Century Therapeutics, Inc. · NASDAQ:IPSC
Century Therapeutics — Investor Presentation (November 2022)
27 slides from Century Therapeutics's investor presentation, Nov 30, 2022
Slide 1: Corporate Overview November 2022
Corporate OverviewNovember 2022
Slide 2: Forward-looking statements
2 Forward-looking statementsThis presentation contains forward-looking statements within the meaning of, and made pursuant to the safe harbour provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this document, other than statements of historical facts or
Slide 3: Emerging leader in cell therapies for cancer
Emerging leader in cell therapies for cancerComprehensive iPSC cell platformFor immune effector cellsTechnical ExpertiseGenetic and protein engineering, process development and immuno-oncologyFoundation in ScienceContinuing investment in innovation drives R&DState-of-the-art GMP manufacturing facili
Slide 4: Century Therapeutics
CENTURY THERAPEUTICS
Slide 5: Building a next generation allogeneic cell therapy platform
5 Building a next generation allogeneic cell therapy platform Gene Editing•Proprietary gene editing platform•CRISPR MAD7-derived gene editing for precise transgene integrationProtein Engineering•Developing proprietary next-generation CARs•Universal tumor targeting platformiPSC Differentiation/Manufa
Slide 6: Foundational investments in iPSC know-how and manufacturing
6 Foundational investments in iPSC know-how and manufacturing Established in-house manufacturing accelerates learnings and enables faster product iteration•53,000 ft2facility •Designed to produce multiple immune cell types•Two sites provides optionality and maximizes flexibilityiPSC license and coll
Slide 7: Precision CRISPR MAD7 mediated sequential gene editing of iPSC
7 Multiple gene edits (KO/KI)iPSC bank Precision CRISPR MAD7 mediated sequential gene editing of iPSC cells generates uniform product candidates Engineered iPSC Master Cell Bank(MCB) Advantages of Century’s PlatformPreciseCRISPR mediated homology directed repair reduces off-target integrationStepwis
Slide 8: Allo-Evasion 1.0 designed to overcome host vs graft rejection
8 Allo-EvasionTM1.0 designed to overcome 3 major pathways of host vs graft rejection1.Deletion of β2M, a protein required to express HLA-1 on the cell surface prevents recognition by CD8 T cells 2.Knock out of CIITA eliminates HLA-II expression to escape elimination by CD4 T cells3.Knock-in of HLA-E
Slide 9: Allo-Evasion 3.0 Provides Additional Protection Against NK Cell Killing
9 Allo-EvasionTM3.0 Provides Additional Protection Against NK Cell Killing1.Deletion of β2M, a protein required to express HLA-1 on the cell surface prevents recognition by CD8 T cells 2.Knock out of CIITA eliminates HLA-II expression to escape elimination by CD4 T cells3.Knock-in of HLA-E prevents
Slide 10: Expression of HLA-E + HLA-G further protects from NK cell killing
10 Expression of HLA-E + HLA-G further protects from NK cell killing HLA-EHLA-GNKG2AKIRs, LIRsActivating ligandActivating receptorProof-of-Concept Study with HLA-I Null K562 Cells Engineered with HLA-E and HLA-G 0.1250.250.512481632 0204060 80100 Donor RC01Ratio (E:T)% KillingParental K562 HLA-G K56
Slide 11: Illustrative potential of Allo-evasion on cellular pharmacokinetics and multiple doses
11 Illustrative potential of Allo-evasion™on cellular pharmacokinetics and multiple dosesWith Allo-EvasionTMengineering Initial doseMinimum threshold to maintain pharmacological pressure Repeat doseRepeat doseWithout Allo-EvasionTMengineeringLack of durable responses seen to date in other allogeneic
Slide 12: Century Therapeutics
CENTURY THERAPEUTICS
Slide 13: Common progenitor milestone enables cost, time efficiencies
13 Common progenitor milestone enables cost, time efficiencies Multiple gene editsEngineered iPSC iNK celliPSC bank Cell engineeringManufacturingCommon ProgenitoriNK3.0 CD34+HSC T cell Reprogramming Reprogramming DifferentiationNK cell •iPSC cell bank with 12 core 3.0 gene edits introduced in 5 sequ
Slide 14: iNK3.0 common progenitor multiple new features for enhanced functionality
14 iNK3.0 common progenitor multiple new features for enhanced functionalityTumor cell killingAllo-Evasion 3.0Cell FitnessImaging + Cytokine support + Safety switch iNK CPBoldface: iNK 3.0-specific gene editsCommon Progenitor Features ENGINEERING PROFILEStepGene EditRationale1KONKG2APotential to blo
Slide 15: iNK common progenitor edits confer improved persistence and anti-tumor efficacy
15 iNKcommon progenitor edits confer improved persistence and anti-tumor efficacy Engineering with IL15/IL15Ra shows increased persistence in vitro and in vivoHigh affinity CD16 demonstrates enhanced ADCC activityGurung, et al, SITC 2022 iNKcells engineered with NKG2D demonstrate enhanced tumor cell
Slide 16: Pipeline and Franchises
Pipeline and Franchises
Slide 17: Century's Key Areas of Internal Focus
17 Century’s Key Areas of Internal Focus B cell malignanciesCNTY-101: Lead product candidate, CD19 targeted CAR-iNKCNTY-102: First γδiTcandidate, multi-specific (CD19 + CD79b) CAR-iTDesigned to increase proportion of patients achieving durable responses through multi-dosing regimens enabled by key A
Slide 18: CNTY-101: differentiated next-gen CD19 targeted product
ELIPSE-1 will assess:CNTY-101: differentiated next-gen CD19 targeted productCNTY-101First cell product candidate designed to avoid all major pathways of host v graft rejectionAllo-EvasionTMedits HLA-I KnockoutIL-15 HLA-IIKnockoutCD19 CARHLA-E Safety Switch* Subject to FDA approvalImpact of Allo-Evas
Slide 19: CNTY-101 shows strong pre-clinical anti-tumor activity
19 CNTY-101 shows strong pre-clinical anti-tumor activity In Vitro Serial killing assay Robust activity against lymphoma xenograftBorges, et al, ASH2021
Slide 20: CNTY-101 Phase 1 dose escalation design
Not for further distribution DL1 (100e6) (n= 1-3) DL1 (100e6) DL2 (300e6) DL3 (1000e6) DL-1 (30e6) No IL-2IL-2 SQ daily days 1-8 (Schedule A) or days 1-22 (Schedule B) Day 1 Day 1 Day 1 aEscalation guided by BOIN. SRC reviews data and implements dosing decisionsbAfter the single dose MTD has been re
Slide 21: Transforming the cell therapy treatment paradigm
21 Transforming the cell therapy treatment paradigm •AUC main predictor of duration of response•Variable cell expansion/exposure drives toxicity and suboptimal responses •Finite repeatdosing regimens have the potential to exceed bar set by autologous cell therapy and deliver more durable responses,
Slide 22: Addressing unmet need in B-cell malignancies
Addressing unmet need in B-cell malignancies Autologous Cell Therapies•Only ~35-40% of patients achieve durable CRs•Manufacturing complexity and toxicities limit community uptake Allogeneic Cell Therapies•Durable CRs inferior to approved autologous therapies•Repeat dosing strategies dependent on add
Slide 23: CNTY-103: first program in CNS malignancies
23 Not for further distribution CNTY-103: first program in CNS malignanciesUniquely positioned to address challenges of GBM ChallengeCentury’s SolutionTraffickingLocal delivery with Ommaya reservoirHeterogeneity•CD133 CAR-mediated tumor cell killing•CD16-mediated killing with mAbsagainst tumor antig
Slide 24: Winning in Solid Tumors
24 Winning in Solid Tumors Trafficking and infiltration γδiTcells -tissue homing TME / Immunosuppressive environment Requirement for chemotherapy conditioning Tumor heterogeneity •Novel conditioning regimens•Genetic engineeringChallengesCentury’s Solution Future engineering strategies •Engage endoge
Slide 25: iPSC-derived GD T cells effective at tumor control
25 iPSC-derived GD T cells effective at tumor control as monotherapy and in combination with antibody Millar, et al, SITC 2022γδ-EGFR-CAR-T cells demonstrate significant CAR killing of ovarian spheroids γδCAR-T demonstrate additive efficacy in combination with trastuzumab Treatment% TGISignificance
Slide 26: Product candidate pipeline across cell platforms and targets
26 ProductiPSC PlatformTargetsIndicationsExpected IND SubmissionDiscoveryPreclinicalClinicalCollaboratorCNTY-101iNKCD19B-Cell MalignanciesCleared to proceed 3Q22CNTY-103iNKCD133Glioblastoma2024CNTY-102iT CD19 + CD79bB-Cell Malignancies2024CNTY-104iNK/iTMulti-specificAcute Myeloid Leukemia2024CNTY-10
Slide 27: Anticipated Catalysts Over Next Months
27 Anticipated Catalysts Over Next 12 MonthsUnderpinned by strong balance sheet with platform synergies and operational excellenceCNTY-101•Phase 1 (ELiPSE-1) trial initiation in B-cell malignancies (by YE22)CNTY-101 Follow On (CNTY-102) •Present pre-clinical data at major medical meeting (2H23)CNTY-
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