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1、F-1 1 formf-1.htm As filed with the U.S.Securities and Exchange Commission on January 3,2025.Registration No.UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington,D.C.20549 FORM F-1 REGISTRATION STATEMENTUNDERTHE SECURITIES ACT OF 1933 EVERFRONT BIOTECH HOLDING COMPANY LIMITED(Exact name of regi

2、strant as specified in its charter)British Virgin Islands 2834 Not Applicable(State or other jurisdiction ofincorporation or organization)(Primary Standard IndustrialClassification Code Number)(I.R.S.EmployerIdentification Number)10F-1,No.130,Songshan Rd.,Xinyi Dist.,Taipei City 110Taiwan+886-2-2756

3、-3796(Address,including zip code,and telephone number,including area code,of registrants principal executive offices)Cogency Global Inc.122 East 42nd Street,18th FloorNew York,NY 10168(212)947-7200(Name,address,including zip code,and telephone number,including area code,of agent for service)With a C

4、opy to:Keith BillottiF.Holt GoddardSeward&Kissel LLPOne Battery Park PlazaNew York,NY 10004Tel:(212)574-1200 Richard I.AnslowCharles PhillipsEllenoff Grossman&Schole LLP1345 Avenue of the AmericasNew York,NY 10105Tel:(212)370-1300 Approximate date of commencement of proposed sale to the public:Promp

5、tly after the effective date of thisregistration statement.If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule415 under the Securities Act of 1933 check the following box:If this Form is filed to register additional securities fo

6、r an offering pursuant to Rule 462(b)under the Securities Act,pleasecheck the following box and list the Securities Act registration statement number of the earlier effective registration statement forthe same offering.If this Form is a post-effective amendment filed pursuant to Rule 462(c)under the

7、 Securities Act,check the following boxand list the Securities Act registration statement number of the earlier effective registration statement for the same offering.If this Form is a post-effective amendment filed pursuant to Rule 462(d)under the Securities Act,check the following boxand list the

8、Securities Act registration statement number of the earlier effective registration statement for the same offering.Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Actof 1933.Emerging growth company If an emerging growth company tha

9、t prepares its financial statements in accordance with U.S.GAAP,indicate by checkmark if the registrant has elected not to use the extended transition period for complying with any new or revised financialaccounting standards provided pursuant to Section 7(a)(2)(B)of the Securities Act The Registran

10、t hereby amends this registration statement on such date or dates as may be necessary to delay itseffective date until the Registrant shall file a further amendment which specifically states that this registration statementshall thereafter become effective in accordance with Section 8(a)of the Secur

11、ities Act of 1933,as amended,or until theregistration statement shall become effective on such date as the U.S.Securities and Exchange Commission,acting pursuantto such Section 8(a),may determine.The information in this preliminary prospectus is not complete and may be changed.We may not sell the se

12、curities until theregistration statement filed with the Securities and Exchange Commission is effective.This preliminary prospectus is not anoffer to sell these securities and we are not soliciting any offer to buy these securities in any jurisdiction where such offer orsale is not permitted.Prelimi

13、nary ProspectusSUBJECT TO COMPLETION,DATED ,2025 Ordinary Shares EVERFRONT BIOTECH HOLDING COMPANY LIMITED This is an initial public offering of ordinary shares of Everfront Biotech Holding Company Limited(the“Company”or“Everfront Holding”,and when referring to the consolidated company including the

14、 Companys subsidiaries,“we”,“us”and“our”),par value$0.01 per share(“Ordinary Shares”).We estimate that the initial public offering price will be between$and$per Ordinary Share.We have reserved the symbol“EFB”for the purpose of listing our Ordinary Shares on the Nasdaq Capital Market(“Nasdaq”).This o

15、ffering is contingent upon the final approval from Nasdaq for the listing of our Ordinary Shares.We will notconsummate this offering if Nasdaq denies our listing application.As such,this offering may not close and our Ordinary Sharesmay not be approved for trading on Nasdaq.Investing in our Ordinary

16、 Shares involves a high degree of risk,including the risk of losing your entire investment.See“Risk Factors”beginning on page 7 of this prospectus to read about factors you should consider before buyingOrdinary Shares.Upon the completion of this offering,we will have Ordinary Shares issued and outst

17、anding.Each Ordinary Share isentitled to one vote.As of the date hereof(after giving effect to this offering),Mr.Ho-Ching Chen holds beneficial ownership of%ofour outstanding Ordinary Shares pursuant to agreements in which certain of our shareholders have given Mr.Chen voting controlover their share

18、s,including in connection with the election of our directors.This means we meet the definition of a“controlledcompany”under the corporate governance standards of Nasdaq and thereby qualify for exemptions from certain Nasdaq corporategovernance requirements.We currently expect to rely on certain of t

19、hese exemptions and may in the future elect to rely on any orall of these exemptions for so long as we remain a“controlled company.”See“ManagementCorporate GovernanceControlledCompany Exemptions”.Everfront Holding is a holding company incorporated in the British Virgin Islands(“BVI”)that conducts it

20、s operationsthrough its 99.96%owned subsidiary,Everfront Biotech Inc.(“Everfront Biotech”),in Taiwan.This is an offering of the OrdinaryShares of Everfront Holding and not equity securities of Everfront Biotech.You may never directly hold any equity interest inEverfront Holdings operating entity.We

21、are an“emerging growth company”as defined under the federal securities laws and will be subject to reduced publiccompany reporting requirements.See“Risk Factors”and“Prospectus Summary Implications of our Being an Emerging GrowthCompany”.Neither the Securities and Exchange Commission nor any state se

22、curities commission nor any other regulatorybody has approved or disapproved of these securities or determined if this prospectus is truthful or complete.Anyrepresentation to the contrary is a criminal offense.Per Ordinary Share Total Initial public offering price(1)$Underwriting discounts and commi

23、ssions(2)$Proceeds to us,before expenses(3)$(1)Assumes an initial public offering price of$per Ordinary Share,which is the midpoint of the range set forth on thecover page of this prospectus.For more information,see“Underwriting.”(2)We have agreed to reimburse the underwriters for certain expenses.F

24、or more information,see“Underwriting.”(3)We expect our cash expenses for this offering(including cash expenses payable to our underwriters for the underwriters out-of-pocket expenses)will not exceed$,exclusive of the underwriters discounts.This offering is being conducted on a firm commitment basis.

25、The underwriters are obligated to purchase all of theOrdinary Shares if they purchase any Ordinary Shares.We have granted the underwriters an option for a period of up to 45 days to purchase up to an additional Ordinary Shares from us at the initial public offering price,less the underwriting discou

26、nts and commissions.The underwriters expect to deliver the Ordinary Shares to purchasers in the offering on or about ,2025.We may amend or supplement this prospectus from time to time by filing amendments or supplements as required.Youshould read this entire prospectus and any amendments or suppleme

27、nts carefully before you make your investment decision.Joint Book-Runners Roth Capital Partners The Benchmark Company Prospectus dated ,2025 TABLE OF CONTENTS PagePROSPECTUS SUMMARY1RISK FACTORS7DISCLOSURE REGARDING FORWARD-LOOKING STATEMENTS28ENFORCEABILITY OF CIVIL LIABILITY30USE OF PROCEEDS32DETE

28、RMINATION OF OFFERING PRICE33DIVIDEND POLICY34CAPITALIZATION35DILUTION36CORPORATE HISTORY AND STRUCTURE37MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OFOPERATIONS38OUR BUSINESS52REGULATIONS72MANAGEMENT83COMPENSATION93PRINCIPAL SHAREHOLDERS95RELATED PARTY TRANSACTIONS96DESCR

29、IPTION OF SHARE CAPITAL98SHARES ELIGIBLE FOR FUTURE SALE108TAXATION110UNDERWRITING118LEGAL MATTERS123EXPERTS123INTERESTS OF NAMED EXPERTS AND COUNSEL123DISCLOSURE OF COMMISSION POSITION ON INDEMNIFICATION FOR SECURITIES ACT LIABILITIES123WHERE YOU CAN FIND MORE INFORMATION123INDEX TO FINANCIAL STATE

30、MENTSF-1 We and the underwriters have not authorized any person to give you any supplemental information or to make anyrepresentations on our behalf.You should not assume that the information contained in this prospectus or any prospectussupplement are accurate as of any date other than their respec

31、tive dates,regardless of the time of delivery of this prospectus or ofany sale of the Ordinary Shares.This prospectus is an offer to sell only the Ordinary Shares offered hereby,but only undercircumstances and in jurisdictions where it is lawful to do so.We are not making an offer to sell these secu

32、rities in any jurisdictionwhere the offer or sale is not permitted or where the person making the offer or sale is not qualified to do so or to any person towhom it is not permitted to make such offer or sale.The information in this registration statement is not complete and is subject tochange.No p

33、erson should rely on the information contained in this document for any purpose other than participating in ourproposed offering,and only the prospectus dated hereof,is authorized by us to be used in connection with our proposed offering.The preliminary prospectus will only be distributed by us and

34、no other person has been authorized by us to use this document tooffer or sell any of our securities.Until ,2025(the 25th day after the date of this prospectus),all dealers that effect transactions in thesesecurities,whether or not participating in this offering,may be required to deliver a prospect

35、us.This is in addition to thedealers obligation to deliver a prospectus when acting as underwriters and with respect to their unsold allotments orsubscriptions.ii COMMONLY USED DEFINED TERMS Unless otherwise indicated or the context requires otherwise,references in this prospectus to:“we”,or“us”in t

36、his prospectus are to Everfront Biotech Holding Company Limited,a British Virgin Islandscompany and its subsidiary,Everfront Biotech Inc.,a company incorporated under the laws of Taiwan,unless thecontext otherwise indicates;“BVI”are to the“British Virgin Islands”;“BVI Act”are to the BVI Business Com

37、panies Act(Law Revision 2020)(as amended);the“Company”or“Everfront Holding”are to Everfront Biotech Holding Company Limited,a BVI company;“Everfront Biotech”are to Everfront Biotech Inc.,a company incorporated under the laws of Taiwan,with limitedliability;“$,”“dollars,”“US$”or“U.S.dollars”are to th

38、e legal currency of the United States;“NTD”are to the legal currency of R.O.C.;“U.S.GAAP”are to generally accepted accounting principles in the United States;“shares”or“Ordinary Shares”are to the ordinary shares of Everfront Biotech Holding Company Limited,par value$0.01 per share;and“R.O.C.”or“Taiw

39、an”refers to Taiwan,the Republic of China.Everfront Holding does not have any material operations of its own and Everfront Holding is a holding company withoperations conducted in Taiwan through its Taiwan subsidiary,Everfront Biotech,using NTD,the currency of Taiwan.Ourreporting currency is NTD.Thi

40、s prospectus contains translations of certain foreign currency amounts into U.S.dollars for theconvenience of the reader.All translations of NTD are calculated at the rate of NTD to US$1.00,representing the exchangerate set forth in the H.10 statistical release of the Federal Reserve Board on ,2025.

41、No representation is made that theNTD amounts could have been,or could be,converted,realized or settled into US$at such rate,or at any other rate.iii PROSPECTUS SUMMARY The following summary is qualified in its entirety by,and should be read in conjunction with,the more detailedinformation and finan

42、cial statements included elsewhere in this prospectus.In addition to this summary,we urge you to read theentire prospectus carefully,especially the risks of investing in Ordinary Shares,discussed under“Risk Factors”before decidingwhether to buy Ordinary Shares.Everfront Holding is a holding company

43、incorporated in the British Virgin Islands(“BVI”)that conducts its operationsthrough its 99.96%owned subsidiary,Everfront Biotech Inc.(“Everfront Biotech”),which is incorporated and operates in Taiwan.Everfront Holding holds no other assets and conducts no operations of its own.Overview We are a cli

44、nical stage biopharmaceutical company dedicated to the discovery,development and commercialization ofnew drugs that have potential as treatments for patients with cancers,neurodegenerative diseases and rare diseases.We are focusedon new drug discovery and development,supported by our research and de

45、velopment(“R&D”)team established in 2010.Our teamis specialized in preclinical study design,chemistry,manufacturing,and controls(“CMC”),investigational new drug(“IND”)submission,and clinical trial design and conduction.Our goal is to develop technology with the commercial potential to helppeople wit

46、h unmet medical needs.As of the date of this prospectus,we are conducting three clinical trials in Taiwan under the approval of the United StatesFood and Drug Administration(the“FDA”)and the Taiwan Food and Drug Administration(the“TFDA”)for the following productcandidates.As of the date of this pros

47、pectus,we have no products approved for commercial sale and have never generated anyrevenue from product sales.Please also see the risk factor entitled“We are a cancer drug development company with a limitedoperating history.”Cerebraca Wafer is a biodegradable implant produced according to Pharmaceu

48、tical Inspection Co-operation Scheme,orPIC/S,Good Manufacturing Practice,or GMP,standards.Cerebraca Wafer has been designed to treat glioblastoma(GBM)bydirectly implanting it into the GBM tumor margin after surgical resection.Cerebraca Wafer is characterized by its 30-daysustained drug release and 5

49、-cm penetration depth observed in preclinical studies(IND128388,Module 2,Report 51904-12-708),with the intention that this will create a high drug concentration environment for treating the cancer.Cerebraca Wafer is a multi-functional drug with the potential to inhibit receptor tyrosine kinases(Epid

50、ermal Growth Factor Receptor,or EGFR,Axl-1Receptor,and c-Mesenchymal-Epithelial Transition Factor Receptor,or cMet Receptor)to halt cancer stem cell proliferation.Additionally,it has the potential to improve patients quality of life by boosting Adenosine Triphosphate,or ATP,levels throughAxl-mTOR(ma

51、mmalian target of rapamycin)(Liu C-A,et al.,Journal of Oncology.2022;2022.)inhibition and AMP-activatedProtein Kinase,or AMPK,activation(Lee J-H,et al.,International Journal of Molecular Science.2021;22(12):6339.).Furthermore,Cerebraca Wafer has been designed to promote methylation of O6-Methylguani

52、ne-DNA Methyltransferase,orMGMT,and Programmed Cell Death Ligand 1,or PD-L1,promoters in order to help overcome chemotherapeutic resistance(LiuC-A,et al.,Cancers.2022;14(4):1051.)and transform a cold tumor microenvironment into an immune-active hotspot(Liu C-A,etal.,Journal of Oncology.2022;2022.).I

53、n the Phase I/IIa clinical trial,recurrent GBM patients with receptor tyrosine kinase markers(EGF receptor,Axl-1receptor,and cMet receptor)who received surgical resection of GBM and implantation of the Cerebraca Wafer followed bytemozolomide therapy showed a median overall survival of 26.2 months in

54、 the preliminary results.However,limited reliablebiomarkers currently exist for GBM diagnosis and treatment selection.Identifying these biomarkers and developing accurate teststo detect them is crucial for personalized medicine but very challenging.In our next clinical study,we will recruit GBM pati

55、entswith IDH wild-type(National Comprehensive Cancer Network,or NCCN,Guidelines Central Nervous System Cancers,Version1.2024),and we will analyze biomarkers in a subgroup analysis.While the preliminary results of the Phase I/IIa clinical trial areencouraging,extending the median overall survival bey

56、ond 26.2 months will require biomarker identification before surgery,whichmay pose significant scientific and clinical challenges.This difficulty is multifaceted and can be attributed to several key factors.Challenge of Companion Diagnostics Development:There is currently no approved Companion Diagn

57、ostics for GBMtreatment or diagnosis.Limited Reliable Biomarkers:One of the primary challenges in GBM treatment is the scarcity of reliable biomarkersfor diagnosis and treatment selection.Heterogeneity of GBM:Identifying and targeting the specific molecular pathways involved in each patients tumorre

58、mains a significant challenge.Treatment Resistance Mechanisms:The ability of GBM to adapt and resist treatment poses a significant hurdle inextending survival times further.EF-009 Wafer is a biodegradable implant produced according to PIC/S GMP standards that is designed to treat pancreaticcancer by

59、 directly implanting it into the pancreatic cancer tumor margin(IND145153,Module 4,Report D06),which is intended tolead to local tumor regression.This neo-adjuvant therapy may allow patients with locally advanced pancreatic cancer to undergotumor resection therapy.EF-009 has been designed to work by

60、 regulating DNA-methyltransferase 1,or DNMT1,and itsdownstream targets,Patched Domain-Containing 4,or PTCHD4,and hedgehog signaling(Huang M-H,et al.,PharmacologicalResearch.2019;139:50.),in order to help reduce pancreatic cancer growth.Additionally,our preclinical studies have demonstratedthat EF-00

61、9 can have synergistic effects with existing chemotherapy drugs,including Gemcitabine,Cisplatin,5-Fluorouracil,Irinotecan,Oxaliplatin,and Paclitaxel(Patents for cancer treatment,p.63,a combination for the treatment of cancer and itsapplication),implying that combining EF-009 with these currently ava

62、ilable chemotherapy drugs may help achieve improvedclinical outcomes.We have received approval from both the U.S.Food and Drug Administration(“USFDA”)and Taiwan Food andDrug Administration(“TFDA”)to conduct a Phase I/IIa clinical study to evaluate the safety profile and therapeutic effects onpatient

63、s with locally advanced pancreatic cancer.We have completed site selection for this study and expect to begin enrollingpatients in the second quarter of 2025.Nevertheless,we will likely need to conduct a proof-of-concept study in humans toreproduce the effects observed in preclinical research.Other

64、risks associated with using the EF-009 Wafer implant may includelocal inflammation caused by laparoscopic intervention and investigational product degradation,as well as surgical procedures,infection,wound bleeding,and anesthesia.EF-031 is a soft-gel capsule formulation produced according to PIC/S G

65、MP standards and designed to serve as a second-generation product to support the therapeutic actions of the Cerebraca Wafer and the EF-009 Wafer.Unlike the CerebracaWafer and the EF-009 Wafer,which require surgical implantation,EF-031 can be administered orally.In a study conducted byPharmaron,a con

66、tract research organization(study report 51904-15-393),systemic oral administration of EF-031 revealed a 5.6times higher concentration of EF-031 in the brain and a 64.2 times higher concentration in the pancreas compared to a plasmaexposure.Nevertheless,we will likely need to conduct a proof-of-conc

67、ept study in humans to replicate the effects observed inpreclinical research.HK-001 is a soft-gel capsule formulation produced according to PIC/S GMP standards and designed for the treatment ofAmyotrophic Lateral Sclerosis(ALS).Animal study results indicate that administration of HK-001 may help pro

68、long the survivalof ALS animals and delay disease progression(Hsueh K-W,et al.,Neuropharmacology.2016;108:152.).A Phase I clinical trial onhealthy subjects is ongoing to determine the maximum tolerated dose(MTD).Nevertheless,we will likely need to conduct a proof-of-concept study in humans to replic

69、ate the effects observed in preclinical research.1 Corporate Information Our principal executive offices are 10F-1,No.130,Songshan Rd.,Xinyi Dist.,Taipei City 110,Taiwan,and our telephonenumber is+886-2-27563796.Our registered office in the British Virgin Islands is at Portcullis Chambers,4th Floor,

70、Ellen SkeltonBuilding,3076 Sir Francis Drake Highway,Road Town,Tortola,British Virgin Islands.We maintain a website athttp:/.The information contained in,or accessible from,our website or any other website does not constitute apart of this prospectus.Risk Factors Summary An investment in our securit

71、ies is subject to a number of risks,including risks related to our industry,business andcorporate structure.The following summarizes some,but not all,of these risks.Please carefully consider all of the informationdiscussed in“Risk Factors”in this prospectus beginning on page 7 for a more thorough de

72、scription of these and other risks.We are a cancer drug development company with a limited operating history.We expect our operating results to fluctuate significantly in the future as our business advances.We have no products approved for commercial sale and have not generated any revenue from prod

