ALLO-715 / Cellectis, Allogene Overland Biopharm, Overland Therapeutics - LARVOL DELTA

Efficacy and Safety of Chimeric Antigen Receptor T-Cell Therapy in Relapsed and Refractory Multiple Myeloma – a Meta-Analysis (ASH 2024) - "We included 7 trials each of Ciltacabtagene autoleucel (cilta-cel) and Idecabtagene vicleucel (ida-cel) while 21 trials used different CAR-T cell therapies including GPRC5D, HDS269B, C-CAR088, HBI0101, CART-ddBCMA, ALLO-715, ARI0002h. This analysis has limitations with significant heterogeneity among studies. There were different CAR T-cell therapies with diverse designs of studies which limit the generalization of results."

CAR T-Cell Therapy • Retrospective data • Anemia • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) (clinicaltrials.gov) - P1 | N=132 | Active, not recruiting | Sponsor: Allogene Therapeutics | Trial completion date: Dec 2027 ➔ Sep 2027 | Trial primary completion date: Dec 2022 ➔ Sep 2027 | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Universal Updated Phase 1 Data Validates the Feasibility of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma (ASH 2021) - P1 | "Several LD regimens are being evaluated: FCA39; FCA60; FCA90; and CA39; with fludarabine [F] 90 mg/m 2 , cyclophosphamide [C] 900 mg/m 2 , and ALLO-647 [A] 39, 60, or 90 mg divided over 3 days...CRS was treated with tocilizumab (21.3%) and corticosteroids (12.8%)...A study using the next generation anti-BCMA CAR (ALLO-605) which supplies cytokine signaling to the CAR bearing cells is ongoing (IGNITE). The current UNIVERSAL trial continues to enroll, including a cohort with consolidation, and updated data will be presented at the meeting."

P1 data • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. (PubMed, Nat Med) - "We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial...Among patients treated with 320 × 10 CAR T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n = 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma."

CAR T-Cell Therapy • Journal • P1 data • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Oncology

[VIRTUAL] BCMA-Directed CAR T-Cells: Early Results and Future Directions (SOHO 2021) - "Other Constructs of Interest Orva-cel (orvacabtagene autoleucel) is an anti-BCMA CAR T product with a construct containing a fully human scFv, an optimized spacer, a 4-1BB co-stimulatory domain, and a CD3z activation domain...Bb21217 has an identical construct to ide-cel except for coculturing with the phosphoinositide 3 kinase inhibitor (PI3K) bb007 during ex vivo culture to enrich for T cells displaying a memory-like phenotype...The ORR was 94%.17 P-BCMA-101 is a novel construct using an anti-BCMA Centyrin™ fused to a 4-1BB costimulatory domain and CD3z signaling domain...Both ide-cel and cilta-cel are being evaluated in various patient populations, including early-relapse and newly diagnosed high-risk patients...The first results of an allogeneic BCMA-directed CAR-T was with ALLO-715. The initial results from the UNIVERSAL phase 1 study in RRMM are encouraging, with responses reported and more attenuated toxicity.26 Others, including CTX120, BCMAUCART, UCART CS1, and..."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma • Oncology • CD19 • CD4 • CD8 • SDC1 • TNFA

"Correction! No anti-ALLO-715 scFv antibodies were detected in any subject!" (@bdermanmd)

Allogene Therapeutics Announces Publication in Nature Medicine of Data from its Phase 1 UNIVERSAL Study of ALLO-715 for the Treatment of Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - P1 | N=132 | UNIVERSAL (NCT04093596) | Sponsor: Allogene Therapeutics | "Allogene Therapeutics, Inc...announced that data from its Phase 1 UNIVERSAL trial of ALLO-715, an anti-BCMA AlloCAR T product candidate for relapsed/refractory (r/r) multiple myeloma (MM) has been published in Nature Medicine....The Nature Medicine publication includes data from the first 48 patients enrolled with a data cutoff of October 2021. All patients treated were refractory to their last line of treatment and no bridging therapy was used in this trial. Data demonstrated the ability for an allogeneic CAR T to achieve response rates in line with certain approved autologous CAR T therapies and durable remissions with a manageable safety profile while treating 92% of all enrolled patients and all product manufactured and released as per product specifications."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

ALLO-715: “UNIVERSAL has demonstrated significant and durable responses with a manageable safety profile and ongoing responses up to 24 months”; Multiple myeloma (Allogene Therapeutics) - R&D Showcase: “ALLO-715 expansion cohorts with FCA lymphodepletion was associated with clinically meaningful efficacy, including VGPR+ rates of nearly 50% without requiring leukapheresis or bridging therapy”

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Universal Updated Phase 1 Data Highlights Role of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma (ASH 2022) - P1 | "Pts receive LD followed by ALLO-715 at 1 of 4 dose levels (DLs) in a 3+3 dose escalation design: 40 (DL1), 160 (DL2), 320 (DL3), and 480 (DL4) x 106 CAR+ T cells with varying doses and schedules of LD including ALLO-647 with fludarabine and cyclophosphamide (FC)...The use of tocilizumab and steroids across all pts was 19% and 15%, respectively...FCA induces a deep and durable window of lymphocyte depletion allowing CAR T cell expansion. The UNIVERSAL trial continues to enroll pts in the FCA60 cohort and updated data will be presented."

P1 data • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

"$ALLO DISCLOSED FULL RESULTS OF ALLO-715?" (@BursatilBiotech)

Allogene Therapeutics R&D Showcase Features Hematologic and Solid Tumor Advances Across its AlloCAR T Platform (GlobeNewswire) - P1 | N=132 | UNIVERSAL (NCT04093596) | Sponsor: Allogene Therapeutics | "The Phase 1 UNIVERSAL study is a dose escalation trial in patients with heavily pretreated r/r multiple myeloma (MM). Dose expansion cohorts comprised of a single dose of ALLO-715 (320 million CAR+ cells) and either FCA39 lymphodepletion (standard flu/cy plus 39 mg of ALLO-647) or FCA60 lymphodepletion (standard flu/cy plus 60 mg of ALLO-647) demonstrated substantial and durable responses....Through a median follow-up of 14.8 months as of the October 11, 2022 data cutoff, the ORR was 67% in the FCA60 cohort and the very good partial response or better rate (VGPR+) was 42%. All VGPR+ were minimal residual disease (MRD) negative. The median duration of response was 9.2 months, with the longest ongoing response at 24 months."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Allogene Therapeutics Announces Poster Presentation of Its Phase 1 UNIVERSAL Trial in Multiple Myeloma at the 64th Annual Meeting of the American Society of Hematology (GlobeNewswire) - "Allogene Therapeutics, Inc...today announced that it will present updated data from its Phase 1 UNIVERSAL trial of ALLO-715...for relapsed/refractory multiple myeloma, in a poster presentation at the 64th Annual Meeting of the American Society of Hematology (ASH) taking place December 10-13, 2022 in New Orleans, LA....The ASH abstract includes longer-term follow up from UNIVERSAL, including the updated safety experience and efficacy results from two expansion cohorts using lymphodepletion of FC (fludarabine, cyclophosphamide) and ALLO-647 at 39mg or 60mg and a single dose of ALLO-715 at 320M CAR positive cells."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Allogene: Possible First Pivotal Study With Allogeneic CAR-T ALLO-501A (SeekingAlpha) - "Allogene Therapeutics, Inc....Initiate a pivotal phase 2 study using an allogeneic CAR-T for the treatment of patients with non-Hodgkin's Lymphoma (NHL). Such a pivotal study is expected to be initiated in the coming weeks....There are going to be trial results released from several long-term follow-up studies including ALPHA, ALPHA2 and UNIVERSAL as well. All of these results will be released by the end of 2022. With a proven allogeneic CAR-T for the treatment of patients with NHL (specifically B-cell lymphoma), plus several trial updates expected by the end of 2022...ALLO-647, it is going to be tested in a trial known as EXPAND. This trial is expected to begin in 2022..."

New P2 trial • P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Allogene Therapeutics Reports Second Quarter 2022 Financial Results (GlobeNewswire) - "In the coming weeks, the Company expects to receive clearance from the U.S. Food and Drug Administration (FDA) to initiate a potential Phase 2 pivotal clinical trial for ALLO-501A in relapsed/refractory (r/r) large B cell lymphoma (LBCL)...Allogene anticipates providing an update on the Phase 1 portion of the ALPHA and ALPHA2 trials toward the end of 2022...The EXPAND trial is expected to begin in 2022 and is planned to support registration of the lymphodepleting agent ALLO-647....Enrollment continues in the Phase 1 UNIVERSAL trial on ALLO-715 in r/r multiple myeloma (MM). Toward the end of 2022, Allogene intends to provide a clinical update that will focus on the longer-term follow up of patients in UNIVERSAL treated with a single dose of ALLO-715."

New P2 trial • P1 data • P1/2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Universal: An Allogeneic First-in-Human Study of the Anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed/Refractory Multiple Myeloma (ASH 2020) - P1 | "These include: FCA (fludarabine (F) 90 mg/m2, cyclophosphamide (C) 900 mg/m2, and ALLO-647 (A) 39 mg divided over 3 days), FCA+ (same F and C but ALLO-647 (A+) dose of 90 mg divided over 3 days); as well as CA (same C and A divided over 3 days, but no F given)...Three episodes were Grade 1 and 1 was Grade 2 (Lee Grading); all resolved without tocilizumab or corticosteroids...Updated safety, efficacy, PK/PD data will be presented. Clinical trial information: NCT04093596."

P1 data • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation • CD38 • CD52

Allogene Therapeutics Announces Preclinical Publication Highlighting Superiority of Healthy Donor-Derived Allogeneic CAR T Cells Over Patient-Derived Cells in Multiple Myeloma (GlobeNewswire) - "Allogene Therapeutics...announced the publication of preclinical study results demonstrating the superior long-term in vitro myeloma-killing activity of allogeneic anti-BCMA CAR T cells from healthy donors compared with anti-BCMA CAR T cells from patients with multiple myeloma....Anti-BCMA allogeneic CAR T cells derived from healthy donors showed efficient killing of primary multiple myeloma cells across different patient sub-groups including those with high-risk disease....Allogene intends to provide a BCMA program clinical update by the end of 2022."

Clinical • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: Allogene Therapeutics | Active, not recruiting ➔ Recruiting | Trial completion date: Nov 2024 ➔ Dec 2027 | Trial primary completion date: Nov 2021 ➔ Dec 2022

CAR T-Cell Therapy • Enrollment open • IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Current state and next-generation CAR-T cells in multiple myeloma. (PubMed, Blood Rev) - "Here, we review the main clinical trials of CAR-T cells in MM with the most advanced autologous BCMA-directed ide-cel and cilta-cel, the human CARs orva-cel and CT053, the alternative manufacturing process with P-BCMA-101 and bb21217, the dual CAR GC012F and the allogenic BCMA-directed CAR-T cells ALLO-715. In light of those clinical data, we provide an overview of CAR-T cells' main potential resistance mechanisms, including antigen loss, antigen spreading, anti-CAR antibodies, CAR-T cell exhaustion, and the emergence of a non-permissive microenvironment. Finally, we describe the principal area of research to build the next generation of CAR-T cells, with armored-, gated- or commuting-CARs, CARs associated with knock out of specific genes, and CAR-T cells made from γδT cells or NK cells."

CAR T-Cell Therapy • Journal • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

ALLO-715: "ALLO-715 with ALLO-647 was well tolerated with low-grade CRS, low-grade reversible neurotoxicity, no GvHD, and manageable safety"; Multiple myeloma (Allogene Therapeutics) - ASH 2021: "71% ORR and 46% VGPR+ with 320M cell dose and FCA comparable to approved autologous CAR T therapy, 92% VGPR+ responses were MRD negative, 8.3 months median durability of response"

P1 data • Multiple Myeloma • Oncology

"just watched allo715 additional Grade 5 reported (re. intensity of conditioning)" (@PDRennert)

Allogene Therapeutics Reports Positive Results from Phase 1 UNIVERSAL Study of Single Dose ALLO-715 AlloCAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma at the 63rd American Society of Hematology Annual Meeting (GlobeNewswire) - P1, N=132; UNIVERSAL (NCT04093596); Sponsor: Allogene Therapeutics; "Allogene Therapeutics...today announced positive updated results from the Phase 1 UNIVERSAL study of single dose ALLO-715 in relapsed/refractory (r/r) multiple myeloma....As of the October 14, 2021 data cutoff, 48 patients were enrolled with 43 patients evaluable for safety and efficacy....The Phase 1 UNIVERSAL trial evaluated lymphodepletion followed by ALLO-715 at one of four dose levels (DL1=40M cells, DL2=160M cells, DL3=320M cells, DL4 = 480M cells) and two LD regimens (FCA: fludarabine, cyclophosphamide and ALLO-647 or CA: cyclophosphamide and ALLO-647 only). The updated presentation primarily focuses on the optimized DL3 cell dose and FCA lymphodepletion....Subject to the clinical hold currently in place, Allogene continues to target 2022 for data from these additional strategies."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Allogene Therapeutics Announces Conference Call to Review ALPHA, ALPHA2 and UNIVERSAL Phase 1 Data Presented at the 2021 American Society of Hematology Annual Meeting (GlobeNewswire) - "Allogene Therapeutics, Inc....announced that management will host a conference call to review data to be presented at the American Society of Hematology Annual Meeting from the ALPHA and ALPHA2 Phase 1 trials in relapsed/refractory non-Hodgkin lymphoma and the UNIVERSAL Phase 1 trial in relapsed/refractory multiple myeloma on December 13, 2021 at 1:30 PM Pacific Time/4:30 PM Eastern Time."

Clinical data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

ALLO-715: Data from P1 UNIVERSAL trial (NCT04093596) in combination with nirogacestat for r/r multiple myeloma in 2022 (Allogene Therapeutics) - Q3 2021 Results

P1 data • Multiple Myeloma • Oncology

Allogene Therapeutics to Showcase Clinical Data from the ALPHA, ALPHA2 and UNIVERSAL AlloCAR T Trials at the 63rd Annual Meeting of the American Society of Hematology (GlobeNewswire) - P1, N=132; UNIVERSAL (NCT04093596); Sponsor: Allogene Therapeutics; "The ASH abstract contains data as of June 21, 2021. As of the data cut-off, 47 patients were enrolled and 42 patients were treated with escalating doses of ALLO-715 and doses of ALLO-647 ranging from 39mg to 90mg. The median time from enrollment to lymphodepletion was five days. Patients were in advanced stage of disease with a median of five prior lines of therapy and 43% of patients being penta refractory. The trial did not permit bridging therapy."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) (clinicaltrials.gov) - P1; N=132; Active, not recruiting; Sponsor: Allogene Therapeutics; Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Clinical • Enrollment closed • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology