AUTO1/22 / Autolus, BioNTech - LARVOL DELTA

CARPALL: Immunotherapy with CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: University College, London | Active, not recruiting ➔ Recruiting | N=38 ➔ 50 | Trial completion date: Dec 2036 ➔ Dec 2041 | Trial primary completion date: Dec 2028 ➔ Dec 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ABL1 • BCR • CD22 • KMT2A • TCF3

Autolus Therapeutics Reports Third Quarter 2024 Financial Results and Business Updates (GlobeNewswire) - "Pipeline programs in collaboration with University College London Clinical programs AUTO8, AUTO6NG and AUTO1/22 are progressing and the Company is planning data updates for all programs in 2025. Operational Updates: The FDA approval for AUCATZYL triggers a $30 million milestone payment to Autolus from Blackstone in accordance with the terms of the collaboration agreement between the parties. In addition, Autolus will make a £10 million regulatory milestone payment to UCL Business Ltd. in accordance with the license agreement between the parties."

Clinical data • Financing • B Acute Lymphoblastic Leukemia

Autolus Therapeutics Reports Second Quarter 2024 Financial Results and Business Updates (GlobeNewswire) - "Clinical programs AUTO8, AUTO6NG and AUTO1/22 are progressing well and we are planning data updates for all programs in 2025...2024 Expected News Flow: Obe-cel FELIX data at American Society of Hematology (ASH) meeting...December 2024...Research and development expenses increased from $33.2 million to $36.6 million for the three months ended June 30, 2024, compared to the same period in 2023. This change was primarily due to increases in operating costs related to our new manufacturing facility, employee salaries and related costs, and clinical trial and manufacturing costs related to obe-cel, partially offset by an increase in our U.K. reimbursable R&D tax credits that reduce R&D expense....Autolus estimates that, with its current cash and cash equivalents, it is well capitalized to drive the full launch and commercialization of obe-cel in r/r adult B-ALL..."

Clinical data • Commercial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Solid Tumor

CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies (clinicaltrials.gov) - P1 | N=38 | Active, not recruiting | Sponsor: University College, London | Trial completion date: Jan 2032 ➔ Dec 2036 | Trial primary completion date: Jan 2024 ➔ Dec 2028

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • ABL1 • BCR • CD22 • IGH • KMT2A • TCF3

BioNTech and Autolus Announce Strategic CAR-T Cell Therapy Collaboration to Advance Pipeline and Expand Late-Stage Programs (GlobeNewswire) - "Autolus will lead the development and commercialization for AUTO1/22 and AUTO6NG in any oncology indication with BioNTech having an option to support certain development activities and co-commercialize both candidates in certain territories. If BioNTech exercises an option, it will receive a profit share with respect to such exercised product candidate worldwide while Autolus will be eligible to receive an option exercise fee, milestone payments and co-funding of development expenses; Autolus granted BioNTech an exclusive license to develop and commercialize therapeutics incorporating certain of Autolus’ proprietary binders along with options to license binders and cell programming technology for use in BioNTech’s in vivo cell therapy development programs and investigational antibody-drug conjugates. If BioNTech exercises an option, Autolus will be eligible to receive exercise fees and milestones payments, with low-single digit royalties on net sales..."

Licensing / partnership • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor

Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study. (ASCO 2023) - P1, P1/2 | "Its clinical activity has been tested in r/r paediatric and adult B-ALL trials (CARPALL, Ghorashian S et al., Nat Med 2019; ALLCAR19, Roddie C et al., JCO 2021) and more recently in adults with r/r B-cell malignancies (NCT02935257)...Patients underwent bridging therapy as necessary and lymphodepletion with fludarabine (4x30mg/m2) and cyclophosphamide (2x500mg/m2)... The pre-specified interim analysis of the FELIX study demonstrated that obe-cel for adult r/r B-ALL is safe with low rates of Grade >3 CRS and/or ICANS, even in patients with high burden disease. Obe-cel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders. The trial has completed dosing of all patients in Cohort A. Additional data and longer follow up will be reported at the conference."

Clinical • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Transplantation

SAFETY AND EFFICACY OF OBECABTAGENE AUTOLEUCEL (OBE-CEL), A FAST-OFF RATE CD19 CAR IN RELAPSED/REFRACTORY ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA:TOP LINE RESULTS OF THE PIVOTAL FELIX STUDY (EHA 2023) - P1, P1/2 | "Its clinical activity has been tested in r/r paediatric and adult B-ALL trials (CARPALL, Ghorashian S et al., Nat Med 2019; ALLCAR19, Roddie C et al., JCO 2021) and more recently in adults with r/r B-cell malignancies (NCT02935257)...Patients underwent bridging therapy as necessary and lymphodepletion with fludarabine (4x30mg/m2) and cyclophosphamide (2x500mg/m2)... The pre-specified interim analysis of the FELIX study demonstrated that obe-cel for adult r/r B-ALL is safe with low rates of Grade > 3 CRS and/or ICANS, even in patients with high burden disease. Obe-cel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders. The trial has completed dosing of all patients in Cohort A. Additional data and longer follow up will be reported at the conference."

Clinical • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Transplantation

CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL. (PubMed, Blood) - P1 | "Twelve patients with advanced B-ALL were treated (CARPALL study, NCT02443831), a third of whom had failed prior licensed CAR therapy...Six and 12-month event free survival (EFS) were 75% (95%CI: 41-91%) and 60% (95%CI: 23-84%). These data suggest dual targeting with co-transduction may prevent antigen negative relapse after CAR T-cell therapy."

CAR T-Cell Therapy • Journal • Inflammation • CD22

Autolus Therapeutics announces data from AUTO1/22 trial in pediatric Acute Lymphoblastic Leukemia published in the journal Blood (GlobeNewswire) - P1 | N=33 | CARPALL (NCT02443831) | "Autolus Therapeutics plc...announces a publication on the AUTO1/22 Phase 1 study (CARPALL) in Pediatric B-cell Acute Lymphoblastic Leukemia in the journal Blood, previously presented this year at the European Society for Blood and Marrow Transplantation in April....AUTO1/22 induced MRD (minimal residual disease)-negative CR in 83% (10 of 12) patients. This includes 2 (of 3) patients who had CD19 negative disease, demonstrating the efficacy of the CD22 CAR....Of 10 responding patients, 5 had emergence of MRD (2) or frank relapse (3) with CD19 and CD22 expressing disease associated with loss of CAR T-cell persistence....Overall survival was 75% at 6 and 12 months. Six and 12-month event free survival (EFS) were 75% and 60% respectively."

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia. (PubMed, Nat Med) - "In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion...Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists."

CAR T-Cell Therapy • IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4 • CD8

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

CD34 SELECTED STEM CELL BOOST CAN SAFELY IMPROVE CYTOPAENIAS FOLLOWING CAR-T THERAPY (EBMT 2022) - P1, P1/2 | "Four(3 CD19, 1 CD19/CD22 directed) received CAR as per CARPALL study(NCT02443831), 1 received CD19/CD22 directed CAR as per AMELIA study(NCT03289455), 1 received licensed product Tisagenlecleucel and 1 received allogenic CD19 directed CAR as per CARD study(NCT02893189).  Unconditioned CD34 stem-cell boost is well tolerated and can ameliorate prolonged cytopaenias post-CART therapy. However, CRS is a potential complication after the infusion due to the presence of CD19+ progenitors within the CD34 selected product."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Neutropenia • Oncology • Pediatrics • Transplantation • CD19 • CD22 • CD34 • CSF3

Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process (ASH 2021) - P1, P1/2 | "Clinical testing in two academic studies in relapsed/refractory (r/r) paediatric [ NCT02443831; CARPALL ] and adult B-ALL, B-NHL and B-CLL [NCT02935257; ALLCAR19] confirmed the intended function of the receptor, with low levels of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term engraftment of CAR T-cells 1,2...CONCLUSION Industrialization of an autologous Miltenyi CAR T process is feasible, leading to a comparable product to that manufactured in an academic setting. We have now opened the pivotal multi-center phase II part of the FELIX study in r/r adult B-ALL patients."

IO biomarker • Chronic Lymphocytic Leukemia • Inflammation • Pediatrics • CD19 • CD4 • CD8 • PD-1

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

Autolus Therapeutics to Present Clinical Data Updates at the American Society of Hematology (ASH) Annual Meeting 2022 (GlobeNewswire) - P1 | N=33 | CARPALL (NCT02443831) | "AUTO1/22 demonstrated a strong level of activity with 83% (10/12) MRD negative complete remissions and a favorable tolerability profile in a very challenging patient population (4 patients failed previous Kymriah treatment with three having CD19-negative disease, 3 had non-central nervous system (CNS) extra-medullary disease, which is associated with poor outcomes with CAR T therapy). AUTO1/22 showed excellent expansion, with a median 7.5 months duration of persistence of CD22 CAR. No antigen negative relapse was seen in responding patients. At a median follow up of 8.7 months, five of 10 responding patients were in MRD negative complete response (4-12 months) with two after further therapy for early loss of CAR T persistence."

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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

Autolus Therapeutics Reports Third Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "Obe-cel in Primary CNS Lymphoma patients – CAROUSEL Trial: In collaboration with UCL, patients continue to be enrolled into the Phase 1 CAROUSEL trial. Data were presented at EHA in June 2022 - and longer-term follow up data is planned in 2023....AUTO1/22 in pediatric ALL patients – CARPALL Trial: In collaboration with UCL, patients continue to be enrolled into the AUTO1/22 Phase 1 CARPALL trial. Data were presented at EHA in June 2022, and longer-term follow up data will be presented at the 2022 ASH Meeting in December."

P1 data • Acute Lymphocytic Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process (TCT-ASTCT-CIBMTR 2022) - P1, P1/2 | "Clinical testing in two academic studies in r/r paediatric [NCT02443831; CARPALL] and adult B-ALL, B-NHL and B-CLL [NCT02935257; ALLCAR19] confirmed the intended function of the receptor, with low levels of cytokine release syndrome (CRS) and neurotoxicity and long-term engraftment of CAR T-cells 1,2...CONCLUSION Industrialization of an autologous Miltenyi CAR T process is feasible, leading to a comparable product to that manufactured in an academic setting. We have now opened the pivotal multi-centre phase II part of the FELIX study in r/r adult B-ALL patients."

IO biomarker • Chronic Lymphocytic Leukemia • Inflammation • Pediatrics • CD19 • CD4 • CD8 • PD-1

A High Sensitivity aCD22 CAR Combined with aCD19 CAR to Generate Dual Targeting CAR T Cells for the Treatment of r/r B-ALL (ASH 2021) - P1 | "In a NSG animal model engrafted with WT CD19+/CD22+ Nalm-6 cells, the dual targeting co-transduced T cells (AUTO1/22) were significantly better at supressing tumour growth compared to single targeting AUTO1 CAR T cells (Figure 1)... We engineered a highly sensitive aCD22 9A8 CAR which when combined with the aCD19 CAT19 CAR allows for improved in vivo function and the targeting of CD19 negative, CD22 positive cells. The use of these dual targeting T cells may reduce the incidence of CD19 negative relapses in the r/r B-ALL setting. 1."

CAR T-Cell Therapy • IO biomarker • Oncology • Pediatrics • CD19

CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: University College, London | Trial completion date: Dec 2030 ➔ Jan 2032 | Trial primary completion date: Nov 2019 ➔ Jan 2024

CAR T-Cell Therapy • IO biomarker • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • ABL1 • BCR • CD19 • CD22 • IGH • KMT2A • TCF3

Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress (GlobeNewswire) - P1 | N=32 | CARPALL (NCT02443831) | "CRS occurred in 7/8 patients (grade 1 n=2, grade 2 n=5), but severe CRS was not seen. 7 of 8 evaluable patients achieved MRD negative complete response (CR) at 1 month post infusion. Overall, at a median follow up of 4.8 months, 5/8 patients remain in MRD negative CR at last follow up. The study results demonstrate that dual CD19/22 targeting CAR T cells generated by co-transduction show an acceptable safety profile, with robust expansion/persistence and early efficacy in a heavily pre-treated cohort."

Cytokine release syndrome • P1 data • Childhood B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • 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

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