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Item 2.02 | Results of Operations and Financial Condition |
On January 13, 2025, Century Therapeutics, Inc. (the “Company”) announced that, as of December 31, 2024, the Company had approximately $220 million of cash, cash equivalents and investments. This unaudited, preliminary amount has been prepared by and is the responsibility of management. This amount is based upon information available to management as of the date of this Current Report on Form 8-K and subject to completion of financial closing procedures that could result in changes to the amount. Furthermore, this amount does not present all information necessary for an understanding of the Company’s financial condition as of December 31, 2024. The Company’s independent registered public accounting firm, Ernst & Young LLP, has not audited, reviewed, compiled or performed any procedures with respect to this preliminary financial data and, accordingly, Ernst & Young LLP does not express an opinion or any other form of assurance with respect thereto. The Company’s actual results for the year ended December 31, 2024 will be included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 and may differ materially from the above estimate.
The information furnished pursuant to this Item 2.02 is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 7.01 | Regulation FD Disclosure |
On January 13, 2025, the Company updated information reflected in a slide presentation, which is attached hereto 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, or otherwise subject to the liabilities of that section and shall not be deemed incorporated by reference in any filing under the Securities Act 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
Exhibit No. |
Document | |
99.1 | Investor Presentation of Century Therapeutics, Inc., dated January 13, 2025 | |
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/ Brent Pfeiffenberger, Pharm.D. | |
Name: | Brent Pfeiffenberger, Pharm.D. | |
Title: | President and Chief Executive Officer |
Date: January 13, 2025
January 2025 Corporate Overview |
2 Forward-looking statements This presentation contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this presentation, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our clinical development plans and timelines and the initial safety and efficacy profiles of CNTY-101 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 through development activities, preclinical studies, and clinical trials; our dependence on the success of our lead product candidate, CNTY-101; our ability to progress CNTY-101 through our CALiPSO and ELiPSE Phase 1 clinical trials; our ability to meet development milestones on anticipated timelines; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials, which may not be predictive of final results or the results of later-stage clinical trials; our ability to obtain FDA clearance of our future IND submissions and commence and complete clinical trials on expected timelines, or at all; our reliance on the maintenance of 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 geopolitical issues, banking instability and inflation on our business and operations, supply chain and labor force; the performance of third parties in connection with the development of our product candidates, including third parties conducting our 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; our ability to recruit and maintain key members of management 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. |
1 3 Century’s ability to create multiple iPSC-derived cell types incorporating Allo-Evasion stands apart from other allogeneic cell therapy approaches • Off-the-shelf therapies • Potential for improved time-to-treatment • Broad availability • Manufacturing dependability Engineerability • Control of differentiation to multiple cell types • Nearly unlimited genetic editing capacity due to infinite replicative capacity Engineering for immune evasion from: • Native T-cells and NK-cells • Antibody immunity Enables potential for persistence and re-dosing of therapy Reproducibility • Fully characterized single cell clones form master cell bank (MCB) • Deep understanding of cell function and safety Profitable Scalability • Large batch sizes with batch-to-batch consistency • Pathway to significantly reduced COGS similar to antibody therapies • Expansion from a single-clone MCB decreases risk of cell exhaustion Allogeneic iPSCs Allo-Evasion Clear differentiation from other allogeneic cell therapies with pathway to antibody-like scale |
4 Adaptive lymphocytes – capable of generating distinct functional attributes Greatest proliferative potential – potentially most useful for ongoing antigenic pressure GvHD risk, eliminated by knockout of T cell receptor (TCR) Potential for long-lived memory, mediating immune surveillance Bridge between innate and adaptive lymphocytes Rapid activation response and capacity for clonal expansion No GvHD risk, TCR is invariant Trafficking and persistence as ‘tissue-resident T-cells’ Innate lymphocytes – most potent cytolytic capacity Less rapid and more limited expansion gives greater control over exposure – potentially more useful for short-term treatment Little GvHD risk, naturally suppressive Traffic to bone marrow and secondary lymphoid tissues Century’s capability to make multiple cell types enables optimal matching of cell characteristics to indication Engineered iPSC MCBs CAR iNK cell CAR iT cell CAR iT cell CD4 CD8 The right cell for the right indication(s) MCB: Master Cell Bank GvHD: Graft vs Host Disease |
5 Century is a leader in immune evasion engineering Continuous evolution of holistic protection from major immunity pathways Allo-Evasion 1.0 Allo-Evasion 3.0 Allo-Evasion 5.0 Protection from: Native T-cells Deletion of HLA-I Deletion of HLA-II Deletion of HLA-I Deletion of HLA-II Deletion of HLA-I Deletion of HLA-II Native NK-cells Insertion of HLA-E Insertion of HLA-E Insertion of HLA-G Insertion of CD300a TASR pan-NK inhibitory ligand1 Humoral immunity Insertion of cell-surface enzyme to degrade IgG antibodies2 CNTY-101 1. https://www.centurytx.com/wp-content/uploads/ASH_Welstead_Universal-Protection-of-Allogenic-T-Cells-Final.pdf 2. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013436/518079/Universal-Protection-of-Allogeneic-T-Cell b2M KO (HLA-I) CIITA KO (HLA-II) CD8+ T Cell CD4+ T Cell Pan NK Inhibitory ligand Fc NK cell CNTY-102 CNTY-108 CNTY-308 CNTY-361 CNTY-107 |
6 Allo-Evasion engineering aims to drive durable responses by enabling repeat dosing for tighter control over drug exposure Ongoing clinical data from CNTY-101 in ELiPSE-1 show persistent exposure in the presence of an intact immune system1 With Allo-Evasion engineering Without Allo-Evasion engineering Dose 1 Dose 2 Dose 3 1. Company data: ELiPSE-1 Phase 1 study in B-cell malignancies |
7 Product iPSC Allo-Evasion Targets Indications Research IND-enabling Clinical P1 P2 P3 CNTY-101 iNK 1.0 CD19 B-cell malignancies Autoimmune diseases CNTY-308 iT 5.0 CD19 Autoimmune diseases B-cell malignancies CNTY-361 iT 5.0 BCMA Myasthenia gravis CNTY-102 iT 3.0 CD19 + CD22 B-cell malignancies CNTY-104* iNK/iT Undisclosed Multi-specific AML CNTY-106* iNK/iT Undisclosed Multi-specific MM CNTY-107 iT 5.0 Nectin-4 Solid tumors CNTY-108 iNK/ iT 3.0 CD19 Autoimmune diseases Century is advancing a diverse iPSC pipeline across cell types and targets in cancer and autoimmune diseases CALiPSO-1 ELiPSE-1 *In partnership with Briseran Myers Squibb. On December 12, 2024, Bristol Myers Squibb informed Century of its intent to terminate the collaboration effective March 12, 2025 Autoimmune diseases Hematologic tumors Solid tumors |
CNTY-101 CAR-iNK cell therapy with Allo-Evasion 1.0 |
9 CNTY-101: A CD19-targeted CAR-iNK product designed to provide precise control of drug exposure and enable repeat dosing CNTY-101 off-the-shelf CAR-iNK cell therapy designed to treat patients with B cell-mediated diseases • Six precision gene edits • CD19-targeted CAR for B-cell depletion • Allo-Evasion technology enables re-dosing without lymphodepletion • Secreted IL-15 enhances cell persistence • Safety switch enables elimination of CNTY-101 with cetuximab, if required for patient safety • iNK cells incorporating Allo-Evasion provide more predictable pharmacokinetics and pharmacodynamics CNTY-101 HLA-I Knockout IL-15 HLA-II Knockout CD19 CAR HLA-E Safety Switch Currently in Phase 1 trials in B-cell malignancies (ELIPSE-1) and autoimmune disorders (CALIPSO-1) https://www.centurytx.com/wp-content/uploads/ASGCT24-CNTY-101-AI-Poster.pdf |
10 CNTY-101 in relapsed/refractory B-cell lymphomas aims to deliver durable responses via repeat dosing Facilitated by Allo-Evasion and extending the period of pharmacologic pressure on tumor cells Unmet need: Potential solution from Century’s platform: • Autologous CD19 CAR-T is curative in ~40%1 of patients • Autologous CD19 CAR-T access is limited and/or can fail in manufacturing as quality is dependent on patient-derived starting material • Limited options and poor prognosis for patients who fail autologous CAR-T • Off-the-shelf product offers immediate access and consistency • Multiple doses to increase pharmacological pressure to increase durability • Host rejection addressed by Allo-Evasion edits CAR-T: Chimeric Antigen Receptor T cell therapy 1Cappell, Nature Reviews Clinical Oncology 2023 |
11 ELiPSE-1 is a dose-escalating Phase 1 study of CNTY-101 in B-cell malignancies (NCT05336409) Patients with CD19+ aggressive and high-risk indolent R/R B-NHL • Part 1 – Dose escalation • Schedule A: Single dose • Schedule B: 1 dose per week x 3 weeks • Part 2 – Dose expansion DLBCL: Diffuse large B cell Lymphoma; HGBL: High-Grade B-cell Lymphoma; MCL: Mantle Cell Lymphoma; PMBCL: Peripheral Mediastinal B-cell Lymphoma; FL3B: Follicular Lymphoma Grade 3B; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma DLT: Dose Limiting Toxicity IL-2: Interleukin-2 (dose: 3e6 IU; subcutaneous) • DLBCL, HGBL, MCL, PMBCL, FL3B, FL, MZL • >2 prior lines of therapy • Prior CD19-targeted cell therapy allowed Dose level 4: 3 billion4 Bayesian Optimal Interval (BOIN) design 1. Standard lymphodepletion regimen: fludarabine (30 mg/c/d) and cyclophosphamide IV (300 mg/m/d) for 3 days 2. Subjects who are assessed as stable disease or better may receive additional cycles of CNTY-101 3. Subjects at DL4A did not receive IL-2 on the day of CNTY-101 infusion but did receive IL-2 daily for 7 days 4. For DL 4B, initial 2 cycles at DL 4B; subsequent cycle regimen depending on response or risk/benefit |
12 ELiPSE-1 enrolled heavily pre-treated R/R B-NHL patients ELiPSE-1 (NCT05336409) Phase 1 study in CD19+ B-cell Malignancies 1 As of 15 October 2024 data snapshot date, data collection ongoing DLBCL: Diffuse Large B Cell Lymphoma, HRFL: High-Risk Follicular Lymphoma; MCL: Mantle Cell Lymphoma, MZL: Marginal Zone Lymphoma Baseline characteristics Safety evaluable (N=20) Median age (range, years) 66 (51–80) Male, n (%) 16 (80) Median follow up (range, months) 3.34 (0.5–18.8) NHL subtype, n (%) DLBCL 11 (55) HRFL 2 (10) MCL 4 (20) MZL 3 (15) Prior therapies, median (range) 4 (2–6) Response to Last Line of Treatment, n (%) Relapsed 8 (40) Refractory 12 (60) Received Prior CAR T, n (%) 9 (45) |
13 CNTY-101 shows evidence of dose-responsive efficacy in ELiPSE-1 Phase 1 Increased ORR at higher dose alongside a favorable safety profile ELiPSE-1 (NCT05336409) Phase 1 study in CD19+ B-cell Malignancies. As of 15 October 2024, data snapshot date, data collection ongoing, efficacy based on Lugano criteria. n=19 total pts evaluable for efficacy, 58% BoR median follow up 3.34 months (range 0.5-18.8 months) Schedule A (1 dose in a 28-day cycle); Schedule B (3 weekly doses in a 28-day cycle) ; DL1: (100e6), DL2: (300e6), DL3: (1e9), DL4: (3e9) ORR: Overall Response Rate, DLTs: Dose Limiting Toxicities, CRS: Cytokine Release Syndrome, ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome, CAR: Chimeric Antigen Receptor | Efficacy (DL3B, N=6) • 83% ORR; median follow up 2.9 months (range 1.2–5.3 months) • All subjects were eligible to receive additional cycle(s) • 4 patients received prior autologous CAR-T therapy Safety & Tolerability (N=20) • No GvHD; no DLTs • CRS: Grade 1 (N=3), Grade 2 (N=3) • Hypotension (n=2) and hypoxia (n=1) lasted <24 hrs. • ICANS: Grade 1 (n=1), resolved in <24hrs • Majority of subjects received at least one dose in the outpatient setting 3 1 1 1 1 1 1 1 1 3 1 1 1 2 0 1 2 3 4 5 6 7 100e6 (1A) 300e6 (2A) 1e9 (3A) 3e9 (4A) 300e6 (2B) 1e9 (3B) Schedule A (One infusion/cycle) Schedule B (Three infusions/cycle) # of subjects Best Overall Response per Lugano PD SD PR CR |
14 PBMC genomic DNA Plasma cell-free DNA CNTY-101 exposure increases with dose and schedule • Extended persistence in circulation at dose level 4A (3 x 10e9 cell infusion) • Persistence outside the bloodstream was detected via a cell-free (cf) DNA assay beyond day 15 • Multiple infusions in Schedule B drive increased exposure throughout the dosing cycle Transgene copies per ug were determined using ddPCR with primers targeting transgene and RPP30. Data shows cycles with LDC across subjects at each dose level. Error bars shown are mean ± SD. LLOQ: Lower limit of quantification. Black triangle indicates infusion. S: Screen Error bars show mean ± SD (due to log10 scale, low values are truncated at 1). Positivity values are determined to be significantly above LOB using two sample Poisson test, p < 0.05. All LDC+ cycles are shown. Black triangles indicate infusions. S: Screen, LOB: Limit of Blank. Schedule A Schedule B Day in cycle Day in cycle ELiPSE-1 (NCT05336409) Phase 1 study in CD19+ B-cell Malignancies. Translational data available as of Oct 28, 2024; Schedule A n=11, Schedule B n=8 Schedule A Day in cycle |
15 • Lymphodepleting Chemotherapy (LDC) depleted patient NK/T cell counts and drove a transient spike of IL-15 cytokine • By post-infusion day 8, NK/T cell counts, IL-15 concentration returned to screening level • Similar PK profile observed for each CNTY-101 infusion within a cycle despite evident patient immune recovery Enabled with Allo-Evasion , CNTY-101 shows persistence in the presence of a restored immune system Translational data available as of Oct 28, 2024 Graphs show data from dose level 3B cohort. Lines in the top panel represent mean and shaded area represents 1*SEM. Triangles mark CNTY-101 infusions within a Schedule B cycle, grey arrow indicates LDC. Dotted blue line is a LOESS fit to medians in bottom panel. S: Screen Similar exposure of CNTY-101 in the presence or absence of endogenous lymphocytes Infusion LDC Model of Allo-Evasion -enabled cellular kinetics |
16 CNTY-101 treatment demonstrates rapid B-cell depletion and was associated with naive non-class switched profile of re-emergent B-cells Data in r/r NHL patients supports the application of CNTY-101 in autoimmune diseases B-cell depletion Re-emergent B-cell profile Rapid and effective depletion of circulating B cells observed in the first cycle 0 20 40 60 80 100 %CD19+CD20+ B cells Non-class switched Class-switched Healthy donors Patients Re-emergent B cells show naive non-class-switched profile • Reduction of class-switched phenotypes in re-emergent B cells has been associated with SLE responses to CD19-targeted cell therapies Graphs show data from the initial cycle of all subjects who had B cell counts of 0.25 cell/ mL or greater (N=10).). Each line represents an individual subject. Data from a subject with supraphysiological levels of circulating malignant B cells was excluded Data shows proportion of non-class switched (IgD+, IgM+ or IgD+IgM+) or switched (IgD-IgM-) circulating B cells (CD19+ CD20+) in healthy donors (N=4) or within earliest evaluable re-emergent B cells in patients (N=4). Majority of the B cells exhibited a naïve profile (IgD+ CD27-, data not shown) Source: Company data, available as of Oct 28, 2024 |
17 ELiPSE-1 initial data validates Century’s iPSC platform Heavily pretreated and refractory patient population treated in first-in-human dose escalation trial, including ~50% patients who had received prior CAR T treatments Favorable initial safety profile; can be delivered in an outpatient setting Increased response rates at higher doses and observations of deepening responses with additional cycles. 83% ORR at Dose Level 3B Dose-dependent increase in CNTY-101 exposure observed Data for CNTY-101 continues to support the potential for Allo-Evasion to enable a multi-dosing regimen in the presence of a restored endogenous immune system ORR: Overall Response Rate |
18 Autoimmune disorders present significant unmet medical need Systemic Lupus Erythematosus (SLE) Lupus Nephritis (LN) Idiopathic Inflammatory Myopathy (IIM) Diffuse cutaneous Systemic Sclerosis (dcSSc) Characteristics Multiorgan, potentially fatal, inflammatory disease with risk for organ damage, including skin, heart, and brain Kidney manifestation of SLE with potential kidney failure requiring dialysis and increased risk for mortality Inflammation of muscle, lungs, skin, joints, and gastrointestinal tract causing weakness, pain, and lung failure which can lead to chronic disability and potentially mortality Fibrosis and vasculopathy of the skin and internal organs, with high risk for disability, disfigurement, and cardiopulmonary mortality US Prevalence1 180,000-340,000 80,000–120,000 >60,000 >85,000 (SSc) Initial addressable subpopulations2 >20,000 >30,000 >10,000 >30,000 Standard of care Corticosteroids, chemotherapy, immunosuppressants, anticoagulants, plasmapheresis Corticosteroids, chemotherapy, immunosuppressants, dialysis Corticosteroids, immunosuppressants, IVIg Slow progression: Immuno-suppressants, vasodilators, antifibrotic agents Limited efficacy with approved therapies3 <35% low disease activity (LLDAS) <40% complete renal response (CRR) <40% total improvement score (TIS) of 60% Slower decline in lung function (FVC decrease >24 mL/year on therapy) Unmet Medical Need Low disease activity, prevention of organ damage, survival Prevention of renal failure, survival Remission, maintain function, prevention of calcinosis, damage, respiratory failure, survival Slow progression, prevent cardiac or respiratory failure, survival Despite approved treatments, significant underappreciated unmet need remains Even effective available treatments leave patients suffering with active disease, shortened lifespan, and prospect of life-long medication SoC relies on chronic treatment with broad-acting corticosteroids & immunosuppressives Treatment toxicity and disease flares leading to organ damage remain common Current treatments fail to significantly improve quality of life or prevent organ failure in majority of patients (1) Tian Ann Rheum Dis 2023; Izmirly Arth Rheum 2021; Duarte-Garcia Ann Rheum Dis 2022; Hocaoglu Arth Rheum 2022; Smoyer-Tomic BMC Musculoskeletal Disorders 2012; Khoo Nat Rev Rheum 2023; Bendewald Arch Dermatol 2010; Bairkdar Rheumatology 2021; Fan J Manag Care Spec Pharm. 2020 (2) Estimates include refractory subpopulations. Morand Ann Rheum Dis 2018; Morand Ann Rheum Dis 2023; Oon Ann Rheum Dis 2019; Morand Arth Rheum 2023; Scherlinger Ann Rheum Dis 2019; Clowse Arthritis Rheumatol 2024 (abstract); Mayes Arth Rheum 2003 (3) Highest efficacy values reported; not necessarily Phase 3 trial primary efficacy endpoints that supported FDA approval. Oon Ann Rheum Dis 2019; Morand Ann Rheum Dis 2023; Aranow Ann Rheum Dis 2024; Rovin Lancet 2021; Hanni CJASN 2024; Saxena Arth& Rheum 2023; Furie NEJM 2020; Aggarwal NEJM 2022; Distler NEJM 2019; Khanna Lancet Respir Med 2020 LLDAS, lupus low disease activity state; FVC, forced vital capacity |
19 Clear opportunity for allogeneic cell therapies to address moderate to severe autoimmune indications by providing long-term, drug-free remission Significant patient population and unmet need • Tens of thousands of patients with unmet need in the US • Heterogeneous nature of patients with autoimmunity supports opportunity for multiple modalities within and across indications • Treatments needed to resolve inflammation, prevent organ failure, normalize lifespan, and avoid toxicity of life-long medication Opportunity to deliver transformational efficacy • Dramatically improve upon standard of care • SLE: LLDAS achievement – predictor for reduction of damage accrual • LN: Complete renal response (CRR) • SSc: High %CRISS, FVC stabilization • IIM: High %TIS • Optimal outcome: drug-free remission Compelling evidence for benefit from deep depletion of pathogenic B-cells • Autologous anti-CD19 CAR-T cell therapies demonstrate potential for long-term drug-free remission • Unmet challenges include safety (CRS, ICANS, neutropenia, B cell aplasia), logistics, and product availability • Emerging data for allogeneic cell therapies2 demonstrate potential for transformative impact and may address above challenges 1. Mackensen Nature Medicine 2022 doi.org/10.1038/s41591-022-02017-5, Muller NEJM 2024 doi/full/10.1056/NEJMoa2308917, Muller ASH 2024 doi.org/10.1182/blood-2024-194525, Sheikh Arthritis Rheumatol. 2024 2. Yu Arthritis Rheumatol. 2024; Goulding Arthritis Rheumatol. 2024, Wang Cell 2024 doi.org/10.1016/j.cell.2024.06.027 CRISS: Composite Response Index for Clinical Trials in Early Diffuse Systemic Sclerosis |
20 Allogeneic iPSC • Available “off-the-shelf” • No patient apheresis required • No manufacturing wait time • Batch-to-batch consistency • Platform enables lower COGs than donor-derived or autologous NK cells • Killing potency (≥ primary CAR-T) leads to deep B-cell depletion1 • Trafficking to secondary lymphoid tissues and marrow favors pathogenic B-cell targeting • Short-lived, more predictable pharmacokinetics and pharmacodynamics • Manageable safety profile, well-tolerated in ELiPSE-1 Allo-Evasion • Avoiding host immune rejection • Ability to repeat dose without continued lymphodepletion • Ability to re-treat, if needed CNTY-101 is a differentiated autoimmune disease treatment: Allogeneic iPSC CAR iNK cell therapy with Allo-Evasion 1. https://www.centurytx.com/wp-content/uploads/ASH_Chin_Natural-Killer-GD-Cells-Final.pdf Tighter control over drug exposure: B-cell depletion without prolonged B-cell aplasia |
21 In vitro studies show that CNTY-101 eliminates B cells with greater potency than primary CAR-T cells https://www.centurytx.com/wp-content/uploads/ASH_Chin_Natural-Killer-GD-Cells-Final.pdf 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 populations. E:T: Effector:Target ratio, UTD: Untransduced donor cells as control 24-hour cytolysis study of CNTY-101 against B-cells from SLE patients, compared to primary CAR-T cells derived from healthy donors |
22 CALiPSO-1 is a Phase 1 study of CNTY-101 in refractory B cell-mediated autoimmune diseases (NCT06255028) infusions in outpatient setting Inclusion: • Participants with moderate to severe SLE, LN, IIM, or dcSSc with treatment-resistant and active disease, after 2+ standard immunosuppressive therapies Endpoints: • Key endpoints: Safety and tolerability, disease activity measures per clinical and laboratory assessments • Translational endpoints: PK, B-cell depletion, autoantibody decline Cycle 1 Cycle 2 No lymphodepletion Schedule Dose level: 1e9 cells Lympho -depletion 28-day DLT Period* Patient enrollment Up to N=48 Response assessments months 2–12 Clinical trial sites open for enrollment (USA); expansion to EU sites expected in 2025 SLE: Systemic Lupus Erythematosus; LN: Lupus Nephrits; IIM: Idiopathic inflammatory Myopathy; dcSSc: Diffuse Cutaneous Systemic Sclerosis *Response assessment conducted at one month; does not gate Cycle 2 | DLT: Dose Limiting Toxicity CNTY-101 CNTY-101 CNTY-101 Day 1 Day 8 Day 15 CNTY-101 CNTY-101 CNTY-101 Day 1 Day 8 Day 15 Day 8 and subsequent infusions allowed in outpatient setting |
CNTY-308 CAR αβ-iT cell with Allo-Evasion 5.0 |
24 CNTY-308 is an iPSC-derived CD19-targeted CAR-iT with preclinical efficacy comparable to autologous CD19 CAR-T cells 1. https://www.centurytx.com/wp-content/uploads/ASH_Heinze_iPSC-Derived-CD4-CD8-Final.pdf CD4+/CD8+ iT-cell • CD19-targeted CAR to target B-cells for cytotoxic depletion • 4-1BB and CD3z co-stim domain to stimulate expansion on target engagement • Allo-Evasion 5.0 edits include protection from host T cell, NK cell, and humoral response • Displays characteristics of autologous CAR-T cells1 • Highly proliferative upon target engagement • Secretes cytokines (e.g., IL-2, IFN, and TNF) • Cytotoxic effector function rapidly eliminates tumor cells • Long-term persistence in vivo CNTY-308 |
25 Century’s iPSC-CAR-T cells display the functional characteristics of adult primary T cells: In vitro activity Effective T cell therapies require the generation of iPSC-CAR-T cells with three key in vitro cell functions Cytotoxicity: Effector function Cell expansion and persistence Therapeutic efficacy requires: Cytokine (IL2) production iPS-CAR-T 1’ CAR-T IL-2 secretion (pg/ml) iPS-CAR-T 1’ CAR-T CD19 iPSC-CART Primary CART 0 5 10 15 20 Fold Change https://www.centurytx.com/wp-content/uploads/ASH_Heinze_iPSC-Derived-CD4-CD8-Final.pdf |
26 1e+06 1e+07 1e+08 1e+09 1e+10 0 10 20 30 40 Days Post−Effector Infusion Luminescence (log axis) Group PBS only 1' CAR−T iPS−CAR−T Group 1: PBS only Group 2: 1' CAR−T Group 3: iPS−CAR−T 0 10 20 30 0 10 20 30 0 10 20 30 1e+07 1e+09 1e+11 Days Post−Effector Infusion Luminescence (log axis) In preclinical animal studies, Century iPSC-CAR-T cells show comparable activity to primary CAR-T cells Complete tumor control Measurable long-term persistence ≥1 mo Cytotoxicity maintained upon re-challenge with engrafted cells 10 100 1000 PBS 1' CAR−T iPS−CAR−T Group hCD45+ count per 100 uL whole blood In vivo experimental details • Disseminated Nalm6 model (1e5 cells infused) • Effectors added 3 days post-tumor infusion • 1’ CAR-T dose: 5e6 cells • iPSC-CAR-T dose: 30e6 cells • No added cytokine or small molecule support Group joined by lines d7 d21 d35 d27 tumor rechallenge Key Tumor challenge • iPSC-CAR-T persist 21 days post-infusion, • iPSC-CAR-T detectable at day 35, 7 days post-tumor rechallenge (at day 28) Tumor challenge Tumor challenge Tumor challenge Tumor challenge 1e+06 1e+07 1e+08 1e+09 1e+10 0 10 20 30 40 Days Post−Effector Infusion L u min e s c e n c e (lo g a xis) Class PBS only 1' CAR−T iPS−CAR−T Group PBS only 1' CAR−T iPS−CAR−T |
Platform: iPSC cell foundry |
28 Century’s robust pre-clinical pipeline has potential to address critical barriers confronting cellular therapies Multiple iPSC-derived immune effector cells iPSC-enabled engineering solutions Opportunity across multiple diseases • Cytokine engineering to reduce or eliminate lymphodepletion • Enhanced Allo-Evasion enables repeat dosing, extended drug exposure and potential for durable remissions • Resistance to suppressive cytokines within the tumor • iNK • iT • iT (CD4+, CD8+) • Next-generation therapies for oncology: • CD19, CD19/22 CARs • Nectin-4 CAR • High-affinity Fc receptors (enable treatment with mAbs) • Key targets in autoimmune diseases: • CD19 and BCMA |
29 Precision CRISPR MAD7-mediated sequential gene editing of iPSCs generates uniform product candidates Multiple gene edits (KO/KI) iPSC Engineered iPSC Master Cell Bank (MCB) Sequential selection steps iPSC Precision Engineering CRISPR-mediated HDR (MAD 7) Advantages of Century’s Platform Precise CRISPR-mediated homology-directed repair1 reduces off-target integration Successive and efficient gene editing through iPSC platform avoids risky multiplex modification and structural variants • Allo-Evasion edits • Protein and cell engineering Quality control through generation of homogenous MCB establishes genomic product integrity Manufacturing begins at the MCB, confirmed to be free from genetic aberrations 1. MAD7 Nuclease: https://www.inscripta.com/wp-content/uploads/2023/03/Liu-et-al-2019-Nature-Communications.pdf |
30 Century platform and in-house manufacturing: Pathway to scalable, profitable cell therapy Established in-house manufacturing from development to launch Quality product at disruptive scale and cost of goods • Built-for-purpose 53,000 ft2 cGMP facility • Key leaders each with 1–2 decades of cell therapy manufacturing expertise, from leading commercial cell therapies • In-house team facilitates aligned priorities, learnings, faster product iteration for efficiency, speed, and product quality • Builds and protects proprietary know-how • Optionality with redundant sites (in-house, active CDMO) • Consistency: Control of manufacturing and single-donor master-cell-bank over product lifetime for batch-to-batch reproducibility • Increased cell fitness: Differentiated immune cells do not undergo excessive expansion cycles which often result in cell exhaustion • Product homogeneity: Clonal origin enables a well-characterized product • Potential to manufacture at antibody-like scale: Scalable platforms and optimized processes to maximize yield, reduce COGs, and meet demand |
31 Century Therapeutics is advancing next-generation iPSC-derived allogeneic NK and T cell therapy candidates for the treatment of cancer and autoimmunity Ended FY24 with cash, cash equivalents, and investments of ~$220M (unaudited*) Cash runway into 2H26 Differentiated pipeline based on iPSC and Allo-Evasion technology ✓ Potential to overcome limitations of conventional allogeneic cell therapy ✓ Preclinical demonstration of CD4+/CD8+ iT cells with characteristics of primary T cells Encouraging preliminary clinical data from Phase 1 trial of CNTY-101 in R/R B-cell lymphomas ✓ 83% ORR at dose level 3B, with favorable safety profile ✓ Data supports the ability to re-dose in the presence of a restored endogenous immune system ✓ Study continuing with escalation to dose level 4B Expansion into additional autoimmune indications ✓ CALiPSO-1 trial initiated in SLE, LN, IIM, and dcSSc participants ✓ CNTY-101 has differentiated profile in AID (allogeneic, iNK with Allo-Evasion ) ✓ Multiple pipeline opportunities in AID In-house manufacturing capabilities ✓ Efficient, scalable manufacturing Phase 1 ELiPSE-1 trial of CNTY-101 in B-cell malignancies • Updated clinical data expected by mid-2025 Phase 1 CALiPSO-1 trial of CNTY-101 in B-cell mediated autoimmune diseases • Enrollment of patients across indications Pre-clinical pipeline prioritization • Prioritized pipeline to be announced in 1Q25 Multiple near-term milestones *This estimate is unaudited and preliminary and actual results may differ due to the completion of our fiscal 2024 closing procedures. As such, this estimate should not be viewed as a substitute for our full audited financial statements prepared in accordance with U.S. generally accepted accounting principles. |
www.centurytx.com |