CNTY-101 / Century Therap - LARVOL DELTA

CNTY-101, an iPSC-Derived Allogeneic CD19 Targeting CAR-NK Product, Exhibits Robust B Cell Depletion and Has Broad Potential for Development in B Cell-Driven Autoimmune Diseases (EULAR 2025) - No abstract available

Immunology

Century Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "CNTY-101 in Autoimmune Disease:... (i) Focus on CALiPSO-1 clinical trial expansion and patient recruitment: Five clinical trial sites in the U.S. are active with additional U.S. clinical trial sites expected to open in 2025. Site activation activities are underway in select European countries, with enrollment at these sites expected to initiate in the second half of 2025...; (ii) The CARAMEL investigator-initiated trial (IIT), a Phase 1/2 trial of CNTY-101 in patients with B-cell-mediated autoimmune diseases led by Professors Georg Schett and Andreas Mackensen and sponsored by the Friedrich-Alexander University Erlangen-Nürnberg, is expected to commence in mid-2025. The CTA has been authorized in Germany; (iii) Clinical data by end of 2025: The company remains on track to report clinical data for CNTY-101 by the end of 2025."

New P1/2 trial • P1 data • Trial status • Lupus Nephritis • Systemic Lupus Erythematosus • Systemic Sclerosis

ELiPSE-1: A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Century Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=75 ➔ 28

Enrollment change • Enrollment closed • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Early discontinuation of ELiPSE-1 program in late-stage R/R NHL (GlobeNewswire) - "While the company remains encouraged by the clinical activity and tolerability profile of CNTY-101 in late-stage relapsed-refractory non-Hodgkin’s lymphoma (R/R NHL), the emerging clinical data do not meet the company’s threshold to be considered transformational in this patient population and the program is being discontinued. The company is committed to providing continued treatment access in the ELiPSE-1 trial for patients showing benefit....in addition to encouraging clinical activity in a difficult to treat R/R NHL population and a favorable tolerability profile, translational data also showed evidence of CNTY-101 trafficking to lymph nodes and deep B cell depletion following treatment. The ELiPSE-1 data continues to support proof-of-concept for Allo-Evasion and the ability to enable repeat dosing of the company’s cell therapies. Further data is expected to be presented in 2025."

P1 data • Trial termination • Non-Hodgkin’s Lymphoma

Century Therapeutics Reports Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Phase 1 CALiPSO-1 trial site expansion in United States and Europe: The first patient in our CALiPSO-1 Phase 1 trial in autoimmune diseases is enrolled and scheduled for dosing in March 2025. Five sites in the U.S. are actively screening patients and Century has increased resourcing for trial site activation and proficient recruitment. The company is also expanding the CALiPSO-1 clinical trial to include additional sites in select European countries and expects enrollment at those sites will initiate in the second half of 2025....CNTY-308 is being developed for B-cell mediated autoimmune diseases...The company expects to initiate IND-enabling studies with CNTY-308 in mid-2025."

Preclinical • Trial status • Immunology • Lupus Nephritis • Myositis • Systemic Lupus Erythematosus • Systemic Sclerosis

Century Therapeutics Announces Investigator-Initiated Phase 1/2 Trial of its iPSC-derived iNK Cell Therapy CNTY-101 in B-cell Mediated Autoimmune Diseases Sponsored by Internationally Renowned Key Opinion Leaders (GlobeNewswire) - "Century Therapeutics, Inc...has entered into an agreement for an investigator-initiated Phase 1/2 trial by Professors Georg Schett and Andreas Mackensen of its CD19 CAR-iNK investigational cell therapy candidate CNTY-101 in patients with B-cell mediated autoimmune diseases....The IIT (known as the CARAMEL trial) will evaluate safety, efficacy, and key translational data of CNTY-101 in systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathy, and diffuse cutaneous systemic sclerosis....The CARAMEL trial with Century is intended to commence in mid-2025 following CTA approval. In addition to the Schett/Mackensen CARAMEL trial, the company plans also to expand the CALiPSO-1 clinical trial to include sites in select European countries. Century will provide timing on initial clinical data from its ongoing CALiPSO-1 clinical trial once a clear cadence of patient enrollment has been established across indications."

New P1/2 trial • Trial status • Lupus Nephritis • Systemic Lupus Erythematosus • Systemic Sclerosis

A Study of CNTY-101 in Participants With Refractory B Cell-mediated Autoimmune Diseases (CALiPSO-1) (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Century Therapeutics, Inc. | N=30 ➔ 48

Enrollment change • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Myositis • Nephrology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • IL2

Century Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - P1 | N=75 | ELiPSE-1 (NCT05336409) | Sponsor: Century Therapeutics, Inc. | "As of the data snapshot October 15, 2024, eight additional participants have been treated with CNTY-101 for a total of 20 participants evaluable for safety and 19 for preliminary efficacy. Treatment with CNTY-101 continued to be safe and generally well tolerated with no dose-limiting toxicities reported, no additional cases of immune effector cell-associated neurotoxicity syndrome (ICANS), and no Grade 3 or higher cytokine release syndrome (CRS)...Dose level DL3B (1 billion cells in each of three weekly doses per cycle), which represents the largest single trial cohort (n=6), has shown an overall response rate (ORR) of 83% and a complete response rate (CRR) of 33%, with all participants receiving additional cycles of treatment."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Century Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "...the company recently amended the Phase 1 CALiPSO-1 trial of CNTY-101 (NCT06255028) and Investigational New Drug (IND) application to include evaluation of idiopathic inflammatory myopathy (IIM) and diffuse cutaneous systemic sclerosis (dcSSc). This builds upon earlier alignment with the U.S. Food and Drug Administration to expand clinical development to lupus nephritis (LN) in addition to systemic lupus erythematosus (SLE)...and expects to activate additional sites in the coming months...To further facilitate enrollment, the company plans to expand trial sites to select European countries....Research and Development (R&D) expenses: R&D expenses were $27.2 million for the three months ended September 30, 2024, compared to $22.8 million for the same period in 2023. The increase in R&D expenses was primarily due to progression of the ELiPSE-1 trial and start-up costs of the CALiPSO-1 trial."

Commercial • Trial status • Immunology • Lupus Nephritis • Systemic Lupus Erythematosus • Systemic Sclerosis

Century Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "The Company expects initial clinical data from CALiPSO-1 by year-end 2024. Furthermore, Century recently amended the protocol to include a new indication-specific cohort of Lupus Nephritis (LN) patients....The Company intends to submit additional regulatory filings for CNTY-101 in autoimmune disease indications with limited current treatment options and high unmet need in the second half of 2024....Research and Development (R&D) expenses: R&D expenses were $27.2 million for the three months ended June 30, 2024, compared to $22.7 million for the same period in 2023. The increase in R&D expenses was primarily due to increased manufacturing activity for CNTY-101 and the acquisition of Clade Therapeutics."

Clinical protocol • Commercial • Filing • P1 data • Lupus Nephritis • Systemic Lupus Erythematosus

Century Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "The Company recently completed dose escalation of schedule A (single dose per cycle) and schedule B (3 doses per cycle) in the ELiPSE-1 trial and is currently enrolling patients in the dose confirmation portion. Progression into dose expansion is expected in the second half of 2024."

Trial status • Non-Hodgkin’s Lymphoma

CALiPSO-1: A Study of CNTY-101 in Participants With Moderate to Severe Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P1 | N=26 | Recruiting | Sponsor: Century Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IL2

Interim results from the ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies. (ASCO 2024) - P1 | "CNTY-101 administered as a single dose in multiple cycles has demonstrated a manageable safety profile and preliminary evidence of efficacy. Allo-Evasion edits may allow for repeat dosing for multiple cycles without allorejection in the absence of lymphodepletion. Preliminary efficacy supports dosing at higher dose levels and with more dose-intense regimens."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Indolent Lymphoma • Marginal Zone Lymphoma • Oncology • IL2

Century Therapeutics Presents Interim Results from Phase 1 ELiPSE-1 Study at ASCO 2024 Annual Meeting (GlobeNewswire) - P1 | N=75 | ELiPSE-1 (NCT05336409) | Sponsor: Century Therapeutics, Inc. | "Century Therapeutics...announced a poster presentation highlighting interim results from the ongoing Phase 1 ELiPSE-1 study evaluating CNTY-101 in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) at the American Society of Clinical Oncology (ASCO) Annual Meeting....Preliminary efficacy in all evaluable patients (n=10) across dose schedules and histologies demonstrated a complete response rate (CRR) of 30% and an objective response rate (ORR) of 40% in heavily pretreated patients, with a 40% CRR and 60% ORR observed in the five patients treated with the two higher Schedule A dose levels, 300 million cells and one billion cells."

P1 data • Non-Hodgkin’s Lymphoma

Century Therapeutics Presents Preclinical Data Highlighting Advances in iPSC Platform Technology and Programs at 2024 ASGCT Annual Meeting (GlobeNewswire) - "Century Therapeutics...today announced two poster presentations at the ASGCT 27th Annual Meeting. The data presented highlights the potential of the Company’s lead candidate, CNTY-101, to treat B-cell driven autoimmune diseases including SLE. Additionally, the Company presented data which further demonstrates the capabilities of its Allo-Evasion technology through new preclinical data of a CD300a agonist which can potentially inhibit natural killer (NK) cell alloreactivity."

Preclinical • Systemic Lupus Erythematosus

Discovery of inhibitory CAR target DSG1 for damping NECTIN4 on-target off-tumor toxicity in iPSC-derived CAR-T cell therapy (AACR 2024) - "NECTIN4 targeted antibody drug conjugate enfortumab vedotin, while generally well tolerated, causes severe skin adverse events in some patients, thought to be driven by on-target off-tumor toxicity against NECTIN4 displaying skin keratinocytes. We include a safety switch in our first clinical-stage iPSC-derived CAR-NK cell therapy, CNTY-101, which provides an antibody target for elimination of the engineered cells should that be necessary...In this study, we compare the expression levels of NECTIN4 to targets associated with tissue and cell-type specific on-target off-tumor toxicity in primary CAR-T cell clinical trials. Our findings support the strategy of DSG1-directed inhibitory CAR incorporation into NECTIN4 specific CAR-T cell therapeutic candidates."

CAR T-Cell Therapy • IO biomarker • Bladder Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NECTIN4

Characterization of CNTY-101, an Allogeneic Anti-CD19 iPSC-Derived NK Product, for the Treatment of B Cell-Driven Autoimmune Diseases (ASGCT 2024) - "EGFRt is an elimination tag that can be engaged using anti-EGFR antibodies to deplete CNTY-101. The inclusion of Allo-EvasionTM edits (B2M and CIITA knockouts and HLA-E knock-in) allows for evasion from recipient PBMCs, enabling repeat dosing with and without lymphodepletion.CNTY-101, an off-the-shelf cell therapy product with multiple precision gene edits targeted to B Cell-driven diseases, including AID, demonstrates rapid B cell depletion with a favorable cytokine secretion profile, in vitro persistence and the opportunity for repeat dosing without host rejection."

Immunology • Inflammatory Arthritis • Lupus • Oncology • Systemic Lupus Erythematosus • B2M • HLA-E

Century Therapeutics Strengthens Position in Autoimmune Disease with Strategic Pipeline Expansion Supported by $60 Million Private Placement and Acquisition of Clade Therapeutics (GlobeNewswire) - "Private placement of $60 million led by Bain Capital Life Sciences supports expansion in autoimmune disease; Reinforcing cash runway into 2026....Century plans to evaluate CNTY-101 in moderate to severe SLE in the Phase 1 CALiPSO-1 trial (NCT06255028)...The trial is on track to be initiated in the first half of 2024 with preliminary data expected by the end of 2024. Additional regulatory filings in other prioritized autoimmune disease indications are expected in the second half of 2024."

Financing • P1 data • Regulatory • Trial status • Systemic Lupus Erythematosus

Century Therapeutics Reports Full Year 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "Received investigational new drug (IND) clearance for CNTY-101 for the treatment of systemic lupus erythematosus (SLE); On track to initiate Phase 1 CALiPSO-1 clinical trial in the first half of 2024....In 2023, $4.0 million was a result of entering into a worldwide license agreement with FCDI for the development and commercialization of iPSC-derived therapies for treatment of inflammatory and autoimmune diseases, and $1.0 million related to a milestone fee paid pursuant to the license for filing of the IND for CNTY-101 in SLE."

Commercial • IND • Trial status • Systemic Lupus Erythematosus

CALiPSO-1: A Study of CNTY-101 in Participants With Moderate to Severe Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P1 | N=26 | Not yet recruiting | Sponsor: Century Therapeutics, Inc.

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IL2

Multiple Doses of Cnty-101, an iPSC-Derived Allogeneic CD19 Targeting CAR-NK Product, Are Safe and Result in Tumor Microenvironment Changes Associated with Response: A Case Study (ASH 2023) - P1 | "Cycles 1 and 2 included three days of standard Fludarabine and Cyclophosphamide lymphodepletion (LDC), cycles 3 and 4 were given with no LDC. The treatment was associated with changes in tumor microenvironment within 8 days post-infusion, augmentation of adaptive T cell responses, and tumor shrinkage. Updated data will be presented at the conference."

Biomarker • Clinical • Tumor microenvironment • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • EGFR • HLA-E • IFNG • IL15 • IL2 • TNFA

Century Therapeutics Presents Initial Data from CNTY-101 Phase 1 ELiPSE-1 Trial Supporting the Potential for a Multi-Dosing Strategy for CAR iNK Enabled by Allo-Evasion Edits (GlobeNewswire) - P1 | N=75 | ELiPSE-1 (NCT05336409) | Sponsor: Century Therapeutics, Inc. | "Data presented at 65th ASH Annual Meeting show CNTY-101 was generally well tolerated at Dose Level 1 (100 million cells) in a high-risk, heavily pretreated R/R B-cell lymphoma patient. Preliminary clinical data demonstrate six-month durable complete response in Dose Level 1 in a single patient following multiple cycles of CNTY-101 without lymphodepletion. Pharmacokinetic data suggests CNTY-101 exposure may be maintained upon administration of additional cycles without lymphodepletion due to lack of observed allo-rejection....'We look forward to advancing the study at both higher and more frequent doses of CNTY-101, and plan to present additional clinical data in mid-2024.'"

P1 data • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Century Therapeutics to Present Initial Clinical Data Supporting the Potential for a Multi-Dosing Strategy for CAR iNK Enabled by Allo-Evasion Edits at the 65th ASH Annual Meeting and Exposition (GlobeNewswire) - P1 | N=75 | ELiPSE-1 (NCT05336409) | Sponsor: Century Therapeutics, Inc. | "Preliminary clinical data from a case study featured in ASH abstract shows complete response maintained in Dose Cohort 1 patient following completion of four 28-day cycles of CNTY-101 in Phase 1 ELiPSE-1 trial, the two most recent of which did not include lymphodepletion; CNTY-101 well tolerated; Additional data from Dose Cohort 1 patients, as well as preliminary data from Dose Cohort 2, to be featured in ASH presentation."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Century Therapeutics Reports Second Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "The first-in-human Phase 1 ELiPSE-1 trial evaluating CNTY-101 in relapsed or refractory CD19 positive B-cell lymphomas is ongoing. The Company remains on track to report preliminary data from Schedule A of the trial, including pharmacokinetics, pharmacodynamics, and safety, by year end."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies. (ASCO 2023) - P1 | "In addition to safety and efficacy endpoints, the trial will evaluate exploratory PK, immunogenicity and pharmacodynamic endpoints including evaluations of tumor cfDNA, iNK tumor trafficking and serum cytokines. Clinical trial information: NCT05336409."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • IL2