Altimmune, Inc. （ALT） 2023年10-K年度報告「NASDAQ」.pdf

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1、Table of ContentsUNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington,D.C.20549FORM 10-K(Mark One)ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d)OF THE SECURITIES EXCHANGE ACT OF1934For the fiscal year ended December 31,2023orTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d)OF THE SECURITIES EXCH

2、ANGE ACTOF 1934For the transition period from to Commission File Number:001-32587ALTIMMUNE,INC.(Exact name of registrant as specified in its charter)Delaware 20-2726770(State or other jurisdiction ofincorporation or organization)(I.R.S.EmployerIdentification No.)910 Clopper Road,Suite 201S,Gaithersb

3、urg,MD 20878(Address of principal executive offices)(Zip Code)Registrants telephone number,including area code(240)654-1450Securities registered pursuant to Section 12(b)of the Act:Title of each classTrading Symbol(s)Name of each exchange on which registeredCommon stock,par value$0.0001 per shareALT

4、The NASDAQ Global MarketSecurities registered pursuant to Section 12(g)of the Act:NoneIndicate by check mark if the registrant is a well-known seasoned issuer,as defined in Rule 405 of the Securities Act.Yes No Indicate by check mark if the registrant is not required to file reports pursuant to Sect

5、ion 13 or 15(d)of the Act.Yes No Indicate by check mark whether the registrant(1)has filed all reports required to be filed by Section 13 or 15(d)of the SecuritiesExchange Act of 1934 during the preceding 12 months(or for such shorter period that the registrant was required to file such reports),and

6、(2)has been subject to such filing requirements for the past 90 days.Yes No Indicate by check mark whether the registrant has submitted electronically every Interactive Data file required to be submitted pursuant toRule 405 of Regulation S-T(232.405 of this chapter)during the preceding 12 months(or

7、for such shorter period that the registrant wasrequired to submit such files).Yes No Indicate by check mark whether the registrant is a large accelerated filer,an accelerated filer,a non-accelerated filer,smaller reportingcompany,or an emerging growth company.See the definitions of“large accelerated

8、 filer,”“accelerated filer,”“smaller reportingcompany,”and“emerging growth company”in Rule 12b-2 of the Exchange Act.Large accelerated filerAccelerated filerNon-accelerated filerSmaller reporting companyEmerging growth companyIf an emerging growth company,indicate by check mark if the registrant has

9、 elected not to use the extended transition period forcomplying with any new or revised financial accounting standards provided pursuant to Section 13(a)of the Exchange Act.Indicate by check mark whether the registrant has filed a report on and attestation to its managements assessment of the effect

10、iveness ofits internal control over financial reporting under Section 404(b)of the Sarbanes-Oxley Act(15 U.S.C.7262(b)by the registered publicaccounting firm that prepared or issued its audit report.Yes No If securities are registered pursuant to Section 12(b)of the Act,indicate by check mark whethe

11、r the financial statements of the registrantincluded in the filing reflect the correction of an error to previously issued financial statements.Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-basedcompensation received by

12、any of the registrants executive officers during the relevant recovery period pursuant to 240.10D-1(b).Indicate by check mark whether the registrant is a shell company(as defined in Rule 12b-2 of the Act).Yes No The aggregate market value of voting and non-voting common equity held by non-affiliates

13、,based upon the closing price of theregistrants common stock on the NASDAQ Global Market on June 30,2023,was approximately$184.4 million.As of March 22,2024,there were 70,895,286 shares of the registrants common stock,$0.0001 par value per share,outstanding.2025/2/11 15:46sec.gov/Archives/edgar/data

14、/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm1/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-2

15、0231231x10k.htm2/252Table of ContentsALTIMMUNE,INC.ANNUAL REPORT ON FORM 10-KTABLE OF CONTENTS PagePART IItem 1.Business5Item 1A.Risk Factors43Item 1B.Unresolved Staff Comments84Item 1C.Cybersecurity84Item 2.Properties85Item 3.Legal Proceedings85Item 4.Mine Safety Disclosures85PART IIItem 5.Market f

16、or Registrants Common Equity,Related Stockholder Matters and IssuerPurchases of Equity Securities86Item 6.Reserved86Item 7.Managements Discussion and Analysis of Financial Condition and Results ofOperations87Item 7A.Quantitative and Qualitative Disclosures about Market Risk95Item 8.Financial Stateme

17、nts and Supplementary Data96Item 9.Changes in and Disagreements with Accountants on Accounting and FinancialDisclosure121Item 9A.Controls and Procedures121Item 9B.Other Information121PART IIIItem 10.Directors,Executive Officers and Corporate Governance123Item 11.Executive Compensation129Item 12.Secu

18、rity Ownership of Certain Beneficial Owners and Management and RelatedStockholder Matters137Item 13.Certain Relationships and Related Transactions,and Director Independence139Item 14.Principal Accountant Fees and Services141PART IVItem 15.Exhibits and Financial Statement Schedules142Item 16.Form 10-

19、K Summary144Signatures1452025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm3/252Table of ContentsForward-looking statementsThis Annual Report on Form 10-K for the year ended

20、December 31,2023(this“AnnualReport”)contains forward-looking statements within the meaning of Section 27A of the Securities Act of1933,as amended(the“Securities Act”),Section 21E of the Securities Exchange Act of 1934,asamended(the“Exchange Act”),and the Private Securities Litigation Reform Act of 1

21、995.Written or oralstatements that constitute forward-looking statements may be made by us or on our behalf.Words such as“expect,”“anticipate,”“intend,”“plan,”“believe,”“estimate,”“may,”“will,”“should,”“could,”“target,”“strategy,”“intend,”“project,”“guidance,”“likely,”“usually,”“potential,”or the ne

22、gative ofthese words or variations of such words,similar expressions,or comparable terminology are intended toidentify such forward-looking statements,although not all forward-looking statements contain theseidentifying words.There are a number of important risks and uncertainties that could cause o

23、ur actualresults to differ materially from those indicated by forward-looking statements.We may not actuallyachieve the plans,intentions or expectations disclosed in our forward-looking statements,and you shouldnot place undue reliance on our forward-looking statements.Actual results or events could

24、 differmaterially from the plans,intentions and expectations disclosed in the forward-looking statements wemake.These forward-looking statements are based on current expectations,estimates,forecasts andprojections about the industry and markets in which we operate,and managements beliefs andassumpti

25、ons.These statements are not guarantees of future performance and involve certain risks,uncertainties and assumptions that are difficult to predict and may cause our actual results,performanceor achievements to be materially different from future results,performance or achievements expressed orimpli

26、ed by any forward-looking statements.These risks,uncertainties and other factors include,but arenot limited to,risks associated with the following:our ability to develop and commercialize our current and future product candidates;our ability to expand our pipeline of product candidates and the succe

27、ss of future productcandidate advancements,including the success of future preclinical studies and clinicaltrials,and our ability to commercialize our products;the reliability of the results of the clinical trials relating to human safety and possibleadverse effects resulting from the administration

28、 of our product candidates;our ability to obtain potential regulatory approvals on the timelines anticipated,or at all;our ability to obtain additional patents or extend existing patents on the timelinesanticipated,or at all;our ability to identify and consummate potential future strategic partnersh

29、ips or businesscombinations;our expectations regarding the potential market size and the size of the patient populationsfor our product candidates,if approved for commercial use;our anticipated financial or operational results;our ability to obtain additional capital resources;risks related to the c

30、onflict in Israel and the Gaza Strip and the conflict in Ukraine on theglobal economy,including causing or contributing to global supply chain disruption,pricefluctuations,including increased costs for raw materials,and other significant economiceffects;breaches of data privacy,or disruptions in our

31、 information technology systems;our ability to continue to satisfy the listing requirements of the NASDAQ Global Market(“NASDAQ”);andrisks detailed under the caption“Risk Factors”in this Annual Report and in our otherreports filed with the U.S.Securities and Exchange Commission(“SEC”),from time toti

32、me hereafter.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm4/25212025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.

33、gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm5/252Table of Contents2We have based the forward-looking statements included in this Annual Report on informationavailable to us on the date of this annual report.Except as required by law we undertake no obligation torevise or u

34、pdate any forward-looking statements,whether as a result of new information,future events orotherwise.You are advised to consult any additional disclosures that we may make in reports that we,inthe future,may file with the SEC,including annual reports on Form 10-K,quarterly reports on Form 10-Q and

35、current reports on Form 8-K.All forward-looking statements included herein are expressly qualified in their entirety by theforegoing cautionary statements.Unless otherwise indicated,the information in this Annual Report is asof December 31,2023.Note regarding trademarks“Altimmune,”our logo and other

36、 trademarks,trade names or service marks of the Companyappearing in this Annual Report,including,NasoVAX,HepTcell,EuPort,Densigen and RespirVec arethe property of the Company.The other trademarks,trade names and service marks appearing in thisAnnual Report are the property of their respective owners

37、.We do not intend our use or display of othercompanies trademarks,trade names or service marks to imply an endorsement or sponsorship of us bysuch companies,or any relationship with such companies.Solely for convenience,trademarks and tradenames referred to in this Annual Report may appear without t

38、he or TM symbol.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm6/252Table of ContentsSummary of Risk FactorsThe risk factors detailed in Item 1A entitled“Risk Factors”in t

39、his Annual Report on Form 10-Kare the risks that we believe are material to our investors and a reader should carefully consider them.Those risks are not all of the risks we face and other factors not presently known to us or that wecurrently believe are immaterial may also affect our business if th

40、ey occur.The following is a summary ofthe risk factors detailed in Item 1A:Risks Related to Our Business,Financing Requirements,Product Development and Clinical Trialswe have incurred significant losses since our founding and anticipate that we will continueto incur significant losses for the forese

41、eable future and may never achieve or maintainprofitabilityour profitability depends on our ability to develop and commercialize our current andfuture product candidatesour ability to raise capital may be limited by applicable laws and regulationswe may encounter substantial delays in our clinical t

42、rials,or our clinical trials may fail todemonstrate the safety and efficacy of our product candidates to the satisfaction ofapplicable regulatory authoritieswe may find it difficult to enroll patients in our clinical trials,which could delay or preventclinical trials of our product candidatesit may

43、be difficult to predict the time and cost of product development for our productcandidates,and unforeseen problems may prevent further development or approval of ourproduct candidateswe rely,and expect to continue to rely,on third parties to conduct preclinical studies andclinical trials for our pro

44、duct candidates,and if they do not properly and successfullyperform their obligations to us,we may not be able to obtain regulatory approvals for ourproduct candidateswe face substantial competition from other pharmaceutical and biotechnology companies,which may result in others discovering,developi

45、ng or commercializing products before,ormore successfully,than we dowe are heavily dependent on the success of our leading product candidate,pemvidutide.Ifwe ultimately are unable to develop,obtain regulatory approval for or commercializepemvidutide,or any other product candidate,our business will b

46、e substantially harmedlabor shortages and constraints in the supply chain could adversely affect our results ofoperationsour overall performance depends in part on worldwide economic conditions anduncertaintiesRisks Related to the Regulatory Approval Processour product candidates have undesirable si

47、de effects or have other properties that delay orprevent their regulatory approval or limit their commercial potentialour ability and the timeline to obtain required regulatory approvals,including in non-U.S.jurisdictionsthe expense and uncertainty of the marketing approval process and ongoing regul

48、atoryreview if our product candidates ever receive regulatory approvalRisks Related to Our Intellectual Propertythe cost and difficulty of protecting our proprietary rights and the potential that ourintellectual property rights do not adequately protect our product candidates2025/2/11 15:46sec.gov/A

49、rchives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm7/25232025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/00013

50、2619024000010/alt-20231231x10k.htm8/252Table of Contents4our ability to protect our intellectual property rights throughout the worldthe adequacy of our patent terms to protect our competitive position on our products for anadequate amount of timethird-party claims of intellectual property infringem

51、ent or misappropriation,includingcircumstances involving our employees,independent contractors or consultantsRisks Related to Commercialization of the Companys Product Candidatesour ability to attain significant market acceptance of our product candidates,if approved,among physicians,patients,third-

52、party payers and others in the medical communityour reliance on third parties to manufacture our product candidates and related materials forour products,if approved,as well as our clinical trials and preclinical studiesour reliance on third parties to obtain regulatory approvals for a manufacturing

53、 facility forour products and if approved,to manufacture our products in sufficient quantities to meetcommercial demand the ability of our contract manufacturers to manufacture any suchproduct to the specifications and the quantities that are needed along the timelines that arespecifiedour ability t

54、o identify and consummate potential future strategic partnerships or businesscombinationsRisks Related to Reimbursement and Government Regulationour ability to obtain coverage and reimbursement in certain market segments for ourproduct candidates,if they are approvedthe imposition of price controlso

55、ur ability to comply with multiple substantial federal and state health care and other laws,and the complexity of our regulatory compliance obligationsthe unknown impact of recent health care reform legislation and other changes in the healthcare industry and in health care spendingRisks Related to

56、our Securitiesthe volatility of the trading price of our common stock and substantial price fluctuations onheavy volume2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm9/252

57、Table of Contents5PART IItem 1.BusinessOverviewAltimmune,Inc.is a clinical stage biopharmaceutical company focused on developingtreatments for obesity and liver diseases.Our lead product candidate,pemvidutide(formerly known asALT-801),is a GLP-1/glucagon dual receptor agonist that is being developed

58、 for the treatment of obesityand metabolic dysfunction-associated steatohepatitis(“MASH”),previously termed non-alcoholicsteatohepatitis(“NASH”).Except where the context indicates otherwise,references to“we,”“us,”“our,”“Altimmune”or the“Company”refer to the company and its subsidiaries.PemvidutideWe

59、 completed an acquisition in July 2019 of all of the equity interests of Spitfire Pharma,Inc.(“Spitfire”).Spitfire was a privately held,preclinical pharmaceutical company with the primary assetbeing pemvidutide,a novel peptide-based GLP-1/glucagon dual receptor agonist product candidatedesigned to t

60、reat obesity and the metabolic dysfunction that causes MASH.Obesity is a significant burden to the global healthcare systems and is implicated in two-thirdsof the leading causes of death from non-communicable diseases worldwide.Some of the leading riskfactors or co-morbidities of obesity include hig

61、h low density lipoprotein cholesterol(“LDL-C”)and otherserum lipids,high liver fat content,high total cholesterol,hypertension,type 2 diabetes,ischemic heartdisease,cerebrovascular events,gallbladder disease,osteoarthritis,sleep apnea and breathing problems,certain cancers and MASH.According to the

62、Center for Disease Control and Prevention,the estimatedannual medical cost of obesity in the U.S.was nearly$173.0 billion in 2019 dollars.Globally,the marketsize for weight loss alone was$2.4 billion in 2022 and is estimated that it will reach$54.0 billion by2030.Previous approaches to the treatment

63、 of obesity were associated with safety concerns,limiting thesuccess of those approaches;however,the new class of incretin-based therapeutics has demonstrated bothsubstantial weight loss and beneficial cardiovascular effects in clinical outcome studies.U.S.prevalence of obesity comorbiditiesMASH inv

64、olves multiple metabolic pathways leading to the abnormal accumulation of liver fat,toxic lipid metabolites,and inflammation,leading to fibrosis and increased risk of death due tocardiovascular disease and to liver2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k

65、.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm10/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm11/252Table of Contents6fail

66、ure.MASLD,the fatty liver precursor to MASH,is present in up to 75%of patients with obesity,andup to 20%of MASLD patients progress to MASH.We believe the treatment of obesity is a cornerstoneof treating MASH and the principal morbidities of MASH.In addition,clinical evidence from recenttrials of pot

67、ential MASH products indicates that reduction in liver fat may play an important role in theresolution of liver inflammation and improvement in liver fibrosis.We believe that combining areduction in liver fat content with weight loss could be the optimal approach for treating MASH.Pemvidutides dual

68、agonist mechanism of action is designed to combine the activity of GLP-1for the reduction of appetite and inflammation,with the activity of glucagon,including increased energyexpenditure,adipose browning and mobilization of the liver fat through lipolysis and reduction of lipidsynthesis.Pemvidutide

69、incorporates a proprietary side chain,referred to as the EuPort domain,which isdesigned to enhance pharmacokinetics for gastrointestinal tolerability and permit weekly dosing.Asobserved in a well-established preclinical model of obesity and MASH,pemvidutide is capable ofinducing significant weight l

70、oss with concomitant decreases in liver fat content,inflammation andfibrosis.In a first-in-human,randomized,placebo-controlled,single-ascending and multiple-ascendingdose study of pemvidutide in overweight and obese volunteers,at 12 weeks,we observed significantreductions in body weight and serum li

71、pids,including LDL-C.In November 2023,we announced toplineresults from our 48-week MOMENTUM Phase 2 trial of pemvidutide in 391 subjects with obesity oroverweight with at least one co-morbidity and without diabetes.We observed robust reductions in bodyweight and serum lipids and improvements in bloo

72、d pressure without imbalances in cardiac events,arrhythmias or clinically meaningful increases in heart rate.Pemvidutide Target ProfileIn addition,pemvidutide demonstrated improved metabolic function and pleiotropic effects inpreclinical testing across multiple metabolic pathways involved in MASH.In

73、 these studies,by usingRNA sequencing,we also observed suppression of genes associated with steatosis,inflammation andstellate cell fibrosis.Additionally,in Phase 1b trials of pemvidutide in subjects with MASLD,weobserved profound rapid decreases and normalization in liver fat content and significan

74、t reductions inbody weight and serum alanine aminotransferase(“ALT”)at both 12 weeks and 24 weeks of treatment.We believe that pemvidutide is one of the only MASH candidates currently in development thatcombines rapid effects on liver fat reduction and liver inflammation with significant weight loss

75、.Regulatory Basis for Clinical Trials of PemvidutideOn November 9,2020,we announced that we received clearance from the Human Research andEthics Committee and filed a Clinical Trial Notification with the Australian regulatory authority prior tocommencing our first-in-human trial of pemvidutide.On Se

76、ptember 28,2021,we announced that wereceived clearance of our Investigational New Drug(“IND”)Application in MASH from the U.S.Foodand Drug Administration(“FDA”)prior to commencing our Phase 1b trial of pemvidutide in MASLD.On January 23,2022,we further announced that we received clearance of our IND

77、 application from theFDA prior to commencing our 48-week MOMENTUM Phase 2 trial of pemvidutide in obesity.OnOctober 24,2023,the FDA granted fast track designation to pemvidutide for the treatment of MASH.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:

78、/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm12/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm13/252Table of Contents7Phase 1 Clinic

79、al Trial Results ObesityIn September 2021,we announced the completion of a 12-week Phase 1 clinical trial ofpemvidutide in Australia under a clinical trial application.The trial was a first-in-human,randomized,placebo-controlled,single-ascending and multiple-ascending dose(“MAD”)study in non-diabeti

80、coverweight and obese volunteers.The endpoints of the Phase 1 trial were to assess the safety,tolerabilityand pharmacokinetics of pemvidutide,with primary readouts on safety,pharmacokinetics and weightloss.Additional readouts included metabolic and lipid profiles,cardiovascular measures and glucoseh

81、omeostasis.At 12 weeks,subjects receiving pemvidutide showed mean weight losses of 4.9%,10.3%and 9.0%at the 1.2 mg,1.8 mg and 2.4 mg doses,respectively,while the placebo group experienced amean weight loss of 1.6%,and in the absence of caloric restriction or lifestyle modification.Weight lossoccurre

82、d rapidly and consistently over 12 weeks.Summary of 12-week MAD weight loss findingsCharacteristicTreatment1.2mg(n=7)1.8mg(n=9)2.4mg(n=11)Pooled Placebo(n=7)Baseline demographicsAge,yearsMean(SD)27.7(10.5)32.0(10.7)31.4(11.7)35.3(12.4)Body weight(kg)Mean(SD)90.5(15.4)86.4(12.9)91.9(15.1)87.6(14.3)BM

83、I(kg/m2)Mean(SD)30.0(3.9)30.1(3.9)31.8(2.9)31.0(4.3)ResultsWeight loss(kg)Mean(SD)-4.7(3.0)-8.8(3.0)-8.4(2.8)-1.5(3.0)Weight loss(%)Mean(SD)-4.9(2.9)%-10.3(3.4)%*-9.0(3.3)%*-1.6(3.0)%*p .01,*p .005,compared to placeboThe 1.8 mg dose cohort experienced the highest weight loss,with 100%of the subjects

84、 losing atleast 5%of body weight and 55%of subjects losing at least 10%of body weight.The amounts of weightloss at the 1.8 mg and 2.4 mg doses were similar given the sample size and overlapping confidenceintervals.No correlation was found between the magnitude of weight loss and either age or baseli

85、ne bodymass index(“BMI”).Favorable or statistically significant trends were observed in secondary measures,including reductions in systolic and diastolic blood pressure,serum lipids and HOMA-IR(a measure ofinsulin resistance).As seen in the table below,the effect on serum lipids was particularly str

86、iking and inthe 1.8mg dose,included a greater than 25%decrease in LDL-C,which is known to increase the risk ofcardiovascular disease,as well as significant decreases in total cholesterol and triglycerides.In addition,a rise in serum ketone bodies and a fall in serum tripalmitin was observed,consiste

87、nt with the stimulatoryeffects of glucagon on hepatic beta-oxidation of lipids and suppressive effects of pemvidutide ontriglyceride synthesis,respectively.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/0001326

88、19024000010/alt-20231231x10k.htm14/252Table of Contents8Side effects in this trial were mild to moderate,with no serious or severe treatment-emergentadverse events reported.No discontinuations due to adverse events were reported.Summary of 12-week MAD safety findingsCharacteristicTreatment1.2mg(n=7)

89、1.8mg(n=9)2.4mg(n=11)PooledPlacebo(n=7)Discontinuations due to adverseevents(n)0000Early withdrawal(n)1022Gastrointestinal adverse eventsNausea Mild14.3%55.6%45.5%14.3%Moderate14.3%11.1%45.5%0%Vomiting Mild14.3%11.1%45.5%14.3%Moderate0%11.1%27.3%0%Diarrhea Mild0%0%18.2%0%Moderate0%0%0%0%Constipation

90、 Mild0%11.1%18.2%0%Moderate0%11.1%9.1%0%Other adverse events(n)0210Unlike the majority of other clinical trials with agents within the GLP-1 class,including dualagonists and tri-agonists,dose titration,a gradual increasing of dose within a subject over a period ofweeks to months to improve tolerabil

91、ity,was not used in the pemvidutide trial.Even without that dosetitration,the symptoms experienced by subjects who received pemvidutide 1.2 mg and 1.8 mg werepredominantly mild,did not require treatment and were consistent with known effects of GLP-1-basedtherapies.Tolerability was observed to decre

92、ase at the highest dose level.One subject receiving placeboand one subject receiving pemvidutide 1.8 mg had a 3 to 5-fold elevation in ALT levels over baseline thatresolved rapidly after a pause in dosing.In this trial,no perturbations of glucose control,as assessed byfasting glucose2025/2/11 15:46s

93、ec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm15/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/13261

94、90/000132619024000010/alt-20231231x10k.htm16/252Table of Contents9and hemoglobin A1c(“HbA1c”),were observed in subjects with obesity/overweight with pre-diabetes;infact,a reduction of insulin resistance was observed,as expected when significant weight loss isexperienced.Phase 1 Clinical Trial Result

95、s Liver Fat ContentAlthough the trial inclusion criteria for the MAD study did not pre-specify a minimum liver fatcontent(“LFC”),the trial did enroll a number of subjects with measurable LFC as determined bymagnetic resonance imaging proton density fat fraction(“MRI-PDFF”).A post-hoc analysis of the

96、 trialdata through 6 weeks showed that 8 subjects had hepatic steatosis,defined as liver fat content greaterthan or equal to 5%at baseline(LFC range from 5.5%to 19.5%in these 8 subjects).LFC fell below thelimit of detection(“LOD”),or less than 1.5%,within 6 weeks of treatment in all subjects with st

97、eatosisreceiving the 1.8 mg or 2.4 mg dose of pemvidutide,representing on average a greater than 90%reduction in the liver fat content(see chart below).These findings reinforce the results from preclinicalstudies of pemvidutide,in which we observed statistically greater reductions in liver fat than

98、anequivalent dose of semaglutide.We believe these findings support the potential combined beneficialeffects of weight loss and glucagon agonism on liver fat content.Images of Representative MRI-PDFF Images at Baseline and Week 62025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/al

99、t-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm17/252Table of Contents10The table below displays the changes in liver fat content at Week 6 compared to baseline in the8 subjects with steatosis at baseline:TreatmentGroupWeightLoss(%)atWeek6MRI-

100、PDFFBaselineWeek6Absolute at Week6(%)Relative at Week 6(%)IndividualMeanIndividualMeanPlacebo0.55.23.71.51.528.828.8pemvidutide1.2 mg1.019.114.05.106.5026.748.25.111.23.47.8069.6pemvidutide1.8 mg4.412.4LOD11.6511.6594.094.0pemvidutide2.4 mg3.717.0LOD16.2511.5095.691.94.95.5LOD4.7586.43.17.0LOD6.2589

101、.34.719.5LOD18.7596.2LOD(limit of detection)=1.5%;for absolute and relative,values LOD are set at 0.75%Clinical Trial Results 12-week Phase 1b(MASLD)In September 2022,we announced the topline results from our 12-week Phase 1b clinical trial ofpemvidutide in subjects with MASLD.The trial was a double

102、-blind,placebo-controlled study.Subjectswere randomized 1:1:1:1 to 1.2 mg,1.8 mg,2.4 mg pemvidutide or placebo administered weekly for 12weeks.No dose titration was used with the 1.2 mg or 1.8 mg dose,while a short 4-week dose titrationwas employed at the 2.4 mg dose.The primary efficacy endpoint wa

103、s the percent(%)reduction in LFCfrom baseline,and the key secondary efficacy endpoint was the%weight loss from baseline,both at 12weeks of treatment.This MASLD trial was conducted without the adjunctive diet and exerciseinterventions that would have been the standard for obesity trials.Ninety-four(9

104、4)subjects were randomized and treated at 13 sites across the U.S.Mean BMI atbaseline was approximately 36 kg/m2 and mean LFC,as measured by MRI-PDFF,was approximately22%.Twenty-seven(29%)subjects had type 2 diabetes at baseline,and approximately 75%of studysubjects were of Hispanic ethnicity.The ta

105、ble below details the baseline study demographics.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm18/252Table of Contents11CharacteristicTreatmentPlacebo(n=24)1.2 mg(n=23)1

106、.8 mg(n=23)2.4 mg(n=24)Age,years Mean(SD)47.9(14)48.6(11)50.3(9)48.8(8)SexFemale,n(%)14(58.3%)9(39.1%)12(52.2%)15(62.5%)RaceWhite,n(%)21(87.5%)21(91.3%)20(87.0%)24(100%)Other,n(%)3(12.5%)2(8.7%)3(13.0%)0(0.0%)EthnicityHispanic,n(%)14(58.3%)20(87.0%)19(82.6%)18(75.0%)Non-Hispanic,n(%)10(41.7%)3(13.0%

107、)4(17.4%)6(25.0%)BMI,kg/m2Mean(SD)36.9(4.7)36.3(5.6)35.4(3.9)35.3(5.0)Body weight,kgMean(SD)105.1(20.8)102.4(14.6)98.9(19.7)98.2(18.9)Diabetes statusT2D,n(%)6(25.0%)7(30.4%)7(30.4%)7(33.3%)LFC,%Mean(SD)23.8(9.2)21.6(7.3)21.8(8.0)20.2(7.0)The trial met its primary endpoint in all pemvidutide treatmen

108、t groups.As seen in the tablebelow showing reduction in LFC as measured by MRI-PDFF in all subjects,at the 1.8 mg dose(with andwithout diabetes),pemvidutide achieved a mean reduction of liver fat content of 68.5%,with 94.4%ofsubjects achieving a 30%reduction in liver fat,72.2%achieving a 50%reductio

109、n in liver fat,and 55.6%of subjects achieving normalization of liver fat,defined as liver fat fraction of 5%or less.EndpointTreatmentPlacebo(n=24)1.2 mg(n=20)1.8 mg(n=18)2.4 mg(n=20)Absolute reduction,%Mean(SE)0.2(1.7)8.9(1.8)*14.7(1.7)*11.3(2.0)*Relative reduction,%Mean(SE)4.4(8.7)46.6(8.1)*68.5(9.

110、7)*57.1(8.0)*30%reductionn(%)1(4.2%)13(65.0%)*17(94.4%)*17(85.0%)*50%reductionn(%)0(0.0%)8(40.0%)*13(72.2%)*14(70.0%)*Normalization(5%LFC)n(%)0(0.0%)4(20.0%)*10(55.6%)*10(50.0%)*p .05,*p.001 compared to placeboIn addition,as shown in the below table,mean serum ALT levels declined in all subjects,and

111、 insubjects with baseline serum ALT above 30 IU/L,levels declined more than 17 IU/L at all dose levelsand 27.0 IU/L in the 2.4 mg dose cohort.EndpointTreatmentPlacebo1.2 mg1.8 mg2.4 mgALT,change from baseline,IU/L,LSM(SE)n=24n=23n=23n=24-6.2(2.8)-11.2(3.1)-13.8(3.0)*-13.6(3.2)*ALT,change from baseli

112、ne,IU/L,LSM(SE),baseline 30 IU/Ln=15n=10n=15n=12-12.6(4.1)-17.8(4.8)-20.8(4.2)-27.0(4.8)*p .052025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm19/2522025/2/11 15:46sec.gov/A

113、rchives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm20/252Table of Contents12The trial also met its key secondary endpoint of weight loss in all pemvidutide treatment groups.As portrayed in the follow

114、ing table,employing an efficacy estimand,mean weight losses of 4.9%(placebo-adjusted 4.7%)in subjects without diabetes and 4.4%in subjects with diabetes(placebo-adjusted 3.9%)were achieved at the 1.8 and 2.4 mg doses,respectively.PopulationTreatmentPlacebo(n=24)1.2 mg(n=23)1.8 mg(n=23)2.4 mg(n=24)No

115、 diabetes,(%change)LSM(SE)-0.2(0.7)-3.4*(0.8)-4.9*(0.8)-3.5*(0.8)Diabetes,(%change)LSM(SE)-0.5(1.3)-3.3*(1.1)-3.8*(1.2)-4.4*(1.3)All subjects(%change)LSM(SE)-0.2(0.7)-3.4*(0.7)-4.3*(0.7)-3.7*(0.7)LSM least square mean;*p .05,*p.001 compared to placeboPemvidutide was reported to be generally well tol

116、erated.Gastrointestinal events comprised themajority of the adverse events(“AEs”).Even without dose titration,the symptoms experienced bysubjects were predominantly mild and transient in nature,consistent with known GLP-1 class effects.Noserious or severe AEs were reported.Two subjects treated with

117、pemvidutide discontinued treatment dueto AEs 1(4.3%)at 1.8 mg and 1(4.2%)at 2.4 mg,both secondary to gastrointestinal intolerability.Noclinically significant ALT elevations(defined as an increase to 3-fold or greater the upper limit ofnormal)were observed.Glycemic control was unaffected,with no clin

118、ically meaningful changes inHbA1c or fasting glucose.Clinically meaningful reductions in systolic blood pressure were observed,along with the 2 to 3 beats per minute increase in heart rate typical for GLP-1 class of drugs.The tablebelow summarizes the safety findings.CharacteristicTreatmentPlacebo(n

119、=24)1.2 mg(n=23)1.8 mg(n=23)2.4 mg(n=24)Severe AEsn(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Serious AEs(“SAE”s)n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)AEs leading totreatmentdiscontinuation n(%)0(0.0%)0(0.0%)1(4.3%)1(4.2%)NauseaMild,n(%)3(12.5%)3(13.0%)6(26.1%)6(25.0%)Mod,n(%)0(0.0%)1(4.3%)6(26.1%)3(12.5%)VomitingMil

120、d,n(%)0(0.0%)3(13.0%)2(8.7%)2(8.3%)Mod,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)DiarrheaMild,n(%)4(16.7%)3(13.0%)5(21.7%)1(4.2%)Mod,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)ConstipationMild,n(%)0(0.0%)3(13.0%)4(17.4%)1(4.2%)Mod,n(%)0(0.0%)1(4.3%)0(0.0%)0(0.0%)Clinical Trial Results 24-week Phase 1b extension(MASLD)In

121、 December 2022,we announced the topline results from our 24-week(12-week extension)Phase 1b clinical trial of pemvidutide in subjects with MASLD.Sixty-six(66)of the 83 subjects whocompleted the initial 12-week Phase 1b MASLD trial consented to participate in this 12-week extensiontrial to receive a

122、total of 24 weeks of treatment,and 642025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm21/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-2023123

123、1x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm22/252Table of Contents13subjects were enrolled.The trial was conducted without adjunctive diet and exercise interventions andthe double-blinding of the trial was maintained during the extension study.The

124、same endpoints as the 12-week parent MASLD trial were employed,with a primary efficacy endpoint of percent(%)reduction inliver fat content;key secondary endpoints were reduction in liver inflammation,as measured by serumALT levels and corrected T1(“cT1”),and percent weight loss.The population of the

125、 12-week extension trial had similar baseline characteristics as thepopulation of the parent,12-week Phase 1b MASLD trial.At baseline,across all treatment groups,meanBMI was 36.7 kg/m2 and mean LFC,as measured by MRI-PDFF,was 22.2%.Type 2 diabetes waspresent in 26.6%of subjects and 73.4%of study sub

