Century Therapeutics, Inc 8-K, filed Nov 30, 2022
Century Therapeutics, Inc. (IPSC)
About this 8-K
Century Therapeutics, Inc filed this 8-K on November 30, 2022.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 9.01: Financial statements and exhibits
UNITED STATES
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CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure |
On November 30, 2022, Century Therapeutics, Inc. (the “Company”) updated information reflected in a slide presentation, which is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference. Representatives of the Company will use the updated presentation in various meetings with investors from time to time.
The information contained in this Item 7.01 (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section and shall not be deemed to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits |
(d) Exhibits
The following exhibit is being furnished herewith:
| Exhibit No. |
Document | |
| 99.1 | Investor Presentation of Century Therapeutics, Inc., dated November 30, 2022 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CENTURY THERAPEUTICS, INC. | ||
| By: | /s/ Osvaldo Flores, Ph.D. | |
| Name: | Osvaldo Flores, Ph.D. | |
| Title: | President and Chief Executive Officer | |
Date: November 30, 2022
| Corporate OverviewNovember 2022 |
| 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. |
| 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 2025, Ended 3Q22 with cash, cash equivalents, and investments of $395.3M~200Employees including experienced leadersand entrepreneursEmerging pipeline of candidatesProduct engine anticipated to deliver 5 INDs over the next3 years; CNTY-101 Phase 1 trial initiating imminentlyBMS Discovery CollaborationInitial focus on AML(CNTY-104) and MultipleMyeloma (CNTY-106) |
| iPSC 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/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 |
| 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 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 |
| 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 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) |
| 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 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 |
| 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 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 |
| 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 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 |
| 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 approaches likely due to rejection of the product |
| Discovery |
| 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 sequential steps•Resetsproduct development starting point:accelerates and de-risks development candidate selection New Starting Point+ CAR |
| 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 block inhibitory signalKIIL15/IL15RaHomeostatic cytokine support2KOB2MAllo-EvasionKIHLA-E-2A-HLA-GAllo-Evasion3KOCIITA ex5Allo-EvasionKIHSV-TK-2A-PSMASafety switch + cell tracer4KOCD70Landing pad, potential to enhance cell fitnessKICD16-2A-NKG2DAb targeting + Tumor stress ligands5INSCLYBLSafe harbor siteKICARTumor targeting CD16NKG2DPSMAHLA-GHLA-EIL-15/IL15RAHSV-TK Safety switch HLA-I KOHLA-II KO CD70 KO NKG2A KO |
| 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 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 Allo-EvasionTMedits GlioblastomaCNTY-103: CD133 CAR iNK for recurrent GBMAddress heterogeneity via multi-tumor antigen targeting and safety and technical trafficking challenges with locoregional deliveryCNTY-107: Nectin-4 targeted CAR GD iTLeveraging gamma deltaiTplatform designed to address several solid tumor indications with high expression of Nectin-4 and unmet need Nectin-4 + Solid tumors |
| 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-Evasion on iNK cell persistence and PK after multiple dosing (schedule B)Multiple dose regimen with up to 6 doses with single LD conditioningPotential to increase durability of responses with Allo-Evasion enabled repeat dosing regimen Day 1 LDDay 50 Subsequent dose(s) without additional LD* ≥1bn cells/dose |
| 19 CNTY-101 shows strong pre-clinical anti-tumor activity In Vitro Serial killing assay Robust activity against lymphoma xenograftBorges, et al, ASH2021 |
| 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 reached or the maximal single dose has been evaluated, or earlier upon the recommendation of theIndependent Data Review Committeeand Sponsor decision, Schedule B will also be explored (ie, given weekly for 3 weeks), starting with a fractionated dose of approximately one-third the MTD. Starting dose Schedule A (n=3/cohorta) Schedule B (n=3/cohorta) Day 15 Day 8 DL2 (300e6) DL2 (300e6) DL2 (300e6) DL3 (1000e6) DL3 (1000e6) DL3 (1000e6) Schedule B opens with ~1/3 schedule A MTD One overall CNTY-101 RP2R will be declared per SRC recommendation, based on both Schedule A and B MTDs, and expanded.No IL-2 IL-2SQ daily days 1-8IL-2 SQ daily days 1-22 3 doses: 1 dose per week for three consecutive weeksELiPSE-1 Treatment Schema All patients receive standard LD Cy (300 mg/m2)/flu (30mg/m2) for 3 days Redosing for patients who demonstrate clinical benefit post-FDA approval |
| 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, ifthe cells are engineered to avoid host rejection (Allo-EvasionTM) Single dose of allogeneic NK cells unlikely to match αβautologous CAR T Illustrative curves |
| 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 additional LD cycles to avoid rejection CD20 x CD3 Bispecifics•Durable CRs inferior to approved autologous therapies•Require chronic or 9-month long treatment cycles•Toxicity profiles anticipated to limit uptake in community settings •Potential for short, finite, repeat-dosing regimen with single LD cycle•Uniform, fully characterized product •Potential for short, finite, repeat-dosingregimen with single LD cycle•Anticipated safety favors community adoption •Allo-Evasion enables multiple dose strategy to potentially generate durable responses that match or exceed those of autologous•Anticipated safety allows for community setting useCNTY-101 has a differentiated target product profile |
| 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 antigens•NKG2D-mediated killing through stress ligand recognitionToxicityPotentially minimize risks like CRS with iNKPersistencePotential to dose as needed NKG2A KO CD133 CARAllo-EvasionTMedits CD16NKG2DPSMAHLA-GHLA-EIL-15/IL15RAHSV-TK Safety switch HLA-I KOHLA-II KO CD70 KO CNTY-103Leverages iNK3.0 common progenitor |
| 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 endogenous immunity•Multi tumor targeting pathways CARCD16TCRCytokine supportAllo-Evasion TMEnhanced fitnessTracer TBD |
| 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 trastuzumab0P=0.9980γδ-CAR-T18P=0.7073γδ-CAR-T + trastuzumab42P=0.0358TGI = Tumor Growth Inhibition |
| 26 ProductiPSC PlatformTargetsIndicationsExpected IND SubmissionDiscoveryPreclinicalClinicalCollaboratorCNTY-101iNKCD19B-Cell MalignanciesCleared to proceed 3Q22CNTY-103iNKCD133Glioblastoma2024CNTY-102iT CD19 + CD79bB-Cell Malignancies2024CNTY-104iNK/iTMulti-specificAcute Myeloid Leukemia2024CNTY-106iNK/iTMulti-specificMultiple Myeloma2024CNTY-107iTNectin-4Solid Tumors2025Discovery Research ProgramsiNKTBDHematological Tumors2023iTTBDSolid TumorsTBD Hematologic TumorsSolid TumorsPipelineProduct candidate pipeline across cell platforms and targets in solid and hematologic cancers |
| 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-103•Disclose pre-clinical data of development candidate at major medical meeting (2H23) |
