AUTO2 / Autolus - LARVOL DELTA

APRIL CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma: A Phase I Clinical Trial (ASH 2024) - P1 | "Safety, efficacy, and APRIL CAR-T cellular kinetics were evaluated.Results : 9 patients received APRIL CAR-T infusions following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 88.8% (8/9), including 2 (22.2%) with complete remission (CR), 4 (44.4%) with very good partial remission (VGPR), and 2 (22.2%) with partial remission (PR).After a median follow-up of 6.63 months (range, 0.50-13.90 months), 1 patients remained in complete remission,and 1 patient died of a cerebrovascular accident. The median overall survival and relapse-free survival for the patients treated with APRIL CAR-T cells was 8.31 months (95% confidence interval [CI], 0.50-13.90 months) and 2.80 months (95% CI, 0.50-6.63 months), respectively.Conclusions : The APRIL CAR-T cell-based therapy appeared to be a promising therapeutic approach in r/r MM, based on its antitumor effects and manageable side effects, meanwhile additional strategies are required to..."

CAR T-Cell Therapy • Clinical • P1 data • Cardiovascular • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

Obecabtagene autoleucel (obe-cel, AUTO1) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL): Overall survival (OS), event-free survival (EFS) and the potential impact of chimeric antigen receptor (CAR)-T cell persistency and consolidative stem cell transplantation (SCT) in the open-label, single-arm FELIX phase Ib/II study. (ASCO 2024) - P1/2 | "Pts received bridging therapy as appropriate and underwent lymphodepletion (fludarabine, 4×30mg/m 2; cyclophosphamide, 2×500mg/m 2 ), followed by obe-cel split dose infusions on Days 1 and 10 based on pre-lymphodepletion leukemic burden at a target dose of 410×10 6 CAR-T cells...At screening, pts' median age was 47 yrs; 42%/31%/44% had received prior blinatumomab/inotuzumab ozogamicin/allogeneic SCT; median bone marrow blast burden was 36% (range: 0−100)... Ongoing CAR-T cell persistency and B-cell aplasia were associated with improved EFS without further consolidation post-obe-cel. At the current follow-up, consolidative SCT for pts in MRD-negative remission post-obe-cel did not improve EFS or OS."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy. (PubMed, J Immunother Cancer) - P1/2 | "The APRIL CAR was well tolerated, but the clinical responses observed in AUTO2 were disappointing. Subsequently, when comparing the APRIL CAR to other BCMA CARs, we observed in vitro functional deficiencies due to reduced target binding by cell-expressed ligand."

CAR T-Cell Therapy • Journal • Hematological Malignancies • Immune Modulation • Multiple Myeloma • Oncology • IL2

Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy (J Immunother Cancer) - P1/2 | N=12 | NCT03287804 | Sponsor: Autolus Limited | "Eleven patients received 13 doses, the first 15×106 CARs, and subsequent patients received 75,225,600 and 900×106 CARs in a 3+3 escalation design....The APRIL CAR was well tolerated. Five (45.5%) patients developed Grade 1 cytokine release syndrome and there was no neurotoxicity. However, responses were only observed in 45.5% patients (1×very good partial response, 3×partial response, 1×minimal response)."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

FIRST IN HUMAN STUDY OF AUTO4, A TRBC1-TRAGETTING CART T CELL THERAPY IN RELAPSED/REFRACTORY TRBC1-POSITIVE PERIPHERAL T-CELL LYMPHOMA (ICML 2023) - P1/2 | "Chemotherapy bridging was given to 70% of patients and 4/8 CD30+ patients recieved brentuximab as bridging or as prior line therapy... AUTO4 was well tolerated with no DLT. Ongoing CMR at months 12 and 15 are encouraging. Updated data and longer follow up using the improved manufacturing process B will be presented."

IO biomarker • P1 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

SAFETY AND PRELIMINARY EFFICACY FINDINGS OF AUTO4, A TRBC1-TARGETTING CAR, IN RELAPSED/REFRACTORY TRBC1 POSITIVE SELECTED T CELL NON-HODGKIN LYMPHOMA (EHA 2022) - P1/2 | "Patients received lymphodepletion with fludarabine (30mg/m 2 x4, day-6 to day-3) and cyclophosphamide (500mg/m 2 x2 on day-6 and day-5) (Flu/Cy) prior to AUTO4 infusion on Day 0...Early data shows encouraging response rates. U pdated data and longer follow up will be presented."

Clinical • IO biomarker • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Transplantation

First in Human Study of AUTO4, a TRBC1-Targeting CAR T-Cell Therapy in Relapsed/Refractory TRBC1-Positive Peripheral T-Cell Lymphoma (ASH 2022) - P1/2 | "Patients received lymphodepletion with fludarabine (30mg/m2 for 4 days) and cyclophosphamide (500mg/m2 for 2 days) (Flu/Cy) prior to AUTO4 infusion... AUTO4 treatment was well tolerated with no DLT. Early responses are encouraging, although no CAR T cell expansion was seen in peripheral blood which may translate to responses that are not durable. To address this, optimisation of the AUTO4 manufacturing process has been performed, resulting in a product with a more naïve phenotype."

CAR T-Cell Therapy • IO biomarker • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

DUAL ANTIGEN TARGETING WITH CO-TRANSDUCED CD19/22 CAR T CELLS MAY PREVENT ANTIGEN-NEGATIVE RELAPSE AFTER CAR T CELL THERAPY FOR RELAPSED/REFRACTORY ALL (EBMT 2023) - P1 | "We evaluated safety/efficacy of AUTO1/22 in a Phase I study in children/young adults with r/rALL (NCT02443831)...Following fludarabine/cyclophosphamide lymphodepletion, patients received 1x106 /kg CAR+ T cells...Six of 12 patients had relapsed post allogeneic stem cell transplant (SCT), 6 had received prior Blinatumomab/Inotuzumab and 4 had relapsed after prior Tisagenlecleucel...Cytokine release syndrome (CRS) occurred in 11/12 patients (grade 1 n=5, grade 2 n=6) requiring Tocilizumab in 4 cases, but there was no severe (≥ grade 3) CRS... Dual CD19/22 targeting CAR T cells generated by co-transduction suggest a good safety profile and efficacy in a heavily pre-treated cohort of patients. Antigen-negative relapse has not been observed to date, indicating that dual targeting may be effective in preventing antigen evasion."

CAR T-Cell Therapy • Bone Marrow Transplantation • CNS Disorders • Hematological Disorders • Inflammation • Pediatrics • Transplantation • CD19 • CD22 • CD34

Dual Antigen Targeting with Co-Transduced CD19/22 CAR T Cells May Prevent Antigen-Negative Relapse after CAR T Cell Therapy for Relapsed/Refractory ALL (ASH 2022) - P1 | "Building on these properties, we developed AUTO1/22 an autologous CAR T cell product co-transduced with two different lentiviral vectors encoding our existing CD19 CAR and a novel CD22CAR designed to recognise targets with low antigen density...Following fludarabine/cyclophosphamide lymphodepletion, patients received 1x106 /kg CAR+ T cells...Six of 12 patients had relapsed post allogeneic SCT, 6 had received prior Blinatumomab/Inotuzumab and 4 had relapsed after prior Tisagenlecleucel...Cytokine release syndrome (CRS) occurred in 11/12 patients (grade 1 n=5, grade 2 n=6) requiring Tocilizumab in 5 cases, but severe (≥ grade 3) CRS was not seen and no patients required ICU admission for CRS... Our data show that dual CD19/22 targeting CAR T cells generated by co-transduction show a favorable safety profile, with robust expansion/persistence and early efficacy in a heavily pre-treated cohort. To date with we have not observed antigen negative relapse. This contrasts..."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Oncology • Pediatrics • CD19 • CD22 • CD34

Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. (PubMed, J Immunother Cancer) - "Antitumor responses with APRIL-CAR T cells were fast but not sustained. Rapid BCMA downmodulation occurred independently of whether an APRIL or antibody-based binding moiety was used. BCMA internalization mostly contributed to this effect, but trogocytosis by CAR T cells was also observed. Our study sheds light on the mechanisms underlying CAR T cell failure in MM when targeting BCMA and can inform the development of improved treatment strategies."

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

APRIL CAR-T Cell Therapy for Patients With BCMA/TACI Positive Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2027 ➔ Aug 2027 | Trial primary completion date: Jan 2024 ➔ Aug 2024

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

APRIL CAR-T Cell Therapy for Patients With BCMA/TACI Positive Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Zhejiang University

CAR T-Cell Therapy • Clinical • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 1 First-in-Human Study of AUTO2, the First Chimeric Antigen Receptor (CAR) T Cell Targeting APRIL for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2019) - "All patients receive lymphodepletion with 30 mg/m2/day fludarabine and 300 mg/m2/day cyclophosphamide for 3 days prior to AUTO2 infusion...Median age was 61 years (range 45-69 years), median 5 prior lines of treatment (range 3-6) ,73% had prior autologous transplant, 100% were refractory to a PI or IMiD, 80% were refractory to both and 45% were refractory to daratumumab...Tocilizumab was given to 3 patients (27%)... AUTO2 is a novel CAR-T therapy, with a manageable safety profile at doses up to 900x10e6 CAR-T cells."

Clinical • IO Biomarker • P1 data • CD8

Autolus Therapeutics to present new data on its advanced programmed T cell therapies at the 61st ASH Annual Meeting (GlobeNewswire) - "Autolus Therapeutics plc...announced four oral and two poster presentations related to its AUTO1, AUTO2 and AUTO3 programs at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition, to be held December 7-10, 2019 in Orlando, FL...'We are pleased that AUTO1 data will be presented in three oral presentations at ASH. The data form the basis for our decision to move AUTO1 into a pivotal clinical trial in adult ALL, our highest priority program'."

Clinical data

APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma (clinicaltrials.gov) - P1/2; N=12; Terminated; Sponsor: Autolus Limited; N=80 ➔ 12; Trial completion date: Oct 2020 ➔ Sep 2019; Recruiting ➔ Terminated; Trial primary completion date: Oct 2020 ➔ Sep 2019; Preliminary efficacy seen to date following treatment with AUTO2 has been determined not sufficient to warrant further development

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Arix Bioscience plc: interim results for the six months ended 30 June 2019 (PRNewswire) - "Key anticipated milestones: Aura Biosciences expects to initiate the AU-011 Phase 3 clinical study for choroidal melanoma in the first half of 2020; Autolus expects to initiate a Phase 2 registration trial of AUTO1 in aALL in the fourth quarter of 2019 and present updated Phase 1 data at The American Society of Hematology (ASH) in December 2019; Autolus expects to present interim Phase 1 data for the Alexander study of AUTO3 in DLBCL at ASH 2019 and initiate a Phase 2 trial in the second quarter of 2020, pending regulatory feedback; Autolus expects to present updated Phase 1 results for the CARPALL study of AUTO1 in pALL at ASH 2019; Autolus expects next generation (NG) programmes for AUTO1, AUTO2, AUTO3 and AUTO6 to enter the clinic in 2020."

Clinical • New P2 trial • New P3 trial • P1 data

Autolus Therapeutics Reports Second Quarter 2019 Financial Results and Operational Progress (GlobeNewswire, Autolus Limited) - "Anticipated Milestones:..Initiation of a Phase 2 registration trial of AUTO1 in adult ALL in the fourth quarter of 2019 (pending regulatory feedback). Updated Phase 1 data from the ALLCAR19 clinical trial is expected at ASH 2019; Decision on Phase 2 initiation for the Alexander study of AUTO3 in DLBCL is expected for mid-2020. Interim Phase 1 data is expected at ASH 2019; Next data update from CARPALL clinical trial is expected at ASH 2019. First preclinical data on CD22 CAR expected to be presented at ASH 2019; Additional presentations targeted for ASH 2019 are: data from AMELIA clinical trial of AUTO3 in pediatric ALL and data from clinical trial of AUTO2 in multiple myeloma; Next generation (NG) programs for AUTO1, AUTO2, AUTO3 and AUTO6 are expected to enter the clinic in 2020."

Clinical • Clinical data • Preclinical • Trial initiation date

Autolus Therapeutics reports first quarter 2019 financial results and operational progress (GlobeNewswire) - “Anticipated Milestones: Presentation of a data update from the ALEXANDER Phase 1/2 trial of AUTO3 in adult relapsed/refractory diffuse large B cell lymphoma (DLBCL) in the third quarter of 2019; Initiation of the Phase 2 portion of the AMELIA trial of AUTO3 in pediatric ALL in the second half of 2019; Initiation of a Phase 2/registration trial of AUTO1 in adult ALL in the second half of 2019 (pending regulatory feedback); Presentation by the end of 2019 of data updates from the following trials: AUTO1 in adult ALL and pediatric ALL; AUTO3 in DLBCL and pALL and AUTO2 in multiple myeloma.”

Clinical data • New P2 trial • P1/2 data • Trial status