1、A Multi-Modality ProbodyTherapeutic Pipeline to Address Major Unmet Needs in OncologyJanuary 2024Forward-Looking StatementsThis presentation may contain projections and other forward-looking statements regarding future events.All statements other than statements of historical facts contained in this

2、 presentation,including statements regarding our future financial condition,technology platform,development strategy,prospective products,preclinical and clinical pipeline and milestones,regulatory objectives,expected payments from and outcomes of collaborations,and likelihood of success,are forward

3、-looking statements.Such statements are predictions only and involve known and unknown risks,uncertainties and other important factors that may cause our actual results,performance or achievements to be materially different from any future results,performance or achievements expressed or implied by

4、the forward-looking statements.These risks and uncertainties include,among others,the costs,timing and results of preclinical studies and clinical trials and other development activities;the uncertainties inherent in the initiation and enrollment of clinical trials;the uncertainties associated with

5、the COVD-19 pandemic;expectations of expanding on-going clinical trials;availability and timing of data from clinical trials;the unpredictability of the duration and results of regulatory review;market acceptance for approved products and innovative therapeutic treatments;competition;the potential n

6、ot to receive partnership milestone,profit sharing or royalty payments;the possible impairment of or inability to obtain intellectual property rights;and possible safety or efficacy concerns,general business,financial and accounting risks and litigation.Because forward-looking statements are inheren

7、tly subject to risks and uncertainties,some of which cannot be predicted or quantified and some of which are beyond our control,you should not rely on these forward-looking statements as predictions of future events.More information concerning us and such risks and uncertainties is available on our

8、website and in our press releases and in our public filings with the U.S.Securities and Exchange Commission.We are providing this information as of its date and do not undertake any obligation to update or revise it,whether as a result of new information,future events or circumstances or otherwise.A

9、dditional information may be available in press releases or other public announcements and public filings made after the date of this presentation.This presentation concerns products that have not yet been approved for marketing by the U.S.Food and Drug Administration(FDA).No representation is made

10、as to their safety or effectiveness for the purposes for which they are being investigated.2Company SnapshotAddressing Major Unmet Need in Oncology3 3Probody Platform:Unique antibody engineering strategy for tumor localization and enhancement of therapeutic indexPipeline:15 Probody programs in multi

11、ple therapeutic modalities;4 clinical-stage molecules,3 with retained commercial rightsLead Programs:CX-904(EGFR-CD3),CX-2051(EpCAM ADC),CX-801(IFN-b),BMS-986288(CTLA-4-NF)Partners:Bristol Myers Squibb,Amgen,Astellas,Regeneron,ModernaFinancials:$194M cash balance as of Q3 2023 with cash runway to th

12、e 2nd half of 2025,excluding any potential milestones or new business developmentOrganization:120 employees;seasoned executive team with 200 years of collective biotech experience;integrated R&D capabilities to support wholly-owned and collaboration programsSouth San Francisco,CAEGFREpCAMCytomX Prod

13、uct Design Strategy Leverages the ProbodyPlatformOptimized Selection of Target,Prodomain and Effector Function4Targets with validated anti-tumor efficacy that need localization to unlock potential Matching“effector”to target to maximize anti-cancer activityOptimized tuning of masks and protease subs

14、trates to maximize potential therapeutic indexTARGET EGFR EpCAM IFN-CTLA-4 TCE ADC Cytokine FcPRODOMAINEFFECTORCytomX Pipeline Addresses Multiple Large Oncology IndicationsMulti-modality,Tumor-Localized ProbodyTherapeutics5Utilize EGFR expression as an“address”to localize T-cells to solid tumors Inc

15、rease therapeutic index for EpCAM through tumor localization and tailored Topo-1 linker-payload Harness IFN2b activity to preferentially impact the tumor microenvironment CX-904(EGFRxCD3)CX-2051(EpCAM)CX-801(IFN2b)Substrate linkersMasksLinker/payloadSubstrate linkersMasksSubstrate linkersMasksProbod

16、y T-Cell EngagerProbody ADCProbody CytokineDesigned to be a cornerstone of combination therapyEpCAM+tumors including CRC Broad applicability in EGFR+tumors regardless of mutational statusOPPORTUNITYOPPORTUNITYOPPORTUNITYProgramEffectorIndicationsPreclinicalPhase 1Phase 22024 MilestonesCX-904(EGFR)T-

17、Cell Engager(CD3)EGFR+Solid tumorsPhase 1a DataDecision to Expand to Phase 1bCX-2051*(EpCAM)ADC Topo1 PayloadEpCAM+Tumors incl.CRCIND Filed in Dec 23Phase 1 initiationCX-801(IFN2b)CytokineIFN2bSolid Tumors incl.Melanoma,Renal,HNSCCIND Filed in Dec 23Phase 1 initiationBMS-986288(CTLA-4)Non-Fucosylate

18、dCTLA-4Solid TumorsPOC Trials in NSCLC&MSS CRC OngoingData Anticipated in 24 CytomX Multi-Modality Clinical Pipeline of ProbodyTherapeuticsCompany Entering a Milestone-Rich Period Starting in 20246*Licensed from ImmunogenWholly-OwnedWholly-OwnedMilestones&Royalties to CytomXShared U.S.Commercial Rig

19、htsCX-904:Conditionally Activated ProbodyT-cell Engager Targeting EGFR and CD3Landscape for T-Cell Engagers(TCEs)for Solid TumorsIncreasing Clinical Validation,Major R&D Investment Across the Industry8Tebentafusp in Uveal MelanomaTarlatamab in SCLCSolid Tumor TCEs are a Key Focus Area for Global Onc

20、ology Leaders Hassel et al.NEJM.2023Tarlatamab-10 mg(N=91)M.-J.Ahn et al.NEJM.2023Tarlatamab 100 mg(N=70)DLL3xCD3DLL3xCD3+detectable DLL3-undetectable DLL3X not evaluable/available*Owned by Immunocore*CytomX Probody T-cell Engagers are Designed to Address Key Limitations of Conventional TCEs in Soli

21、d Tumors 9Probody T-Cell Engagers Conventional T-cell engagers are highly potent,but their use in solid tumors is significantly limited by:Systemic toxicities such as CRS and ICANS On-target,off-tumor toxicity Conditionally activated Probody T-cell engagers are designed to retain potent anti-tumor a

22、ctivity while having less systemic toxicities CytomX has a broad pipeline of partnered Probody TCE programs with retained commercial rights on select programs,including CX-904Substrate linkersMasksEGFRCD3TCE CD3 Potent anti-tumor activity across hematological malignancies Growing validation in solid

23、 tumorsCX-904CX-904:Optimized DesignConditionally Activated ProbodyT-Cell Engager Targeting EGFR and CD310Optimized Masking Customized masks and protease cleavable linkers for EGFR and CD3 binding domains 60-fold increase in MTD preclinically for Probody TCE vs.unmasked EGFR TCEValidated,High Potent

24、ial Target Broad expression across solid tumors Clinical validation across multiple modalities Limited therapeutic index(e.g.,skin rash,gastrointestinal toxicities)CD3EGFRPRODOMAINEFFECTORTARGETEFFECTORCX-904 Broad Market Opportunity Across Multiple Indications 112023 US Metastatic,Addressable Patie

25、ntsColorectal100,000 PatientsSq.,Adeno NSCLC210,000 PatientsEsophageal38,000 Patients%of Patients with EGFR+Tumors(TPM 8+)98%95%99%90%88%450,000 EGFR+Addressable PatientsGEJ/Gastric 30,000HNSCC40,000 PatientsPancreatic65,00093%Source:TPM 8+equivalent to 2+by IHC(internal prevalence study);TPM=Transc

26、ripts per million;TCGA RNA Seq Data;Epidemiology data from DRG CX-904 Progress and 2024 Milestones Phase 1a ongoing in patients with advanced solid tumors with known EGFR expression Backfilling of certain dose escalation cohorts initiated in Q4 2023 Initial Phase 1a data anticipated in the 2nd half

27、of 2024 Potential decision(to be taken with Amgen)to initiate Phase 1b expansion cohorts in specific EGFR positive tumor types is anticipated in 2024Study CTMX-904-101*Phase 1a:Dose EscalationPhase 1b:Dose ExpansionDose Escalation:Cohort BackfillsSingle patient cohorts followed by“3+3”designExplore

28、multiple doses to further assess safety and PK for Phase 1b/2 dose(s)Dose TBDRecommended Ph 2 dose(s)Specific EGFR+tumor cohort expansionsDose TBDDose TBD*Illustrative Example12CX-2051:Conditionally Activated ProbodyADC Targeting EpCAMAntibody Drug Conjugates,a Growing and Potent Modality in Solid a

29、nd Liquid TumorsApproved Solid Tumor ADCs14Approved Liquid Tumor ADCsTF1HER2TROP2HER2Nectin4FR CD79bCD19CD30CD22CD33EpCAM Has Been Clinically Validated But Not as a Systemic Therapy 15AssetCompanyMOAStageStatusSolitomabAmgenEpCAM x CD3 BiTEPh 1GI tox reported;discontinuedING-1XOMAEpCAM mAbPh 1Pancre

30、atitis reported;discontinued3622W94GSKEpCAMmAbPh 1Pancreatitis reported;discontinued VicineumTM fusion protein:anti-EpCAM scFv linked to a truncated form of Pseudomonas exotoxin A Delivered by intravesical administration 40%3-month complete response in bladder cancer Systemic EpCAM approaches have s

31、ignificant toxicity concernsLocally administered EpCAM therapies have been validated in the clinic Removab(catumaxomab):EpCAM x CD3 bispecific Delivered by intraperitoneal infusion Approved for treatment of malignant ascites(but later withdrawn for commercial reasons)Sesen BioInsys TherapeuticsTailo

32、red Payload Next-gen camptothecin analog(Topo-1)linker-payload,DAR8 Optimized to drive bystander activity Payload known efficacy in EpCAM+tumor typesCX-2051:Optimized DesignConditionally Activated EpCAM ProbodyADC with Topoisomerase-1 Linker-Payload16Program licensed fromEPCAMCX-2051Cancer CellOptim

33、ized Masking Protease-cleavable substrate with broad cleavability across multiple tumors Peptide mask with masking efficiency 100 x by ELISAValidated,High Potential Target Broad expression profile Proven localized anti-cancer activity Limited therapeutic index that requires maskingTARGETEFFECTORPROD

34、OMAINPreclinical Profile of CX-2051 Shows DXd-like Potency with Substantially Improved Tolerability Compared to the Unmasked ADC17Tolerability in Cyno Toxicology StudyVehicleCX-2051 6 mk/kgEpCAM-DXd 6 mk/kgAnti-Tumor Xenograft Activity in CRC ModelSource:14th Annual World ADC Conference,October 2023

35、 CX-2051 Broad Opportunity Across Multiple EpCAM+Indications 182023 US Metastatic,Addressable PatientsColorectal106,000 PatientsNSCLC85,000 PatientsGastric 28,000 PatientsOvarian 50,000 PatientsEndometrial 26,000 Patients%of Patients with EpCAM+Tumors(IHC 2+)30%80%95%92%80%295,000 EpCAM+Addressable

36、PatientsSource:DRG Epidemiology&Forecast Dashboards,2021 2023CX-2051 Phase 1 Strategy Designed to Rapidly Demonstrate Proof of Concept in EpCAM Expressing Tumors19Part 1:Dose EscalationPart 2:Dose ExpansionAdvanced/Metastatic CRC*EpCAM+Cancer#2CX-2051 MTD/MADCX-2051 MTD/MADCX-2051Starting DoseDose E

37、scalation per BOIN DesignCX-2051 MTD/MADIndication-Specific Expansion CohortsBOIN=Bayesian optimal interval;MAD=Maximum assessed dose;MTD=Maximum tolerated dose*ExampleAdvanced/metastatic solid tumors with known/documented EpCAM expressionEpCAM+Cancer#3Determine dose(s)for indication specific expans

38、ions;assess for early evidence of anti-tumor activity Evaluate safety and tolerability and efficacy in multiple EpCAM+tumorsCX-2051 Cohort 2CX-2051 Cohort 3CX-2051 Cohort 5Illustrative ExampleCX-2051 Cohort 4CX-801:Conditionally Activated Probody Cytokine,IFN-2bImmuno-oncology Treatment LandscapeSig

39、nificant Unmet Need Remains,Creating Major Opportunity for CX-801CONFIDENTIAL21IO Sensitive TumorsIndications where PD-(L)1s are Approved10 50%Source:1Sun et al.Biomarker Research.2020;2DFCI and NCI Data CommonsEndometrial&CervicalGastric/GEJ&EsophagealTNBCMelanoma&Non-MelanomaHNSCCRenalNSCLC&SCLCLi

40、verBladderIO Resistant TumorsInsensitive to PD-(L)1s/CPIMSI-H/Pan TumorOverall Response Rates with Single-Agent PD-(L)11,2HR+/-BreastMSS CRCProstatePancreaticOvarian50%Change50%ChangeMasking of IFN Significantly Increases Tolerability and Lowers Peripheral Activity(Murine Models)Cxcl10GzmbMurine Mod

41、els RNA-seq from tumors following treatment show an increase in IFN stimulated Genes(CXcl10)and increased markers for T-cell activation(Gzmb)Pb-IFNa-A/DComboAnti-PD-1VehicleEach bar=1 tumor from 1 modelT-Cell ActivationPhase 1 Dose Escalation is Designed to Assess CX-801 Clinical Profile as Monother

42、apy and in Combination with PD-1 InhibitionMonotherapy Dose EscalationCombination Dose EscalationNOTE:PD-1 Inhibitor administered on approved dose and schedule,BOIN=Bayesian Optimal Interval;MTD=Maximum tolerated dose;MAD=Maximum assessed doseDemonstrate signs of clinical activity as monotherapy wit

43、h improved safety profile vs.native IFNMelanoma,RCC,HNSCC Demonstrate safety&tolerability profile supportive of combination therapy with PD-1 inhibitionDose Escalation per BOIN DesignDose Escalation per BOIN DesignCX-801+PD-1 Cohort 3CX-801+PD-1 Cohort 4CX-801 Monotherapy MTD/MAD+PD-1Cohort 1CX-801+

44、PD-1Cohort 2CX-801Starting DoseCX-801 Cohort 2CX-801 Cohort 3CX-801 Cohort 5Illustrative ExampleCX-801 Cohort 42627Strategic PartnershipsBusiness Development as a Strategic Engine for Value CreationBMS-986288 Anti-CTLA-4Phase 2 CX-904EGFRxCD3 Phase 1*Multiple Programs*Multiple Programs Multiple Prog

45、ramsMultiple MRNA ProgramsT-Cell Engagers$500M of funds raised through collaborations 10 Active,Preclinical Collaboration ProgramsCommercial Rights,Near-and Long-term milestonesPreclinical ProgramsT-Cell EngagersBispecificImmunotherapiesMRNA Oncology&Other DiseasesMultiple Modalities*Co-development&

46、Commercialization with retained U.S.Rights*CytomX retains US rights on select programs28Next Generation CTLA-4 ProgramPoC Trials in NSCLC&MSS CRC;Data Anticipated in 2024*29Non-Fucosylated(NF)Probody Therapeutic with increased CD16 affinity CTLA-4:established MOA,with Yervoy approved across solid tu

47、mors Challenges(toxicity and patient selection)associated with targeting CTLA-4 have limited development BMS-986288 is a next-generation CTLA-4 designed to improve the benefit/risk:NF(enhanced CD16 binding)biology increases immune priming via Fc engagement enhancing anti-tumor responseImproves safet

48、y profile with Probodytechnology added to NF allowing for combinations and moving to earlier lines of therapy*Bristol Myers Squib 2023 R&D Day,September 14,2023BMS-986288(CTLA-4)YERVOY is a registered trademark of Bristol-Myers Squibb CompanyOutlook&MilestonesMilestones&RoyaltiesShared U.S.RightsMil

49、estones&RoyaltiesCytomX is Entering a Catalyst Rich Period2024&2025 Potential MilestonesProgramStage20242025CX-904(EGFR TCB)Phase 1 Dose EscalationPhase 1a Data in 2H 2024Decision to Expand to Phase 1b in Conjunction with AmgenPhase 1b InitiationCX-2051(EpCAM ADC)IND Filed(Dec 23)Phase 1 Initiation

50、in EpCAM+tumors including CRC in 1H 2024Initial Phase 1 DataCX-801(IFN2b)IND Filed(Dec 23)Phase 1 Initiation in Solid Tumors including Melanoma,Renal and HNSCC in 1H 2024Initial Phase 1 DataBMS-986288(CTLA-4)Phase 2POC Trials in NSCLC&MSS CRC OngoingData Anticipated in 24 Continued Updates by BMSRes

51、earch CollaborationsPreclinicalMore than 10 ongoing preclinical research programs with partners Research milestones achievable across 2024 2025 and beyond2024 202531CytomX Therapeutics:Building for the Future3232 Differentiated Probody Platform Robust Multi-Modality Pipeline Large Market Opportunities High-Quality Partners Strong Financial Position Talented Organization