73、uct sales.If we fail to raise additional funds,our ability to execute our business and development strategies may be affected.Raising additional capital may cause dilution to our shareholders,restrict our operations,or require us to relinquishrights to our technologies or product candidates.We have

74、never successfully completed clinical development for any of our product candidates,and we may be unableto do so.Certain of our cancer drugs are still in preclinical development and may never advance to clinicaldevelopment.Clinical product development involves a lengthy and expensive process,with an

75、 uncertain outcome.Interim,top-line,and initial data from our clinical trials that we announce or publish from time to time may change asmore patient data become available and are subject to confirmation,audit and verification procedures that could resultin material changes in the final data.We may

76、incur additional costs or experience delays in initiating or completing,or ultimately be unable to complete,the development and commercialization of our product candidates.If we experience delays or difficulties in the enrollment of patients in clinical trials,our receipt of necessaryregulatory appr

77、ovals could be delayed or prevented.We may not be able to replicate the results from our earlier preclinical and clinical studies in later preclinical studiesand clinical trials,and this could prevent us from successfully developing,obtaining regulatory approval for andcommercializing our product ca

78、ndidates.Our growth depends on our ability to successfully develop,acquire or license new drugs.Clinical trials may be subject to liability claims,which may delay or even cause our R&D plans to fail,consume ourresources,cause us to incur significant liability and limit the development of our product

79、s.We conduct clinical trials on some of our product candidates at locations outside the United States,approval by theFDA is critical to our development,and the FDA may not accept data from trials conducted at certain locations.If clinical trials of our product candidates fail to demonstrate safety a

80、nd efficacy,we may incur additional costs ordelays,or ultimately fail to complete the development and commercialization of our product candidates.We have no history of obtaining regulatory approval or commercialization of any new drug candidates.We face substantial competition,which may result in ot

81、hers discovering,developing or commercializing productsbefore,or more successfully than,we do.If our current product candidates or any future product candidates do not achieve broad market acceptance,therevenue that we generate from their sales may be limited,and we may never become profitable.If si

82、de effects associated with our current or future products are discovered prior to marketing and sale,we may berequired to withdraw these products from the market,conduct lengthy additional clinical trials or change the labelingof our products,any of which could adversely affect our growth.We may be

83、subject to product liability claims in the future,which may consume our resources,expose us tosignificant liability and limit the commercialization of any products we may develop.Even if our product candidates are approved for marketing,they may not be acceptable to physicians,patients,third-party p

84、ayers and others in the medical community,and the market opportunity for our product candidates may besmaller than we estimate to achieve the market size required for commercial success.Obtaining and enforcing pharmaceutical patents involve highly complex legal and factual questions,which,ifdetermin

85、ed adversely to us,could negatively impact our business,financial position,operations and prospects,andinterrupt our research activities.Developments in patent law could have a negative impact on our patent positions and business.If we are unable to protect the confidentiality of our trade secrets,o

86、ur business and competitive position would beharmed,respectively.We and our licensors may not be able to enforce our intellectual property rights throughout the world.We may seek to partner with third parties to develop and commercialize our product candidates,and if we fail to enterinto such collab

87、orations,or if such collaborations are unsuccessful,we may not be able to realize the market potentialof our product candidates.We are a development-stage drug discovery company and therefore face risks associated with the development of newbusinesses in the industry.Obtaining and maintaining regula

88、tory approval of our product candidates in one jurisdiction does not mean that wewill be successful in obtaining regulatory approval of our product candidates in other jurisdictions.We may seek orphan drug designation for certain of our product candidates,and we may be unsuccessful or may beunable t

89、o maintain the benefits associated with orphan drug designation,including the potential for marketexclusivity.If we fail to comply with environmental,health and safety laws and regulations,we could become subject to fines orpenalties or incur costs that could have a material adverse effect on the su

90、ccess of our business.We have convertible debt that will be converted into our Ordinary Shares upon the closing of this offering,which willcause immediate and substantial dilution to our shareholders.There has been no public market for our Ordinary Shares prior to this offering,and if an active trad

91、ing market doesnot develop,you may not be able to resell our Ordinary Shares at or above the price you paid,or at all.As a“controlled company”under Nasdaq Listing Rules,we plan to rely on certain exemptions from Nasdaq corporategovernance rules,which means our shareholders will not have the same pro

92、tections afforded to shareholders of othercompanies.Nasdaq may apply additional and more stringent criteria for our initial and continued listing because we plan to havea small public offering and we insiders will hold a large portion of our listed securities.Our Ordinary Shares may be thinly traded

93、 and you may be unable to sell at or near ask prices or at all if you need tosell your shares to raise money or otherwise desire to liquidate your shares.The initial public offering price for our Ordinary Shares may not be indicative of prices that will prevail in the tradingmarket and such market p

94、rices may be volatile.Our management team has limited experience managing a public company.The obligations associated with becoming a public company may strain our resources,result in more litigation anddivert managements attention from operating our business.You will experience immediate and substa

95、ntial dilution in the net tangible book value of Ordinary Shares purchased.Substantial future sales of our Ordinary Shares or the anticipation of future sales of our Ordinary Shares in the publicmarket could cause the price of Ordinary Shares to decline.We do not intend to pay dividends for the fore

96、seeable future.If securities or industry analysts do not publish research or reports about our business,or if they publish a negativereport regarding our Ordinary Shares,the price of our Ordinary Shares and trading volume could decline.We may experience extreme stock price volatility unrelated to ou

97、r actual or expected operating performance,financialcondition or prospects,making it difficult for prospective investors to assess the rapidly changing value of ourOrdinary Shares,and such volatility may subject us to securities litigation.You may face difficulties in protecting your interests,and y

98、our ability to protect your rights through U.S.courts maybe limited,because Everfront Holding is incorporated under British Virgin Islands law.2 As a foreign private issuer,we are permitted to rely on certain home country rules in lieu of the correspondingcorporate governance standards of the Nasdaq

99、 Listing Rules applicable to domestic U.S.issuers.This may afford lessprotection to holders of our shares.If we cannot satisfy,or continue to satisfy,the initial listing requirements and other rules of the Nasdaq CapitalMarket,our securities may not be listed or may be delisted,which would negativel

100、y impact the price of our securitiesand your ability to sell them.Because our business is conducted in New Taiwan dollars and the price of our Ordinary Shares is quoted in UnitedStates dollars,changes in currency conversion rates may affect the value of your investments.We have broad discretion in t

101、he use of the net proceeds from this offering and may not use them effectively.Our pre-initial public offering,or pre-IPO,shareholders will be able to sell their shares after completion of thisoffering subject to restrictions under Rule 144.We could be deemed to be a passive foreign investment compa

102、ny(“PFIC”),for U.S.federal income tax purposes forany taxable year,which could result in adverse U.S.federal income tax consequences to U.S.holders of our OrdinaryShares.We will be an emerging growth company within the meaning of the Securities Act upon the consummation of thisoffering and may take

103、advantage of certain reduced reporting requirements.Implications of Being an“Emerging Growth Company”As a company with less than$1.235 billion in revenue during our last fiscal year,we qualify as an“emerging growthcompany”as defined in the Jumpstart Our Business Startups Act of 2012,or the JOBS Act.

104、An“emerging growth company”maytake advantage of reduced reporting requirements that are otherwise generally applicable to public companies.In particular,as anemerging growth company,we:may present only two years of audited financial statements and only two years of related Managements Discussionand

105、Analysis of Financial Condition and Results of Operations,or MD&A;are not required to provide a detailed narrative disclosure discussing our compensation principles,objectives andelements and analyzing how those elements fit with our principles and objectives,which is commonly referred to as“compens

106、ation discussion and analysis”;are not required to obtain an attestation and report from our independent registered accounting firm on itsmanagements assessment of our internal control over financial reporting pursuant to the Sarbanes-Oxley Act of 2002;are not required to obtain a non-binding adviso

107、ry vote from our shareholders on executive compensation or goldenparachute arrangements(commonly referred to as the“say-on-pay,”“say-on frequency”and“say-on-golden-parachute”votes);are exempt from certain executive compensation disclosure provisions requiring a pay-for-performance graph andchief exe

108、cutive officer,or CEO,pay ratio disclosure;are eligible to claim longer phase-in periods for the adoption of new or revised financial accounting standards under107 of the JOBS Act;and will not be required to conduct an evaluation of our internal control over financial reporting for two years.We inte

109、nd to take advantage of all of these reduced reporting requirements and exemptions,including the longer phase-inperiods for the adoption of new or revised financial accounting standards under 107 of the JOBS Act.Our election to use thephase-in periods may make it difficult to compare our financial s

110、tatements to those of non-emerging growth companies and otheremerging growth companies that have opted out of the phase-in periods under 107 of the JOBS Act.Under the JOBS Act,we may take advantage of the above-described reduced reporting requirements and exemptions forup to five years after our ini

111、tial sale of common equity pursuant to a registration statement declared effective under the SecuritiesAct of 1933,as amended,herein referred to as the Securities Act,or such earlier time that we no longer meet the definition of anemerging growth company.We will remain an emerging growth company unt

112、il the earliest of:(i)the last day of the first fiscal year in which ourannual gross revenue exceeds$1.235 billion;(ii)the last day of the fiscal year during which the fifth anniversary of the date of thisoffering occurs;(iii)the date that we become a“large accelerated filer”as defined in Rule 12b-2

113、 under the Securities Exchange Actof 1934,as amended(the“Exchange Act”),which would occur if the market value of Ordinary Shares that are held by non-affiliates exceeds$700 million as of the last business day of our most recently completed second fiscal quarter;or(iv)the date onwhich we have issued

114、more than$1.00 billion in non-convertible debt securities during any three-year period.3 Implications of Being a Foreign Private Issuer Because we are incorporated in the British Virgin Islands and more than 50%of our outstanding voting securities are notdirectly or indirectly held by residents of t

115、he United States,we are a“foreign private issuer”under U.S.securities laws.This meansthat we will be subject to reporting obligations that,to some extent,are more lenient and less frequent than those of U.S.domesticreporting companies,including the following.We will not be required to provide as man

116、y Exchange Act reports or provide periodic and current reports asfrequently,as a domestic public company.For interim reporting,we will not be required to file quarterly reports on Form 10-Q containing unaudited financialand other specific information or current reports on Form 8-K upon the occurrenc

117、e of specified significant events;instead,SEC rules will only require that we comply with our home country requirements,which are less rigorous thanthe rules that apply to U.S.domestic public companies.We will be required to file an annual report on Form 20-F,rather than Form 10-K,and therefore will

118、 be permitted toprovide less detailed disclosure on certain issues,such as executive compensation.We will be exempt from provisions of Regulation FD aimed at preventing issuers from making selective disclosuresof material information.We will be exempt from compliance with the sections of the Exchang

119、e Act regulating the solicitation of proxies,consents or authorizations in respect of a security registered under the Exchange Act,including the requirement to filea proxy statement that complies with SEC rules and regulations.Section 16 of the Exchange Act,which requires insiders to file public rep

120、orts of their share ownership and tradingactivities and establishes insider liability for profits realized from any“short-swing”trading transaction will not applyto us.We will cease to be a foreign private issuer,and lose the benefits of these rules,once 50%or more of our outstandingvoting securitie

121、s are held by U.S.residents and any of the following three conditions are true:(i)the majority of the members ofour board of directors and senior management are U.S.citizens or residents;(ii)more than 50%of our assets are located in theUnited States;or(iii)our business is administered principally in

122、 the United States.Both foreign private issuers and emerging growth companies are also exempt from certain more stringent executivecompensation disclosure rules.Thus,even if we no longer qualify as an emerging growth company,but remain a foreign privateissuer,we will continue to be exempt from the m

123、ore stringent compensation disclosures required of companies that are neither anemerging growth company nor a foreign private issuer.In addition,because we are a foreign private issuer,the Nasdaq Listing Rules permit us to follow certain home countryrules rather than the corresponding corporate gove

124、rnance standards of Nasdaq.The standards applicable to us may be considerablydifferent than the standards applied to domestic U.S.issuers,including requirements to:have a majority of our board consist of independent directors(although all of the members of the audit committeemust be independent unde

125、r the Exchange Act);have a compensation committee or a nominating and corporate governance committee consisting entirely ofindependent directors;have regularly scheduled executive sessions with only independent directors;or have executive sessions of solely independent directors each year.Implicatio

126、ns of Being a Controlled Company As of the date hereof(after giving effect to this offering),Mr.Ho-Ching Chen holds beneficial ownership of%ofour outstanding Ordinary Shares pursuant to agreements in which certain of our shareholders have given Mr.Chen voting controlover their shares,including in co

127、nnection with the election of our directors.For so long as these agreements provide Mr.Chen withmore than 50%of the voting power for the election of our directors,we will be a“controlled company”under Nasdaq rules.As acontrolled company,we will be permitted not to comply with certain of Nasdaqs corp

128、orate governance requirements,includingexemptions from the following rules:that a majority of our board of directors must be independent directors;that we have a Compensation Committee that will determine or recommend the compensation of our executiveofficers and that it be composed solely of indepe

129、ndent directors;and that our director nominees must be selected or recommended solely by independent directors.We currently intend to rely on the controlled company exemptions in respect of our Compensation Committee andNominating and Corporate Governance Committee,each of which will include directo

130、rs that are not independent under NasdaqListing Rules.Further,although we do not intend to rely on the exemption in respect of a majority independent board,we will havethe right to use this exemption in the future.As a result,you may not have the same protections afforded to shareholders ofcompanies

131、 that are subject to,or voluntarily follow,these Nasdaq corporate governance requirements.Following this offering,as long as Mr.Ho-Ching Chen maintains control over a majority of the voting power of ouroutstanding Ordinary Shares with respect to the election of our directors,we may utilize certain o

132、f these exemptions.Accordingly,you will not have the same protections afforded to shareholders of companies that are subject to all of the Nasdaq corporategovernance requirements of Nasdaq.If we cease to be a“controlled company”and our common stock continues to be listed onNasdaq,we will be required

133、 to comply with these provisions within the applicable transition periods.4 The Offering Ordinary Shares in this offering Ordinary Shares Price per Ordinary Share Between$and$per Ordinary Share Ordinary Shares outstanding prior to completionof this offering 52,237,745 Ordinary Shares Ordinary Shares

134、 outstanding immediately afterthis offering Ordinary Shares Transfer Agent Nasdaq Capital Market symbol We have applied to have our Ordinary Shares listed on the Nasdaq CapitalMarket under the symbol“EFB”.This offering is contingent upon the finalapproval from Nasdaq for the listing of our Ordinary

135、Shares on the NasdaqCapital Market,and we will not proceed to consummate this offering ifNasdaq denies our listing application.No assurance can be given that ourapplication will be approved.Use of proceeds We intend to use the proceeds from this offering for(i)Glioblastomaclinical trial expenses Cer

136、ebraca Wafer Phase I/IIa;(ii)Glioblastomaclinical trial expenses Cerebraca Wafer Phase IIb/III;(iii)Oncologyclinical trial expenses HK-001/EF-031;(iv)Pancreatic cancer clinicaltrial expenses EF-009 Wafer;(v)general research and developmentexpenses;(vi)patent maintenance and application expenses;and(

137、vii)working capital and other general corporate expenses.See“Use ofProceeds.”Lock-up We and all of our directors and officers and shareholders that hold 5%ormore of our outstanding Ordinary Shares have agreed with therepresentatives of the underwriters,subject to certain exceptions,not to sell,trans

138、fer,or dispose of,directly or indirectly,any Ordinary Shares orsecurities convertible into or exercisable or exchangeable for OrdinaryShares for a period of six months after the closing of his offering.See“Shares Eligible for Future Sale”and“Underwriting.”Risk factors The Ordinary Shares offered her

139、eby involve a high degree of risk.Youshould read“Risk Factors”for a discussion of factors to consider beforedeciding to invest in our Ordinary Shares.Here and elsewhere in this prospectus,we have based the number of Ordinary Shares outstanding after this offering on(1)Ordinary Shares outstanding on

140、,2025 and(2)our issuance and sale in this offering of thenumber of Ordinary Shares set forth on the cover page of this prospectus.These figures do not reflect outstanding rights topurchase Ordinary Shares under our employee benefit plan or the warrants to purchase our Ordinary Shares that we will is

141、sue to therepresentatives of the underwriters on the closing of this offering.See“Underwriting.”5 Summary Consolidated Financial Data We have derived the following summary consolidated financial data as of June 30,2024 and for the six months endedJune 30,2024 and 2023 from our unaudited consolidated

142、 financial statements,which you can find elsewhere in this prospectus.Wehave derived the following summary consolidated financial data as of and for the years ended December 31,2023 and 2022 fromour audited consolidated financial statements,which you can find elsewhere in this prospectus.We prepared

143、 these financialstatements in accordance with generally accepted accounting principles of the United States of America,or U.S.GAAP.Ourhistorical results are not necessarily indicative of the results that may occur in the future.You should read the following summaryconsolidated financial data in conj

144、unction with“Managements Discussion and Analysis of Financial Condition and Results ofOperations”and our consolidated financial statements,including the notes thereto,which you can find elsewhere in this prospectus.For the Six Months Ended June30,For the Years Ended December31,2024 2023 2023 2022 US

145、$US$US$US$(Unaudited)Revenue$-$-$-$79,908 Operating costs -Gross profit -79,908 Total operating expenses 792,673 984,599 2,385,870 1,783,902 Loss from operations (792,673)(984,599)(2,385,870)(1,703,994)Total non-operating income,net 4,961 36,582 92,673 209,400 Loss before income tax (787,712)(948,01

146、7)(2,293,197)(1,494,594)Income tax expense -Net loss$(787,712)$(948,017)$(2,293,197)$(1,494,594)Basic and diluted earnings per share$(0.02)$(0.02)$(0.04)$(0.03)As of June 30,As of December 31,2024 2023 2022 US$US$US$Summary Consolidated Balance Sheet Data Cash and cash equivalents$432,932$1,220,559$

147、548,138 Total current assets 867,975 1,690,317 992,392 Total assets 1,198,579 2,065,005 1,353,450 Total current liabilities 2,645,751 2,679,458 174,696 Total liabilities 2,652,479 2,689,622 175,893 Total stockholders(deficit)equity$(1,453,772)$(624,638)$1,177,236 6 RISK FACTORS An investment in Ordi

148、nary Shares involves a high degree of risk.Before deciding whether to invest in Ordinary Shares,you should consider carefully the risks described below,together with all of the other information set forth in this prospectus,including the section titled“Managements Discussion and Analysis of Financia

149、l Condition and Results of Operation”and ourconsolidated financial statements and related notes.If any of these risks actually occurs,our business,financial condition,resultsof operations or cash flow could be materially and adversely affected,which could cause the trading price of Ordinary Shares t

150、odecline,resulting in a loss of all or part of your investment.The risks described below are not the only ones that we face.Additional risks not presently known to us or that we currently deem immaterial may also affect our business.You should onlyconsider investing in Ordinary Shares if you can bea

151、r the risk of loss of your entire investment.Risks Related to Our Financial Position and Need for Additional Capital We are a cancer drug development company with a limited operating history.We are a cancer drug development company with a limited operating history.Biopharmaceutical product developme

152、nt is ahighly speculative undertaking and involves a substantial degree of risk.Since our inception,we have devoted substantially all ofour efforts to organizing and staffing our company,acquiring and developing intellectual property,business planning,raisingcapital,conducting discovery,research and

153、 development and clinical trial activities,and providing general and administrativesupport for these operations.We have no products approved for commercial sale and therefore have never generated any revenuefrom product sales,and we do not expect to in the foreseeable future.We expect to continue to

154、 incur significant expenses andoperating losses over the next several years and for the foreseeable future.Our prior losses,combined with expected future losses,have had and will continue to have an adverse effect on cash and cash equivalent holdings,our shareholders equity and workingcapital.If we

155、were to expend our cash resources more quickly than we anticipate as we advance into and through the drugdevelopment and approval process,our cash runway may be shorter than the target we may disclose from time to time.We expect our operating results to fluctuate significantly in the future as our b

156、usiness advances.The amount of our future losses is uncertain and our quarterly and annual operating results may fluctuate significantly ormay fall below the expectations of investors or securities analysts,which may cause our share price to fluctuate or decline.Ourquarterly and annual operating res

157、ults may fluctuate significantly in the future due to a variety of factors,many of which areoutside of our control and may be difficult to predict,including the following:the timing and success or failure of on-going and future clinical trials for our product candidates or competing productcandidate

158、s,or any other change in the competitive landscape of our industry,including consolidation among ourcompetitors or partners;our ability to obtain INDs for our pipeline product candidates,successfully open clinical trial sites and recruit andretain subjects for clinical trials,and any delays caused b

159、y difficulties in such efforts;our ability to obtain regulatory approval for our product candidates,and the timing and scope of any such approvalswe may receive;the timing and cost of,and level of investment in,research and development activities relating to our productcandidates and any future prod

160、uct candidates and research-stage programs,which may change from time to time;the cost of manufacturing our product candidates and products,should they receive regulatory approval,which mayvary depending on FDA,TFDA and other comparable foreign regulatory requirements,the quantity of production andt

161、he terms of our agreements with manufacturers;expenditures that we will or may incur to develop additional product candidates;the level of demand for our product candidates should they receive regulatory approval,which may vary significantly;the risk/benefit profile,cost and reimbursement policies w

162、ith respect to our product candidates,if approved,andexisting and potential future cancer drugs that compete with our product candidates;7 future accounting pronouncements or changes in our accounting policies.As a result,comparing our operating results on a period-to-period basis may not be meaning

163、ful.This variability andunpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period.If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to themarket

164、,or if the forecasts we provide to the market are below the expectations of analysts or investors,the price of our OrdinaryShares could decline substantially.Such a share price decline could occur even when we have met any previously publicly statedguidance we may provide.We have no products approve

165、d for commercial sale and have not generated any revenue from product sales.Our ability to become profitable depends upon our ability to generate revenue.To date,we have not generated anyrevenue from product sales,and we do not expect to generate any revenue from the sale of products in the near fut

166、ure.Our abilityto generate revenue depends on a number of factors,including,but not limited to,our ability to:successfully complete our planned preclinical studies for our EF-031 oral formulation;timely file INDs for our programs,and obtain clearance of these INDs to allow for commencement of such f

167、utureclinical trials;successfully complete our Cerebraca Wafer and EF-009 Wafer clinical trials and any future clinical trials;initiate and successfully complete all safety and efficacy studies required to obtain U.S.and foreign regulatoryapproval for our product candidates;make and maintain arrange

168、ments with third-party manufacturers for clinical supply and commercial manufacturing;obtain and maintain patent and trade secret protection or regulatory exclusivity for our product candidates;launch commercial sales of our products,if and when approved,whether alone or in collaboration with others

169、;obtain and maintain acceptance of our products,if and when approved,by patients,the medical community and third-party payers;position our products to effectively compete with other cancer drugs;obtain and maintain healthcare insurance coverage and adequate reimbursement for our products,if and when

170、approved;enforce and defend intellectual property rights and claims;andmaintain a continued acceptable safety profile of our products following approval.If we fail to raise additional funds,our ability to execute our business and development strategies may be affected.We have limited funds,and only

171、a small amount of service income and government subsidy income partially supports ouroperations.The majority of our working capital comes from capital invested by shareholders.From time to time,we may seekadditional funding to provide the funds necessary to expand our R&D program and working capital

172、.We cannot predict with 100%certainty the timing or amount of any such capital requirement.If we do not raise sufficient funds to fund ongoing R&D activities,we may not be able to execute the intended businessdevelopment plan.Even if we receive financing for near-term operations and product developm

173、ent,we may need additionalfunding in the short term.In addition,additional capital may not be available in sufficient amounts or on reasonable terms,and ourability to raise additional capital may be adversely affected by the potential deterioration in global economic conditions andsubsequent disrupt

174、ions.If we are unable to raise capital when required,our business,financial condition and results of operationswill be materially and adversely affected and we may be forced to reduce or cease our operations.8 Raising additional capital may cause dilution to our shareholders,restrict our operations,

175、or require us to relinquish rights toour technologies or product candidates.Until such time,if ever,as we can generate substantial product revenue,we expect to finance our cash needs through oneor a combination of private and public equity offerings,debt financings,collaborations,strategic alliances

176、,and licensingarrangements.We do not have any committed external source of funds.The terms of any financing may adversely affect theholdings or the rights of our shareholders and the issuance of additional securities,whether equity or debt,by us,or the possibilityof such issuance,may cause the marke

177、t price of our Ordinary Shares to decline.To the extent that we raise additional capitalthrough the sale of Ordinary Shares or securities convertible or exchangeable into our Ordinary Shares,the ownership interests ofour existing shareholders will be diluted,and the terms of those securities may inc

178、lude liquidation or other preferences that maymaterially adversely affect your rights as a holder of our Ordinary Shares.Debt financing,if available,would increase our fixedpayment obligations and may involve agreements that include covenants limiting or restricting our ability to take specific acti

179、ons,such as incurring additional debt,acquiring,selling,or licensing intellectual property rights,and making capital expenditures,declaring dividends,repurchasing our Ordinary Shares,or other operating restrictions that could adversely impact our ability toconduct our business.We could also be requi

180、red to meet certain milestones in connection with debt financing and the failure toachieve such milestones by certain dates may force us to relinquish rights to some of our technologies or product candidates orotherwise agree to terms unfavorable to us which could have a material adverse effect on o

181、ur business,operating results,andprospects.We also could be required to seek funds through arrangements with additional collaborators or otherwise at an earlierstage than otherwise would be desirable.If we raise funds through additional collaborations,strategic alliances or licensingarrangements wit

182、h third parties,we may have to relinquish valuable rights to our intellectual property,future revenue streams,research programs or product candidates,grant licenses on terms that may not be favorable to us or grant rights to develop andmarket our product candidates that we would otherwise prefer to

183、develop and market ourselves,any of which may have a materialadverse effect on our business,operating results and prospects.Risks Related to Clinical Development of Our Product Candidates We have never successfully completed clinical development for any of our product candidates,and we may be unable

184、 to do so.Certain of our cancer drugs are still in preclinical development and may never advance to clinical development.We have not yet successfully completed clinical development for any of our product candidates.Completing clinicaldevelopment is a costly,complex endeavor that requires that we,amo

185、ng other things,enroll and complete clinical trials(includinglarge-scale,pivotal or Phase IIb/III clinical trials),obtain regulatory approvals,manufacture a commercial scale product or arrangefor a third party to do so on our behalf,and conduct sales and marketing activities necessary for successful

186、 commercialization.Wereceived FDA and TFDA clearance of one IND application for each of Cerebraca Wafer and EF-009 Wafer.We may not be ableto file future INDs for any of our other product candidates on the timelines we expect,if at all.Further,timelines for developingand filing INDs are subject to s

187、ignificant uncertainties and projected timelines can be improved upon or delayed.Moreover,wecannot be sure that submission of an IND will result in either the FDA or TFDA allowing clinical trials to begin,or that,oncebegun,issues will not arise that require us to suspend or terminate any clinical tr

188、ials.Any guidance we receive from the FDA,TFDA or other regulatory authorities is subject to change.These regulatory authorities could change their position,including on theacceptability of our trial designs or the clinical endpoints selected,which may require us to complete additional clinical tria

189、ls orresult in the imposition of stricter approval conditions than we currently expect.Successful completion of our clinical trials is aprerequisite to submitting a new drug application(“NDA”)to the FDA,a marketing authorization application(“MAA”)to theEuropean Medicines Agency(“EMA”)or other market

190、ing applications to regulatory authorities in other jurisdictions,for eachproduct candidate and,consequently,the regulatory approval of each product candidate.While the INDs for Cerebraca Waferand EF-009 Wafer were cleared by the FDA and TFDA,it is possible that an adequate number of patients may no

191、t be enrolled on atimely basis,or at all,and the studies may not be completed(and preliminary,initial or final trial results may not be available)ontime.Similarly,future clinical trials may not begin on time or be completed on schedule,if at all.If we are required to conduct additional preclinical s

192、tudies or clinical trials of our product candidates beyond those that wecurrently contemplate,if we are unable to successfully complete clinical trials of our product candidates or other testing,if theresults of these trials or tests are not positive or are only modestly positive or if there are saf

193、ety and/or efficacy concerns,we may,among other things:be delayed in obtaining regulatory approval for our product candidates;not obtain regulatory approval at all;9 obtain regulatory approval for indications or patient populations that are not as broad as intended or desired;be subject to post-mark

194、eting testing requirements;orhave the product removed from the market after obtaining regulatory approval.Clinical product development involves a lengthy and expensive process,with an uncertain outcome.Our preclinical studies,our Cerebraca Wafer and EF-009 Wafer clinical trials and future clinical t

195、rials may not besuccessful.It is impossible to predict when or if any of our product candidates will prove effective and safe in humans or willreceive regulatory approval.Before obtaining regulatory approval from regulatory authorities for the sale of any product candidate,we must complete preclinic

196、al studies and then conduct extensive clinical trials to demonstrate the safety and efficacy of our productcandidates in humans.Clinical testing is expensive,difficult to design and implement,can take many years to complete andoutcomes are uncertain.A failure of one or more clinical trials can occur

197、 at any stage of testing.The outcome of preclinicaldevelopment testing and early clinical trials may not be predictive of the success of later clinical trials,and interim or preliminaryresults of a clinical trial do not necessarily predict final results(or be indicative of safety and efficacy if com

198、mercialized and usedin a broader population).Moreover,preclinical and clinical data are often susceptible to varying interpretations and analyses,andmany companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials havenonetheless failed t

199、o obtain regulatory approval of their product candidates.Interim,top-line,and initial data from our clinical trials that we announce or publish from time to time may change as morepatient data become available and are subject to confirmation,audit and verification procedures that could result in mat

200、erialchanges in the final data.From time to time,we may publicly disclose interim,top-line or initial data from our current and future clinical trials,which is based on a preliminary analysis of then-available data,and the results and related findings and conclusions are subject tochange following a

201、 more comprehensive review of the data,including audit and verification procedures,and as results fromadditional clinical trial participants become available and trial participants spend additional time on therapy.We may also makeassumptions,estimations,calculations and conclusions as part of our an

202、alyses of data,and we may not have received or had theopportunity to evaluate all data fully and carefully.As a result,initial,interim and top-line data should be viewed with caution untilthe final data are available.In addition,we may report interim analyses of only certain endpoints rather than al

203、l endpoints.Interimdata from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materiallychange as patient enrollment continues and more patient data become available.Adverse differences between initial or interim dataand final data could sign

204、ificantly harm our business prospects and may cause the price of our Ordinary Shares to fluctuate ordecline.Further,regulatory agencies and others may not accept or agree with our assumptions,estimates,calculations,conclusionsor analyses or may interpret or weigh the importance of data differently,w

205、hich could adversely impact the potential of a particularprogram,the likelihood of obtaining regulatory approval of the particular product candidate,the scope of product label,andcommercialization of any approved product.In addition,the information we choose to publicly disclose regarding a particul

206、arstudy or clinical trial is derived from information that is typically extensive,and you or others may not agree with what wedetermine is material or otherwise appropriate information to include in our disclosure.If the initial,interim or top-line data that we report differ from final or actual res

207、ults,or if others,including regulatoryauthorities,disagree with the conclusions reached,our ability to obtain approval for,and commercialize,our product candidatesmay be significantly impaired,which could materially harm our business,operating results,prospects or financial condition.We may incur ad

208、ditional costs or experience delays in initiating or completing,or ultimately be unable to complete,thedevelopment and commercialization of our product candidates.We may experience delays in initiating or completing our preclinical studies or clinical trials,including as a result ofdelays in obtaini

209、ng,or failure to obtain,the FDAs and/or TFDAs clearance to initiate clinical trials under future INDs.Additionally,we cannot be certain that preclinical studies or clinical trials for our product candidates will not require redesign,willenroll an adequate number of subjects on time,or will be comple

210、ted on schedule,if at all.We may experience numerous unforeseenevents during,or as a result of,preclinical studies and clinical trials that could delay or prevent our ability to receive regulatoryapproval or commercialize our product candidates,including the following:we may receive feedback from re

211、gulatory authorities that require us to modify the design or implementation of ourpreclinical studies or clinical trials or to delay or terminate a clinical trial;10 regulators or institutional review boards(“IRB”),or ethics committees may delay or may not authorize us or ourinvestigators to commenc

212、e a clinical trial or conduct a clinical trial at a prospective trial site;we may experience delays in reaching,or fail to reach,agreement on acceptable terms with prospective trial sites andprospective Contract Research Organizations,or CROs,the terms of which can be subject to extensive negotiatio

213、nand may vary significantly among different CROs and trial sites;preclinical studies or clinical trials of our product candidates may fail to show safety or efficacy or otherwise producenegative or inconclusive results,and we may decide,or regulators may require us,to conduct additional preclinicals

214、tudies or clinical trials,or we may decide to abandon product research or development programs;preclinical studies or clinical trials of our product candidates may not produce differentiated or clinically significantresults across tumor types or indications;the number of patients required for clinic

215、al trials of our product candidates may be larger than we anticipate,enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trialsor fail to return for post-treatment follow-up at a higher rate than we anticipate;our third-party contractor

216、s may fail to comply with regulatory requirements,fail to maintain adequate qualitycontrols,be unable to provide us with sufficient product supply to conduct or complete preclinical studies or clinicaltrials,fail to meet their contractual obligations to us in a timely manner,or at all;our clinical t

217、rial sites or investigators may deviate from the clinical trial protocol or drop out of the trial,which mayrequire that we add new clinical trial sites or investigators in order to ensure our trials generate statistically significantresults;we may elect to,or regulators or IRBs or ethics committees

218、may require us or our investigators to,suspend orterminate clinical research for various reasons,including noncompliance with regulatory requirements or a findingthat the participants in our clinical trials are being exposed to unacceptable health risks;the cost of clinical trials of our product can

219、didates may be greater than we anticipate;the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our productcandidates may be insufficient or inadequate;our product candidates may have undesirable side effects or other unexpected characteristics,ca

220、using us or ourinvestigators,regulators or IRBs or ethics committees to suspend or terminate the trials,or reports may arise frompreclinical or clinical testing of other cancer drugs that raise safety or efficacy concerns about our product candidates;regulators may revise the requirements for approv

221、ing our product candidates,or such requirements may not be as weanticipate;andregulatory developments with respect to our competitors products,including any developments,litigation or publicconcern about the safety of such products.We could encounter delays if a clinical trial is suspended or termin

222、ated by us,by the IRBs of the institutions at which suchtrials are being conducted or by the FDA,TFDA or other regulatory authorities.Such authorities may impose such a suspension ortermination or clinical hold due to a number of factors,including failure to conduct the clinical trial in accordance

223、with regulatoryrequirements for our clinical protocols,adverse findings upon an inspection of the clinical trial operations or trial site by the FDA,TFDA or other regulatory authorities,unforeseen safety issues or adverse side effects,failure to demonstrate a benefit from using aproduct,changes in g

224、overnmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.Many of the factors that cause,or lead to,a delay in the commencement or completion of clinical trials may also ultimately lead tothe denial of regulatory approval of our product candidates.F

225、urther,the FDA or TFDA may disagree with our clinical trial designor our interpretation of data from clinical trials or may change the requirements for approval even after each has reviewed andcommented on the design for our clinical trials.11 Moreover,principal investigators for our current or futu

226、re clinical trials may serve as scientific advisors or consultants tous from time to time and receive compensation in connection with such services.Under certain circumstances,we may be requiredto report some of these relationships to the FDA,TFDA or comparable foreign regulatory authorities.The FDA

227、,TFDA orcomparable foreign regulatory authority may conclude that a financial relationship between us and a principal investigator hascreated a conflict of interest or otherwise affected the interpretation of the study.The FDA,TFDA or comparable foreign regulatoryauthority may therefore question the

228、 integrity of the data generated at the applicable clinical trial site,and the utility of the clinicaltrial itself may be jeopardized.This could result in a delay in approval,or rejection,of our marketing applications by the FDA,TFDA or comparable foreign regulatory authority and may ultimately lead

229、 to the denial of regulatory approval of one or more ofour product candidates.Our product development costs will also increase if we experience delays in testing or regulatory approvals.We do notknow whether any of our current or future clinical trials will begin as planned,or whether any of our cur

230、rent or future clinical trialswill need to be restructured or will be completed on schedule,if at all.Significant preclinical study or clinical trial delays alsocould shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow ourcompetitors to b

231、ring products to market before we do,which would impair our ability to successfully commercialize our productcandidates and may significantly harm our business,operating results,financial condition and prospects.If we experience delays or difficulties in the enrollment of patients in clinical trials

232、,our receipt of necessary regulatoryapprovals could be delayed or prevented.We may not be able to continue or initiate clinical trials for our product candidates if we are unable to locate and enroll asufficient number of eligible patients to participate in these trials as required by the FDA,TFDA o

233、r comparable foreign regulatoryauthorities,or as needed to provide appropriate statistical power for a given trial.In particular,because some of the indications weare pursuing are orphan indications that have small populations,our ability to enroll eligible patients may be limited or may resultin sl

234、ower enrollment than we anticipate.In addition,some of our competitors have ongoing clinical trials for product candidates that treat the same indications asdo our product candidates,and patients who would otherwise be eligible for our clinical trials may choose instead to enroll inclinical trials o

235、f our competitors product candidates.In addition to the competitive clinical trial environment,the eligibility criteria of our clinical trials will further limit thepool of available study participants as we will require that patients have specific characteristics that we can measure to assure their

236、cancer is either severe enough or not too advanced to include them in a study.The process of finding patients may prove costly.Wealso may not be able to identify,recruit or enroll a sufficient number of patients to complete our clinical studies because of theperceived risks and benefits of the produ

237、ct candidates under study,the availability and efficacy of competing therapies and clinicaltrials,the proximity and availability of clinical trial sites for prospective patients,and the patient referral practices of physicians.Ifpatients are unwilling to participate in our studies for any reason,the

238、 timeline for recruiting patients,conducting studies,reportinginitial and final trial results and obtaining regulatory approval of potential products may be delayed.Further,if our patient recruitment for our clinical trials proceeds more slowly than we expect,this could compromise ourability to seek

239、 designations under applicable FDA expedited review and development programs,including Breakthrough TherapyDesignation and Fast Track Designation(to the extent these are available to us),or otherwise seek to accelerate clinicaldevelopment and regulatory timelines.Patient enrollment may be affected b

240、y other factors,including:the severity of the disease under investigation;the efforts to obtain and maintain patient consents and facilitate timely enrollment in clinical trials;the ability to monitor patients adequately during and after treatment;the ability to recruit clinical trial investigators

241、with the appropriate competencies and experience;reporting of the initial results of any of our clinical trials;andfactors we may not be able to control,including the impacts of events such as global pandemics,which may limitpatients,principal investigators or staff or clinical site availability.12

242、We may not be able to replicate the results from our earlier preclinical and clinical studies in later preclinical studies andclinical trials,and this could prevent us from successfully developing,obtaining regulatory approval for and commercializingour product candidates.You should not view results

243、 from our earlier preclinical studies of our programs and product candidates to be predictive ofthe results of subsequent preclinical studies and clinical trials.Any results from the earlier preclinical and clinical studies of ourprograms or our product candidates may not necessarily be predictive o

244、f the results from Later preclinical studies and clinical trialsoften fail to replicate or confirm the results of earlier preclinical and clinical studies for a variety of reasons,including that laterstudies may be more rigorous and involve a larger,more diverse patient population.Many companies in

245、the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stageclinical trials after achieving positive results in early-stage development,and we cannot be certain that we will not face similarsetbacks.These setbacks have been caused by,among other things,preclinical

246、 and other nonclinical findings made while clinicaltrials were underway,or safety,pharmacokinetic or efficacy observations made in preclinical studies and clinical trials,includingpreviously unreported adverse events.Moreover,preclinical,nonclinical and clinical data are often susceptible to varying

247、interpretations and analyses and many companies that believed their product candidates performed satisfactorily in preclinicalstudies and clinical trials have nonetheless failed to obtain regulatory approval.Our growth depends on our ability to successfully develop,acquire or license new drugs.Our c

248、urrent development is supported by sustained investment of time,resources and capital to identify and develop newdrugs suitable for the market.If we are unable to develop new products ourselves or license new products from other parties,ourability to generate revenue and develop market share will be

249、 adversely affected.In addition,we may not recoup our investment innew drug development because our projects may be interrupted,unsuccessful,not as profitable as originally envisaged,or we maynot receive the necessary capital investment.Similarly,there can be no assurance that we will be able to suc

250、cessfully obtain neededrights from third parties on an economically viable basis.Clinical trials may be subject to liability claims,which may delay or even cause our R&D plans to fail,consume our resources,cause us to incur significant liability and limit the development of our products.As we conduc

251、t clinical trials of our products,we face the inherent risk of product liability claims resulting from thosetrials.If any of the products we develop are suspected of causing harm or are found to be unsuitable during clinical trials,we maybe liable for damages.Any product liability claims may include

252、 allegations of manufacturing defects,design defects,failure towarn of the inherent dangers of the product,negligence,strict liability,or violations of specifications.If we are unable tosuccessfully defend a product liability claim,we may be liable for substantial damages and/or required to cease pr

253、oceeding with thetrial and the development of our product.Regardless of the circumstances or final outcome,liability claims can result in:significant negative attention that damages our reputation and the reputation of our products;participants quitting or declining to participate in our clinical tr

254、ials;significant costs of defending litigation;substantial monetary compensation to plaintiffs and other trial participants;anddifficulty commercializing our developed products.We currently have insurance policies to cover liability under clinical trials,but no general liability insurance.Even if we

255、have general liability insurance in the future,it may not fully cover any potential liability we may incur.The cost of any productliability litigation or other proceedings,even in our favor,can be substantial.13 We conduct clinical trials on some of our product candidates at locations outside the Un

256、ited States,approval by the FDA iscritical to our development,and the FDA may not accept data from trials conducted at certain locations.We have conducted one or more clinical trials outside the United States.Although the FDA may accept data from clinicaltrials conducted outside the United States,ac

257、ceptance of such data is subject to certain conditions imposed by the FDA.Forexample,clinical trials must be carefully designed,conducted,and executed by qualified researchers in accordance with ethicalprinciples.The trial population must also be fully representative of the U.S.population,and the da

258、ta must be applicable to the U.S.population and U.S.medical practice in a manner deemed clinically significant by the FDA.In addition,while these clinical trialsare subject to applicable local laws,FDAs acceptance of any trial data will depend on its determination that the trials also complywith all

259、 applicable U.S.laws and regulations.There is no guarantee that the FDA will accept data from trials conducted outside theUnited States.If the FDA does not accept data from a clinical trial that we decide to conduct outside the United States,it may resultin the need for additional trials,which would

260、 be expensive and time-consuming,and could delay or permanently halt ourdevelopment of product candidates.In addition,the conduct of international clinical trials in the future may have a significant impact on us.The inherent risksof conducting international clinical trials include:foreign regulator

261、y requirements that could restrict or limit our ability to conduct our clinical trials;administrative burdens of conducting clinical trials under multiple foreign regulatory schema;foreign exchange fluctuations;anddiminished protection of intellectual property in some countries.If clinical trials of

262、 our product candidates fail to demonstrate safety and efficacy,we may incur additional costs or delays,orultimately fail to complete the development and commercialization of our product candidates.Clinical trials are expensive,complex to design and conduct,can take years to complete,and have highly

263、 uncertainoutcomes.Any failure to successfully complete preclinical and clinical development could result in additional costs for us andcompromise our product commercialization milestones and ability to generate revenue from our products.In addition,if(a)weneed to consider additional clinical trials

264、 or other testing of a product candidate,(b)we are unable to successfully complete clinicaltrials or other testing of a product candidate,(c)the results of any trials or tests are unfavorable,uncertain,or only moderatelyfavorable,or(d)there is an unacceptable safety issue with a product candidate,in

265、 addition to incurring additional costs,we may:suffer delays in obtaining marketing approval of candidate products;find there is no way to obtain marketing authorization;see results that do not meet the approval requirements for the broad indications or broad patient populations we hadexpected;obtai

266、n approval for labels that contain significant use or distribution restrictions or significant safety warnings,including“boxed”warnings;be subject to additional post-market testing or other requirements;orobtain marketing approval,and afterwards find that the product must be removed from the market.

267、Risks Related to Obtaining Regulatory Approval for Our Product Candidates We have no history of obtaining regulatory approval or commercialization of any new drug candidates.Due to our limited operating history,we have never received regulatory approval or achieved commercialization for anynew drug

268、candidates.Regulatory authorities such as the FDA or the TFDA may reject New Drug Applications(or“NDAs”)forsubstantive review of our planned drugs or conclude after reviewing our data that our applications are insufficient to obtainregulatory approval for new drug candidates.Although our R&D units h

269、ave experience participating in New Drug Application(or“NDA”)filings,the process and timeline for obtaining NDA approval can vary significantly.If the FDA does not accept or approveour planned product candidate NDA,additional clinical,preclinical or manufacturing validation studies may be required f

270、rom us,which can be costly.Depending on the FDA-required research,approval of any NDA or application we submit may be significantlydelayed,possibly up to several years,or may require us to spend more resources than we anticipate.Any delay in obtaining or theinability to obtain regulatory approval fo

271、r any of our drug candidates will prevent us from licensing such products.If other studiesare conducted and completed,the FDA may also consider them inadequate.If any of these results occur,we may be forced toabandon planned NDAs for such drug candidates,which would have a material adverse effect on

272、 our business and may result in usceasing operations.We face similar regulatory risks in foreign jurisdictions.14 Risks Related to Commercialization of Our Product Candidates We face substantial competition,which may result in others discovering,developing or commercializing products before,ormore s

273、uccessfully than,we do.The development and commercialization of new products in the biopharmaceutical and related industries is highlycompetitive.We compete in the segments of the pharmaceutical,biotechnology,and other related markets that address structuralbiology-guided chemistry-based drug design

274、 to develop therapies in the fields of cancer and genetic diseases.There are othercompanies focusing on precision oncology to develop therapies in the fields of cancer and other diseases.We also compete more broadly across the market for cost-effective and reimbursable cancer treatments.Some of thes

275、ecompetitive products and therapies are based on scientific approaches that are the same as or similar to our approach,and others arebased on entirely different approaches.These companies include divisions of large pharmaceutical companies and biotechnologycompanies of various sizes.We face competit

276、ion with respect to our current product candidates,and will face competition withrespect to any product candidates that we may seek to develop or commercialize in the future,from major pharmaceuticalcompanies,specialty pharmaceutical companies and biotechnology companies worldwide.Potential competit

277、ors also includeacademic institutions,government agencies and other public and private research organizations that conduct research,seek patentprotection and establish collaborative arrangements for research,development,manufacturing and commercialization.Any product candidates that we successfully

278、develop and commercialize will compete with currently approved therapiesand new therapies that may become available in the future from segments of the pharmaceutical,biotechnology and other relatedmarkets.Key product features that would affect our ability to effectively compete with other therapeuti

279、cs include the efficacy,safety and convenience of our products.We believe the principal competitive factors to our business include,among other things,our ability to identify biomarkers,the ability to successfully transition research programs into clinical development,the ability toraise capital,and

280、 the scalability of our platform,pipeline,and business.Many of the companies that we compete against or which we may compete against in the future have significantly greaterfinancial resources and expertise in research and development,manufacturing,preclinical and clinical testing,obtaining regulato

281、ryapprovals and marketing,promoting and selling approved products than we do.Mergers and acquisitions in the pharmaceutical,biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of ourcompetitors.Smaller or early-stage companies may also

282、prove to be significant competitors,particularly through collaborativearrangements with large and established companies.These competitors also compete with us in recruiting and retaining qualifiedscientific and management personnel and establishing clinical trial sites and patient registration for c

283、linical trials,as well as inacquiring technologies complementary to,or necessary for,our programs.If these or other barriers to entry do not remain in place,other companies may be able to more directly or effectively compete with us.Our commercial opportunity could be reduced or eliminated if our co

284、mpetitors develop and commercialize products thatare safer,more effective,have fewer or less severe side effects,are more convenient or are less expensive than any products that weor our collaborators may develop.Our competitors also may obtain FDA,TFDA or other regulatory approval for their product

285、ssooner than we may obtain approval for ours,which could result in our competitors establishing a strong market position before weor our collaborators are able to enter the market.The key competitive factors affecting the success of all of our product candidates,if approved,are likely to be their ef

286、ficacy,safety,convenience,price,level of generic competition and novel competition thatutilize the same mechanism of action and availability of reimbursement from government and other third-party payers.15 If our current product candidates or any future product candidates do not achieve broad market

287、 acceptance,the revenue thatwe generate from their sales may be limited,and we may never become profitable.We have never commercialized a product candidate for any indication.Even if our current product candidates and anyfuture product candidates are approved by the appropriate regulatory authoritie

288、s for marketing and sale,they may not gainacceptance among physicians,patients,third-party payers,and others in the medical community.If any product candidates forwhich we obtain regulatory approval do not gain an adequate level of market acceptance,we may not generate significant revenueand may not

289、 become profitable or may be significantly delayed in achieving profitability.Market acceptance of our current productcandidates and any future product candidates by the medical community,patients and third-party payers will depend on a numberof factors,some of which are beyond our control.For examp

290、le,physicians are often reluctant to switch their patients,and patientsmay be reluctant to switch,from existing therapies even when new and potentially more effective or safer treatments enter themarket.If public perception is influenced by claims that the use of certain precision oncology product c

291、andidates orimmunotherapies and targeted therapies is unsafe,whether related to our or our competitors products,our potential future productsmay not be accepted by the general public or the medical community.Future adverse events in precision oncology,immuno-oncology or the biopharmaceutical industr

292、y could also result in greater governmental regulation,stricter labeling requirements andpotential regulatory delays in the testing or approvals of our product candidates.Efforts to educate the medical community and third-party payers on the benefits of our current product candidates and anyfuture p

293、roduct candidates may require significant resources and may not be successful.If our current product candidates or anyfuture product candidates are approved but do not achieve an adequate level of market acceptance,which will depend on a numberof factors,we could be prevented from or significantly d

294、elayed in achieving profitability.If side effects associated with our current or future products are discovered prior to marketing and sale,we may be required towithdraw these products from the market,conduct lengthy additional clinical trials or change the labeling of our products,anyof which could

295、 adversely affect our growth.We are currently developing the following drugs:Cerebraca Wafer(Glioblastoma),EF-009 Wafer(Pancreatic cancer),EF-031(Solid tumor),HK-001(Amyotrophic lateral sclerosis),TSCA-001(Spinocerebellar ataxia),EF-005(Alzheimers disease),EF-002(Liver cirrhosis),EF-011(Pulmonary fi

296、brosis),and EF-012(Immunotherapy).The use of certain medications can result inserious adverse events(SAEs).For instance,the administration of Cerebraca Wafer has been associated with recorded treatmentemergent AEs such as fever,abnormal wound healing,convulsions,and headache.After approval,if receiv

297、ed,the occurrence of any AE would harm our future sales of these drugs and significantly increasethe costs and expenses of marketing these drugs,which in turn could result in a decline in our revenue and net income.In addition,the reputation and sales of our future drugs may be adversely affected du

298、e to the serious side effects found.We may be subject to product liability claims in the future,which may consume our resources,expose us to significant liabilityand limit the commercialization of any products we may develop.If our products cause adverse side effects,we face the inherent business ri

299、sk of product liability claims.Side effects ormarketing or manufacturing issues related to any of our products in development may result in product liability claims or negativepublicity.These risks will exist in products in clinical development and in products that receive regulatory approval for co

300、mmercialsale in the future.In addition,although we have historically not encountered any issues related to product user claims because wedo not yet sell our products,we do not currently have product liability insurance and cannot guarantee that we will be able to obtaincommercially viable product li

301、ability insurance in the future.As a result of selling any product we develop,there is an inherent risk of product liability claims.For example,we may beliable for damages if any of the products we develop are suspected of causing injury or are found to be unsuitable duringmanufacturing,marketing,or

302、 sales.Any such product liability claims may include allegations of manufacturing defects,designdefects,failure to warn of the inherent dangers of the product,negligence,strict liability,or breach of regulations.Claims underconsumer protection laws may also be brought.If we are unable to successfull

303、y defend against a product liability claim,we may bematerially liable or required to limit the commercialization of our product candidates.Regardless of the circumstances or finaloutcome,liability claims can result in:Reduced demand for our product candidates or products we may develop;Significant n

304、egative attention that damages our reputation;The resulting significant costs of litigation defense;16 Substantial monetary compensation to patients;Loss of income;andReducing our resources and hindering the progress of our business.If we start selling any candidate products that are approved for ma

305、rketing,we will need to increase our insurancecoverage.In addition,insurance coverage is becoming more expensive.If we are unable to obtain or maintain adequate insurancecoverage at an acceptable cost,or otherwise prevent potential product liability claims,this could prevent or inhibit the developme

306、ntand commercial production and sale of our product candidates,which could adversely affect our business,financial condition,results of operations and prospects.We may not commercialize,market,promote or sell any product candidate in any jurisdiction without marketing approvalfrom each countrys regu

307、latory authorities,such as the FDA.We may never receive such approval,and we must complete extensivepreclinical development and clinical trials to demonstrate the safety and efficacy of our product candidates in humans beforeobtaining these approvals.Even if our product candidates are approved for m

308、arketing,they may not be acceptable to physicians,patients,third-partypayers and others in the medical community,and the market opportunity for our product candidates may be smaller than weestimate to achieve the market size required for commercial success.We have never completed the FDA approval an

309、d commercialization of new drug development processes,and even if ourproducts receive marketing and sales approval from the relevant regulatory authorities,they may not receive adequate marketacceptance from physicians,patients,third-party payers,and others in the medical community.For example,docto

310、rs are oftenreluctant to switch patients from existing therapies,even if new drugs may be more effective or convenient treatments enter themarket.In addition,patients are often adapted to the treatment they are currently taking and do not want to switch unless theirdoctor recommends a replacement me

311、dication or needs to switch treatment due to lack of reimbursement for an existing treatment.The potential market opportunity for our products is difficult to estimate accurately.Our estimates of potential marketopportunity are based on a number of assumptions,including industry knowledge and public

312、ations,third-party research reports,and other surveys.While we believe that our internal assumptions are reasonable,these assumptions involve important judgmentsof our R&D team and are inherently uncertain,and the reasonableness of these assumptions has not been evaluated by independentsources.If an

313、y assumptions prove to be inaccurate,the actual market for our products may be smaller than our estimate of thepotential market opportunity.Risks Related to Our Intellectual Property Obtaining and enforcing pharmaceutical patents involve highly complex legal and factual questions,which,if determined

314、adversely to us,could negatively impact our business,financial position,operations and prospects,and interrupt our researchactivities.The patent positions of pharmaceutical companies and research institutions can be highly uncertain and involve complexlegal and factual questions.The interpretation a

315、nd breadth of claims allowed in some patents covering pharmaceuticalcompositions may be uncertain and difficult to determine and are often affected materially by the facts and circumstances thatpertain to the patented compositions and the related patent claims.The standards of the U.S.Patent and Tra

316、demark Office,orUSPTO,are sometimes uncertain and could change in the future.The standards are also,in some instances subject to interpretationby examiners at the USPTO.Consequently,the issuance and scope of patents cannot be predicted with certainty.Patents,if issued,may be challenged,invalidated o

317、r circumvented.U.S.patents and patent applications may also be subject to interferenceproceedings,and U.S.patents may be subject to re-examination proceedings,post-grant review and/or inter parties review in theUSPTO.Foreign patents may be subject to opposition or comparable proceedings in the corre

318、sponding foreign patent office,whichcould result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of theclaims of the patent or patent application.In addition,such interference,re-examination,post-grant review,inter parties review ando

319、pposition proceedings may be costly.Accordingly,rights under any issued patents may not provide us with sufficient protectionagainst competitive products or processes.17 In addition,we may not be able to prevent unauthorized use of our intellectual property which could harm our businessand competiti

320、ve position.Changes in or different interpretations of patent laws in the U.S.and foreign countries may permit othersto use our inventions and discoveries of or to develop and commercialize their new drug candidates without providing anycompensation to us,or may limit the number of patents or claims

321、 that we can obtain.The laws of some countries do not protectintellectual property rights to the same extent as U.S.laws and those countries may lack adequate rules and procedures fordefending and enforcing our intellectual property rights.Additionally,some of our competitors may have more resources

322、 than wedo to pursue claims of infringement or misappropriation.We may conclude that even if they are infringing our patents or otherintellectual property rights,the risk-adjusted costs of bringing claims against them may be too high or otherwise not in our interest.Failure to adequately protect,enf

323、orce,or be able to use our intellectual property rights could result in our competitors using ourintellectual property to offer products,potentially resulting in the loss of some of our competitive advantage,a decrease in ourrevenue and reputational harm caused by inferior products offered by third

324、parties,which would adversely affect our business,prospects,financial condition and operating results.Developments in patent law could have a negative impact on our patent positions and business.From time to time,the U.S.Supreme Court,other federal courts,the U.S.Congress or the USPTO may change the

325、standards of patentability and any such changes may negatively affect our business.We cannot know what new developments inintellectual property law will impact future use and the value of our intellectual property rights.In addition,the Leahy-Smith America Invents Act,or the America Invents Act,whic

326、h was signed into law in 2011,includes a number of significant changes to U.S.patent law.These changes include a transition from a“first-to-invent”system to a“first-to-file”system,changes the way issued patents are challenged,and changes the way patent applications are disputed duringthe examination

327、 process.These changes may favor larger and more established companies that have greater resources to devote topatent application filing and prosecution.The USPTO has developed regulations and procedures to govern the full implementationof the America Invents Act,and many of the substantive changes

328、to patent law associated with the America Invents Act,and,inparticular,the first-to-file provisions,became effective on March 16,2013.If we are unable to protect the confidentiality of our trade secrets,our business and competitive position would be harmed,respectively.We have entered into intellect

329、ual property assignment,confidentiality and non-disclosure agreements with our employees,consultants,outside scientific and commercial collaborators,sponsored researchers,and other advisors.These agreements generallyrequire that the other party keep confidential and not disclose to third parties any

330、 confidential information developed by the partyor made known to the party by us during the course of the partys relationship therewith.Where appropriate,they also generallyrequire that the other party assign intellectual property developments to us.However,these agreements may not be honored andmay

331、 not effectively protect our rights in our intellectual property.Our security measures may not prevent an employee or consultant from misappropriating our trade secrets and providingthem to a competitor,and recourse we elect to take against such misconduct may not provide an adequate remedy to prote

332、ct ourinterests fully.Enforcing a claim that a party illegally disclosed or misappropriated a trade secret can be difficult,expensive,andtime-consuming,and the outcome is unpredictable.For these reasons,it is possible that we would decide not to attempt to enforceour rights against a third party who

333、 we believe has engaged in unauthorized use of our trade secrets or that we would beunsuccessful in our efforts to enforce rights against such a third party.We and our licensors may not be able to enforce our intellectual property rights throughout the world.The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the U.S.Many companies have