AUTO4 / Autolus - LARVOL DELTA

TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "The LibraT1 study is an ongoing, multicenter, international, single-arm phase 1/2 study of TRBC1-directed autologous chimeric antigen receptor (CAR) T cells (AUTO4) in relapsed/refractory TRBC1-positive PTCL...These results support the continuing exploration of TRBC1 targeting in PTCL. ClinicalTrials.gov registration: NCT03590574 ."

CAR T-Cell Therapy • IO biomarker • Journal • P1/2 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Phase I/II Study Evaluating AUTO4 in Patients with TRBC1 Positive T Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Autolus Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2025 ➔ Oct 2026 | Trial primary completion date: Jul 2023 ➔ Oct 2026

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

Autolus Therapeutics announces publication in Nature Communications (GlobeNewswire) - "Autolus Therapeutics plc...today announces a publication in Nature Communications...AUTO4 may allow for treatment of TRBC1 T cell lymphomas but should preserve the normal TRBC2 T cell compartment, preventing immunosuppression...In this publication, the research team at Autolus first describe the structural basis for selective AUTO4 CAR recognition of TRBC1. This structure shows that some amino acid residues stabilize the interaction with the TCR generally, while others result in selectivity. By exploiting this structure, the research team used in silico design and phage display to flip selectivity of the AUTO4 binder from TRBC1 to TRBC2 to generate AUTO5, a TRBC2-specific CAR T cell therapeutic."

Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

AUTO4 CAR T-Cell Therapy Is Well Tolerated in R/R TRBC1+ Peripheral T-Cell Lymphoma (OncLive) - P1/2 | N=200 | AUTO4-TL1 (NCT03590574) | Sponsor: Autolus Limited | "The CAR T-cell therapy AUTO4 was not associated with dose-limiting toxicities (DLTs) and led to early indications of efficacy in patients with relapsed/refractory TRBC1-positive peripheral T-cell lymphoma (PTCL), according to findings from the first-in-human AUTO4-TL1 trial...that were presented at the 17th Annual International Conference on Malignant Lymphoma....In all patients infused with the product (n = 13), any-grade and grade 3 or higher treatment-emergent adverse effects (TEAEs) were observed in 92.3% (n = 12) of patients each. TEAEs included neutropenia/decreased neutrophil counts (grade ≥ 3, 69%), infections and infestations (any-grade, 53.8%; grade ≥3, 7.7%), serious TEAEs (any-grade, 38.5%; grade ≥3, 30.8%), and cytokine release syndrome (any-grade, 53.8%; grade ≥3, 7.7%)."

P1/2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

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

Autolus Therapeutics to Present Clinical Data Updates at the American Society of Hematology (ASH) Annual Meeting 2022 (GlobeNewswire) - P1/2 | N=200 | NCT03590574 | Sponsor: Autolus Limited | "Having shown proof of concept at EHA in June 2022, AUTO4 treatment for peripheral T-cell Lymphoma continues to be observed to be well tolerated with no dose-limiting toxicities. Ongoing responses at 9- and 12-months post-dosing at the highest dose tested (450x106) are encouraging, and suggests a potential clinical benefit for patients. No CAR T cell expansion was observed in peripheral blood, but CAR T cells were detected in an on-treatment lymph node biopsy. Optimization of the AUTO4 manufacturing process has been performed, resulting in a product candidate with a more naive and central memory phenotype. The study is ongoing, with additional patients due to be treated to define the recommended Phase 2 dose."

P1/2 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

A Novel Low Affinity CD19CAR Results in Durable Disease Remissions and Prolonged CAR T Cell Persistence without Severe CRS or Neurotoxicity in Patients with Paediatric ALL (ASH 2017) - P1; "...Cytokine release syndrome occurred in all patients (grade 1 n=4, grade 2 n=4), but to date none have developed ≥ grade 3 CRS, required ICU admission or therapy with Tocilizumab...These interim results with a novel low affinity CD19 CAR show similar remission rates to those reported by US studies in paediatric ALL with an improved safety profile. No severe (grade ≥3) CRS or neurotoxicity has occurred to date despite high tumour burden in 4 patients. Excellent CAR T cell expansion has been documented, as well as long duration of CAR T cell persistence and associated B cell aplasia."

CAR T-Cell Therapy • Biosimilar • Hematological Malignancies

Autolus Therapeutics Reports Third Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "AUTO4 in T Cell Lymphoma patients – LibrA T1 Trial: Autolus has optimized the manufacturing process for AUTO4, and is currently enrolling additional patients into the trial to test this manufacturing change. Data were presented at EHA in June 2022, and longer-term follow up data will be presented at the 2022 ASH Meeting in December....AUTO8 in Multiple Myeloma – MCARTY Trial: In collaboration with UCL, patients continue to be enrolled into the AUTO8 Phase 1 clinical trial, with first data expected in H2 2023....AUTO6NG in Neuroblastoma – MCARGD2 Trial: In collaboration with UCL, the first patient is expected to be dosed in the Phase 1 MCARGD2 clinical trial in H1 2023, with initial data expected towards the end of 2023."

P1 data • P1/2 data • Trial status • Hematological Malignancies • Lymphoma • Multiple Myeloma • Neuroblastoma • Oncology • Solid Tumor

"AUTO4 is one of the most unique treatments for Autolus compared to competition. The persistence of ongoing 6 and 9 months is encouraging too, so ditching it would be wrong." (@DavidJu83087868)

Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress (GlobeNewswire) - P1/2 | N=100 | NCT03590574 | Sponsor: Autolus Limited | "AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS). Three patients experienced cytokine release syndrome (CRS) (1 patient with Grade 1, 1 patient with Grade 2 and 1 patient with Grade 3). Of the 9 patients treated, 5 patients had achieved complete metabolic responses (CMR) by PET-CT at Month 1, 1 patient remains with a partial response (PR) 6 months post AUTO4 infusion, and 3 patients did not respond."

P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Autolus Therapeutics Reports First Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "Key Anticipated Clinical Milestones: Initial clinical data from the FELIX Phase 2 trial in H2 2022 and full data in H1 2023. Updated Phase 1 data from the ALLCAR19 extension trial in patients with r/r B-NHL and CLL presented as a poster at the EHA Congress in June 2022. Updates on the obe-cel Phase 1 CAROUSEL trial in Primary CNS Lymphoma presented as a poster at the EHA Congress in June 2022. Initial clinical data from the AUTO1/22 CARPALL extension trial in pediatric ALL presented as an oral presentation at the EHA Congress in June 2022, with longer follow up in H2 2022. Initial clinical data from AUTO4 LibraT1 Phase 1 trial in TRBC1+ Peripheral TCL presented as an oral presentation at the EHA Congress in June 2022. AUTO6NG Phase 1 clinical trial in neuroblastoma expected to start in H2 2022. Expect first data in H2 2023. AUTO8 Phase 1 clinical trial in patients with multiple myeloma has started, expect first data in H2 2023."

Clinical data • New P1 trial • Hematological Malignancies • Multiple Myeloma • Neuroblastoma • Oncology • Solid Tumor

Phase I/II Study Evaluating AUTO4 in Patients With TRBC1 Positive T Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Autolus Limited | N=55 ➔ 200 | Trial completion date: Dec 2023 ➔ Jul 2025 | Trial primary completion date: Jun 2022 ➔ Jul 2023

CAR T-Cell Therapy • Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Autolus Therapeutics Reports Third Quarter 2021 Financial Results and Operational Progress (GlobeNewswire) - "Key Anticipated Clinical Milestones: Non-clinical data and initial data from the AUTO1/22 CARPALL extension trial in pediatric ALL expected at ASH in December 2021; Updates on the AUTO4 Phase 1 trial in TRBC1+ Peripheral TCL expected in H1 2022; Phase 1 trials are expected to be initiated in Q4 2021 with AUTO8 in Multiple Myeloma; Phase 1 trials are expected to be initiated in H1 2022 with AUTO6NG in solid tumors and AUTO5 in TRBC2+ Peripheral TCL."

Clinical data • New P1 trial • Childhood B Acute Lymphoblastic Leukemia • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Autolus Therapeutics Reports Second Quarter 2021 Financial Results and Operational Progress (GlobeNewswire) - “Updates on the obe-cel Phase 1 trial, CAROUSEL, in Primary CNS Lymphoma in Q1 2022; Updates on the AUTO4 Phase 1 trial in TRBC1+ Peripheral TCL in H1 2022; Phase 1 trials are expected to be initiated in H1 2022 with AUTO6NG in solid tumors and AUTO5 in TRBC2+ Peripheral TCL; First exploratory allogeneic development candidate expected to enter the clinic in 2021.”

New P1 trial • New trial • P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma

Autolus Therapeutics Receives Innovation Passport and entry into ILAP for AUTO4 for the treatment of T cell receptor constant region beta chain 1 (TRBC1) positive T cell lymphomas (GlobeNewswire) - “Autolus Therapeutics plc…announced that it has received innovative licensing and access pathway (ILAP) designation from the UK Medicines and Healthcare products Regulatory Agency (MHRA) for AUTO4 being studied in a Phase 1 study in TRBC1 positive Peripheral T Cell Lymphoma (PTCL)…‘We look forward to working with the MHRA as we progress AUTO4 through the clinic and to providing an interim update on the Phase 1 program later this year.’”

European regulatory • P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Autolus Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Operational Progress (GlobeNewswire) - “AUTO7 in prostate cancer: Autolus plans to progress AUTO7 into the clinic in H1 2022...AUTO1 updates in 2021 on ALLCAR19 in patients with r/r B-NHL and longer term follow up of the fully enrolled r/r aALL cohort; AUTO1 - Currently enrolling Phase 1b/2 pivotal study (FELIX) in r/r adult ALL patients with data expected in 2022; Updates on Phase 1 programs AUTO1/22 in pediatric ALL, as well as AUTO4 in TRBC1+ Peripheral TCL, in 2021; Phase 1 trials are expected to be initiated in 2021 with AUTO1 in Primary CNS Lymphoma, AUTO5 in TRBC2+ Peripheral TCL, AUTO6NG in Neuroblastoma, and AUTO8 in Multiple Myeloma; First exploratory allogeneic program expected to enter the clinic in H1 2021.”

New P1 trial • New trial • P1 data • P1/2 data • Acute Lymphocytic Leukemia • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Multiple Myeloma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Prostate Cancer • Small Cell Lung Cancer

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

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

Phase I/II Study Evaluating AUTO4 in Patients With TRBC1 Positive T Cell Lymphoma (clinicaltrials.gov) - P1/2; N=55; Recruiting; Sponsor: Autolus Limited; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: Jul 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Autolus Therapeutics Reports Second Quarter 2020 Financial Results and Operational Progress (GlobeNewswire) - "Key Upcoming Clinical Milestones: Further update for AUTO3 at ESMO in Q3 2020. Further data updates for both AUTO1 and AUTO3 in Q4 2020. First data from outpatient cohort in the AUTO3 ALEXANDER study in H2 2020. Interim Phase 1 data for AUTO4 in T cell lymphoma in H1 2021. Initiation of Phase 1 study for AUTO1NG in pediatric ALL in H2 2020. Initiation of Phase 1 study for AUTO8 in multiple myeloma in H2 2020. Progression of additional next generation programs from preclinical stages to Phase 1 throughout 2021."

Clinical data • New P1 trial • Preclinical • Trial status • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

AMELIA: CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell ALL (clinicaltrials.gov) - P1/2; N=50; Recruiting; Sponsor: Autolus Limited

New P1/2 trial • Acute Lymphocytic Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

"Autolus dosed a CAR today that targets both BCMA and TACI. https://t.co/9g2qXQb6D1" (@bradloncar)

Biosimilar

Autolus Therapeutics reports first quarter 2020 financial results and operational progress (GlobeNewswire) - "Key Upcoming Clinical Milestones: Ph2 decision for AUTO3 in DLBCL mid-2020; Initiation of an outpatient cohort in the AUTO3 ALEXANDER study in H2 2020; Further updates for both AUTO1 and AUTO3 in Q4 2020; Interim Ph1 data for AUTO 4 in T cell lymphoma in Q4 2020; Progression of additional next generation programs from preclinical stages to Ph1 through H2 2020 into H1 2021."

Enrollment status • P1 data • Preclinical • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma