1、F-1 1 ny20012777x5_f1.htm F-1TABLE OF CONTENTSAs filed with the Securities and Exchange Commission on January 25,2024Registration No.333-UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWASHINGTON,D.C.20549FORM F-1REGISTRATION STATEMENTUNDERTHE SECURITIES ACT OF 1933APRINOIA Therapeutics Inc.(Exact na

2、me of Registrant as specified in its charter)Not Applicable(Translation of Registrants name into English)Cayman Islands 2834 Not Applicable(State or Other Jurisdiction ofIncorporation or Organization)(Primary Standard IndustrialClassification Code Number)(I.R.S.EmployerIdentification Number)245 Main

3、 Street,2nd FloorCambridge,MA 02142Telephone:617-225-4415(Address,including zip code,and telephone number,including area code,of Registrants principal executive offices)245 Main Street,2nd FloorCambridge,MA 02142Telephone:617-225-4415(Name,address,including zip code,and telephone number,including ar

4、ea code,of agent for service)Copies to:Will H.Cai,Esq.Timothy Pitrelli,Esq.Cooley LLPc/o 35th FloorTwo Exchange Square8 Connaught PlaceCentral,Hong Kong+852 3758-1200 Reid S.Hooper,Esq.Cooley LLP1299 Pennsylvania AvenueNW,Suite 700Washington,DC 20004(202)842 7899 Michael J.BlankenshipWinston&Strawn

5、LLP800 Capitol Street,Suite 2400Houston,Texas 77002(713)651 2600Approximate date of commencement of proposed sale to the public:as soon as practicable after the effective date of this registrationstatement.If any of the securities being registered on this Form are to be offered on a delayed or conti

6、nuous basis pursuant to Rule 415 under theSecurities Act of 1933,check the following box.If this Form is filed to register additional securities for an offering pursuant to Rule 462(b)under the Securities Act,please check thefollowing box and list the Securities Act registration statement number of

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

8、 same offering.If this Form is a post-effective amendment filed pursuant to Rule 462(d)under the Securities Act,check the following box and list theSecurities Act registration statement number of the earlier effective registration statement for the same offering.Indicate by check mark whether the re

9、gistrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933.Emerging growth company If an emerging growth company that prepares its financial statements in accordance with U.S.GAAP,indicate by check mark if theregistrant has elected not to use the extended transition

10、period for complying with any new or revised financial accounting standardsprovided pursuant to Section 7(a)(2)(B)of the Securities Act.The term“new or revised financial accounting standard”refers to any update issued by the Financial Accounting Standards Board to itsAccounting Standards Codificatio

11、n(“ASC”)after April 5,2012.The Registrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective dateuntil the Registrant shall file a further amendment which specifically states that this Registration Statement shall thereafterbecome effective in

12、accordance with Section 8(a)of the Securities Act of 1933 or until the Registration Statement shall becomeeffective on such date as the Securities and Exchange Commission,acting pursuant to said Section 8(a),may determine.TABLE OF CONTENTSThe information in this preliminary prospectus is not complet

13、e and may be changed.We maynot sell these securities until the registration statement filed with the Securities and ExchangeCommission is effective.This preliminary prospectus is not an offer to sell these securities andwe are not soliciting offers to buy these securities in any state where the offe

14、r or sale is notpermitted.PRELIMINARY PROSPECTUS(Subject to Completion)Issued,2024Ordinary SharesAPRINOIA Therapeutics Inc.This is an initial public offering of the ordinary shares of APRINOIA Therapeutics Inc.We are offering ordinary shares,par value$0.10 per share.Prior to this offering,there has

15、been no public market for our ordinary shares.We anticipate the initial publicoffering price per share will be between$and$.We intend to apply for the listing of the ordinary shares on the Nasdaq Capital Market(“Nasdaq”),under thesymbol“APRI.”There is no assurance that such application will be appro

16、ved,and if our application is notapproved,this offering will not be completed.We are an“emerging growth company”and a“foreign private issuer”under applicable U.S.federal securitieslaws and are eligible for reduced public company reporting requirements.See“Prospectus SummaryImplications of Being an E

17、merging Growth Company”and“Prospectus SummaryImplications of Being aForeign Private Issuer”for additional information.Investing in our ordinary shares involves a high degree of risk,including the risk of losing your entireinvestment.See“Risk Factors”beginning on page 16 of this prospectus for a disc

18、ussion of information thatshould be considered in connection with an investment in our ordinary shares.Neither the Securities and Exchange Commission nor any other state securities commission has approvedor disapproved of these securities or passed upon the accuracy or adequacy of this prospectus.An

19、yrepresentation to the contrary is a criminal offense.Perordinaryshare TotalPublic offering price$Underwriting discounts and commissions(1)$Proceeds,before expenses,to APRINOIA Therapeutics Inc.$(1)See“Underwriting”for additional disclosure regarding compensation payable by us to the underwriters.We

20、 have granted the underwriters the right to purchase up to an additional ordinary shares at the initialpublic offering price,less underwriting discounts and commissions.The underwriters expect to deliver the ordinary shares to purchasers on or about ,2024 through thebook-entry facilities of The Depo

21、sitory Trust Company.US Tiger Securities,Inc.,2024TABLE OF CONTENTSTable of ContentsPROSPECTUS SUMMARY 1THE OFFERING 12SUMMARY CONSOLIDATED FINANCIAL DATA 14RISK FACTORS 16SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS 59USE OF PROCEEDS 61DIVIDEND POLICY 62CAPITALIZATION 63DILUTION 65ENFORCEABILI

22、TY OF CIVIL LIABILITIES 67MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OFOPERATIONS 68MARKET,INDUSTRY AND OTHER DATA 84BUSINESS 85GOVERNMENT REGULATION 110MANAGEMENT 121PRINCIPAL SHAREHOLDERS 129CERTAIN RELATIONSHIPS AND RELATED PARTY TRANSACTIONS.131DESCRIPTION OF SHARE CA

23、PITAL 134SHARES ELIGIBLE FOR FUTURE SALE 145TAXATION 146UNDERWRITING 151EXPENSES RELATED TO THIS OFFERING 157LEGAL MATTERS 158EXPERTS 159WHERE YOU CAN FIND ADDITIONAL INFORMATION 160INDEX TO CONSOLIDATED FINANCIAL STATEMENTS F-1No dealer,salesperson or other person is authorized to give any informat

24、ion or to represent as to anything notcontained in this prospectus or in any free writing prospectus we may authorize to be delivered or made available toyou.You must not rely on any unauthorized information or representations.This prospectus is an offer to sell,andwe are seeking offers to buy,only

25、the ordinary shares offered hereby,and only under circumstances and injurisdictions where it is lawful to do so.The information contained in this prospectus is current only as of its date,regardless of the time of delivery of this prospectus or any sale of the ordinary shares.Neither we nor the unde

26、rwriters have done anything that would permit this offering or the possession ordistribution of this prospectus or any filed free writing prospectus in any jurisdiction where other action for thatpurpose is required,other than in the United States.Persons outside the United States who come into poss

27、ession ofthis prospectus or any free writing prospectus filed with the U.S.Securities and Exchange Commission(the“SEC”)must inform themselves about,and observe any restrictions relating to,the offering of the ordinary shares and thedistribution of this prospectus or any filed free writing prospectus

28、 outside of the United States.Until,2024(the 25th day after the date of this prospectus),all dealers that buy,sell or trade theordinary shares,whether or not participating in this offering,may be required to deliver a prospectus.This isin addition to the obligation of dealers to deliver a prospectus

29、 when acting as underwriters and with respectto their unsold allotments or subscriptions.iTABLE OF CONTENTSPROSPECTUS SUMMARYThe following summary is qualified in its entirety by,and should be read in conjunction with,the more detailedinformation and financial statements appearing elsewhere in this

30、prospectus.This summary does not contain all ofthe information that may be important to you in making your investment decision.In addition to this summary,weurge you to read the entire prospectus carefully,especially the risks of investing in our ordinary shares discussedunder“Risk Factors,”before d

31、eciding whether to invest in our ordinary shares.OverviewWe are a clinical-stage biotechnology company committed to protecting patients brain health and changingclinical outcomes for a broad range of neurodegenerative diseases by developing novel,highly sensitive andselective diagnostic tools and no

32、vel therapeutics.Our name,APRINOIA,merges“apricum,”the Latin word for sunlight,and“noia,”the Greek suffix for themind,reflecting our mission to shed light on ways to better diagnose and treat dreaded neurodegenerative diseaseswith a vision to offer a brighter future for patients with novel diagnosti

33、c tools and targeted therapeutics worldwide.Neurodegenerative diseases are relentless and largely fatal,resulting from progressive loss of nerve cells in thebrain and,depending on the specific disorders,can affect a broad range of cognitive,behavioral,and motorfunctions,such as memory,thinking,speak

34、ing,walking,and breathing.Although our understanding of theunderlying pathophysiology has grown over the past decade due to advances in neuroscience,a significant unmetneed remains for both accurate,safe and personalized diagnostics and effective and safe treatments.In harnessing the power of precis

35、ion neuroscience,we are developing several different diagnostic andtherapeutic platforms to detect and target both common and neurodegenerative disorders marked by abnormalprotein aggregates of tau and alpha-synuclein(“-Syn”)that are toxic to brain cells.Tau&Tauopathies.Tau is an important protein i

36、n the brain that exists in different forms and plays acritical role in brain function.Tauopathies are neurodegenerative diseases characterized by accumulationof aggregated tau protein in distinct brain regions,such as Progressive Supranuclear Palsy(“PSP”),Alzheimers disease(“AD”)and Picks disease(“P

37、iD”).Cumulative increases of these abnormalaggregates correlate with disease progression,and depending on the disorder can result in loss of memory,balance,walking and control of eye movements with the eventual loss of independent neurologic function.-Syn&synucleinopathies.-Syn is an important and h

38、ighly abundant protein in the brain that regulatesthe release of neurochemicals between brain cells.Synucleinopathies are neurodegenerative diseasescharacterized by aggregation of abnormal-Syn proteins.In synucleinopathies such as Parkinsons disease(“PD”),Lewy Body Dementia(“LBD”)and Multiple System

39、 Atrophy(“MSA”),abnormal-Synaggregates accumulate in specific brain regions,and depending on the disorder can result in progressiveloss of neurologic function,leading to problems with motor control,walking,balance,behavior andmemory.Tauopathies and synucleinopathies affect approximately 50 million a

40、nd 10 million people worldwide,respectively,and collectively account for most cases of dementia and movement disorders,resulting in devastatingemotional and socio-economic consequences,including prolonged hospitalizations,nursing home placement anddeath.See“BusinessOverview of Unmet Medical Needs an

41、d Market Opportunities in NeurodegenerativeDiseases”for more information.As detailed below,we are developing three platforms to diagnose and treat these disorders,namely:(1)positronemission tomography(“PET”)diagnostic tracers for tau and-Syn aggregates,with 18F-APN-1607(INN:florzolotau)(“APN-1607”)b

42、eing a 3 carboxy-terminal(“3R”)/4 carboxy-terminal domains(“4R”)tau PET tracerfor the diagnosis of PSP and related disorders,as well as AD;(2)an antibody platform,with APNmAb005 being anovel monoclonal antibody designed to offer greater selectivity for pathologic forms of tau that contribute to thep

43、athogenesis of AD and primary tauopathies;and(3)a protein degrader platform based on the proteolysis targetingchimeras(“PROTAC”)that targets pathological-Syn and tau proteins,which we believe potentially represents oneof the more innovative therapeutic approaches for the treatment of neurodegenerati

44、ve diseases,an area previouslythought to be undruggable by traditional small molecules.PET diagnostic tracer APN-1607.We are developing APN-1607 as a PET imaging tracer for the detectionof 3R and 4R tau aggregates,which contribute to the pathogenesis of various tauopathies,including PSP,arare1TABLE

45、OF CONTENTSneurodegenerative disease.There is no FDA-approved diagnostic marker for PSP.Based on Title 21 of theCode of Federal Regulations,Part 315,Diagnostics Radiopharmaceuticals,we seek two indication claimsfor APN-1607:(1)as a pathological or disease marker of 4R tau in PSP and(2)as clinically

46、useful markerfor the diagnostic management in patients who present with parkinsonian syndromes in whom thediagnosis of PSP is uncertain or requires confirmation.We have received an Orphan Drug Designation(“ODD”)from the U.S.Food and Drug Administration(the“FDA”)in 2017 for APN-1607 as a diagnosticag

47、ent for PSP.Under the U.S.Orphan Drug Act,the FDA may grant ODDs to drugs or biologics intendedto treat a“rare disease or condition”(defined as affecting fewer than 200,000 individuals in the UnitedStates).If a product with an ODD receives an initial FDA marketing approval,the product is entitled to

48、orphan exclusivity,which means the FDA may not approve any other applications to market the same drugfor the same indication for a period of seven years following marketing approval,except in certain verylimited circumstances,such as if the later product shows clinical superiority to the orphan prod

49、uct orwhere the manufacturer of the earlier product is unable to assure sufficient product quantity.However,wemay not be the first to obtain marketing approval for the orphan indication due to the competition from themarket.Further,ODD neither curtails the development period or regulatory review tim

50、e needed before thecommercialization of a product candidate nor presents the product candidate any advantage in theregulatory review or approval process.We are developing APN-1607 in PSP and AD globally,independently or in collaboration with our partner:We obtained a Study May Proceed letter from th

51、e FDA on December 8,2023 allowing us to conduct aPhase 3 clinical trial to evaluate the efficacy and safety of APN-1607 as a diagnostic marker for PSP.Wealso have a Phase 2 clinical trial for APN-1607 in AD in the United States,Japan and Taiwan,which isactive and not recruiting for the time being du

52、e to a reprioritization of resources,with the last patientenrolled on July 11,2022.Additionally,in collaboration with Yantai Yitai Pharmaceutical Technology Co.,Ltd.(“Yitai”),we launched a Phase 3 clinical trial,also for AD,in mainland China,which met its targetenrollment of 230 subjects,with the la

53、st subject enrolled on December 21,2023.Contingent on the resultsof this trial,Yitai plans to submit an NDA to Chinas National Medical Products Administration(“NMPA”)for the marketing approval of APN-1607 for the diagnosis of AD in mainland China.Seebelow for further details regarding these clinical

54、 programs.Antibody platform and APNmAb005.APNmAb005 is a humanized anti-tau antibody we are developingfor the treatment of AD,non-AD primary tauopathies including rare neurodegenerative disorders,such asPSP,cortico-basal degeneration(“CBD”)and behavioral variant Frontal Temporal Dementia(“FTD”)orits

55、 subcategory,Picks Disease(“PiD”).Unlike most other anti-tau antibodies currently in clinicaldevelopment that bind to all forms of tau or phospho-tau(i.e.,sites on tau protein that undergophoshoprylation in disease state),APNmAb005 is designed to target a specific conformation epitope in tauoligomer

56、s/aggregates formed at axons/dendrites at early stages of disease that may contribute to diseaseprogression.Based on existing clinical studies,we believe that blocking the pathological tau transmissionhas the potential to offer an effective treatment to slow down the disease progression for AD patie

57、nts.While the recent approval of two anti-amyloid antibody treatments aducanumab(Aduhelm)andlecanemab(Leqembi)represents a significant advance in the field,their widespread use will be likelylimited due to safety concerns arising from anti-amyloid imaging related abnormalities(“ARIA”).Furthermore,de

58、spite the dramatic reductions in amyloid pathology,suggested by recent studies,theirefficacy in slowing cognitive decline in such studies was modest.These findings are consistent with thelong-standing notion that although the accumulation of amyloid plays a critical role in the pathogenesis ofAD,cle

59、aring amyloid alone is insufficient to completely block or prevent disease progression and arguesfor the discovery of other disease modifying targets such pathological forms of tau,which correlate withdisease progression and cognitive decline.An IND for APNmAb005 was filed on February 24,2022,andthe

60、 FDA granted a Study May Proceed letter on April 20,2022,for the Phase 1 trial to evaluate the safetyof APNmAb005 in healthy volunteers.The first cohort of 8 subjects was dosed and the safety review wascompleted on August 18,2023.There were no clinically significant safety findings.The study is curr

61、entlyactive and not recruiting for the time being due to a reprioritization of resources.Dosing of the remainingcohorts is anticipated to resume in the fourth quarter of 2024.Protein degrader platform and PROTAC degraders.Our proprietary PROTAC degrader programs for-Syn and tau are our most innovati

62、ve and cutting-edge platforms and have the potential to herald an entirelynew class of drugs for the treatment of neurodegenerative disorders such as AD and PD.Our tau and-Syn degrader programs are currently in the preclinical stages.Empowered by our knowledge of2TABLE OF CONTENTSaggregated protein

63、binder chemistry from our PET tracer programs we have generated a proprietarydegrader library of 800+compounds in-Syn and tau degrader space.Potent-Syn degraders areidentified from a cellular model of human dopaminergic neurons and the active degraders have beenvalidated in animal models for selecti

64、vity,mechanism of action,physicochemical and metabolicproperties.Our data,as included elsewhere in the prospectus,demonstrate that it is feasible for this classof molecules to achieve reasonable brain penetration.Importantly,in preliminary studies we haveobserved significant reduction of pathologica

65、l-Syn in transgenic mice.Our tau degrader program issupported by Alzheimers Drug Discovery Foundation(“ADDF”)following their rigorous scientificreview process.The active compounds identified from our degrader library are highly selective foraggregated pathological tau while sparing the normal monome

66、r tau.Similar to that with-Syn degraders,we have conducted extensive work to validate the degrader mechanism and characterize metabolic andpharmacokinetic features.Both degrader programs are currently at lead optimization stages aiming forimproved physicochemical properties,brain exposure and eventu

67、ally robust in vivo efficacy by oraldosing.Our goal is to advance at least one degrader compound to IND-enabling GLP toxicology studies in2025.See“Business Our Next-Generation Diagnostic Pipeline”and“Business Our Differentiated TherapeuticPlatforms and Pipeline Our Therapeutic Platforms”below for fu

68、rther details regarding our platforms.Aninherent risk in all clinical trials,is that these trials may fail for different reasons if the results do not meet theprimary endpoint.For a detailed discussion of the risks associated with clinical trials,see“Risk Factors If theclinical trials of any of our

69、product candidates fail to demonstrate safety and efficacy to the satisfaction of the FDAor other regulatory authorities,or do not otherwise produce favorable results,we may incur additional costs orexperience delays in completing,or ultimately be unable to complete,the development and commercializa

70、tion of ourproduct candidates.”Our PipelineLeveraging our three platforms,we are developing a pipeline as shown below:Notes:(1)Phase 2 clinical trial of APN-1607 tau tracer for AD in the United States,Japan and Taiwan,is active non-recruiting.(2)Our tau PET tracer APN-1607 improved upon a previously

71、 developed first generation compound from National Institute forQuantum Science and Technology(“QST”)in Japan.We obtained an exclusive worldwide license from QST for its patentfor APN-1607 in 2016.We have an exclusive license for worldwide rights to develop and commercialize APN-1607,exceptfor mainl

72、and China,where we granted an exclusive sublicense for its development,manufacture,marketing and distributionto Yantai Yitai Pharmaceutical Technology Co.,Ltd.Diagnostics PipelineWe are developing PET imaging agents for the diagnosis and tracking of neurodegenerative disorders such asAD,PSP and rela

73、ted tauopathies and synucleinopathies.Our diagnostic pipeline includes PET tracers that targetabnormal tau and-Syn protein aggregates and enable(i)the visualization of their distribution in brain regions and(ii)their quantification.Currently,early diagnostic markers for most neurodegenerative diseas

74、es do not exist.This is particularly truefor patients who may have PSP or one of its variants,where in most cases clinicians cannot differentiate amongthese3TABLE OF CONTENTSdisorders or make specific diagnoses without pathological confirmation(i.e.,autopsy).Our diagnostic productcandidates,if appro

75、ved,may provide clinicians with powerful and quantifiable tools to make more accurate clinicaldiagnoses earlier in the course of a neurodegenerative disease,potentially enable differentiation among differentneurodegenerative disorders that clinically can resemble each other,such as PSP and PD,and im

76、portantly,enableclinicians to intervene with novel therapies that may be more likely effective at earlier stages of the disorder.Thesetracers may also improve the probability of success of clinical trials,by enabling the recruitment of patients at earlierstages of disease,who are more likely respond

77、 to treatment as was recently shown in the Phase 3 clinical trials forlecanemab and donanemab.Our lead diagnostic product candidate(APN-1607).APN-1607 is our 3R/4R tau PET tracer and mostclinically advanced diagnostic product candidate.APN-1607 is designed as a new generation tau PETtracer to achiev

78、e a higher specificity for the pathological tau aggregates.We believe that APN-1607,ifapproved,has the potential to be a powerful enabling tool for the diagnosis of various tauopathies,as it hasshown low non-specific binding to other brain proteins,and the ability to detect different forms of tau in

79、clinical studies.APN-1607 may therefore potentially be used in more precise diagnosis and stageclassification of various tauopathies,including PSP,AD and PiD.APN-1607 is being studied in PSP,for which we hold an ODD.In July 2023,the FDA agreed that wecould conduct a single Phase 3 clinical trial of

80、APN-1607 as a basis for approval without a pathologystudy,normally required for these types of programs.In lieu of a second trial,we will provideconfirmatory evidence to support the diagnostic accuracy of the APN-1607 using other data sources suchas the existing clinical imaging data obtained from o

81、ur investigator-initiated studies in PSP patients.On November 9,2023,we filed an IND with the FDA to launch a single Phase 3 global clinical trial forAPN-1607 in subjects suspected to have PSP.On December 8,2023,the FDA issued a Study May Proceedletter,allowing us to conduct a Phase 3 trial to evalu

82、ate the efficacy and safety of APN-1607 as adiagnostic marker for PSP.We plan to implement this trial in the United States,Europe,the UnitedKingdom,Japan and Taiwan and submit results from this trial as a basis for regulatory approval in theUnited States,and subsequently seek marketing authorization

83、 in Europe and Asia.We have also initiated aPhase 2 clinical trial of APN-1607 in AD in the United States,Japan and Taiwan,which is active and notrecruiting for the time being due to a reprioritization of resources,with the last patient enrolled on July 11,2022.APN-1607 is also being studied in a Ph

84、ase 3 clinical trial in AD in mainland China through ourcollaboration with Yitai,a wholly-owned subsidiary of Yantai Dongcheng Biochemicals Co.,Ltd(togetherwith its subsidiaries,“Dongcheng Pharma”).The trial has met its target enrollment of 230 patients,withthe last patient dosed on December 21,2023

85、.Contingent on the results of this trial,Yitai plans to submitan NDA to the NMPA for the marketing approval of APN-1607 for the diagnosis of AD in mainlandChina.We also plan to combine(i)the results from APN-1607s Phase 2 clinical trial in AD in the United States,Japan and Taiwan,(ii)the results fro

86、m APN-1607s Phase 3 clinical trial in AD in mainland China togetherwith(iii)imaging data of APN-1607 collected from investigator-initiated studies in over 3,300 patients toseek concurrence from the FDA for a single pivotal trial of APN-1607 as a diagnostic marker for AD in theUnited States and poten

87、tially other markets.See“Business Our Next-Generation Diagnostic Pipeline”below for more details about APN-1607 and ourother preclinical stage tracers.Therapeutics PipelineOur lead clinical therapeutic product candidates arise through our screening platforms with the aim to preciselyrecognize and ne

88、utralize the pathological tau and-Syn aggregates that contribute to the pathogenesis underlyingseveral neurodegenerative disorders.Our monoclonal antibodies to pathological forms of tau aim to reduce thedamaging effects and“spreading”of such tau forms outside the affected neuron cells to slow or eve

89、n prevent diseaseprogression.Meanwhile,our degrader pipeline aims to tackle the diseases from inside neurons by removing distinctprotein aggregates inside cells by delivering these toxic proteins to the cells machinery for degradation.Our lead therapeutic product candidate(APNmAb005).APNmAb005 is a

90、humanized anti-tau antibodyand our most clinically advanced therapeutic product candidate.APNmAb005 is designed to preferentiallybind pathological tau aggregates,not normal tau,that accumulate at the neuronal synapses with disease.In4TABLE OF CONTENTSaddition,based on preclinical studies we conducte

91、d,APNmAb005 recognizes a three-dimensionalconformation-dependent epitope that is only present in tau abnormal aggregates but not in normal tauprotein,thus suggesting this product candidate may achieve a high level of selectivity for pathologicalforms of tau.An IND for APNmAb005 was filed on February

92、 24,2022,and the FDA granted a Study May Proceedletter on April 20,2022,for the Phase 1 trial to evaluate the safety of APNmAb005 in healthy volunteers.The first cohort of 8 subjects was dosed and the safety review was completed on August 18,2023.Therewere no clinically significant safety findings.T

93、he study is currently active and not recruiting for the timebeing due to a reprioritization of resources.Dosing of the remaining cohorts is anticipated to resume in thefourth quarter of 2024.Our lead therapeutic product candidate(Degrader).PROTACs offer a highly novel platform for thetargeted degrad

94、ation of toxic proteins that are causative in a number of neurodegenerative disorders asdescribed above.These are bifunctional molecules that combine an active site selective for binding to thetarget of interest(tau or-Syn)and a ligand(a binding site)for E3 ubiquitin ligase to drive the selectivedeg

95、radation of these proteins inside the cells proteasome.First-generation degraders are now enteringclinical trials for cancer treatment,but currently there are no degraders in clinical development forneurodegenerative diseases.PROTAC is a potentially ground-breaking approach for the treatment ofprote

96、inopathies in neurodegenerative diseases that have been considered undruggable targets fortraditional small molecules.Most of the PROTAC drugs currently in development are based on publishedE3 ligand structures,which leaves the warhead that targets the protein of interest as the key componentthat dr

97、ives target specificity.It is noteworthy that the popular PROTAC targets in cancer are wellcharacterized by soluble proteins such as CDK2,BTK4 and ER and in some cases allow for structureguided drug design.By contrast,the pathological proteins implicated in neurodegenerative diseases aremore complex

98、 for warhead discovery as well as degrader screening.In this regard,we believe ourPROTAC program is highly competitive in this field due to innovation in our PET ligand chemistry andexpertise in disease biology which have enabled us to generate a diverse library to screen tau and-Syndegraders and ch

99、aracterize them in cellular assays and animal models that recapitulate pathological-Synor tau formation.Our tau and-Syn degrader programs are currently in the preclinical stage.Built upon our PET tracerprograms we have generated a degrader sub-library by combining our collection of pathological tau

100、and-Syn binders with various linkers and E3 ligands.We have since identified candidate degraders that wereshown to selectively drive the degradation of pathological-Syn and tau in cellular models.We are in theprocess of further charactering these candidate degraders in preclinical studies and hope t

101、o eventuallyadvance them into clinical development.See“Business Our Differentiated Therapeutic Platforms and Pipeline Our Therapeutic ProductCandidates”below for more details about APNmAb005,tau degraders and-Syn degraders.Our StrategyWe aim to combine novel diagnostic tools and targeted therapies t

102、o better diagnose and treat debilitating anddeadly neurodegenerative diseases.Our strategy encompasses the following clinical and commercializationelements:Develop novel solutions to overcome the challenges in diagnosing and treating neurodegenerativediseases.Continue to execute our versatile R&D an

103、d commercialization strategy to maximize asset value.Create product-by-product and region-by-region commercialization strategies in anticipation of our futureproduct launches.Our Management TeamWe have brought together a world-class management team with extensive experience to bring drugs forward.Ou

104、r founder and chairman of the board,Dr.Ming-Kuei Jang,Ph.D.,has over 20 years of experience inneurodegenerative diseases.He also serves as the Chief Scientific Officer of APRINOIA USA andPresident of our Asia operations.Prior to founding our company,Dr.Jang held an associate director role atGlaxoSmi

105、thKline in Shanghai,served as senior research biologist of Merck&Co in Boston,Massachusetts,and led Neurodegeneration Consortium at MD Anderson Cancer Center in Houston,Texas.5TABLE OF CONTENTSOur Chief Executive Officer,Dr.Mark S.Shearman,Ph.D.,has extensive experience in pharmaceuticalresearch,dru

106、g development and strategic partnerships.Prior to joining us,Dr.Shearman served as theChief Scientific Officer at Editas Medicine,Chief Scientific Officer at Applied Genetic TechnologiesCorporation,a Senior Vice President of research and early development at Merck KGAa.He also served atMerck&Co.,wit

107、h his last position as an executive director,and Merck,Sharp&Dohme,with his lastposition as a senior director of department of cellular&molecular neuroscience responsible for theresearch and development of AD.Our Chief Medical Officer,Dr.Bradford A.Navia,M.D.,Ph.D.,has over 17 years of experience in

108、 clinicaldevelopment(including Phase 1 through Phase 3),neuroimaging and biomarkers in psychiatry andneurology,including several INDs,sNDAs and an NDA.Prior to joining us,Dr.Navia was an AssociateProfessor of Neurology and Psychiatry at Tufts Medical School,and the recipient of numerous awards andfu

109、nding from National Institute of Health;executive director of Sunovion Pharmaceuticals,where he wasthe global project lead for the development of KYNMOBI;senior director,strategic and clinical lead in theneuroscience division at AbbVie Inc.;senior director and head of neuroimaging at Eisai Co.,Ltd.a

110、nddirector in the neuroscience clinical development division at Johnson&Johnson.Our Chief Financial Officer,Brian Achenbach,M.B.A.,has over 30 years of experience in finance andaccounting primarily in the biotech,pharmaceutical and medical device industries.Prior to joining us,Mr.Achenbach served as

111、 Chief Financial Officer at On Demand Pharmaceuticals,Senior Vice President ofFinance&Corporate Controller at Mustang Bio(Nasdaq:MBIO),and has held leadership positions infinance and accounting in multiple life sciences companies.Our General Counsel,Lana Gladstein,J.D.,has over 23 years of experienc

112、e in legal and pharmaceuticalindustry.Prior to joining us,Ms.Gladstein served as Chief Legal Officer and General Counsel of ArrantaBio(acquired by Recipharm),Chief Legal Officer of Recipharm(Americas)post acquisition of ArrantaBio,Executive VP and General Counsel at Brammer Bio(acquired by Thermo Fi

113、sher Scientific),andGeneral Counsel of Viral Vector Services of Thermo Fisher Scientific post acquisition of Brammer Bio.Prior to that,Ms.Gladstein spent over 16 years in private practice,including as partner at NutterMcClennen&Fish LLP and Pepper Hamilton LLP,where she focused her practices in inte

114、llectualproperty litigation and strategies.Summary of Risk FactorsOur business is subject to numerous risks and uncertainties that you should be aware of before making adecision to invest in our ordinary shares.These risks are more fully described in the section entitled“Risk Factors”immediately fol

115、lowing this prospectus summary.These risks include,among others,the following:Risks Related to Our Limited Operating History,Financial Position and Need for Additional CapitalWe are a clinical-stage biotechnology company with a limited operating history and face significantchallenges and expenses as

116、 we build our capabilities and develop our pipeline of diagnostic andtherapeutic product candidates.We have incurred net losses since our inception and anticipate that we will continue to incur significantlosses for the foreseeable future.We have never generated any revenue from product sales and ma

117、y neverbe profitable.We recorded net cash outflow from operating activities since our inception.We may need to acquirefunding from time to time to complete the development and commercialization of our pipeline candidates,which may not be available on acceptable terms,or at all.If we are unable to ra

118、ise capital when needed,we may be forced to delay,reduce or eliminate certain of our product development programs or otheroperations.Our independent registered public accounting firms report contains an explanatory paragraph thatexpresses substantial doubt about our ability to continue as a“going co

119、ncern.”Raising additional capital may cause dilution to the interests of our shareholders,restrict our operations orrequire us to relinquish rights to our technologies or product candidates.6TABLE OF CONTENTSRisks Related to the Development of Our Product CandidatesWe depend heavily on the success o

120、f our lead diagnostic product candidate APN-1607,and,to a lesserextent,our anti-tau antibody product candidate,APNmAb005,and our degrader programs,all of which arecurrently or expected to be in clinical development.If our clinical trials are unsuccessful,we or ourcollaboration partner,Yantai Yitai P

121、harmaceutical Technology Co.,Ltd.(“Yitai”),a wholly-ownedsubsidiary of Dongcheng Pharma,do not obtain regulatory approval in the targeted jurisdictions,or we orYitai are unable to commercialize APN-1607,APNmAb005 or degraders,or experience significant delaysin doing so,our business,our financial con

122、dition and results of operations will be materially adverselyaffected.We operate in highly competitive and rapidly changing industries.Our competitors are evaluatingdiagnostic product candidates in the same indication as our lead diagnostic product candidate,APN-1607,such as AD and PSP,and could ent

123、er the market with competing products of our product candidates,whichmay result in a material decline in sales of affected product candidates.A fast track,breakthrough therapy or other designation by the FDA may not actually lead to a fasterdevelopment or regulatory review or approval process.Even i

124、f we successfully obtain regulatory approvals for our product candidates,they may not gain marketacceptance,in which case we may not be able to generate product revenues,which will materiallyadversely affect our business,financial condition and results of operations.Risks Related to Our OperationsAs

125、 a company with operations outside of the United States,our business is subject to economic,political,regulatory and other risks associated with international operations.Our future growth and ability to compete depend on retaining our key personnel and recruiting additionalqualified personnel.We are

126、 a fast-growing emerging company and expect to expand our development and regulatorycapabilities,and as a result,we may encounter difficulties in managing our growth,which could disruptour operations.Risks Related to Our Relationships with Third PartiesIf we fail to maintain our relationships with o

127、ur current or future business and licensing partners,ourbusiness,commercialization prospects and financial condition may be materially adversely affected.We may seek to form additional strategic alliances in the future with respect to our product candidates,andif we do not realize the benefits of su

128、ch alliances,our business,financial condition,commercializationprospects and results of operations may be materially adversely affected.We rely on third parties to conduct our nonclinical studies and clinical trials and perform other tasks forus.If these third parties do not successfully carry out t

129、heir contractual duties,meet expected deadlines,orcomply with regulatory requirements,we may not be able to obtain regulatory approval for orcommercialize our product candidates and our business could be substantially harmed.Risks Related to Regulatory Approval of Our Product Candidates and Other Le

130、gal Compliance MattersAll material aspects of the research,development,manufacturing and commercialization ofpharmaceutical products are heavily regulated,and we may face difficulties in complying with or beunable to comply with such regulations,which could have a material adverse effect on our busi

131、ness.The approval processes of regulatory authorities in the United States are lengthy,time-consuming andinherently unpredictable.If we are ultimately unable to obtain regulatory approval for our productcandidates,our business will be substantially harmed.Even if we complete the necessary preclinica

132、l studies and clinical trials,the regulatory approval process isexpensive,time-consuming and uncertain and may prevent us from obtaining approvals for thecommercialization of some or all of our product candidates.As a result,we cannot predict when or if,andin which territories,we will obtain marketi

133、ng approval to commercialize product candidates.7TABLE OF CONTENTSObtaining and maintaining regulatory approval of our product candidates in one jurisdiction does notmean that we will be successful in obtaining regulatory approval of our product candidates in otherjurisdictions.Risks Related to the

134、Commercialization of Our Product CandidatesIf we are unable to establish sales,marketing and distribution capabilities for our product candidates,orenter into sales,marketing and distribution agreements with third parties,we may not be successful incommercializing our product candidates,if and when

135、they are approved.The successful commercialization of our product candidates will depend in part on the extent to whichgovernmental authorities and health insurers establish adequate coverage and reimbursement levels andpricing policies.We have never commercialized a product candidate before,which m

136、ay make it difficult to evaluate theprospects for our future viability,and may lack the necessary expertise,personnel and resources tosuccessfully commercialize our product candidates on our own or together with suitable partners.Risks Related to Our Intellectual PropertyWe may not have sufficient p

137、atent terms to effectively protect our future approved product candidates andbusiness.If we or our collaboration partner are unable to obtain,maintain,defend and enforce patent and otherintellectual property rights for our technologies and product candidates,or if the scope of the patent andother in

138、tellectual property rights obtained is not sufficiently broad,our competitors and other third partiescould develop and commercialize technology and biologics similar or identical to ours,and our ability tosuccessfully commercialize our technology and product candidates may be impaired.We or our coll

139、aboration partner may become subject to intellectual property-related litigation or otherproceedings to protect or enforce our patents or the patents of our licensors or collaborators,any of whichcould be expensive,time-consuming,and unsuccessful,and may ultimately result in our loss of ownershipof

140、intellectual property.General Risk FactorsBusiness interruptions could seriously harm our future revenue and financial condition,increase our costsand expenses and delay us in the process of developing our product candidates.We may be subject to claims by third parties asserting that we or our emplo

141、yees,consultants orindependent contractors have misappropriated,wrongfully used or disclosed their confidential informationor trade secrets or other intellectual property or claiming ownership of what we regard as our ownintellectual property.Corporate History and InformationWe commenced our operati

142、ons under APRINOIA Therapeutics,Inc.,which was incorporated under the laws ofTaiwan in May 2015(“APRINOIA Taiwan”).In June 2016,our company,APRINOIA Therapeutics,Inc.wasincorporated in the Cayman Islands as the holding company for APRINOIA Taiwan,which was subsequentlydissolved in May 2022.In June 2

143、017,we incorporated APRINOIA Therapeutics Limited(“APRINOIA HK”)as ourwholly-owned subsidiary in Hong Kong.Subsequently in July 2017,APRINOIA HK incorporated a direct wholly-owned subsidiary,Suzhou APRINOIA Therapeutics Co,Ltd.,in Suzhou.In September 2017 and April 2021,respectively,we incorporated

144、APRINOIA Therapeutics as our wholly-owned subsidiary in Japan,andAPRINOIA Therapeutics,LLC as our wholly-owned subsidiary in the United States.In December 2023,weincorporated APRINOIA Therapeutics Limited as our wholly-owned subsidiary in Ireland.Our principal executiveoffices are located at 245 Mai

145、n Street,2nd Floor,Cambridge,MA 02142.Our telephone number at this address is617-225-4415.Our registered office is located at the offices of Maples Corporate Services Limited,PO Box 309,Ugland House,Grand Cayman,KY1-1104,Cayman Island.Investors should submit any inquiries to the address andtelephone

146、 number of our principal executive offices set forth above.Our main website is .The information contained on this website is not a part of thisprospectus.8TABLE OF CONTENTSThis prospectus includes certain trademarks,service marks and trade names,such as“APRINOIA,”which areregistered under applicable

147、 intellectual property laws and are APRINOIAs property or for which APRINOIA haspending applications or common law rights.Solely for convenience,trademarks,service marks and trade namesreferred to in this prospectus are listed without any,or other symbols,but APRINOIA intends to assert,to thefullest

148、 extent under applicable law,its right or the rights of the applicable licensors to these trademarks,servicemarks and trade names.The use or display of other companies trademarks,service marks or trade names should notbe interpreted to imply a relationship with,or endorsement or sponsorship of APRIN

149、OIA by,any other companies.Implications of Being an Emerging Growth CompanyWe are an“emerging growth company”as defined in the Jumpstart Our Business Startups Act(“JOBS Act”)enacted in April 2012,and we may remain an emerging growth company for up to five years following thecompletion of this offeri

150、ng.For so long as we remain an emerging growth company,we are permitted and intend torely on certain exemptions from various public company reporting requirements,including not being required tohave our internal control over financial reporting audited by our independent registered public accounting

151、 firmpursuant to Section 404(b)of the Sarbanes-Oxley Act of 2002(“Sarbanes-Oxley Act”)reduced disclosureobligations regarding executive compensation in our periodic reports and proxy statements,and exemptions from therequirements of holding a nonbinding advisory vote on executive compensation and an

152、y golden parachute paymentsnot previously approved.In particular,in this prospectus,we have provided only two years of audited financialstatements and have not included all of the executive compensation-related information that would be required if wewere not an emerging growth company.Accordingly,t

153、he information contained herein may be different than theinformation you receive from other public companies in which you hold shares.In addition,the JOBS Act provides that an emerging growth company can take advantage of an extendedtransition period for complying with new or revised accounting stan

154、dards.This provision allows an emerging growthcompany to delay the adoption of some accounting standards until those standards would otherwise apply to privatecompanies.We have elected to take advantage of the benefits of this extended transition period and,therefore,weare not subject to the same re

155、quirements to adopt new or revised accounting standards as other public companiesthat are not emerging growth companies;however,we may adopt certain new or revised accounting standards early.We would cease to be an“emerging growth company”upon the earliest to occur of:(i)the last day of the fiscal y

156、earin which we have$1.235 billion or more in annual revenue;(ii)the date on which we first qualify as a largeaccelerated filer under the rules of the SEC;(iii)the date on which we have,in any three-year period,issued morethan$1.0 billion in non-convertible debt securities;and(iv)the last day of the

157、fiscal year ending after thefifth anniversary of this offering.We are also a“smaller reporting company”as defined in the Securities Exchange Act of 1934,as amended(the“Exchange Act”).We may continue to be a smaller reporting company even after we are no longer an emerginggrowth company.We may take a

158、dvantage of certain of the scaled disclosures available to smaller reportingcompanies and will be able to take advantage of these scaled disclosures for so long as our ordinary shares held bynon-affiliates is less than$250.0 million measured on the last business day of our second fiscal quarter,or o

159、urannual revenue is less than$100.0 million during the most recently completed fiscal year and our ordinary sharesheld by non-affiliates is less than$700.0 million measured on the last business day of our second fiscal quarter.Implications of Being a Foreign Private IssuerUpon completion of this off

160、ering,we will report under the Exchange Act as a non-U.S.company with foreignprivate issuer status.Even after we no longer qualify as an emerging growth company,as long as we qualify as aforeign private issuer under the Exchange Act we will be exempt from certain provisions of the Exchange Act thata

161、re applicable to U.S.domestic public companies,including:the sections of the Exchange Act regulating the solicitation of proxies,consents or authorizations inrespect of a security registered under the Exchange Act;the sections of the Exchange Act requiring insiders to file public reports of their sh

162、are ownership andtrading activities and liability for insiders who profit from trades made in a short period of time;andthe rules under the Exchange Act requiring the filing with the SEC of quarterly reports on Form 10-Qcontaining unaudited financial and other specified information,or current report

163、s on Form 8-K,upon theoccurrence of specified significant events.Additionally,Nasdaq market rules permit a foreign private issuer like us to follow the corporate governancepractices of its home country.Certain corporate governance practices in the Cayman Islands,which is our home9TABLE OF CONTENTSco

164、untry,may differ significantly from Nasdaq corporate governance listing standards.We may elect to follow homecountry practice in lieu of one or more of the following requirements:the requirement that a majority of the board of directors must be comprised of independent directors asdefined in Nasdaq

165、Rule 5605(a)(2);the requirement that each member of the compensation committee must be an independent director as setforth in Nasdaq Rule 5605(d)(2)(A);the requirement that director nomination should be made by a vote in which only independent directorsparticipate or by a nominations committee compr

166、ised solely of independent directors as set forth inNasdaq Rule 5605(e)(1);the requirement to obtain shareholder approval for certain issuances of securities,including shareholderapproval of stock option plans;the requirement that the board of directors shall have regularly scheduled meetings at whi

167、ch onlyindependent directors are present as set forth in Nasdaq Rule 5605(b)(2);andthe requirement that an annual shareholders meeting must be held no later than one year after the end ofthe fiscal year-end as set forth in Nasdaq Rule 5620(a).Both foreign private issuers and emerging growth companie

168、s are also exempt from certain more stringentexecutive compensation disclosure rules.Thus,even if we no longer qualify as an emerging growth company,butremain a foreign private issuer,we will continue to be exempt from the more stringent compensation disclosuresrequired of companies that are neither

169、 an emerging growth company nor a foreign private issuer.Conventions that Apply to this ProspectusUnless otherwise indicated or the context otherwise requires,in this prospectus:“Cayman Islands Companies Act”or“Companies Act”means the Companies Act(As Revised)of theCayman Islands.“option”means an op

170、tion to purchase Ordinary Shares granted under an incentive plan.“ordinary shares”means ordinary shares of our company,par value$0.10 per share.“our incentive plans”means,collectively,(i)the equity incentive plan we adopted in 2018,(ii)the equityincentive plan#2 we adopted in 2019,(iii)the equity in

171、centive plan#3 we adopted in 2022,and(iv)the equityincentive plan#4 we adopted in 2023,and each individually,an“incentive plan.”“preferred shares”means,collectively,Series B Shares,Pre-Series C Shares and Series C Shares.“Pre-Series C Shares”means Pre-Series C preferred shares of our company,of a no

172、minal or par value of$0.10each.“Series B Shares”means Series B preferred shares of our company,of a nominal or par value of$0.10 each.“Series C Shares”means Series C preferred shares of our company,of a nominal or par value of$0.10 each.“shares”means,collectively,ordinary shares and preferred shares

173、.“U.S.”means the United States.“we,”“us,”“our company”and“our”means to APRINOIA Therapeutics Inc.and its subsidiaries.“$,”“U.S.dollars,”“$,”or“dollars”means the legal currency of the United States.Conventions that Apply to this ProspectusUnless otherwise indicated or the context otherwise requires,i

174、n this prospectus:“3R”means 3 carboxy-terminal domains.“4R”means 4 carboxy-terminal domains.“AD”means Alzheimers disease.“APN-1607”means 18F-APN-1607(INN:florzolotau).10TABLE OF CONTENTS“ARIA”means antiamyloid imaging related abnormalities.“a-Syn”means alpha-synuclein.“CBD”means cortico-basal degene

175、ration.“CMO”means contract manufacturing organization.“CNS”means central nervous system.“cryoEM”means cryogenic electron microscopy.“CTE”means Chronic Traumatic Encephalopathy.“FTD”means Frontal Temporal Dementia.“IND”means Investigational New Drug.“LBD”means Lewy Body Dementia.“MSA”means Multiple S

176、ystem Atrophy.“NDA”means New Drug Application.“ODD”means Orphan Drug Designation.“PD”means Parkinsons disease.“PET”means positron emission tomography.“PiD”means Picks disease.“PROTAC”means proteolysis targeting chimeras.“PSP”means Progressive Supranuclear Palsy.“PSPRS”means Progressive Supranuclear

177、Palsy Rating Scale.“SUVr”means Standardized Uptake Value Ratio.“UPS”means ubiquitin-proteasome system.11TABLE OF CONTENTSTHE OFFERINGOffering priceWe expect that the initial public offering price will bebetween$and$per ordinary shares.Ordinary shares offered by usordinary shares(or ordinary shares i

178、f theunderwriters exercise their option to purchase additionalordinary shares in full).Over-allotment optionWe have granted to the underwriters an option,exercisable within 45 days from the date of thisprospectus,to purchase up to an aggregate of additional ordinary shares.Ordinary shares issued and

179、 outstanding immediatelyafter this offeringordinary shares(or ordinary shares if theunderwriters exercise their option to purchase additionalordinary shares in full).Use of proceedsWe expect that we will receive net proceeds ofapproximately$million from the sale of ordinaryshares in this offering,as

180、suming an initial publicoffering price of$per ordinary shares,which is themidpoint of the price range set forth on the cover pageof this prospectus,after deducting the estimatedunderwriting discounts and commissions and estimatedoffering expenses payable by us.We intend to use the net proceeds from

181、this offering,together with our existing cash and cash equivalents,toadvance the clinical development of APN-1607 andAPNmAb005,research and development of ourdegrader therapeutic candidates,other research anddevelopment activities as well as for working capital andother general corporate purposes.Se

182、e“Use of Proceeds”for additional information.Lock-upWe and certain of our shareholders have agreed with theunderwriters not to sell,transfer or dispose of anyordinary shares or similar securities for a period of180 days after the date of this prospectus,subject tocertain exceptions.See“Shares Eligib

183、le for Future Sale”and“Underwriting.”Risk factorsSee“Risk Factors”and other information included inthis prospectus for a discussion of the risks relating toinvesting in our ordinary shares.You should carefullyconsider these risks before deciding to invest in ourordinary shares.ListingWe intend to ap

184、ply to have the ordinary shares listed onthe Nasdaq.The ordinary shares and shares will not belisted on any other stock exchange or traded on anyautomated quotation system.Nasdaq trading symbolAPRIPayment and settlementThe underwriters expect to deliver the ordinary sharesagainst payment therefor th

185、rough the facilities of theDepositary Trust Company on,2023.12TABLE OF CONTENTSThe number of ordinary shares that will be issued and outstanding immediately after this offering:is based on the ordinary shares issued and outstanding as of the date of this prospectus,whichconsists of ordinary shares i

186、ssued and outstanding as of,2023,and the conversion of all of ourissued and outstanding preferred shares into ordinary shares immediately prior to the closing of thisoffering;excludes ordinary shares issuable upon the exercise of options outstanding as of,2023,with aweighted average exercise price o

187、f$per ordinary share;andexcludes ordinary shares available for future issuance under our equity incentive plans.Except as otherwise indicated,all information in this prospectus reflects and assumes:no exercise of the outstanding options described above;no exercise of the underwriters option to purch

188、ase additional ordinary shares;andthe effectiveness of our amended and restated memorandum and articles of association,which will occurimmediately prior to the completion of this offering.13TABLE OF CONTENTSSUMMARY CONSOLIDATED FINANCIAL DATAThe following summary consolidated statements of operation

189、s data for the years ended December 31,2022 and2021,summary consolidated balance sheets data as of December 31,2022 and 2021,and summary consolidatedstatements of cash flows data for the years ended December 31,2022 and 2021 have been derived from our auditedconsolidated financial statements include

190、d elsewhere in this prospectus.The following summary consolidatedstatements of operations data for the six months ended June 30,2023 and 2022,summary consolidated balance sheetdata as of June 30,2023,and summary consolidated statements of cash flows data for the six months ended June 30,2023 and 202

191、2 have been derived from our unaudited condensed consolidated financial statements includedelsewhere in this prospectus.Our consolidated financial statements are prepared and presented in conformity withgenerally accepted accounting principles in the United States of America(“U.S.GAAP”).Our historic

192、al results arenot necessarily indicative of results expected for future periods.You should read this section together with ourconsolidated financial statements and the related notes and“Managements Discussion and Analysis ofFinancial Condition and Results of Operations”included elsewhere in this pro

193、spectus.The following table sets forth a summary of our consolidated statements of operations for the periods/yearsindicated.For the six monthsended June 30,Year EndedDecember 31,2023 2022 Change%2022 2021 Change%($in thousands,except percentages)Selected consolidated statements ofoperations:Revenue

194、$496$295$201 68$394$550$(156)(28)Revenue related party 8,538 8,538 Total revenue 9,034 295 8,739 2,962 394 550 (156)(28)Operating expenses Research and development 11,067 11,289 (222)(2)21,617 19,660 1,957 10General and administrative 4,704 2,849 1,855 65 7,041 4,787 2,254 47Total operating expenses

195、 15,771 14,138 1,633 12 28,658 24,447 4,211 17Loss from operations (6,737)(13,843)7,106 (51)(28,264)(23,897)(4,367)18Other(expense)income:Interest expense,net (1,444)(13)(1,431)11,008 (67)(36)(31)86Change in fair value of derivativeliabilities 498 498 Other income(expense),net 551 186 365 196 117 67

196、2 (555)(83)Total other income(expense),net (395)173 (568)(328)50 636 (586)(92)Loss before income taxes (7,132)(13,670)6,538 (48)(28,214)(23,261)(4,953)21Provision for income taxes (53)(6)(47)783 (17)(17)Net loss$(7,185)$(13,676)$6,491 (47)$(28,231)$(23,261)$(4,970)21The following table sets forth se

197、lected consolidated balance sheets as of the periods/years indicated.As ofJune 30,As ofDecember 31,2023 2022 2021 ($in thousands)Selected consolidated balance sheets:Assets Current assets:Cash$7,731$1,221$9,674Prepaid expenses and other current assets 1,162 590 429Note receivable-related party 660 1

198、55Total current assets 9,553 1,811 10,258Property and equipment,net 1,957 2,153 509Deferred offering costs 2,807 1,288 Operating lease right-of-use assets 115 154 322Prepaid expenses,net of current portion and other long-term assets 44 237 1,677Total assets$14,476$5,643$12,76614TABLE OF CONTENTS As

199、ofJune 30,As of December 31,2023 2022 2021 ($in thousands)Liabilities,Redeemable Convertible Preferred Shares,and ShareholdersDeficit Current liabilities:Accounts payable$7,318$8,887$432Accrued expenses and other current liabilities 4,940 2,466 2,993Operating lease liabilities,current 102 124 154Rel

200、ated party payable 904 Short-term borrowings 690 1,450 785Convertible notes(including related parties convertible notes of$10,762 and$753as of June 30,2023 and December 31,2022,respectively,net of debt discountand issuance costs)14,788 1,093 Derivative liabilities(including related parties derivativ

201、e liabilities of$1,685 and$173 as of June 30,2023 and December 31,2022,respectively)2,679 251 Total current liabilities 30,517 15,175 4,364Operating lease liabilities,net of current portion 15 42 177Total liabilities 30,532 15,217 4,541Commitments and Contingencies Redeemable convertible preferred s

202、hares(Series B,Pre-C and C),$0.1 par value;56,973,336 shares authorized;53,622,601 shares issued and outstanding;redemption and liquidation value of$66,166 as of June 30,2023 andDecember 31,2022 65,876 65,876 56,913Shareholders deficit:Ordinary shares,$0.1 par value,443,026,664 shares authorized;40,

203、492,206 and38,617,056 shares issued and outstanding as of June 30,2023 and December 31,2022,respectively 4,049 3,862 3,835Additional paid-in capital 13,176 12,296 10,373Accumulated deficit (97,823)(90,638)(62,407)Accumulated other comprehensive loss (1,334)(970)(489)Total shareholders deficit (81,93

204、2)(75,450)(48,688)Total liabilities,redeemable convertible preferred shares,and shareholders deficit$14,476$5,643$12,766The following table sets forth a consolidated statements of cash flows for the periods/years indicated.For the Six Months EndedJune 30,For the Year EndedDecember 31,2023 2022 2022

205、2021 ($in thousands)Selected consolidated cash flow:Net cash used in operating activities$(5,451)$(9,808)$(17,237)$(24,303)Net cash used in investing activities (781)(878)(2,016)(317)Net cash provided by financing activities 13,287 9,002 11,354 31,492Effect of exchange rates on cash (545)(303)(554)(

206、60)Net increase(decrease)in cash$6,510$(1,987)$(8,453)$6,81215TABLE OF CONTENTSRISK FACTORSAn investment in our ordinary shares involves a high degree of risk.You should carefully consider the risks anduncertainties described below,together with all of the information contained in this prospectus,in

207、cluding ourfinancial statements and the related notes,before making an investment decision regarding the ordinary shares.Ifany of the following risks are realized,our business,financial condition,results of operations or prospects could bematerially and adversely affected.In that event,the market pr

208、ice of our securities could decline,and you could losepart or all of your investment.The risks discussed below also include forward-looking statements,and our actualresults may differ substantially from those discussed in these forward-looking statements.See“Special NoteRegarding Forward-Looking Sta

209、tements.”Risks Related to Our Limited Operating History,Financial Position and Need for Additional CapitalWe are a clinical-stage biotechnology company with a limited operating history and face significant challengesand expenses as we build our capabilities and develop our pipeline of diagnostic and

210、 therapeutic productcandidates.We are a clinical-stage biotechnology company with limited operating history.We expect to continue to incursignificant operating losses in the future as we continue our research and development efforts for our current andfuture diagnostic and therapeutic product candid

211、ates and seek to obtain regulatory approval and commercializationof such diagnostic and therapeutic product candidates,if approved.Investments in biotechnology and pharmaceutical product development are highly speculative because theyentail substantial upfront capital expenditures and a significant

212、risk that any potential product candidate will fail todemonstrate adequate effect or an acceptable safety profile,gain regulatory approval and become commerciallyviable.All of our diagnostic and therapeutic product candidates,including our lead diagnostic candidate,18F-APN-1607(“APN-1607”),a tau PET

213、 tracer,are still under clinical or preclinical development and none have beenapproved for commercial sale.We have not demonstrated an ability to successfully complete late-stage clinicaltrials,obtain regulatory approvals,arrange for a third-party to manufacture our product candidates at a commercia

214、lscale on our behalf,conduct sales and marketing activities necessary for successful commercialization,or obtainreimbursement in the countries of sale.We may encounter unforeseen expenses,difficulties,complications,anddelays in achieving our business objectives.Our short history as an operating comp

215、any makes any evaluation of ourfuture success or capability subject to significant uncertainty.If we do not address these risks successfully or areunable to transition at some point from a company with a research and development focus to a company capable ofsupporting commercial activities,then our

216、business may be materially harmed.We have incurred net losses since our inception and anticipate that we will continue to incur significant losses forthe foreseeable future.We have never generated any revenue from product sales and may never be profitable.We have no products approved for commercial

217、sale and have never generated any revenue from product salesand may never be profitable.We have incurred substantial operating losses since we commenced operations in 2015,despite that we have generated certain revenue through our product licensing by providing our third-party andrelated-party licen

218、sees with the right to access our product candidates,and through research and developmentservices performed.For the six months ended June 30,2023 and the years ended December 31,2022 and 2021,ournet losses were$7.2 million,$28.2 million and$23.3 million,respectively.Our losses have resulted principa

219、lly fromresearch and development expenses and general and administrative expenses.We have been devoting the majority ofour financial resources and efforts to our research and development activities,including preclinical testing,researchand development of our diagnostic and therapeutic product candid

220、ates for tauopathies and-synucleinopathies aswell as building our tauopathies and-synucleinopathies research and development capabilities.None of our diagnostic or therapeutic product candidates have received marketing approval,and we may neverbe successful in obtaining marketing approval and commer

221、cializing them.We expect to continue to incur significantexpenses and increasing operating losses for the foreseeable future.These net losses will adversely impact ourshareholders deficit and net assets and may fluctuate significantly from quarter to quarter and year to year.Weanticipate that our ex

222、penses will increase substantially as we:continue our ongoing and planned research and development of our lead diagnostic product candidate,APN-1607;continue our ongoing and planned research and development of our pipeline of diagnostic and therapeuticproduct candidates,such as-Syn PET tracers and A

223、PNmAb005;16TABLE OF CONTENTSconduct preclinical studies and clinical trials for any additional product candidates that we may pursue inthe future,including ongoing and planned development of additional diagnostic or therapeutic productcandidates for the diagnosis or treatment of tauopathies,such as

224、Alzheimers Disease(“AD”)andProgressive Supranuclear Palsy(“PSP”),and-synucleinopathies,such as Parkinsons Disease(“PD”)andMultiple System Atrophy(“MSA”);seek to discover and develop additional diagnostic and therapeutic product candidates and further expandour current pipeline;seek regulatory approv

225、als for any product candidates that successfully complete clinical trials;meet the requirements for clinical trials and potential commercialization;establish sales,marketing and distribution infrastructure to commercialize any product candidate for whichwe may obtain regulatory approval;develop,main

226、tain,expand and protect our intellectual property portfolio;add clinical,operational,financial and management information systems and/or personnel,includingpersonnel to support our product development and planned future commercialization efforts;expand our operations in the United States,Japan,Taiwa

227、n and other geographic regions;andincur additional legal,accounting and other expenses associated with operating as a public company.To become and remain profitable,we must succeed in developing and eventually commercializing products thatgenerate significant revenue.This will require us to be succe

228、ssful in a range of challenging activities,includingcompleting preclinical studies and clinical trials of our product candidates,obtaining regulatory approval,manufacturing,marketing and selling any products for which we may obtain regulatory approval,as well asdiscovering and developing additional

229、product candidates.We may never succeed in these activities and,even if wedo,may never generate revenue that is significant enough to achieve profitability.Because of the numerous risks anduncertainties associated with the development and commercialization of biotechnologies and biopharmaceuticals,w

230、e are unable to accurately predict the timing or amount of expenses or when,or if,we will be able to achieveprofitability.If we are required by regulatory authorities to perform studies in addition to those currently expected,or if there are any delays in the initiation and completion of our clinica

231、l trials or the development of any of ourproduct candidates,our expenses could increase and profitability could be further delayed.If we are unable tomaintain adequate working capital,we may default on our payment obligations and may not be able to meet ourcapital expenditure requirements,which may

232、have a material adverse effect on our business,financial condition andresults of operations.Even if we achieve profitability,we may not be able to sustain or increase profitability on aquarterly or annual basis.Our failure to become and remain profitable after this offering would depress the value o

233、four ordinary shares and could impair our ability to raise capital,expand our business,maintain our research anddevelopment efforts or continue our operations.A decline in the value of our ordinary shares after this offering couldalso cause you to lose all or part of your investment.We recorded net

234、cash outflow from operating activities since our inception.We may need to acquire funding fromtime to time to complete the development and any commercialization of our pipeline candidates,which may notbe available on acceptable terms,or at all.If we are unable to raise capital when needed,we may be

235、forced todelay,reduce or eliminate certain of our product development programs or other operations.Since our inception in 2015,we have recorded net cash outflow from operating activities and used substantialamounts of cash to fund our operations and expect our expenses to increase substantially duri

236、ng the next few years.The development of biotechnology and biopharmaceutical product candidates is capital intensive.As our productcandidates enter and advance through preclinical studies and clinical trials,we will require substantial additionalfunding to meet our financial needs and to pursue our

237、business objectives.Based upon our current operating plan,we have determined that additional financing will be required to fundour operations for the next 12 months from the date of the issuance of the accompanying consolidated financialstatements included elsewhere in this prospectus and our abilit

238、y to continue as a going concern is dependent uponobtaining additional capital and financing,including through the consummation of this offering.See“Ourindependent registered public accounting firms report contains an explanatory paragraph that expresses substantialdoubt about our ability to continu

239、e as a“going concern”below for a risk relating our ability to continue as a goingconcern.We do not expect to generate any revenue from product sales unless and until we successfully complete17TABLE OF CONTENTSdevelopment and obtain regulatory approval for one or more of our product candidates which

240、we expect will takeseveral years.As a result,until we can generate substantial product revenue,we expect to finance our cash needsthrough equity offerings,debt financings or other capital sources,including collaborations,licenses and other similararrangements,to complete the development and commerci

241、alization of our lead diagnostic product candidate APN-1607,and our other diagnostic and therapeutic product candidates.Our future capital requirements will depend onmany factors,including:the progress,results and costs of laboratory testing,manufacturing,and preclinical and clinicaldevelopment for

242、our current product candidates;the scope,progress,results and costs of preclinical development,laboratory testing and clinical trials ofother diagnostic and/or therapeutic product candidates that we may pursue;the development requirements of other diagnostic and/or therapeutic product candidates tha

243、t we maypursue;the timing and amounts of any milestone or royalty payments we may be required to make under futurelicense agreements if we enter into such agreements;the costs of improving our research and development capacities and infrastructure,including hiringadditional research and development,

244、clinical,and quality control personnel;the costs,timing and outcome of regulatory review of our product candidates;the costs and timing of future commercialization activities,including product manufacturing,marketing,sales and distribution,for any of our product candidates for which we receive marke

245、ting approval;the amount of revenue,if any,received from commercial sales of our product candidates for which wereceive marketing approval;the costs and timing of preparing,filing and prosecuting patent applications,obtaining,maintaining,protecting and enforcing our intellectual property rights and

246、defending against any intellectual property-related claims;the costs associated with operating as a public company;andthe extent to which we acquire or in-license other product candidates and technologies.It is a time-consuming,expensive and uncertain process to identify potential product candidates

247、 and conductpreclinical testing and clinical trials,which takes years to complete.We may never generate the necessary data orresults required to obtain regulatory approval and achieve product sales.Furthermore,our preclinical or clinicalproduct candidates,if approved,may not achieve commercial succe

248、ss.To date,we have no products approved forcommercial sale,nor have we generated any revenue from product sales.Accordingly,we will need to continue torely on additional financing to achieve our business objectives.Sufficient additional financing may not be availableto us on acceptable terms or may

249、not be available to us at all.Also,we may seek additional capital due to favorablemarket conditions or strategic considerations even if we believe we have sufficient funds for our current or futureoperating plans.If we raise additional funds through collaboration and licensing arrangements with thir

250、d parties,wemay have to relinquish some rights to our technologies or our product candidates on terms that are not favorable tous.Any additional capital-raising efforts may divert our management from their day-to-day activities,which mayadversely affect our ability to develop and commercialize our c

251、urrent and future product candidates if approved.Ifwe are unable to raise capital when needed or on acceptable terms,we may be forced to delay,reduce or altogethercease our research and development programs or future commercialization efforts.Our independent registered public accounting firms report

252、 contains an explanatory paragraph that expressessubstantial doubt about our ability to continue as a“going concern.”In connection with our assessment of going concern considerations in accordance with Financial AccountingStandard Boards Accounting Standards Update(“ASU”)2014-15,“Disclosures of Unce

253、rtainties about an EntitysAbility to Continue as a Going Concern,”our independent registered public accounting firm expresses substantialdoubt regarding our ability to continue as a going concern within one year from the date of issuance of ourconsolidated financial statements absent of the completi

254、on of this offering.We cannot provide assurance that we canincrease our cash balance or limit our cash consumption,complete offerings or obtain other capital resources,andthus maintain a sufficient cash balance for our18TABLE OF CONTENTSplanned operations.We will need to raise additional capital in

255、the future and cannot assure that we will be able to doso on favorable terms,or at all.If we are not able to raise capital,we may reduce costs through delaying thedevelopment timelines of certain programs or termination of such programs.Raising additional capital may cause dilution to the interests

256、of our shareholders,restrict our operations orrequire us to relinquish rights to our technologies or product candidates.We expect that significant additional capital may be needed in the future to continue our planned operations,including conducting clinical trials,commercialization efforts,expanded

257、 research and development activities andcosts associated with operating a public company after the consummation of the offering.If we cannot generatesubstantial product revenue,until then,we expect to finance our cash needs through any or a combination ofsecurities offerings,debt financings,equity f

258、inancings,license and collaboration agreements,and research grants.Our additional financing and capital raising activities may cause material dilution to the interests of our shareholdersimmediately upon the consummation of the offering.As new investors could gain rights,such activities may alsoresu

259、lt in preferences and privileges senior to our existing shareholders.To the extent that we raise additional capitalthrough the sale of equity or convertible debt securities,your ownership interest after the offering will be diluted,and the terms of these securities may include liquidation or other p

260、references that adversely affect your rights as ashareholder.Debt financing and preferred equity financing,if available,could result in fixed payment obligations,and we may be required to accept terms that restrict our ability to incur additional indebtedness,force us to maintainspecified liquidity

261、or other ratios or restrict our ability to pay dividends or make acquisitions.If we raise additionalfunds through collaborations,strategic alliances or marketing,distribution or licensing arrangements with thirdparties,we may be required to relinquish valuable rights to our technologies,future reven

262、ue streams,researchprograms or product candidates or to grant licenses on terms that may not be favorable to us.In addition,we couldalso be required to seek funds through arrangements with collaborators or others at an earlier stage than otherwisewould be desirable.If we raise funds through research

263、 grants,we may be subject to certain requirements,which maylimit our ability to use the funds or require us to share information from our research and development.If we areunable to raise additional funds through equity or debt financings when needed,we may be required to delay,limit,reduce or termi

264、nate our product development or future commercialization efforts or grant rights to a third party todevelop and market product candidates that we would otherwise prefer to develop and market ourselves.Raisingadditional capital through any of these or other means could adversely affect our business a

265、nd the holdings or rightsof our shareholders and may cause the market price of our ordinary shares to decline.Risks Related to the Development of Our Product CandidatesWe depend heavily on the success of our lead diagnostic product candidate APN-1607,and,to a lesser extent,ouranti-tau antibody produ

266、ct candidate,APNmAb005,and our degrader programs,all of which are currently orexpected to be in clinical development.If our clinical trials are unsuccessful,we or our collaboration partner,Yantai Yitai Pharmaceutical Technology Co.,Ltd.(“Yitai”),a wholly-owned subsidiary of Dongcheng Pharma,donot ob

267、tain regulatory approval in the targeted jurisdictions,or we or Yitai are unable to commercialize APN-1607,APNmAb005 or degraders,or experience significant delays in doing so,our business,our financialcondition and results of operations will be materially adversely affected.We have no products appro

268、ved for commercial sale and invested a significant portion of our efforts andfinancial resources in the development of our lead diagnostic product candidate,APN-1607,our anti-tau antibodyproduct candidate,APNmAb005,and degrader programs,all of which are currently or expected to be in clinicaldevelop

269、ment.We cannot commercialize our product candidates in the United States without first obtainingregulatory approval for the product from the U.S.Food and Drug Administration(the“FDA”);similarly,we cannotcommercialize our product candidates in jurisdictions without us or our collaboration partner obt

270、aining regulatoryapproval from comparable regulatory authorities in relevant jurisdictions.To gain regulatory approvals for thecommercial sale of any product candidate for a particular indication,we must demonstrate with substantial evidencegathered in preclinical studies and clinical trials that th

271、e product candidate is safe and effective for that indicationand that the manufacturing facilities,processes and controls comply with regulatory requirements with respect tosuch product candidate.Before seeking approval for any of our product candidates,we will also need to consult withthe FDA or ot

272、her regulatory authorities regarding the design of our clinical trials and the type and amount of clinicaldata necessary to pursue and obtain approval for our product candidates.Furthermore,approval policies,regulations,or the type and amount of preclinical and clinical data necessary to gain approv

273、al may change during a productcandidates research and development and may vary among jurisdictions.Our ability to generate revenues fromproduct sales,if ever,will depend heavily on successful clinical development,obtaining regulatory approval andeventual commercialization of these product candidates

274、.We currently generate no revenues from product sales,andwe may never be able to develop or commercialize a marketable product.The success of our current and futureproduct candidates will depend on several factors,including the following:19TABLE OF CONTENTScompleting clinical trials that demonstrate

275、 the efficacy and safety of our product candidates;receiving marketing approvals from applicable regulatory authorities;obtaining commercial manufacturing capabilities;launching commercial sales,marketing and distribution operations;acceptance of our diagnostic and therapeutic product candidates by

276、patients,the medical communityand/or third-party payors,if such product candidates are approved;a continued acceptable safety profile following approval;competing effectively with other diagnostics or therapies;andqualifying for,obtaining,maintaining,enforcing and defending our intellectual property

277、 rights and claimsand not infringing on third parties intellectual property rights.If we or Yitai do not achieve one or more of these factors promptly or at all,we could experience significantdelays or an inability to successfully commercialize our current or future product candidates,which wouldmat

278、erially adversely affect our business,financial condition and results of operations.We operate in highly competitive and rapidly changing industries.Our competitors are evaluating diagnosticproduct candidates in the same indication as our lead diagnostic product candidate,APN-1607,such as AD andPSP,

279、and could enter the market with competing products of our product candidates,which may result in amaterial decline in sales of affected product candidates.We operate in highly competitive and rapidly changing industries.Our competitors could enter the market withproducts that compete with our produc

280、t candidates,which may result in a material decline in sales of our affectedproduct candidates after they are approved for marketing.For instance,certain of our competitors might beevaluating a tau PET tracer candidate in clinical development and/or the same indication as our lead diagnosticproduct

281、candidate,APN-1607,such as AD and PSP.Our competitors may be able to obtain marketing approval fortheir respective tau PET tracer candidates before us.Should this occur,the sales of our tau PET tracer candidates,when approved,may experience strong market competition.As a result,our business,financia

282、l condition and resultsof operations may be materially impacted.A fast track,breakthrough therapy or other designation by the FDA may not actually lead to a faster developmentor regulatory review or approval process.We may seek fast track,breakthrough therapy or similar designation for our drug cand

283、idates.For example,weplan to apply for fast track designation in the United States for APN-1607.If a drug is intended for the treatment of aserious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for thiscondition,the drug sponsor may apply for FD

284、A fast track designation.The FDA has broad discretion whether or notto grant this designation,and even if we believe a particular drug candidate is eligible for this designation,we cannotassure you that the FDA would decide to grant it.Even if we do receive fast track designation,we may notexperienc

285、e a faster development process,review or approval compared to conventional FDA procedures.The FDAmay withdraw fast track designation if it believes that the designation is no longer supported by data from ourclinical development program.Additionally,we may,in the future seek a breakthrough therapy d

286、esignation for some of our product candidatesthat reach the regulatory review process.A breakthrough therapy is a drug candidate that is intended,alone or incombination with one or more other drugs,to treat a serious or life-threatening disease or condition,and that,asindicated by preliminary clinic

287、al evidence,may demonstrate substantial improvement over existing therapies on oneor more clinically significant endpoints,such as substantial treatment effects observed early in clinical development.Drugs designated as breakthrough therapies by the FDA are eligible for accelerated approval and incr

288、easedinteraction and communication with the FDA designed to expedite the development and review process.As with fast-track designation,designation as a breakthrough therapy is within the discretion of the FDA.Accordingly,even if we believe one of our product candidates meets the criteria for designa

289、tion as a breakthroughtherapy,the FDA may disagree and may determine not to grant such a designation.Even if we receive abreakthrough therapy designation for any of our product candidates,the designation may not result in a materiallyfaster development process,review or approval compared to conventi

290、onal FDA procedures.Further,obtaining a20TABLE OF CONTENTSbreakthrough therapy designation does not assure or increase the likelihood of the FDAs approval of the applicableproduct candidate.In addition,even if one or more of our product candidates qualifies as a breakthrough therapy,theFDA could lat

291、er determine that those products no longer meet the conditions for the designation or determine not toshorten the time period for FDA review or approval.Even if we successfully obtain regulatory approvals for our product candidates,they may not gain marketacceptance,in which case we may not be able

292、to generate product revenues,which will materially adversely affectour business,financial condition and results of operations.Our product candidates may not achieve market acceptance among physicians,patients,hospitals,includingpharmacy directors and/or third-party payors,as applicable,even if we su

293、ccessfully obtain regulatory approvalsfrom the FDA or other regulatory authorities and can initiate commercialization of our product candidates or anyother product candidates we may develop.Thus,our product candidates ultimately may not be commerciallysuccessful.The market acceptance of our product

294、candidates,when approved,for commercial sale,will depend onseveral factors,which may include:the accuracy of diagnosis for which our diagnostic product candidates are approved;the clinical indications for which our product candidates are approved;the accuracy and specificity to the pathological prot

295、ein aggregates of our PET tracer candidates;hospitals and medical imaging centers establishing the infrastructure required,such as the PET scanners,for the administration of PET scan;the cost of our PET tracer candidates and the cost of administrating PET scan in relation to alternativediagnostic me

296、thods;the cost of product candidates in relation to alternative therapies;physicians,hospitals,and patients considering our product candidates as safe and effective therapies;the potential and perceived advantages of our product candidates over alternative therapies;the prevalence and severity of an

297、y side effects;product labeling or product insert requirements of the FDA or other regulatory authorities;limitations or warnings contained in the labeling approved by the FDA or other regulatory authorities;the timing of market introduction of our product candidates as well as competitive products;

298、the amount of upfront costs or training required for physicians to administer our product candidates;the availability of coverage,adequate reimbursement,and pricing by third-party payors and governmentauthorities;the willingness of patients to pay out-of-pocket in the absence of comprehensive covera

299、ge andreimbursement by third-party payors and government authorities;relative convenience and ease of administration of our diagnostics,including as compared to alternativediagnostic methods and competitive diagnostics;relative convenience and ease of administration of our product candidates includi

300、ng as compared toalternative treatments and therapies;andthe effectiveness of our sales and marketing efforts and distribution support.We may need significant resources to educate physicians,patients,third-party payors and others in the medicalcommunity on the benefits of our product candidates if a

301、pproved,and we may never be successful despite ourtremendous efforts.Such efforts may require more resources than are typically required due to the complexity anduniqueness of our product candidates.Because we expect sales of our product candidates,if approved,to generatesubstantially most of our pr

302、oduct revenue for the foreseeable future,the failure of our product candidates to findmarket acceptance would harm our business and could require us to seek additional financing.Furthermore,we may21TABLE OF CONTENTSnot be able to maintain market acceptance over time,even if we achieve market accepta

303、nce for our products,as newproducts or technologies are introduced and may become more favorably received than our future approvedproducts,are more cost-effective or render our affected products obsolete.Results of preclinical studies or early phases of clinical trials may not be predictive of futur

304、e study results ormarketing approval.Results from preclinical or early-stage studies may not be predictive of late-stage clinical studies or productapproval by the FDA or comparable foreign regulatory authorities.Positive or timely results observed in preclinicalor early-stage studies do not guarant

305、ee positive or timely results in late-stage clinical studies.Also,productcandidates that show positive preclinical or early clinical results may not show sufficient safety or efficacy in later-stage clinical studies and therefore may fail to obtain regulatory approvals.We also have a pipeline of ear

306、lier-stagediagnostic and therapeutic product candidates,and because they are in earlier stages of development,we do notknow whether these candidates will be effective and safe for the intended indications in humans.Our productcandidates may fail to show the desired safety and efficacy in clinical de

307、velopment despite results in preclinicalstudies or,in the future,having successfully advanced through Phase 1 clinical trials that are supportive of furtherdevelopment.For example,we received FDA clearance in March 2022 to initiate Phase 1 clinical trial ofAPNmAb005 but we may fail to achieve succes

308、s in such trial.If we fail to establish sufficient efficacy and safetyprofiles for our product candidates,we may need to abandon the clinical development of such product candidates.Moreover,preclinical and clinical data are frequently susceptible to varying interpretations and analyses.Manycompanies

309、 have nonetheless failed to obtain marketing approval for the product candidates,despite their productcandidates satisfactory performances in preclinical studies and clinical trials.The FDA and other regulatoryauthorities have substantial discretion in the approval process and in determining when or

310、 whether regulatoryapproval will be obtained for any of our product candidates.Even if we believe the data collected from clinical trialsof our product candidates are promising,such data may not be sufficient to support approval by the FDA or otherregulatory authorities.If we or our collaboration pa

311、rtners are required to conduct additional clinical trials or other testing of any of ourcurrent or future product candidates that we or our collaboration partners develop beyond the studies and testing thatwe or our collaboration partners contemplate if we or our collaboration partners are unable to

312、 successfully completeclinical trials of our product candidates or another testing,if the results of these studies or tests are unfavorable orare only modestly favorable or if there are safety concerns associated with our current or future product candidates,we may:be delayed in obtaining marketing

313、approval for our product candidates;not obtain marketing approval;obtain approval for indications or patient populations that are not as broad as intended or desired;obtain approval with labeling that includes significant use or distribution restrictions or significant safetywarnings,including boxed

314、 warnings;be subject to additional post-marketing testing or other requirements;orremove the product from the market after obtaining marketing approval.If we experience delays in testing or marketing approvals,our product development costs may increase and wemay be required to obtain additional fund

315、s to bring our clinical studies to their completion.We cannot assure youthat our clinical studies will start as planned or complete on schedule,if at all,or that we will not need to restructureour studies after they have begun.Also,significant clinical study delays could shorten any periods during w

316、hich wemay have the exclusive right to commercialize our product candidates or allow our competitors to bring products tomarket before we do or shorten any periods during which we have the exclusive right to commercialize our productcandidates,which may harm our business and results of operations.Fu

317、rthermore,some of the factors that cause,orlead to,clinical study delays may ultimately lead to the denial of regulatory approval of our product candidates.Clinical trials are difficult to design and implement,involve uncertain outcomes and may not be successful.Human clinical trials are difficult t

318、o design and implement,in part because they are subject to rigorousregulatory requirements.The failure rate is high for pharmaceutical product candidates proceeding through clinicaltrials.The design of a clinical trial is crucial and could affect whether its results will support the approval of apro

319、duct22TABLE OF CONTENTScandidate.The flaws in the design of a clinical trial may not become apparent until the clinical trial has proceededinto an advanced stage.Many companies in the pharmaceutical and biotechnology industries have sufferedsignificant setbacks in late-stage clinical trials even aft

320、er achieving results in preclinical testing and earlier-stageclinical trials that are supportive of further development.As a clinical-stage biotechnology company with limitedoperating history,we have limited experience designing clinical trials and may be unable to design and executeclinical trials

321、to support regulatory approval.We cannot assure you that any clinical studies that either we or ourcollaboration partners may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatoryapproval to market our product candidates.In some instances,there can be significant v

322、ariability in safety and/orefficacy results between different studies of the same product candidate due to numerous factors,including changesin study procedures set forth in protocols,differences in the size and type of the patient populations,adherence to thedosing regimen and other study protocols

323、 and the rate of dropout among clinical study participants.In the case ofour late-stage clinical diagnostic product candidate,APN-1607,results may differ in general because of the largernumber of clinical study sites and additional countries and languages involved in the clinical studies.We mayexper

324、ience regulatory delays or rejections because of many factors,including changes in regulatory policy duringthe period of our product candidate development.Any such delays could negatively impact our business,financialcondition,results of operations and prospects.We depend on enrollment of patients i

325、n our clinical trials for our product candidates.If we encounter difficultiesenrolling patients in our clinical trials,our clinical development activities could be delayed or otherwise adverselyaffected.Patient enrollment in clinical trials of our product candidates is essential to our success.We ma

326、y experiencedifficulties in identifying and qualifying patients to participate in our clinical trials for a variety of reasons,includingdue to disease outbreaks,such as an epidemic or pandemic.The timely completion of clinical trials according to theprotocols depends,among other things,on our abilit

327、y to enroll enough patients who remain in the study until itscompletion.The enrollment of patients depends on various factors,including:the patient eligibility criteria defined in the protocol;the number of patients with the disease or condition being studied;the understanding of risks and benefits

328、of the product candidate in the clinical trial;clinicians and patients perceptions as to the potential advantages of the product candidate being studiedin relation to other available diagnostic methods or therapeutics,including any diagnostics that may beapproved to diagnose the indications or new t

329、herapeutics that may be approved for the indications we areinvestigating or therapeutics that may be used off-label for these indications;the size and nature of the patient population who meet inclusion criteria;the proximity of patients to study sites;sufficient supply of PET tracer by third-party

330、suppliers,including contract manufacturing organizations(“CMOs”);the design of the clinical trial;competing clinical trials for similar or other new diagnostics or therapeutics for tauopathies and-synucleinopathies;andour ability to obtain and maintain patient consents.In particular,some of our clin

331、ical trials aim to enroll patients with characteristics that are found in a very smallpopulation.For example,PSP and Frontotemporal Dementia(“FTD”),two indications for our lead tau PET tracercandidate,are rare tauopathies with low incidence overall and therefore clinical study enrollment will take l

332、onger.Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the plannedclinical trials,which could prevent the completion of these clinical trials and adversely affect our ability to advancethe development of our product candidates.In addition,many of the

333、factors that may lead to a delay in thecommencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of ourproduct candidates.23TABLE OF CONTENTSIf serious adverse,undesirable or unacceptable side effects are identified during the development of our productcandidates or following approval,if any,we may need to abandon our development of such product ca