AUTO3 / Autolus - LARVOL DELTA

ALEXANDER: CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=73 | Completed | Sponsor: Autolus Limited | Active, not recruiting ➔ Completed | Trial completion date: Nov 2024 ➔ Dec 2023 | Trial primary completion date: Nov 2024 ➔ Dec 2023

CAR T-Cell Therapy • Trial completion • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

Dual targeting of CD19 and CD22 with Bicistronic CAR-T cells in Patients with Relapsed/Refractory Large B Cell Lymphoma. (PubMed, Blood) - P1/2 | "Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities."

CAR T-Cell Therapy • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22

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

[VIRTUAL] Phase 1 Alexander Study of AUTO3, the First CD19/22 Dual Targeting CAR T Cell Therapy, with Pembrolizumab in Patients with Relapsed/Refractory (r/r) DLBCL (ASH 2020) - "AUTO3 at RP2D dose range of > 50 x 106 CAR T cells with D-1 pembrolizumab induces durable complete remissions. None of the patients in CR experienced severe CRS or neurotoxicities of any grade. Outpatient cohort is currently enrolling."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Cardiovascular • Constipation • Diffuse Large B Cell Lymphoma • Fatigue • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Metabolic Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock • Thrombocytopenia • CD19

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

DUAL ANTIGEN TARGETING WITH CO-TRANSDUCED CD19/22 CAR T CELLS FOR RELAPSED/REFRACTORY ALL (EHA 2022) - P1 | "Aims To determine the safety/biological efficacy of AUTO1/22 Methods Patients with r/r B-ALL age < 25 ywho were ineligible for/relapsed after Tisagenlecleucel were recruited. Following fludarabine/cyclophosphamide lymphodepletion, patients received 1x10 6 /kg CAR + T cells...Five of 8 patients had relapsed post allogeneic SCT, 4 had received prior Blinatumomab/Inotuzumab and 3 had relapsed after prior Tisagenlecleucel...CAR T cell products had a central memory phenotype with predominance of CD19/22 double positive cells (median 59.3%) and balanced populations of CD19 and CD22 single positive cells (16% and 10.9% respectively).Cytokine release syndrome (CRS) occurred in 7/8 patients (grade 1 n=2 , grade 2 n=5 ) requiring Tocilizumab in 3 cases, but severe (≥ grade 3) CRS was not seen and no patients required ICU admission for CRS...Conclusion We demonstrate that dual CD19/22 targeting CAR T cells generated by co-transduction show an acceptable safety profile, with..."

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

[VIRTUAL] Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL. (ASCO 2020) - P1/2 | "AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Research Funding: Autolus Therapeutics"

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Lymphoma • Neutropenia • Oncology • Thrombocytopenia • PD-L1 • TNFRSF4

ALEXANDER: CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma (clinicaltrials.gov) - P1/2; N=73; Active, not recruiting; Sponsor: Autolus Limited; N=171 ➔ 73; Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Clinical • Enrollment change • Enrollment closed • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL."

CAR T-Cell Therapy • Clinical • Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Inflammation • Leukemia • Oncology • Pediatrics • CD19 • CD22

Simultaneous Targeting of CD19 and CD22: Phase I Study of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Amelia Study (ASH 2018) - "...Patients receive lymphodepletion with 30 mg/m2/day fludarabine x 4 days and 500 mg/m2/day cyclophosphamide x 2 days prior to AUTO3 infusion...One patient (13%) had prior anti-CD19 CAR-T cells and blinatumomab...Five patients (63%) experienced neurotoxicity: 4 had Gr 1 and 1 patient (13%) had Gr 3 encephalopathy that was considered likely related to prior intrathecal methotrexate...Promising efficacy was demonstrated at a dose level of 3 × 106 CAR T cells/kg, as 4/4 patients achieved MRD complete remission with no antigen negative escape at this early stage. The study continues to enrol and updated follow up and additional patient data at higher dose levels, as well as cellular kinetics and additional biomarker analysis, will be presented."

Clinical • P1 data • Acute Lymphocytic Leukemia • Biosimilar • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology

[VIRTUAL] Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR.T cell, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL (ESMO 2020) - P1/2 | "Funding: Autolus Therapeutics. Clinical trial identification: EudraCT Number: 2016-004682-11."

CAR T-Cell Therapy • Clinical • IO Biomarker • P1 data • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • CD19

Study of AUTO3, the First Bicistronic Chimeric Antigen Receptor (CAR) Targeting CD19 and CD22, Followed By Anti-PD1 Consolidation in Patients with Relapsed/Refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Alexander Study (ASH 2018) - "All patients receive lymphodepletion with 30 mg/m2/day fludarabine and 300 mg/m2/day cyclophosphamide for 3 days prior to AUTO3 infusion. The ALEXANDER study continues to enroll patients with AUTO3 followed by pembro. Updated follow up and additional patient data at higher dose levels, as well as cellular kinetics, relevant product characteristics, and biomarkers, will be presented."

Clinical • PD(L)-1 Biomarker • Biosimilar • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Indolent Lymphoma • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Transplantation

Phase I Study of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy Targeting CD19 and CD22, in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Amelia Study (ASH 2019) - "Patients receive lymphodepletion with 30 mg/m2/day fludarabine x 4 days and 500 mg/m2/day cyclophosphamide x 2 days prior to AUTO3 infusion...One patient (10%) had prior anti-CD19 CAR-T cells...Only one patient was treated with tocilizumab and none required admission to ICU due to CRS...The most common cause of relapse was antigen positive relapse due to lack of CAR T cell persistence. Evaluation of patients with a modified manufacturing process is planned."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombocytopenia

[VIRTUAL] PHASE 1 ALEXANDER STUDY OF AUTO3 THE FIRST BICISTRONIC CHIMERIC ANTIGEN RECEPTOR (CAR) TARGETING CD19 AND CD22 WITH PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (EHA 2020) - "Lymphodepletion was done with fludarabine and cyclophosphamide. Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusion AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade."

Clinical • IO biomarker • P1 data • CNS Disorders • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • PD-L1 • TNFRSF4

Phase 1/2 Study of AUTO3 the First Bicistronic Chimeric Antigen Receptor (CAR) Targeting CD19 and CD22 Followed By an Anti-PD1 in Patients with Relapsed/Refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of Cohort 1 and 2 of the Alexander Study (ASH 2019) - "In this study, we are evaluating the safety and efficacy of AUTO3, a CAR T cell therapy designed to target CD19 and CD22 simultaneously followed by 3 doses of anti-PD1 monoclonal antibody pembrolizumab (Pem) treatment...All patients received lymphodepletion with 30 mg/m2/day fludarabine and 300 mg/m2/day cyclophosphamide for 3 days prior to AUTO3 infusion...Only one case (9%) of neurotoxicity was noted which was grade 3 and treated with steroids and tocilizumab... AUTO3, a novel bicistronic anti CD19/CD22 CAR T therapy, has a manageable safety profile in combination with Pem. Notable is the lack of severe CRS (0%). The efficacy data with 2/4 patients achieving CR at dose 150 x 10e6 cells is promising."

Clinical • IO biomarker • P1/2 data • CNS Disorders • Constipation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • PD-L1

Sarah Cannon to present latest cancer research insights at ASCO20 Virtual Meeting (Businesswire) - "Sarah Cannon announced that it will present its latest cancer research insights at the American Society of Clinical Oncology’s (ASCO®) Annual Meeting being held virtually May 29 – 31, 2020. This year, Sarah Cannon’s drug development and research expertise is featured through more than 110 abstracts and presentations, including data from more than 50 phase 1 studies....Jesus Berdeja, MD...is the discussant on the plenary session focused on 'Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide, and Dexamethasone for Initial Therapy of Newly Diagnosed Multiple Myeloma' on Sunday, May 31 from 12-2:30 PM CT. Dr. Berdeja will also highlight data in an oral presentation on 'Update of CARTITUDE-1: A Phase Ib/II Study of JNJ-4528, a B-Cell Maturation Antigen-Directed CAR-T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma.' (Abstract 8505)."

Clinical data • Breast Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Indolent Lymphoma • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Rectal Cancer • Small Cell Lung Cancer • Solid Tumor

ALEXANDER: CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma (clinicaltrials.gov) - P1/2; N=171; Recruiting; Sponsor: Autolus Limited; Trial completion date: Mar 2022 ➔ Sep 2024; Trial primary completion date: Mar 2022 ➔ Sep 2024

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

Sarah Cannon to Present Latest in Blood Cancer Research at the 62nd ASH Annual Meeting & Exposition (Businesswire) - "Today, Sarah Cannon announced that 53 abstracts and presentations authored by Sarah Cannon experts have been selected for presentation at the upcoming American Society of Hematology (ASH) Annual Meeting & Exposition. Held virtually December 5-8, 2020, the ASH Annual Meeting & Exposition will bring together thought leaders from across the globe to discuss innovative research in malignant and non-malignant blood cancer....Jesus G. Berdeja, MD...will participate in an Education Session on ‘The Emerging Role of Targeted Therapies and Cell Therapy in Transplant - Live Q&A’ on December 5 from 2-2:45 p.m. PST....Dr. Berdeja will present on ‘Efficacy and Safety of Idecabtagene Vicleucel (ide-cel, bb2121) in Elderly Patients with Relapsed and Refractory Multiple Myeloma: KarMMa Subgroup Analysis’ on December 5 from 7 a.m.-3:30 p.m. PST."

Online posting • P1 data • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Sarah Cannon to Present Latest in Blood Cancer Research at the 62nd ASH Annual Meeting & Exposition (Businesswire) - "Today, Sarah Cannon announced that 53 abstracts and presentations authored by Sarah Cannon experts have been selected for presentation at the upcoming American Society of Hematology (ASH) Annual Meeting & Exposition. Held virtually December 5-8, 2020, the ASH Annual Meeting & Exposition will bring together thought leaders from across the globe to discuss innovative research in malignant and non-malignant blood cancer."

P1 data • P1/2 data • P3 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Sickle Cell Disease

ALEXANDER: CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma (clinicaltrials.gov) - P1/2; N=171; Recruiting; Sponsor: Autolus Limited; Trial completion date: Mar 2021 ➔ Mar 2022; Trial primary completion date: Mar 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

Autolus Therapeutics provides business outlook for 2021 & 2022 (Autolus) - "Additional clinical data points in 2021 are expected from AUTO1/22...and AUTO4 in Peripheral T Cell Lymphoma (PTCL), which will continue in 2021 through a dose escalation phase...the company plans to seek a partner for the AUTO3 program...before progressing the program into the next phase of development....'Our organizational focus will position us well to realize the potential of AUTO1 and lay the foundation for the next opportunities in our pipeline with several clinical proof of concepts targeted during 2021 and 2022'..."

Clinical • Clinical data • New trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology • Peripheral T-cell Lymphoma

Sarah Cannon to Present Latest in Blood Cancer Research at the 62nd ASH Annual Meeting & Exposition - "Ian Flinn...will chair the Satellite Symposia 'Addressing the Medical Need in CLL: How BTK Inhibitors Are Improving Outcomes' on December 4 from 7:30-9 a.m. PST...Jesus G. Berdeja...will participate in an Education Session on 'The Emerging Role of Targeted Therapies and Cell Therapy in Transplant - Live Q&A' on December 5 from 2-2:45 p.m. PST...William Donnellan...will present on 'Use of Venetoclax (VEN) and Hypomethylating Agents (HMA) in Newly Diagnosed Acute Myeloid Leukemia (AML) in the United States (US) - Real World (RW) Response, Treatment Duration, Dose and Schedule Modifications' on December 6 from 7 a.m.-3:30 p.m. PST. Flinn will present on 'Debulking Regimens Prior to Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Interim Results from a Phase 3b Study' on December 7 from 7 a.m.-3:30 p.m. PST."

Autolus Therapeutics presents additional data on AUTO3 in DLBCL during the 62nd ASH Annual Meeting (GlobeNewswire) - P1/2, N=171; ALEXANDER (NCT03287817); Sponsor: Autolus; "Autolus Therapeutics...announced new data highlighting progress on AUTO3, the company’s CD19 and CD22 dual targeting CAR T product candidate being investigated in the ALEXANDER study, a Phase 1/2 clinical study in relapsed/refractory diffuse large B cell lymphoma (DLBCL), during the American Society of Hematology (ASH) All-Virtual Annual Meeting, held between December 5-8, 2020....None of the patients achieving a complete response (CR) experienced any NT and all cases of NT were seen in a setting of disease progression and with confounding factors. No prophylactic measures of any kind have been used to manage patients in this study."

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

Autolus Therapeutics to host Investor Conference Call to discuss AUTO1 and AUTO3 data presented at ASH and to participate in the Jefferies Virtual London Healthcare Conference (GlobeNewswire) - “Autolus Therapeutics plc…announced that management will host an investor conference call to discuss AUTO1 and AUTO3 data presented at the American Society of Hematology (ASH) Virtual Congress 2020 and will also participate in the Jefferies Banking Conference.”

Clinical data • Hematological Malignancies • Oncology

Autolus Therapeutics Reports Third Quarter 2020 Financial Results and Operational Progress (GlobeNewswire) - "Key Upcoming Clinical Milestones: Clinical updates for AUTO1 in adult ALL (ALLCAR study) at ASH in December 2020. Clinical update for AUTO3 in DLBCL (ALEXANDER study) at ASH. Initiation of Phase 1 study for AUTO1/22 in pediatric ALL in Q4 2020. Phase 1 interim data for AUTO4 in T cell lymphoma in 2021. Initiation of Phase 1 studies for AUTO6NG and AUTO7 in solid tumors in 2021. First exploratory allogeneic program expected to enter the clinic in Q1 2021."

Clinical data • Enrollment status • P1/2 data • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology