Century Therapeutics, Inc. · NASDAQ:IPSC
Century Therapeutics — Investor Presentation (March 2024)
35 slides from Century Therapeutics's investor presentation, Mar 14, 2024
Slide 1: Corporate Overview March 2024
Corporate Overview March 2024
Slide 2: Forward-looking statements
2 Forward-looking statements This 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: Building an industry-leading allogeneic iPSC-derived cell therapy platform
3 Century Therapeutics: Building an industry-leading, next-generation allogeneic iPSC-derived cell therapy platform LIMITLESS POTENTIAL… PRECISION DESIGN… ENDURING IMPACT… Foundational investments in iPSC technology, genetic editing, protein engineering, and manufacturing Progressing differentiated
Slide 4: Overview of Foundational Platform Technologies
Overview of Foundational Platform Technologies
Slide 5: Century's next-generation allogeneic iPSC technology platform
5 Versatility and unprecedented control: Century’s next-generation allogeneic iPSC technology platform Iterative optimization of product functionality and manufacturability • Consistency • Yield • Fitness: No exhaustion Product design Manufacturing iPSC iT cell iNK cell Engineered iPSC MCB SINGLE CE
Slide 6: Precision CRISPR MAD7 sequential gene editing of iPSC cells
6 Precision CRISPR MAD7 mediated sequential gene editing of iPSC cells generates uniform product candidates Multiple gene edits (KO/KI) iPSC bank Engineered iPSC Master Cell Bank (MCB) Sequential selection steps iSPC Precision Engineering CRISPR-mediated HDR (MAD 7) Advantages of Century’s Platform
Slide 7: Allo-Evasion edits and repeat dosing for potential greater durability
7 Allo-EvasionTM edits + repeat dosing = potential greater durability Potential to drive durable responses with engineering to resist immune rejection Next-wave of allogeneic cell therapies must solve for challenge of rejection With Allo-EvasionTM engineering Without Allo-EvasionTM engineering
Slide 8: Allo-Evasion designed to overcome host vs. graft rejection
8 Allo-EvasionTM designed to overcome major pathways of host vs. graft rejection Core edits disarm host cells from eliminating therapy 2M KO (HLA-I) HLA-E KI CIITA KO (HLA-II) CD8+ T Cell CD4+ T Cell NK cell HLA-G KI 1. Deletion of β2M, a protein required to express HLA-1 on the cell surface prevent
Slide 9: Foundational investments in iPSC manufacturing
9 Foundational investments in iPSC manufacturing Established in-house manufacturing Developing fit-for-purpose products • Accelerates learnings and enables faster product iteration • 53,000 ft2 facility • Designed to produce multiple immune cell types • Two sites (FCDI GMP manufacturing, Century in-
Slide 10: Century Therapeutics
CENTURY THERAPEUTICS
Slide 11: Diversified pipeline across cell platforms and targets
11 Product iPSC Platform Targets Indications Discovery Preclinical Clinical Collaborator P1 P2 P3 CNTY-101 iNK CD19 B-Cell Malignancies Systemic Lupus Erythematosus CNTY-102 iT CD19 + CD22 B-Cell Malignancies CNTY-107 iT Nectin-4 Solid Tumors Programs in Collaboration CNTY-104 iNK/iT Multi-specific
Slide 12: CNTY-101 Clinical Programs
CNTY-101 Clinical Programs
Slide 13: CNTY-101: Differentiated next-gen CD19 targeted product
13 CNTY-101: Differentiated next-gen CD19 targeted product Delivering on our vision to change the cell therapy treatment paradigm • Goal to improve durability, tolerability and ease of outpatient administration • Potential to eliminate need for lymphodepletion with subsequent cycles of therapy • Fir
Slide 14: CNTY-101 in relapsed/refractory B-cell lymphomas
14 CNTY-101 in relapsed/refractory B-cell lymphomas Aim: To deliver durable responses via repeat dosing facilitated by Allo-EvasionTM and extending the period of pharmacologic pressure on tumor cells R/R: Relapsed or Refractory, NHL: Non-Hodgkin Lymphoma, CAR-T: Chimeric Antigen Receptor T cell ther
Slide 15: CNTY-101: ELiPSE-1 trial design
15 CNTY-101: ELiPSE-1 (NCT05336409) Phase 1 BOIN design 1 Standard lymphodepletion regimen: Fludarabine (30 mg/m2/d) and cyclophosphamide IV (300 mg/m2/d) for 3 days 2Subjects who are assessed as stable disease or better may receive additional cycles of CNTY-101 BOIN: Bayesian Optimal Interval, DLBC
Slide 16: ELiPSE-1 initial data: Key takeaways
16 ELiPSE-1 initial data: Key takeaways Heavily pretreated and refractory patient population treated in first-in-human dose escalation trial Favorable safety profile; can be delivered in an outpatient setting Encouraging early efficacy signals at lowest dose levels • 2 patients achieving CR, includi
Slide 17: ELiPSE-1 enrolled heavily pretreated patients
17 ELiPSE-1 enrolled heavily pretreated patients Baseline characteristics Patients treated 7 Median age (range) 68 (60-72) Prior therapy Median # of prior therapies (range) 4 (2-6) Prior CD-19-targeted CAR T-cell therapy 3 a (43%) Disease characteristics Aggressive histology 5 (71%) Refractory to la
Slide 18: ELiPSE-1: Favorable initial safety profile
18 ELiPSE-1: Favorable initial safety profile *Data cutoff date of November 13, 2023; represents data verified post data cut a. CAR T manufacturing failure COHORT PATIENT DISEASE HISTORY TREATMENT SAFETY Indication Prior Lines Therapy Prior CAR T? Relapse or Refractory to Last Line Dose Cycles Compl
Slide 19: ELiPSE-1: Early evidence of anti-lymphoma activity at lowest dose levels
19 ELiPSE-1: Early evidence of anti-lymphoma activity at lowest dose levels *Data cutoff date of November 13, 2023; represents data verified post data cut a. CAR T manufacturing failure COHORT PATIENT DISEASE HISTORY TREATMENT SAFETY RESPONSE Indication Prior Lines Therapy Prior CAR T? Relapse or Re
Slide 20: ASH case study: Patient with 6-month durable complete response
20 ASH case study: Dose level 1 patient with 6-month durable complete response *Data cutoff date of November 13, 2023; represents data verified post data cut Patient subsequently progressed Ramachandran, et al. 2023 ASH Annual Conference Multiple Doses of CNTY-101, an iPSC-Derived Allogeneic CD19 Ta
Slide 21: ASH case study: Favorable initial safety profile
21 ASH case study: Favorable initial safety profile *Data cutoff date of November 13, 2023; represents data verified post data cut AC: Additional Cycle Ramachandran, et al. 2023 ASH Annual Conference • No DLTs, no CRS, no ICANS • No AEs related to CNTY-101 • Factors associated with CRS and neuroto
Slide 22: ASH case study: Early evidence of anti-lymphoma activity
22 Patient subsequently progressed Ramachandran, et al. 2023 ASH Annual Conference ASH case study: Early evidence of anti-lymphoma activity with durable 6-month complete response Baseline Post-initial dose (Day 28)
Slide 23: ASH case study: CNTY-101 persists outside of circulation
23 ADCC CDC cfDNA: cell -free DNA, LD: lymphodepletion Ramachandran, et al. 2023 ASH Annual Conference ASH case study: CNTY -101 persists outside of circulation and humoral immunogenicity is not detected PK shows CNTY -101 cells traffic out of circulation shortly after infusion; consistent levels at
Slide 24: ASH case study: Intra-tumoral adaptive immune response
24 ASH case study: Intra-tumoral adaptive immune response observed following initial dose without IL-2 SCREEN CD8+ T cells Total Ki67+ CD8Ki67 CD8Ki67 Endogenous NK cells Total Ki67+ CD56Ki67 CD56Ki67 Secreting cells TNF-α IFN-γ 0 200 400 600 800 1000 Cells per mm2 CARTNFAIFNG CARTNFAIFNG DAY 8
Slide 25: Summary of ELiPSE-1 data
25 Summary of ELiPSE-1 data Cohorts of 1 billion cells/1 monthly dose and 300 million/weekly x 3 doses are open; Additional clinical data expected in mid-2024 Heavily pretreated and refractory patient population treated in first-in-human dose escalation trial Favorable safety profile; can be delive
Slide 26: Opportunity in systemic lupus erythematosus
26 Opportunity in systemic lupus erythematosus to improve long-term disease control 1. Tian J, et al. Ann Rheum Dis 2023;82:351–356 http://dx.doi.org/10.1136/ard-2022-223035 2. MackensenA, et al.. Nature Medicine 2022 28:10 (2124-2132) https://doi.org/10.1038/s41591-022-02017-5 CNS: Central Nervous
Slide 27: CNTY-101 aims to eliminate pathogenic B-cells in SLE
27 CNTY-101 aims to eliminate pathogenic B-cells in SLE leading to remission via repeat dosing facilitated by Allo-EvasionTM HDR: Homology-Directed Repair Aim: Safely provide immune reset with an immediately available therapy CNTY-101 has the potential to improve on current SLE treatments • Anti-CD1
Slide 28: CNTY-101 comparable to primary CAR-T at B-cell killing
28 Isolated B cells or CD19+ target cells were co-cultured with CNTY-101 or primary CAR-T at several E:Ts in 96-well U bottom plates in NKCM with assay harvested at 24h. Assay plates were harvested and stained for Fixable Live/Dead. Cells were fixed and run on cytometer to determine Target+Dead Cell
Slide 29: CNTY-101: Systemic lupus erythematosus Phase 1 study
29 CNTY-101: Systemic lupus erythematosus Phase 1 study Inclusion: • Patients with moderate to severe SLE after 2+ standard immunosuppressive therapies Endpoints: • Key endpoints: Safety, SLE manifestations per SLEDAI, LLDAS, DORIS • Translational Endpoints: B-cell depletion, auto-antibody decline T
Slide 30: Multiple near-term catalysts and cash resources
30 MULTIPLE NEAR-TERM CATALYSTS CASH RESOURCES Advancing next-generation iPSC-derived allogeneic NK and T cell therapy candidates for the treatment of cancer and autoimmunity Phase 1 ELiPSE-1 trial of CNTY-101 in B-cell malignancies • Additional data expected in mid-2024 Phase 1 trial of CNTY-101 in
Slide 31: Century Therapeutics
CENTURY THERAPEUTICS
Slide 32: CNTY-102: Leveraging the γδ iT platform
32 CNTY-102: Leveraging the γδ iT platform designed to deliver best-in-class potential Designed to address factors that limit durability of cell therapy in B-cell malignancies • γδ iT cells expand, persist, and traffic to lymphoid tissues leading to potentially sustained anti-tumor activity • Dual t
Slide 33: Vision for winning in solid tumors with γδ iT platform
33 Challenges Century’s Solution Vision for winning in solid tumors with γδ iT platform CAR CD16 TCR Cytokine support Allo-Evasion TM Enhanced fitness Tracer TBD Trafficking and infiltration γδ iT cells – tissue homing TME/immunosuppressive environment Tumor heterogeneity Requirement for chemotherap
Slide 34: CNTY-107: First in class Nectin-4 targeted γδ iT cell therapy
34 CNTY-107: First in class Nectin-4 targeted γδ iT cell therapy Leveraging the power of the γδ iT cell platform for solid tumors Nectin-4 has been validated by ADC approaches • Opportunity to address multiple Nectin-4 positive solid tumors — Potential indications include bladder, breast, pancreatic
Slide 35: Building an industry-leading allogeneic iPSC-derived cell therapy platform
35 Century Therapeutics: Building an industry-leading, next-generation allogeneic iPSC-derived cell therapy platform LIMITLESS POTENTIAL… PRECISION DESIGN… ENDURING IMPACT… Foundational investments in iPSC technology, genetic editing, protein engineering, and manufacturing Progressing differentiated
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