl,a subsidiary of Cullinan Management,Inc.,formerlyCullinan Oncology,LLC,for the research,development,manufacturing and commercialization of CLN-081 in Greater China in all uses in humans andanimals.For further details of the exclu

145、sive license,see“Overview of Our Material License and Strategic Collaboration AgreementsCullinan.”Cullinan Pearl is currently conducting a Phase I/IIa dose escalation and expansion trial evaluating oral,twice-daily administration of various dosesin patients with NSCLC harboring EGFR exon 20 insertio

146、n mutations that have had at least one prior treatment with platinum-based chemotherapy oranother approved standard therapy.We anticipate that we will join the Cullinan Phase I/IIa study.TPX-0022TPX-0022 is an orally bioavailable multi-targeted kinase inhibitor with a novel three-dimensional macrocy

147、clic structure that inhibits the MET,CSF1R(colony stimulating factor 1 receptor)and SRC kinases.In January 2021,we entered into an exclusive license agreement with Turning Point to develop and commercialize TPX-0022 in Greater China.For further details of the exclusive license,see“Overview of Our Ma

148、terial License and Strategic Collaboration AgreementsTurning Point.”Turning Point has enrolled patients with previously treated advanced or metastatic solid tumors,including non-small cell lung cancer,colorectalcancer,gastroesophageal junction(GEJ)or gastric cancer,and glioblastoma multiforme(GBM)in

149、 its SHIELD-1 Phase I clinical trial of TPX-0022.Weanticipate that we will join Turning Points registrational Phase II study.TebotelimabTebotelimab(previously known as MGD013)is an investigational,bispecific,tetravalent IgG4 monoclonal antibody designed to independently orcoordinately block PD-1 and

150、 LAG-3 checkpoint molecules to sustain or restore the function of exhausted T cells for the treatment of cancer.In November 2018,we entered into the MacroGenics Agreement pursuant to which we obtained an exclusive license to develop andcommercialize tebotelimab in Greater China in all human fields o

151、f use except to the extent limited by any applicable third party agreement ofMacroGenics.For further details of the exclusive license,see“Overview of Our Material License and Strategic Collaboration AgreementsMacroGenics.”We are currently enrolling patients in China in MAHOGANY,a MacroGenics-sponsor

152、ed global Phase II/III clinical trial designed to evaluatemargetuximab in combination with retifanlimab or tebotelimab,with or without chemotherapy,as a potential first-line treatment for patients withadvanced or metastatic HER2+GEJ cancer and gastric cancer.We are also working with MacroGenics to p

153、repare for our participation in an ongoingglobal Phase I basket trial of tebotelimab sponsored by MacroGenics.In April 2020,we initiated a study of tebotelimab in combination with brivanib,a compound that we in-licensed from Bristol-Myers Squibb,in aPhase I proof-of-concept China-only dose escalatio

154、n and expansion trial in patients with advanced hepatocellular carcinoma(HCC).The dose escalationphase to determine the recommended Phase II dose of tebotelimab as monotherapy and in combination with brivanib was completed.Preliminary resultsfrom this dose escalation phase were presented at the 2020

155、 Chinese Society of Clinical Oncology(CSCO)annual meeting.In China,HCC is the mostcommon type of primary liver cancer.In 2020,according to the World Health Organization,there were approximately 410,038 newly diagnosed casesand 391,152 deaths related to liver cancer in China.The five-year survival ra

156、te of HCC in China is estimated to be 12.1%.Current treatments of HCCinclude surgery,localized treatments,hepatic artery chemoembolization,radiation therapy and immunotherapy.-10-Table of ContentsIn November 2020,we enrolled the first patient in China in a Phase I proof of concept clinical trial in

157、China of tebotelimab as second-line therapyfor melanoma patients after treatment with checkpoint inhibitors.During 2020 in China,there were approximately 7,700 newly diagnosed cases andapproximately 4,100 deaths related to melanoma.RetifanlimabRetifanlimab is an investigational humanized,hinge-stabi

158、lized,IgG4k monoclonal antibody that inhibits interactions between PD-1 and itsligands,PD-L1 and PD-L2.In July 2019,we entered into an exclusive license agreement with Incyte Corporation,or Incyte,to develop and commercialize retifanlimab inGreater China in hematology and oncology.Incyte retains an

159、option to assist in the promotion of retifanlimab.For further details of the exclusivelicense,see“Overview of Our Material License and Strategic Collaboration AgreementsIncyte.”In 2017,Incyte entered into an exclusive collaboration and license agreement with MacroGenics for global rights to retifanl

160、imab.Retifanlimabmonotherapy is being evaluated in Phase II clinical trials for endometrial cancer with abnormalities in DNA repair(microsatellite instability highMSI-H)or mismatch repair phenotype(dMMR),or POLE mutations),unresectable locally advanced or metastatic Merkel cell carcinoma,andprevious

161、ly treated locally advanced or metastatic squamous cell anal carcinoma(SCAC).In October 2020,the first patient in China was dosed in the global POD1UM-101 study evaluating retifanlimab in patients with MSI-Hendometrial cancer that had progressed following platinum-based chemotherapy.In January 2021,

162、Incyte announced that the FDA accepted PriorityReview of Incytes Biologics License Application(BLA)for retifanlimab in patients with locally advance or metastatic SCAC that has progressedfollowing platinum therapy.Retifanlimab in combination with platinum-based chemotherapy is currently in Phase III

163、 for chemotherapy-nave NSCLCand unresectable locally advanced or metastatic SCAC.In the second half of 2020,we enrolled the first patient in China in the Phase III NSCLC study.ZL-2309(Simurosertib)Simurosertib is an orally active,selective and ATP-competitive cell division cycle 7(CDC7)kinase inhibi

164、tor.In December 2020,we entered intoan exclusive worldwide license agreement(excluding Japan)with Takeda Pharmaceutical Company Limited to research,develop and commercializesimurosertib in all uses in humans or animals.A Phase Ib dose escalation clinical trial of simurosertib was completed.Anti-canc

