cemacabtagene ansegedleucel (ALLO-501A) / Allogene Therap, Cellectis - LARVOL DELTA

Pivotal Phase 2 ALPHA3 Trial with Cemacabtagene Ansegedleucel (Cema-Cel) in First Line (1L) Consolidation in Large B-Cell Lymphoma (LBCL) (GlobeNewswire) - "Nearly 50 Sites Activated Across U.S. with Strong Enthusiasm from Investigators. Lymphodepletion Selection and Futility Analysis Shifted to 1H 2026 in Part Due to Site-Related. Factors that Impacted Expected Pace of Screening Immediately Following Site Activation. Over 250 Patients Consented for MRD Screening to Date, with Nearly Half in the Last Three Months and Awaiting Completion of 1L Treatment as Earliest Activated Sites Build Momentum. International Expansion of ALPHA3 Trial to Begin with Site Activations in Canada in Q2 2025."

P2 data • Trial status • Large B Cell Lymphoma

Allogene Therapeutics to Present Updated ALLO-316 Clinical Results in Kidney Cancer in Oral Presentation and ALPHA3 Trial-in-Progress Poster for Cema-Cel at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Allogene Therapeutics...announced that it will present updated data from the completed Phase 1 TRAVERSE trial of ALLO-316 in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting....In addition, a trial-in-progress poster is also being presented to highlight the ongoing pivotal Phase 2 ALPHA3 trial, which is evaluating cemacabtagene ansegedleucel (cema-cel) as part of first-line (1L) treatment for patients with large B-cell lymphoma (LBCL)."

P1 data • Trial status • Large B Cell Lymphoma • Renal Cell Carcinoma

Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in LBCL (GlobeNewswire) - "The lymphodepletion selection and futility analysis are anticipated around mid-2025. Efficacy analyses from the ALPHA3 trial are expected to occur in 2026 and will include an interim EFS analysis monitored by the independent Data Safety Monitoring Board (DSMB) in 1H 2026 and the data readout of the primary EFS analysis around YE 2026. A potential biologics license application (BLA) submission is targeted for 2027."

DSMB • FDA filing • P2 data • Large B Cell Lymphoma

Allogene Therapeutics Expands Strategic Partnership with Foresight Diagnostics to Advance Joint Development Activities Outside the US Across Europe, UK, Canada, and Australia (GlobeNewswire) - "Allogene Therapeutics...announced an expanded strategic collaboration with Foresight Diagnostics, Inc. to include the development of Foresight’s minimal residual disease (MRD) assay as a companion diagnostic to identify patients with large B-cell lymphoma (LBCL) for treatment with cemacabtagene ansegedleucel (cema-cel). Under the Amended and Restated Strategic Collaboration Agreement, Allogene and Foresight will work together to support the development of Foresight Diagnostics’ MRD assay as a companion diagnostic in the EU, UK, Canada and Australia in support of Allogene’s clinical development of cema-cel....In the ALPHA 3 trial, patients who achieve remission following initial treatment but remain positive for MRD will be identified by using Foresight Diagnostics’ ultra-sensitive ctDNA-based Foresight CLARITY investigational use only (IUO) assay, powered by PhasED-Seq."

Diagnostic • Licensing / partnership • Large B Cell Lymphoma

Allogene Therapeutics Announces Publication of Durable Response Data from Phase 1 ALPHA/ALPHA2 Trials of the Allogeneic CAR T Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma in the Journal of Clinical Oncology (GlobeNewswire) - P1 | N=74 | ALPHA | P1/2 | N=160 | ALPHA2 (NCT04416984) | Sponsor Allogene Therapeutics | "As of the data cutoff date (September 26, 2024), 87 heavily pretreated patients with R/R non-Hodgkin lymphoma (NHL) were treated in the ALPHA/ALPHA2 studies....Patients who achieved a CR had excellent outcomes with a median DOR, PFS (progression free survival) and OS of 23.1 months, 24 months, and not reached, respectively. For patients receiving the selected Phase 2 regimen, median DOR was 23.1 months and median OS was not reached.....ORR and CR rates in the ALPHA/ALPHA2 trials were consistent with those observed with approved autologous CD19 CAR T cell products for patients with R/R LBCL after two or more lines of systemic therapy. All treatment regimens studied demonstrated clinical benefit."

P1 data • Large B Cell Lymphoma

ALPHA-2: Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults with Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2) (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: Allogene Therapeutics | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2025 ➔ Aug 2025

Enrollment closed • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Clinical Response after Allogeneic CAR T Cell Therapy Is Linked to Expansion of Identical CD8+ Effector-like T Cell Clones (ASH 2024) - P1/2 | "We identified patients with relapsed/refractory large B-cell lymphoma treated on the ALPHA-2 phase 1 trial (NCT04416984) with a single lot of ALLO-501A, a healthy donor-derived CD19 CAR T with T cell receptor (TCR) and CD52 knockout using Cellectis technologies...Moreover, our data highlight clones with effector-like molecular states as a key subset which could mediate antitumor responses to allogeneic CAR T cell products. These findings, as well as the presence of this phenotype in donor PBMCs prior to manufacturing, carry important implications for future development of these therapies."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD52 • CD8 • GZMH • GZMK • KLRG1 • NKG7

Allogene abandons leukemia plans for CAR-T in wake of Breyanzi approval (FierceBiotech) - "Allogene Therapeutics has dropped plans to target one of its allogeneic CAR-Ts at leukemia in the face of competition from the likes of Bristol Myers Squibb...The biotech had been enrolling patients in a phase 1 trial of a CD19 CAR-T cell therapy called cemacabtagene ansegedleucel—cema-cel for short—for relapsed or refractory chronic lymphocytic leukemia (CLL) in patients previously treated with BTKi and BCL2i therapies....'While there is an ongoing need for additional treatment options for these patients, and interest in this cohort remains high among investigators, enrollment in the trial has been slower than anticipated due in part to the emergence of new alternative treatment options.'....'Consequently, the company is discontinuing enrollment in this trial and reallocating resources to other programs.'"

Trial termination • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Cellectis Provides Business Updates and Financial Results for Third Quarter 2024 (GlobeNewswire) - "Allogene announced that enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel, and that initial data readout from the CLL cohort is projected by early 2025. Allogene announced that a Phase 1 data update of the TRAVERSE trial of ALLO-316 from approximately 20 patients with CD70 positive RCC is planned by YE 2024."

P1 data • Chronic Lymphocytic Leukemia • Renal Cell Carcinoma

Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL) (Allogene Therapeutics Press Release) - "The pivotal Phase 2 ALPHA3 trial is the main focus for the Company. The trial was initiated in June 2024 and now has almost 30 sites activated and screening for patients with minimal residual disease (MRD)...This innovative ALPHA3 trial will identify patients at high risk for relapse after 1L treatment by utilizing Foresight CLARITY powered by PhasED-Seq...This randomized trial will enroll approximately 240 patients and is designed to demonstrate a meaningful improvement in event free survival (EFS) in patients treated with cema-cel relative to patients who receive the current standard of care (observation). ALPHA3 is expected to complete enrollment in 1H 2026. Efficacy analyses are expected to occur in 2026 and will include an interim EFS analysis monitored by the independent Data Safety Monitoring Board (DSMB) in 1H 2026 and the data readout of the primary EFS analysis by YE 2026. A potential biologics license application (BLA) submission is targeted for 2027."

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

Allogene Therapeutics Activates Three Community Cancer Centers as First Sites for the Pivotal Phase 2 ALPHA3 Trial Evaluating Cemacabtagene Ansegedleucel (cema-cel) as First Line (1L) Consolidation Treatment for Patients with Large B-Cell Lymphoma (LBCL) (Allogene Therapeutics Press Release) - "Allogene Therapeutics...announced that Rocky Mountain Cancer Centers (RMCC), part of the US Oncology Network and Sarah Cannon Research Institute (SCRI); Astera Cancer Care (ACC), a multi-specialty community oncology practice and part of the OneOncology network; and Norton Cancer Institute, are open for enrollment in the pivotal Phase 2 ALPHA3 trial. The ALPHA3 trial is evaluating the use of cemacabtagene ansegedleucel (cema-cel) as part of the first line (1L) consolidation treatment regimen for newly diagnosed and treated large B-cell lymphoma (LBCL) patients who remain positive for minimal residual disease (MRD)....ALPHA3 Expected to Complete Enrollment in 1H 2026...."

Trial status • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Initiates Pivotal Phase 2 Trial Investigating Cemacabtagene Ansegedleucel (cema-cel), an Allogeneic CAR T Product, as Part of First Line Treatment for Patients with Large B-Cell Lymphoma (LBCL) Likely to Relapse (GlobeNewswire) - "Allogene Therapeutics...announced the initiation of the pivotal Phase 2 ALPHA3 trial evaluating the use of cemacabtagene ansegedleucel (cema-cel) as part of the first line (1L) treatment regimen for newly diagnosed LBCL patients who are likely to relapse after standard 1L treatment and need further therapy....This randomized study will enroll approximately 240 patients and is designed to demonstrate a meaningful improvement in event free survival (EFS) in patients treated with cema-cel relative to patients who receive the current standard of care (observation). Efficacy analyses are expected to occur in 2026 and will include an interim EFS analysis monitored by the independent Data Safety Monitoring Board (DSMB) in 1H 2026 and the data readout of the primary EFS analysis in 2H 2026 with a potential biologics license application (BLA) submission targeted for 2027."

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

EXPAND: Evaluation of Lymphodepletion With ALLO-647 in Adults With R/R Large B Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Allogene Therapeutics | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2025 ➔ Feb 2024

CAR T-Cell Therapy • Enrollment closed • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis Reports Financial Results for First Quarter 2024 (GlobeNewswire) - "Anti-CD19 program:...Allogene further announced that enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel....Anti-CD70 program:...Allogene announced that a Phase 1 data update of the ongoing TRAVERSE trial with ALLO-316 in RCC from approximately 20 patients with CD70 positive RCC is planned by YE 2024."

Enrollment status • P1 data • Chronic Lymphocytic Leukemia • Clear Cell Renal Cell Carcinoma

Allogene Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Business Update (GlobeNewswire) - "ALPHA3 will randomize approximately 230 patients who are in clinical remission but remain MRD positive at the end of standard 1L chemoimmunotherapy to either consolidation with cema-cel or the current standard of care, observation, which means to 'watch and wait' for the disease to relapse. The primary endpoint of the ALPHA3 trial is event free survival (EFS). The trial will initially test two lymphodepletion regimens (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647). One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population. Start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024."

New P2 trial • Diffuse Large B Cell Lymphoma

Allogene Therapeutics and Foresight Diagnostics Announce Partnership to Develop MRD-based In-Vitro Diagnostic for Use in ALPHA3, the First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma (GlobeNewswire) - "Allogene Therapeutics...and Foresight Diagnostics (Foresight)...announced a strategic partnership to develop a minimal residual disease (MRD) in-vitro diagnostic (IVD) to determine eligibility in ALPHA3, the first pivotal trial for first line (1L) consolidation treatment of large B-cell lymphoma (LBCL). The ALPHA3 trial uses Foresight’s investigational PhasED-Seq™ ctDNA-MRD platform to identify patients with MRD after 1L treatment for LBCL. The study will evaluate whether such patients benefit from consolidation with cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A)....The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL is expected to begin mid-2024."

Diagnostic • Licensing / partnership • New P2 trial • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Announces 2024 Platform Vision to Redefine the Future of CAR T Led by ALPHA3, the Industry's First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma (GlobeNewswire) - "The new Phase 1 ALPHA2 cohort of 12 patients treated with the investigational product cema-cel provides the opportunity to set a higher bar where patients with CLL are not reliant on their own T cells’ fitness to benefit from the curative potential of CAR T. This study, driven by investigator enthusiasm, will leverage currently active ALPHA2 trial sites in the U.S. which should allow it to advance quickly. It is expected to begin enrolling in Q1 2024 with initial data projected by YE 2024."

P1/2 data • Trial status • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Announces 2024 Platform Vision to Redefine the Future of CAR T Led by ALPHA3, the Industry's First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma (GlobeNewswire) - "Start-up activities for the ALPHA3 trial have been initiated. The study will randomize approximately 230 patients who are MRD positive at the end of 1L therapy to either consolidation with cema-cel or the current standard of care (observation). The design, with a primary endpoint of event free survival (EFS), will initially include two lymphodepletion arms (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647)...the Company will focus on quickly advancing this market-defining ALPHA3 trial and deprioritize the currently enrolling third line (3L) ALPHA2 and EXPAND trials."

Clinical protocol • Enrollment status • Diffuse Large B Cell Lymphoma

Cellular Mechanisms Affecting Allogeneic CAR T Cell Expansion and Rejection in Large B-Cell Lymphoma (ASH 2023) - P1/2 | "We identified 11 patients with relapsed/refractory large B-cell lymphoma treated on the ALPHA-2 phase 1 trial (NCT04416984) with ALLO-501A, a healthy donor-derived CD19 CAR T with T cell receptor (TCR) knockout...We revealed the impact of recipient alloreactive CD8+ T cells in allogeneic CAR T rejection and identified expansion of identical allogeneic CAR T clonotypes with retained clonal hierarchy in multiple patients. While patient factors such as tumor burden and target antigen expression likely play a role as well, our results suggest that strategies to eliminate alloreactive recipient cells and enhance allogeneic CAR T fitness through improved product design, manufacturing and lymphodepletion could improve allogeneic CAR T expansion, persistence and efficacy."

CAR T-Cell Therapy • IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8

ALLO-647 for Lymphodepletion in the Allogeneic CAR T Setting: Safety Experience with ALLO-501/501A in Patients (Pts) with Relapsed/Refractory (r/r) Large B-Cell and Follicular Lymphomas (ASH 2023) - P1, P1/2 | "Updated phase 1 data for ALLO-501 (ALPHA; NCT03939026) and ALLO-501A (ALPHA2; NCT04416984) showed that administration of anti-CD19 allogeneic CAR T product following use of lymphodepletion that includes ALLO-647 plus fludarabine and cyclophosphamide provided durable responses and an acceptable safety profile in CAR T-cell–naive pts with r/r large B-cell lymphoma (LBCL; Locke FL, et al. These data suggest allogeneic CAR T-cell products administered following lymphodepletion consisting of FC and ALLO-647 can provide a safe and tolerable alternative to autologous CAR T-cell therapy."

Clinical • Anemia • CNS Disorders • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombocytopenia

DURABLES RESPONSES ACHIEVED WITH ANTI-CD19 ALLOGENEIC CAR T ALLO-501/501A IN PHASE 1 TRIALS OF AUTOLOGOUS CAR T-NAÏVE PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (R/R LBCL) (EHA 2023) - P1, P1/2 | "Conditioning with a regimen of fludarabine (F)/cyclophosphamide (C)/ALLO-647 (A, a humanized anti-CD52 monoclonal IgG1) targets host CD52+ immune cells for elimination while allowing subsequently infused CD52-knock-out ALLO-501/501A cells to persist. A single dose of AlloCAR T therapy following FCA90 conditioning provided durable responses with a manageablesafety profile in autologous CAR T-naïve pts with r/r LBCL. Among 8 pts who received FCA90 and ALLO-501/501A and had the opportunity to be evaluated for 6 months, 50% maintained that response for at least 6 months, with a median DOR of 23.1 months. These findings support broader evaluation of ALLO-501A/ALLO-647 in the ongoing, first potentially pivotal phase 2 trial (ALPHA2) of AlloCAR T therapy."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 results with anti-CD19 allogeneic CAR T ALLO-501/501A in relapsed/refractory large B-cell lymphoma (r/r LBCL). (ASCO 2023) - P1, P1/2 | " In these two multicenter, single-arm, open-label, phase 1 trials, a cohort of autologous CAR T-naïve pts with r/r LBCL underwent 3-day lymphodepletion (LD) with FCA90, fludarabine (F, 30 mg/m2/day), cyclophosphamide (C, 300 mg/m2/day), and ALLO-647 (A [anti-CD 52 mAb] 30 mg/day; total dose: 90 mg) followed by a single dose of ALLO-501 or ALLO-501A produced by the Alloy manufacturing process. A one-time dose of allogeneic CAR T therapy following LD with FCA90 provided durable responses with a manageable safety profile in patients with r/r/ LBCL comparable to those treated with autologous CAR T cells. This treatment enables rapid access to off-the-shelf treatment with a median time from trial enrollment to treatment of 3 days. These findings support broader evaluation of ALLO-501A in the ongoing, first potentially pivotal phase 2 trial (ALPHA2) of off-the-shelf allogeneic CAR T cells."

P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Allogene Therapeutics Reports Third Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "The single-arm ALPHA2 trial in relapsed/refractory (R/R) large B cell lymphoma (LBCL) utilizes a single dose of ALLO-501A (120 million CAR+ cells) following lymphodepletion with FCA90....Enrollment is expected to be completed by the 1H 2024 with the first data readout by the end of 2024."

Enrollment status • P1/2 data • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Announces Poster Presentations at the 65th Annual Meeting of the American Society of Hematology (GlobeNewswire) - "The first poster is a comprehensive safety review of all 85 patients treated in the Phase 1 ALPHA/ALPHA2 studies in relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL) to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion....The second poster showcases translational results from ALPHA2 generated through a collaboration with researchers from The University of Texas MD Anderson Cancer Center."

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

Allogene Therapeutics Reports Second Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "The Company is enrolling patients in the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A across sites in the United States and Canada. The European Medicines Agency (EMA) recently approved the ALPHA2 Clinical Trial Application (CTA) and patient enrollment in Europe is expected to begin in Q3 2023 and in Australia by year-end....ALPHA2 trial expected to complete enrollment in 1H 2024 with the first data readout planned by year-end 2024."

P1/2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology