CTX131 / CRISPR Therap - LARVOL DELTA

First-in-human study of CTX130, a CD70-directed allogeneic CAR T therapy, in adult T-cell leukemia/lymphoma: Clinical and genomics findings from a long-term follow-up of subgroup analysis from the cobalt-LYM Phase 1 trial (ASH 2025) - "Eligible patients underwentlymphodepletion with fludarabine and cyclophosphamide prior to CTX130 infusion, with repeat dosingpermitted per protocol...These findings supportfurther development of CD70-directed CAR-T therapies, with next-generation CTX131 currently beingevaluated in a follow-up clinical trial... Our subgroup analysis demonstrates that CTX130, an allogeneic CRISPR-Cas9-engineered CAR-T therapytargeting CD70, shows promising efficacy and a manageable safety profile in relapsed/refractory ATLL. AnORR of 50% was observed, which is notable given the historically poor outcomes in treatingrelapsed/refractory ATLL. Importantly, two patients remain long-term survivors, representing the firstdocumented durable remissions observed in our center's ATLL CAR-T program."

Clinical • First-in-human • IO biomarker • P1 data • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • CD4 • CD70 • STAT3

A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=19 | Completed | Sponsor: CRISPR Therapeutics AG | Recruiting ➔ Completed | N=250 ➔ 19 | Trial completion date: May 2030 ➔ Sep 2025 | Trial primary completion date: Apr 2030 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Endometrial Cancer • Esophageal Cancer • Genito-urinary Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pleural Mesothelioma • Renal Cell Carcinoma • Solid Tumor

CTX131, targeting CD70, was previously in development for both solid tumors and hematologic malignancies (GlobeNewswire) - "While the Phase 1 data are encouraging, the Company has strategically redirected resources away from this program to advance other programs with the greatest potential for long-term value creation."

Discontinued • Hematological Malignancies • Solid Tumor

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

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

Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. (PubMed, Lancet Oncol) - P1 | "In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development."

CAR T-Cell Therapy • Journal • P1 data • Cutaneous T-cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • CD70

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

A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=290 | Recruiting | Sponsor: CRISPR Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed/Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=290 | Not yet recruiting | Sponsor: CRISPR Therapeutics

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

A phase 1/2, open-label, multicenter, dose escalation and cohort expansion study of the safety and efficacy of anti-CD70 allogeneic CRISPR-Cas9–engineered T cells (CTX131) in adult patients with relapsed or refractory solid tumors. (ASCO 2024) - P1/2 | "Pts will receive standard lymphodepleting chemotherapy with fludarabine 30 mg/m 2 and cyclophosphamide 500 mg/m 2 daily x 3 days followed by CTX131 IV infusion at doses ranging from 30-900 million cells in 4 dose level cohorts. 3. Terrett 2023."

Clinical • P1/2 data • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Graft versus Host Disease • Hematological Disorders • Hepatology • Immunology • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • B2M • CD70 • TGFBR2 • TNFA

CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Long-term follow-up and translational data from the phase 1 COBALT-RCC study (AACR 2024) - "After receipt of standard lymphodepletion with fludarabine and cyclophosphamide for 3 days (dosed at 30 mg/m2 and 500 mg/m2, respectively), patients received infusion of CTX130. Among the 16 patients enrolled and treated in dose escalation, the median age was 63 (range, 53-77) and all were stage IV at the time of enrollment. . Updated results from the COBALT-RCC study reinforce both the encouraging antitumor activity and exceptional safety profile of CTX130. The durable CR, now in excess of 3 years, reflects the first and longest seen with allogeneic CAR T cell therapy in refractory solid tumors. A study of CTX131™ (building on CTX130 with CRISPR edits to enhance potency and persistence) is ongoing."

Clinical • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. (PubMed, Cancer Discov) - "Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors."

CAR T-Cell Therapy • Journal • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

CRISPR Therapeutics Highlights Strategic Priorities and 2024 Outlook (GlobeNewswire) - "CRISPR Therapeutics is expanding trials of CTX131 into hematologic malignancies, including T- and B-cell malignancies, in addition to the ongoing clinical trial in solid tumors."

Trial status • Hematological Malignancies • 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....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

CTX112 and CTX131: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumors (AACR 2023) - P1 | "CRISPR Therapeutics’ first generation allo CAR T cell products, CTX110® (CD19-directed) and CTX130TM (CD70-directed), have shown encouraging efficacy in ongoing clinical trials (NCT04035434, NCT04502446, NCT04438083), including complete and durable responses in B- and T-cell lymphoma and renal cell carcinoma (RCC). In summary, CTX112 and CTX131 are the first CAR T programs to incorporate novel Regnase-1 and TGFBR2 edits, with the potential to increase expansion and functional persistence, which may translate clinically to deeper, more durable responses. CTX112 will be developed in patients with B cell malignancies, and CTX131 will be developed in patients with advanced solid tumors, including RCC."

CAR T-Cell Therapy • Clinical • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Renal Cell Carcinoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • B2M • CD19 • CD70 • TGFBR2

"$CRSP's slide deck (CTX112 and CTX131) from #AACR23 #AACR2023 https://t.co/Lk9YIXxyXx" (@JamesPe11062557)

Oncology

A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: CRISPR Therapeutics AG

New P1/2 trial • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor

CRISPR Therapeutics to Present at the American Association for Cancer Research 2023 Annual Meeting (GlobeNewswire) - "CRISPR Therapeutics...announced an oral presentation of preclinical data at the American Association for Cancer Research (AACR) 2023 Annual Meeting, taking place April 14 - 19, 2023, in Orlando, FL."

Preclinical • Hematological Malignancies • Oncology • Solid Tumor

CRISPR Therapeutics Provides Business Update and Reports Second Quarter 2022 Financial Results (GlobeNewswire) - "Announced plans to advance next-generation investigational therapies with additional gene edits that have the potential to improve upon first-generation programs. The Company expects to advance two next-generation constructs to IND by year end: CTX131™ and CTX112™ targeting CD70 and CD19, respectively; Announced plans for a next-generation allogeneic CAR-T therapy targeting B-cell maturation antigen (BCMA) that incorporates proprietary edits to enhance the potency of the CAR-T cells."

IND • Pipeline update • Oncology • Solid Tumor