126、jects were of Hispanic ethnicity.The trial met its primary endpoint in all pemvidutide treatment groups.At the 1.8 mg and 2.4mg doses,subjects receiving pemvidutide achieved mean relative reductions of liver fat content of 75.2%and 76.4%,respectively;92.3%and 100%of subjects at the 1.8 mg and 2.4 mg

127、 doses,respectively,achieved a 30%reduction in liver fat,84.6%and 72.7%of subjects,respectively,achieved a 50%reduction in liver fat,and 53.8%and 45.5%of subjects,respectively,achieved normalization of liver fatcontent to below 5%.As in the 12-week Phase 1b MASLD trial,statistically significant decl

128、ines in meanserum ALT levels were observed in all pemvidutide-treated subjects,and in subjects with baseline serumALT 30 IU/L,ALT levels declined at least 17 IU/L at all pemvidutide dose levels.In a subset of subjectsevaluated for cT1 response,75.0%and 100%of subjects receiving 1.8 mg or 2.4 mg pemv

129、idutide,respectively,achieved an 80 millisecond(ms)decrease in cT1 relaxation time.cT1 is an MRI-basedquantitative metric for assessing a composite of liver inflammation and fibrosis.Elevated cT1 relaxationtimes have been associated with increased risk of major adverse cardiac events(“MACE”)and majo

130、radverse liver outcomes(“MALO”),and an 80 ms reduction has been associated with a 2-point reductionof NAFLD Activity Score(“NAS”).2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x1

131、0k.htm23/252Table of Contents14The trial also met its key secondary endpoint of weight loss in all pemvidutide treatment groups.Employing an efficacy estimand,mean weight losses of 7.2%(placebo-adjusted 6.0%)in subjectswithout diabetes and 6.2%(placebo-adjusted 4.8%)in all subjects were achieved at

132、the 1.8 mg dose.Asummary of the key primary and secondary efficacy findings is below:EndpointTreatmentPlacebo1.2 mg1.8 mg2.4 mgPrimary EndpointLiver Fat Contentn=18n=14n=13n=11Liver fat reduction,absolute,%change,LSM(SE)1.6(0.8)11.2(2.3)*17.0(2.4)*15.6(2.1)*Liver fat reduction,relative,%change,LSM(S

133、E)14.0(3.8)56.3(11.6)*75.2(8.1)*76.4(5.9)*Proportion of subjects with 30%reduction,(%)5.676.9*92.3*100.0*Proportion of subjects with 50%reduction,(%)0.061.5*84.6*72.7*Proportion of subjects with normalization,(%)0.030.8*53.8*45.5*Secondary EndpointMarkers of InflammationALT,change from baseline,IU/L

134、,LSM(SE)n=19n=16n=15n=14-2.2(2.5)-13.3(3.7)*-13.7(5.1)*-15.2(5.8)*ALT,change from baseline,IU/L,LSM(SE),baseline 30 IU/n=13n=7n=10n=9-3.1(3.5)-17.0(7.6)*-17.7(7.2)*-20.6(9.8)*Proportion of subjects with cT1 response,(%)n=6n=7n=4n=20.085.7*75.0*100.0*Secondary EndpointWeight LossWeight loss,no diabet

135、es,(%change),LSM(SE)n=14n=13n=9n=111.2(0.7)5.2(1.7)*7.2(1.1)*5.8(1.6)*Weight loss,diabetes,(%change),LSM(SE)n=5n=3n=6n=33.4(2.1)4.3(1.9)5.3(2.7)3.5(2.5)Weight loss,all subjects,(%change),LSM(SEn=19n=16n=15n=141.4(0.7)5.1(1.4)*6.2(1.3)*5.2(1.4)*Normalization of liver fat defined as 5%;cT1 response de

136、fine as an 80 ms change from baseline;LSM,least square mean High variability due to the small numbers of diabetic subjects(n=5,3,6,3 in respective treatment groups)*p .05;*p 0.01,*p 0.001,*p 0.0001 compared with placebo2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-2023123

137、1x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm24/252Table of Contents15Pemvidutide was generally well tolerated.A total of three serious or severe AEs were reported,each unrelated to study drug administration(chest pain post-elective cardiac stent pla

138、cement;Salmonellainfection;and hypertension greater than three weeks after the completion of treatment).Three AEs led totreatment discontinuation,one being the Salmonella infection,and mild(Grade 1)instances of abdominalpain AEs in two subjects,one(6.3%)at the 1.2 mg dose and one(6.7%)at the 1.8 mg

139、dose.As expected,gastrointestinal events comprised the majority of AEs and were predominantly mild in nature.Noclinically significant ALT elevations were observed.Meaningful reductions in systolic blood pressurewere observed,and increases in heart rate,typical of the incretin class of agents,were mi

140、nimal at 0 to 4beats per minute and independent of dose.Below is a summary of the safety findings:CharacteristicTreatmentPlacebo(n=19)1.2 mg(n=16)1.8 mg(n=15)2.4 mg(n=14)Serious or severe AEsn(%)1(5.3%)1(6.3%)1(6.7%)0(0.0%)AEs leading totreatmentdiscontinuationn(%)0(0.0%)2(12.5%)1(6.7%)0(0.0%)Nausea

141、Mild,n(%)0(0.0%)0(0.0%)0(0.0%)1(7.1%)Moderate,n(%)0(0.0%)0(0.0%)3(20.0%)0(0.0%)VomitingMild,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Moderate,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)DiarrheaMild,n(%)1(5.3%)0(0.0%)1(6.7%)0(0.0%)Moderate,n(%)0(0.0%)1(6.3%)0(0.0%)0(0.0%)ConstipationMild,n(%)0(0.0%)0(0.0%)1(6.7%)0(0.0%)

142、Moderate,n(%)1(5.3%)1(6.3%)0(0.0%)0(0.0%)Systolic Blood Pressure,mm Hg,LSM(SE)-2.3(2.8)-10.1(4.2)*-5.5(3.7)-12.0(3.5)*Diastolic Blood Pressure,mm Hg,LSM(SE)-2.5(1.5)-2.9(2.6)-4.0(3.7)-3.8(2.8)Heart Rate,mmHg,LSM(SE)-1.0(1.7)3.7(1.8)0.5(2.8)-0.1(1.8)*p .05 compared with placebo.2025/2/11 15:46sec.gov

143、/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm25/252Table of Contents16As detailed in the table below,glycemic control was maintained in subjects with diabetes,allpemvidutide groups demonstrat

144、ing trends toward improvements in fasting glucose and either maintainingor demonstrating trends toward improvement in HbA1c over the 24 weeks of treatment:CharacteristicTreatmentPlacebo1.2 mg1.8 mg2.4 mgNon-diabetesn=14n=13n=9n=11Fasting glucoseBaseline,mg/dL,mean(SD)96.2(12.4)99.4(11.9)96.0(12.4)99

145、.3(13.6)Week 24,mg/dL,mean(SD)93.3(12.1)99.1(13.1)96.9(12.5)98.4(24.5)HbA1cBaseline,%,mean(SD)5.8(0.2)5.7(0.3)5.7(0.2)5.5(0.4)Week 24,%,mean(SD)5.7(0.3)5.8(0.3)5.8(0.3)5.6(0.3)Diabetesn=5n=3n=6n=3Fasting glucose Baseline,mg/dL,mean(SD)111.5(19.2)132.1(28.2)120.2(37.1)147.4(40.4)Week 24,mg/dL,mean(SD

146、)109.4(14.8)123.4(50.8)109.0(13.1)75.5(29.0)HbA1cBaseline,%,mean(SD)6.1(0.6)7.8(1.46.4(0.5)6.8(1.3)Week 24,%,mean(SD)6.4(1.1)7.4(2.36.4(0.3)6.3(1.3)Phase 1b Trial 12-Week Type 2 Diabetes Safety TrialIn March 2023,we announced topline results from a 12-week Phase 1b safety trial ofpemvidutide,which e

147、valuated the safety profile of pemvidutide in subjects with overweight or obesityand type 2 diabetes.The trial was comprised of 54 subjects randomized 1:1:1:1 to 1.2 mg,1.8 mg,2.4 mgpemvidutide or placebo administered weekly for 12 weeks.No caloric restrictions or lifestyleinterventions were employe

148、d.Subjects were required to be 18-65 years of age with BMI 28 kg/m2 andtype 2 diabetes on a stable regimen of diet and exercise,metformin with absent or mild GI symptoms,orSGLT-2 therapy for at least 3 months.Subjects receiving pemvidutide achieved mean weight losses of 4.4%,6.1%and 7.7%at the 1.2mg

149、,1.8 mg,and 2.4 mg doses,respectively,over 12 weeks of treatment,with the placebo groupexperiencing a mean weight gain of 0.8%(efficacy estimand using MMRM analysis).Below is asummary of the efficacy findings:Body weightPlacebo(n=14)1.2 mg(n=14)1.8 mg(n=13)2.4 mg(n=13)Body weight,all subjects%,LSM(S

150、E)1+0.8(0.7)-4.4(1.1)*-6.1(1.6)*-7.7(1.4)*1 MMRM(mixed model for repeated measures),*p 0.001 compared with placeboGlucose homeostasis was maintained throughout the 12 weeks of treatment,with no significantchanges in fasting glucose or HbA1c and no hyperglycemic AEs.No SAEs were observed in patientst

151、reated with pemvidutide.Rates of GI AEs were low,and there were no AEs leading to studydiscontinuation.Below is a summary of the safety findings:2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010

152、/alt-20231231x10k.htm26/252Table of Contents17Placebo(n=14)1.2 mg(n=14)1.8 mg(n=13)2.4 mg(n=13)Glycemic ControlFasting glucose Baseline,mg/dLmean(SD)140.9(41.6)132.6(25.0)124.9(31.0)128.2(22.8)Week 24,mg/dLmean(SD)140.4(45.4)132.0(32.8)126.2(15.7)140.6(28.7)HbA1c Baseline,%mean(SD)6.6(1.3)6.5(1.0)6.

153、6(0.7)6.9(0.7)Week 24,%mean(SD)7.0(1.4)6.5(0.5)6.7(0.8)7.0(0.6)Adverse events(AEs)Serious AEsn(%)1(7.1%)20(0.0%)0(0.0%)0(0.0%)Discontinuations due to AEn(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Hyperglycemia AEsn(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Gastrointestinal AEsNausea AEsMild,n(%)0(0.0%)0(0.0%)0(0.0%)2(15.4%

154、)Moderate,n(%)0(0.0%)0(0.0%)0(0.0%)1(7.7%)Vomiting AEsMild,n(%)0(0.0%)0(0.0%)1(7.7%)1(7.7%)Moderate,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Diarrhea AEsMild,n(%)0(0.0%)0(0.0%)1(7.7%)0(0.0%)Moderate,n(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Constipation AEsMild,n(%)1(7.1%)0(0.0%)0(0.0%)2(15.4%)Moderate,n(%)0(0.0%)0(0.

