zugocaptagene geleucel (CTX112) / CRISPR Therap, NKure Therapeutics - LARVOL DELTA

CRSP-AID-501: Safety and Preliminary Efficacy of CTX112 in Adult Participants with Relapsed/Refractory Hematologic Autoimmune Disease (clinicaltrialsregister.eu) - P1 | N=30 | Not yet recruiting | Sponsor: CRISPR Therapeutics AG

New P1 trial • Hematological Disorders • Immunology

CRSP-AID-500: A Phase 1 Study of the Safety and Preliminary Efficacy of CTX112 in Adult Subjects With Refractory Autoimmune Disease. (clinicaltrialsregister.eu) - P1 | N=38 | Recruiting | Sponsor: CRISPR Therapeutics AG

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Recent Highlights and Outlook:…Immuno-Oncology (GlobeNewswire) - "In immuno-oncology, the Phase 1/2 clinical trial of zugo-cel in B-cell malignancies is ongoing. The Company expects to provide updates in the second half of 2026."

P1/2 data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Large B Cell Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma

Recent Highlights and Outlook:…Autoimmune Disease (GlobeNewswire) - "In autoimmune disease, Phase 1 clinical trials of zugo-cel are ongoing across multiple indications, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myositis and a second Phase 1 trial in immune thrombocytopenia purpura (ITP) and warm autoimmune hemolytic anemia (wAIHA), with continued progress across studies. The Company expects to provide updates in the second half of 2026."

P1 data • Trial status • Autoimmune Hemolytic Anemia • Immune Thrombocytopenic Purpura • Myositis • Systemic Lupus Erythematosus • Systemic Sclerosis

CRISPR Therapeutics anticipates several key milestones across its portfolio (GlobeNewswire) - "Global regulatory submissions for CASGEVY in patients ages 5 – 11 are expected to be initiated by Vertex in the first half of 2026; Updates from CTX310 are expected in the second half of 2026; Updates from the Lp(a) program are expected in 2026; Updates across autoimmune disease and immuno-oncology for zugocabtagene geleucel (zugo-cel; formerly CTX112) are expected in the second half of 2026."

Filing • Trial status • Autoimmune Hemolytic Anemia • Beta-Thalassemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Immune Thrombocytopenic Purpura • Immunology • Myositis • Severe Hypertriglyceridemia • Sickle Cell Disease • Systemic Lupus Erythematosus • Systemic Sclerosis

Positive clinical data generated to date support the advancement of zugo-cel into the Phase 2 portion of the ongoing Phase 1/2 trial in patients with (R/R) CD19-positive B-cell malignancies. (GlobeNewswire) - "An overall response rate (ORR) of 90% (9/10) and a complete response rate (CRR) of 70% (7/10) were observed, including a complete response (CR) in a patient who relapsed following autologous CAR T cell therapy. Among patients who have completed 12-months of follow-up, 67% (2/3) remained in CR at the 12-month evaluation. Peak mean CAR T cell expansion of approximately 1,700 cells/µL was observed at the RP2D, representing approximately a four-fold higher expansion compared with patients receiving 300 million cells....The Company expects to provide additional updates in the second half of 2026."

P1 data • Follicular Lymphoma • Large B Cell Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma

CRISPR Therapeutics Provides Broad Update on Zugocaptagene Geleucel (Zugo-cel; formerly CTX112) in Autoimmune Diseases… (GlobeNewswire) - "All patients demonstrated significant clinical improvement at the Day 28 assessment. The first patient with SLE, refractory to 9 prior therapies with a baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 8, has maintained drug-free DORIS clinical remission through Month 6 following CAR T therapy. Treatment has been well-tolerated, with no high-grade cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity syndrome (ICANS) observed."

P1 data • Myositis • Systemic Lupus Erythematosus • Systemic Sclerosis

CTX112, a Next-Generation Allogeneic CRISPR-Cas9 Engineered CD19 CAR T Cell with Novel Potency Edits: Data from Phase 1 Dose Escalation Study in Patients with Relapsed or Refractory B-Cell Malignancies (ASH 2024) - P1/2 | "This editing strategy was chosen based on a large scale phenotypic CRISPR screen to identify novel potency edits, and further informed by our first-generation CTX110 data...Patients received standard lymphodepleting chemotherapy (LDC) with fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 days followed by CTX112 infusion...Dose optimization within disease-specific cohorts is ongoing. These data demonstrate that CTX112 has the potential to be a highly effective allogeneic CAR T cell therapy for B-cell malignancies."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Small Lymphocytic Lymphoma • B2M • TGFBR2

Autoimmune Disease and Immuno-Oncology (GlobeNewswire) - "CTX112...has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. A Phase 1 clinical trial in autoimmune disease is underway in systemic lupus erythematosus (SLE), systemic sclerosis and inflammatory myositis. In parallel, a Phase 1 clinical trial of CTX112 in relapsed or refractory B-cell malignancies is ongoing. The Company plans to provide a broad update on CTX112 by year-end."

Clinical data • FDA event • Trial status • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Marginal Zone Lymphoma • Myositis • Small Lymphocytic Lymphoma • Systemic Lupus Erythematosus • Systemic Sclerosis

Best of Cell Therapy for Lymphoma: What We Learned in 2024 and 2025 (SOHO 2025) - P1/2, P2 | "Autologous CAR-T Therapy CD19 CAR-T New Regulatory Approvals In March 2024, the United States Food and Drug Administration (FDA) granted accelerated approval to lisocabtagene maraleucel (lisocel) for relapsed/refractory (R/R) chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) after Bruton tyrosine kinase inhibitors (BTKis) and B-cell lymphoma 2 (BCL2) inhibitors, making it the first CAR-T approval in this disease...Long-Term Follow-up of Pivotal CD19 CAR-T Trials TRIAL (PRODUCT) LYMPHOMA SUBTYPE MEDIAN FU (MONTHS) ORR (%) CR (%) MEDIAN PFS (MONTHS) PFS (%) OS (%) NOTABLE SAFETY FINDINGS 64.6 90 75 (79% in FL cohort, 65% in MZL cohort) 62.2 53 (5 yr) 69 (5 yr) No new late signals ZUMA-5 (AXICEL) FL/MZL ( ≥ 3L) ELARA (TISA-CEL) FL ( ≥ 3L) 53 – * 69.1 53.3 50.2 (4 yr) 79.3 (4 yr) No new late signals; 6.2% secondary primary malignancies TRANSCEND FL (LISO-CEL) FL (2L+ high-risk/3L+) 29.5 – 30 95.7 – 97.1 94.2 – 95.7 NR 72.5 – 82.6 (2 yr) 88.2 –..."

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hodgkin Lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Oncology • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma • CD22 • CD5 • IL15 • TNFRSF8

CRISPR Therapeutics Provides Business Update and Reports Second Quarter 2025 Financial Results (GlobeNewswire) - "Recent Highlights and Outlook:...Immuno-Oncology and Autoimmune Disease Programs:...(i) CTX112, targeting CD19, is in development for hematologic malignancies and autoimmune diseases....The Company plans to provide a broad update for CTX112 in oncology and autoimmune disease in the second half of 2025; (ii) CTX131, targeting CD70, is in development for both solid tumors and hematologic malignancies. Clinical trials for CTX131 are ongoing, with an update expected in 2025; (iii) CRISPR Therapeutics’ immuno-oncology and autoimmune disease efforts are supported by a wholly-owned, U.S. manufacturing facility located in Framingham, MA. This investment enables the production of clinical and commercial-stage good manufacturing practice (GMP) materials across the Company’s allogeneic cell therapy programs."

Clinical data • Commercial • Acute Myelogenous Leukemia • Lupus Nephritis • Non-Hodgkin’s Lymphoma • Solid Tumor • Systemic Lupus Erythematosus • Systemic Sclerosis

Nkure Therapeutics And CRISPR Therapeutics Partner To Advance CTX112 For Cancer Treatment In India (Passionate In Marketing) - "NKure Therapeutics Private Limited...and CRISPR Therapeutics...announced a strategic partnership to co-develop and co-commercialise CTX112, a next-generation, off-the-shelf CAR T therapy, for oncology indications in India. This collaboration marks an important step toward expanding access to advanced cell therapies in India, where B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL) and other forms of non-Hodgkin’s lymphoma pose significant health challenges....The collaboration with NKure Therapeutics, an Indian biotech committed to cost-effective immunotherapies, is intended to align with India’s healthcare system, and facilitate a streamlined path to regulatory approval and patient access."

Licensing / partnership • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

Radiomic features associated with anti-tumor activity in Non-Hodgkin lymphoma patients treated with CD19 directed allogenic CAR T therapy (AACR 2025) - "Multivariate analysis of [18F] FDG PET/CT scans shows that CTX110 and CTX112 exhibit consistent dose-dependent anti-tumor activity, as measured by decrease in MTV, across patients with diverse radiomic features. Across multiple methods estimating MTV-reduction efficacy, CTX112 is approximately 10-fold more efficacious than CTX110, despite the CTX112-treated cohort containing patients with baseline radiomic features associated with poor response."

Clinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TGFBR2

A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: CRISPR Therapeutics

New P1 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Myositis • Nephrology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Orphan Designation: treatment of follicular lymphoma (FDA) - Date Designated: 04/04/2025

Orphan drug • Follicular Lymphoma

CRISPR Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "CTX112 is also in an ongoing Phase 1 clinical trial in systemic lupus erythematosus (SLE), systemic sclerosis and inflammatory myositis....Based on favorable oncology data, CRISPR Therapeutics expanded the CTX112 trial in SLE to include patients with systemic sclerosis and inflammatory myositis in a basket study, with updates expected in mid-2025....CTX310 is in an ongoing Phase 1 clinical trial targeting ANGPTL3 in patients with homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (SHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias...Dose escalation is ongoing, with an update expected in the first half of 2025."

P1 data • Familial Hypercholesterolemia • Immunology • Myositis • Severe Hypertriglyceridemia • Systemic Lupus Erythematosus • Systemic Sclerosis

CRISPR Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "CRISPR Therapeutics has formed a strategic partnership with Nkure Therapeutics Private Limited ('NKure') to co-develop and co-commercialize CTX112 in India. This alliance aims to accelerate the global development of CTX112 in countries with significant unmet medical needs, while also highlighting the potential for lower costs associated with allogeneic cell therapy platform."

Licensing / partnership • Hematological Malignancies

CRISPR Therapeutics Highlights Strategic Priorities and Anticipated 2025 Milestones (GlobeNewswire) - "CRISPR Therapeutics plans to engage with regulatory authorities to align on the path forward for CTX112 in B-cell malignancies, with an update expected in mid-2025....Clinical trials are on-going for CTX131 in both solid tumors and hematologic malignancies, with updates expected in 2025. Additionally, we are advancing an autologous, gene-edited CAR T therapy targeting glypican-3 (GPC3) for the potential treatment of solid tumors and expect to initiate a clinical trial in the first half of 2025."

New trial • P1/2 data • Regulatory • Hematological Malignancies • Solid Tumor

CRISPR Therapeutics Presents Data at the 2024 American Society of Hematology (ASH) Annual Meeting (CRISPR Therap Press Release) - "CTX112 is also in a Phase 1 clinical trial in systemic lupus erythematosus (SLE), with the potential to expand into additional autoimmune indications in the future...Company expects to provide a broader update...autoimmune indications in mid-2025."

New P1 trial • Systemic Lupus Erythematosus

CRISPR Therapeutics Presents Data at the 2024 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - P1/2 | N=120 | NCT05643742 | Sponsor: CRISPR Therapeutics AG | "CRISPR Therapeutics...today presented data from the Company’s ongoing Phase 1/2 dose escalation clinical trial evaluating the safety and efficacy of CTX112...Additionally, the Company announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX112 for the treatment of R/R follicular lymphoma and marginal zone lymphoma...There were no reported dose limiting toxicities (DLTs) and no reported Grade ≥3 infections...There were no reported cases of Graft versus Host Disease (GvHD)...Objective and complete responses were seen at all dose levels and in all treated NHL subtypes (i.e., FL, MZL, MCL and LBCL). Responses were also seen in patients with poor prognostic factors including primary refractory disease, early relapse, and high baseline tumor burden (e.g., SPD > 4000 mm2)."

FDA event • P1/2 data • Hematological Malignancies • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CRISPR Therapeutics Provides Business Update and Reports Third Quarter 2024 Financial Results (GlobeNewswire) - P1/2 | N=120 | NCT05643742 | Sponsor: CRISPR Therapeutics AG | "CRISPR Therapeutics announced that it will present a poster from the Company’s ongoing Phase 1 dose escalation study evaluating the safety and efficacy of CTX112, a next-generation CD19 allogeneic CAR T cell therapy, in relapsed or refractory (r/r) CD19-positive B-cell malignancies at the American Society of Hematology (ASH) 2024 Annual Meeting. The ASH abstract includes preliminary data on nine high-risk/heavily pretreated lymphoma patients showing an overall response rate (ORR) of 67% across multiple histologies and a complete response rate (CRR) of 44%, with four patients having achieved responses lasting for more than 6 months, including one patient treated at DL1 who remains in complete remission over a year after CTX112 infusion."

P1 data • Hematological Malignancies • Oncology

CRISPR Therapeutics Provides Business Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "CTX131 is currently in an ongoing clinical trial in solid tumors. In addition, the Company has opened a clinical trial for CTX131 in hematologic malignancies including T cell lymphomas (TCL); In oncology settings, CTX112 is in a Phase 1/2 trial for CD19 positive relapsed or refractory B-cell malignancies, and the Company expects to report preliminary clinical data this year."

New trial • P1/2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CRISPR Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "...we plan to initiate a clinical trial of CTX112 in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future."

New trial • Systemic Lupus Erythematosus

CRISPR Therapeutics Announces Updates to Immuno-Oncology Pipeline and Expansion into Autoimmune Disease (GlobeNewswire) - "CRISPR Therapeutics...provided an update on its immuno-oncology pipeline of CRISPR/Cas9 gene-edited allogeneic chimeric antigen receptor (CAR) T cell product candidates....Preliminary data from ongoing clinical trials of its next-generation candidates, CTX112 targeting CD19 and CTX131 targeting CD70, suggest that these candidates may improve upon that clinical profile. Emerging pharmacology data, including pharmacokinetics, indicate that the novel potency gene edits in CTX112 and CTX131 lead to significantly higher CAR T cell expansion and functional persistence in patients compared to the first-generation candidates....Based on these considerations, the Company is focusing on the development of CTX112 and CTX131 and will be transitioning patients treated with CTX110 and CTX130 to long-term follow-up where applicable."

Clinical • Pipeline update • Oncology

CRISPR Therapeutics Announces Updates to Immuno-Oncology Pipeline and Expansion into Autoimmune Disease (GlobeNewswire) - "CRISPR Therapeutics...provided an update on its immuno-oncology pipeline of CRISPR/Cas9 gene-edited allogeneic chimeric antigen receptor (CAR) T cell product candidates....The Company plans to expand the evaluation of CTX112 beyond oncology into autoimmune diseases....The Company plans to initiate a clinical trial in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future."

New trial • Systemic Lupus Erythematosus