165、er activity was observed in both pre-clinical and clinical data.Simurosertib is under investigation in clinical trial NCT03261947(A Study to Evaluate the Safety,Tolerability and Activity of TAK-931 in Participantswith Metastatic Pancreatic Cancer,Metastatic Colorectal Cancer and Other Advanced Solid

166、 Tumors).ZL-1201(CD 47)ZL-1201 is a humanized,IgG4 monoclonal antibody engineered to reduce effector function that specifically targets CD-47.We mademodifications to the antibody that may reduce the incidence of hemolysis seen with other agents in the class based on preclinical data.CD47 hasrecently

167、 emerged as a novel target for macrophage immune checkpoint inhibition and a promising target for therapeutic intervention.Our pipelineincludes several assets,including a novel bi-specific T cell engager and checkpoint inhibitors that lend themselves to potential combination with aCD47-targeted ther

168、apeutic.The therapeutic potential of these ZL-1201 combinations will be assessed in both solid tumors and hematologicalmalignancies.In June 2020,we had achieved initiated dosing of a Phase I clinical trial for ZL-1201.Depending on the results of this trial,we mayproceed with a Phase II clinical tria

169、l in potentially promising indications.-11-Table of ContentsOur Autoimmune Disease PipelineEfgartigimodEfgartigimod is an investigational antibody fragment designed to reduce disease-causing immunoglobulin G(IgG)antibodies and block the IgGrecycling process.Efgartigimod binds to the neonatal Fc rece

170、ptor(FcRn),which is widely expressed throughout the body and plays a central role inrescuing IgG antibodies from degradation.In January 2021,we entered into an exclusive license agreement with argenx BV,or argenx,to develop and commercialize efgartigimod in GreaterChina.For further details of the ex

171、clusive license,see“Overview of Our Material License and Strategic Collaboration Agreementsargenx.”In February 2020,argenx announced that it received Fast Track designation for efgartigimod from the FDA for gMG.In January 2021,argenxannounced that it submitted a BLA for efgartigimod to the FDA for g

172、MG.ZL-1102(IL-17)ZL-1102 is a human nanobody targeting interleukin-17,or IL-17,with high affinity and avidity.It is a smaller molecule than other IL-17antibodies,a characteristic that may enable it to penetrate the psoriatic skin barrier,thereby avoiding significant systemic exposure.In May 2018,wee

173、ntered into an exclusive worldwide license agreement with Crescendo Biologics Limited to develop,manufacture and commercialize CB001Humabody,antibody VH domain therapeutic.Principles for treating mild to moderate psoriasis are different from those for moderate to severe psoriasis.For mild to moderat

174、e psoriasis patients,topical treatment is often the first-line choice,and dermatologists tend to avoid systemic treatment.For moderate to severe patients,the use of systemictreatments is usually inevitable.Dermatologists tend to choose IL-17 monoclonal antibodies because they have consistently demon

175、strated lesionclearance relative to older therapeutics.While therapy with IL-17 antibodies can result in safety issues due to immunosuppression and labeling currentlyrestricts their use to more severely affected patient populations,they are generally considered safer than other immunosuppression ant

176、ibodies such asanti-TNF-alpha or anti-IL-12/23 antibodies.Traditionally,it was considered that IL-17 antibodies,like other large molecules,could not penetrate theskin so it was considered unlikely for an antibody to be effective when topically applied.Like other full-size monoclonal antibodies,curre

177、nt IL-17antibodies must be administered by intravenous or subcutaneous injection.In July 2020,the first patient was dosed in the global Phase I study in Australia.ZL-1102 is being tested to determine whether it may provide anew treatment option for patients with mild to moderate psoriasis,providing

178、the efficacy of IL-17 inhibition generally used in moderate to severepsoriasis while avoiding systemic exposure through a unique topical application.Our Infectious Disease PipelineSulbactam/DurlobactamSulbactam/durlobactam,or SUL-DUR,is a combination of a beta-lactam antibiotic(sulbactam)and a beta-

179、lactamase inhibitor(durlobactam)forthe treatment of serious infections caused by Acinetobacter,including multidrug-resistant(MDR)strains.Acinetobacter is a group of bacteria commonlyfound in the environment,such as in soil and water.Acinetobacter baumannii,which accounts for most Acinetobacter infec

180、tions in humans causesinfections in the blood,the urinary tract,the lungs(pneumonia)and in wounds in other parts of the body.There are currently no effective antibioticsindicated for the treatment of MDR Acinetobacter infections.In September 2017,the FDA granted SUL-DUR Qualified Infectious Disease

181、Product,Fast Track and Priority Review status for the treatment of hospital-acquired and ventilator-acquired bacterial pneumonia and bloodstream infections dueto Acinetobacter.-12-Table of ContentsIn April 2018,we entered into an exclusive license agreement with Entasis Therapeutics Holdings Inc.,or

182、 Entasis,to develop and commercializedurlobactam in all human diagnostic,prophylactic and therapeutic uses in Greater China,Korea,Vietnam,Thailand,Cambodia,Laos,Malaysia,Indonesia,the Philippines,Singapore,Australia,New Zealand and Japan.For further details of the exclusive license,see“Overview of O

183、ur MaterialLicense and Strategic Collaboration AgreementsEntasis.”In 2019,Entasis initiated the ATTACK(Acinetobacter Treatment Trial Against Colistin)Phase III pivotal clinical trial to evaluate SUL-DUR,acombination of its broad-spectrum lactamase inhibitor,durlobactam(formerly,ETX2514),with sulbact

184、am,for the treatment of patients withpneumonia and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii.In 2016,based on a national survey of over 1,300hospitals in China,there were approximately 210,000 Acinetobacter baumannii infections.In May 2020,the first patient in Chi

185、na was enrolled in the ATTACK clinical trial.We also completed a pharmacokinetic study in the fall of 2020for SUL-DUR in China in normal healthy volunteers.Internally Discovered and Internally Developed Product CandidatesWe have assembled an integrated drug discovery and development team with extens

186、ive experience in discovery,translational medicine andpreclinical and clinical development and who have been directly involved in the discovery and development of several innovative product candidates.We identify pre-clinical assets through both internal-discovery efforts and co-development collabor

187、ation with our business partners.Through theseefforts over the past few years,we have advanced our internally-developed pipeline to include three product candidates that are currently in global PhaseI development.-13-Table of ContentsOVERVIEW OF OUR MATERIAL LICENSE AND STRATEGIC COLLABORATION AGREE

188、MENTSGSKIn September 2016,we entered into a collaboration,development and license agreement with Tesaro,Inc.,a company later acquired by GSK,pursuant to which we obtained an exclusive sublicense under certain patents and know-how of GSK(including such patents and know-how licensedfrom Merck,Sharp&Do

189、hme Corp.,a subsidiary of Merck&Co.,Inc.,and AstraZeneca UK Limited)to develop,manufacture and commercializeGSKs proprietary PARP inhibitor,niraparib,in China,Hong Kong and Macau for the diagnosis and prevention of any human diseases or conditions(other than prostate cancer).We also obtained the rig

190、ht of first negotiation to obtain a license to develop and commercialize certain follow-oncompounds of niraparib being developed by GSK in the licensed territory.Under the agreement,we agreed not to research,develop or commercializecertain competing products,and we also granted GSK the right of firs

191、t refusal to license certain immuno-oncology assets developed by us.In February2018,we entered into an amendment with GSK that eliminated GSKs option to co-market niraparib in the licensed territory.To date,we have paid GSK a$15.0 million upfront payment and accrued two milestone payments in total o

192、f$4.5 million to GSK.We may berequired to pay an additional aggregate amount of up to$36.0 million in regulatory,development and commercialization milestone payments;we arealso required to pay GSK certain tiered royalties(from mid-to high-teens on a percentage basis and subject to certain reductions

193、)based on annual netsales of ZEJULA in the licensed territory.We are not obligated to purchase ZEJULA or other licensed products from GSK.We have entered into a separate supply agreement pursuant towhich GSK manufactures and supplies ZEJULA to us for commercial use in Hong Kong.Unless terminated ear

194、lier pursuant to its terms,the agreementwith GSK will remain in effect until the expiration of the royalty term for ZEJULA,where the royalty term for ZEJULA in a region continues until thelatest of(i)the expiration of the last-to-expire valid claim within the licensed patent rights that covers the l

195、icensed product in such region;(ii)theexpiration of market or data exclusivity for such licensed product in such region;or(iii)ten(10)years after the date of the first commercial sale of suchlicensed product in such region.The agreement may be terminated for customary reasons,including upon the othe

196、r partys uncured material breach,bankruptcy,insolvency or similar event.In addition,we have the right to terminate the agreement for convenience at any time,subject to a certain noticeperiod.Turning PointTPX-0022In January 2021,we entered into a license agreement with Turning Point pursuant to which

197、 we received an exclusive license under certain patentsand know-how to develop and commercialize products containing Turning Points product candidate,TPX-0022,as an active ingredient in all humantherapeutic indications in Greater China.We may,at our election and expense,subject to specified exceptio

198、ns,participate in future global clinical studiesof the licensed products through clinical trial sites in the licensed territory.In addition,we granted Turning Point a first right to negotiate a licenseoutside the original licensed territory to a potential product candidate from one of our pipeline p

199、rograms if we file an investigational new productapplication for the product candidate.To date,we have paid to Turning Point a$25.0 million upfront payment.We may be required to pay an additional aggregate amount of up to$336.0 million in development,regulatory and sales-based milestone payments,alo

200、ng with certain tiered royalties(from mid-teen to low twenties on apercentage basis and subject to certain reductions)based on annual net sales of all licensed products in the licensed territory.We will purchase licensed products exclusively from Turning Point.Unless terminated earlier pursuant to i

201、ts terms,the license agreement willcontinue in effect until expiration of the last royalty term set forth in the agreement with respect to any licensed product in any region in the Territory,where the royalty term for a licensed product in a region continues until the latest of(i)the expiration of t

202、he last-to-expire valid claim within-14-Table of Contentsthe licensed patent rights that cover the licensed product in such region,(ii)the expiry of the regulatory exclusivity for the licensed product in suchregion;or(iii)the close of business of the day that is exactly ten(10)years after the date o

203、f the first commercial sale of the licensed product in suchregion.In addition,we may terminate the license agreement for convenience,subject to a certain notice period.Turning Point may terminate theagreement under specified circumstances if we or our affiliates or sublicensees challenge its patent

204、rights,subject to a certain cure period.Either partymay terminate the agreement for the other partys uncured material breach of the agreement,subject to a certain cure period,for the other partysbankruptcy or insolvency or if the other party or its affiliates mergers with or acquires a third party e

205、ngaged in activities with a competing product,which is not divested or discontinued within a specified period.Turning PointRepotrectinibIn July 2020,we entered into an exclusive license agreement with Turning Point pursuant to which Turning Point exclusively licensed to us therights to develop and c

206、ommercialize in Greater China products containing repotrectinib as an active ingredient in all human therapeutic indications.To date,we have paid to Turning Point a$25.0 million upfront payment.We may be required to pay an additional aggregate amount of up to$151.0 million in development,regulatory

207、and sales-based milestone payments,along with certain tiered royalties(from mid-to-high teen royalties on apercentage basis and subject to certain reductions)based on annual net sales of licensed products in the territory.Under the exclusive license agreement,we are responsible for funding all devel

208、opment and commercialization activities related to the products in our licensed territory,subject to certainexceptions pursuant to which Turning Point may be responsible for the cost.Turning Point will be responsible for funding global clinical studies of thelicensed products subject to certain exce

209、ptions pursuant to which we may bear the costs of certain studies.We will purchase licensed products exclusively from Turning Point.Unless terminated earlier pursuant to its terms,the license agreement willcontinue in effect until expiration of the last royalty term set forth in the agreement with r

210、espect to any licensed product in any region in the Territory,where the royalty term for a licensed product in a region continues until the latest of(i)the expiration of the last-to-expire valid claim within thelicensed patent rights that covers the licensed product in such region;(ii)the expiry of

211、the regulatory exclusivity for such licensed product in suchregion;or(iii)the close of business of the day that is exactly 10 years after the date of the first commercial sale of such licensed product in such region.In addition,we may terminate the agreement for convenience,subject to a certain noti

212、ce period.Turning Point may terminate the agreement underspecified circumstances if we or our affiliates or sublicensees challenge its patent rights,subject to a certain cure period.Either party may terminate theagreement for the other partys uncured material breach of the agreement,subject to a cer

213、tain cure period,for the other partys bankruptcy or insolvencyor if the other party or its affiliates merges with or acquires a third party engaged in activities with a competing product,which is not divested ordiscontinued within a specified period.argenxIn January 2021,we entered into a collaborat

214、ion and license agreement with argenx,pursuant to which we obtained an exclusive license undercertain patents and know-how of argenx to develop and commercialize products containing efgartigimod as an active ingredient in all human and animaluses for any preventative or therapeutic indications in Gr

215、eater China.Under the terms of the agreement,we will be responsible for recruiting patients inChina to argenxs global registrational trials for the development of efgartigimod.To date,we have paid argenx a$75.0 million upfront payment in the form of 568,182 newly issued ordinary shares of Zai Lab Li

216、mited and haveincurred,but not yet paid,$75.0 million in cash as a guaranteed non-creditable,non-refundable development cost-sharing payment.We expect to makethis second payment in March 2021.We may be required to pay an additional$25.0 million in development milestone payments to argenx,along withc

217、ertain tiered royalties(from mid-teen to low-twenties on a percentage basis and subject to certain reductions)based on annual net sales of licensedproducts in licensed territory.-15-Table of ContentsWe will purchase licensed products exclusively from argenx.The agreement continues in effect until,on

218、 a jurisdiction-by-jurisdiction and licensedproduct-by-licensed product basis,the date of expiration of the applicable royalty term set forth in the agreement,where the royalty term for a licensedproduct in a jurisdiction continues until the latest of(i)the expiration of the last-to-expire valid cla

219、im within the licensed patent rights that covers thelicensed product,its manufacture or use in such jurisdiction,(ii)the expiration of regulatory exclusivity in such jurisdiction for such licensed product or(iii)twelve(12)years after the date of the first commercial sale of such licensed product in

220、such jurisdiction.In addition,we may terminate the licenseagreement for convenience,subject to a certain notice period.Argenx may terminate the agreement under specified circumstances if we or our affiliatesor sublicensees challenge its patent rights,subject to a certain cure period.Either party may

221、 terminate the agreement for the other partys uncuredmaterial breach of the agreement,subject to a certain cure period,or for the other partys bankruptcy or insolvency.CullinanIn December 2020,we entered into a license agreement with Cullinan Pearl,a subsidiary of Cullinan Management,Inc.,formerly C

222、ullinanOncology,LLC,or Cullinan,pursuant to which we obtained an exclusive license under certain patents and know-how of Cullinan to develop,manufacture and commercialize products containing CLN-081 as an active ingredient in all uses in humans and animals in Greater China.To date,wepaid Cullinan an

223、 upfront payment in the amount of$20.0 million.We may be required to pay an additional aggregate amount of up to$211.0 million indevelopment,regulatory and sales-based milestone payments,along with certain tiered royalties(from high-single-digit to low-teen on a percentagebasis and subject to certai

224、n reductions)based on annual net sales of licensed products in the licensed territory.Cullinan Pearl received worldwide rightsfor CLN-081,excluding Japan,from Taiho Pharmaceutical,Co.,Ltd.in 2018.We have the sole right to manufacture the licensed products for commercialization in the licensed territ

225、ory.The agreement continues in effect untilthe expiration of the last royalty term for a licensed product in any region in the licensed territory,where the royalty term for a licensed product in ajurisdiction continues until the later of(i)the expiration of the last-to-expire valid claim within the

226、licensed patent rights that covers the licensed productin such region or(ii)the close of business of the tenth(10th)anniversary of the date of the first commercial sale of such licensed product in such region.Either party may terminate the agreement on a region-by-region basis or in its entirety upo

227、n a material breach by the other party or bankruptcy ofthe other party.We may terminate the agreement in its entirety or on a product-by-product basis at any time and for any or no reason,provided,however,that we will terminate the agreement upon prior written notice to Cullinan Pearl if we determin

228、e that we shall discontinue all development andcommercialization activities with respect to the products.Furthermore,Cullinan Pearl may terminate the agreement in its entirety,if we or our affiliatescommence a legal,administrative or other action challenging the validity,enforceability or scope of a

229、ny licensed patent or patent(other than the licensedpatent)owned or controlled by Cullinan Pearl and its affiliates.In addition,if no active development activities have been conducted by us and ouraffiliates or a permitted sublicensee within ten(10)months of the execution of the agreement and such i

230、nactivity is not caused by a serious adverse eventor serious adverse drug reaction,a force majeure event or Cullinan Pearls failure to supply sufficient quantities of clinical supply product,then we willbe deemed to have abandoned development for the product and Cullinan Pearl shall have the right t

231、o terminate the agreement upon written notice,unlesswe have cured such abandonment within sixty(60)days of such written notice.The agreement may also be terminated by mutual written agreement.Unless earlier terminated,the agreement continues in effect on a product-by-product basis until the expirati

232、on of all applicable royalty terms withrespect to all products in any region in the territory.RegeneronIn April 2020,we entered into a collaboration agreement with Regeneron Ireland Designated Activity Company,an affiliate of Regeneronpursuant to which we obtained for Greater China the oncology deve

233、lopment and exclusive commercialization rights for products containingodronextamab as the sole active ingredient.-16-Table of ContentsTo date,we have paid Regeneron a$30.0 million upfront payment.We are responsible for contributing to the global development costs ofodronextamab for certain trials.We

234、 may also be required to pay an additional aggregate amount of up to$160.0 million in regulatory and salesmilestone payments.Additionally Zai Lab will make payments to Regeneron based on net sales,such that Regeneron shares in a significant portion ofany potential profits.We will purchase odronextam

235、ab exclusively from Regeneron.The agreement continues in effect after the date of the agreement and until suchtime when we have ceased development and commercialization activities on odronextamab for six consecutive months,subject to certain exceptions.Inaddition,subject to certain conditions,we and

236、 Regeneron each may terminate the collaboration agreement for convenience,subject to a certain noticeperiod,or for violation of anti-corruption law,subject to a certain cure period.Regeneron may terminate the agreement under specified circumstances ifwe or our affiliates or subcontractors challenge

237、its patent rights,or upon a change of control of us,if Regeneron reasonably determines the acquirer of usdoes not have the resources or expertise to perform the obligations under this agreement.Either party may terminate the agreement for the other partysuncured material breach of the agreement,subj

238、ect to a certain cure period,or for the other partys bankruptcy or insolvency.IncyteIn July 2019,we entered into a collaboration and license agreement with Incyte,pursuant to which we obtained an exclusive license under certainpatents and know-how of Incyte,to develop and commercialize products cont

239、aining retifanlimab(INCMGA012)as an active ingredient in the treatment,palliation,diagnosis or prevention of diseases in the fields of hematology or oncology in humans in Greater China.To date,we have paid Incyte an upfront license fee in the amount of$17.5 million and have not paid Incyte any miles

240、tone payment.We may berequired to pay an additional aggregate amount of up to$60.0 million in development,regulatory and commercial milestone payments,along withcertain tiered royalties(from low-to high-twenties on a percentage basis and subject to certain reductions)based on annual net sales of lic

241、ensed productsin licensed territory.We will purchase licensed products exclusively from Incyte.The agreement continues,on a region-by-region and licensed product-by-licensedproduct basis,in effect until the expiration of the applicable royalty term for such licensed product and such region as specif

242、ied in the agreement,wherethe royalty term for a licensed product in a region continues until the latest of(i)the expiration of the last-to-expire valid claim within the licensedpatents rights that covers the composition of matter,formulations or a method of treatment or use of such licensed product

243、 in such region,(ii)theexpiration of regulatory exclusivity for such licensed product in such region or(iii)twelve(12)years from the first commercial sale of such licensedproduct in such region.In addition,each party may terminate the agreement upon the material breach of the agreement by the other

244、party,subject to acertain cure period,or for the other partys bankruptcy or insolvency.We may terminate the agreement for convenience,subject to a certain noticeperiod,and Incyte may terminate the agreement under specified circumstances if we or our affiliates or sublicensees challenge its patent ri

245、ghts,subjectto a certain cure period,or due to our certain development or commercialization diligence failures(subject to the dispute resolution mechanisms ifdisputes arise with respect to such failures).DecipheraIn June 2019,we entered into a license agreement with Deciphera,pursuant to which we ob

246、tained an exclusive license under certain patents andknow-how of Deciphera to develop and commercialize products containing ripretinib in the field of the prevention,prophylaxis,treatment,cure oramelioration of any disease or medical condition in humans in Greater China.To date,we have paid Decipher

247、a an upfront payment in the amount of$20.0 million and two milestone payments in an aggregate amount of$7.0 million.We may be required to pay an additional aggregate amount of up to$178.0 million in additional development,regulatory and-17-Table of Contentscommercial milestone payments,along with ce

248、rtain tiered royalties(from low-to high-teens on a percentage basis and subject to certain reductions)based on annual net sales of the licensed products in the licensed territory.We will purchase the licensed products exclusively from Deciphera.The agreement continues,on a region-by-region and licen

249、sedproduct-by-licensed product basis,in effect until the expiration of and payment by us of all of our royalty payment obligations applicable to suchlicensed product and such region,where the royalty term for a licensed product in a region continues until the latest of(i)the abandonment,expiry orfin

250、al determination of invalidity of the last valid claim within the licensed patents rights that covers the composition of matter,formulations or a methodof making or use of such licensed product in such region,(ii)the expiration of regulatory exclusivity for such licensed product in such region or(ii

251、i)theclose of business of the day that is exactly ten(10)years after the date of the first commercial sale of such licensed product in such region.Subject to theterms of the agreement,we may terminate the agreement for convenience by providing written notice to Deciphera,which termination will be ef

252、fectivefollowing a prescribed notice period.In addition,Deciphera may terminate the agreement under specified circumstances if we or certain other partieschallenge Decipheras patent rights,or if we or our affiliates do not conduct certain development activities with respect to one or more licensed p

253、roductsfor a specified period of time,subject to specified exceptions.Either party may terminate the agreement for the other partys uncured material breach ofa material term of the agreement,with a customary notice and cure period,or insolvency.After termination(but not natural expiration),Deciphera

254、 isentitled to retain a worldwide and perpetual license from us to exploit the licensed products.On a region-by-region and a licensed product-by-licensedproduct basis,upon the natural expiration of the agreement as described above,the licenses granted by Deciphera to us under the agreement in suchre

255、gion with respect to the licensed product become fully paid-up,perpetual,and irrevocable.In January 2020,we entered into an amendment withDeciphera to clarify several operational matters.MacroGenicsIn November 2018,we entered into a collaboration agreement with MacroGenics,pursuant to which we obtai

256、ned an exclusive license undercertain patents and know-how of MacroGenics to develop and commercialize margetuximab,tebotelimab and an undisclosed multi-specific TRIDENTmolecule in pre-clinical development,each as an active ingredient in all human fields of use,except to the extent limited by any ap

257、plicable third partyagreement of MacroGenics in Greater China.To date,we have paid MacroGenics an upfront payment in the amount of$25.0 million and two milestonepayments in total of$4.0 million.We may also be required to pay certain additional development and regulatory-based milestone payments of u

258、p to anaggregate of$136.0 million,along with certain tiered royalties(from mid-teens to twenty for margetuximab,mid-teens for tebotelimab,and low-teensfor the TRIDENT molecule,on a percentage basis and subject to certain reductions)based on annual net sales of licensed products in licensed territory

259、.We will purchase licensed products exclusively from MacroGenics.The collaboration agreement continues in effect until the expiration of the lastroyalty term under the collaboration agreement,where the royalty term for a licensed product in a region continues until the latest of(i)the expiration oft

