CTX110 / CRISPR Therap - LARVOL DELTA

A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON) (clinicaltrials.gov) - P1/2 | N=62 | Terminated | Sponsor: CRISPR Therapeutics AG | N=227 ➔ 62 | Trial completion date: Aug 2026 ➔ Oct 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2026 ➔ Oct 2024; Patients to be followed up in the CRSP-ONC-LTF study

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Real-World Outcomes of Patients with High-Grade B-Cell Lymphoma with MYC and BCL2 rearrangements Treated in the Contemporary Era (ASH 2024) - "Front-line induction therapy included R-CHOP (n=29), DA-R-EPOCH (n=29), R-CODOX-M/IVAC (n=4), Pola-R-CHP + glofitamab (n=2), R-ICE (n=2), R-HyperCVAD/MA (n=1), obinutuzumab (G)-CHOP (n=1), R-CHOP + glofitamab (n=1), R-CHOP + tafasitamab (n=1), R-CHOP + lenalidomide (n=1), DA-G-EPOCH (n=1), and R-ESHAC (n=1), as well as palliative regimens including R-mini-CHOP (n=2), PEP-C (n=1), and rituximab + prednisolone (n=1)...Nineteen patients received CAR-T therapy (8 at first relapse, 11 at subsequent relapse), including axicabtagene ciloleucel (n=10), tisagenlecleucel (n=5), rapcabtagene autoleucel (n=2), and CTX110 (n=2); the 4-year PFS and OS rates from date of CAR-T infusion were 62% and 55%, respectively. Conclusions : Our series indicates that intensification of front-line induction in patients with HGBL-MYC/BCL2-R maximizes first response and PFS, and incorporation of CNS prophylaxis into initial therapy minimizes risk of CNS relapse and improves OS. CAR-T represents a..."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

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 Disorders • 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

A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON) (clinicaltrials.gov) - P1/2 | N=227 | Active, not recruiting | Sponsor: CRISPR Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • 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

CTX110 ALLOGENEIC CRISPR-CAS9–ENGINEERED CAR T CELLS IN PATIENTS WITH RELAPSED OR REFRACTORY LARGE B-CELL LYMPHOMA: RESULTS FROM THE PHASE 1 DOSE ESCALATION CARBON STUDY (EBMT 2023) - P1 | "Pts received standard lymphodepleting chemotherapy (LDC) with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX110. CTX110 at DL≥3 or higher resulted in clinically meaningful ORR, CR rates, and durable remissions, accompanied by a favorable safety profile in pts with R/R LBCL. Nearly half of all patients who achieved a CR maintained it out to at least 6 months. CTX110 offers a potential novel off-the-shelf treatment option with a median time from enrollment to LDC of 2 days."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • CNS Disorders • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • B2M • BCL2 • BCL6 • CD19 • MYC • NOS1

Development of CTX112 a next generation allogeneic multiplexed CRISPR-edited CART cell therapy with disruptions of the TGFBR2 and Regnase-1 genes for improved manufacturing and potency (SITC 2023) - P1/2 | "Background CTX110, a CD19-directed first-generation CRISPR-edited CAR T cell therapeutic candidate for B-cell lymphoma, has induced clinical responses and durable remissions (2+ years) in some patients (CARBON trial, NCT04035434). Thus, we hypothesize that CTX112 will show increased functional persistence at the site of tumor and will continue to kill cancer cells for longer as compared to other allogeneic CAR T cell products through its persistent effector function and TME suppression resistance. CTX112 is being evaluated in a clinical trial for B cell malignancies (NCT05643742)."

CAR T-Cell Therapy • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • TGFB1 • TGFBR2

A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON) (clinicaltrials.gov) - P1/2 | N=227 | Recruiting | Sponsor: CRISPR Therapeutics AG | Phase classification: P1 ➔ P1/2 | N=143 ➔ 227

Enrollment change • Phase classification • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Exciting day at #EBMT23 for @CRISPRTX. Two Presidential symposia talks - one on Exa-cel by Dr. Locatelli and one on CTX110 by Dr. McGuirk. Kudos to the team and thanks to our investigators" (@CrisprSam)

CARBON: results of Phase I study of CTX110 allogeneic CRISPR-CAS9-engineered CAR-Ts in R/R LBCL (YouTube) - "Joseph McGuirk, DO...comments on the design and advantages of CTX110, a third-party allogeneic CRISPR-CAS9-engineered CAR-T product, currently under investigation in a Phase I dose-escalation study in patients with relapsed/refractory (R/R) large B-cell lymphoma (NCT04035434)."

Interview • Video

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

CTX110 Allogeneic CRISPR-Cas9–Engineered CAR T Cells in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 1 Dose Escalation Carbon Study (ASH 2022) - P1 | "Pts received standard lymphodepleting chemotherapy (LDC) with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX110. In a heavily pre-treated patient population with R/R LBCL (46.9% with 3 or more prior lines of therapy), CTX110 at DL≥3 or higher resulted in clinically meaningful ORR, CR rates, and durable remissions, accompanied by a favorable safety profile during dose escalation. Nearly half of all patients who achieved a CR maintained it out to at least 6 months. CTX110 offers a potential off-the-shelf treatment option; only 2 enrolled pts were unable to receive CTX110 and the median time from enrollment to LDC was just 2 days, followed by infusion of CTX110 a median of 3 days afterwards."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • CNS Disorders • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • CD19

CRISPR Therapeutics Provides Update on Its Ongoing Phase 1 CARBON Trial of CTX110 (GlobeNewswire) - P1 | N=143 | CARBON (NCT04035434) | Sponsor: CRISPR Therapeutics AG | "CRISPR Therapeutics...today provided an update for both Part A and Part B of the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110®, its wholly-owned allogeneic CAR T cell therapy targeting CD19+ B-cell malignancies. Part A data, presented at ASH, showed the potential for CTX110 to achieve long-term durable complete remissions (CRs) with a positively differentiated safety profile in heavily pre-treated patients, and emerging data from Part B showed an encouraging efficacy profile with several patients in ongoing CR beyond six months."

P1 data • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

CRISPR Therapeutics Announces Poster Presentation on CTX110 at the American Society of Hematology (ASH) 2022 Annual Meeting (GlobeNewswire) - "CRISPR Therapeutics... today announced that it will present a poster on CTX110, its wholly-owned allogeneic CAR-T cell investigational therapy targeting CD19+ B-cell malignancies, at the American Society of Hematology (ASH) 2022 Annual Meeting....The ASH abstract includes preliminary data from 32 patients with Large B-Cell Lymphoma (LBCL) who have been dosed in the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110."

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

CRISPR Therapeutics Provides Business Update and Reports Third Quarter 2022 Financial Results (GlobeNewswire) - "CRISPR Therapeutics continues to enroll and dose patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The Company expects to report additional data in 2022....CRISPR Therapeutics announced the clearance of its Investigational New Drug (IND) application by the FDA for CTX112™, its next generation chimeric antigen receptor T cell (CAR-T) candidate targeting CD19+ B-cell malignancies. The Company expects to initiate clinical trials for CTX112 in the first half of 2023."

IND • New P1 trial • P1 data • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CRISPR Therapeutics Provides Business Update and Reports First Quarter 2022 Financial Results (GlobeNewswire) - "CRISPR Therapeutics continues to enroll and dose patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The Company expects to report additional data in 2022....CRISPR Therapeutics’ Phase 1 clinical trials for CTX-120...and CTX130...are ongoing....The Company expects to provide updates from each trial in the first half of 2022."

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

A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON) (clinicaltrials.gov) - P1; N=131; Recruiting; Sponsor: CRISPR Therapeutics AG; N=95 ➔ 131

Clinical • Enrollment change • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"CRISPR CAR-T cells is the solution, such as $CRSP CTX110" (@HassanAesthetic)

CAR T-Cell Therapy

[VIRTUAL] A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR-Cas9–engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON). (ASCO 2021) - P1 | "Pts will receive lymphodepleting chemotherapy with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX110 infusion . Key secondary efficacy endpoints include duration of response, progression-free survival, and overall survival . The trial is currently open and enrolling."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • B2M

CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX110 for the Treatment of Relapsed or Refractory CD19+ B-cell malignancies (GlobeNewswire) - "CRISPR Therapeutics....announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX110™, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies."

FDA event • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

CRISPR Therapeutics Provides Business Update and Reports Third Quarter 2021 Financial Results (GlobeNewswire) - "The pharmacokinetic data provide a strong rationale that consolidation dosing can improve on an already competitive profile for CTX110. Based on the safety and efficacy profile, the Company plans to expand into a potential registrational trial that incorporates consolidation dosing in Q1 2022....Company is implementing consolidation dosing protocols for its CTX120 and CTX130 clinical trials and expects to report top-line data in the first half of 2022."

New trial • Hematological Malignancies • Multiple Myeloma • Oncology

"Yes, the denominator shenanigans are brassnecked, as is $CRSP referring to the CTX110-related death as "other death"" (@JacobPlieth)

CRISPR Therapeutics Reports Positive Results from its Phase 1 CARBON Trial of CTX110 in Relapsed or Refractory CD19+ B-cell malignancies (GlobeNewswire) - P1, N=143; CARBON (NCT04035434); Sponsor: CRISPR Therapeutics AG; "A single dose of CTX110 at DL2 and above resulted in a 58% ORR and 38% CR rate on an ITT basis....The data demonstrate the potential for CTX110 to produce durable remissions, as evidenced by a 21% six-month CR rate (4 of the 9 patients who achieved CR at Day 28, remained in CR at 6 months; 5 patients had not reached their 6-month evaluation point), which is in the range of durable remissions observed with approved autologous CAR-T therapies on an ITT basis....Based on this safety and efficacy profile, the Company plans to expand into a potential registrational trial that incorporates consolidation dosing in Q1 2022."

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

CRISPR Therapeutics to Host Virtual Event Highlighting CTX110 Clinical Data (GlobeNewswire) - "CRISPR Therapeutics...announced that management will host a virtual event on October 12, 2021 at 4:30 p.m. ET to highlight clinical data from its ongoing Phase 1 CARBON trial assessing the safety and efficacy of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19, for the treatment of relapsed or refractory B-cell malignancies."

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

CRISPR Therapeutics Provides Business Update and Reports Second Quarter 2021 Financial Results (GlobeNewswire) - "The Company expects to report additional clinical data in 2021 from its ongoing Phase 1 CARBON trial assessing the safety and efficacy of several dose levels of CTX110...for the treatment of relapsed or refractory B-cell malignancies...The Company expects to report top-line data from...Phase 1 clinical trial assessing the safety and efficacy of several dose levels of CTX120 for the treatment of relapsed or refractory multiple myeloma...in 2021."

P1 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology