CTX130 / 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

Universal CAR-T Cell Therapy for Cancer Treatment: Advances and Challenges. (PubMed, Oncol Res) - "Although trials for solid tumors (e.g., CYAD-101, CTX130) show modest responses, challenges such as tumor heterogeneity and T cell exhaustion remain. Future research should focus on optimizing gene editing precision, integrating combination therapies, and advancing scalable manufacturing platforms. With expanded targets and cell types, UCAR therapies show promise for both hematologic and solid tumors, reshaping cancer treatment and patient outcomes."

Journal • Review • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplant Rejection • CD52

Can Immunotherapy Become a Reality for T-Cell Lymphoma? (SOHO 2025) - P=N/A, P1, P1/2, P2 | "Results/Discussion Immunotherapy has already shown some efficacy in TCL in the form of brentuximab vedotin (BV) and mogamulizumab (Moga)...Mogamulizumab — a monoclonal antibody targeting CC chemokine receptor 4 (CCR4) — is used in cutaneous TCL, based on a randomized control trial showing a significant improvement in median progression-free survival compared to vorinostat (7.7 months vs 3.1 months, P < 0.0001)...CTX130 is a CD70-targeted allogeneic CAR T-cell therapy that has shown some efficacy in a phase 1 study when administered to 39 patients with relapsed/ refractory (r/r) peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL)...Search conducted at clinicaltrials.gov on 5/18/25. 15 CAR Target Clinicaltrials.gov ID CD4 NCT06925464, NCT05290155, NCT03829540 CD5 NCT06909474, NCT06316856, NCT03081910, NCT06699771, NCT06534060, NCT06420089 CD7 NCT03690011, NCT05995028, NCT04599556 CD30 NCT06850285, NCT04083495, NCT02917083,..."

IO biomarker • B Cell Lymphoma • Cutaneous T-cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • CCR4 • CD4 • CD7 • CD70 • EGFR • IL15

FIRST-IN-HUMAN CART CELLS FOR ADULT T-CELL LEUKEMIA/LYMPHOMA USING CTX130, A CD70-TARGETED ALLOGENEIC CRISPR-Cas9-ENGINEERED CART-CELLS. COBALT-LYM STUDY COHORT (ICML 2025) - "Standard lymphodepletion with fludarabine and cyclophosphamide was delivered before receiving CTX130 infusions. Between August 28, 2020 and May 30, 2023, nine patients with ATLL were enrolled and treated with CTX130. The median age was 56 years (range 33–79), and all patients had advanced-stage disease (Stage IV). Median number of prior therapy lines: 1 (range 1–5); ECOG performance status: 0 (44%), 1 (56%)."

CAR T-Cell Therapy • Clinical • P1 data • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD70

A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory Renal Cell Carcinoma (COBALT-RCC) (clinicaltrials.gov) - P1 | N=19 | Terminated | Sponsor: CRISPR Therapeutics AG | N=107 ➔ 19 | Trial completion date: Apr 2027 ➔ Oct 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2027 ➔ Oct 2024; Patients to be followed up in the CRSP-ONC-LTF study

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM) (clinicaltrials.gov) - P1 | N=49 | Terminated | Sponsor: CRISPR Therapeutics AG | Trial completion date: May 2027 ➔ Aug 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2027 ➔ Aug 2024; Patients to be followed up in the CRSP-ONC-LTF study

Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

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

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 (Lancet Oncol) - P1 | N=45 | COBALT-LYM (NCT04502446) | Sponsor: CRISPR Therapeutics AG | "Between Aug 28, 2020, and May 30, 2023, 41 patients were enrolled and 39 (95%) received CTX130. The median patient follow-up was 7·4 months (IQR 3·1–12·2). 21 (54%) of 39 patients were female and 18 (46%) were male....21 patients died, 16 from progressive disease and five from adverse events considered unrelated to CTX130 treatment. 18 of 39 patients (46·2% [95% CI 30·1–62·8) had an objective response. Of those treated at dose level 3 and higher, 16 of 31 patients (51·6% [33·1–69·8]) had objective responses, including six (19·4% [7·5–37·5]) with complete response and ten (32·3% [16·7–51·4]) with a partial response."

P1 data • Diffuse Large B Cell Lymphoma

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

CTX130 Provides Disease Control and Manageable Safety in Advanced ccRCC (OncLive) - P1 | N=107 | COBALT-RCC (NCT04438083) | Sponsor: CRISPR Therapeutics AG | "The investigational allogeneic, CRISPR- and Cas9-engineered, CD70-targeted CAR T-cell therapy CTX130 continued to demonstrate an acceptable safety profile and early antitumor activity, including 1 complete response (CR) at 3 years of follow-up, in patients with advanced clear cell renal cell carcinoma (ccRCC), according to updated findings from the phase 1 COBALT-RCC trial (NCT04438083)....Moreover, 75.0% of patients in the overall population (n = 16) achieved stable disease (SD), including 1 patient who maintained SD beyond 12 months. The disease control rate was 81.3%, the median progression-free survival (PFS) was 2.9 months (95% CI, 1.7-6.0), and the median overall survival (OS) was 20.5 months (95% CI, 14.3–not applicable)."

P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

AACR: Novel immunotherapies show promise for patients with kidney cancer and for solid organ transplant recipients with skin cancer (MD Anderson Press Release) - P1 | N=107 | COBALT-RCC (NCT04438083) | Sponsor: CRISPR Therapeutics AG | "Results from the COBALT-RCC study were presented today by Samer Srour...and published concurrently in Cancer Discovery, a journal of the AACR...Among patients with advanced clear cell renal cell carcinoma (ccRCC) who were treated with CTX130, an allogeneic CAR T cell therapy, 81% experienced a clinical benefit, including 75% with stable disease, and one participant who experienced a durable complete response of more than three years....The trial’s findings provide a proof of concept, meriting further exploration of CD70-targeted CAR T cell therapy in ccRCC and other CD70-positive cancers. Srour and his colleagues utilized findings from this trial to develop CTX131, which improves on CTX130, and currently are enrolling patients in a Phase I/II clinical trial (NCT05795595) to evaluate the new therapy."

P1 data • Trial status • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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

A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM) (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: CRISPR Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

City of Hope to Present New Research at the American Association of Cancer Research (AACR) Annual Meeting 2024, Highlighting Promising Data on Prostate, Colorectal and Pancreatic Cancer (Businesswire) - "Researchers with City of Hope, one of the largest cancer research and treatment organizations in the United States, will present new findings at the AACR Annual Meeting, which will take place April 5 to 10 in San Diego."

Clinical data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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

CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: results from the phase 1 COBALT-RCC study (KCRS 2023) - P=1 | N=107 | COBALT-RCC (NCT04438083) | Sponsor: CRISPR Therapeutics AG | "This first-in-human clinical trial exploring CD70 CAR T-cell therapy in ccRCC showed an excellent safety profile with no unexpected on-target off-tumor toxicities and encouraging antitumor activity. To our knowledge, this durable CR is the first to be achieved with allogeneic CAR T cell therapy in patients with R/R solid tumors and represent a proof-ofconcept for further exploration of CD70-targeted CAR T cells in ccRCC and other CD70+ malignancies."

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

Research Aims to Make Inroads With CAR T-Cell Therapy in Advanced RCC (OncLive) - P1 | N=107 | COBALT-RCC (NCT04438083) | Sponsor: CRISPR Therapeutics AG | "Hurwitz first discussed the phase 1 COBALT-RCC trial (NCT04438083), which evaluated CTX130 allogeneic CRISPR-Cas9–engineered CAR T cells in patients with advanced clear cell RCC....The trial evaluated 4 dose levels ranging from 3x107 to 9x108 CAR T cells, but only 1 response was seen in the first dose level cohort. Nine patients experienced stable disease, translating to a disease control rate (DCR) of 77% (n = 10). By 4 months, only 4 patients remained in stable disease. The 1 patient with partial response reached complete response by month 3 and has sustained this response through month 18."

Media quote • P1 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Research Aims to Make Inroads With CAR T-Cell Therapy in Advanced RCC (OncLive) - P1 | N=107 | COBALT-RCC (NCT04438083) | Sponsor: CRISPR Therapeutics AG | "Hurwitz first discussed the phase 1 COBALT-RCC trial (NCT04438083), which evaluated CTX130 allogeneic CRISPR-Cas9–engineered CAR T cells in patients with advanced clear cell RCC....The trial evaluated 4 dose levels ranging from 3x107 to 9x108 CAR T cells, but only 1 response was seen in the first dose level cohort. Nine patients experienced stable disease, translating to a disease control rate (DCR) of 77% (n = 10). By 4 months, only 4 patients remained in stable disease. The 1 patient with partial response reached complete response by month 3 and has sustained this response through month 18."

P1 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory Renal Cell Carcinoma (COBALT-RCC) (clinicaltrials.gov) - P1 | N=107 | Active, not recruiting | Sponsor: CRISPR Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the Phase 1 COBALT-RCC study (SITC 2022) - P1 | "Patients received standard lymphodepleting chemotherapy with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX130 infusion. The Ethics Committee/IRB Approval Numbers/IDs for each participating institution are as follows: City of Hope (189473), Huntsman Cancer Institute (00133621), MD Anderson Cancer Center (2020-0151), Yale Cancer Center (20202730), Princess Margaret Cancer Centre (20-5071), Netherlands Cancer Institute (METC20.1170/M20CTX), and Peter MacCallum Cancer Centre (20/16). All participants provided informed consent before taking part in the study."

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

Early Promise Is Seen With CTX130 for RCC (Targeted Oncology) - "'This first-in-human clinical trial exploring CD70 CAR T-cell therapy in clear cell renal cell carcinoma showed a tolerable safety profile, with no unexpected on-target, off-tumor toxicities and encouraging antitumor activity,' lead study author Sumanta K. Pal, MD...said in a presentation during the meeting."

Media quote • Renal Cell Carcinoma

Going after CD70 with CAR T, NK Cells. (PubMed, Cancer Discov) - "CD70 has emerged as a promising solid tumor target for chimeric antigen receptor (CAR)-bearing T or natural killer (NK) cells, with one allogeneic CAR T-cell therapy, CTX130, showing preliminary efficacy in renal cell carcinoma. Further, assessments of a cord blood-derived CAR-NK alternative have started; the trial will be the first to use cryopreserved NK cells."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

CRISPR Therapeutics Presents Data at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting (GlobeNewswire) - "'At present, a treatment that offers patients with advanced kidney cancer the possibility of a durable remission with limited toxicity remains elusive. Our data shared today show encouraging activity for an allogeneic CAR-T therapy in this setting and highlights the potential of this modality for these patients,' added Sumanta Pal, M.D..."

Media quote

CTX130 Allogeneic CAR T-cell Therapy Shows Tolerability, Intriguing Activity in Advanced RCC (OncLive) - "'This first-in-human clinical trial exploring CD70 CAR T-cell therapy in clear cell renal cell carcinoma showed a tolerable safety profile with no unexpected on-target off-tumor toxicities and encouraging antitumor activity,' lead study author Sumanta K. Pal, MD..."

Media quote

Off-the-shelf CAR-T produces complete remission in patient with advanced kidney cancer (Healio) - "Kidney cancer is one of the most common cancer types, with about 50,000 patients diagnosed in the U.S. annually, according to Sumanta K. Pal...Clear cell is the most common subtype among patients with renal cell carcinoma - comprising approximately 70% to 80% of cases - and tends to respond poorly to currently available therapies, he added."

Media quote • Renal Cell Carcinoma