firicabtagene autoleucel (CRG-022) / Stanford University, Adaptive Biotech, CARGO Therap - LARVOL DELTA

CARGO Therapeutics to Discontinue FIRCE-1 Phase 2 Study of Firi-cel… (GlobeNewswire) - P2 | N=123 | FIRCE-1 (NCT05972720) | Sponsor: CARGO Therapeutics | "Based on an ad hoc analysis of FIRCE-1 prompted by recent safety events, the Company believes the results do not support a competitive benefit-risk profile of firi-cel for the intended patient population. While data from 51 patients with at least one post baseline scan demonstrated an overall response rate of 77% and complete response rate (CR) of 43%, the durability of CR at three months was 18%. Safety data indicated 18% of patients developed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) that were grade 3 or higher, including grade 4 and grade 5 serious adverse events....CARGO intends to present an analysis of the FIRCE-1 Phase 2 study at a future medical conference."

P2 data • Trial termination • Large B Cell Lymphoma

Effects of an initial anti-CD19 CAR T-cell therapy on subsequent anti-CD22 CAR T-cell manufacturing and clinical outcomes in patients with r/r LBCL. (PubMed, Cancer Discov) - P1 | "High and low percentages of CAR22 TCM and TEM, respectively, were correlated with CAR22 transduction efficiency and achieving complete response. Residual CAR19 and leukapheresis timing did not significantly affect outcomes, while CAR22 product composition was significantly correlated with treatment response."

Clinical data • Journal • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8

CARGO Therapeutics Provides Corporate Update and Anticipated Milestones for 2025 (GlobeNewswire) - "As of December 31, 2024, 71 patients have been dosed in the potentially pivotal Phase 2 study of firi-cel, FIRCE-1; CARGO continues to achieve strong manufacturing success of firi-cel. The Company is partnering with National Resilience, Inc. and ElevateBio to manufacture drug product for the FIRCE-1 study; CARGO expects to share topline data from an interim analysis for a meaningful patient sample size with at least 3 months of follow-up in 1H’25."

Licensing / partnership • P2 data • Trial status • Large B Cell Lymphoma

Safe and Effective Combination of Donor-Derived, Allogeneic CD19/CD22-CAR T Cells with Myeloablative Graft-Engineered Allo-HCT for High-Risk B-ALL (ASH 2024) - P1 | "Myeloablative conditioning with cyclophosphamide and total body irradiation precede infusion of investigational Orca-T, which consists of infusions of HSPCs and Tregs on Day 0 and an infusion of T conventional (Tcon) cells on Day 2. This paradigm shifting combination of allogeneic CAR T and allo-HCT resulted in 100% MRD- CR with full donor chimerism but without GVHD or severe CAR-mediated toxicity. These data, which demonstrate antigen-specific anti-tumor benefit of allogeneic CAR T cells in combination with GVHD prophylaxis mediated by Tregs and tacrolimus, have potential implications that could benefit patients with other hematologic diseases."

CAR T-Cell Therapy • IO biomarker • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • ABL1 • CD22 • TP53

CD22-Directed CAR T-Cell Therapy for Large B-Cell Lymphomas Progressing after CD19-Directed CAR T-Cell Therapy: Continued Durable Remissions at 3-Year Follow-up (ASH 2024) - P1 | "The long-term safety profile is manageable, though it reflects the heavily pre-treated cohort, particularly regarding the risk of tMDS/AML. This risk warrants lifelong follow-up of these patients and underscores the need to study this therapy in earlier lines of treatment, given its favorable safety and response profile."

CAR T-Cell Therapy • Clinical • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD22

Firi-Cel Produces Durable Remissions After CD19 CAR-T Failure (Hematology Advisor) - P1 | N=52 | NCT04088890 | "Firicabtagene autoleucel (firi-cel)...can produce 'durable' remissions in patients whose large B-cell lymphoma (LBCL) progressed after CD19-directed CAR T-cell therapy, according to a presenter at the ASH Annual Meeting 2024...At a median follow-up of 39.8 months, 53% of patients had a CR, including 52% of those treated with dose level 1 and 56% treated with dose level 2. The overall response rates were 68%, 66%, and 78%, respectively. The median progression-free survival (PFS) was 3.0 months overall, 3.0 months in patients treated with dose level 1, and 2.6 months in patients treated with dose level 2. The 3-year PFS rate was 30% overall and 58% among patients who achieved a CR...The median overall survival (OS) was 18 months overall, 25.7 months in patients treated with dose level 1, and 13.8 months in patients treated with dose level 2. The 3-year OS rate was 41% overall and 74% among patients who achieved a CR."

P1 data • Diffuse Large B Cell Lymphoma • Lymphoma

CARGO Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Firi-cel:...CARGO expects to complete its interim analysis and report the results in the first half of 2025...IND application submission for CRG-023 in Non-Hodgkin’s lymphoma anticipated in the first quarter of 2025; first patient dosed planned for 2025."

IND • New trial • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

CARGO Therapeutics Announces Phase 1 Clinical Study of Firi-cel CAR T-Cell Therapy Published in The Lancet (CARGO Therapeutics Press Release) - P1 | N=52 | NCT04088890 | "CARGO Therapeutics, Inc...today announced that The Lancet has published favorable data from a Phase 1, single-center clinical study (NCT04088890) by Stanford Medicine...'We believe that the patient subset analyses further support the study design of our potentially pivotal Phase 2 program, which continues to progress as planned and is on track for interim analysis in first half 2025.' The Lancet publication titled 'CD22-Directed CAR T-Cell Therapy for Large B-Cell Lymphomas Progressing After CD19-Directed CAR T-cell Therapy: A dose-finding Phase 1 study,' demonstrated for all patients treated (n=38), an Overall Response Rate (ORR) and CR rate of 68% and 53%, respectively, at a median follow-up of 23.3 months...For Dose Level 1 (DL1), the selected dose for the potentially pivotal Phase 2 study FIRCE-1, the ORR and CR rates were 66% and 52%, respectively."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 2 open label, multicenter study evaluating CRG-022, a CD22-directed autologous CAR T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after CD19-directed CAR T-cell therapy. (ASCO 2024) - P1, P2 | "This CD22 CAR construct was developed at the National Cancer Institute and was investigated in phase (ph) 1 studies of pediatric/young adult pts with R/R CD22+ malignancies (Shah, 2020; NCT02315612) and at Stanford University in adults with R/R LBCL (Baird, 2021; NCT04088890) primarily in pts who received prior CD19-directed CAR-T therapy...Lymphodepletion with fludarabine 30 mg/m 2 /day and cyclophosphamide 500 mg/m 2 /day for 3 days will be administered ahead of a single infusion of CRG-022. The study is designed to enroll approximately 123 pts. Study enrollment commenced in the US in August 2023, with 9 pt infused as of 08 JAN 2024."

CAR T-Cell Therapy • Clinical • P2 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Rare Diseases • Transplantation • CD22

CARGO Therapeutics Announces $110.0 Million Private Placement Equity Financing (GlobeNewswire) - "CARGO Therapeutics, Inc...today announced that it has entered into a securities purchase agreement for a private investment in public equity financing that is expected to result in gross proceeds of approximately $110.0 million, before deducting placement agent fees and other expenses...'As we continue to make great progress on our potentially pivotal Phase 2 study of firi-cel in LBCL patients who have R/R from CD19 CAR T therapy, this financing will be key in supporting BLA preparations in addition to advancing our CRG-023 program, which is a novel tri-specific CAR T designed to overcome multiple mechanisms of resistance.'"

Financing • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Autologous CD22 CAR T Cells Following Commercial CD19 CAR T Cells in B Cell Malignancies (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

CARGO Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Update (CARGO Therapeutics Press Release) - "FIRCE-1 Phase 2 clinical study updates: Currently 26 sites have been activated and over 20 patients have been dosed with impressive manufacturing success. Further, the IDMC completed its review of safety data with a recommendation for FIRCE-1 to continue to enroll patients without modifications to the protocol."

Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

CARGO Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Update (CARGO Therapeutics Press Release) - P1 | N=52 | NCT04088890 | "Phase 1 clinical study updates:...New data for Dose Level 1* (DL1) (n=29) at a median follow-up of 29.8 months included: Median overall survival (mOS) is 25.7 months (95% CI: 9.2, NE). Estimated 2-year survival remains at 52%. The median progression-free survival (PFS), duration of response, and OS have not been reached for patients who achieved a CR. No grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) events occurred at DL1."

P1 data • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Autologous CD22 CAR T Cells Following Commercial CD19 CAR T Cells in B Cell Malignancies (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Stanford University

CAR T-Cell Therapy • New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

CARGO Therapeutics Names Kapil Dhingra, M.B.B.S., to Board of Directors (CARGO Therapeutics Press Release) - "CARGO Therapeutics, Inc...today announced it has appointed Kapil Dhingra, M.B.B.S., to the Company’s Board of Directors. Dr. Dhingra is a medical oncologist and a physician-scientist bringing more than 25 years of strategic clinical development experience in oncology, including cell therapy, with a proven track record in drug development, patient care and academic research...'CARGO has already made tremendous clinical progress with their differentiated anti-CD22 approach and rapidly enrolling Phase 2 clinical trial in relapsed or refractory large B-cell lymphoma'....'I look forward to contributing to CARGO’s continued success as we prioritize developing firi-cel and an exciting pipeline with potential to expand to other B-cell malignancies.'"

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

CARGO Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "To date, 20 sites have been initiated and are enrolling for the potentially pivotal Phase 2 clinical study, FIRCE-1. The Phase 2 trial (NCT05972720) is an open-label, multicenter Phase 2 clinical study evaluating the efficacy and safety of firicabtagene autoleucel (firi-cel) (CRG-022) in patients with relapse or refractory (R/R) large B-cell lymphoma (LBCL) whose disease has progressed after CD19-directed CAR T-cell therapy, an area of high unmet need. Interim results are anticipated in the first half of 2025."

P2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. (PubMed, Leukemia) - "Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting."

CAR T-Cell Therapy • Journal • P1 data • Immunology • Oncology • Pediatrics • Rare Diseases • CD22

IRB-50836: Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: Stanford University | Trial completion date: Dec 2024 ➔ Dec 2037

CAR T-Cell Therapy • Trial completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22

CD22-CAR T Cells in Children and Young Adults With B Cell Malignancies (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Stanford University | Suspended ➔ Active, not recruiting | N=52 ➔ 10 | Trial completion date: Aug 2035 ➔ Sep 2036 | Trial primary completion date: Aug 2025 ➔ Oct 2023

CAR T-Cell Therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD22

CD22 CAR T-Cells Manufactured in Prodigy System and in Bag Culture Yield Equivalent Responses for B-ALL (TCT-ASTCT-CIBMTR 2024) - P1 | "Conclusion While different expansion patterns were observed, CD22 CAR T-cells manufactured in the Prodigy were as safe and effective as those made by bag culture. As commercial CAR T-cells move to automated manufacture, CAR T-cell phenotype, expansion, and functionality especially in patients with EMD may require further study."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Immunology • Rare Diseases • CD22 • CD4 • CD8 • CRP

IRB-50836: Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: Stanford University | Recruiting ➔ Active, not recruiting | N=92 ➔ 52 | Trial completion date: Sep 2034 ➔ Dec 2024 | Trial primary completion date: Apr 2023 ➔ Dec 2024

CAR T-Cell Therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22

CD22-CAR T Cells in Children and Young Adults With B Cell Malignancies (clinicaltrials.gov) - P1 | N=52 | Suspended | Sponsor: Stanford University

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD22

CARGO Therapeutics Reports Business Updates and Third Quarter 2023 Results (GlobeNewswire) - P1 | N=92 | NCT04088890 | "CARGO announced that it has dosed the first seven patients in its potentially pivotal Phase 2 multicenter clinical trial (NCT05972720) after successfully manufacturing CRG-022, the Company’s autologous CD22 chimeric antigen receptor (CAR) T-cell product candidate...Interim results from CARGO’s Phase 2 trial are anticipated in 2025...During the American Society of Hematology (ASH) 2023 Annual Meeting in early December, Stanford shared updated data from its ongoing Phase 1 clinical trial in patients with LBCL that was R/R to CD19 CAR T-cell therapy (NCT04088890)...For all patients treated (n=38), the ORR and CR rates were 68% and 53% respectively....Five patients who died of non-relapse causes were in CR at the time of death; 2 of 5 patients were in Dose Level 1 and 3 of 5 patients were in Dose Level 2."

P1 data • P2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CD22 CAR T Cell-Related IEC-HS Is Associated with an IFN-γ Cytokine Signature (ASH 2023) - P1 | "Patients most commonly received high-dose glucocorticoids, tocilizumab and anakinra. Additional agents for grade 4 IEC-HS included anti-thymoglobulin, dasatanib and emapalumab...The observed IFN-γ cytokine signature is consistent with myeloid cell activation and Th1 T-cell skewing that likely contributes to IEC-HS pathogenesis. These cytokines may be amenable to therapeutic intervention and further study of approaches targeting JAK/STAT and IFN-γ are warranted."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Rare Diseases • CD22 • CXCL10 • CXCL9 • FASLG • IFNG • IL18 • IL1B • IL6 • TNFA

Transcriptional Profiling Associated with CD22 CAR T Cell Clinical Response in LBCL (ASH 2023) - P1 | "This study identifies specific cell features that are associated with the clinical outcome CAR22 therapy, which has implications for optimizing CAR22 products for improved clinical outcomes. Further analyses are ongoing to examine the clonal dynamics of the CAR22 T cells in vivo by including patient samples at later timepoints to our scRNA-seq dataset."

CAR T-Cell Therapy • Clinical • CD22 • CD4 • CD8 • FOS • IL2 • JUN • KIR2DS2