| Corporate OverviewJanuary 2023 |
| 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 statements that relate to present facts or current conditions, including but not limited to, statements regarding possible or assumed future results of operations, business strategies, research and development plans, regulatory activities, market opportunity, competitive position and potential growth opportunities are forward-looking statements. These statements 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 the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates throughdevelopment activities, preclinical studies, and clinical trials; our reliance on the maintenance on certain key collaborative relationships for the manufacturing and development of our product candidates; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of the COVID-19 pandemic, geopolitical issues and inflation on our business and operations, supply chain and laborforce; the performance of third parties in connection with the development of our product candidates, including third parties conducting our future clinical trials as well as third-party suppliers and manufacturers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of our most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. |
| 3 Investment Thesis Next generation platforms for iNKand gamma delta iTcandidates Foundational investments in iPSC technology, genetic editing, and manufacturing Experienced team in R&D, immuno-oncology, manufacturing and commercializationExemplified by FDA clearance of Century’s first IND for CNTY-101 Well capitalized with cash runway into 2026 Operational efficiencies designed to enable delivery on key milestones, clinical data |
| 4 Finding operational efficiencies to extend the cash runwayPortfolio Prioritization Operational efficiencies•Prioritization of key pipeline assets enabled by de-prioritizing further investment in CNTY-103•CNTY-107 (Nectin-4+ tumors), CNTY-102 (lymphomas) have BIC potential•Not overinvesting in any disease area •Realizing further synergies across the organization•Streamlining R&D lab operations in Philadelphia•While executing on key milestones Cash runway extended into 2026 following portfolio reprioritization |
| iPSC Platform |
| 6 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/Manufacturing•Scalable protocols and processes to produce highly functional iNKand iTcell productsiPSC Reprogramming•Comprehensive collection of clinical grade lines (CD34+ HSC, αβT cell, γδT cell derived) Vertically integrated capabilities differentiate Century’s approach |
| 7 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 collaboration agreement established in 2018•Access to clinical grade iPSC lines •Exclusive IP and know-how to generate immune effector cells using feeder-free methods (NK, T, Mac, DC)•FCDI GMP manufacturing capacity for Century’s product candidates•Leveraging two decades of research & investment at University of Wisconsin and FCDI |
| 8 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 integrationStepwise and efficient gene editing avoids risky multiplex modificationand structural variantsQuality control through generation of homogenous MCB establishes genomic product integrityManufacturing begins at the MCB, confirmed to be free from genetic aberrations Sequential selection steps iSPCPrecision EngineeringCRISPR-mediated HDR (MAD 7) |
| 9 Potential to drive durable responses with engineering to resist immune rejectionAllo-EvasionTMedits + repeat dosing = potential greater durability Next-wave of allogeneic cell therapies must solve for challenge of rejection |
| 10 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 prevents killing by NK cells β 2M KO (HLA-I) HLA-E KICIITA KO (HLA-II) CD8+ T Cell CD4+T Cell NK cell 3 core edits disarm host cells from eliminating therapy |
| 11 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 killing by NK cells4.Knock-in of HLA-G prevents killing by NK cells β 2M KO (HLA-I) HLA-E KICIITA KO (HLA-II) CD8+ T Cell CD4+T Cell NK cell 4 core edits disarm host cells from eliminating therapy HLA-G KI |
| 12 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 02040 60 80100 Donor RC01Ratio (E:T)% KillingParental K562 HLA-G K562 HLA-E K562 HLA-E+G K562 Te Coination o HLA-E + HLA-G roved Protection to Killing y Allogeneic NK Cells•HLA-E and HLA-G engage different receptors on NK cells including NKG2A, KIRs, and LIRs•The expression of NKG2A, KIRs, and LIRs varies among NK cells from different donorsAgglomerated Data from 22 NK Cell Donors No editHLA-GHLA-EHLA-E/G 0.00.20.40.60.81.0 Relative cytolysis |
| Discovery |
| 14 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 sequential steps•Resetsproduct development starting point: accelerates and de-risks development candidate selection New Starting Point+ CAR |
| 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 killing |
| Pipeline and Franchises |
| 17 ProductiPSC PlatformTargetsIndicationsDiscoveryPreclinicalClinicalCollaboratorCNTY-101iNKCD19B-Cell MalignanciesCNTY-102iT CD19 + CD79bB-Cell MalignanciesCNTY-107iTNectin-4Solid TumorsPrograms in Collaboration CNTY-104iNK/iTMulti-specificAcute Myeloid LeukemiaCNTY-106iNK/iTMulti-specificMultiple MyelomaResearch ProgramsDiscoveryiNK/iTTBDHematological / Solid TumorsUpdated pipelineProduct candidate pipeline across cell platforms and targets in solid and hematologic cancers Hematologic TumorsSolid Tumors |
| 18 Promise of allogeneic cell therapies in lymphoma intact Large unmet need remains despite progress with autologous cell therapies•~25% of eligible patients receive CAR-T therapy1•~35% of patients achieve long- term remission even in earlier lines of therapy1Off-the-shelf modalities approaching bar set by autologous but falling short on durability •Rejection limits potential of durable responses for first wave of allogeneic cell products•Bispecifics lack curative potential of cell therapyGoal to deliver more durable response rates vs autologous X •CNTY-101 is designed to protect cell product from rejection (Allo-EvasionTM)•Shift from “one and done” to finite repeat dosing to increase pharmacological pressure1. Targeted Oncology, Many Challenges, Opportunities for CAR T-Cell Therapies in Lymphoma, Sept 2022 |
| 19 Differentiating features:First cell therapy product candidate designed to avoid all major pathways of host vs graft rejection to realize potential of repeat dosingPotential to exceed bar set by autologous and deliver durable responses Vision to eliminate need for lymphodepletion with subsequent cycles to increase tolerability and ease of outpatient administration CNTY-101: Differentiated next-gen CD19 targeted productCNTY-101Allo-EvasionTMedits HLA-I KnockoutIL-15 HLA-IIKnockoutCD19 CARHLA-E Safety Switch Currently enrolling patients with relapsed/refractory CD19+ B-cell malignancies |
| 20 CNTY-101 shows strong pre-clinical anti-tumor activity In Vitro Serial killing assay Robust activity against lymphoma xenograftBorges, et al, ASH2021 |
| 21 ELiPSE-1: First-in-Human Study CNTY-101Study will assess:Impact of Allo-EvasionTMon iNK cell persistence and PK after multiple dosing (Schedule B)Multiple dose regimen with up to 6 doses with single lymphodepletion conditioningPotential to increase durability of responses with Allo-EvasionTMenabled repeat dosing regimen Day 1 LDDay 50 Subsequent dose(s) without additional LD* ≥1bn cells/dose* Subject to FDA approvalSchedule A: Single ascending dose study (3+3 escalation design) DL1DL2DL3100M300M1BnSchedule B: Accessing multiple doses per cycle+ IL-22ndcycle of single dose allowed for patients who demonstrate benefit |
| 22 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 endogenous immunity•Multi tumor targeting pathways CARCD16TCRCytokine supportAllo-Evasion TMEnhanced fitnessTracer TBD |
| 23 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 trastuzumab0P=0.9980γδ-CAR-T18P=0.7073γδ-CAR-T + trastuzumab42P=0.0358TGI = Tumor Growth Inhibition |
| 24 CNTY-107: First in Class Nectin-4 Targeted GD iTCell TherapyNectin-4 has been validated by ADC approaches•Opportunity to address multiple Nectin-4 positive solid tumors•Potential indications include bladder, breast, pancreatic, non-small cell lung cancer, esophageal/gastric, head and neck, and/or ovarian cancers1GD iTallogeneic therapies provide potential to improve upon ADC toxicity profile and efficacy•Intrinsic homing of GD iTcells to tissues and solid malignancies•Multi-tumor killing modalities to tackle heterogeneity Tumor cell killingAllo-EvasionTM Cell FitnessCNTY-107 Illustrative construct Nectin-4 CARCD16Tracer TCR Cytokine support 1. Cancer Res . 2016 May 15;76(10):3003-13 |
| 25 Strategy and 3-year vision for growthDelivering on potential for allogeneic cell therapies by exceeding efficacy, safety and logistics of autologous approaches2026+Advancing multiple development candidatesClinical trial execution (ELiPSE-1) CNTY-102 development candidate pre-clinical data Multiple clinical stage candidatesCNTY-101 clinical data providing initial proof of conceptPoised for pivotal start in lymphomaInitial clinical data with gamma delta T cell programs: CNTY-107 in Nectin-4 + tumors and CNTY-102 in lymphoma 2023Execution2024Acceleration2025Validation Estimated cash runway to fund operations into 2026 |
| 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 facilityFully operational, enabling improved and faster product iteration Financial StrengthCash runway into 2026, Ended 3Q22 with cash, cash equivalents, and investments of $395.3M~165Employees including experienced leadersand entrepreneursEmerging pipeline of candidatesProduct engine anticipated to deliver multiple INDs over the next 3 yearsBMS Discovery CollaborationInitial focus on AML(CNTY-104) and MultipleMyeloma (CNTY-106) |
