1、J.P.Morgan Healthcare Conference 2024Patient-Centric Innovation|Global Breakthrough Therapies(Ticker:6855.HK)January 10,2024Dr.Dajun Yang,Chairman&CEO2Ascentage PharmaDisclaimer3Ascentage PharmaAscentage PharmaPatient-Centric Innovation|Global Breakthrough TherapiesMISSIONTo address global unmet med

2、ical needsVISIONTo become a global leading integrated biopharmaceutical companyVALUEPatients first;Science-based;Data-driven34Ascentage Pharma1.24 million6%Global blood cancer annual incidence of all cancer casesUS$90bn30%Global hematological malignancy treatment market(2028E)of total cancer therapy

3、 marketSource:American Cancer Society,Mordor Intelligence,Leukemia and Lymphoma Society,Company forecast and dataBlood cancer market at a glanceWell-positioned to capture the US$10bn+global blood cancer market opportunitiesCML$7.2bnALL$2.3 bnCLL$13.2 bnAML$3.1 bnMM$25.7 bnMDS$3.3 bnAscentage PharmaW

4、ith proper treatments keeping the disease at bay,patients with certain blood cancers such as chronic myeloid leukemia(CML)can expect to have a normal length of life45Ascentage PharmaAscentage Pharma pipeline summaryCompoundsTargetIndicationsPreclinicalPhase IPhase IIRegistration TrialNDA ApprovalTri

5、al RegionRights RegionOlverembatinib(HQP1351)BCR-ABL/KITResistant CMLTN Ph+ALLGISTResistant CML，Ph+ALLLisaftoclax(APG-2575)Bcl-2 SelectiveBTKi treated CLL/SLL(Global-FDA)r/r CLL/SLL(China)TN CLL/SLL(Global)WMAMLMDSMMT-PLLMCLER+/HER2-BC and Solid TumorsArizomadlin(APG-115)MDM2-p53Melanoma and Solid T

6、umorsACCAML,MDSAPG-1387IAP/XIAPSolid tumors(IO Combo)PDAC+ChemoCHBPelcitoclax(APG-1252)Bcl-2/Bcl-xLNSCLC+TKISCLC+ChemoNETNHLAPG-2449FAK/ALK/ROS1NSCLC/Solid tumorsAPG-5918EED SelectiveTumors/HemoglobinopathyAPG-265PROTACs MDM2 TumorsUBX1967/1325Bcl FamilyDMESource:Company data6Ascentage Pharma2023 ac

7、hievementsCLINICAL PROGRESS Lisaftoclax to submit NDA in China in 2024 Data releases at ASCO and ASH:Olverembatinib on CML,Ph+ALL and GISTLisaftoclax on CLL/SLL,WM,MM,AML and MDSOther first-in-class productsOLVEREMBATINIBFULL APPROVAL Approved for CML-CP adult patients who are resistant and/or intol

8、erant to 1G and 2G TKIs The first and only marketed 3G BCR-ABL inhibitor in China NRDL covered since March 2023,revenue continued to ramp up3 REGISTRATIONAL TRIALS CLEARED Lisaftoclax(APG-2575)cleared for Phase 3 registrational trial for BTKi previously treated CLL/SLL by FDA Lisaftoclax(APG-2575)cl

9、eared for Phase 3 registrational trial for combo with Acala for CLL/SLL first line treatment by CDE Olverembatinib cleared for Phase 3 registrational trial for Ph+ALL first line treatment by CDESource:Company data7Ascentage PharmaBest-in-class product portfolio:targeting US$10bn+global markets Natio

10、nal Reimbursement Drug List,Represents 2G TKI 2022 sales,ponatinib 2025 forecast sales and asciminib 2028 forecast sales.Represents venetoclax 2029 forecast sales;4Not head-to-head clinical results;based on released data analysisSource:Company data,published clinical dataEffective in 1G/2G/3G TKI(in

11、cluding ponatinib and asciminib)resistant/intolerant CML patientsSafety profile suitable for long duration of treatment(DoT)Commercialized in China for CML;NRDL coveredGlobal phase 3 registrational trial for Ph+ALLOlverembatinibGlobal best-in-class 3rdgen BCR-ABL TKICommercializedBest-in-class poten

12、tial with better safety profile and dose ramp-up schedule than venetoclax4100%and 98%ORR in combination with BTKi in treatment-nave and R/R CLL/SLL patients,respectivelyGlobal phase 3 registrational trial for CLL,cleared by FDALisaftoclax2nd Bcl-2 inhibitor globallyChina launch in 2025US$6bn global

13、marketUS$4bn+global market8Ascentage Pharma3 global registrational studies ongoing targeting Ph+ALL and CLL/SLLClinically validated products,well-designed clinical trials,maximizing probability of successLisaftoclaxOlverembatinibGlobal Phase III Registrational Trial for Ph+ALLGlobal Phase III Regist

14、rational Trial for CLL/SLLPotentially the 2nd approved Bcl-2 inhibitor globallyTo become the 1st 3rdgen TKI for first line treatment of Ph+ALL in China U.S.FDA cleared for global registrational phase III trial Lisaftoclax+BTKi for patients who did not achieve CR from BTKi treatment China CDE cleared

15、 for global registrational Phase III trial Olverembatinib+chemo for newly diagnosed patients(i.e.,1stline treatment)FDASource:Company dataCDEGlobal Phase III Registrational Trial for CLL/SLL China CDE cleared for global registrational phase III trial Lisaftoclax+acalabrutinib for newly diagnosed pat

16、ients(i.e.,1stline treatment)CDE100%and 98%ORR achieved in TN and r/r CLL/SLL patients when given lisaftoclax+BTK inhibitor,respectively,based on global phase II clinical trial dataAbundant real-world patient and clinical data demonstrating efficacy and safety9Ascentage PharmaOlverembatinib received

17、 full approval for CML in China The first and only marketed 3G BCR-ABL inhibitor in China 2G TKI includes dasatinib and nilotinib,2022 sales；ponatinib 2025 forecast sales；asciminib 2028 forecast salesSource:Company dataExpanding market potential in ChinaApproved for CML-CP adult patients who are res

18、istant and/or intolerant to 1G and 2G TKIs200K+Existing CML patient pool in China20-30k Annual new casesResistance to 1G and 2G TKIs is commonGlobal best-in-class:to capture significant market sharesUS$6bn market potential and was included in Emerging Treatment Optionson 2024 NCCN Guidelines for CML

19、Olverembatinib10Ascentage PharmaNext steps:Execute Phase 3 trial for Ph+ALL and obtain FDA clearance to commence registrational trial for CMLPh+ALLGISTFor patients with TKI-resistant CML-CP or CML-AP harboring T315I mutationFor adult patients with CML-CP resistant and/or intolerant to 1st and 2nd ge

20、neration TKIsCombo with chemo in newly diagnosed patients(first-line treatment)Combo with APG-2575 for patients with r/r Ph+ALLr/r CMLMonotherapy for SDH-deficient GISTCMLApprovedRegistrationalPhase 1 and 2Approved in ChinaApproved in ChinaIn active discussion with FDA to commence global registratio

21、nal trialPatient enrollment begunStrong synergistic therapeutic valueLarge unmet medical needsOlverembatinibSource:Company data11Ascentage PharmaRegistrational phase 2 study:Efficacy versus Best Available Treatment(BAT)in TKI-resistant CML-CP patients BAT includes interferon,hydroxyurea,and homoharr

22、ingtonine or TKIs imatinib,dasatinib,and nilotinib and combinationsSource:Jiang Q,et al.(ASH 2023)Olverembatinib Demonstrates Efficacy versus Best Available Therapy in Patients with Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia in Chronic-Phase in a Registrational Randomized Phase 2 S

23、tudyOlverembatinibOlverembatinib significantly improved event-free survival(EFS)at 21.22 months,compared with BAT arm EFS at 2.86monthsOlverembatinib reduced the event risk 65%,compared with the BAT control arm12Ascentage PharmaPhase 1 5-year data on R/R CML:Durable efficacy and differentiated safet

24、y profileMCyR=major cytogenetic responses,CCyR=complete cytogenetic responses,MMR=major molecular responses Source:Jiang Q et al.(2022)A Five-Year Follow-up on Safety and Efficacy of Olverembatinib(HQP1351),a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor(TKI),in Patients with TKI-Resistan

25、t Chronic Myeloid Leukemia(CML)in China 80%and 71%of CML-CP patients achieved MCyR and CCyR,respectively Therapy responses increased over time and correlated with favorable long-term outcomes 80%of patients remain on therapy for more than 5 years Prevalence of most TRAEs decreased over timeOlveremba

26、tinib13Ascentage PharmaGlobal phase 2 study:Favorable clinical benefit and tolerability in heavily pretreated,particularly ponatinib-or asciminib-failed patientsSource:Jabbour E,et al.(ASH 2023)Update of olverembatinib(HQP1351)overcoming ponatinib and/or asciminib resistance in patients(pts)with hea

27、vily pretreated/refractory chronic myeloid leukemia(CML)and Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL)Olverembatinib56.8%53.3%42.9%42.9%37.5%37.5%0.0%10.0%20.0%30.0%40.0%50.0%60.0%TotalPonatinib resistantAsciminib resistantCCyRMMROlverembatinib monotherapy in heavily pre-t

28、reated CML-CP patients(N=44)(N=49)(N=15)(N=16)(N=7)(N=8)Olverembatinib monotherapy is efficacious and well tolerated in patients with TKI-refractory CML and Ph+ALL patientsIn ponatinib resistant CML patients,53.3%of the patients achieved CCyR and 37.5%of patients achieved MMR14Ascentage PharmaRespon

29、sen/N(%）CR/CRi45/45(100)CR43(95.6)CRi2(4.4)Early death0/45(0)CMR*after cycle 124/45(53.3)after cycle 227/45(60.0)after cycle 328/45(62.2)*The median copies of ABL1 were 645878.Olverembatinib+venetoclax and reduced-intensity chemotherapy for patients with newly diagnosed Ph+ALLMedian follow-up time:8

30、 months(range,3-14)No relapses to date Survival OutcomeHigh rates of CMR in the absence of intensive chemotherapy or immunotherapy53.3%60.0%62.2%28.9%35.6%31.1%17.8%4.4%6.7%0%20%40%60%80%100%C1D28C2D28C3D28CMRMMRLess than MMRAt the end of cycle 1,all patients achieved CR and 53.3%of patients achieve

31、d CMRWith reduced-intensity chemotherapy,the regimen was well-tolerated and safe.Most side effects were grade 1-2No patients developed relapses or deaths at the last follow-upSource:Gong X,et al.(ASH 2023)Olverembatinib Combined With Venetoclax and Reduced-Intensity Chemotherapy for Patients with Ne

32、wly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia:Early results from a phase II study;Olverembatinib15Ascentage PharmaOlverembatinib+chemo for 1L Ph+ALLSources:G.Xu,et al.(2023),Combination of Olverembatinib and VP Regimen As First-Line Therapy for Adult Patients with Phila

33、delphia Chromosome-Positive Acute Lymphoblastic LeukemiaKaibo Zhu,et al.(2023),Frontline Combination of Olverembatinib and PDT-ALL-2016 Pediatric Inspired Protocol in Philadelphia Chromosome-Positive Acute Lymphoblastic LeukemiaCombination of olverembatinib and VP regimen as first-line therapy for a

34、dult Ph+ALL patientsOlverembatinib100%overall response,including 96%CR and 4%CRpTotal CMR rate of 84%at any time.CMR rate was 36%,76%and 82.6%at 4 weeks,8 weeks and 12 weeks respectivelyFrontline combination of olverembatinib and pdt-all-2016 pediatric inspired protocol in Ph+ALL patientsAll 13 enro

35、lled patients achieved CR,representing an ORR of 100%Promising efficacy results and acceptable safety data,indicating that this strategy may become another treatment option in frontline Ph+ALL 15.4%38.5%61.3%84.6%0%20%40%60%80%100%Day 14Day 30Day 60Day 90Molecular responseCMRNon-CMR16Ascentage Pharm

36、aOlverembatinib+blinatumomab for Ph+/Ph-like ALL patientsOlverembatinibSource:Zhang T,et al.(2023)Frontline combination of 3rd generation TKI olverembatinib and blinatumomab for Ph+/Ph-like ALL patientsFewer cardiovascular adverse events that required discontinuation of treatment compared to ponatin

37、ib were observedPotential to become a new chemo-free,standard of care in the frontline treatment of Ph+/Ph-like ALLAll patients achieved CR after one cycle of treatment and CMR within 3 months of treatment100%6-month OS rate and 87.5%6-month EFS rate17Ascentage PharmaMVHO(liposome mitoxantrone,venet

38、oclax,homo-harringtonine and olverembatinib)therapy in pediatric patients with R/R AMLAfter cycle one,ORR(CR+CRi and PR)was 94.4%,and the remission rate(CR+CRi)was 72.2%For 6 patients with relapsed AML,the ORR and one cycle remission rate was 100%and 66.7%,respectivelySource:Hu W.,et al.(ASH 2023)Co

39、mbination of Liposomal Mitoxantrone,Venetoclax,Homoharringtonine,and Olverembatinib(HQP1351)(MVHO)in Pediatric Patients with Refractory or Relapsed Acute Myeloid Leukemia(AML):Case Series.Other citations please see appendixCR55.6%CRi 16.7%PR22.2%NR5.6%1 cycle response18 patients:9 boy and 9 girlsOlv

40、erembatinibMVHO therapy was effective and reasonably well tolerated in pediatric patients with R/R AML,suggesting that it may comprise a suitable first-line treatment option for pediatric AML patients18Ascentage PharmaOlverembatinib:global best-in-class 3rd generation BCR-ABL TKI SafetyEffective in

41、other 3G TKI failed patients Hematologic adverse events were mostly mild and manageable TRAE decreases over time 80%of patients continue treatment after 5 years of treatment Effective and durable anti-leukemic effects in CML and Ph+ALL patients including those harboring T315I mutation 80%of CML-CP p

42、atients achieved MCyR4 Demonstrated efficacy and safety profile in adult and pediatric Ph+ALL patients with potential to be first-line treatment Effective in CML patients who are resistant to ponatinib and asciminib-58%CCyR in ponatinib-failed CML patients Stronger inhibition than other TKIs of kina

43、se activity of many mutations orcompound mutations Analysis based on published data,not head-to-head comparison trials;Based on preliminary data(Jabbour E,et al.(ASH 2023)Update of olverembatinib(HQP1351)overcoming ponatinib and/or asciminib resistance in patients(pts)with heavily pretreated/refract

44、ory chronic myeloid leukemia(CML)and Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL);Based on the results of in vitro studies;4Jiang Q et al.(2022)A Five-Year Follow-up on Safety and Efficacy of Olverembatinib(HQP1351),a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor(

45、TKI),in Patients with TKI-Resistant Chronic Myeloid Leukemia(CML)in ChinaSource:company data and public literatureEfficacySafetyOlverembatinib19Ascentage PharmaLisaftoclax to launch in China in 2025FDA clearance for phase 3 registrational trialGlobally the 2nd Bcl-2 selective inhibitor entering glob

46、al registrational clinical trialSource:Company data Venetoclax 2029 forecast salesChina launch in 2025 for r/r CLLTo submit NDA in 2024 and to be approved in 2025Global registrational Ph3 for CLLFDA clearedLisaftoclax+BTKi,adds-on clinical trials for patients who do not achieveCR from BTKi treatment

47、Global registrational Ph3 for 1L CLLChina CDE clearedLisaftoclax+Acalabrutinib for newly diagnosed patientsOther indicationsPh 1/2 trials for AML,MM,MDS,WM,etc.Synergisitic combination with olverembatinib and APG-115US$4bn+Global marketopportunityLisaftoclax20Ascentage PharmaUnique and differentiate

48、d clinical designDaily Dose Ramp-up:More convenient to HCPs&patients,lower TLS risks and faster to achieve therapeutic dose Lisaftoclax and BTKi combination therapy can begin quickly(Cycle 1 Day 8)Source:Davids M et al.(2022)Lisaftoclax(APG-2575)Safety and Activity As Monotherapy or Combined with Ac

49、alabrutinib or Rituximab in Patients(pts)with Treatment-Nave,Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma(R/R CLL/SLL):Initial Data from a Phase 2 Global Study,64th ASH annual meetingLisaftoclax+Ritux or AcalaNo BTKi or mAb Lead-in2050100200400X target doseD1D2D3D4D

50、5Daily Ramp-upC1D1-C1D8 at TargetLisaftoclax continued at target dose from C1D1Combination starts Cycle 1 Day 82 weeksLisaftoclax21Ascentage PharmamPFS was 18.53 monthsmOS not reached30-month OS rate was 86.3%Best overall responsesUpdated data from 14-month follow-up in R/R CLL patientsMedian time t

51、o first response:2.07 monthsSource:Updated Efficacy and Safety Results of Lisaftoclax(APG-2575)in Patients(pts)with Heavily Pretreated Chronic Lymphocytic Leukemia(CLL):Pooled Analyses of Two Clinical TrialsFavorable tolerability and efficacy in R/R CLL patients,including heavily pretreated and BTKi

52、-treated patientsNo significant new or unmanageable safety findings were observedLisaftoclax22Ascentage PharmaLisaftoclax+Acalabrutinib(N=74)%SPD lymph nodeORRMonotherapy(n=43)67%Lisaftoclax+Rituximab(n=34)79%Lisaftoclax+Acalabrutinib(TN)(n=16)100%Lisaftoclax+Acalabrutinib(R/R)(n=57)98%Lisaftoclax+A

53、calabrutinib(R/R)-BTKi nave(n=46)100%Lisaftoclax+Acalabrutinib(R/R)-venetoclax resistant(n=4)75%Global phase 2 study:Lisaftoclax efficacy on CLLSource:Davids M et al.(2022)Lisaftoclax(APG-2575)Safety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients(pts)with Treatme

54、nt-Nave,Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma(R/R CLL/SLL):Initial Data from a Phase 2 Global Study,64th ASH annual meetingLisaftoclax alone or combined with acalabrutinib or rituximab had favorable clinical activity in treatment-nave patients and patients wi

55、th R/R CLL/SLLLisaftoclax23Ascentage PharmaGlobal phase 2 study:Lisaftoclax safety profile in CLL patients Source:Davids M et al.(2022)Lisaftoclax(APG-2575)Safety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients(pts)with Treatment-Nave,Relapsed or Refractory Chroni

56、c Lymphocytic Leukemia/Small Lymphocytic Lymphoma(R/R CLL/SLL):Initial Data from a Phase 2 Global Study,64th ASH annual meetingManageable safety profile as a single agent or in combination with rituximab or with acalabrutinib with initial daily dose ramp-up of Lisaftoclax812.815.6131728.296.41011.51

57、.323055HematuriaHeadacheThrombocytopeniaAnemiaCovid-19 infectionDiarrheaNeutropeniaReported Treatment Emergent AEs in 10%of pts(n=79)Grade 1 and 2Grade 3Grade 4Lisaftoclax+acalabrutinibNo DLTs observedMTD has not been reachedNo DDI in combination with BTKiLow TLS(n=4;2 clinical/2 laborato

58、ry)No treatment-related discontinuation or deathsLisaftoclax24Ascentage PharmaDemonstrated preliminary anti-tumor activity and favorable safety profile in R/R MM or AL amyloidosis patientsSource:Ailawadhi S,et al.(ASH 2023)First Report on the Effects of Lisaftoclax(APG-2575)in Combination with Novel

59、 Therapeutic Regimens in Patients with Relapsed or Refractory Multiple Myeloma(R/R MM)or Immunoglobulin Light-Chain(Amyloid Light-Chain AL)AmyloidosisLisaftoclaxA total of 7 patients experienced grade 3 lisaftoclax-related TEAEs,including:neutropenia(10.0%)febrile neutropenia(3.3%)iron deficiency an

60、emia(3.3%)thrombocytopenia(3.3%)prolonged electrocardiogram QT interval(3.3%)acute kidney injury(3.3%)Two patients experienced lisaftoclax-related serious TEAEs,including 1 acute kidney injury and 1 febrile neutropenia(3.3%each).30 patients(with a median of 4 lines of prior therapy)were enrolled in

61、this multi-center trialFavorable safety profile;grade 3 or 4 AEs were minimal and toleratedBest overall response,n(%)Arm AN=21Arm BN=2Arm CN=5PatientsR/R MMR/R MMAL amyloidosisTreatmentLisaftoclax+pomalidomide&dexamethasoneLisaftoclax+daratumumab,lenalidomide&dexamethasoneLisaftoclax+pomalidomide&de

62、xamethasoneVGPR6(28.6)1(50.0)3(60.0)PR8(38.1)1(50.0)0SD7(33.3)01(20.0)ORR(VGPR+PR)14(66.7)2(100.0)3(60.0)NR001(20.0)VGFR,very good partial response;PR,partial response;SD,stable disease;ORR,overall response rate;NR,no response25Ascentage PharmaEncouraging clinical efficacy and tolerability in AML an

63、d MDS patientsLisaftoclax+azacitidine(AZA)resulted in 75%and 71%ORR in R/R AML and TN older/unfit AML patients,respectivelyNo TLS was reported during the study,and dose-limiting toxicities were observed in 1 patientAll 13 patients who received lisaftoclax monotherapy experienced TEAEs,of which all w

64、ere grade 3;4(30.8%)patients experienced SAEs.In patients treated with lisaftoclax combined with HHT,12(85.7%)experienced TEAEs,of which all were grade 3;2(14.3%)were SAEs.Of the 75 evaluable patients treated with lisaftoclax combined with AZA,100%experienced TEAEs,including 55(73.3%)who experienced

65、 grade 3 TEAEs and 18(24.0%)SAEs.Favorable tolerability as monotherapy and when combined with AZA or HHTTherapyDiagnosis#evaluable ptsORR,n(%)CR/CRi,n(%)ALisaftoclax+LD-HHTR/R AML30.0%0.0%BLisaftoclax+SD-HHTR/R AML875.0%75.0%CLisaftoclax+AZA R/R AML 3675.0%44.4%ELisaftoclax+AZATN,older/unfit AML2171

66、.4%47.6%DLisaftoclax+AZA HR-MDS1070.0%60.0%In AML,ORR=CR+CRi+MLFS+PR;in MDS,ORR=CR+mCR+PR.Including 1 CMML,2 MPAL,and 1 BPDCNSource:Wang H,et al.(ASH 2023)Safety and Efficacy of Lisaftoclax(APG-2575),a Novel BCL-2 Inhibitor(BCL-2i),in Relapsed or Refractory(R/R)or Treatment-Nave(TN)Patients(Pts)with

67、 Acute Myeloid Leukemia(AML),Myelodysplastic Syndrome(MDS),or Other Myeloid NeoplasmsLisaftoclaxIn R/R AML patients treated with lisaftoclax and azacitidine,the median time to CR/CRi/MLFS was 1.25 months;and median PFS was 10.22 monthsAs of July 19,2023,115 pts were enrolled.26Ascentage PharmaLisaft

68、oclax:potential best-in-class Bcl-2 inhibitor globallyImproved benefit-risk and superior overall convenience 800+subjects enrolled into lisaftoclax studies,including CLL,AML,MM,MCL,T-PLL,WM,MDS patients 400 CLL subjects treated with lisaftoclaxdemonstrating safety and efficacy 98%ORR in combination

69、with BTKi in r/r CLL/SLL patients 100%ORR in combination with BTKi in treatment-nave CLL/SLL patients Clinical benefit shown in subjects who progressed on venetoclax and BTKi-resistant patients Much lower clinical TLS vs venetoclax Well tolerated-No DLTs observed,MTD not reached Lower incidence of n

70、eutropenia and thrombocytopenia and less infections vs venetoclax Daily dose ramp-up vsweekly dose ramp-up required by venetoclax Highly convenient to patients and healthcare systemClinical validationEfficacySafetyUnique clinical profileSource:Company data;Davids M et al.(2022)Lisaftoclax(APG-2575)S

71、afety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients(pts)with Treatment-Nave,Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma(R/R CLL/SLL):Initial Data from a Phase 2 Global Study,64th ASH annual meetingNote:analysis based on publish

72、ed data,not head-to-head comparison trials No DDI observed with BTKi Achieving target treatment dose and BTK combination in as quickly as 1 weekLisaftoclax27Ascentage PharmaFirst-in-class pipeline:multiple shots-on-goal in untapped marketsAPG-5918EED inhibitorAPG-115MDM2-P53 inhibitorAPG-1252Bcl-2/B

73、cl-XL inhibitorAPG-2449ALK/FAK/ROS1 inhibitorAPG-1387IAP inhibitorGlobal First-in-classConducting clinical studies in melanoma,MPNST,AML,CMML,MDS,liposarcoma and pediatric neuroblastoma and solid tumors Potential synergies with APG-2575 to achieve“synthetic lethality”205 patients treated:SCLC,NSCLC,

74、neuroendocrine tumor,and non-Hodgkins lymphoma260 patients treated:advanced solid tumors and chronic HBV infectionGood safety and tolerability and preliminary efficacy in ALK-positive NSCLC patientsPotent antiproliferative activity in cancer cell linesPotential for treating beta hemoglobinopathy,inc

75、luding sickle cell disease and-thalassemia MPNST:malignant peripheral nerve sheath tumor;CMML:chronic myelomonocytic leukemia Source:Company data28Ascentage PharmaAlrizomadlin(APG-115)Product highlightsIndications targeted by Clinical Development Melanomas Malignant Peripheral Nerve Sheath Tumor(MPN

76、ST)AML Chronic myelomonocytic leukemia(CMML)MDS Salivary gland cancer Liposarcoma(LPS)Neuroblastoma or other solid tumors Orally bioavailable,highly selective,small molecule inhibitor targeting MDM2-p53.Designed to restore the activation of p53 tumor suppressor activity by blocking the MDM2-p53 inte

77、raction PPI(protein-protein interaction)6 orphan drug designations(ODDs)from FDA 2 rare pediatric disease designations(RPDs)from FDA28MDM2-p53 inhibitorFirst-in-Class potentialAscentage PharmaSource:Company data29Ascentage PharmaAlrizomadlin(APG-115)in combination with lisaftoclax has promising pote

78、ntial in the treatment of pediatric tumorsClinical NeedsMechanismProgress Update Pediatric tumors are the leading cause of death in children The prognosis for these tumors is poor,especially in patients with recurrence and metastasis Phase 1 clinical study of the safety,tolerability,PK and efficacy

79、of APG-115 alone or in combination with lisaftoclax is ongoing The first dose cohort of APG-115 monotherapy for children with solid tumors did not reach DLT and was well tolerated Compared with adult tumors,pediatric solid tumors are characterized by low TP53 mutation frequency and high MDM2 amplifi

80、cation frequency APG-115 in combination withlisaftoclax simultaneously target BCL-2,BCL-xL and MCL-1 and synergistically trigger apoptosis in cancer cellsTargeting the MDM2-P53 and BCL-2 apoptosis pathways simultaneously can achieve synthetic lethalitySource:company data30Ascentage PharmaALK/FAK/ROS

81、1triple ligase kinase inhibitorAPG-2449Potentially the 1stALK/FAK/ROS1 triple inhibitor globallyIndications targeted in clinical development NSCLCSelected for poster discussion at 2023 ASCOOvarian cancer30Source:Fang,D.D.,Tao,R.,Wang,G.et al.Discovery of a novel ALK/ROS1/FAK inhibitor,APG-2449,in pr

82、eclinical non-small cell lung cancer and ovarian cancer models.BMC Cancer 22,752(2022).https:/doi.org/10.1186/s12885-022-09799-4 Innovative drug aiming at high FAK-expressing tumors and ALK/ROS1 fusion mutant NSCLC Through(1)effective ALK/ROS1 inhibitor and(2)FAK inhibitor in combination with chemot

83、herapy or targeted therapies,effectively overcoming resistance Simultaneous blocking of FAK and ALK can significantly improve efficacy and overcome resistance to ALK single-target inhibitors Effective for intracranial lesions in patients with brain metastases Well tolerated;no obvious neurotoxicity

84、occursAscentage Pharma31Ascentage PharmaNovel FAK/ALK inhibitor APG-2449 could overcome ALK resistance in NSCLC In TKI-nave NSCLC and ROS1+treatment-nave patients,ORR was 78.6%and 70.6%,respectively Among 28 ALK+NSCLC patients resistant to 2G ALK TKI,8 achieved PR,ORR 28.6%In 13 brain metastases pat

85、ients resistant to 2G ALK TKI,8 achieved intracranial PRs,intracranial ORR is 61.5%Compared to baseline,those who experienced PR showed greater reduction in phosphorylated FAK(pFAK)levels,patients with higher FAK expression at baseline were likely to achieve deeper clinical responses to APG-2449 APG

86、-2449 was well tolerated.There was no neurotoxicity in 136 NSCLC patients receiving APG-2449Clinical resultsConclusion APG-2449 showed a favorable preliminary safety profile and antitumor activity in patients with NSCLC FAK inhibition may be a novel approach to overcome ALK resistance in NSCLC patie

87、nts resistant to 2G ALK inhibitorsSafetyAny grade Grade 3 Population136136Subjects with at least one TRAE,n(%)123(90.4)19(14.0)Preferred term,n(%)Increased blood creatinine63(46.3)0Increased ALT55(40.4)4(2.9)Increased AST45(33.1)1(0.7)Nausea37(27.2)1(0.7)Vomiting31(22.8)2(1.5)Decreased leukocyte cou

88、nt30(22.1)1(0.7)Diarrhea29(21.3)0Decreased neutrophil count24(17.6)1(0.7)Rash17(12.5)0EfficacyBest tumor response(%)in patients with 2nd gen TKI resistant ALK+NSCLCBest tumor response(%)in patients with TKI-nave ALK/ROS1+NSCLCpFAK fold change from baseline in PBMCs collected from pts with NSCLC post

89、 treatment with APG-2449 at different doses.Best tumor response vs.pFAK expression at the tumor tissues collected from ALK-TKI resistant 8 pts with NSCLC,who treated with APG-2449 at RP2D.Best tumor response(%)of brain metastases observed in patients with 2nd gen TKI resistant ALK+NSCLC C1D1-0hC1D28

90、-24h0.00.51.01.5pFAK in PBMCFold change from baselinePR(n=11)PD(n=7)SD(n=30)Source：Yuxiang Ma,et al.(2023),FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors32Ascentage PharmaProduct highlightsIndicat

91、ions targeted in clinical development Restore apoptosis through dual inhibition of the Bcl-2 and Bcl-xL proteins Novel combination in solid tumors and hematologic malignancies ODD received from FDA for the treatment of SCLC A total of 205 patients have been treated with pelcitoclax as monotherapy or

92、 in combination with other anti-tumor agentsBcl-2/Bcl-xL inhibitorPelcitoclax(APG-1252)32SCLCNSCLCPresented in mini-oral format at 2023 ESMONeuroendocrine tumor(NET)Non-Hodgkins lymphoma(NHL)Ascentage PharmaSource:Company data33Ascentage PharmaPelcitoclax plus osimertinib is well tolerated,and preli

93、minary efficacy observed in EGFR-mutant NSCLC patientsSource:Y.Ma,et al.(2023 ESMO),Updated study results of pelcitoclax(APG-1252)combined with osimertinib in patients(pts)with EGFR-mutant non-small cell lung cancer(NSCLC)Best tumor response1G TKI resistant n=73G TKI resistant n=28TKI-nave n=26Overa

94、ll n=61ORR71.4%10.7%80.8%47.5%PR71.4%10.7%80.8%47.5%SD28.6%64.3%15.4%39.3%PD0.0%25.0%3.8%13.1%DCR100.0%75.0%96.2%86.9%Patients with high Bcl-xL expression experienced better efficacy,with longer PFS,in the 3G TKI resistant groupPelcitoclax plus osimertinib may improve clinical outcomes of patients w

95、ith NSCLC harboring TP53-and EGFR-positive mutations34Ascentage Pharma Completed phase I study of monotherapy in treatment-naive CHB patients Conducting phase II clinical trial of APG-1387 combined with entecavir in CHB patients,compared to entecavir monotherapyAn Antagonist of IAP/XIAP(SMAC Mimetic

96、)DimmerAPG-1387Chronic HBV infection34 Completed a phase I clinical trial in the US for the combination of APG-1387 and pembrolizumab in the treatment of solid tumors Conducting phase Ib/II clinical trial of APG-1387 in combination with toripalimab in solid tumors Conducting phase I/II study to inve

97、stigate the combination of APG-1387 with chemotherapy,nab-paclitaxel and gemcitabine in advanced pancreatic cancer patientsSolid tumorsAscentage PharmaSource:Company data35Ascentage Pharma APG-5918 binds to the H3K27me3-interacting EED domain,resulting in a conformational change in the EED H3K27me3

98、binding pocket,and prevents EED from interacting with histone methyltransferase EZH2 APG-5918 has potent in vitro and in vivo targeted pharmacological activity in cancer cell lines and xenograft modelsEED inhibitorAPG-5918Chinas first EED inhibitor to enter clinical trials35Indications targeted in c

99、linical development Solid tumors and hematologic malignanciesAnemiaSLEAscentage PharmaSource:Company data36Ascentage PharmaKey catalysts in 2024Lisaftoclax NDALisaftoclax to file NDA for R/R CLL/SLL in ChinaOlverembatinib FDA clearance for registrational trialOlverembatinib to obtain FDA clearance f

100、or phase 3 registrational trial for CMLExecution of global registrational trialsLisaftoclax adds-on clinical trial,CLL patients previously treated with BTKiLisaftoclax+acalabrutinib-1L CLLOlverembatinib+Reduced-Intensity Chemotherapy-1L Ph+ALLExpanding NRDL coverageNRDL negotiation to cover olveremb

101、atinibs expanded indicationsSource:Company data37Ascentage PharmaAddressing clinical needs through innovative therapeutics:Substantial global opportunitiesTwin product engines driving salesLisaftoclax to be approved in ChinaOlverembatinib NRDL coverage to be expandedMore pipeline products to enter l

102、ate-stage clinical trialsOlverembatinib full approved and NRDL coveredOlverembatinib full approval for CML in China,NRDL coveredInitiated olverembatinib and lisaftoclax global registrational trials for Ph+ALL and CLL/SLL,respectivelyLeading international biopharma with multiple blockbuster productsL

103、isaftoclax and olverembatinib to enter global markets,continue to expand indications to cover all major hematological malignanciesFund future product development with ample cash flowsFirst proprietary product approvedOlverembatinib approved in ChinaRMB200m sales in the first year of launchSuzhou R&D

104、 HQ and manufacturing facilities operational2026-beyond2025202420232021-2022China salesGlobal salesSource:Company dataExecuting global registrational trials Lisaftoclax to submit NDA in ChinaOlverembatinib to commence global registrational trial for CMLLisaftoclax to initiate global registrational t

105、rial for AML/MDS/MM38Ascentage PharmaPatient-Centric Innovation|Global Breakthrough TherapiesFocus on global BIC and FIC products with unique and valuable advantagesUnique clinical advantages establish commercial value,driving global market penetrationProducts strategically target the US$10bn+global

106、 blood cancer marketProducts cover all major hematological malignancies,with each product entering billion+USD marketAccelerating growth of olverembatinib sales Propelled by increasing prescriptions under NRDL coverageExpansion of indication to benefit more patientsGlobal leading R&D team possesses

107、comprehensive capabilitiesSeamlessly executing the entire R&D lifecycle from discovery to registrationOlverembatinib commercialized;Lisaftoclax in global registrational Phase III trialKey products have begun global pivotal trials.International sales to be generated in the foreseeable futureStrong IP

108、 position468 issued patents and 1,200+applications globallySource:Company data39Ascentage PharmaAscentage PharmaPatient-Centric Innovation;Global Breakthrough TherapiesContact us:Major HematologyMalignancy+AnemiaCMLALLCLLAMLMDSMM700 King Farm Blvd.,Suite 510 Rockville,MD 20850,USALisaftoclaxBcl-2 Selective InhibitorAlrizomadlinMDM2-p53 IOlverembatinibSuite 30.03,Level 30,133 Castlereagh Street,Sydney NSW 2000 Australia68 Xinqing Road,Suzhou Industrial Park,Suzhou,Jiangsu,P.R.C