260、he last-to-expire valid claim within licensed patent rights covering the composition,manufacture,use,sale or importation of such licensed products insuch region,(ii)the expiration of data exclusivity for such licensed product in such region or(iii)the twelfth(12th)anniversary of the first commercial

261、sale of such licensed product in such region.In addition,either party may terminate the collaboration agreement upon the material breach of thecollaboration agreement by the other party,subject to certain cure periods.At any time after November 29,2020,we may terminate the collaborationagreement for

262、 convenience,subject to a certain notice period.MacroGenics may terminate the collaboration agreement in its entirety or on a licensedproduct-by-licensed product or region by region basis with a certain notice period if one or more major safety issues have occurred with respect to suchlicensed produ

263、ct prior to the first commercial sale of such licensed product in the territory and MacroGenics has discontinued the global development,manufacturing and commercialization activities with respect to such licensed product and publicly announced it.-18-Table of ContentsNovocureIn September 2018,we ent

264、ered into a license and collaboration agreement with Novocure,pursuant to which we obtained an exclusive licenseunder certain patents and know-how of Novocure to develop and commercialize Tumor Treating Fields products in all human therapeutic andpreventative uses in the field of oncology in Greater

265、 China.To date,we have paid Novocure an upfront payment in the amount of$15.0 million and twomilestone payments in an aggregate amount of$10.0 million.We may be required to pay an additional aggregate amount of$68.0 million indevelopment,regulatory and commercial milestone payments,along with certai

266、n tiered royalties(from low-to mid-teens on a percentage basis andsubject to certain reductions)based on annual net sales of the licensed products in licensed territory.We will purchase licensed products exclusively from Novocure.The agreement continues,on a region-by-region and licensed product-by-

267、licensedproduct basis,in effect until the expiration of the last royalty term and payment by us of all of our royalty payment obligations applicable to suchlicensed product and such region,where the royalty term for a licensed product in a region continues until the latest of(i)the expiration of the

268、last-to-expire valid claim within licensed patent rights covering such licensed products(including composition,method of use or making)in such region,(ii)the expiration of regulatory exclusivity of such licensed product and(iii)the tenth(10th)anniversary of the first commercial sale of such licensed

269、product in such region.In addition,either party may terminate the agreement upon the material breach of the agreement by the other party,subject to acertain cure period,or for the other partys bankruptcy or insolvency.We may terminate the agreement for convenience,subject to a certain noticeperiod,a

270、nd Novocure may terminate the agreement under specified circumstances if we or our affiliates or sublicensees challenge its patent rights or dueto our certain development or commercialization diligence failures,subject to a certain cure period and dispute resolution mechanisms if disputes arisewith

271、respect to such failures.EntasisIn April 2018,we entered into a license and collaboration agreement with Entasis,pursuant to which we obtained an exclusive license undercertain patents and know-how of Entasis to develop and commercialize Entasiss proprietary compounds,durlobactam with sulbactam(the

272、combination,SUL-DUR)with the possibility of developing and commercializing a combination of such compounds with imipenem in all human diagnostic,prophylactic and therapeutic uses in Greater China,Korea,Vietnam,Thailand,Cambodia,Laos,Malaysia,Indonesia,the Philippines,Singapore,Australia,New Zealand

273、and Japan.Our rights to develop and commercialize the licensed products are limited to the lead product(SUL-DUR)until suchlead product receives initial FDA approval in the United States.Pursuant to the terms of the agreement,we are responsible for(i)developing and commercializing the licensed produc

274、ts in the territory under amutually agreed development plan;and(ii)providing Entasis(or its CRO)with clinical and financial support in the territory for the global pivotal PhaseIII ATTACK clinical trial of SUL-DUR as set forth in mutually agreed development plans.To date,we have made an upfront paym

275、ent of$5.0 million and two development milestone payments in total of$7.0 million to Entasis.Additionally,we may be required to pay Entasis an additional aggregate amount of up to$91.6 million in development and commercial milestonepayments,along with certain tiered royalty payments(from high single

276、 digits to low-teens on a percentage basis and subject to certain reductions)basedon annual net sales of licensed products in the licensed territory.We are also responsible for a portion of the costs of the global pivotal Phase IIIATTACK clinical trial of SUL-DUR outside of the licensed territory.We

277、 will purchase the licensed products exclusively from Entasis.The agreement will expire on a country-by-country basis upon the expiration ofthe royalty term and payment by us of our payment obligations applicable to such country,where the royalty term for a licensed product in a countrycontinues unt

278、il the latest of(i)the tenth(10th)anniversary of the first commercial sale of such licensed product in such country,(ii)the-19-Table of Contentsexpiration or abandonment of the last-to-expire valid claim within certain Entasis patents covering such licensed product in such country,and(iii)theexpirat

279、ion of regulatory exclusivity with respect to such licensed product in such country.We may terminate the agreement upon written notice toEntasis at any time and for any reason.Either party may terminate the agreement if the other party is in material breach after a permitted cure period,orwith immed

280、iate effect upon the occurrence of specified events of insolvency.Further,Entasis can terminate the agreement if we cease to commercializethe licensed products or challenge any of the patents we licensed.If we have the right to terminate the agreement due to Entasiss uncured materialbreach,we may el

281、ect to continue the agreement and Entasis would be obligated to pay us a premium on the amount of damages arising from suchbreach.In the event of any termination of the agreement,we will assign or grant a right of reference to any regulatory documentation related to thelicensed products to Entasis,a

282、ll rights and licenses to us will terminate and we will grant Entasis a license under our technology to make andcommercialize licensed products in the territory.Five PrimeIn December 2017,we entered into a license and collaboration agreement with Five Prime,pursuant to which we obtained an exclusive

283、 licenseunder certain patents and know-how of Five Prime to develop and commercialize products containing Five Primes proprietary afucosylated FGFR2bantibody known as bemarituzumab(FPA144)as an active ingredient in the treatment or prevention of any disease or condition in humans in GreaterChina.Pur

284、suant to the terms of the agreement,we are responsible for(i)developing and commercializing licensed products under a territory developmentplan;and(ii)performing certain development activities to support Five Primes global development and registration of licensed products,including FivePrimes global

285、 Phase III registrational trial of bemarituzumab(FPA144)in combination with FOLFOX in front-line gastric and gastroesophageal cancer,or the bemarituzumab FPA144-004 Study,in the licensed territory under a global development plan.To date,we have made an upfront payment of$5.0 million and a milestone

286、payment of$2.0 million to Five Prime.Additionally,we may berequired to pay an additional aggregate amount of up to$37.0 million to Five Prime in development and regulatory milestone payments,along withcertain tiered royalties(from high teens or low twenties depending on the number of patients we enr

287、oll in the bemarituzumab FPA144-004 study,andsubject to certain reductions)based on annual net sales of licensed product in the licensed territory.Pursuant to the terms of the agreement,provided that we enroll and treat a specified number of patients in the bemarituzumab FPA144-004 studyin China,we

288、are eligible to receive a low single-digit percentage quarterly royalty,on a licensed product-by-licensed product basis on net sales of alllicensed product outside the licensed territory until the tenth(10th)anniversary of the first commercial sale of each such licensed product outside thelicensed t

289、erritory.We will purchase licensed products exclusively from Five Prime.The agreement will expire on a region-by-region basis upon the expiration of theroyalty term and payment by us of all of our payment obligations with respect to each licensed product and region under the agreement,where theroyal

290、ty term for a licensed product in a region continues until the latest of(i)the eleventh(11th)anniversary of the first commercial sale of such licensedproduct in such region,(ii)the expiration of the last valid claim within the Five Prime patents covering such licensed product in such region,and(iii)

291、theexpiration of regulatory exclusivity with respect to such licensed product in such region.In addition,we may terminate the agreement in its entirety atany time,subject to a certain notice period.Either party may terminate the agreement in its entirety with written notice for the other partys mate

292、rialbreach,subject to a certain cure period,or for the other partys bankruptcy or insolvency.Five Prime may terminate the agreement in its entirety withwritten notice for the material breach of our diligence obligations with respect to development and obtaining marketing approval in China,and mayter

293、minate the agreement on a region-by-region basis for the breach of our diligence obligations with respect to-20-Table of Contentstimely initiation of commercialization of a licensed product in a region following the marketing approval of such licensed product.Five Prime may alsoterminate the agreeme

294、nt in its entirety if we or one of our affiliates or sublicensees commences a legal action challenging the validity,enforceability orscope of any of Five Primes patents.ParatekIn April 2017,we entered into a license and collaboration agreement with Paratek Bermuda Ltd.,a subsidiary of Paratek,pursua

295、nt to which weobtained both an exclusive license under certain patents and know-how of Paratek Bermuda Ltd.and an exclusive sub-license under certain intellectualproperty that Paratek Bermuda Ltd.licensed from Tufts University to develop,manufacture and commercialize products containing omadacycline

296、(ZL-2401)as an active ingredient in Greater China in the field of all human therapeutic and preventative uses other than biodefense.Under certaincircumstances,our exclusive sub-license to certain intellectual property Paratek Bermuda Ltd.licensed from Tufts University may be converted to anon-exclus

297、ive license if Paratek Bermuda Ltd.s exclusive license from Tufts University is converted to a non-exclusive license under the TuftsAgreement.We also obtained the right of first negotiation to be Paratek Bermuda Ltd.s partner to develop certain derivatives or modifications ofomadacycline in our lice

298、nsed territory.Paratek Bermuda Ltd.retains the right to manufacture the licensed product in our licensed territory to supportdevelopment and commercialization of the same outside our licensed territory.We also granted to Paratek Bermuda Ltd.a non-exclusive license tocertain of our intellectual prope

299、rty.Under the agreement,we agreed not to commercialize certain competing products in our licensed territory.To date,we have made an upfront payment of$7.5 million and two milestone payments in an aggregate amount of$8.0 million to ParatekBermuda Ltd.We may be required to pay an additional aggregate

300、amount of up to$46.5 million in milestone payments,along with certain tieredroyalties(from low-to mid-teens on a percentage basis and subject to certain reductions)based on annual net sales of licensed products in licensedterritory.We have the right to manufacture the licensed products for commercia

301、lization in the licensed territory.The agreement with Paratek Bermuda Ltd.will remain in effect until,on a region-by-region basis,the expiration of the royalty term and payment by us of all of our royalty payment obligations insuch region,where the royalty term for a licensed product in a region con

302、tinues until the later of(i)the abandonment,expiration or invalidation of thelast-to-expire valid claim within the licensed patents covering the licensed product or(ii)the close of business of the eleventh(11th)anniversary of thefirst commercial sale of the licensed product in such region.In additio

303、n,either party may terminate this agreement for the other partys uncured materialbreach,subject to a certain cure period,or for the other partys bankruptcy or insolvency.We have the right to terminate the agreement for convenienceat any time,subject to a certain notice period.Paratek Bermuda Ltd.has

304、 the right to terminate the agreement if we or our affiliates or sublicenseeschallenge its patents.Upon termination of the agreement,our license of certain intellectual property to Paratek Bermuda Ltd.will continue for ParatekBermuda Ltd.to develop,manufacture and commercialize licensed products wor

305、ldwide.Bristol-Myers Squibb(BMS)In March 2015,we entered into a license agreement with BMS,pursuant to which we obtained an exclusive license under certain patents andknow-how of BMS to develop,manufacture and commercialize products containing BMSs proprietary multi-targeted kinase inhibitor,brivani

306、b inChina,Hong Kong and Macau in the field of diagnosis,prevention,treatment or control of oncology indications with the exclusive right to expand ourlicensed territory to include Taiwan and Korea under certain conditions.BMS retains the non-exclusive right to use the licensed compound to conductint

307、ernal research and the exclusive right to use the licensed compound as an intermediate or starting material to manufacture compounds that are not thelicensed compound.Under the agreement,we agreed not to develop and commercialize certain competing products for specified time periods.-21-Table of Con

308、tentsWe are obligated to use commercially reasonable efforts to develop and commercialize the licensed products in our licensed field and licensedterritory.BMS has the option to elect to co-promote the licensed products in our licensed territory.If BMS exercises its co-promotion option,BMS willpay u

309、s an option exercise fee and we will share equally with BMS the operating profits and losses of the licensed products in our licensed territory.IfBMS does not exercise its co-promotion option,we may be required to pay BMS milestone payments for the achievement of certain development andsales milesto

310、ne events of up to an aggregate of$114.5 million,and also certain tiered royalties(from mid-to high-teens on a percentage basis and subjectto certain reductions)based on annual net sales of the licensed products in our licensed territory.We also have the right to opt-out of the commercialization of

311、the licensed products in our licensed territory under certain conditions.If we elect toopt-out,BMS will have the right to commercialize the licensed products in our licensed territory and will pay us royalties on the net sales of the licensedproducts in our licensed territory.We have the right to ma

312、nufacture the licensed products for commercialization in the licensed territory.The agreement with BMS will remain ineffect until such time when there are no outstanding payment obligations for a period of twelve(12)consecutive months,where the royalty term for alicensed product in a region continue

313、s until the later of the expiration of the last-to-expire licensed patent that contains a valid claim covering thelicensed product,the expiration of any market or data exclusivity for the licensed product,or the twelfth(12th)anniversary of the first commercial saleof the licensed product,in each cas

314、e on a product-by-product and region-by-region basis.In addition,either party may terminate this agreement for theother partys uncured material breach,subject to a certain cure period,for safety reasons or failure of the development of the licensed products.We havethe right to terminate the agreemen

315、t for convenience upon a certain notice period.BMS may also terminate the agreement for our bankruptcy orinsolvency.INTELLECTUAL PROPERTYOur commercial success depends in part on our ability to obtain and maintain proprietary or intellectual property protection for our productcandidates and our core

316、 technologies and other know-how to operate without infringing,misappropriating or otherwise violating the proprietary rights ofothers and to prevent others from infringing,misappropriating or otherwise violating our proprietary or intellectual property rights.We expect that wewill seek to protect o

317、ur proprietary and intellectual property position by,among other methods,licensing or filing our own U.S.,international andforeign patent applications related to our proprietary technology,inventions and improvements that are important to the development andimplementation of our business.We also rel

318、y on trade secrets,know-how and continuing technological innovation to develop and maintain ourproprietary and intellectual property position,which we generally seek to protect through contractual obligations with third parties.PatentsPatents,patent applications and other intellectual property right

319、s are important in the sector in which we operate.We consider on a case-by-casebasis filing patent applications with a view to protecting certain innovative products,processes,and methods of treatment.We may also license oracquire rights to patents,patent applications or other intellectual property

320、rights owned by third parties,academic partners or commercial companieswhich are of interest to us.For the internally developed product candidates,we identify patents through both self-development effort and joint-development through collaboration with business partners such as academic institutions

321、.As with other biotechnology and pharmaceutical companies,our ability to maintain and solidify our proprietary and intellectual property positionfor our drug candidates and technologies will depend on our success in obtaining effective patent claims and enforcing those claims if granted.However,our

322、pending patent-22-Table of Contentsapplications,and any patent applications that we may in the future file or license from third parties may not result in the issuance of patents.We alsocannot predict the breadth of claims that may be allowed or enforced in our patents.Any issued patents that we may

323、 receive or license in the future maybe challenged,invalidated or circumvented.For example,we cannot be certain of the priority of our patents and patent applications over third-partypatents and patent applications.In addition,because of the extensive time required for clinical development and regul

324、atory review of a productcandidate we may develop,it is possible that,before any of our product candidates can be commercialized,any related patent may expire or remain inforce for only a short period following commercialization,thereby limiting protection such patent would afford the respective pro

325、duct and anycompetitive advantage such patent may provide.For more information regarding the risks related to our intellectual property,please see“Risk FactorsRisks Related to Intellectual Property.”The term of a patent depends upon the laws of the country in which it is issued.In most jurisdictions

326、 that we principally operate in,a patent termis 20 years from the earliest filing date of a non-provisional patent application.Under current China Patent Law,the term of patent protection starts fromthe date of application.Patents relating to inventions are effective for twenty years,and utility mod

327、els and designs are effective for ten years from thedate of application.The Fourth Amendment to the China Patent Law,expected to come into effect on June 1,2021,will increase the term of patentsrelating to designs to fifteen years from the date of application.The laws of each jurisdiction vary,and p

328、atent term adjustment or patent term extension may not be available in any or all jurisdictions in whichwe own or license patents.The following describes representative patents and/or pending applications related to our product candidates.ZEJULAAs of December 31,2020,we exclusively licensed two issu

329、ed patents in China directed to ZEJULAs free base compound,and salts thereof,andanalog of ZEJULA.These issued patents are projected to expire in 2027 and 2028.We also exclusively licensed one pending patent application in Chinadirected to the 4-methylbenzenesulfonate monohydrate salt of the compound

330、,the API of ZEJULA.If this patent application issues as a patent,suchpatent will be projected to expire in 2029.We also exclusively licensed one pending patent application in China directed to methods of treating ovariancancer.If this patent application issues as a patent,such patent will be project

331、ed to expire in 2037.Additionally,we have filed an application in Chinaand a PCT application that covers intermediate synthesis process.The claims in the Chinese application have been allowed,and the PCT application hasentered into the United States,the European Union,Israel,Japan,Korea and India.We

332、 own this PRC application and the PCT application.Tumor Treating FieldsAs of December 31,2020,we licensed eight issued patents in China and one issued patent in Hong Kong that relate to Tumor Treating Fields.Additional patent applications that relate to Tumor Treating Fields are pending,including fi

333、ve in China and in Hong Kong.We are pursuing patent rightsto protect our rights in these technologies and have continued our efforts to secure patent rights in China for our devices and technologies for applyingelectric fields to a patient for treating a disease or condition,especially diseases that promote tumor growth.QINLOCKAs of December 31,2020,we exclusively licensed one issued patent and tw