EX-99.2 3 tm259654d1_ex99-2.htm EXHIBIT 99.2

 

Exhibit 99.2

 

Mar 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 fa cts 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 f orward - looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achieve men ts 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 - look ing statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “beli eve ,” “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, fi nancial 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 an d 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 an d 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 clinical development; our ability to meet development milestones on anticipated timelines; uncertainties inherent in the results of pr eli minary 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 cl earance 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 relat ion ships 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 pro duct 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 c onn ection 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 succes sfully 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 man agement and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “R isk 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 pred ictions of future events. The events and circumstances reflected in our forward - looking statements may not be achieved or occur, and actual results could differ material ly 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 t o t ime, 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 up date or revise any forward - looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

 

 

Extending cash runway into 4Q26; re - allocating resources to enable key value milestones Enhanced preclinical pipeline and platform aiming to expand and multiply cell therapy value • Four potentially transformative programs engineered with industry - leading Allo - Evasion 5.0 • Leading programs focus on iPSC - derived ‘tunable’ CD4+/CD8+ αβ T cells • Selective expansion to non - immune effector cells in high impact diseases Enhanced Preclinical Pipeline Concentrated Clinical Focus Resourcing for Value Concentrating clinical focus with CNTY - 101 on autoimmune disorders with transformational potential • Unique profile of CD19 - targeting iNK cell product engineered with Allo - Evasion with clinical data from R/R NHL reinforcing potential in autoimmune disorders • Expansion of Phase 1 CALiPSO - 1 trial in US and EU with CARAMEL IIT expected to commence in mid - 2025 Century Therapeutics: Clear focus on transformational value with unique iPSC - derived cell therapies GOAL: E xpand and enhance cell therapy value • Ended FY24 with cash, cash equivalents, and investments of $220M • CNTY - 308 T cell program expected to enter IND - enabling stage in mid - 2025 • CNTY - 101 autoimmune clinical data expected in 2025

 

 

4 Clear differentiation from other allogeneic cell therapies with pathway to antibody - like scale Century’s ability to create multiple iPSC - derived cell types incorporating Allo - Evasion stands apart from other allogeneic cell therapy approaches Engineerability • Control of differentiation to multiple cell types • Nearly unlimited genetic editing capacity due to infinite replicative capacity 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 Allo - Evasion iPSCs Off - the - shelf therapies Potential for improved time - to - treatment Broad availability Manufacturing dependability Enables potential for persistence and re - dosing of therapy Engineering for immune evasion from: • Native T - cells and NK - cells • Antibody immunity 4

 

 

5 Allo - Evasion engineering aims to drive durable responses by enabling repeat dosing for tighter control over drug exposure Clinical data from CNTY - 101 in ELiPSE - 1 show persistent exposure in the presence of an intact immune system 1 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

 

 

6 Continued evolution to enhance holistic protection from major immunity pathways Century is a leader in immune evasion engineering Allo - Evasion 1.0 Deletion of HLA - I Deletion of HLA - II Insertion of HLA - E Protection from: Native T - cells Native NK - cells Humoral immunity CNTY - 101 1. Company data: ELiPSE - 1 Phase 1 study in B - cell malignancies 2. https://www.centurytx.com/wp - content/uploads/ASH_Welstead_Universal - Protection - of - Allogenic - T - Cells - Final.pdf 3. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013436/518079/Universal - Protection - of - Allogeneic - T - Cell 4. Peraro et al, Mol. Therapy 2021, 29(12), 3398 - 3409; https://pmc.ncbi.nlm.nih.gov/articles/PMC8636170 CNTY - 308 CNTY - ST CNTY - 341 Deletion of HLA - I Deletion of HLA - II Insertion of CD300a TASR pan - NK inhibitory ligand 2, 3 Insertion of cell - surface enzyme to degrade IgG antibodies 4 b2M KO (HLA - I) CIITA KO (HLA - II) CD8 + T Cell CD4 + T Cell Pan NK Inhibitory ligand Fc NK cell Allo - Evasion 5.0

 

 

7 The CD300a TASR ligand mimics natural signaling to provide broad protection from host NK cells CD300a detects disordered membrane lipids TASR mimics signaling of dead or dying cells Drug Product (live) Inhibit NK Cell TASR CD300a Dead/dying c ell NK Cell Inhibit CD300a Male Female <50 >50 Gender Age Ethni- city CMV Caucasian Other African American Hispanic Negative Positive N = 45 PBMC Donors 0.01 0.1 10 0.01 0.1 1 0 25 50 75 100 0 E:T Ratio T Cell Survival (%) No Cloak CD300a TASR CD47 HLA - I+ 20 hours Target (T) T Cell NK Effector (E) CD300a NKG2A KIR 0 20 40 60 80 100 Inhibitory Receptor Expression on NK Cells (n = 46 donors) % o f N K C e l l s CD300a is expressed broadly TASR provides protection from NK cells in vitro NK Donor 2 (2C dom ) NK Donor 1 (2A dom ) NK Donor 3 (2A dom ) TASR KI B2M KO https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013436/518079/Universal - Protection - of - Allogeneic - T - Cell ; https://www.centurytx.com/wp - content/uploads/ASH_Welstead_Universal - Protection - of - Allogenic - T - Cells - Final.pdf

 

 

8 Clinical IND - enabling Research Indications Targets Product Phase 3 Phase 2 Phase 1 B - cell - mediated autoimmune diseases CD19 CNTY - 101 iNK ( Allo - Evasion 1.0) B - cell - mediated autoimmune diseases CD19 CNTY - 308 αβ iT ( Allo - Evasion 5.0) B - cell malignancies B - cell malignancies CD19 + CD22 CNTY - 341 iT ( Allo - Evasion 5.0) Solid tumors Nectin - 4/other Solid tumors iT ( Allo - Evasion 5.0) Undisclosed Undisclosed Undisclosed Non - immune effector 1. Agreement in place for an investigator - initiated trial (IIT) by Professors Georg Schett and Andreas Mackensen at Friedrich - Alexander University Erlangen - Nürnberg. CARAMEL trial intended to commence in mid - 2025 following CTA approval. Century is advancing a focused iPSC pipeline across cell types and targets in cancer and autoimmune diseases CALiPSO - 1 CARAMEL IIT 1 Autoimmune diseases Hematologic tumors Solid tumors

 

 

CNTY - 101 CAR - iNK cell therapy with Allo - Evasion 1.0

 

 

10 Currently in Phase 1 in autoimmune disorders https://www.centurytx.com/wp - content/uploads/ASGCT24 - CNTY - 101 - AI - Poster.pdf CNTY - 101: A CD19 - targeted CAR - iNK product candidate designed to provide precise control of drug exposure and enable repeat dosing CNTY - 101 off - the - shelf CAR - iNK cell therapy candidate designed to treat patients with B cell - mediated diseases • Six precision gene edits designed to enable: • 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

 

 

11 Autoimmune disorders present significant unmet medical need Diffuse cutaneous Systemic Sclerosis (dcSSc) Idiopathic Inflammatory Myopathy (IIM) Lupus Nephritis (LN) Systemic Lupus Erythematosus (SLE) Fibrosis and vasculopathy of the skin and internal organs, with high risk for disability, disfigurement, and cardiopulmonary 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 Kidney manifestation of SLE with potential kidney failure requiring dialysis and increased risk for mortality Multiorgan, potentially fatal, inflammatory disease with risk for organ damage, including skin, heart, and brain Characteristics >85,000 ( SSc ) >60,000 80,000 – 120,000 180,000 – 340,000 US Prevalence 1 >30,000 >10,000 >30,000 >20,000 Initial addressable subpopulations 2 Slow progression: Immuno - suppressants, vasodilators, antifibrotic agents Corticosteroids, immunosuppressants, IVIg Corticosteroids, chemotherapy, immunosuppressants, dialysis Corticosteroids, chemotherapy, immunosuppressants, anticoagulants, plasmapheresis Standard of care Slower decline in lung function (FVC decrease >24 mL/year on therapy) <40% total improvement score (TIS) of 60% <40% complete renal response (CRR) <35% low disease activity (LLDAS) Limited efficacy with approved therapies 3 Slow progression, prevent cardiac or respiratory failure, survival Remission, maintain function, prevention of calcinosis, damage, respiratory failure, survival Prevention of renal failure, survival Low disease activity, prevention of organ damage, survival Unmet Medical Need Despite approved treatments, significant underappreciated unmet need remains Even effective available t reatments 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

 

 

12 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: C omplete 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 c hallenges include safety (CRS, ICANS, neutropenia, B cell aplasia), logistics, and product availability • Emerging data for allogeneic cell therapies 2 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

 

 

13 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 depletion 1 • Trafficking to secondary lymphoid tissues and marrow favors pathogenic B - cell targeting • Short - lived, more predictable pharmacokinetics and pharmacodynamics • Manageable safety profile, w ell - 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

 

 

14 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 plate s 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 in vitro cytolysis study of CNTY - 101 against B - cells from SLE patients, compared to primary CAR - T cells derived from healthy donors

 

 

15 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

 

 

16 CNTY - 101 ELiPSE - 1 first - in - human study: Initial clinical experience in relapsed/refractory B - cell lymphoma validates Century’s IPSC platform Heavily pre - treated patient population (n=23 safety; n=22 efficacy) • Median 4 prior lines (range 2 - 6); 48% (11/23) of patients received prior CART Favorable initial safety and tolerability profile (n=23) • No dose - limiting toxicities (DLTs); no events of graft - versus - host disease (GvHD) • Majority of participants received CNTY - 101 infusions in an outpatient setting • In DL 3B and 4B (n=9), No ICANs; 3 patients (33%) had G1 or G2 cytokine release syndrome (CRS) Activity Profile in Relapsed / Refractory Aggressive BCL • ORR for DL 3B and 4B (n=9) was 77% (7/9) and complete response rate was 22% (2/9) Source: Company data available as of March 1, 2025 Emerging data reinforce potential of CNTY - 101 in autoimmune diseases at targeted dose levels (DL3B, 4B) • CNTY - 101 cells were detected in lymph node tumor biopsies early post - treatment • CNTY - 101 treatment demonstrates deep B cell depletion • CNTY - 101 infusions showed similar exposure in the presence or absence of endogenous lymphocytes

 

 

17 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 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 billion 4 Bayesian Optimal Interval (BOIN) design

 

 

18 Source: Company data available as of March 7, 2025 CNTY - 101 exposure increased with dose, sustained exposure at doses intended for CALiPSO - 1 study Error bars show mean ± SD on original scale, subsequently log10 transformed. Due to log scale, low values are truncated at 1. All schedule B LDC+ cycles are included. S: Screen, LOB: Limit of Blank. • Persistence, inclusive of cells outside the bloodstream, is detected via a cell - free ( cf ) DNA assay out to day 28 at dose level 4B • Multiple infusions in Schedule B drives exposure throughout the dosing cycle Transgene copies/mL of Plasma (LDC+ Cycles)

 

 

19 Infusion LDC • 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 • PK profile is comparable between cycles with and without LDC* Enabled with Allo - Evasion , CNTY - 101 infusions in dose level 3B showed similar exposure in the presence or absence of endogenous lymphocytes * Based on a Two One - Sided T test approach (TOST) comparing log cfDNA concentration two - days post each infusion with and without LDC, and assuming equivalence bounds +/ - 25% the mean cfDNA concentration with LDC. Translational data available as of March 7, 2025 Graphs show data from 3B cohort (N=6). 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 curve is a LOESS fit to medians in bottom panel. S: Screen Lymphocyte counts and PK profile Model of Allo - Evasion enabled cellular kinetics

 

 

20 Source: Company data as of March 7, 2025 CNTY - 101 cells were detected in lymph node tumor biopsies early post - treatment in Dose Level 3B and 4B CNTY - 101 iNK cells traffic to lymph nodes, observed more frequently at higher doses CAR TNFA IFNG CAR TNFA IFNG CAR CAR Day 10 Baseline CAR TNFA IFNG Scale bar 10µm CAR CAR TNFA IFNG CAR ROI #1 ROI #2 Subject from Dose Level 3B CNTY - 101 trafficking o bserved i n 3 out of 7 evaluable subjects in DL3B & DL4B CNTY - 101 cells detected by RNAscope on day 10 (two days post - second CNTY - 101 infusion)

 

 

21 CNTY - 101 treatment demonstrated deep 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 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 in 3B and 4B who had baseline B cell counts of 1 cell/ L or greater (N=7). Each line represents an individual subject. 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 profi le (IgD+ CD27 - , data not shown) Source: Company data, available as of March 7, 2024

 

 

CNTY - 308 CAR αβ - iT cell with Allo - Evasion 5.0

 

 

23 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 2. Company data on file CD4+/CD8+ αβ 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 designed to include protection from host T cell, NK cell, and humoral response • Native TCR knock - out to eliminate the risk of GvHD • Displays characteristics of autologous CAR - T cells 1 • 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 • Eliminates CD19+ primary B - cells in vitro 2 CNTY - 308

 

 

24 https://www.centurytx.com/wp - content/uploads/ASH_Heinze_iPSC - Derived - CD4 - CD8 - Final.pdf Century’s process is designed to control the ratio of CD4+ to CD8+ while expanding differentiating engineered CAR iPSC cells to αβ CAR - T cells Ending Viability Expansion from iPSCs ( - fold) Stage 90% 3 1 48% 54,000 2 80% 860,000 3+4 77% CD8+/CD4 - CD8+ skewing CD4+ skewing Stage 3 Stage 2: CD4+CD8+ DP T cells CD8 CD4 CD8 CD4 CD8 CD4 80% CD8 - /CD4+

 

 

25 CNTY - 308 1’ CAR - T Function ~2,000 ~3,000 IL - 2 secretion (pg/mL) No No Requires exogenous IL - 2/IL - 15 > 10 > 10 Repeat killing (rounds) 32 32 Persistence in blood (days) Yes Yes Tumor control after rechallenge ( in vivo) CNTY - 308 and 1’ CAR - T • Self - supports with own target - mediated IL - 2 • High functional persistence: kills for >10 rounds, persists in blood for 32+ days, controls tumor after in vivo rechallenge Source: Company data on file In preclinical studies, Century’s αβ iPS - CAR - T cells show characteristics similar to primary CAR - T cells

 

 

26 Century’s iPSC - CAR - αβ 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 iPS - CAR - T 1’ CAR - T IL - 2 secretion (pg/ml) iPS - CAR - T 1’ CAR - T https://www.centurytx.com/wp - content/uploads/ASH_Heinze_iPSC - Derived - CD4 - CD8 - Final.pdf

 

 

27 1e+06 1e+07 1e+08 1e+09 1e+10 0 10 20 30 40 Days Post−Effector Infusion L u m i n e s c e n c e ( l o g a x i s ) 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 L u m i n e s c e n c e ( l o g a x i s ) In preclinical animal studies, Century iPSC - CAR - T cells showed comparable activity to primary CAR - T cells Source: Company data Complete tumor control Cytotoxicity maintained upon re - challenge with engrafted cells Measurable long - term persistence ≥1 mo 10 100 1000 PBS 1' CAR−T iPS−CAR−T Group h C D 4 5 + c o u n t p e r 1 0 0 u L w h o l e b l o o d 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

 

 

28 Century’s early - stage programs target best - in - class profiles in oncology 1. Majzner and Mackall. Cancer Discovery. 2018. • αβ CAR - iT cells • Dual - targeting CD19 and CD22 to reduce potential for resistance in malignancy setting • Loss of CD19 in B cell malignancies treated by CD19 CAR T cells is a known mechanism of relapse 1 • Includes Allo - Evasion 5.0 designed to evade host T - cell, NK - cell, and humoral immunity • Incorporates other platform enhancements designed to improve cell persistence and long - term engraftment • CAR iT cells • Novel targeting approaches include • Proprietary nectin - 4 CAR • Novel TCRs providing additional functions • Novel CARs directed to other validated targets • Includes Allo - Evasion 5.0 designed to evade host T - cell, NK - cell, and humoral immunity • Cytokine engineering designed to improve cell persistence post infusion • Engineering designed to enhance trafficking and sustained function in tumor microenvironment CNTY - 341 Solid Tumors

 

 

Platform: iPSC cell foundry

 

 

30 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 • αβ iT (CD4+, CD8+) • Next - generation therapies for oncology: ​ • CD19, CD19/22 CARs • Nectin - 4, CD70, GPC3, and mesothelin CAR ​ • High - affinity Fc receptors (enable treatment with mAbs ​) • Key targets in autoimmune diseases : ​ • CD19

 

 

31 Potential for long - lived memory , mediating immune surveillance GvHD risk, eliminated by knockout of T cell receptor (TCR) Greatest proliferative potential – potentially most useful for ongoing antigenic pressure Adaptive lymphocytes – capable of generating distinct functional attributes Trafficking and persistence as ‘tissue - resident T - cells’ No GvHD risk, TCR is invariant Rapid activation response and capacity for clonal expansion Bridge between innate and adaptive lymphocytes Traffic to bone marrow and secondary lymphoid tissues Little GvHD risk, naturally suppressive Less rapid and more limited expansion gives greater control over exposure – potentially more useful for short - term treatment Innate lymphocytes – most potent cytolytic capacity 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 αβ iT cell CD4 CD8 The right cell for the right indication(s) MCB: Master Cell Bank GvHD: Graft vs Host Disease

 

 

32 Precision CRISPR MAD7 - mediated sequential gene editing of iPSCs generates uniform product candidates Multiple gene edits (KO/KI) iPSC Engineered iPSC Master C ell Bank (MCB) Sequential selection steps iPSC Precision Engineering CRISPR - mediated HDR (MAD 7) Advantages of Century’s Platform Precise CRISPR - mediated homology - directed repair 1 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

 

 

33 Century platform and in - house manufacturing: Pathway to scalable, profitable cell therapy Quality product at disruptive scale and cost of goods Established in - house manufacturing from development to launch • 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 • Built - for - purpose 53,000 ft 2 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)

 

 

Extending cash runway into 4Q26; re - allocating resources to enable key value milestones Enhanced preclinical pipeline and platform aiming to expand and multiply cell therapy value • Four potentially transformative programs engineered with industry - leading Allo - Evasion 5.0 • Leading programs focus on iPSC - derived ‘tunable’ CD4+/CD8+ αβ T cells • Selective expansion to non - immune effector cells in high impact diseases Enhanced Preclinical Pipeline Concentrated Clinical Focus Resourcing for Value Concentrating clinical focus with CNTY - 101 on autoimmune disorders with transformational potential • Unique profile of CD19 - targeting iNK cell product engineered with Allo - Evasion with clinical data from R/R NHL reinforcing potential in autoimmune disorders • Expansion of Phase 1 CALiPSO - 1 trial in US and EU with CARAMEL IIT expected to commence in mid - 2025 Century Therapeutics: Clear focus on transformational value with unique iPSC - derived cell therapies GOAL: E xpand and enhance cell therapy value • Ended FY24 with cash, cash equivalents, and investments of $220M • CNTY - 308 T cell program expected to enter IND - enabling stage in mid - 2025 • CNTY - 101 autoimmune clinical data expected in 2025

 

 

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