IntelGenx Technologies Corp. (IGX) 2020年年度報告「TSX-V」.pdf

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1、10-K 1 form10k.htm FORM 10-KUNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington,D.C.20549FORM 10-K ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d)OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31,2020 or TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d)OF THE SECURITIES

2、 EXCHANGE ACT OF 1934For the transition period from _ to _Commission file number 000-31187IntelGenx Technologies Corp.(Exact Name of Registrant as Specified in Its Charter)Delaware 87-0638336State or Other Jurisdiction ofIncorporation or Organization I.R.S.Employer Identification No.6420 Abrams,Vill

3、e Saint Laurent,Quebec,Canada H4S 1Y2Address of Principal Executive Offices Zip CodeRegistrants telephone number,including area code (514)331-7440Securities registered pursuant to Section 12(b)of the Act:NoneSecurities registered pursuant to Section 12(g)of the Act:Title of each classTrading Symbol(

4、s)Name of each exchange on which registeredCommon Stock,$0.00001 par valueIGXTIGXOTCQBTSX Venture ExchangeIndicate 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 repo

5、rts pursuant to Section 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 Securities Exchange Act of1934 during the preceding 12 months(or for such shorter period that the registrant was required to fi

6、le such reports),and(2)has been subject to suchfiling 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 to Rule 405of Regulation S-T(232.405 of this chapter)during the prec

7、eding 12 months(or for such shorter period that the registrant was required to submit suchfiles).Yes No Indicate by check mark whether the registrant is a large accelerated filer,an accelerated filer,a non-accelerated filer,smaller reporting company,oran emerging growth company.See the definitions o

8、f large accelerated filer,accelerated filer,smaller reporting company,and emerging growthcompany in Rule 12b-2 of the Exchange Act.Large accelerated filer Accelerated filer Non-accelerated filer Smaller reporting company Emerging growth company If an emerging growth company,indicate by check mark if

9、 the registrant has elected not to use the extended transition period for complying with anynew or revised financial accounting standards provided pursuant to Section 13(a)of the Exchange Act.1Indicate by check mark whether the registrant has filed a report on and attestation to its managements asse

10、ssment of the effectiveness of its internalcontrol over financial reporting under Section 404(b)of the Sarbanes-Oxley Act(15 U.S.C.7262(b)by the registered public accounting firm that preparedor issued its audit report.Indicate by check mark whether the registrant is a shell company(as defined in Ru

11、le 12b-2 of the Act).Yes No As of June 30,2020,the aggregate market value of the registrants voting and non-voting common equity held by non-affiliates of the registrant was$20,920,883 based on the closing price of the registrants common stock of U.S.$0.21,as reported on the OTCQB on that date.Share

12、s of theregistrants common stock held by each officer and director and each person who owns 10%or more of the outstanding common stock of the registranthave been excluded in that such persons may be deemed to be affiliates.This determination of affiliate status is not necessarily a conclusivedetermi

13、nation for other purposes.ClassOutstanding at March 24,2021Common Stock,$.00001 par value111,909,533 shares Indicate the number of shares outstanding of each of the registrants classes of common stock,as of the latest practicable date.DOCUMENTS INCORPORATED BY REFERENCEPortions of the Companys Proxy

14、 Statement for its 2021 Annual Meeting of Shareholders(the 2021 Proxy Statement)are incorporated by reference intoPart III2TABLE OF CONTENTS PagePART I Item 1.Business.6Item 1ARisk Factors.26Item 1BUnresolved Staff Comments.38Item 2.Properties.38Item 3.Legal Proceedings.38Item 4.Mine Safety Disclosu

15、res.39 PART II Item 5.Market for Registrants Common Equity,Related Stockholder Matters and Issuer Purchases of Equity Securities.39Item 6Selected Financial Data.40Item 7.Managements Discussion and Analysis of Financial Condition and Results of Operations.40Item 7AQuantitative and Qualitative Disclos

16、ures About Market Risk.53Item 8.Financial Statements and Supplementary Data.53Item 9.Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.53Item 9A.Controls and Procedures.54Item 9B.Other Information.54 PART III Item 10.Directors,Executive Officers,and Corporate Gover

17、nance.54Item 11.Executive Compensation.54Item 12.Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.54 Item 13.Certain Relationships and Related Transactions,and Director Independence.55Item 14Principal Accounting Fees and Services55 PART IV Item 15.Exhibi

18、ts,Financial Statement Schedules55Item 16Form 10-K Summary Page57Financial StatementsF-1-F-35Terminology and referencesIn this Annual Report on Form 10-K,the words Company,IntelGenx,we,us,and our,refer collectively to IntelGenx Technologies Corp.andIntelGenx Corp.,our wholly-owned Canadian subsidiar

19、y.In this Form 10-K,unless otherwise specified,all monetary amounts are in United States dollars,all references to$,U.S.$,U.S.dollars and dollarsmean U.S.dollars and all references to C$,Canadian dollars and CA$mean Canadian dollars.To the extent that such monetary amounts arederived from our consol

20、idated financial statements included elsewhere in this Form 10-K,they have been translated into U.S.dollars in accordance withour accounting policies as described therein.Unless otherwise indicated,other Canadian dollar monetary amounts have been translated into UnitedStates dollars at the average a

21、nnual exchange rate for 2020 as reported by the Bank of Canada,being U.S.$1.00=CA$1.3412.3PART ICautionary Statement Concerning Forward-Looking StatementsCertain statements included or incorporated by reference in this report constitute forward-looking statements within the meaning of applicable sec

22、uritieslaws.All statements contained in this report that are not clearly historical in nature are forward-looking,and the words anticipate,believe,continue,expect,estimate,intend,may,plan,will,shall and other similar expressions are generally intended to identify forward-looking statementswithin the

23、 meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.All forward-looking statementsare based on our beliefs and assumptions based on information available at the time the assumption was made.These forward-looking statements arenot based on hist

24、orical facts but on managements expectations regarding future growth,results of operations,performance,future capital and otherexpenditures(including the amount,nature and sources of funding thereof),competitive advantages,business prospects and opportunities,exchangelistings,and the pending transac

25、tion with ATAI Life Sciences AG(atai).Forward-looking statements involve significant known and unknown risks,uncertainties,assumptions and other factors that may cause our actual results,levels of activity,performance or achievements to differ materially fromthose implied by forward-looking statemen

26、ts.These factors should be considered carefully and prospective investors should not place undue reliance onthe forward-looking statements.Although the forward-looking statements contained in this report or incorporated by reference herein are based uponwhat management believes to be reasonable assu

27、mptions,there is no assurance that actual results will be consistent with these forward-lookingstatements.These forward-looking statements are made as of the date of this report or as of the date specified in the documents incorporated byreference herein,as the case may be.We undertake no obligation

28、 to update any forward-looking statements to reflect events or circumstancesafter the date on which such statements were made or to reflect the occurrence of unanticipated events,except as may be required byapplicable securities laws.Forward-looking statements are subject to a variety of known and u

29、nknown risks,uncertainties and other factors which could cause actual events orresults to differ from those expressed or implied by the forward-looking statements,including,without limitation:risks related to our ability to continue as a going concern;risks related to our history of losses;risks rel

30、ated to the potential need for additional capital;risks related to the incurrence of unforeseen costs;risks related to our dependence on business partners for clinical trials,regulatory approvals and the marketing and selling of our products;the competition in our industry;the size and experience of

31、 our competitors;the laws,regulations and guidelines applicable to cannabinoid-based products;risks related to our dependence on suppliers;risks related to the manufacturing of our VersaFilm products;risks related to regulatory approval and regulatory review of our products;our ability to expand or

32、enhance our product offerings;the markets reception of our products that incorporate drug delivery technologies;risks related to environmental regulations;the impact of COVID-19;risks related to the Investment(as defined below);the risk the Investment is terminated;the restrictions on our business a

33、ctivities contained in the Securities Purchase Agreement(as defined below);that our existing shareholders will have reduced ownership and voting interest after the closing of the Investment;the influence atai may have on our business;the risk that the Strategic Development Agreement(as defined below

34、)may not result in commercially viable products;risks related to default on our loan agreements;risks related to the developments of compounds that have psychedelic,entactogenic and/or oneirophrenic properties;risks related to public controversy with respect to compounds that may contain controlled

35、substances;our ability to adequately protect our intellectual property;the risk we infringe on the intellectual property rights of third parties;the risk that certain of our products may be subject to litigation;the risk of litigation in the ordinary course of business;risks related to cyber securit

36、y and the protection of our information systems;risks related to the high risk nature of our Common Stock;4our failure to achieve and maintain profitability;actual or anticipated variations in our quarterly results of operations;the application of penny stock rules to our Common Stock and its impact

37、 on trading and liquidity;the lack of public market for certain of our outstanding securities;the risk of dilution upon the conversion or exercise of outstanding securities;risks related to events of default with respect to our Debentures(as defined below)and Notes(as defined below);risks related to

38、 foreign currency fluctuations;the impact of securities analyst downgrades of our Common stock;andrisks associated with the prior activities of the public company we merged with.The factors set forth in Item 1A.,Risk Factors,as well as any cautionary language in this report,provide examples of risks

39、,uncertainties and events thatmay cause our actual results to differ materially from the expectations we describe in our forward-looking statements.Before you invest in the commonstock of the Company(the Common Stock),you should be aware that the occurrence of the events described as risk factors an

40、d elsewhere in thisreport could have a material adverse effect on our business,operating results and financial condition.In addition,there is an ongoing uncertainty aboutthe spread of the COVID-19 virus and the impact it will have on our operations,the demand for its products,global supply chains an

41、d economic activity ingeneral.5ITEM 1.BUSINESS.Corporate HistoryOur predecessor company,Big Flash Corp.,was incorporated in Delaware on July 27,1999.On April 28,2006,Big Flash,through its Canadian holdingcorporation,completed the acquisition of IntelGenx Corp.,a Canadian company incorporated on June

42、 15,2003.The Company did not have anyoperations prior to the acquisition of IntelGenx Corp.In connection with the acquisition,we changed our name from Big Flash Corp.to IntelGenxTechnologies Corp.IntelGenx Corp.has continued operations as our operating subsidiary.OverviewWe are a drug delivery compa

43、ny established in 2003 and headquartered in Montreal,Quebec,Canada.Our focus is on the development andmanufacturing of novel oral thin film products for the pharmaceutical market.More recently,we have made the strategic decision to enter the Canadiancannabis market with a non-prescription cannabis i

44、nfused oral film expected to be launched in early 2021 and in 2020 we made the decision to enter thepsychedelic market.In addition,we are offering partners a comprehensive portfolio of pharmaceutical services,including pharmaceutical research anddevelopment(R&D),clinical monitoring,regulatory suppor

45、t,tech transfer,manufacturing scale-up and commercial manufacturing.Our business strategy is to leverage our proprietary drug delivery technologies and develop pharmaceutical products with tangible benefits forpatients and,once the viability of a product has been demonstrated,license the commercial

46、rights to our partners in the pharmaceutical industry.Incertain cases,we rely upon partners in the pharmaceutical industry to fund the development of licensed products,complete the regulatory approvalprocess with the FDA or other regulatory agencies for the licensed products and assume responsibilit

47、y for marketing and distributing such products.In addition,we may choose to pursue the development of certain products until the project reaches the marketing and distribution stage.We willassess the potential for successful development of a product and associated costs,and then determine at which s

48、tage it is most prudent to seek apartner,balancing such costs against the potential for additional returns earned by collaborating later in the development process.Managing our project pipeline is a key Company success factor.We have undertaken a strategy under which we will work with pharmaceutical

49、companies in order to apply our oral film technology to pharmaceutical products for which patent protection is nearing expiration,a strategy which is oftenreferred to as lifecycle management.Under 505(b)(2)of the Food,Drug,and Cosmetics Act(the FDCA),the FDA may grant market exclusivity for aterm of

50、 up to three years following approval of a listed drug that contains previously approved active ingredients but is approved in a new dosage,dosageform,route of administration or a combination.The 505(b)(2)pathway is also the regulatory approach to be followed if an applicant intends to file an appli

51、cation for a product containing a drugthat is already approved by the FDA for a certain indication and for which the applicant is seeking approval for a new indication or for a new use,theapproval of which is required to be supported by new clinical trials,other than bioavailability studies.We have

52、implemented a strategy under which weactively look for such so-called repurposing opportunities and determine whether our proprietary VersaFilm technology adds value to the product.Wecurrently have two such drug repurposing projects in our development pipeline.We continue to develop the existing pro

53、ducts in our pipeline and may also perform research and development on other potential products asopportunities arise.We have established a state-of-the-art manufacturing facility with the intent to manufacture all of our VersaFilm products in-house as webelieve that this:represents a profitable bus

54、iness opportunity;will reduce our dependency upon third-party contract manufacturers,thereby protecting our manufacturing process know-how and intellectualproperty;andallows us to offer our clients and development partners a full service from product conception through to supply of the finished prod

55、uct.Our website address is .6Technology PlatformsOur main product development efforts are based upon three delivery platform technologies:(1)VersaFilm,an oral film technology,(2)AdVersa,amucoadhesive tablet technology and(3)the VetaFilmTM technology platform for veterinary applications.VersaFilm is

56、a drug delivery platform technology that enables the development of oral thin films,improving product performance through:rapid disintegration without the need for water;quicker buccal or sublingual absorption;potential for faster onset of action and increased bioavailability;potential for reduced a

57、dverse effects by bypassing first-pass metabolism;easy administration for patients who have problems swallowing tablets or capsules;pediatric and geriatric patients as well as patients who fearchoking and/or are suffering from nausea(e.g.,nausea resulting from chemotherapy,radiotherapy or any surgic

58、al treatment);pleasant taste;andsmall and thin size,making it convenient for consumers.Our VersaFilm technology consists of a thin(25-35 micron)polymeric film comprised of United States Pharmacopeia components that are approved bythe FDA for use in food,pharmaceutical,and cosmetic products.Derived f

59、rom the edible film technology used for breath strips and initially developed forthe instant delivery of savory flavors to food substrates,the VersaFilm technology is designed to provide a rapid response compared to existingconventional tablets.Our VersaFilm technology is intended for indications re

60、quiring rapid onset of action,such as migraine,opioid dependence,chronicpain,motion sickness,erectile dysfunction,and nausea.Our AdVersa platform technology allows for the development of oral controlled-release products.It is designed to adhere to the oral mucosa andrelease the drug to the site of a

61、pplication at a controlled rate.The AdVersa platform provides the following advantages relative to competingtechnologies:(i)it avoids the first pass effect,whereby the liver metabolizes the active ingredient and greatly reduces the level of drug reaching thesystemic circulation,(ii)it leads to a hig

62、her absorption rate in the oral cavity as compared to the conventional oral route,and(iii)it achieves a rapid onsetof action for the drug.Our AdVersa technology is versatile in order to permit the site of application,residence time,and rate of release of the drug to bemodulated to achieve the desire

63、d results.Our VetaFilm platform technology is designed for the application in companion animals.Dose acceptance and compliance are often a challenge for thecare giver which can be overcome with our newly designed VetaFilm platform.VetaFilm is specifically formulated with flavors that are appealing t

64、opets and to achieve rapid adhesion to the oral mucosa of the animal to achieve compliance.Our Product PortfolioOur product portfolio includes a blend of generic and branded products based on our proprietary delivery technology(generic products areessentially copies of products that have already rec

65、eived FDA approval).Of the eleven projects currently in our product portfolio,ten use ourVersaFilm technology and one uses our VetaFilmTM technology.Our most advanced projects:INT0008/2008:We developed a Rizatriptan oral film product based on our VersaFilm technology.In March 2013 we submitted a 505

66、(b)(2)New Drug Application(NDA)to the FDA for our novel oral thin-film formulation of Rizatriptan,which demonstrated to be bioequivalent to the active drugin Maxalt-MLT orally disintegrating tablets.Maxalt-MLT is a leading branded anti-migraine product marketed by Merck&Co.The thin-film formulationo

67、f Rizatriptan was originally developed under a co-development and commercialization agreement with RedHill Biopharma Ltd.(RedHill)which wasterminated December 5,2017,following which Redhill transferred all rights and obligations to us.In February 2014 we received a Complete Response Letter(CRL)from

68、the FDA,noting issues the Company needed to address beforeapproval.These issues have all been addressed and the Company is preparing its response to the CRL.On December 12,2018,we announced the execution of a definitive licensing,development and supply agreement with Gensco Pharma,aspecialty pharmac

69、eutical company focusing on research,development and marketing of prescription products,for the exclusive right to commercializeRIZAPORT in the United States.In return,we are entitled to receive royalty payments based on the net profits of RIZAPORT.We are also eligible toreceive milestone payments u

70、pon FDA approval and product launch.This agreement also grants Gensco Pharma a right of first refusal for theexclusive rights to develop,market,sell,distribute and fully commercialize products as a partner for the Peoples Republic of China.7On January 30,2019,we announced that the FDA had performed

71、a Pre-Approval Inspection(PAI)of our manufacturing facility in Montreal,relating to our NDA for RIZAPORT.At the conclusion of the PAI on January 25,the FDA issued a Form 483 with five inspectional observations thatneeded attention before final approval.More recently,on March 27,2020,we received an a

72、dditional CRL from the FDA.The Agency requested additional information,but no newbioequivalence study.We have addressed the issues raised in the CLR and are currently preparing the CLR response.On November 9,2015,BfArM granted marketing authorization of RIZAPORT 5mg and 10mg for the treatment of acu

73、te migraines.ThisGerman national approval was granted under the DCP,in which Germany served as the Reference Member State.This authorization was the firstnational marketing approval of RIZAPORT.Additionally,in April 2017,RIZAPORT received national marketing approval in Luxembourg,whichcompleted the

74、approval process under the DCP.On February 18,2016,the USPTO granted a patent protecting Rizaport.This patent protects the composition of Rizaport and will be listed inthe Orange Book(a list of approved drugs upon FDA approval of the product.This patent application,entitled Instantly Wettable Oral F

75、ilm Dosage FormWithout Surfactant or Polyalcohol covers rapidly disintegrating film oral dosage forms and is valid until 2034.On July 5,2016,we announced the signing of a definitive agreement with Grupo Juste S.A.Q.F.(now Exeltis Healthcare,S.L.(Exeltis)for thecommercialization of RIZAPORT for the t

76、reatment of acute migraines in Spain.Exeltis is a prominent private Spanish company with over 90 years ofexperience in the research,development and commercialization of proprietary pharmaceutical products,including migraine and other central nervoussystem drugs,in Europe,Latin America and other terr

77、itories.Under the definitive agreement,Exeltis obtained exclusive rights to register,promote and distribute RIZAPORT in Spain.In exchange,we andRedhill received upfront payments and are entitled to milestone payments,together with a share of the net sales of RIZAPORT in Spain.The initialterm of this

78、 agreement is ten years from the date of first commercial sale of the product and shall automatically renew for one additional two-year term.More recently,on August 27,2020,we announced that we had granted Exeltis an exclusive license to manufacture and commercialize RIZAPORT inthe European Union(EU

79、).Exeltis will pay us prespecified royalties on net RIZAPORT sales in the EU.In addition,we have a right of first refusal tomanufacture this product for the EU market.Effective September 9,2020,we signed a technology transfer agreement with LTS Lohmann TherapySystems for future manufacture and suppl

80、y of the product for Spain.National marketing authorization from the Spanish Agency of Medicines and Medical Devices was received for RIZAPORT(10mg)in Spain onOctober 31,2018.On December 14,2016,we announced the signing of an exclusive license agreement with Pharmatronic Co.for the commercialization

81、 ofRIZAPORT in the Republic of Korea(South Korea).Under the terms of such agreement,we granted Pharmatronic Co.the exclusive rights to registerand commercialize RIZAPORT in South Korea.IntelGenx have received an upfront payment and will be eligible to receive additional milestonepayments upon achiev

82、ement of certain predefined regulatory and commercial targets,as well as tiered royalties.The initial term of the definitiveagreement with Pharmatronic Co.is for ten years from the date of first commercial sale and shall automatically renew for an additional two-year term.INT0046/2018:Our first cann

83、abis project based on our VersaFilm technology is currently in preparation for launch.We started this project inanticipation of the amended cannabis regulations that would allow adult-use consumers to purchase edible products in Canada.On November 7,2018 we announced the execution of a definitive li

84、cense,development and supply agreement with Tilray,Inc.(Tilray),a globalleader in cannabis production and distribution.Under such agreement,the two companies will co-develop and commercialize oral film products infusedwith adult-used medical cannabis(cannabis infused VersaFilm).8Under the agreement

85、with Tilray,us and Tilray will fund 20%and 80%,respectively,of the costs associated with the development of thecannabis infused Versafilm products.We will have the exclusive right to manufacture and supply the co-developed products to Tilray,and will alsoreceive a fixed single-digit royalty on net p

86、roduct sales.Tilray will have the exclusive,worldwide marketing and distribution rights for the co-developedproducts.In connection with the Tilray agreement,we and Tilray also executed a subscription agreement under which Tilray made a strategic investment inIntelGenx through a non-brokered private

87、placement(the Tilray Private Placement).As a result,we issued Tilray 1,428,571 shares of Common Stockat a subscription price of US$0.70 per share of Common Stock for gross proceeds of US$1,000,000.We used the proceeds of the Tilray PrivatePlacement for cannabis infused VersaFilm product development

88、under the agreement with Tilray.In May 2019,we received the first extract from Tilray in sufficient quantities to commence batch production of cannabis-infused VersaFilmfollowed by an announcement in October that the formulation had progressed to the scale-up manufacturing stage.The manufacturing sc

89、ale-up workwas completed successfully in January 2020.In the spring of 2019,we applied for a micro-processing license under the Canadian Cannabis Act(the Cannabis Act),which would allow us toprocess 600kg of cannabis per year,perform analytical testing and begin sales and research on cannabis.On Jun

90、e 5,2020,we received the cannabismicro-processing license from Health Canada for our Montreal,Quebec facility,in accordance with the Cannabis Act and the regulations thereunder.On July 20,2020,we announced that the exclusivity terms of the November 2018 license,development and supply agreement with

91、Tilray hadbeen amended to allow for the Companys co-development and commercialization of cannabidiol(CBD)products with additional partners.Inconsideration,we shall pay a royalty to Tilray on all CBD products sold under this amendment.All other terms of such agreement,including thosepertaining to Til

92、rays exclusive,worldwide marketing and distribution rights for non-CBD cannabis infused VersaFilm,remained unchanged.On October 29,2020,we signed a letter of intent with Heritage Cannabis Holding Corp.(Heritage Cannabis)for long term cannabis filmstripsupply agreement.Shortly after on January 7,2021

93、,we announced the execution of a definitive supply agreement with Heritage Cannabis for themanufacturing and supply of filmstrip products containing 10 mg of CBD using our VersaFilm technology for the Canadian and Australian markets.Inaddition,we received our first purchase order from Heritage for 5

94、0,000 CBD Filmstrips.The first shipment of product to Heritage is expected in thesecond quarter of 2021.INT0007/2006:We are developing an oral film product based on our VersaFilm technology containing the active ingredient tadalafil.Thisproduct is intended for the treatment of erectile dysfunction(E

95、D).The results of a phase I pilot study conducted in the second quarter of 2015 confirmedthat the product is bioequivalent with the brand product,Cialis.On November 21,2016,we announced the signing of a binding term sheet for a license to Eli Lilly and Companys(Eli Lilly)tadalafil dosingpatent,Unite

96、d States Patent No.6,943,166(the 166 dosing patent).Any exclusivity associated with the tadalafil compound patent is not affected bythis agreement.Subject to FDA approval,this license allows us to commercialize a tadalafil ED VersaFilm product in the United States before theexpiration of the 166 dos

97、ing patent.This license terminates all of our current tadalafil-related litigation activities.On March 28,2017,we announced thatEli Lilly granted us an exclusive license for tadalafil film product under the 166 dosing patent.On May 8,2019,we executed a worldwide collaboration agreement for tadalafil

98、 with Aquestive Therapeutics,Inc.(Aquestive).Under the termsof this agreement,we and Aquestive will each grant to the other exclusive worldwide licenses to their respective intellectual property relating to tadalafiloral film formulation and manufacturing.The companies will jointly undertake further

99、 co-development and commercialization of tadalafil oral filmproducts,and will equally share(50/50)net profits from worldwide product sales.Aquestive previously submitted an NDA for its tadalafil oral film for thetreatment of ED to the FDA.In November 2018,Aquestive received a CRL from the FDA reques

100、ting additional safety data from healthy volunteers.Bothcompanies are currently waiting for FDAs comments on resubmission and approval and are in active discussions with several companies tocommercialize the product.INT0039/2013:This product is based on one of our proprietary technologies and was be

101、ing developed under another development andcommercialization agreement with Par Pharmaceuticals(Par).On September 18,2015,Endo International plc(Endo)acquired Par.As a result of thisacquisition,Par had a conflict and was unable to remain as the partner for this product.Therefore,the product was retu

102、rned to us with full rights and norequirement for any compensation for work paid by Par.9On September 12,2016,we entered into a licensing,development and supply agreement with Chemo Group(Chemo)granting Chemo theexclusive license to commercialize two generic products for the United States market and

103、 one product on a worldwide basis.Under the terms of thisagreement,Chemo obtained certain exclusive rights to market and sell our products in exchange for upfront and milestone payments,together with ashare of the profits of commercialization.Chemo also has a right of first negotiation to obtain the

104、 exclusive commercialization rights for two of theproducts to include any country outside the United States.On October 4,2018,we submitted an Abbreviated New Drug Application(ANDA)to the FDA for a generic buccal film product for our partner,Insud Pharma(formerly Chemo Group).On January 30,2019,the F

105、DA confirmed the acceptance for review of this ANDA with a GDUFA date ofOctober 18,2019.In March 2019,the FDA conducted a pre-approval inspection for the buccal film that resulted in the FDA issuing us a Form 483,a report from aninvestigator noting conditions that in their judgment may constitute vi

106、olations of the FDCA and related acts.Further,in October 2019,we received a CRLin which the FDA declined to approve our product.A CRL does not necessarily indicate that a drug or biologic is not safe or effective.Rather,the FDAissues a CRL when it has reviewed the submitted data and has outstanding

107、questions.A CRL allows the FDA to provide an applicant with a systematiclist of deficiencies detected within the submission package sent to the agency that stop short of requiring an entire resubmission.We are currentlypreparing a response to both the 483 and the CRL.INT0027/2011:We developed this o

108、ral film product based on our VersaFilm technology under a co-development and commercializationagreement with Par(now an operating company of Endo).The product is a generic formulation of a commercial buprenorphine and naloxone-containingsublingual film for the treatment of opioid dependence.With Pa

109、r,we developed a bioequivalent film formulation,scaled-up to a commercialmanufacturing process and manufactured and tested pivotal batches during a subsequent pivotal clinical study.Par filed an ANDA with the FDA in July2013.In August 2013,we were notified that,in response to the filing of the ANDA,

110、we were named as a co-defendant in a lawsuit under Paragraph IVof the Hatch-Waxman Act filed by Reckitt Benckiser Pharmaceuticals(Reckitt)and Monosol RX(Monosol)in the United States District Court for theDistrict of Delaware(the Delaware Court)alleging infringement of United States Patent Nos.8,475,

111、832,8,603,514 and 8,017,150,each of which relateto Suboxone.We believe the ANDA product does not infringe those or any other patents.Under the terms of the co-development andcommercialization agreement,Par was financially responsible for the costs of the defense.In June 2016,the Delaware Court ruled

112、 that our product is notinfringing on two out of the three patents.Subsequently,both parties filed appeals.In December 2014,Reckitt and Monosol filed another lawsuit for patent infringement in the Delaware Court relating to the Suboxone ANDAproduct.We were named as a co-defendant in this action alle

113、ging patent infringement of United States Patent Nos.8,900,497(the 497 patent)and8,906,277(the 277 patent),each of which related to a process for making a uniform oral film(the process patents).The trial on the process patentswas held in November 2016.On May 14,2018,us,Par,Indivior,Inc.,Indivior UK

114、Limited,and Aquestive(previously Monosol RX)settled all patent litigation related toSuboxone film.The settlement agreement permits Par to begin selling a generic version of Suboxone film on January 1,2023 or earlier under certaincircumstances.Our earlier stage projects:INT0043/2015:We developed an o

115、ral film containing montelukast as the active ingredient based on our proprietary VersaFilm edible filmtechnology,which is in the early clinical trial phase.We are collaborating with Dr.Ludwig Aigner,a member of our Scientific Advisory Board and head of the Institute of Molecular RegenerativeMedicin

116、e at the Paracelsus Medical University in Salzburg,Austria.Dr.Aigner has made major contributions in the field of brain and spinal cordregeneration over the last 25 years.He was the first to develop tools to visualize neurogenesis in living animals and identified crucial signalingmechanisms that are

117、 involved in limiting brain regeneration.One of these mechanisms,leukotriene signaling,is related to asthma.In consequence,Dr.Aigner and his team recently demonstrated that the anti-asthmatic drug montelukast structurally and functionally rejuvenates the aged brain.His mainaim is to develop molecula

118、r and cellular therapies for patients with neurodegenerative diseases and for the aged population.On July 13,2016,we announced the successful completion of a pilot clinical study for our montelukast VersaFilm that demonstrated asignificantly improved pharmacokinetic profile compared to the reference

119、 product.The study data confirmed that buccal absorption of the drug from themontelukast film product resulted in a significantly improved bioavailability of the drug compared to the commercial tablet.In addition,the study dataconfirmed that montelukast crosses the blood brain barrier when administe

120、red using our Versafilm delivery technology.10In 2017 we announced receiving a no objection letter from Health Canada regarding a Phase IIa proof-of-concept study.The objectives of this26-week,randomized,double-blind and placebo-controlled Phase IIa proof of concept study to be conducted at eight cl

121、inical study sites across Canadawill be to evaluate the safety,feasibility,tolerability and efficacy of montelukast buccal film in patients with mild to moderate Alzheimers Disease(AD).The trial design includes testing of up to 70 patients.Based on the outcome of this first efficacy trial in humans,

122、we will be actively seeking a partnership or alliance opportunity to further advancedevelopmental work and commercialization of this product.On September 25,2018,we announced the beginning of patient recruitment for the proposed AD study.In October 2019,an independent DataSafety Monitoring Board(DSM

123、B)completed its first interim analysis of the ongoing montelukast AD Phase IIa(BUENA)clinical trial in patients withmild to moderate AD.The DSMB reviewed compiled safety data from 25 subjects enrolled in the BUENA trial,13 of whom have completed 26 weeks ofdaily treatment.The DSMB did not raise any

124、concerns regarding safety and recommended that the trial continue.Based on additional efficacy testing of montelukast in an AD mouse model,conducted in collaboration with Prof.Dr.Ludwig Aigners group atthe Paracelsus Medical University in Salzburg suggesting that montelukast,when given at higher dos

125、es,significantly improves cognition in patientssuffering from memory impairment and dementia,a revision of the dosage regiment was requested to Health Canada through the filing of a clinical trialapplication.Health Canada issued a non-objection letter in January 2020.The study is presently on hold d

126、ue to the COVID-19 pandemic.INT0040/2014:An oral film product based on our proprietary VersaFilm technology.On December 27,2016,we entered into a co-development and commercialization agreement with Endo for this product in the United States market.Under such agreement,Endo obtained certainexclusive

127、rights to market and sell our product in the United States.We received an upfront payment and will receive future milestone payments.Endoand us will share the expected profits of commercialization.INT0036/2013:This oral film product is based on our proprietary oral film technology VersaFilm.Loxapine

128、 is indicated for the treatment ofanxiety and aggression in patients suffering from schizophrenia or bipolar 1 disorder.Using our VersaFilm technology allows an improved product tooffer patients significant therapeutic benefits compared to existing medications.We expect to effectively treat acute ag

129、itation associated withschizophrenia or bipolar 1 disorder in non-institutionalized patients while reducing the risk of pulmonary problems.Our product is needed,as it couldsubstantially reduce the potential risks of violence and injury to patients and others by preventing or reducing the duration an

130、d severity of an episode ofacute agitation.Our first clinical study on this product,completed in Q4 2014,suggested improved bioavailability compared to the currently approvedtablet.In late 2015.we completed a second pilot clinical study which demonstrated that buccal absorption of the drug from the

131、Loxapine oral film resultsin a significantly higher bioavailability of the drug compared to oral tablets.We were working to optimize the film to further improve the time to reach peakplasma concentrations,however,due to the prioritization of our project line,we directed resources to other projects,l

132、eading to a temporary hold of theoptimization work during 2019.This project is currently on hold due to the difficulty of sourcing a necessary active pharmaceutical ingredient.Other projects:INT0048/2020 VetaFilm:On January 9,2020 we entered the animal health market by signing a feasibility agreemen

133、t for its VetaFilmplatform.We have performed all of our obligations under such agreement and the successfully developed high loading VetaFilm which was sent forevaluation by our partner.Based on a successful feasibility study,we are in discussions to further develop the product with the partner.On F

134、ebruary 8,2021,we announced that we have filed a new provisional patent application at the United States Patent and Trademark Office(USPTO)entitled High Loading Oral Film Formulation.The patent application covers the incorporation of high concentrations of active ingredients inproducts based on Inte

135、lGenxs VetaFilm proprietary veterinary oral film technology.This higher loading capability enables a formulation with a ratio ofactive-to-polymer of 1-to-1,thereby pushing the limit of the film capabilities and distinguishing it from known oral film technology.11INT0052/2020.On July 7,2020 we entere

136、d into a feasibility agreement with Cybin Corp.for a fast-acting,orally-dissolving psilocybin film.Weare currently developing a formulation intended for a clinical phase 1 study.INT0053/2020.On August 20,2020 we entered into a feasibility agreement with atai to develop pharmaceutical-grade polymeric

137、 film-basedpsychedelics.Some material was received and we are currently developing a formulation.However,in parallel,both companies are currently working onthe required import and export licenses to continue the R&D work.INT0010/2006:This product is based on our proprietary AdVersa technology and ha

138、s been transferred to Tetra BioPharma.We initially enteredinto an agreement with Cynapsus Therapeutics Inc.(formerly Cannasat Therapeutics Inc.,Cynapsus)for the development of a buccal muco-adhesivetablet product containing a cannabinoid-based drug for the treatment of neuropathic pain and nausea in

139、 cancer patients undergoing chemotherapy.In2009,we completed a clinical biostudy on this product.The study results indicated improved bioavailability and reduced first-pass metabolization of thedrug.In the fourth quarter of 2010,we acquired full control of,and interest in,this project from Cynapsus

140、going forward.We also obtained worldwiderights to United States Patent 7,592,328 and all corresponding foreign patents and patent applications to exclusively develop and further secureintellectual property protection for this project.On April 5,2017,we announced signing of a definitive agreement wit

141、h Tetra Bio-Pharma Inc.(Tetra)for the development andcommercialization of a drug product containing the cannabinoid Dronabinol(the Tetra Product)for the management of anorexia and cancerchemotherapy-related pain.Under the definitive agreement,Tetra has exclusive rights to sell the Tetra Product in N

142、orth America,with a right of first negotiation for territoriesoutside of the United States and Canada.Tetra made an upfront payment to the Issuer,in addition to fixed future milestone and royalty payments,basedon the completion of an efficacy study,approvals from the FDA and Health Canada and the co

143、mmercial launch of the Tetra Product.We are responsiblefor the research and development of the Tetra Product,including optimization of the prototype,scale-up activities and preparation of a phase II proof ofconcept clinical study.We are developing the Tetra Product as an oral mucoadhesive tablet bas

144、ed on our proprietary AdVersa controlled-releasetechnology.Tetra is responsible for funding the product development,and will own and control all regulatory approvals,including the related applicationsand any other marketing authorizations.Tetra will also be responsible for all aspects of commerciali

145、zing the Tetra Product.On October 21,2020,we entered into an amended and restated licensing agreement with Tetra Bio-Pharma under which Tetra is purchasing theworldwide Adversa technology rights as it relates to its PPP-002(Dronabinol)drug product candidate for three undisclosed milestone payments:4

146、5%tobe paid on November 15,2020;45%to be paid on March 1,2021,and a final payment of 10%upon successful technology transfer.In addition,Tetra willpay us a royalty on future net sales of Dronabinol mucoadhesive tablets.INT0004/2006:We developed a new,higher strength of the antidepressant Bupropion HC

147、l,the active ingredient in Wellbutrin XL,and,inNovember 2011,the FDA approved the drug for patients with Major Depressive Disorder.In February 2012,we entered into an agreement withEdgemont Pharmaceuticals LLC(Edgemont)for commercialization of this product in the United States.Under the terms of thi

148、s agreement,Edgemontobtained certain exclusive rights to market and sell the product in the United States.In exchange,we received a$1 million upfront payment,agreed tolaunch-related milestone payments totaling up to$4 million and additional milestones of up to a further$23.5 million upon achieving c

149、ertain sales andexclusivity targets,in addition to tiered double-digit royalties on the net sales of the product.The product was launched in the United States in October 2012 under the brand name Forfivo XL.As of December 31,2015,we had receivedan upfront payment of$1 million and a$1 million milesto

150、ne payment related to the launch.Edgemont reaching$7 million of cumulative net trade sales forthis product as of July 2015 over the preceding 12 months triggered a launch-related milestone payment of$3 million from Edgemont.In August 2013,we announced receipt of a Paragraph IV Certification Letter f

151、rom Wockhardt Bio AG,advising of the submission of an ANDA tothe FDA requesting authorization to manufacture and market generic versions of Forfivo XL 450 mg tablets in the United States.In November 2014 weannounced that the Paragraph IV litigation with Wockhardt had been settled and that,under the

152、terms of the settlement,Wockhardt has been granted theright,with effect from January 15,2018,to be the exclusive marketer and distributor of an authorized generic of Forfivo XL in the United States.In December 2014,Edgemont exercised its right to extend the license for the exclusive marketing of For

153、fivo XL 450 mg tablets.In exchange,we received milestone payments of$650,000 in December 2014 and$600,000 in February 2015.All other financial obligations contained in theEdgemont license agreement,specifically launch-related and sales milestones,together with the contractual royalty rates on net sa

154、les of the product,remained in effect.12On August 5,2016,we sold our United States royalty on future sales of Forfivo XL to SWK Holdings Corporation(SWK)for$6 Million(CA$8million).Under that agreement,we received$6 million from SKW for:(i)100%of any and all royalties(as defined in the Edgemont licen

155、se agreement)orsimilar royalty amounts received on or after April 1,2016;(ii)100%of the$2 million milestone payment due when Edgemont reached annual net sales of$15 million;and(iii)35%of all potential future milestone payments.Patent protection for Forfivo XL in the United States expires in 2027.In

156、the first quarter of 2017,we were informed that Edgemont had assigned its product business,including Forfivo XL,to Alvogen GroupHoldings 3 LLC.We retained all patent rights to Forfivo XL,which is sold on the US market.INT0037/2013:We discontinued this project due to discontinuation of the reference

157、product.The current status of each of our products as of the date of this Annual Report is summarized in the table below.ProductIndicationStatus of DevelopmentINT0008/2008MigrainePreparing CRL responseINT0046/2018Adult UsePreparing for commercial manufacturingINT0007/2006Erectile dysfunctionAwaiting

158、 FDAs comment for the response toAquestives CRLINT0039/2013UndisclosedUndisclosedINT0027/2011Opioid additionSettlement agreementINT0043/2015AlzheimerStudy on hold due to COVID-19INT0040/2014UndisclosedUndisclosedINT0010/2006Treatment of neuropathic pain and nausea incancer patients undergoing chemot

159、herapyTransferred to TetraBioINT0036/2013Schizophrenia or bipolar 1 disorderOn hold due to sourcing issuesINT0048/2020Animal HealthPreparing second phase of the project INT0052/2020UndisclosedFormulation development ongoingINT0053/2020UndisclosedFormulation development ongoingAwaiting import and exp

160、ort permitRecent DevelopmentsStrategic Development AgreementOn March 14,2021,IntelGenx Corp.entered into a strategic development agreement(the Strategic Development Agreement)with atai.Under theStrategic Development Agreement,atai and us will cooperate to conduct research and development projects in

161、 areas relating to the parties respectivetechnologies.A portion of the funds(20%)that we receive through atais equity investment under the Securities Purchase Agreement described belowwill be available to be credited against the costs to us of the research and development projects.So long as atai ma

162、intains certain levels of its initialequity ownership in us,atai will have exclusive commercialization rights in the field of compounds for the prevention or treatment of mental healthdiseases or disorders or compounds that have psychedelic,entactogenic and/or oneirophrenic properties,but excluding

163、certain specific compounds andveterinary applications.The commercialization of any technologies that result from the research and development projects under the strategic development agreement will besubject to agreements to be negotiated,as well as to specified pricing and royalty terms for manufac

164、turing conducted by us or third parties.13Securities Purchase AgreementOn March 14,2021,we also entered into a securities purchase agreement,as may be amended(the“Securities Purchase Agreement”)with atai.Underthe Securities Purchase Agreement,atai has agreed to purchase(A)an aggregate of 37,300,000

165、units of the Company(the“Initial Units”)at a price of$0.331 per Initial Unit,each Initial Unit to be issued being comprised of one share of Common Stock of the Company(an“Initial Share”)and 0.60 of awarrant(each whole warrant,an“Initial Warrant”)for an aggregate consideration of$12,346,300,and(B)a w

166、arrant(in a form to be agreed by the partiesreflecting the terms set out in the Securities Purchase Agreement)(the“Additional Units Warrant”)to acquire up to 130,000,000 additional units of theCompany(the“Additional Units”),each Additional Unit to be issued being comprised of one share of Common Sto

167、ck of the Company(an“AdditionalShare”)and 0.5 of one warrant(each such whole warrant,an“Additional Warrant”and collectively with the Initial Warrants,the“Warrants”),(the“Investment”)following receipt of approval of our shareholders(the“Shareholders”)at our Annual Meeting of the Shareholders(the“Meet

168、ing”).Paymentfor the Additional Units may be in cash or in certain circumstances in,atai equity.Each Initial Warrant will entitle atai to purchase one share of CommonStock at a price of$0.35 for a period of three years from closing of the initial investment.The Additional Units Warrant exercise pric

169、e for the Additional Units will be(i)until the date which is 12 months following the closing,$0.331(subject tocertain exceptions),and(ii)following the date which is 12 months following the closing,the lower of(A)a 20%premium to the market price on the date ofpurchase,and(B)$0.50 if purchased in the

170、second year following closing and$0.75 if purchased in third year following closing.Each Additional Warrantwill entitle atai,for a period of three years from the date of issuance,to purchase one Share at the lesser of either(i)a 20%premium to the price of thecorresponding Additional Share,or(ii)the

171、price per share under which shares of the Company are issued under convertible instruments that wereoutstanding on February 16,2021,the date on which the parties entered into a non-binding letter of intent to enter into a definitive Securities PurchaseAgreement(“Outstanding Convertibles”),provided t

172、hat atai may not exercise Additional Warrants to purchase more than the lesser of(x)44,000,000shares of Common Stock,and(y)the number of shares of Common Stock issued by the us under Outstanding Convertibles.Under the Securities Purchase Agreement,we also granted atai a pro-rata equity participation

173、 right for any issuances of new securities,subject to certainexceptions.Following the initial closing,atai will hold approximately 25%(approximately 35%on a partially diluted basis)of the issued and outstanding shares ofCommon Stock and therefore become a new Control Person of us as such term is def

174、ined under the policies of the TSX Venture Exchange(the TSX-V).Based on the number of issued and outstanding shares of Common Stock and outstanding convertible instruments on March 15,2021,assumingthe full exercise of Additional Units Warrant to acquire the Additional Units and exercise of the Warra

175、nts and Additional Warrants,atai would holdapproximately 60%(approximately 60%on a partially diluted basis)of the issued and outstanding shares of Common Stock.Under the Securities Purchase Agreement,we have agreed to use reasonable efforts to list the shares of Common Stock on the Toronto Stock Exc

176、hange(the“TSX”)with a target to achieve such listing shortly after the initial closing contemplated by the Securities Purchase Agreement and we intend topromptly submit a listing application to the TSX.There is no assurance that the TSX will approve the listing application and any listing of our sha

177、res ofCommon Stock on the TSX is subject to us meeting all of the listing requirements of and obtaining the approval of the TSX.The Additional Units Warrantis only exercisable if our shares of Common Stock are listed on the TSX.Purchaser Rights AgreementOn March 14,2021,we also entered into a purcha

178、ser rights agreement(the Purchaser Rights Agreement)with atai.Under the Purchaser RightsAgreement,atai will have the right to appoint nominees in the same proportion to the number of our board members as the shares of Common Stockthen held by atai,registration rights,and financial and other informat

179、ion rights.We will have the right to terminate the Purchaser Rights Agreement if atai ceases to own a certain amount of our equity.Term LoanOn March 9,2021 atai funded a secured loan in the amount of$2,000,000 bearing interest at 8%pursuant to a loan agreement entered into betweenIntelGenx Corp.and

180、atai(the Loan Agreement).The loan is repayable on the date that is 120 days following the date of the Meeting,but in any eventnot later than September 30,2021.The Securities Purchase Agreement provides that an amendment is to be entered into at the initial closing of the ataiinvestment under which t

181、he maturity date will be following the first closing of a subscription for Additional Units if the proceeds from such subscriptionamount to at least$3,000,000.The loan provides for the possibility of an additional advance to us of up to$500,000,subject to certain conditions.Theloan is guaranteed by

182、IntelGenx Technologies Corp.in a guarantee entered into by IntelGenx Technologies Corp.concurrently with the Loan Agreementand is secured by all of the present and future fixed assets of IntelGenx Corp.,excluding any intellectual property or technology controlled or owned byIntelGenx Corp.14IntelGen

183、x Corp.has applied approximately CA$800,000($628,000)from the loan to fully repay the outstanding amount on the Companys credit facilitieswith its Bank.We intend to use the balance of the loan for general working capital purposes.Growth StrategyOur primary growth strategy is based on three pillars:(

184、1)out licensing commercial rights of our existing pipeline products,(2)partnering on contractdevelopment and manufacturing projects leveraging our various technology platforms,and(3)expanding our current pipeline through:identifying lifecycle management opportunities for existing market leading phar

185、maceutical products,developing oral film products that provide tangible patient benefits,development of new drug delivery technologies,entering the veterinary market with VetaFilm,repurposing existing drugs for new indications,anddeveloping generic drugs where high technology barriers to entry exist

186、 in reproducing branded films.Contract Development and Manufacturing based on our various technology platformsWe have established a state-of-the-art manufacturing facility for the future manufacture of our VersaFilm and VetaFilm products.We believe that this(1)represents a profitable business opport

187、unity,(2)will reduce our dependency upon third-party contract manufacturers,thereby protecting ourmanufacturing process know-how and intellectual property,and(3)allows us to offer our development partners a full service from product conceptionthrough to supply of the finished product.With our curren

188、t manufacturing equipment,we are only able to manufacture products that do not contain flammable organic solvents.We initiated aproject to expand the existing manufacturing facility,the timing of which will be dictated in part by the completion of agreements with our commercialpartners.This expansio

189、n became necessary following requests by commercial partners to increase manufacturing capacity and provide solvent filmmanufacturing capabilities.The new facility should create a fivefold increase of our production capacity in addition to offering a one-stop shoppingopportunity to our partners and

190、provide better protection of our Intellectual Property.Lifecycle Management OpportunitiesWe are seeking to position our delivery technologies as an opportunity for lifecycle management of products for which patent protection of the activeingredient is nearing expiration.While the patent for the unde

191、rlying substance cannot be extended,patent protection can be obtained for a new andimproved formulation by filing an application with the FDA under Section 505(b)(2)of the United States Federal Food,Drug and Cosmetic Act.Suchapplications,known as a 505(b)(2)NDA,are permitted for new drug products th

192、at incorporate previously approved active ingredients,even if theproposed new drug incorporates an approved active ingredient in a novel formulation or for a new indication.A 505(b)(2)NDA may include informationregarding safety and efficacy of a proposed drug that comes from studies not conducted by

193、 or for the applicant.The first formulation for a respectiveactive ingredient filed with the FDA under a 505(b)(2)application may qualify for up to three years of market exclusivity upon approval.Based upon areview of past partnerships between third party drug delivery companies and pharmaceutical c

194、ompanies,management believes that drug deliverycompanies which possess innovative technologies to develop these special dosage formulations present an attractive opportunity to pharmaceuticalcompanies.Accordingly,we believe 505(b)(2)products represent a viable business opportunity for us.Product Opp

195、ortunities that provide Tangible Patient BenefitsOur focus will be on developing oral film products leveraging our VersaFilm technology that provide tangible patient benefits versus existing drugdelivery forms.Patients with difficulties swallowing medication,pediatrics or geriatrics may benefit from

196、 oral films due to the ease of use.Similarly,we areworking on oral films to improve bio-availability and/or response time versus existing drugs and thereby reducing side effects.15Development of New Drug Delivery TechnologiesThe rapidly disintegrating film technology contained in our VersaFilm,and o

197、ur AdVersa mucosal adhesive tablet,are two examples of our efforts todevelop alternate technology platforms.As we work with various partners on different products,we seek opportunities to develop new proprietarytechnologies.Repurposing Existing DrugsWe are working on the repurposing of already appro

198、ved drugs for new indications using our VersaFilm film technology.This program represents aviable growth strategy for us as it will allow for reduced development costs,improved success rates and shorter approval times.We believe that throughour repurposing program we will be able minimize the risk o

199、f developmental failure and create value for us and potential partners.Generic Drugs with High Barriers to EntryWe plan to pursue the development of generic drugs that have certain barriers to entry,e.g.,where product development and manufacturing is complexand can limit the number of potential entr

200、ants into the generic market.We plan to pursue such projects only if the number of potential competitors isdeemed relatively insignificant.CompetitionThe pharmaceutical industry is highly competitive and is subject to the rapid emergence of new technologies,governmental regulations,healthcarelegisla

201、tion,availability of financing,patent litigation and other factors.Many of our competitors,including Aquestive Therapeutics Inc.(formerly MonosolRx),Tesa-Labtec GmbH,BioDelivery Sciences International,Inc.and LTS Lohmann Therapy Systems Corp.,have longer operating histories and greaterfinancial,tech

202、nical,marketing,legal and other resources than we have.In addition,many of our competitors have significantly greater experience than wehave in conducting clinical trials of pharmaceutical products,obtaining FDA and other regulatory approvals of products,and marketing and sellingproducts that have b

203、een approved.We expect that we will be subject to competition from numerous other companies that currently operate or areplanning to enter the markets in which we compete.The key factors affecting the development and commercialization of our drug delivery products are likely to include,among other f

204、actors:the regulatory requirements;the safety and efficacy of our products;the relative speed with which we can develop products;generic competition for any product that we develop;our ability to defend our existing intellectual property and to broaden our intellectual property and technology base;o

205、ur ability to differentiate our products;our ability to develop products that can be manufactured on a cost effective basis;our ability to manufacture our products in compliance with current Good Manufacturing Practices(cGMP)and any other regulatory requirements;andour ability to obtain financing.In

206、 order to establish ourselves as a viable industry partner,we plan to continue to invest in our research and development activities and in ourmanufacturing technology expertise,in order to further strengthen our technology base and to develop the ability to manufacture our VersaFilmproducts ourselve

207、s,and our VersaTab and AdVersa products through our manufacturing partners,at competitive costs.16Our Competitive StrengthsWe believe that our key competitive strengths include:our comprehensive service portfolio;our diversified pipeline;our ability to swiftly develop products through to regulatory

208、approval;the versatility of our drug delivery technologies,and our highly qualified,dedicated professional team.Dependence on Major CustomersWe currently rely on a few major customers for our end products.We also currently depend upon a limited number of partners to develop ourproducts,to provide fu

209、nding for the development of our products,to assist in obtaining regulatory approvals that are required in order to commercializethese products,and to market and sell our products.Intellectual Property and Patent ProtectionWe protect our intellectual property and technology by using the following me

210、thods:(i)applying for patent protection in the United States and inthe appropriate foreign markets,(ii)non-disclosure agreements,license agreements and appropriate contractual restrictions and controls on thedistribution of information,and(iii)trade secrets,common law trademark rights and trademark

211、registrations.We plan to file core technology patentscovering the use of our platform technologies in any pharmaceutical products.We have obtained 20 patents and have an additional 30 published pending patent applications,as described below.The patents expire 20 yearsafter submission of the initial

212、application.In the United States,the term of a patent sometimes extends over the 20-year period.The initial term of 20years is extended by a period(the patent term adjustment)determined by the USPTO according to delays in the prosecution of the patent applicationthat are not applicant delays.Our pat

213、ent portfolio is dynamic in nature and constantly under review to assess the business priorities,as such any of the currently pendingapplication and issued patent may be abandoned if the expense of pursuing prosecution or maintaining the patent or application active is no longerwarranted by our busi

214、ness targets.Patent No.TitleSubjectDate issued/Expiration US 6,660,292 Rapidly disintegrating film for precooked foods Composition and manufacturing offlavored films for releasing flavors to precooked foodsubstrates Issued December 9,2003 Expires June 19,2021 US 7,132,113Flavored filmComposition and

215、 manufacturingmethod of multi-layered films Issued November 7,2006 Expires April 16,2022 US 7,674,479 Sustained-release bupropion and bupropion/mecamylamine tablets Formulation and method of makingtablets containing bupropion andmecamylamine Issued March 9,2010 Expires July 25,2027 US 8,691,272Multi

216、layer tabletFormulation of multilayered tabletsIssued April 8,2014 Expires January 28,2033 US 8,703,191Controlled release pharmaceutical tablets Formulation of tablets containingbupropion and mecamylamine Issued April 22,2014 Expires January 10,2032 US 8,735,374Oral mucoadhesive dosage formDirect co

217、mpression formulation forbuccal and sublingual dosage forms Issued May 27,2014 Expires April 15,2032 US 9,301,948Instantly wettable oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive pharmaceutical ingredientsIssued April 5,2016 Expires July 30,2033 US

218、9,668,970 Film Dosage Form with ExtendedReleaseMucoadhesive Particles Film containing mucoadhesive particle Issued June 6,2017Expires November 26,2034 US 9,717,682 Solid Oral Film Dosage Forms andMethods for Making Same Optimization of film strip technology Issued August 1,2017Expires September 21,2

219、031 US 9,949,934 Device and method of treatingconditions associated withneuroinflammation Formulation of oral films containingmontelukast Issued April 24,2018Expires October 20,2036 US 10,272,038 Film dosage form with extendedrelease mucoadhesive particles Film containing mucoadhesive particle Issue

220、d April 30,2019Expires November 26,2034 US 10,610,528 Solid oral film dosage forms andmethods for making same Formulation of oral films containingtadalafil Issued April 7,2020Expires June 28,2031 US 10,722,476 Device and method of treatingconditions associated withneuroinflammation Formulation of or

221、al films containingmontelukast Issued July 28,2020Expires October 20,2036 US 10,828,254 Oral film formulation for modulatingabsorption profile Formulation of oral films containingtadalafil Issued November 10,2020Expired September 28,2038 CA 2,998,223 Loxapine film oral dosage form Formulation of ora

222、l films containingloxapine Issued October 9,2018Expires January 24,2037 CL 61.052 Instantly wettable oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive pharmaceutical ingredients Issued October 13,2020Expires July 30,203417 EP 3,027,179 Instantly wettab

223、le oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive pharmaceutical ingredients Issued October 17,2018Expires July 30,2034JP 6,482,552 Instantly wettable oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive

224、pharmaceutical ingredients Issued March 13,2019Expires July 30,2034 MX 366,595 Instantly wettable oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive pharmaceutical ingredients Issued July 15,2019Expires July 30,2034 ZL 201480043392.8 Instantly wettable

225、oral film dosageform without surfactant or polyalcohol Formulation of oral films containingactive pharmaceutical ingredients Issued February 26,2021Expires July 30,2034Patent Application No.TitleSubjectDate Filed Korean Appl.KR20167005581Immediately wet oral films dosageforms have no surfactant and

226、apolyhydric alcohol Formulation of oral films containingactive pharmaceutical ingredientsFiled July 30,2014 Korean Appl.KR20180119627 Montelukast transmucosal film Formulation of oral films containingmontelukast Filed March 1,2017 Korean Appl.KR20190071692 Devices and methods for treatingdiseases as

227、sociated withneuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 Korean Appl.KR20190128637 Therapeutic Methods and Apparatusfor Improved Bioavailability ofLeukotriene Receptor Antagonists Formulation of oral films containingmontelukast Filed March 29,2018 EU Appl.

228、EP 3,528,796 Device and method of treatingconditions associated withneuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 EU Appl.Film dosage form with extendedrelease mucoadhesive particles Film containing mucoadhesive particle Filed May 8,2018 Chinese Appl.CN10984

229、3273 The device and method for treatingillness relevant to neuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 Chinese Appl.CN110381931 The treatment method and device ofthe bioavilability of improvedleukotriene receptor antagonists Formulation of oral films conta

230、iningmontelukast Filed March 29,2018 Mexican Appl.MX2019004096 Device and method of treatingconditions associated withneuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 Mexican Appl.MX2019010573 Method of treatment and device forthe improved bioavailability ofleu

231、kotriene receptor antagonists Formulation of oral films containingmontelukast Filed March 29,2018 South African Appl.2016/00785 Immediately wet oral films dosageforms have no surfactant and apolyhydric alcohol Formulation of oral films containingactive pharmaceutical ingredients Filed July 30,2014 I

232、ndian Appl.IN201947014213 Device and method of treatingconditions associated withneuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 Indian Appl.IN201947035380 Method of treatment and device forthe improved bioavailability ofleukotriene receptor antagonists Formul

233、ation of oral films containingmontelukast Filed March 29,2018 Japanese Appl.JP2019508437 Montelukast transmucosal film Formulation of oral films containingmontelukast Filed March 1,2017 Canadian Appl.CA2,998,218 Device and method of treatingconditions associated withneuroinflammation Formulation of

234、oral films containingmontelukast Filed October 17,2017 Canadian Appl.CA3,015,555 Loxapine film oral dosage form Formulation of oral films containingloxapine Filed January 25,2017 Canadian Appl.CA3,017,264 Montelukast transmucosal film Formulation of oral films containingmontelukast Filed March 1,201

235、7 Canadian Appl.CA3,017,526 Method of treatment and device forthe improved bioavailability ofleukotriene receptor antagonists Formulation of oral films containingmontelukast Filed September 14,2018 Canadian Appl.CA3,056,944 Method of treatment and device forthe improved bioavailability ofleukotriene

236、 receptor antagonists Formulation of oral films containingmontelukast Filed March 29,201818 Canadian Appl.CA 3,062,704 Film dosage form with extendedrelease mucoadhesive particles Film containing mucoadhesive particle Filed May 8,2018 Canadian Appl.CA 3,061,086 Lipophilic active oral film formulatio

237、nand method of making the same Film containing lipophilic actives Filed Nov 6,2019 Australian Appl.AU2017344764 Device and method of treatingconditions associated withneuroinflammation Formulation of oral films containingmontelukast Filed October 17,2017 Australian Appl.AU2018241534 Method of treatm

238、ent and device forthe improved bioavailability ofleukotriene receptor antagonists Formulation of oral films containingmontelukast Filed March 29,2018 US Appl.15/940,288 Method of treatment and device forthe improved bioavailability ofleukotriene receptor antagonists Formulation of oral films contain

239、ingmontelukast Filed March 29,2018 US Appl.16/110,737 Film dosage form with extendedrelease mucoadhesive particles Film containing mucoadhesive particle Filed August 23,2018 US Appl.16/053,383 Loxapine film oral dosage form Formulation of oral films containingloxapine Filed August 2,2018 US Appl.16/

240、131,995 Method of treatment and device forthe improved bioavailability ofleukotriene receptor antagonists Formulation of oral films containingmontelukast Filed September 14,2018 US Appl.16/391,430 Film Dosage Forms ContainingAmorphous Active Agents Film containing amorphousagent Filed April 23,2019

241、US Appl.15/067,309 Lipophilic active oral film formulationand method of making the same Filed April 15,2019 US Appl.17/063,644 Oral film formulation for modulatingabsorption profile Filed October 5,2020 PCT Appln.WO2020093146 Lipophilic active oral film formulationand method of making the same Formu

242、lation of oral films containinglipophilic actives Filed November 4,201919COVID-19Our operations and financial condition have been affected by the COVID-19 pandemic.Though we were granted an exemption by local authorities whichpermitted us to continue operations during the COVID-19 pandemic,we nevert

243、heless faced multiple operational and financial challenges.Despite thesechallenges,we have continually been able to minimize the impact on our overall performance.In response to the COVID-19 pandemic,we partially reorganized our operations,adopted a remote work policy for employees and management an

244、dimplemented a compensation deferral program.We also benefited from the Canada Emergency Wage Subsidy as well as the Canada EmergencyCommercial Rent Assistance program from our landlord.There is uncertainty as to the duration of these benefits and hence the potential impact.Throughout the COVID-19 p

245、andemic,we have been,and remain,in compliance with all federal,provincial,and municipal regulations that have been putin place since the beginning of the pandemic.We will continue to monitor any further developments in this regard,with the health and safety of ouremployees and management as the prim

246、ary concern.Government RegulationThe pharmaceutical industry is highly regulated.The products we participate in developing require certain regulatory approvals.In the UnitedStates,drugs are subject to rigorous regulation by the FDA.The FDCA,and other federal and state statutes and regulations,govern

247、,among otherthings,the research,development,testing,manufacture,storage,record keeping,packaging,labeling,adverse event reporting,advertising,promotion,marketing,distribution,and import and export of pharmaceutical products.Failure to comply with applicable regulatory requirements may subject acompa

248、ny to a variety of administrative or judicially-imposed sanctions and/or the inability to obtain or maintain required approvals or to market drugs.Thesteps ordinarily required before a new pharmaceutical product may be marketed in the United States include:preclinical laboratory tests,animal studies

249、 and formulation studies under FDAs good laboratory practices regulations,(GLPs);the submission to the FDA of an investigational new drug application,which must become effective before human clinical trials may begin;the completion of adequate and well-controlled clinical trials according to good cl

250、inical practice regulations,(GCPs),to establish the safety andefficacy of the product for each indication for which approval is sought;after successful completion of the required clinical testing,submission to the FDA of an NDA,or an ANDA,for generic drugs.In certain cases,an application for marketi

251、ng approval may include information regarding safety and efficacy of a proposed drug that comes from studies notconducted by or for the applicant.Such applications,known as a 505(b)(2)NDA,are permitted for new drug products that incorporate previouslyapproved active ingredients,even if the proposed

252、new drug incorporates an approved active ingredient in a novel formulation or for a newindication;satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product is to be produced,toassess compliance with cGMPs to assure that the facilities,

253、methods and controls are adequate to preserve the drugs identity,strength,qualityand purity;andFDA review and approval of the NDA or ANDA.The cost of complying with the foregoing requirements,including preparing and submitting an NDA or ANDA,may be substantial.Accordingly,we typically rely upon our

254、partners in the pharmaceutical industry to spearhead and bear the costs of the FDA approval process.We also seek tomitigate regulatory costs by focusing on 505(b)(2)NDA opportunities.By applying our drug delivery technology to existing drugs,we seek to developproducts with lower research&development

255、(R&D)expenses and shorter time-to-market timelines as compared to regular NDA products.The preclinical and clinical testing and approval process takes many years and the actual time required to obtain approval,if any,may varysubstantially based upon the type,complexity and novelty of the product or

256、disease.20Preclinical tests include laboratory evaluation of product chemistry,formulation and toxicity,as well as animal studies to assess thecharacteristics and potential safety and efficacy of the product.The conduct of the preclinical tests must comply with federal regulations andrequirements,in

257、cluding GLPs.The results of preclinical testing are submitted to the FDA as part of an Investigational New Drug(IND)application alongwith other information,including information about product chemistry,manufacturing and controls and a proposed clinical trial protocol.Long-termpreclinical tests,such

258、as animal tests of reproductive toxicity and carcinogenicity,may continue after the IND application is submitted.The IND application automatically becomes effective 30 days after receipt by the FDA,unless the FDA,within the 30-day time period,raisesconcerns or questions relating to one or more propo

259、sed clinical trials and places the clinical trial on a clinical hold,including concerns that humanresearch subjects will be exposed to unreasonable health risks.In such a case,the IND sponsor and the FDA must resolve any outstanding concernsbefore the clinical trial can begin.A separate submission t

260、o an existing IND application must also be made for each successive clinical trial conductedduring product development.Further,an independent institutional review board,(IRB),covering each site proposing to conduct the clinical trial mustreview and approve the plan for any clinical trial and informe

261、d consent information for subjects before the trial commences at that site and it must monitorthe study until completed.The FDA,the IRB,or the sponsor may suspend a clinical trial at any time on various grounds,including a finding that thesubjects or patients are being exposed to an unacceptable hea

262、lth risk or for failure to comply with the IRBs requirements,or may impose otherconditions.Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualifiedinvestigator in accordance with GCP requirements,which includes

263、the requirement that all research subjects provide their informed consent in writing fortheir participation in any clinical trial.Sponsors of clinical trials generally must register and report,at the NIH-maintained website ClinicalTrials.gov,keyparameters of certain clinical trials.For purposes of a

264、n NDA submission and approval,human clinical trials are typically conducted in the followingsequential phases,which may overlap or be combined:In Phase 1,through the initial introduction of the drug into healthy human subjects or patients,the drug is tested to assess metabolism,pharmacokinetics,phar

265、macological actions,side effects associated with increasing doses,and,if possible,early evidence on effectiveness.Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication,dosagetolerance and optimum dosage,and to identify

266、common adverse effects and safety risks.Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients,typically atgeographically dispersed clinical trial sites,to permit the FDA to evaluate the overall benefit-risk relationship o

267、f the drug and to provide adequateinformation for the labeling of the drug.In most cases,the FDA requires two adequate and well controlled Phase 3 clinical trials to demonstrate theefficacy of the drug.A single Phase 3 trial with other confirmatory evidence may be sufficient in rare instances where

268、the study is a large multicenter trialdemonstrating internal consistency and a statistically persuasive finding of a clinically meaningful effect on mortality,irreversible morbidity or prevention ofa disease with a potentially serious outcome and confirmation of the result in a second trial would be

269、 practically or ethically impossible.After completion of the required clinical testing,an NDA is prepared and submitted to the FDA.FDA approval of the NDA is required beforemarketing of the product may begin in the United States.The NDA must include the results of all preclinical,clinical and other

270、testing and a compilation ofdata relating to the products pharmacology,chemistry,manufacture and controls.Under federal law,the submission of most NDAs is subject to asubstantial application user fee,and applicant under an approved NDA is also subject to an annual program fee for each prescription d

271、rug product,whichbeginning in Fiscal Year 2018 replaced the product and establishment fees.The FDA has 60 days from its receipt of an NDA to determine whether the application will be accepted for filing based on the agencys thresholddetermination that it is sufficiently complete to permit substantiv

272、e review.The FDA may request additional information rather than accept an NDA forfiling.In this event,the NDA must be resubmitted with the additional information and is subject to payment of additional user fees.The resubmittedapplication is also subject to review before the FDA accepts it for filin

273、g.Once the submission is accepted for filing,the FDA begins an in-depthsubstantive review.Under the Prescription Drug User Fee Act,the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification system,Standard Review and Priority Review.Priority Review desi

274、gnation is given to drugs that offer major advances in treatment orprovide a treatment where no adequate therapy exists.The FDA endeavors to review applications subject to Standard Review within ten to twelvemonths,whereas the FDAs goal is to review Priority Review applications within six to eight m

275、onths.21The FDA may refer applications for proprietary drug products or drug products which present difficult questions of safety or efficacy to anadvisory committee for review,evaluation and recommendation as to whether the application should be approved and under what conditions.Before approving a

276、n NDA,the FDA will typically inspect one or more clinical sites to assure compliance with GCP requirements.Additionally,theFDA will inspect the facility or the facilities at which the drug is manufactured.The FDA will not approve the product unless it determines that themanufacturing process and fac

277、ilities are in compliance with cGMP requirements and are adequate to assure consistent production of the product withinrequired specifications and the NDA contains data that provide substantial evidence that the drug is safe and effective in the indication studied.After the FDA evaluates the NDA and

278、 the manufacturing facilities and possibly conducts a sponsor inspection,it issues either an approval letteror a complete response letter.A complete response letter generally outlines the deficiencies in the NDA and may require substantial additional testing,orinformation,in order for the FDA to rec

279、onsider the application.Even with submission of this additional information,the FDA may ultimately decide that anapplication does not satisfy the regulatory criteria for approval.If,or when,the deficiencies have been addressed to the FDAs satisfaction in aresubmission of the NDA,the FDA will issue a

280、n approval letter.The review by the FDA is two months for a Class I resubmission and six months for aClass 2 resubmission.An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.As a condition of NDA approval,the FDA may require a

281、 REMS,or Risk Evaluation and Mitigation Strategy,to help ensure that the benefits of thedrug outweigh the potential risks.If the FDA determines a REMS is necessary during review of the application,the drug sponsor must agree to theREMS plan at the time of approval.A REMS may be required to include v

282、arious elements,such as a medication guide or patient package insert,acommunication plan to educate healthcare providers of the drugs risks,limitations on who may prescribe or dispense the drug,or other elements toassure safe use,such as special training or certification for prescribing or dispensin

283、g,dispensing only under certain circumstances,special monitoringand the use of patient registries.In addition,the REMS must include a timetable to periodically assess whether the REMS plan is effective.Therequirement for a REMS can materially affect the potential market and profitability of a drug.M

284、oreover,product approval may require substantial post-approval testing and surveillance to monitor the drugs safety or efficacy,and the FDAhas the authority to prevent or limit further marketing of a product based on the results of these post-marketing programs.Once granted,productapprovals may be w

285、ithdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.Drugs may bemarketed only for the approved indications and in accordance with the provisions of the approved label,and,even if the FDA approves a product,it maylimit the approved

286、 indications for use for the product or impose other conditions,including labeling or distribution restrictions or other risk-managementmechanisms.Further changes to some of the conditions established in an approved application,including changes in indications,labeling,or manufacturingprocesses or f

287、acilities,require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented,which mayrequire us to develop additional data or conduct additional preclinical studies and clinical trials.An NDA supplement for a new indication typically requiresclinical data simila

288、r to that in the original application,and the FDA uses similar procedures in reviewing NDA supplements as it does in reviewing NDAs.Post-Approval RequirementsOngoing adverse event reporting and submission of periodic reports are required following FDA approval of an NDA.The FDA also may requirepost-

289、marketing testing,known as Phase 4 testing,REMS,and surveillance to monitor the effects of an approved product,or the FDA may placeconditions on an approval that could restrict the distribution or use of the product.In addition,quality control,drug manufacture,packaging,and labelingprocedures must c

290、ontinue to conform to cGMPs and NDA specifications after approval.Drug manufacturers and certain of their subcontractors arerequired to register their establishments with FDA.Accordingly,manufacturers must continue to expend time,money,and training and compliance effortsin the areas of production an

291、d quality control to maintain compliance with cGMPs or other applicable laws.Regulatory authorities may requireremediation,withdraw product approvals or request product recalls if a company fails to comply with regulatory standards,if it encounters problemsfollowing initial marketing,or if previousl

292、y unrecognized problems or new concerns are subsequently discovered.In addition,other regulatory action,including,among other things,warning letters,the seizure of products,injunctions,consent decrees placing significant restrictions on or suspendingmanufacturing operations,civil penalties,and crimi

293、nal prosecution may be pursued.22The Hatch-Waxman AmendmentsANDA Approval ProcessThe Hatch-Waxman Amendments established abbreviated FDA approval procedures for drugs that are shown to be equivalent to drugspreviously approved by the FDA through its NDA process.Approval to market and distribute thes

294、e drugs is obtained by submitting an ANDA to the FDA.An ANDA is a comprehensive submission that contains,among other things,data and information pertaining to the active pharmaceutical ingredient,drug product formulation,specifications and stability of the generic drug,as well as analytical methods,

295、manufacturing process validation data and qualitycontrol procedures.Premarket applications for generic drugs are termed abbreviated because they generally do not include preclinical and clinical data todemonstrate safety and effectiveness.Instead,a generic applicant must demonstrate that its product

296、 is bioequivalent to the innovator drug.In certainsituations,an applicant may obtain ANDA approval of a generic product with a strength or dosage form that differs from a referenced innovator drugpursuant to the filing and approval of an ANDA Suitability Petition.The FDA will approve the generic pro

297、duct as suitable for an ANDA application if it findsthat the generic product does not raise new questions of safety and effectiveness as compared to the innovator product.A product is not eligible forANDA approval if the FDA determines that it is not equivalent to the referenced innovator drug,if it

298、 is intended for a different use,or if it is not subject toan approved Suitability Petition.However,such a product might be approved under an NDA,with supportive data from clinical trials.505(b)(2)NDAsAs an alternative path to FDA approval for modifications to formulations or uses of products previo

299、usly approved by the FDA,an applicant maysubmit an NDA under Section 505(b)(2)of the FDCA.Section 505(b)(2)was enacted as part of the Hatch-Waxman Amendments and permits the filing ofan NDA where at least some of the information required for approval comes from studies not conducted by,or for,the ap

300、plicant.If the 505(b)(2)applicantcan establish that reliance on FDAs previous findings of safety and effectiveness is scientifically appropriate,it may eliminate the need to conduct certainpreclinical or clinical studies of the new product.The FDA may also require companies to perform additional stu

301、dies or measurements,including clinicaltrials,to support the change from the approved branded reference drug.The FDA may then approve the new product candidate for all,or some,of thelabel indications for which the branded reference drug has been approved,as well as for any new indication sought by t

302、he 505(b)(2)applicant.Orange Book ListingIn seeking approval for a drug through an NDA,including a 505(b)(2)NDA,applicants are required to list with the FDA certain patents withclaims that cover the applicants product.Upon approval of an NDA,each of the patents listed in the application for the drug

303、 is then published in theOrange Book.Any applicant who files an ANDA seeking approval of a generic equivalent version of a drug listed in the Orange Book or a 505(b)(2)NDAreferencing a drug listed in the Orange Book must certify to the FDA that(i)no patent information on the drug product that is the

304、 subject of theapplication has been submitted to the FDA;(ii)such patent has expired;(iii)the date on which such patent expires;or(iv)such patent is invalid or will notbe infringed upon by the manufacture,use or sale of the drug product for which the application is submitted.This last certification

305、is known as aparagraph IV certification.A notice of the paragraph IV certification must be provided to each owner of the patent that is the subject of the certification andto the holder of the approved NDA to which the ANDA or 505(b)(2)application refers.The applicant may also elect to submit a sect

306、ion viii statementcertifying that its proposed label does not contain(or carves out)any language regarding the patented method-of-use rather than certify to a listedmethod-of-use patent.If the reference drug NDA holder and patent owners assert a patent challenge directed to one of the Orange Book li

307、sted patents within 45 days ofthe receipt of the paragraph IV certification notice,the FDA is prohibited from approving the application until the earlier of 30 months from the receipt ofthe paragraph IV certification,expiration of the patent,settlement of the lawsuit or a decision in the infringemen

308、t case that is favorable to the applicant.The ANDA or 505(b)(2)application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the brandedreference drug has expired as described in further detail below.Non-Patent ExclusivityIn addition to patent exclus

309、ivity,the holder of the NDA for the listed drug may be entitled to a period of non-patent related exclusivity,duringwhich the FDA cannot review,or in some cases,approve an ANDA or 505(b)(2)application that relies on the listed drug.For example,a company mayobtain five years of non-patent exclusivity

310、 upon NDA approval of a new chemical entity(NCE),which is a drug that contains an active moiety that hasnot been approved by the FDA in any other NDA.An active moiety is defined as the molecule or ion responsible for the drug substances physiologicalor pharmacologic action.During the five-year exclu

311、sivity period,the FDA cannot accept for filing any ANDA seeking approval of a generic version of thatdrug or any 505(b)(2)NDA for the same active moiety and that relies on the FDAs findings regarding that drug,except that FDA may accept anapplication for filing after four years if the follow-on appl

312、icant makes a paragraph IV certification.23A drug,including one approved under Section 505(b)(2),may obtain a three-year period of exclusivity for a particular condition of approval,orchange to a marketed product,such as a new formulation of a previously approved product,if one or more new clinical

313、studies(other than bioavailabilityor bioequivalence studies)was essential to the approval of the application and was conducted/sponsored by the applicant.Should this occur,the FDAwould be precluded from approving any ANDA or 505(b)(2)application for the protected modification until after that three-

314、year exclusivity period has run.However,unlike NCE exclusivity,the FDA can accept an application and begin the review process during the exclusivity period.International RegulationIn addition to regulations in the United States,we are and will be subject to a variety of foreign regulations regarding

315、 development,approval,commercial sales and distribution of our products.Whether or not we obtain FDA approval for a product,we must obtain the necessary approvals by thecomparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those

316、countries.The approvalprocess varies from country to country and can involve additional product testing and additional review periods,and the time may be longer or shorterthan that required to obtain FDA approval.The requirements governing,among other things,the conduct of clinical trials,product li

317、censing,pricing andreimbursement vary greatly from country to country.Regulatory approval in one country does not ensure regulatory approval in another,but a failure ordelay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.If we fail to comply wi

318、th applicable foreignregulatory requirements,we may be subject to fines,suspension or withdrawal of regulatory approvals,product recalls,seizure of products,operatingrestrictions and criminal prosecution.In the EU,we may seek marketing authorization under either the centralized authorization procedu

319、re or nationalauthorization procedures.Centralized procedure.The European Medicines Agency,(EMA),implemented the centralized procedure for the approval of human medicinesto facilitate marketing authorizations that are valid throughout the EU.This procedure results in a single marketing authorization

320、 issued by the EuropeanCommission following a favorable opinion by the EMA that is valid across the European Union,as well as Iceland,Liechtenstein and Norway.Thecentralized procedure is compulsory for human medicines that are:derived from biotechnology processes,such as genetic engineering,contain

321、a newactive substance indicated for the treatment of certain diseases,such as HIV/AIDS,cancer,diabetes,neurodegenerative disorders or autoimmunediseases and other immune dysfunctions,and officially designated orphan medicines.For medicines that do not fall within these categories,an applicanthas the

322、 option of submitting an application for a centralized marketing authorization to the EMA,as long as the medicine concerned is a significanttherapeutic,scientific or technical innovation,or if its authorization would be in the interest of public health.National authorization procedures.There are als

323、o two other possible routes to authorize medicinal products in several European Union countries,which are available for investigational medicinal products that fall outside the scope of the centralized procedure:the decentralized procedure and themutual recognition procedure.Under the decentralized

324、procedure,an applicant may apply for simultaneous authorization in more than one EU countryfor medicinal products that have not yet been authorized in any EU country and that do not fall within the mandatory scope of the centralized procedure.Under the mutual recognition procedure,a medicine is firs

325、t authorized in one EU Member State,in accordance with the national procedures of thatcountry.Following a national authorization,the applicant may seek further marketing authorizations from other EU countries under a procedure wherebythe countries concerned agree to recognize the validity of the ori

326、ginal,national marketing authorization.In the EU,medicinal products designated as orphan products benefit from financial incentives such as reductions in marketing authorizationapplication fees or fee waivers and 10 years of market exclusivity following medicinal product approval.For a medicinal pro

327、duct to qualify as orphan:(i)itmust be intended for the treatment,prevention or diagnosis of a disease that is life-threatening or chronically debilitating;(ii)the prevalence of thecondition in the EU must not be more than five in 10,000 or it must be unlikely that marketing of the medicine would ge

328、nerate sufficient returns to justifythe investment needed for its development;and(iii)no satisfactory method of diagnosis,prevention or treatment of the condition concerned can beauthorized,or,if such a method exists,the medicine must be of significant benefit to those affected by the condition.Othe

329、r RegulationWe are also subject to various laws and regulations regarding laboratory practices,the experimental use of animals,and the use and disposal ofhazardous or potentially hazardous substances in connection with our research.While we believe we are in compliance with applicable environmentala

330、nd other regulations,in each of these areas,as above,the FDA and other government agencies have broad regulatory and enforcement powers,including,among other things,the ability to levy fines and civil penalties,suspend or delay issuance of approvals,seize or recall products,and withdrawapprovals,any

331、 one or more of which could have a material adverse effect on us.24Canadian Medical and Adult-UseMedical and adult-use cannabis in Canada is regulated under the federal Cannabis Act and the Cannabis Regulations(CR)promulgated underthe Cannabis Act.Both the Cannabis Act and CR came into force in Octo

332、ber 2018,superseding earlier legislation that only permitted commercialdistribution and home cultivation of medical cannabis.The following are the highlights of the current federal legislation:a federal license is required for companies to cultivate,process and sell cannabis for medical or non-medic

333、al purposes;Health Canada,federal government entity,is the oversight and regulatory body for cannabis licenses in Canada.As of December 31,2020,Health Canada has issued approximately 570 active licenses to licensees under the CR(Licensed Producers);allows individuals to purchase,possess and cultivate limited amounts of cannabis for medical purposes and,for individuals over the ageof 18 years,for a