Century Therapeutics, Inc. · NASDAQ:IPSC
Century Therapeutics — Technical Presentation (December 2023)
32 slides from Century Therapeutics's technical presentation, Dec 11, 2023
Slide 1: Initial Data from Phase 1 ELiPSE-1 Trial of CNTY-101 and Overview of Planned Phase 1 SLE Study
Initial Data from Phase 1 ELiPSE-1 Trial of CNTY-101 in Relapsed/Refractory B-cell Lymphomas and Overview of Planned Phase 1 Study in Systemic Lupus Erythematosus December 11, 2023
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: Today's agenda
3 Today’s agenda • Introduction Brent Pfeiffenberger, Pharm.D., Chief Executive Officer • Overview of Foundational Platform Technologies Hy Levitsky, M.D., President of Research and Development • Review of Initial ELiPSE-1 Data for CNTY-101 Nick Trede, M.D., Ph.D., SVP, Head of Clinical Development
Slide 4: Century Therapeutics: Building an industry-leading, next-generation allogeneic iPSC-derived cell therapy platform
4 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, and manufacturing Progressing multiple clinical programs in
Slide 5: Overview of Foundational Platform Technologies: iPSCs, Allo-Evasion and the Creation of CNTY-101
Overview of Foundational Platform Technologies: iPSCs, Allo-EvasionTM and the Creation of CNTY-101
Slide 6: Versatility and unprecedented control: Century's next-generation allogeneic iPSC technology platform
6 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 7: Allo-Evasion 1.0 designed to overcome major pathways of host vs. graft rejection
7 Allo-EvasionTM 1.0 designed to overcome 3 major pathways of host vs. graft rejection 1. 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 cells 3. Knock-in o
Slide 8: CNTY-101: Differentiated next-gen CD19 targeted product
8 CNTY-101: Differentiated next-gen CD19 targeted product 2M KO (HLA-I) HLA-E KI CIITA KO (HLA-II) CD8+ T Cell CD4+ T Cell NK cell CD19 CAR Safety Switch IL-15 • Goal to improve durability, tolerability and ease of outpatient administration • Potential to eliminate need for lymphodepletion with subs
Slide 9: CNTY-101: Extending drug exposure in R/R B-cell NHL via repeat dosing
9 CNTY-101: Extending drug exposure in R/R B-cell NHL via repeat dosing and changing the treatment paradigm with Allo-EvasionTM R/R: relapsed or refractory, NHL: non-Hodgkin lymphoma, CAR-T: chimeric antigen receptor T cell therapy Potential solution from Century’s platform: • Off-the-shelf product
Slide 10: Review of Initial ELiPSE-1 Data for CNTY-101
Review of Initial ELiPSE-1 Data for CNTY-101
Slide 11: CNTY-101: ELiPSE-1 Phase 1 study design
11 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 12: ELiPSE-1 initial data: Key takeaways
12 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 o 2 patients achieving CR, i
Slide 13: ELiPSE-1 enrolled heavily pretreated patients
13 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 last line of therapy 6 (86%) Elevated LDH at scr
Slide 14: ELiPSE-1: Overview of patients
14 COHORT PATIENT DISEASE HISTORY TREATMENT Indication Prior Lines Therapy Prior CAR T? Relapse or Refractory to Last Line Dose Cycles Completed DOSE LEVEL 1 1 iFL 4 N Refractory 100 x 106 7 2 DLBCL/tFL 4 Y Refractory 100 x 106 1 3 DLBCL 2 Na Refractory 100 x 106 1 4 DLBCL/tMZL 4 N Refractory 100 x
Slide 15: ELiPSE-1: Favorable initial safety profile
15 COHORT PATIENT DISEASE HISTORY TREATMENT SAFETY Indication Prior Lines Therapy Prior CAR T? Relapse or Refractory to Last Line Dose Cycles Completed DLTs CRS (Grade) ICANS CNTY-101 Related Gr3+ AE/SAE DOSE LEVEL 1 1 iFL 4 N Refractory 100 x 106 7 N N N N 2 DLBCL/ tFL 4 Y Refractory 100 x 106 1 N
Slide 16: ELiPSE-1: Early evidence of anti-lymphoma activity at lowest dose levels
16 ELiPSE-1: Early evidence of anti-lymphoma activity at lowest dose levels COHORT PATIENT DISEASE HISTORY TREATMENT SAFETY RESPONSE Indication Prior Lines The rapy Prior CAR T? Relapse or Refractory to Last Line Dose Cycles Completed DLTs CRS ICANS CNTY-101 Related Gr3+ AE/SAE Best Overall Response
Slide 17: ASH case study: patient treatment course with multiple doses of CNTY-101
17 Initial Dose lympho-depletion No IL-2 Sex/Age: Female/63 Tumor Subtype: Follicular Lymphoma Dose/Schedule: 100e6 cells x 1 per cycle (Dose Level 1; Schedule A) Prior Therapy: • 4 prior lines of therapy including anti-CD20, bispecific, and investigational therapy • High-risk R/R - Relapsed within
Slide 18: ASH case study: Favorable initial safety profile
18 *Data cutoff date of November 13, 2023; represents data verified post data cut AC: Additional Cycle Ramachandran, et al. 2023 ASH Annual Conference ASH case study: Favorable initial safety profile With LD No LD Safety profile in first 7 subjects: • No DLTs, no CRS, no ICANS • No AEs related to
Slide 19: ASH case study: Early evidence of anti-lymphoma activity with durable 6-month complete response
19 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 20: ASH case study: CNTY-101 persists outside of circulation and humoral immunogenicity is not detected
20 ASH case study: CNTY-101 persists outside of circulation and humoral immunogenicity is not detected cfDNA: cell-free DNA, LD: lymphodepletion Ramachandran, et al. 2023 ASH Annual Conference PK shows CNTY-101 cells traffic out of circulation shortly after infusion; consistent levels at 1 hour post
Slide 21: ASH case study: Intra-tumoral adaptive immune response observed following initial dose without IL-2
21 ASH case study: Intra-tumoral adaptive immune response observed following initial dose without IL-2 CD8Ki67 CD8Ki67 CD56Ki67 CD56Ki67 CARTNFAIFNG CARTNFAIFNG Total Ki67+ TNF-α IFN-γ Total Ki67+ 0 200 400 600 800 1000 Cells per mm2 CD8+ T cells Endogenous NK cells Secreting cells SCREEN DAY 8
Slide 22: Summary of ELiPSE-1 data
22 Summary of ELiPSE-1 data • 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 o 2 patients achieving CR, including 1 p
Slide 23: CNTY-101 in Systemic Lupus Erythematosus
CNTY-101 in Systemic Lupus Erythematosus
Slide 24: SLE: global prevalence and significant unmet need
24 Estimated global prevalence of 3.4 million patients1 • Abnormal B cell function and autoantibody production are central to disease pathogenesis • Major causes of morbidity and mortality involve multiple systems o Renal, CNS and cardiovascular involvement are major causes of morbidity and mortalit
Slide 25: CNTY-101 aims to eliminate pathogenic B-cells in SLE via repeat dosing
25 CNTY-101 aims to eliminate pathogenic B-cells in SLE leading to remission via repeat dosing facilitated by Allo-EvasionTM CNTY-101 has the potential to improve on current SLE treatments • Anti-CD19 CAR-iNK cells derived from an HDR precision-edited iPSC clone, including IL-15 cytokine support, a
Slide 26: CNTY-101 cytolysis of B cells versus CAR-T in preclinical assays
26 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 27: CNTY-101: Systemic lupus erythematosus Phase 1 study
27 CNTY-101: Systemic lupus erythematosus Phase 1 study 1 Standard lymphodepletion regimen: fludarabine (30 mg/m2/d) and cyclophosphamide IV (300 mg/m2/d) for 3 days Initial Dose Additional Cycle No lymphodepletion Schedule • Dose level 1: 300e6 • Dose level 2: 1000e6 LYMPHO-DEPLETION1 28-DAY DLT PE
Slide 28: Century Therapeutics pipeline of iPSC-derived allogeneic NK and T cell therapies
28 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 29: Century Therapeutics
CENTURY THERAPEUTICS
Slide 30: Century Therapeutics: Building an industry-leading, next-generation allogeneic iPSC-derived cell therapy platform
30 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, and manufacturing Progressing multiple clinical programs in
Slide 31: Q&A participants
31 Q&A participants • Brent Pfeiffenberger, Pharm.D., Chief Executive Officer • Hy Levitsky, M.D., President of Research and Development • Nick Trede, M.D., Ph.D., SVP, Head of Clinical Development • Adrienne Farid, Ph.D., Chief Operations Officer and Head of Early Development • Michael Diem, M.D.,
Slide 32: Initial Data from Phase 1 ELiPSE-1 Trial of CNTY-101 and Overview of Planned Phase 1 SLE Study
Initial Data from Phase 1 ELiPSE-1 Trial of CNTY-101 in Relapsed/Refractory B-cell Lymphomas and Overview of Planned Phase 1 Study in Systemic Lupus Erythematosus December 11, 2023
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