155、0%)0(0.0%)0(0.0%)2 Cervical radiculopathyMOMENTUM Phase 2 Obesity Trial 48-Week AnalysisOn November 30,2023,we announced topline results from our 48-week MOMENTUM Phase 2obesity trial of pemvidutide.The trial enrolled 391 subjects with obesity or overweight with at least oneco-morbidity and without

156、diabetes.Subjects were randomized 1:1:1:1 to 1.2 mg,1.8 mg,2.4 mgpemvidutide or placebo administered weekly for 48 weeks in conjunction with diet and exercise.The 1.2mg and 1.8 mg doses were administered without dose titration,while a short 4-week titration period wasemployed for the 2.4 mg dose.Unl

157、ike other obesity studies with GLP-1 based agents,dose-reduction wasnot allowed.At baseline,subjects had a mean age of approximately 50 years,mean BMI ofapproximately 37 kg/m2 and mean body weight of approximately 104 kg.Approximately 75%of subjectswere female.At Week 48,subjects receiving pemviduti

158、de achieved mean weight losses of 10.3%,11.2%,15.6%at the 1.2 mg,1.8 mg,and 2.4 mg doses,respectively,compared to weight loss of 2.2%forplacebo.A near-linear trajectory of continued weight loss was observed on the 2.4 mg dose at the end oftreatment.Over 50%of subjects achieved at least 15%weight los

159、s and over 30%of subjects achieved atleast 20%weight loss on the 2.4 mg dose.As in prior clinical trials,pemvidutide resulted in robustreductions in serum lipids and improvements in blood pressure without imbalances in cardiac events,arrhythmias or clinically meaningful increases in heart rate.Gluco

160、se homeostasis was maintained,withno significant changes in fasting glucose or HbA1c.Below is a summary of the efficacy findings:2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10

161、k.htm27/252Table of Contents18Primary Endpoint:Body weightPlacebo(N=97)1.2 mg(N=98)1.8 mg(N=99)2.4 mg(N=97)Body weight,all subjects%,LSM(SE)1-2.2(1.4)-10.3(1.4)*-11.2(1.4)*-15.6(1.4)*Responder AnalysesPlacebo(N=51)1.2 mg(N=70)1.8 mg(N=63)2.4 mg(N=56)%Subjects w/5%weight loss%217.6%68.6%*76.2%*83.9%*

162、%Subjects w/10%weight loss3.9%42.9%*49.2%*71.4%*%Subjects w/15%weight loss2.0%21.4%*28.6%*51.8%*%Subjects w/20%weight loss2.0%10.0%9.5%32.1%*Secondary EndpointsPlacebo(N=50)1.2 mg(N=69)1.8 mg(N=58)2.4 mg(N=55)Total cholesterol%,LSM(SE)3-2.8(2.0)-11.6(1.7)*-13.1(1.9)*-15.1(2.0)*LDL cholesterol-2.8(4.

163、1)-6.2(3.5)-11.2(3.8)-9.9(3.9)Triglycerides+7.3(4.6)-21.7(3.9)*-22.3(4.3)*-34.9(4.4)*Blood Pressure and Heart RatePlacebo(N=97)1.2 mg(N=98)1.8 mg(N=99)2.4 mg(N=97)Systolic BPmm Hg,LSM(SE)1+3.5(2.3)-2.3(2.2)-1.6(2.2)-4.6(2.3)Diastolic BP+1.8(1.4)-2.1(1.3)-1.0(1.3)-2.9(1.4)Heart ratebpm,LSM(SE)1-1.4(1

164、.6)0.1(1.5)3.1(1.5)2.5(1.6)1MMRM,2CMH(Cochran Mantel Haenszel),3ANCOVA(analysis of covariance)*p .05;*p 0.05,*p 0.001,*p 0.0001 compared with placeboMore subjects receiving pemvidutide stayed on study compared to those receiving placebo,with74.1%of pemvidutide subjects completing the trial compared

165、to 61.9%of placebo subjects.Nausea andvomiting comprised the majority of AEs,which were predominantly mild to moderate in severity.Onlyone subject experienced a drug-related SAE,a case of vomiting at the 2.4 mg dose.Rates of AEs leadingto treatment discontinuation were 6.2%in subjects receiving plac

166、ebo and 5.1%,19.2%,and 19.6%insubjects receiving 1.2 mg,1.8 mg and 2.4 mg of pemvidutide,respectively.Study discontinuationsrelated to study drug occurred in 2.1%of placebo subjects and 4.1%,16.2%and 15.5%in subjectsreceiving 1.2 mg,1.8 mg and 2.4 mg of pemvidutide,respectively,with most discontinua

167、tions due to AEsin the pemvidutide groups occurring in the first 16 weeks of treatment.No AEs of special interest orMACE were observed,and there were low rates of cardiac AEs,including arrhythmias,with noimbalance across pemvidutide or placebo groups.Below is a summary of the safety findings:2025/2/

168、11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm28/252Table of Contents19Adverse events(AEs)Placebo(N=97)1.2 mg(N=98)1.8 mg(N=99)2.4 mg(N=97)SAEs related to study drugN(%)0(0.0%)0

169、(0.0%)0(0.0%)1(1.0%)4All AEs leading todiscontinuationN(%)6(6.2%)5(5.1%)19(19.2%)19(19.6%)Drug-related AEs leading todiscontinuationN(%)2(2.1%)4(4.1%)16(16.2%)15(15.5%)Gastrointestinal AEsmainly mild to moderateNauseaN(%)11(11.3%)25(25.5%)59(59.6%)50(51.5%)VomitingN(%)3(3.1%)6(6.1%)27(27.3%)27(27.8%

170、)DiarrheaN(%)5(5.2%)8(8.2%)10(10.1%)18(18.6%)ConstipationN(%)8(8.2%)17(17.3%)13(13.1%)22(22.7%)MACEN(%)0(0.0%)0(0.0%)0(0.0%)0(0.0%)Cardiac AEs includingarrhythmiasN(%)4(4.1%)3(3.1%)4(4.0%)3(3.1%)4 VomitingSummary of Glycemic ControlPlacebo(N=50)1.2 mg(N=68)1.8 mg(N=58)2.4 mg(N=55)Fasting glucose Bas

171、eline,mg/dLmean(SE)95.5(1.5)99.4(1.4)101.6(1.4)101.5(1.6)Week 48,mg/dLmean(SE)95.2(1.5)98.6(1.7)100.6(1.6)99.4(2.0)HbA1c Baseline,%mean(SE)5.6(0.0)5.5(0.0)5.5(0.1)5.6(0.0)Week 48,%mean(SE)5.5(0.0)5.5(0.0)5.6(0.1)5.5(0.1)Clinical Development PlanIn August 2023 we initiated a 48-week Phase 2b trial,IM

172、PACT,to evaluate the safety andefficacy of pemvidutide in subjects with MASH.The biopsy-driven trial is expected to enrollapproximately 190 subjects with and without diabetes randomized 1:2:2 to receive 1.2 mg,1.8 mgpemvidutide or placebo weekly for 48 weeks.The key efficacy endpoints are MASH resol

173、ution andfibrosis improvement after 24 weeks of treatment,with subjects to be followed for an additional 24weeks to a total of 48 weeks for assessment of safety and additional biomarker responses.Top-line 24-week results from this trial are expected in the first quarter of 2025.HepTcellHepTcell is a

174、n immunotherapeutic product candidate for patients chronically infected with thehepatitis B virus(“HBV”).Approximately 300 million people worldwide live with chronic HBVinfection,including approximately 2.4 million in the United States.Chronic HBV infection can lead toserious complications,including

175、 cirrhosis and liver cancer.Approximately 820,000 people die per yearworldwide due to cirrhosis and liver cancer.Current antivirals prevent disease progression but rarelyclear chronic infection.HepTcell is designed to drive CD4+and CD8+T-cell responses against all HBVgenotypes in patients of all eth

176、nic backgrounds.Stimulating T-cell responses in chronically infected HBVpatients has been challenging because chronic infection with HBV strongly suppresses T-cell immunitydirected against the virus.HepTcell focuses the T cell response on discrete,highly conserved regions ofthe HBV proteome.We belie

177、ve our approach allows HepTcell to break immune tolerance by activating T-cells against critical viral sequences with decreased probability of immune escape due to viral mutation.HepTcell is based on our synthetic peptide technology platform and is given by intramuscular injection.In 2018,we complet

178、ed a Phase 1 trial in the United Kingdom and South Korea in adult patients withchronic HBV.The HepTcell Phase 1 trial was a double-blinded,placebo-controlled,randomized,dose-escalation2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archive

179、s/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm29/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm30/252Table of Contents20study that enrolled 61 subjects w

180、ith chronic HBV who were HBeAg-negative and well-controlled onlicensed antivirals.A total of 41 patients received one of two dose levels of HepTcell,with and withoutIC31,a depot-forming TLR9 adjuvant developed by Valneva SE,while 20 control patients receivedeither IC31 alone or placebo.Patients rece

181、ived three injections 28 days apart and were followed forsix months after the final dose.All dose combinations were generally well-tolerated and met the primaryendpoint of safety.In the two adjuvanted HepTcell arms,T-cell responses against HBV markedlyincreased over baseline compared to placebo.The

182、chart below presents the immunogenicity against hepatitis B epitopes that wasdemonstrated in our Phase 1 clinical trial:We initiated a Phase 2 trial during the fourth quarter of 2020 in the United States,Canada,Europe and Asia that is a double-blind,randomized,placebo-controlled study of 80 adult pa

183、tients withHBeAg-negative inactive CHB and HBsAg 200 IU/mL Patients with approximately low HBsAg aremore likely to mount effective T cell responses against HBV than those with higher levels.The rationalefor the study design is based in our understanding that HepTcell could be used in combination wit

184、hnewer,direct acting agents that may be more effective than the current nucleosides analogs in reducingHBsAg to this level.Accordingly,selection of patients with HBsAg levels 200 IU/mL may mimic theeventual combination of HepTcell with the newer antiviral drugs in development.HepTcell was beingadmin

185、istered in six doses at the low dose level of HepTcell plus IC31 at 4-week intervals for 24 weeks,and patients will be followed for one year to evaluate safety and durability of response.The primaryefficacy endpoint is virological response,defined as a 1-log reduction in HBsAg levels from baseline o

186、rHBsAg clearance at 24 weeks.Secondary efficacy endpoints include reactivation of anti-HBV T cellresponses and other assessments of virologic response.Enrollment in this trial was completed in April2023.On March 27,2024,we announced that the overall response in the Phase 2 trial was deemed tobe insu

187、fficient to warrant further advancement in clinical trials.As a result,we have stopped any furtherdevelopment related to HepTcell.Our StrategyKey elements of our strategy include the following:Strategically partner or out-license certain product candidates at later stages ofdevelopment to focus our

188、efforts on early to mid-stage product development;In-license or acquire complementary metabolic or immunotherapeutic technologies andproduct candidates that are either synergistic or complementary to our capabilities toexpand our pipeline;and2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/0001326

189、19024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm31/2522025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm

190、32/252Table of ContentsApply our EuPort platform technologies to design and develop treatments for obesity,MASH and other metabolic diseases.Our Technology PlatformsCertain product candidates are based on our proprietary platform technologies as describedbelow:EuPort-based Peptide TechnologyEuPort i

191、s a platform technology that comprises a hydrophobic domain(e.g.,substituted orunsubstituted alkyl chain)and a hydrophilic group(e.g.,saccharide)conjugated to a non-terminal aminoacid of the peptide.The technology,on which pemvidutide is based,allows the peptide to bindextensively to albumin,an abun

192、dant protein in the blood,slowing the elimination of the peptide andincreasing its serum half-life,allowing for weekly instead of daily dosing,for example.EuPorttechnology may also slow the entry of the peptide into the circulation following subcutaneous injectionwhich may lead to improvements in to

193、lerability,cardiovascular risk and other characteristics of thepeptide as have been observed with pemvidutide.We have license rights to develop oxynomodulin(GLP1/glucagon dual receptor agonist)-based peptide therapeutics based on EuPort technology for anyindication.Key aspects of our EuPort technolo

194、gy,supported by findings in our preclinical studies andclinical trials,include its potential to:increase the serum half-life of the peptide allowing for extended dosing intervals;andslow the entry of the peptide into the circulation,decreasing the Cmax(maximalconcentration)increasing the Tmax(time t

195、o maximal concentration)of the peptide,andpotentially improving the tolerability of the peptide and preventing the increases in heartrate that have been observed with other agents.Synthetic Peptide Technology-DensigenDensigen is our synthetic fluorocarbon peptide technology platform.HepTcell,animmun

196、otherapeutic developed using our Densigen platform,is designed to activate T-cells to generate acytotoxic immune response against intracellular pathogens.This synthetic peptide technology is based onpeptides of 30 40 amino acids that comprise a high density of CD4 and CD8 T-cell epitopes selected to

197、focus the T-cell response on highly conserved targets and allow diverse populations to respond to theproduct candidate.Densigen technology is protected by patents owned by us.Key aspects of our Densigen technology,supported by findings in our preclinical studies andclinical trials,include its potent

198、ial to:elicit responses across multiple targets for the disease;direct an immune response precisely to specific antigen sites,thereby avoiding morereactive but less effective sites present in the full-length protein;andprompt a stronger immune response than naked peptides due to depot effect caused

199、byattaching a biologically inert fluorocarbon chain to each peptide.CompetitionThe biopharmaceutical industry is intensely competitive and is characterized by rapidtechnological progress.In general,competition among pharmaceutical products is based in part onproduct efficacy,safety,reliability,avail

200、ability,price and patent position.An important factor is therelative timing of the market introduction of our products and our competitors products.Accordingly,thespeed with which we can develop products,complete the clinical trials and approval processes andsupply commercial quantities of the produ

201、cts to the market is an important competitive factor.Ourcompetitive position also depends upon our ability to show differentiation with a product that is eithermore efficacious,particularly in the relevant target populations,offers a better safety or tolerabilityprofile,is less expensive or quicker

202、to manufacture,or represents a combination of these advantages.Wealso depend upon our ability to attract and retain2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm33/252212

203、025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm34/252Table of Contentsqualified personnel,obtain patent protection or otherwise develop proprietary products or processes an

204、dsecure sufficient capital resources for the often substantial period between technological conception andcommercial sale.Large and established companies such as Eli Lilly,Roche through its acquisition of Carmot andD&D Pharma,Novo Nordisk,Pfizer,AstraZeneca,Amgen,Boehringer Ingelheim and Merck,among

205、others,compete in the same market as our product candidates.These companies compete with us withtheir greater experience and resources to support their research and development efforts,conduct testingand clinical trials,obtain regulatory approvals to market products,manufacture such products on a br

206、oadscale and market approved products.These companies also compete with us by having significantlygreater research and marketing capabilities than we do and may also have products that have beenapproved or are in late stages of development and have collaborative arrangements in our target marketswit

207、h leading companies and research institutions.Established pharmaceutical companies may also investheavily to accelerate discovery and development of novel compounds or to in-license novel compoundsthat could make the products that we develop obsolete.We also face competition from smaller companieswh

208、o,like us,rely on investors to fund research and development and compete for co-development andlicensing opportunities from large and established pharmaceutical companies.We face competition for pemvidutide,our dual GLP-1/glucagon dual agonist for the treatmentof obesity and MASH.For obesity,we face

209、 competition from companies such as Novo Nordisk,whoseGLP-1 agonist,brand named Wegovy,or compound name semaglutide,was approved for weight loss inJune 2021.Other companies with potentially competitive products or product candidates,include EliLilly with GLP-1/glucose-dependent insulinotropic polype

210、ptide receptor(“GIP”)dual agonists,includingZepbound,or compound name tirzepatide,approved for obesity in November 2023;BoehringerIngelheim,AstraZeneca,Innovent Biologics/Eli Lilly,and Roche through its acquisition of Carmot andD&D Pharma,with GLP-1/glucagon receptor dual agonists;Hanmi Pharmaceutic

211、al and Eli Lilly withGLP-1/glucagon/GIP triple agonists;Amgen with its GLP-1 agonist/GIP antagonist antibody;and NovoNordisk with Amylin and Amylin-GLP-1 combination candidates.Other companies have beendeveloping oral candidates for the treatment of obesity with GLP-1 monoagonist or GLP-1/GIP dualre

212、ceptor agonists including Pfizer,Lilly,Structure Therapeutics,AstraZeneca through its acquisition ofEccogene and Roche through its acquisition of Carmot.In addition,Novo Nordisk has an FDA-approvedoral GLP-1 therapy,Rybelsus or compound name semaglutide.We face competition in MASH fromcompanies such

213、 as Madrigal Pharmaceuticals,Terns,Aligos and Viking Therapeutics,which aredeveloping orally administered,thyroid hormone receptor(“THR”)-selective agonist;AkeroTherapeutics,89Bio,Novo Nordisk and Boston Pharmaceuticals,which are developing fibroblast growthfactor 21(“FGF-21”)analogs;Novo Nordisk,wh

214、ich is developing a GLP-1 agonist;Merck/HanmiPharmaceutical,which is developing a GLP-1/glucagon dual agonist,Eli Lilly,which is developing aGLP-1/GIP dual agonist,Inventiva,which is developing a pan-peroxisome proliferator-activated receptor(“PPAR”)agonist;Sagimet which is developing a fatty acid s

215、ynthetase inhibitor,HEC Pharma which isdeveloping a GLP-1/FGF-21dual agonist;and Pfizer and Eli Lilly,which are developing small moleculeGLP-1 agonists.In addition,many other small companies are developing other new technologies directedtowards obesity or MASH.Intellectual PropertyWe generally seek

216、patent protection for our technology and product candidates in the UnitedStates and abroad.The patent coverage available to biotechnology companies is generally uncertainbecause it involves complex legal and factual considerations.Our success will depend,in part,onwhether we can:obtain patents to pr

217、otect our own technologies and product candidates;obtain licenses to use the technologies of third parties,which may be protected by patents;protect our trade secrets and know-how;andoperate without infringing the intellectual property and proprietary rights of others.We have relied upon certain pro

218、prietary trade secrets,know-how and continuing technologicaladvances to develop a competitive position.In efforts to maintain confidentiality and ownership of tradesecrets,proprietary information and developments,all of our employees are required to execute2025/2/11 15:46sec.gov/Archives/edgar/data/

219、1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm35/25222agreements regarding confidentiality and assign to us all rights to any inventions and processes theydevelop while they are employed by us.We may in the future

220、2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm36/252Table of Contentsuse license agreements to access external products and technologies as well as to convey our ownintel

221、lectual property to others.We will be able to protect our proprietary rights from unauthorized use bythird parties only to the extent that our proprietary rights are covered by valid and enforceable patents orare effectively maintained as trade secrets.Patent Rights Related to our EuPort Platform Te

222、chnologyEuPort Technology In-Licensed from Mederis Diabetes,LLCPursuant to a license agreement between the Company and Mederis Diabetes,LLC(“Mederis”)(the“Mederis IP License Agreement”),we are the exclusive licensee of patent rights owned by Mederisto develop and commercialize surfactant functionali

223、zed(“EuPort domain”)incretin-based peptidetherapeutics,including(GLP-1-glucagon)/oxyntomodulin,and variants thereof,including pemvidutide,for any indication,and Mederis has certain patent rights granted back to it for the use of the EuPorttechnology outside of the Companys exclusive field of increti

224、n-based peptide therapeutics.The EuPortdomain comprises a hydrophobic domain(e.g.,substituted or unsubstituted alkyl chain)and ahydrophilic group(e.g.,saccharide)conjugated to a non-terminal amino acid of the peptide.Patentsunder Mederis IP License Agreement have been granted in the United States,Ja

225、pan and Korea,andapplications are pending in the United States,Japan as well as other commercially relevant jurisdictions.The claims are directed to peptides(at least four amino acids in length),including peptides that bindreceptors for glucagon and/or GLP-1,conjugated to an alkyl saccharide surfact

226、ant,including an alkylglycoside surfactant.The patents and,if issued,the patent(s)resulting from the pendingapplication(s)have an expiration date of no earlier than May 2032,not giving effect to any potentialextensions and assuming payment of all associated fees.Patents subject to the Mederis IP Lic

227、enseAgreement have also been granted in the United States,Canada,Europe,Korea,Australia,Israel andJapan,and applications are pending in the United States,Europe,Japan,China and other commerciallyrelevant jurisdictions,wherein the claims are directed to specific GLP-1 and/or glucagon peptidesconjugat

228、ed to the EuPort domain.The patents and,if issued,the patent(s)resulting from the pendingapplication(s)have an expiration date of no earlier than May 2035.Patent Rights Related to our Densigen Platform TechnologyFluorocarbon Antigen Delivery VectorsWe are developing a fluorocarbon antigen construct

229、platform technology.Our patents coveringthis technology are issued in the United States,China,Japan and certain European countries,includingthe United Kingdom,Germany and France.Additional patents are issued in other commercially relevantjurisdictions and an application is pending in the United Stat

230、es.The claims are directed to thefluorocarbon linked antigen construct,compositions comprising the construct and methods of using theconstruct to stimulate an immune response.The patents and,if issued,the patent(s)resulting from thepending patent applications,are expected to have an expiration date

231、no earlier than April 2025,not givingeffect to any potential extensions and assuming payment of all associated fees.Formulation of Antigen Delivery Vectors Manufacturing Process for the Final Formulation of theAntigen Delivery VectorsWe are developing a manufacturing process for solubilizing certain

232、 fluorocarbon peptides andfinal lyophilized compositions thereof that are soluble in an aqueous solution,for which we have patentsissued in the United States,Europe,Korea and Japan as well as other commercially relevant jurisdictions,and a patent application pending in the United States.The claims a

233、re directed to methods of solubilizingcertain fluorocarbon antigen peptides using acetic acid formulations and manufactured lyophilizedcompositions thereof that are soluble in an aqueous solution.The patents and,if issued,thepatent(s)resulting from the pending patent applications,are expected to hav

234、e an expiration date noearlier than December 2031,not giving effect to any potential extensions and assuming payment of allassociated fees.Patent Rights Related to our Product CandidatesPemvidutide,Dual GLP-1/Glucagon Dual Agonist for Obesity and MASHWe are the exclusive licensee of patent rights ow

235、ned by Mederis to develop and commercializesurfactant functionalized(GLP-1-glucagon)/oxyntomodulin-based peptide therapeutics,and variants2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20

236、231231x10k.htm37/25223thereof,including pemvidutide,for any use including the treatment of obesity,metabolic syndrome,insulin resistance,diabetes and cardiovascular disease.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/dat

237、a/1326190/000132619024000010/alt-20231231x10k.htm38/252Table of ContentsPatents under the Mederis IP License Agreement have been granted in the United States,Europe,Japan,Australia and Mexico with pending applications in the United States,Europe,Japan and Korea,as well asother commercially relevant

238、jurisdictions.The claims are directed to GLP-1/glucagon dual agonistpeptides conjugated to a surfactant and their use to treat metabolic syndrome,obesity and other relateddiseases.The patents and,if issued,the patent(s)resulting from the pending application(s)have anexpiration date of no earlier tha

239、n May 2032 and extending to May 2035,not giving effect to any potentialextensions and assuming payment of all associated fees.Use of pemvidutide for treating MASH orMASLD(referred to as NASH or NAFLD in the patent and patent applications)is further covered by,and subject to the Mederis IP License Ag

240、reement,with a granted patent in the United States,and pendingapplications in the United States,Europe,Japan and other commercially relevant jurisdictions.Thepatents and,if issued,the patent(s)resulting from the pending patent applications,are expected to havean expiration date of no earlier than Ja

241、nuary 2039,not giving effect to any potential extensions andassuming payment of all associated fees.Use of pemvidutide in methods with improved tolerability,dosing and therapeutic regimens isfurther covered in pending applications in the United States,Europe,Japan and Korea,as well as othercommercia

242、lly relevant jurisdictions,which are owned by us and not subject to the Mederis IP LicenseAgreement.The claims are directed to liquid formulations and the use of pemvidutide in a therapeuticdosing regimen with improved tolerability.If issued,the patent(s)resulting from the pendingapplication(s)have

243、an expiration date of no earlier than February 2041 not giving effect to any potentialextensions and assuming payment of all associated fees.Use of pemvidutide in methods for inducing weight loss is further covered in pendingapplications in the United States,Europe,Japan and Korea,as well as other c

244、ommercially relevantjurisdictions owned by us and not subject to the Mederis IP License Agreement.The claims are directedto the use of pemvidutide in a therapeutic dosing regimen for chronic weight management.If issued,thepatent(s)resulting from the pending application(s)have an expiration date of n

245、o earlier than December2041,not giving effect to any potential extensions and assuming payment of all associated fees.Use of pemvidutide in methods for reducing body weight in a human with fatty liver disease isfurther covered in United States patent application and corresponding international(PCT)p

246、atentapplication owned by us and not subject to the Mederis IP License Agreement,and from which we expectto file National Phase patent applications in commercially relevant jurisdictions.The claims are directedto the use of pemvidutide in methods for reducing body weight in a human with MASH or MASL

247、D(referred to as NASH or NAFLD in the patent and patent applications),with or without also having typeII diabetes.If issued,the patent(s)resulting from the pending application(s)have an expiration date of noearlier than September 2043,not giving effect to any potential extensions and assuming paymen

248、t of allassociated fees.Use of pemvidutide in methods for reducing the risk of cardiovascular(CV)disease is furthercovered in a United States patent application and corresponding international(PCT)patent applicationowned by us and not subject to the Mederis IP License Agreement,and from which we exp

249、ect to fileNational Phase patent applications in commercially relevant jurisdictions.The claims are directed to theuse of pemvidutide in methods for reducing the risk of cardiovascular(CV)disease in a human with orwithout also having type 2 diabetes.If issued,the patent(s)resulting from the pending

250、application(s)havean expiration date of no earlier than November 2043,not giving effect to any potential extensions andassuming payment of all associated fees.HepTcell,Chronic Hepatitis B ImmunotherapyWe have issued patents for HBV immunotherapy technology directed to compositionscomprising fluoroca

251、rbon constructs with specific peptide HBV antigen sequences in the United States,Europe,Japan and Korea,and pending applications in the United States,Europe,Japan and China,aswell as other commercially relevant jurisdictions.The claims are directed to HBV antigen peptidesequences comprising T-cell e

252、pitopes linked to fluorocarbon chains and compositions comprising acombination of HBV antigen peptide sequences.The patents,and if issued,the patent(s)resulting fromthe pending patent applications,are expected to have an expiration date no earlier than December 2033,not giving effect to any potentia

253、l extensions and assuming payment of all associated fees.HepTcell isalso covered by the patents and patent applications relating to our Densigen platform technology.Use of HepTcell for treating patients with chronic HBV infection is further covered by apending United States provisional patent applic

254、ation,from which we expect to file United States and2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm39/25224international(PCT)patent applications.The claims are directed to

255、 treating patients with chronic HBVinfection characterized with low hepatitis B surface antigen2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm40/252Table of Contents(“HBsA

256、g”).If issued,the patent(s)resulting from the pending patent application(s)are expected to havean expiration date no earlier than December 2044,not giving effect to any potential extensions andassuming payment of all associated fees.United States Government RegulationThe FDA regulates drugs and biol

257、ogical products under the Federal Food,Drug,and CosmeticAct(“FD&C Act”),the Public Health Service Act(“PHS Act”),the regulations under Titles 21 and 42 ofthe Code of Federal Regulations(21 CFR and 42 CFR),as well as other federal,state and local statutesand regulations.The FD&C Act and the PHS Act a

258、nd their corresponding regulations govern,amongother things,the testing,research,manufacturing,approval,safety,efficacy,labeling,packaging,storage,record keeping,distribution,import,export,reporting,sale,advertising and other promotional practicesinvolving drugs and biological products.An IND applic

259、ation must be in effect before clinical testing ofdrugs and biological products can begin.FDA approval must be obtained before drugs and biologicalproducts can be marketed.The process of obtaining regulatory approvals and the subsequent compliancewith appropriate federal,state,local and foreign stat

260、utes and regulations require the expenditure ofsubstantial time and financial resources,and each process may take several years to complete,althoughcertain expedited programs potentially applicable to our product candidates,such as FDA fast trackdesignation for certain new drugs with the potential t

261、o address unmet medical needs for certain serious orlife-threatening conditions,may potentially expedite development and/or approval processes.Certainfederal incentive programs are also potentially applicable to our product candidates,such as for“orphandrugs”that treat rare conditions.Data obtained

262、from clinical activities is not always conclusive and maybe susceptible to varying interpretations,which could delay,limit or prevent regulatory approval.TheFDA may not grant approval on a timely basis,or at all,and we may encounter difficulties orunanticipated costs in our efforts to secure necessa

263、ry governmental approvals,which could delay orpreclude us from marketing our product candidates.In addition,the FDA may limit the indications foruse or place other conditions on any approvals that could restrict the commercial application of theproducts.After approval,some types of changes to the ap

264、proved product,such as adding new indications,manufacturing changes and additional labeling claims,are subject to further testing requirements andFDA review and approval.In addition,our failure,or the failure of our third-party manufacturers,tocomply with applicable regulations could result in sanct

265、ions being imposed on us,including clinicalholds,fines,injunctions,civil penalties,delays,suspension or withdrawal of approvals,licenserevocation,seizures or recalls of product candidates or products,operating restrictions and criminalprosecutions,any of which could adversely affect our ability to c

266、ommercialize our product candidates.Drug and Biological Products Development ProcessThe process required by the FDA before a drug or biological product may be marketed in theUnited States generally involves the following:completion of preclinical laboratory tests and animal studies according to appl

267、icable goodlaboratory practices(“GLP”),applicable requirements for the humane use of laboratoryanimals,such as the Animal Welfare Act or other applicable regulations;submission to the FDA of an application for an IND which must become effective beforehuman clinical trials may begin;obtaining approva

268、l by an independent Institutional Review Board(“IRB”)at each clinicalsite before a clinical trial may be initiated at that site;performance of adequate and well-controlled human clinical trials according to the FDAsregulations commonly referred to as good clinical practices(“GCP”)and any additionalr

269、equirements for the protection of human research subjects and their health information,toestablish the safety and efficacy of the proposed product for its intended use;submission to the FDA of a new drug application(“NDA”)or biologics license application(“BLA”)for marketing approval that includes su

270、bstantial evidence of safety,purity andpotency from results of clinical trials,as well as the results of preclinical testing,detailedinformation about the chemistry,manufacturing and controls,and proposed labeling andpackaging for the product candidate;2025/2/11 15:46sec.gov/Archives/edgar/data/1326

271、190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm41/252252025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-202

272、31231x10k.htm42/252Table of Contentsreview of the product candidate by an FDA advisory committee,if applicable;satisfactory completion of an FDA inspection of the manufacturing facility or facilitieswhere the product candidate is produced to assess compliance with cGMP and to confirmthat the facilit

273、ies,methods and controls are adequate to assure the product candidatesidentity,strength,quality and purity;satisfactory completion of potential FDA audits of the preclinical study and clinical trialsites that generated the data in support of the NDA or BLA;andFDA review and approval,or licensure,of

274、the NDA or BLA,including agreement on post-marketing commitments,if applicable.Before testing any drug or biological product candidate in humans,the product candidate entersthe preclinical study stage.Preclinical studies include laboratory evaluations of product chemistry,toxicity and formulation,as

275、 well as animal studies to assess the potential safety and activity of theproduct candidate.The conduct of certain preclinical studies must comply with federal regulations andrequirements including GLP and the Animal Welfare Act.The clinical trial sponsor must submit the results of the preclinical s

276、tudies,together withmanufacturing information,analytical data,any available clinical data or literature and a proposedclinical trial protocol,to the FDA as part of the IND.Some preclinical studies may continue even afterthe IND is submitted.The FDA requires a 30-day waiting period after the filing o

277、f each IND beforeclinical trials may begin.The FDA may also place the clinical trial on a clinical hold within that 30-daytime period.In such a case,the IND sponsor and the FDA must resolve any outstanding concerns beforethe clinical trial can begin.Even after the IND has gone into effect and clinic

278、al testing has begun,theFDA may impose a partial or complete clinical hold on clinical trials due to safety concerns or non-compliance.A partial clinical hold can limit a trial,for example,to certain doses or for a certain length oftime or to a certain number of subjects.A complete clinical hold ord

279、er issued by the FDA would delay aproposed clinical study or suspend an ongoing study until all outstanding concerns have been adequatelyaddressed and the FDA has notified the company that clinical investigations may proceed or resume.Accordingly,we cannot be sure that submission of an IND will resu

280、lt in the FDA allowing clinical trialsto begin,or that,once the trials have begun,issues will not arise that suspend or terminate such studies.Clinical trials involve the administration of the product candidate to healthy volunteers orpatients under the supervision of qualified investigators.Clinica

281、l trials are conducted under protocolsdetailing,among other things,the objectives of the clinical trial,dosing procedures,subject selection andexclusion criteria,and the parameters to be used to monitor subject safety,including stopping rules thatassure a clinical trial will be stopped if certain ad

282、verse events(“AEs”)should occur.Each protocol andany amendments to the protocol must be submitted to the FDA as part of the IND during applicablephases of development.Clinical trials must be conducted and monitored in accordance with the FDAsregulations and GCP requirements,which establish standards

283、 for conducting,recording data from,andreporting the results of clinical trials,with the goals of assuring that the data and results are credible andaccurate and that study participants rights,safety,and well-being are protected.GCP requirementsinclude the requirement that all research subjects prov

284、ide informed consent.Further,each clinical trialmust be reviewed and approved by an IRB at or servicing each institution at which the clinical trial willbe conducted.An IRB is charged with protecting the welfare and rights of trial participants and considerssuch items as whether the risks to individ

285、uals participating in the clinical trials,not only from theinvestigational product itself but also from any required procedures or study visits to be conducted duringthe trial,are minimized and are reasonable in relation to anticipated benefits.The IRB also approves theform and content of the inform

286、ed consent that must be signed by each clinical trial subject or his or herlegal representative and must monitor the clinical trial until completed.Human clinical trials are typically conducted in three sequential phases that may overlap or becombined:Phase 1.The drug or biological product is initia

287、lly introduced into a small group of healthyhuman subjects(e.g.,10 to 20 volunteers)and tested for safety and to develop detailedprofiles of its pharmacological and pharmacokinetic actions,determine side effectsassociated with increasing doses,and,if possible,gain early evidence of effectiveness.Int

288、he case of some products for severe or life-threatening diseases,especially when the2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm43/25226product may be too inherently to

289、xic to ethically administer to healthy volunteers,the initialhuman testing is often conducted in patients.2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm44/252Table of Con

290、tentsPhase 2.The drug or biological product is evaluated in a larger but limited patientpopulation(e.g.,a few hundred patients with the disease or conduction under study)toidentify possible adverse effects and safety risks,to preliminarily evaluate the efficacy ofthe product for specific targeted di

291、seases and to determine dosage tolerance,optimaldosage and dosing schedule.Phase 3.These clinical trials are undertaken to further evaluate dosage,clinical efficacy,potency and safety in an expanded patient population(e.g.,several hundred to severalthousand patients)at geographically dispersed clini

292、cal trial sites.These clinical trials areintended to establish the overall risk/benefit profile of the product and provide an adequatebasis for product labeling.Post-approval clinical trials,sometimes referred to as Phase 4 clinical trials,may be conductedafter initial marketing approval.These clini

293、cal trials are used to gain additional experience from thetreatment of patients in the intended therapeutic indication,particularly for long-term safety follow-up.During all phases of clinical development,regulatory agencies require extensive monitoring andauditing of all clinical activities,clinica

294、l data and clinical trial investigators.Annual progress reportsdetailing the results of the clinical trials must be submitted to the FDA.Written IND safety reports mustbe promptly submitted to the FDA and the investigators for serious and unexpected AEs,any findingsfrom other studies,tests in labora

295、tory animals or in vitro testing and other sources that suggest asignificant risk for human subjects,or any clinically important increase in the rate of a serious suspectedadverse reaction over that listed in the protocol or investigator brochure.The sponsor must submit anIND safety report within 15

296、 calendar days after the sponsor determines that the information qualifies forreporting.The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspectedadverse reaction within 7 calendar days after the sponsors initial receipt of the information.Phase 1,Phase 2 and Phase 3

297、clinical trials may not be completed successfully within any specified period,if atall.The FDA or the sponsor may suspend a clinical trial at any time on various grounds,including afinding that the research subjects or patients are being exposed to an unacceptable health risk.Similarly,an IRB can su

298、spend or terminate approval of a clinical trial at its institution if the clinical trial is notbeing conducted in accordance with the IRBs requirements or if the drug or biological product has beenassociated with unexpected serious harm to patients.In limited circumstances,FDA also permits the admin

299、istration of investigational small moleculedrug or biological products to patients under its expanded access regulatory authorities.Under the FDAsexpanded access authority,patients who are not able to participate in a clinical trial may be eligible foraccessing investigational products,including thr

300、ough individual compassionate or emergency use inconcert with their requesting physician.Concurrent with clinical trials,companies usually complete additional animal studies,developadditional information about the physical characteristics of the drug or biological product candidate andfinalize a pro

301、cess for manufacturing the product in commercial quantities in accordance with cGMPrequirements.To help reduce the risk of the introduction of adventitious agents with use of biologicalproducts,the PHS Act emphasizes the importance of manufacturing controls for products whoseattributes cannot be pre

302、cisely defined.The manufacturing process must be capable of consistentlyproducing quality batches of the product candidate and,among other things,the sponsor must developmethods for testing the identity,strength,quality,potency and purity of the final product.Additionally,appropriate packaging must

303、be selected and tested,and stability studies must be conducted todemonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.Certain FDA programs are available to facilitate and expedite the development and review ofnew drugs intended to address unmet needs

304、 in the treatment of serious or life-threatening conditions.These expedited programs include fast track designation,breakthrough therapy designation,priorityreview and accelerated approval.Each of these programs has its own features and qualifying criteria.Asponsor must submit a request for fast tra

305、ck designation,breakthrough therapy designation,or priorityreview,which may or may not be granted by the FDA.For fast track and breakthrough therapydesignations,FDA may later decide the product no longer meets the conditions for designation and mayrescind the designation.For accelerated approval,a s

306、ponsor generally discusses the possibility ofaccelerated approval with the FDA during development,and the FDA may or may not agree thataccelerated approval is an appropriate pathway for a particular drug.Some of these expedited programs2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/0001326190240

307、00010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm45/25227could potentially apply to our product candidates,although this cannot be assured,and we do notcurrently have any products with expedited program designations.2025/2/11 15:46sec.go

308、v/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm46/252Table of ContentsThe sponsor of a clinical trial or the sponsors designated responsible party may be required toregister certain informatio

309、n about the trial and disclose certain results on government or independentregistry websites,such as ClinicalTrials.gov.Additionally,a manufacturer of an investigational drug for aserious disease or condition is required to make available,such as by posting on its website,its policy onevaluating and

310、 responding to requests for individual patient access to such investigational drug.Thisrequirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigationaldrug or,as applicable,15 days after the drug receives a designation as a breakthrough therapy,fast tra

311、ckproduct,or regenerative medicine advanced therapy.Review and Approval ProcessesAfter the completion of clinical trials of a drug or biological product candidate,the FDAsapproval of an NDA or BLA must be obtained before commercial marketing of the product may begin.The NDA or BLA must include resul

312、ts of product development,laboratory and animal studies,humanstudies,information on the manufacture and composition of the product,proposed labeling and otherrelevant information.In addition,under the Pediatric Research Equity Act,as amended,an NDA or BLAor supplement to an NDA or BLA generally must

313、 contain data to assess the safety and effectiveness ofthe product for the claimed indications in all relevant pediatric subpopulations and to support dosing andadministration for each pediatric subpopulation for which the product is safe and effective.The FDA maygrant deferrals for submission of da

314、ta or full or partial waivers depending on the designated pathway forsubmission.The testing and approval processes require substantial time and effort and there can be noassurance that the FDA will accept the NDA or BLA for filing and,even if filed,that any approval willbe granted on a timely basis,

315、if at all.Under the Prescription Drug User Fee Act(“PDUFA”),as amended,each NDA or BLA must beaccompanied by a significant application fee.PDUFA also imposes an annual prescription drug productprogram fee for biologics.Fee waivers or reductions are available in certain circumstances,including awaive

316、r of the application fee for the first application filed by a small business.Following submission of the application,the FDA reviews the NDA or BLA to determine if it issubstantially complete before the agency accepts it for filing.The FDA may refuse to file any NDA orBLA that it deems incomplete or

317、 not properly reviewable at the time of submission and may requestadditional information.In this event,the NDA or BLA must be resubmitted with the additionalinformation.The resubmitted application also is subject to review before the FDA accepts it for filing.Once the submission is accepted for fili

318、ng,the FDA begins an in-depth substantive review of the NDA orBLA.FDA performance goals generally provide for action on an NDA or BLA within 10 months of the60-day filing date,which would be within 12 months of its submission.That deadline can be extendedunder certain circumstances,including by the

319、FDAs requests for additional information.The targetedaction date can also be shortened to 6 months of the 60-day filing date,or 8 months after submission,forproducts that are granted priority review designation because they are intended to treat serious or life-threatening conditions and demonstrate

320、 the potential to address unmet medical needs.The FDA reviewsthe NDA or BLA to determine,among other things,whether the proposed product is safe and effectivefor its intended use,and whether the product is being manufactured in accordance with cGMP to assurethe products identity,safety,quality,poten

321、cy and purity.The FDA may refer applications for drugs orbiological products that are novel or that present difficult questions of safety or efficacy to an advisorycommittee,typically a panel that includes clinicians and other experts,for review,evaluation and arecommendation as to whether the appli

322、cation should be approved and under what conditions.The FDAis not bound by the recommendations of an advisory committee,but it considers such recommendationscarefully when making decisions.During the NDA or BLA review process,the FDA also will determine whether a RiskEvaluation and Mitigation Strate

323、gy(“REMS”)is necessary to assure the safe use of the drug orbiological product.If the FDA concludes a REMS is needed,the sponsor of the NDA or BLA mustsubmit a proposed REMS;the FDA will not approve the NDA or BLA without a REMS,if required.AREMS could include medication guides,physician communicati

324、on plans or elements to assure safe use,such as restricted distribution methods,patient registries and other risk minimization tools.Any of theselimitations on approval or marketing could restrict the commercial promotion,distribution,prescriptionor dispensing of products.Before approving an NDA or

325、BLA,the FDA will inspect the facilities at which the product ismanufactured.The FDA will not approve the NDA or BLA unless it determines that the manufacturing2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives/edgar/data/1326190/0001

326、32619024000010/alt-20231231x10k.htm47/25228processes and facilities are in compliance with cGMP requirements and adequate to assure consistentproduction of the product within required2025/2/11 15:46sec.gov/Archives/edgar/data/1326190/000132619024000010/alt-20231231x10k.htmhttps:/www.sec.gov/Archives

327、/edgar/data/1326190/000132619024000010/alt-20231231x10k.htm48/252Table of Contentsspecifications.Additionally,before approving an NDA or BLA,the FDA will typically inspect one ormore clinical sites to assure that the clinical trials were conducted in compliance with IND studyrequirements and GCP req

328、uirements.To assure cGMP and GCP compliance,an applicant must incursignificant expenditure of time,money and effort in the areas of training,record keeping,production andquality control.Notwithstanding the submission of relevant data and information,the FDA may ultimatelydecide that the NDA or BLA d

329、oes not satisfy its regulatory criteria for approval.Data obtained fromclinical trials are not always conclusive and the FDA may interpret data differently than how we interpretthe same data.If the agency decides not to approve the NDA or BLA in its present form,the FDA willissue a complete response

330、 letter that usually describes all of the specific deficiencies in the NDA or BLAidentified by the FDA.The deficiencies identified may be minor,for example,requiring labelingchanges;or major,for example,requiring additional clinical trials.Additionally,the complete responseletter may include recomme

331、nded actions that the applicant may take for the FDA to reconsider theapplication.If a complete response letter is issued,the applicant may either resubmit the NDA or BLA,addressing all of the deficiencies identified in the complete response letter,or withdraw the application.If a product receives r

332、egulatory approval,the approval may be significantly limited to specificdiseases and dosages or the indications for use may otherwise be limited,which could restrict thecommercial value of the product.Further,the FDA may require that certain contraindications,warningsor precautions be included in th

333、e product labeling.The FDA may impose restrictions and conditions onproduct distribution,prescribing,or dispensing in the form of a REMS,or otherwise limit the scope ofany approval.In addition,the FDA may require post-marketing clinical trials,sometimes referred to asPhase 4 clinical trials,designed to further assess a products safety and effectiveness,and testing andsurveillance programs to monit