ペルセウスプロテオミクス（4882） – Presentation Material for FY2021 Business Results

Perseus Proteomics Inc.(Securities code:4882)FY2021 Business ResultsMay 16, 2022Contents01020304About Perseus ProteomicsFY2021 ReviewFY2021 Business ResultsFY2022 Business Plan / Forecast201 About Perseus Proteomics3Company outlineCompany namePerseus Proteomics Inc.EstablishedFebruary 2001Business⚫ Develop Ab drugs⚫ Support research on Ab⚫ Sales of Abs/reagentsOffice: 4-7-6 Komaba, Meguro-ku, TokyoHQNagoya : 2-22-8 Chikusa-ku, Nagoya-shi, AichiCapital1,939 million yen*Employee21 (R&D: 16, Administration: 5) ** as of 31 Mar. 20222001.2Established2005.9Sales of Ab against 48 nuclear receptors starts2006.92011.12014.12PPMX-T001 licensed out to Chugai PharmaceuticalsPPMX-T002 licensed out to FUJIFILM(2022.3 returned to PPMX)PPMX-T003selected as JST drug discovery project (940 M yen)2015.9PPMX-T004 licensed out to FUJIFILM(2022.3 returned to PPMX)2019.1Nagoya Laboratory opens2019.11 PPMX-T003 in-house P1 starts2021.6 Listed on Mothers (Growth) TSE2022.3 PPMX-T003 Adopted as AMEDproject on ANKL (250 M yen)4Sales/Profit creating structure1. Drug discoveryInformation on clinical needsTechnical seeds, collaborative research• Analysis of disease• New target• Ab engineering• Production technologyR&D costInformation on clinical needs• Opinions from clinicians• Clinical studies• Unmet medical needs• Design of clinical trialsLicense-outContract feeMilestone incomeAcademiaPharmaceutical companyLicense- out timing flexibly decided depending on situationR&D of Ab drugsRoyalty income2.Support of Ab research3.Sales of Abs/reagentsP1P2P3Filing for approvalLaunch salesPharmaceutical companyAcademiaIncome• Ab• ReagentsPharmaceutical companyAcademia5Obtainment & optimization of Ab, Pre-clinical studyIncome• Ab production• R&D support• Analysis ofsequencingWhat are Ab drugs?Abs are substances that remove foreign objects in human bodyAb drugs are Abs obtained against targets expressed on cancers or pathogensCharacteristicsAbBinds to targeting antigens onlyCDR=Part binding to antigenNumber of Ab drugs approvalMouse AbChimeric Ab Humanised AbHuman AbExpected effects• Blocks signal transmission and inhibits multiplication functions, etc.• Activates immune cells including T cells to induce cytotoxicity• Activates physiological functions• Transmits drugs to cells where targets are expressedNo. of Approved Ab drugs increasingHumanized or human Abs are in mainstreamMouse AbChimeric AbHumanised AbHuman AbSource: data from National Institute of Health SciencesCalculated based on Approval date in Japan, USA and Europe6Ab creation technology now requiredDifficulty=High antigen The most important targetsStill untouchedQuaternary structureDifficulty=Medium antigenReceptor-type targetsNeeds functional AbTertiary structureDifficulty=Easy antigenAntigen as targets already developedα helixΒ sheetAmino acidT003Important targets are not easily reachable.Small molecules might cause side effects. They may not have enough efficacy.Technology required for obtaining Abs efficiently against medium to high level antigensAny technology to help us to get the fruit on the treetop easily?Antigen preparation is the core task!7Our technology to obtain Abs1) Hybridoma method2) Phage display methodImmunizationAb producing cellPhage Ab preparationInfect E.coliMyelomaAntigen-antibody reactionElution CleaningMeritProbemlMouse IgGHybridoma⚫ Easy method, established technique⚫ Increased biological affinity⚫ Low costHuman single chain Ab⚫ Possible to obtain human Ab⚫ No animals used⚫ No need to consider biological toxicity⚫ Rich in screening conditions⚫ Abs with species crossing are hard to obtain⚫ Needs humanisation due to immunnogenicity⚫ Abs against complex antigens are hard to obtain⚫ Easy-to-obtain Abs already developed⇒ Focusing on new targets and modified Abs including ADC*1 and RIT*2⚫ Needs skills in creation of libraries⚫ More expensive than animal immunization⚫ Low affinity of antigen-antibody⇒ Conquered this problem by maximising library diversity*1 ADC: Antibody drug conjugate. It delivers drug combined with Ab by utilizing Ab function. *2 RIT: Radioimmunotherapy. Radioisotope combined with Ab irradiates cancer cells by utilizing Ab function.8Our strength: Phage Ab library1What is phage Ab library?Ab-producing cells（Human cells that produce Abs)Produce Abs artificially2Our design of phage Ab library A mass of approx. 100billion(1011) different Absto obtain Ab that binds to specific antigenPPMXH H chainchainH chainL chainCompetitor ACompetitor BL chainH chainL chainL chainH chainWe maximise diversity of H chain by focusing on H chain (our unique library)OthersWhile numbers of Abs are the same 10 billion, diversities are differentPhage display method utilizing maximised diversity of Ab library9Our strength: Ab screening using cell (PPMX exclusive method)Problem 1SolutionDuring preparation of antigen, steric structure is lost.Ab screening using living cells• Reflects complex steric structure through using living cells• Directly obtains Abs against antigens on cell membraneProblem 2SolutionICOS* method:Ab screening utilizing organic solvent• Obtains Abs that bind to antigen onlyPatent registered•Numerous unrelated Abs also bind to cells.OthWater layerOrganic layerEfficiently separates Abs difficult to obtain by targeting cells*Isolation of antigen/antibody Complexes through Organic Solvent 10Summary of technology to obtain AbsOur technology on Ab drug developmentOur unique technology platform sophisticated to aim at drug discovery for highly difficult targetsHybridoma methodPhage display methodICOS methodMature and reliabletechnologyMaximizing human Ab diversityScreening to reflect complex steric structure on cell membraneShowing our maximum value in developing anti-cancer drugsPPMX’s sophisticated Ab obtaining platform1102 FY2021 Review12Topics1234PPMX-T003:Development of medical drug for Aggressive NK Cell Leukemia adopted as AMED programPPMX-T003: Recruit of Phase I clinical trial among polycythemia vera patients=> Changed protocol to expand inclusion criteriaPPMX-T002/T004:License agreement w/FUJIFILM terminatedDevelop new RIT/ADC respectivelyJoint research w/pharmaceutical companies and universitiesSmooth progress in various themes13PPMX-T003First-in-class anti-cancer drug candidate targeting transferrin receptorTransferrin receptor (TfR):• Strong target molecule for anti-cancer drug• Expressed on cell membrane. Binds to transferrin (Tf) carrying iron for cellular iron uptake1TfR binds to TfTransferrin (Tf)Iron2Cell proliferationTransferrin receptor（TfR)[ Cells where TfR is highly expressed ]CellCell membrane◼ Erythroblast (normal cell, RBC producing cell)◼ Cancer cell (especially acute cancer which is actively proliferating)Well-known conceptBlocking iron⇒ Death or proliferation inhibition of cellsInhibiting cellular iron uptake leads to death/proliferation inhibition of cancer cells* Erythroblast: primitive red blood cell (RBC)14PPMX-T003Highly functional Ab obtained by our phage display technologyShows unprecedented result in inhibiting ratio of binding Tf to TfRInhibits iron uptake into erythroblast and cancer cells and leads to cell death/proliferation inhibitionPPMX-T003-Transferrin competitive assay1PPMX-T003 binds to TfR more tightly than TfA4501.61.41.21.00.80.60.40.20.0Ratioof I inhbitingbndngii HighHighA24(conventional Ab)TransferrinPPMX-T003PPMX-T003Binds to TfR to inhibit ironuptakeIronTransferrin(Tf)Transferrinreceptor（TfR)0.000.010.101.0010.00100.001000.00濃度 ug/mLAffinity2Iron uptake inhibited. Death or proliferation inhibition of cellsInhibition of iron uptake has been difficult, however, PPMX-T003 is expected to bring it to reality as the first therapeutic drug for cancer and PV.Anti-Transferrin receptor Ab with incomparable function of inhibiting binding151PPMX-T003:Development of medical drug for Aggressive NK Cell Leukemia adopted as AMED program*Title: “Development of Therapeutic Drug for Aggressive NK Cell Leukemia”⚫ About ANKLAggressive NK Cell LeukemiaUltra-orphan disease whose cases are reported only in South/Middle Americas and AsiaVery poor prognosis with unknown critical causes/ unestablished treatment method(Patent application filed in Apr. 2022)PPMX-T003Found that transferrin is related to proliferation and treatment of tumorAnti-TfR AbPPMX-T003obtained by PPMXConfirmed tumor disappearance by PPMX-T003 administration in mouse transplanted human-cancer cell experimentFY2022:FY2023:FY2024:Subsidy (max) total:50M yen100M yen100M yen250M yenAim at approval of world-first effective therapeutic drug for ANKL after investigator-initiated clinical trials* Project Promoting Support for Drug Discovery Support Program for Orphan drug prior to the Designation162PPMX-T003: Recruit of Phase I clinical trial among polycythemia vera (PV)patients => Changed protocol to expand inclusion criteriaJun. 2021Clinical trial notification approvedMay 2021Clinical trialnotificationsubmittedAug. 2021Contract w/hospitalEarly summer or afterwards, 2021 Administration to PV patients (plan)Prepa-rationP1 (Safety/efficacy to be confirmed among PV patients)⚫ Clinical trial informationjRCTjRCT2051210083: https://jrct.niph.go.jp/en-latest-detail/jRCT2051210083clinicaltrials.govNCT05074550： https://clinicaltrials.gov/ct2/show/NCT05074550< Protocol amendment>(expansion of subjects) BeforeAfterExclude patients w/high EPO＊Not exclude patients w/high EPO＊considering affects of phlebotomy PV judgment:Prioritize WHO standardsPV judgment:Prioritize clinicians’ judgment＊ EPO (Erythropoietin)Hormone to create RBC. EPO increases in case of anemia and functions to increase RBC.17PPMX-T003Indication: Polycythemia vera (PV)• RBC increases to an abnormal level.• Thrombosis is easily formed due to thick and slow blood flow. Various organs are affected by thrombosis.• 2 out of 100,000 people develop this disease. Number of patients in Japan: 30,000 (estimated by PPMX. Average life expectancy: 16 yrs) Current therapeuticsNew candidateTherapeutic phlebotomyAnti-cancer drug, etc.PPMXPPMX－T003Half of patients are treated by therapeutic phlebotomy only.Hematopoieticstem cellAnti-cancerdrugHematopoieticstem cellErythroblastMegakaryocytePromyeloidcellErythroblastPromyeloidcellMegakaryocytePPMX-T003RBCWBCBlood plateletRBCWBCBlood platelet•Entire hematopoietic stem cell affectedSecondary cancer risk•• Many side effects•••Acts only on erythroblastFew side effectsSafe to use•Anemia•Lassitude•Depression•Restless hands and legs• Other diseases by iron deficiency PPMX-T003: effects on inhibiting abnormal proliferation of RBC expected18PPMX-T003: Confirmed efficacy against blood cancers in mice⚫ AMLTumor volume (mm3)⚫ Malignant LymphomaTumor volume (mm3)Control1 mg/kg3 mg/kg10 mg/kgControl0.3 mg/kg1 mg/kg3 mg/kg30002500200015001000500025002000150010005000001020304050607020406080Days after inoculationDays after inoculationExcellent efficacy against AML and various blood cancers is confirmedSource: Zhang et al.(2017) AACR Annual Meeting, Chicago, USA DOI: 10.1158/1538-7445.AM2017-5586 19PPMX-T003: Development planCodeIndicationCountryAs ofMar. 2022PV (Polycythemiavera）AML (Acute myelomaleukemia）ANKL (Aggressive NK cell leukemia)ML (Malignant lymphoma)(Solid tumor)Number of patientsIndicationAML (Acute myelomaleukemia）P1 (PV patients) under preparation in-houseLicense-outApprovalPPMX-T003JP, othersInvestigator-led clinical trialP1/P2a endApprovalJoint research with academia ongoingJoint research with academia ongoingJoint research with academia ongoingPeritoneal dissemination by digestive organ cancer (clinical trial led by doctor)ApprovalP2b/P3No. of patients ww (rounded)Note PV (Polycythemia vera)Chronic blood disease280,000Calculated with onset risk rate at 2 in 100,000*, life expectancy at 14 years*, population at 1 billion (developed countries)Blood cancer200,000WHO data (assumes 40% of leukemia)Malignant lymphomaBlood cancer590,000WHO data (number of non-Hodgkin lymphoma patients)Multiple myeloma Blood cancer190,000WHO dataPeritoneal dissemination of cancerSolid tumorN/AOver 10,000 and several thousand new patients annually in Japan* This chart is based on our assumption and does not guarantee the progress as shown here.* All the development after out-licensing is determined by the development strategies of licensing partners.203PPMX-T002/T004:License agreement w/FUJIFILM terminatedDevelop new RIT/ADC respectivelyMar. 2022 FUJIFILM transferred its radiopharmaceutical business to PeptiDream GroupJan. 2011Licensing agreementMar. 2022Agreement terminatedStarted TXR of clinical trial dataFinish developmentafter P1 expansion/P1PPMX-T002（RI-labelled AbTarget: CDH3)USAResearchPre-clinicalP1JPResearchPre-clinicalP1(ongoing)P1 expansion(ongoing)Sep. 2015Licensing agreementMar. 2022Agreement terminatedPPMX-T004（ADCTarget: CDH3)Research21PPMX-T002: Result of P1 in USAClinical trial among stage IV ovarian cancer patients Confirmed efficacy in 11 out of 15 cases, Published at conference, paper submittedSubbiah V, et al. Phase I Study of P-cadherin-targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors. Clin Cancer Res. 2020;26(22):5830-5842.Subbiah et al. (2017) AACR Annual Meeting, Chicago, USA DOI: 10.1158/1538-7445.AM2017-CT097 2016/1 – 2019/3: P1 in USA2019/3: P1 expansion (P2) started▼▼2020/4: P1 started in JPCRSDSDSDPDPDPDPDSDSDSDSDSDSDCR: Complete remission=tumor disappeared (almost cured)SD: Stable disease＝proliferation preventedEffectiveInitial administrationSDPD: Progressive diseaseIneffective4 months after114: Administered day1.6cm0.6cm0102030405060708090100110120130(wk)Complete remission on poor prognosis patient with no therapeutics (POC obtained*)※ POC(proof of concept) obtained: Efficacy of new drug candidate under development was confirmed by administration to human.22PPMX-T002:Develop as new RI-labelled AbIndicationbiliary tract cancer, ovarium cancer, cancer of thehead and neck, etc.TargetCDH3 (Cadherin 3)[Development strategy]New partner（RI drug discovery company)Confirmed accumulation on cancerUtilize as isAbRI90Y(beta emitter)177Lu (beta emitter)or225Ac (alpha emitter)Utilize Ab as is, change RI from 90Y to that w/higher effectiveness23PPMX-T002:Promote development through RI change to increase effectivenessRIRadiationHalf-lifeEnergy Max rangeFeatureMedical drugs90Y177Lu225AcBeta emitterBeta emitterAlpha emitter64 hrs 2.27MeV11.0 mm Impact on cancer cells greater than LuZevalin (2002)6.7 days 0.50MeV2.2 mmFew side effects. Therapeutic effect in wider area. Most advancedLutathera (2018)Pluvicto (2022)10 days 5.83MeV0.090 mmHigh cell-killing nature in narrow area. Next generation RITAc-PSMA617, etc.Under development90Y 177LuBone marrowHematopoieticstem cellSide effectsDamages/Kills hematopoietic stem cells when passing through bone marrowCancercellsEfficacyAb accumulates on cancer cells, radiation from RI damages/kills cancer cellsBlood vesselSelect the best RI after study of side effects and efficacy24PPMX-T004:Develop as new ADC (Ab drug conjugate)IndicationVarious solid tumorsTargetCDH3 (Cadherin 3)[Development strategy]Develop through change to small molecule cancer drug w/higher effectiveness.Make cancer cells take Ab & drug inside so that the released drug may damage/kill cancer cellsAbSmall molecule anti-cancer drugPPMX-T004 Ab and drug taken into a human cancer cell. Confirmed functionality of AbUtilize Ab as is. Change drug to that w/higher effectiveness254Joint research w/pharmaceutical companies and universitiesSmooth progress in various themes●Development of Quick Detection Kit of PTX3Determine exacerbation of diseases associated with inflammationof blood vessels including sepsisUtilize as blood vessels inflammation marker●Designing/Establishment of BBB-Permeable molecule Design/Establish molecule that permeates blood-brain barrier (BBB)with high efficiencyDevelop technology to deliver medical drug to cerebrospinalWakunagaPharmaceuticalUniversityof Tokyo● Practical use of PKCδJikei University School of MedicineNew diagnosis w/high sensitivity for early-stage lever cancerPractical use of PKCδ as biomarker26PPMX-T001:Phase I clinical trial of GC33 combination therapy, ERY974 monotherapy and combination therapy ongoing by Chugai Pharmaceutical ➔Jun. 2022 related patent to be expiredCode No.IndicationStagePPMX-T001Liver cancer, solid tumor•••GC33 in combination with immune checkpoint inhibitor (ICI):P1 ongoing (JP, TW)ERY974 monotherapy:P1 finished (US, EU), P1 ongoing (JP)ERY974 in combination with ICI and angiogenic inhibitor:P1 started (JP, TW)Out-licensedChugai PharmaceuticalChugai Pharmaceutical development code: GC33, ERY974⚫ GPC3 AbBinds to cancercell⚫ CD3 AbBinds to T cellGC33ERY974 (bispecific Ab)2 arms respectively bind to different antigens.Contract will terminate in Jun. 2022. No impact on future income/profit27CodeIndicationRegionPreclinicalP1P2P3Out-licensedDrug discovery/ResearchRITADCGC33 MonotherapyPipeline progressPPMX-T002➔ New codePPMX-T004➔ New codePPMX-T003ANKLJapanSolidtumorSolidtumorBlood cancerLivercancerSolidtumorLivercancerUSAJapanJapanJapanUSAEuropeJapanTaiwanUSAEuropeJapanJapanTaiwanGC33 w/ICIERY974 w/ICI, angiogenic inhibitorPPMX-T001ERY974 monotherapyChugai PharmaceuticalFUJIFILM➔ PPMXFUJIFILM➔ PPMX－－2803 FY2021 Business Results29FY2020FY2021ForecastFY2021ResultsVs FY2020*Vs Forecast*FY2021 business results⚫ Profit & lossSalesGross profitSG & AR&D costOtherOperatingincomeOrdinaryincomeExtraordinary incomeExtraordinary lossNet income6764475313162-411-4101-7065630411219-564-583-407167539308231-472-481117-5995.9%5.7%13.5%-1.6%42.5%—2100.0％9,860.1%193.7％(million yen)*Increase/decrease rate2.4%3.1%-14.3%-25.0%5.7%Ab/reagent sales, research supportPPMX-T003Recruit delayPatent fee,etc.—-Impairment loss due to capexincrease30-413-625⚫ Sales/Profit: almost as planned⚫ SG&A: patents fee, etc. increased while P1 among PV patients delayedFY2021 financial status⚫ Balance sheetAssetsLiabilities2021/3/312022/3/312021/3/312022/3/31Cash & depositsAccounts receivable – tradeOtherTotal current assetsNon-current assetsTotal assets1,0693,214Current liabilities83091,1083,2901,1183,30010659Total liabilitiesShare capitalCapital surplusRetained earningsTotal shareholders’ equityTotal net assetsTotal liabilities and net assets(million yen)1481481,9392,225-1,0123,1523,1523,3003434604889-4131,0801,0831,118⚫ Cash & deposits, share capital, capital surplus: increased due to IPO⚫ Capital ratio: 95.5％3104 FY2022 Business Plans / Forecast32PPMX-T003:Start and finish administration in P1 among PV patientsPPMX-T003:Develop medical drug for ANKL – finish preparation forinvestigator-led clinical trialFY2022 Plans1２３4PPMX-T002：Determine new partnerPPMX-T004:Plan re-development 33FY2022 business results forecastFY2021resultsFY2022(forecast)Vs. FY2021Incr/decr rate(million yen)7167539308231-472-4812117-5997772776522253-703-736-116-8547.4%7.1%43.8%69.5%9.5%—–1.5%SalesGross profitSG & AR&D costOtherOperating incomeOrdinary incomeExtraordinary incomeExtraordinary lossNet income⚫ Sales: slight increase from FY2021⚫ R&D cost: P1 among PV patients cost included34Bring more Ab drugs to patientsAiming at highly functional Ab drugsAb drugs in the futurePerseus PlatformAb based on higher order structurePPMX-T003PPMX-T005PPMX-T006PPMX-T007・・・Current Ab drugsAbs based on steric structurePPMX-T002/004Develop Ab drugs one step aheadPhageDifficulty=High antigen“Blue ocean” due to technical entry barrierPPMX-T001Difficulty=Medium antigen“Severe development competition”by pharmaceuticalsPast Ab drugsAbs with simple structureDifficulty=Easy antigen“Barren land” already developed35This presentation material is prepared only to provide information for reference on investment, not to promote investment. The final decision on investment shall be made on your own.This presentation material includes forecast or estimates for the future. The Company has created these forward-looking statements based on the information currently available. Please note that they will change depending on the economic and/or medical business industry trends, etc.Perseus Proteomics Inc.EmailTELURL: ir@ppmx.com: +81-3-5738-1705: https://www.ppmx.com/en/