8-K
Century Therapeutics, Inc. (IPSC)
8-K
2025-01-13
For: 2025-01-13
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April 11, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):January 13, 2025
Century Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-40498 | 84-2040295 |
|---|---|---|
| (State or other jurisdiction of<br><br>incorporation or organization) | (Commission File Number) | (I.R.S. Employer<br><br>Identification No.) |
| 25 North 38th Street, 11th Floor<br><br> <br>Philadelphia, Pennsylvania | 19104 | |
| --- | --- | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code:
(267) 817-5790
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of Each Class | Trading Symbol | Name of Exchange on Which Registered |
|---|---|---|
| Common Stock, par value $0.0001 per share | IPSC | Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
| Item2.02 | 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
| ExhibitNo. | 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
Exhibit 99.1
| January 2025<br>Corporate Overview | |
|---|---|
| 2<br>Forward-looking statements<br>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<br>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<br>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<br>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<br>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,”<br> “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these<br>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<br>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<br>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<br>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,<br>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<br>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<br>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<br>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<br>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<br>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<br>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<br>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<br>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<br>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<br>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<br>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.<br>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<br>events, changed circumstances or otherwise. | |
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| 1 3<br>Century’s ability to create multiple iPSC-derived cell types incorporating<br>Allo-Evasion stands apart from other allogeneic cell therapy approaches<br> • Off-the-shelf therapies<br> • Potential for improved time-to-treatment<br> • Broad availability<br> • Manufacturing dependability<br>Engineerability<br> • Control of differentiation<br>to multiple cell types<br> • Nearly unlimited genetic<br>editing capacity due to<br>infinite replicative<br>capacity<br>Engineering for immune evasion<br>from:<br> • Native T-cells and NK-cells<br> • Antibody immunity<br>Enables potential for persistence<br>and re-dosing of therapy<br>Reproducibility<br> • Fully characterized single<br>cell clones form master<br>cell bank (MCB)<br> • Deep understanding of<br>cell function and safety<br>Profitable Scalability<br> • Large batch sizes with<br>batch-to-batch consistency<br> • Pathway to significantly<br>reduced COGS similar to<br>antibody therapies<br> • Expansion from a single-clone MCB decreases risk<br>of cell exhaustion<br>Allogeneic iPSCs Allo-Evasion<br>Clear differentiation from other allogeneic cell therapies with pathway to antibody-like scale | |
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| 4<br>Adaptive<br>lymphocytes –<br>capable of<br>generating distinct<br>functional<br>attributes<br>Greatest proliferative<br>potential – potentially<br>most useful for ongoing<br>antigenic pressure<br>GvHD risk,<br>eliminated by<br>knockout of<br>T cell receptor<br>(TCR)<br>Potential for<br>long-lived<br>memory,<br>mediating<br>immune<br>surveillance<br>Bridge between<br>innate and<br>adaptive<br>lymphocytes<br>Rapid activation<br>response and capacity<br>for clonal expansion<br>No GvHD risk,<br>TCR is invariant<br>Trafficking and<br>persistence as<br> ‘tissue-resident<br>T-cells’<br>Innate<br>lymphocytes –<br>most potent<br>cytolytic capacity<br>Less rapid and more<br>limited expansion gives<br>greater control over<br>exposure – potentially<br>more useful for short-term treatment<br>Little GvHD risk,<br>naturally<br>suppressive<br>Traffic to bone<br>marrow and<br>secondary<br>lymphoid tissues<br>Century’s capability to make multiple cell types enables optimal matching of<br>cell characteristics to indication<br>Engineered iPSC<br>MCBs<br>CAR iNK cell<br>CAR iT cell<br>CAR iT cell<br>CD4<br>CD8<br>The right cell for the right indication(s)<br>MCB: Master Cell Bank<br>GvHD: Graft vs Host Disease | |
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| 5<br>Century is a leader in immune evasion engineering<br>Continuous evolution of holistic protection from major immunity pathways<br>Allo-Evasion 1.0 Allo-Evasion 3.0 Allo-Evasion 5.0<br>Protection from:<br>Native T-cells Deletion of HLA-I<br> Deletion of HLA-II<br> Deletion of HLA-I<br> Deletion of HLA-II<br> Deletion of HLA-I<br> Deletion of HLA-II<br>Native NK-cells Insertion of HLA-E<br> Insertion of HLA-E<br> Insertion of HLA-G<br> Insertion of CD300a TASR pan-NK<br>inhibitory ligand1<br>Humoral immunity Insertion of cell-surface enzyme<br>to degrade IgG antibodies2<br>CNTY-101<br>1. https://www.centurytx.com/wp-content/uploads/ASH_Welstead_Universal-Protection-of-Allogenic-T-Cells-Final.pdf<br>2. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013436/518079/Universal-Protection-of-Allogeneic-T-Cell<br>b2M KO (HLA-I)<br>CIITA<br>KO (HLA-II)<br>CD8+<br>T Cell<br>CD4+<br>T Cell<br>Pan NK Inhibitory<br>ligand<br>Fc<br>NK cell<br>CNTY-102 CNTY-108 CNTY-308 CNTY-361 CNTY-107 | |
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| 6<br>Allo-Evasion engineering aims to drive durable responses by enabling repeat<br>dosing for tighter control over drug exposure<br>Ongoing clinical data from CNTY-101 in ELiPSE-1 show persistent exposure in the presence<br>of an intact immune system1<br>With Allo-Evasion engineering<br>Without Allo-Evasion engineering<br>Dose 1 Dose 2 Dose 3<br>1. Company data: ELiPSE-1 Phase 1 study in B-cell malignancies | |
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| 7<br>Product iPSC Allo-Evasion Targets Indications Research IND-enabling<br>Clinical<br>P1 P2 P3<br>CNTY-101 iNK 1.0 CD19<br>B-cell malignancies<br>Autoimmune diseases<br>CNTY-308 iT 5.0 CD19<br>Autoimmune diseases<br>B-cell malignancies<br>CNTY-361 iT 5.0 BCMA Myasthenia gravis<br>CNTY-102 iT 3.0 CD19 + CD22 B-cell malignancies<br>CNTY-104* iNK/iT Undisclosed Multi-specific AML<br>CNTY-106* iNK/iT Undisclosed Multi-specific MM<br>CNTY-107 iT 5.0 Nectin-4 Solid tumors<br>CNTY-108 iNK/ iT 3.0 CD19 Autoimmune diseases<br>Century is advancing a diverse iPSC pipeline across cell types and targets in<br>cancer and autoimmune diseases<br>CALiPSO-1<br>ELiPSE-1<br>*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<br>Autoimmune diseases<br>Hematologic tumors<br>Solid tumors | |
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| CNTY-101<br>CAR-iNK cell therapy with Allo-Evasion 1.0 | |
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| 9<br>CNTY-101: A CD19-targeted CAR-iNK product designed to provide precise<br>control of drug exposure and enable repeat dosing<br>CNTY-101 off-the-shelf CAR-iNK cell therapy designed to<br>treat patients with B cell-mediated diseases<br> • Six precision gene edits<br> • CD19-targeted CAR for B-cell depletion<br> • Allo-Evasion technology enables re-dosing without<br>lymphodepletion<br> • Secreted IL-15 enhances cell persistence<br> • Safety switch enables elimination of CNTY-101 with<br>cetuximab, if required for patient safety<br> • iNK cells incorporating Allo-Evasion provide more<br>predictable pharmacokinetics and pharmacodynamics<br>CNTY-101<br>HLA-I<br>Knockout<br>IL-15<br>HLA-II<br>Knockout<br>CD19 CAR<br>HLA-E Safety<br>Switch<br>Currently in Phase 1 trials in B-cell malignancies (ELIPSE-1)<br>and autoimmune disorders (CALIPSO-1)<br>https://www.centurytx.com/wp-content/uploads/ASGCT24-CNTY-101-AI-Poster.pdf | |
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| 10<br>CNTY-101 in relapsed/refractory B-cell lymphomas aims to deliver durable<br>responses via repeat dosing<br>Facilitated by Allo-Evasion and extending the period of pharmacologic pressure on tumor cells<br>Unmet need: Potential solution from Century’s platform:<br> • Autologous CD19 CAR-T is curative in ~40%1 of<br>patients<br> • Autologous CD19 CAR-T access is limited and/or<br>can fail in manufacturing as quality is dependent<br>on patient-derived starting material<br> • Limited options and poor prognosis for patients<br>who fail autologous CAR-T<br> • Off-the-shelf product offers immediate access<br>and consistency<br> • Multiple doses to increase pharmacological<br>pressure to increase durability<br> • Host rejection addressed by Allo-Evasion edits<br>CAR-T: Chimeric Antigen Receptor T cell therapy 1Cappell, Nature Reviews Clinical Oncology 2023 | |
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| 11<br>ELiPSE-1 is a dose-escalating Phase 1 study of CNTY-101 in B-cell malignancies<br>(NCT05336409)<br>Patients with CD19+<br>aggressive and high-risk<br>indolent R/R B-NHL<br> • Part 1 – Dose escalation<br> • Schedule A: Single dose<br> • Schedule B: 1 dose per week x 3 weeks<br> • Part 2 – Dose expansion<br>DLBCL: Diffuse large B cell Lymphoma; HGBL: High-Grade B-cell Lymphoma; MCL: Mantle Cell Lymphoma; PMBCL: Peripheral<br>Mediastinal B-cell Lymphoma; FL3B: Follicular Lymphoma Grade 3B; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma<br>DLT: Dose Limiting Toxicity<br>IL-2: Interleukin-2 (dose: 3e6 IU; subcutaneous)<br> • DLBCL, HGBL, MCL, PMBCL, FL3B, FL, MZL<br> • >2 prior lines of therapy<br> • Prior CD19-targeted cell therapy allowed<br>Dose level 4: 3 billion4<br>Bayesian Optimal Interval (BOIN) design<br>1. Standard lymphodepletion regimen: fludarabine (30 mg/c/d) and cyclophosphamide IV (300 mg/m/d) for 3 days<br>2. Subjects who are assessed as stable disease or better may receive additional cycles of CNTY-101<br>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<br>4. For DL 4B, initial 2 cycles at DL 4B; subsequent cycle regimen depending on response or risk/benefit | |
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| 12<br>ELiPSE-1 enrolled<br>heavily pre-treated<br>R/R B-NHL patients<br>ELiPSE-1 (NCT05336409) Phase 1 study in CD19+ B-cell Malignancies<br>1 As of 15 October 2024 data snapshot date, data collection ongoing<br>DLBCL: Diffuse Large B Cell Lymphoma, HRFL: High-Risk Follicular Lymphoma; MCL: Mantle Cell Lymphoma, MZL: Marginal Zone<br>Lymphoma<br>Baseline characteristics Safety evaluable<br>(N=20)<br>Median age (range, years) 66 (51–80)<br>Male, n (%) 16 (80)<br>Median follow up (range, months) 3.34 (0.5–18.8)<br>NHL subtype, n (%)<br>DLBCL 11 (55)<br>HRFL 2 (10)<br>MCL 4 (20)<br>MZL 3 (15)<br>Prior therapies, median (range) 4 (2–6)<br>Response to Last Line of Treatment, n (%)<br>Relapsed 8 (40)<br>Refractory 12 (60)<br>Received Prior CAR T, n (%) 9 (45) | |
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| 13<br>CNTY-101 shows evidence of dose-responsive efficacy in ELiPSE-1 Phase 1<br>Increased ORR at higher dose alongside a favorable safety profile<br>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)<br>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)<br>ORR: Overall Response Rate, DLTs: Dose Limiting Toxicities, CRS: Cytokine Release Syndrome, ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome, CAR: Chimeric Antigen Receptor | <br>Efficacy (DL3B, N=6)<br> • 83% ORR; median follow up 2.9 months<br>(range 1.2–5.3 months)<br> • All subjects were eligible to receive additional<br>cycle(s)<br> • 4 patients received prior autologous CAR-T therapy<br>Safety & Tolerability (N=20)<br> • No GvHD; no DLTs<br> • CRS: Grade 1 (N=3), Grade 2 (N=3)<br> • Hypotension (n=2) and hypoxia (n=1) lasted<br> <24 hrs.<br> • ICANS: Grade 1 (n=1), resolved in <24hrs<br> • Majority of subjects received at least one dose in the<br>outpatient setting<br>3<br>1 1 1 1 1<br>1 1 1<br>3<br>1<br>1<br>1<br>2<br>0<br>1<br>2<br>3<br>4<br>5<br>6<br>7<br>100e6 (1A) 300e6 (2A) 1e9 (3A) 3e9 (4A) 300e6 (2B) 1e9 (3B)<br>Schedule A<br> (One infusion/cycle)<br>Schedule B<br> (Three infusions/cycle)<br># of subjects<br>Best Overall Response per Lugano<br>PD SD PR CR |
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| 14<br>PBMC genomic DNA Plasma cell-free DNA<br>CNTY-101 exposure increases with dose and schedule<br> • Extended persistence in circulation at dose level 4A (3 x 10e9 cell infusion)<br> • Persistence outside the bloodstream was detected via a cell-free (cf) DNA assay beyond day 15<br> • Multiple infusions in Schedule B drive increased exposure throughout the dosing cycle<br>Transgene copies per ug were determined using ddPCR with primers targeting transgene and<br>RPP30. Data shows cycles with LDC across subjects at each dose level. Error bars shown are<br>mean ± SD. LLOQ: Lower limit of quantification. Black triangle indicates infusion. S: Screen<br>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 <<br>0.05. All LDC+ cycles are shown. Black triangles indicate infusions. S: Screen, LOB: Limit of Blank.<br>Schedule A Schedule B<br>Day in cycle Day in cycle<br>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<br>Schedule A<br>Day in cycle | |
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| 15<br> • Lymphodepleting Chemotherapy (LDC) depleted patient NK/T cell<br>counts and drove a transient spike of IL-15 cytokine<br> • By post-infusion day 8, NK/T cell counts, IL-15 concentration<br>returned to screening level<br> • Similar PK profile observed for each CNTY-101 infusion within a cycle<br>despite evident patient immune recovery<br>Enabled with Allo-Evasion , CNTY-101 shows persistence in the presence of a<br>restored immune system<br>Translational data available as of Oct 28, 2024<br>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<br>Similar exposure of CNTY-101 in the presence or absence<br>of endogenous lymphocytes<br>Infusion<br>LDC<br>Model of Allo-Evasion -enabled cellular kinetics | |
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| 16<br>CNTY-101 treatment demonstrates rapid B-cell depletion and was associated<br>with naive non-class switched profile of re-emergent B-cells<br>Data in r/r NHL patients supports the application of CNTY-101 in autoimmune diseases<br>B-cell depletion Re-emergent B-cell profile<br>Rapid and effective depletion of circulating B cells<br>observed in the first cycle<br>0<br>20<br>40<br>60<br>80<br>100<br>%CD19+CD20+ B cells<br>Non-class switched Class-switched<br>Healthy donors Patients<br>Re-emergent B cells show naive non-class-switched profile<br> • Reduction of class-switched phenotypes in re-emergent B cells has<br>been associated with SLE responses to CD19-targeted cell therapies<br>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<br>represents an individual subject. Data from a subject with supraphysiological levels of circulating malignant B cells was excluded<br>Data shows proportion of non-class switched (IgD+, IgM+ or IgD+IgM+) or switched (IgD-IgM-) circulating B cells (CD19+ CD20+) in healthy<br>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<br>not shown)<br>Source: Company data, available as of Oct 28, 2024 | |
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| 17<br>ELiPSE-1 initial data validates Century’s iPSC platform<br>Heavily pretreated and refractory patient population treated in first-in-human dose escalation<br>trial, including ~50% patients who had received prior CAR T treatments<br>Favorable initial safety profile; can be delivered in an outpatient setting<br>Increased response rates at higher doses and observations of deepening responses with additional<br>cycles.<br>83% ORR at Dose Level 3B<br>Dose-dependent increase in CNTY-101 exposure observed<br>Data for CNTY-101 continues to support the potential for Allo-Evasion to enable a multi-dosing regimen<br>in the presence of a restored endogenous immune system<br>ORR: Overall Response Rate | |
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| 18<br>Autoimmune disorders present significant unmet medical need<br>Systemic Lupus<br>Erythematosus (SLE) Lupus Nephritis (LN) Idiopathic Inflammatory<br>Myopathy (IIM)<br>Diffuse cutaneous Systemic Sclerosis<br>(dcSSc)<br>Characteristics<br>Multiorgan, potentially fatal,<br>inflammatory disease with risk for<br>organ damage, including skin, heart,<br>and brain<br>Kidney manifestation of SLE with<br>potential kidney failure requiring<br>dialysis and increased risk for<br>mortality<br>Inflammation of muscle, lungs, skin,<br>joints, and gastrointestinal tract causing<br>weakness, pain, and lung failure which<br>can lead to chronic disability and<br>potentially mortality<br>Fibrosis and vasculopathy of the skin<br>and internal organs, with high risk for<br>disability, disfigurement, and<br>cardiopulmonary mortality<br>US Prevalence1 180,000-340,000 80,000–120,000 >60,000 >85,000 (SSc)<br>Initial addressable<br>subpopulations2<br> >20,000 >30,000 >10,000 >30,000<br>Standard of care<br>Corticosteroids, chemotherapy,<br>immunosuppressants, anticoagulants,<br>plasmapheresis<br>Corticosteroids, chemotherapy,<br>immunosuppressants, dialysis<br>Corticosteroids, immunosuppressants,<br>IVIg<br>Slow progression: Immuno-suppressants, vasodilators, antifibrotic<br>agents<br>Limited efficacy with<br>approved therapies3<br> <35% low disease activity (LLDAS) <40% complete renal response<br>(CRR)<br> <40% total improvement score (TIS) of<br>60%<br>Slower decline in lung function (FVC<br>decrease >24 mL/year on therapy)<br>Unmet Medical Need Low disease activity, prevention of<br>organ damage, survival<br>Prevention of renal failure,<br>survival<br>Remission, maintain function,<br>prevention of calcinosis, damage,<br>respiratory failure, survival<br>Slow progression, prevent cardiac or<br>respiratory failure, survival<br>Despite approved treatments, significant underappreciated unmet need remains<br>Even effective available treatments leave patients<br>suffering with active disease, shortened lifespan, and<br>prospect of life-long medication<br>SoC relies on chronic treatment with<br>broad-acting corticosteroids &<br>immunosuppressives<br>Treatment toxicity and disease<br>flares leading to organ damage<br>remain common<br>Current treatments fail to significantly<br>improve quality of life or prevent organ<br>failure in majority of patients<br>(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<br>(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<br>(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;<br>Distler NEJM 2019; Khanna Lancet Respir Med 2020<br>LLDAS, lupus low disease activity state; FVC, forced vital capacity | |
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| 19<br>Clear opportunity for allogeneic cell therapies to address moderate to severe<br>autoimmune indications by providing long-term, drug-free remission<br>Significant patient population and<br>unmet need<br> • Tens of thousands of patients with<br>unmet need in the US<br> • Heterogeneous nature of patients<br>with autoimmunity supports<br>opportunity for multiple modalities<br>within and across indications<br> • Treatments needed to resolve<br>inflammation, prevent organ failure,<br>normalize lifespan, and avoid<br>toxicity of life-long medication<br>Opportunity to deliver<br>transformational efficacy<br> • Dramatically improve upon standard of<br>care<br> • SLE: LLDAS achievement –<br>predictor for reduction of damage<br>accrual<br> • LN: Complete renal response (CRR)<br> • SSc: High %CRISS, FVC stabilization<br> • IIM: High %TIS<br> • Optimal outcome: drug-free remission<br>Compelling evidence for benefit from<br>deep depletion of pathogenic B-cells<br> • Autologous anti-CD19 CAR-T cell<br>therapies demonstrate potential for<br>long-term drug-free remission<br> • Unmet challenges include safety<br>(CRS, ICANS, neutropenia, B cell<br>aplasia), logistics, and product<br>availability<br> • Emerging data for allogeneic cell<br>therapies2 demonstrate potential for<br>transformative impact and may address<br>above challenges<br>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<br>2. Yu Arthritis Rheumatol. 2024; Goulding Arthritis Rheumatol. 2024, Wang Cell 2024 doi.org/10.1016/j.cell.2024.06.027<br>CRISS: Composite Response Index for Clinical Trials in Early Diffuse Systemic Sclerosis | |
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| 20<br>Allogeneic iPSC<br> • Available “off-the-shelf”<br> • No patient apheresis required<br> • No manufacturing wait time<br> • Batch-to-batch consistency<br> • Platform enables lower COGs<br>than donor-derived or<br>autologous<br>NK cells<br> • Killing potency (≥ primary CAR-T)<br>leads to deep B-cell depletion1<br> • Trafficking to secondary lymphoid<br>tissues and marrow favors<br>pathogenic B-cell targeting<br> • Short-lived, more predictable<br>pharmacokinetics and<br>pharmacodynamics<br> • Manageable safety profile, well-tolerated in ELiPSE-1<br>Allo-Evasion<br> • Avoiding host immune<br>rejection<br> • Ability to repeat dose<br>without continued<br>lymphodepletion<br> • Ability to re-treat, if needed<br>CNTY-101 is a differentiated autoimmune disease treatment: Allogeneic iPSC<br>CAR iNK cell therapy with Allo-Evasion<br>1. https://www.centurytx.com/wp-content/uploads/ASH_Chin_Natural-Killer-GD-Cells-Final.pdf<br>Tighter control over drug exposure:<br>B-cell depletion without prolonged B-cell aplasia | |
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| 21<br>In vitro studies show that CNTY-101 eliminates B cells with greater potency<br>than primary CAR-T cells<br>https://www.centurytx.com/wp-content/uploads/ASH_Chin_Natural-Killer-GD-Cells-Final.pdf<br>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.<br>Assay plates were harvested and stained for Fixable Live/Dead. Cells were fixed and run on cytometer to determine Target+Dead Cell populations.<br>E:T: Effector:Target ratio, UTD: Untransduced donor cells as control<br>24-hour cytolysis study of CNTY-101 against B-cells from SLE patients,<br>compared to primary CAR-T cells derived from healthy donors | |
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| 22<br>CALiPSO-1 is a Phase 1 study of CNTY-101 in refractory B cell-mediated<br>autoimmune diseases (NCT06255028)<br>infusions in outpatient setting<br>Inclusion:<br> • Participants with moderate to severe SLE,<br>LN, IIM, or dcSSc with treatment-resistant<br>and active disease, after 2+ standard<br>immunosuppressive therapies<br>Endpoints:<br> • Key endpoints: Safety and tolerability, disease activity measures per clinical and<br>laboratory assessments<br> • Translational endpoints: PK, B-cell depletion, autoantibody decline<br>Cycle 1<br>Cycle 2<br>No lymphodepletion<br>Schedule<br>Dose level: 1e9 cells<br>Lympho<br>-depletion<br>28-day DLT<br>Period*<br>Patient<br>enrollment<br>Up to N=48<br>Response<br>assessments<br>months 2–12<br>Clinical trial sites open for enrollment (USA); expansion to EU sites expected in 2025<br>SLE: Systemic Lupus Erythematosus; LN: Lupus Nephrits; IIM: Idiopathic inflammatory Myopathy; dcSSc: Diffuse Cutaneous Systemic Sclerosis<br>*Response assessment conducted at one month; does not gate Cycle 2 | DLT: Dose Limiting Toxicity<br>CNTY-101<br>CNTY-101<br>CNTY-101<br>Day 1 Day 8 Day 15<br>CNTY-101<br>CNTY-101<br>CNTY-101<br>Day 1 Day 8 Day 15<br>Day 8 and subsequent infusions allowed in outpatient setting |
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| CNTY-308<br>CAR αβ-iT cell with Allo-Evasion 5.0 | |
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| 24<br>CNTY-308 is an iPSC-derived CD19-targeted CAR-iT with preclinical efficacy<br>comparable to autologous CD19 CAR-T cells<br>1. https://www.centurytx.com/wp-content/uploads/ASH_Heinze_iPSC-Derived-CD4-CD8-Final.pdf<br>CD4+/CD8+ iT-cell<br> • CD19-targeted CAR to target B-cells for cytotoxic depletion<br> • 4-1BB and CD3z co-stim domain to stimulate expansion<br>on target engagement<br> • Allo-Evasion 5.0 edits include protection from host T cell,<br>NK cell, and humoral response<br> • Displays characteristics of autologous CAR-T cells1<br> • Highly proliferative upon target engagement<br> • Secretes cytokines (e.g., IL-2, IFN, and TNF)<br> • Cytotoxic effector function rapidly eliminates tumor cells<br> • Long-term persistence in vivo<br>CNTY-308 | |
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| 25<br>Century’s iPSC-CAR-T cells display the functional characteristics of adult<br>primary T cells: In vitro activity<br>Effective T cell therapies require the generation of iPSC-CAR-T cells<br>with three key in vitro cell functions<br>Cytotoxicity:<br>Effector function<br>Cell expansion and<br>persistence<br>Therapeutic<br>efficacy requires:<br>Cytokine (IL2)<br>production<br>iPS-CAR-T 1’ CAR-T<br>IL-2 secretion (pg/ml)<br>iPS-CAR-T 1’ CAR-T CD19 iPSC-CART Primary CART<br>0<br>5<br>10<br>15<br>20<br>Fold Change<br>https://www.centurytx.com/wp-content/uploads/ASH_Heinze_iPSC-Derived-CD4-CD8-Final.pdf | |
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| 26<br>1e+06<br>1e+07<br>1e+08<br>1e+09<br>1e+10<br>0 10 20 30 40 Days Post−Effector Infusion<br>Luminescence (log axis)<br>Group<br>PBS only<br>1' CAR−T<br>iPS−CAR−T<br>Group 1: PBS only Group 2: 1' CAR−T Group 3: iPS−CAR−T<br>0 10 20 30 0 10 20 30 0 10 20 30<br>1e+07<br>1e+09<br>1e+11<br>Days Post−Effector Infusion<br>Luminescence (log axis)<br>In preclinical animal studies, Century iPSC-CAR-T cells show comparable<br>activity to primary CAR-T cells<br>Complete tumor control<br>Measurable long-term persistence ≥1 mo Cytotoxicity maintained upon re-challenge with engrafted cells<br>10<br>100<br>1000<br>PBS 1' CAR−T iPS−CAR−T Group<br>hCD45+ count per 100 uL whole blood<br>In vivo experimental details<br> • Disseminated Nalm6 model (1e5 cells infused)<br> • Effectors added 3 days post-tumor infusion<br> • 1’ CAR-T dose: 5e6 cells<br> • iPSC-CAR-T dose: 30e6 cells<br> • No added cytokine or small molecule support<br>Group joined by lines<br>d7 d21<br>d35<br>d27 tumor rechallenge<br>Key<br>Tumor<br>challenge<br> • iPSC-CAR-T persist 21 days post-infusion,<br> • iPSC-CAR-T detectable at day 35, 7 days post-tumor rechallenge (at day 28)<br>Tumor<br>challenge<br>Tumor<br>challenge<br>Tumor<br>challenge<br>Tumor<br>challenge<br>1e+06<br>1e+07<br>1e+08<br>1e+09<br>1e+10<br>0 10 20 30 40<br>Days Post−Effector Infusion<br>L<br>u<br>min<br>e<br>s<br>c<br>e<br>n<br>c<br>e (lo<br>g<br>a<br>xis)<br>Class<br>PBS only<br>1' CAR−T<br>iPS−CAR−T<br>Group<br>PBS only<br>1' CAR−T<br>iPS−CAR−T | |
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| Platform: iPSC cell foundry | |
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| 28<br>Century’s robust pre-clinical pipeline has potential to address critical barriers<br>confronting cellular therapies<br>Multiple iPSC-derived<br>immune effector cells<br>iPSC-enabled<br>engineering solutions<br>Opportunity across<br>multiple diseases<br> • Cytokine engineering to reduce or<br>eliminate lymphodepletion<br> • Enhanced Allo-Evasion enables<br>repeat dosing, extended drug<br>exposure and potential for durable<br>remissions<br> • Resistance to suppressive<br>cytokines within the tumor<br> • iNK<br> • iT<br> • iT (CD4+, CD8+)<br> • Next-generation therapies for oncology:<br> • CD19, CD19/22 CARs<br> • Nectin-4 CAR<br> • High-affinity Fc receptors<br> (enable treatment with mAbs)<br> • Key targets in autoimmune diseases:<br> • CD19 and BCMA | |
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| 29<br>Precision CRISPR MAD7-mediated sequential gene editing of iPSCs generates<br>uniform product candidates<br>Multiple gene edits (KO/KI)<br>iPSC<br>Engineered iPSC Master Cell<br>Bank (MCB)<br>Sequential selection steps<br>iPSC Precision Engineering<br>CRISPR-mediated HDR (MAD 7)<br>Advantages of Century’s Platform<br>Precise CRISPR-mediated homology-directed repair1<br>reduces off-target integration<br>Successive and efficient gene editing through iPSC<br>platform avoids risky multiplex modification and<br>structural variants<br> • Allo-Evasion edits<br> • Protein and cell engineering<br>Quality control through generation of homogenous MCB<br>establishes genomic product integrity<br>Manufacturing begins at the MCB, confirmed to be free<br>from genetic aberrations<br>1. MAD7 Nuclease: https://www.inscripta.com/wp-content/uploads/2023/03/Liu-et-al-2019-Nature-Communications.pdf | |
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| 30<br>Century platform and in-house manufacturing: Pathway to scalable, profitable<br>cell therapy<br>Established in-house manufacturing from development to launch Quality product at disruptive scale and cost of goods<br> • Built-for-purpose 53,000 ft2 cGMP facility<br> • Key leaders each with 1–2 decades of cell therapy manufacturing<br>expertise, from leading commercial cell therapies<br> • In-house team facilitates aligned priorities, learnings, faster<br>product iteration for efficiency, speed, and product quality<br> • Builds and protects proprietary know-how<br> • Optionality with redundant sites (in-house, active CDMO)<br> • Consistency: Control of manufacturing and single-donor master-cell-bank over product lifetime for batch-to-batch reproducibility<br> • Increased cell fitness: Differentiated immune cells do not undergo<br>excessive expansion cycles which often result in cell exhaustion<br> • Product homogeneity: Clonal origin enables a well-characterized<br>product<br> • Potential to manufacture at antibody-like scale: Scalable platforms and<br>optimized processes to maximize yield, reduce COGs, and meet demand | |
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| 31<br>Century Therapeutics is advancing next-generation iPSC-derived allogeneic<br>NK and T cell therapy candidates for the treatment of cancer and autoimmunity<br>Ended FY24 with cash, cash equivalents,<br>and investments of ~$220M (unaudited*)<br>Cash runway into 2H26<br>Differentiated pipeline based on iPSC and Allo-Evasion technology<br> ✓ Potential to overcome limitations of conventional allogeneic cell therapy<br> ✓ Preclinical demonstration of CD4+/CD8+ iT cells with characteristics of primary T cells<br>Encouraging preliminary clinical data from Phase 1 trial of CNTY-101 in<br>R/R B-cell lymphomas<br> ✓ 83% ORR at dose level 3B, with favorable safety profile<br> ✓ Data supports the ability to re-dose in the presence of a restored endogenous immune system<br> ✓ Study continuing with escalation to dose level 4B<br>Expansion into additional autoimmune indications<br> ✓ CALiPSO-1 trial initiated in SLE, LN, IIM, and dcSSc participants<br> ✓ CNTY-101 has differentiated profile in AID (allogeneic, iNK with Allo-Evasion )<br> ✓ Multiple pipeline opportunities in AID<br>In-house manufacturing capabilities<br> ✓ Efficient, scalable manufacturing<br>Phase 1 ELiPSE-1 trial of CNTY-101 in B-cell<br>malignancies<br> • Updated clinical data expected by mid-2025<br>Phase 1 CALiPSO-1 trial of CNTY-101 in B-cell mediated<br>autoimmune diseases<br> • Enrollment of patients across indications<br>Pre-clinical pipeline prioritization<br> • Prioritized pipeline to be announced in 1Q25<br>Multiple near-term milestones<br>*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<br>for our full audited financial statements prepared in accordance with U.S. generally accepted accounting principles. | |
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| www.centurytx.com | |
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