AZD0120 / AstraZeneca - LARVOL DELTA

Preliminary results of CD19/BCMA Dual-Targeting FasTCAR-T Cells GC012F (AZD0120) in patients with refractory Systemic Lupus Erythematosus-an open-label, single-arm study (EULAR 2025) - P1, P1/2 | "Standard lymphodepleting regimen (fludarabine 25 mg/m^2/day and cyclophosphamide 250 mg/m^2/day for 3 days, Day -5 to -3) was given before CAR-T cell infusion...The Grade 2 CRS event was observed at dose of 3×10 5 CAR-T cells/kg, with onset on day 7 and resolved on day 8 after treatment with dexamethasone and tocilizumab...At month 9, out of 10 patients, 7 patients stopped glucocorticoids and 4 of them also discontinued hydroxychloroquine, the other 3 patients were treated with prednisone 5mg/day... GC012F, a CD19/BCMA dual-targeting CAR-T, induced disease remission in refractory SLE patients with early favorable safety profile. A multicenter phase1/2 study (NCT06530849) is ongoing to further evaluate the safety and efficacy of GC012F in a broader range of patients with SLE."

CAR T-Cell Therapy • Clinical • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Otorhinolaryngology • Pneumonia • Renal Disease • Respiratory Diseases • Systemic Lupus Erythematosus

UPDATED RESULTS OF A PHASE I OPEN-LABEL SINGLE-ARM STUDY OF DUAL TARGETING BCMA AND CD19 FASTCAR-T (GC012F/AZD0120) AS FIRST-LINE THERAPY FOR TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED HIGH-RISK MULTIPLE MYELOMA (EHA 2025) - P1/2 | "TE NDMM patients aged 18 to 70 were eligible if they had at least one of the following high risk features: R-ISS stage II or III; del (17p), t (4; 14), t (14; 16), or ≥ 4 copies of 1q21; extramedullary disease (EMD); IgD or IgE subtype; LDH levels above the upper limit of normal; any of the HR criterion defined by mSMART3.0.GC012F/AZD0120 was administered as a single infusion at 3 dose levels: 1x105/kg (n=1), 2x105/kg (n=4), or 3x105/kg (n=17), following a standard 3-day lymphodepletion regimen of fludarabine and cyclophosphamide.A total of 22 patients with a median age of 59 years old were enrolled and evaluable...Two pts received tocilizumab and 1 pt received tocilizumab and corticosteroid... Consistent with findings from the previous relapsed/ refractory MM cohort treated with GC012F/AZD0120, initial data from this study demonstrates that GC012F/AZD0120 induced deep and durable responses in TE HR NDMM pts, with a highly favorable safety profile. All patients..."

Clinical • P1 data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

AUTOLOGOUS B CELL MATURATION ANTIGEN (BCMA) AND CD19 DUAL TARGETING FASTCAR-T CELLS (GC012F/AZD0120) AS FIRST-LINE THERAPY FOR ELDERLY PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS (EHA 2025) - P1, P1/2 | "After enrollment, patients were permitted to receive up to two cycles of bortezomib, lenalidomide and dexamethasone (VRd) induction therapy before or after apheresis, at the discretion of investigators...All pts recovered from CRS within 5 days and only 1 pt received tocilizumab... GC012F/AZD0120 exhibited a high clinical efficacy, and a favorable safety profile in this study of patients aged > 70. Given these excellent efficacy and safety data, chronological age should not be used as a criterion to exclude patients from CAR T cell clinical trials or from receiving anti-BCMA CAR T-cell therapy in a real-world setting. Future studies with larger cohorts are needed to confirm this approach as a standard of care."

CAR T-Cell Therapy • Clinical • Geriatric Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

FIRST-IN-HUMAN STUDY OF CD19/BCMA DUAL-TARGETING FASTCAR-T GC012F (AZD0120) FOR PATIENTS WITH REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS (EHA 2025) - P1, P1/2 | "Lymphodepletion was achieved using fludarabine (30 mg/m²/day on days -5 to -3) and cyclophosphamide (1000 mg/m²/day on day -3), followed by GC012F infusion on day 0 in three escalating dose groups (1, 2, and 3 ×10⁵ CAR+ T cells/kg)...One patient had Grade 2 ICANS at Day 7, resolved with dexamethasone and levetiracetam... Preliminary results suggest that GC012F, a CD19/BCMA dual-targeting CAR-T therapy, has a favorable early safety profile and promising efficacy in rSLE patients. A Phase 1/2 study (NCT06530849) is ongoing to further evaluate its safety and efficacy."

Clinical • P1 data • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus

A Study to Investigate the Safety, Tolerability, and Efficacy of AZD0120 in Adults With Refractory SLE (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study of GC012F (AZD0120), a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Apr 2027 ➔ Aug 2027

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Investigate the Safety, Tolerability, and Efficacy of AZD0120 in Adults With Refractory SLE (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: AstraZeneca

New P1/2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study of GC012F (AZD0120), a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2028 ➔ Sep 2028 | Trial primary completion date: Dec 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

KY2024-853: An Early Exploratory Clinical Study of GC012F Injection in the Treatment of Refractory Generalized Myasthenia Gravis (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Chongbo Zhao

New P1 trial • CNS Disorders • Myasthenia Gravis

Autologous B Cell Maturation Antigen (BCMA) and CD19 Dual Targeting Fastcar-T Cells (GC012F/AZD0120) As First-Line Therapy for Elderly Patients with Newly Diagnosed Multiple Myeloma Patients (ASH 2024) - P1, P1/2 | "After enrollment, patients were permitted to receive up to two cycles of bortezomib, lenalidomide and dexamethasone (VRd) induction therapy before or after apheresis, at the discretion of investigators...All pts recovered from CRS within 5 days and only 1 pt received tocilizumab...Conclusion Consistent with the data from previous RRMM and transplant-eligible NDMM studies of GC012F, data from this study demonstrate that GC012F/AZD0120 resulted in a very favorable safety profile and promising, deep responses in elderly NDMM pts. Our results suggest that age alone should not preclude patients from receiving highly effective treatments aimed at cure or long-term disease control."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

AstraZeneca showcases strength of haematology portfolio and pipeline at ASH 2024 (AstraZeneca Press Release) - P1/2 | N=20 | NCT04935580 | Sponsor: Shanghai Changzheng Hospital | "Early data for AZD0120 (GC012F)...will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM. Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population. An oral presentation will share preclinical data demonstrating the anti-tumour activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform."

P1/2 data • Preclinical • Multiple Myeloma • Oncology

A Study of GC012F Injection in Subjects With Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1/2 | N=118 | Recruiting | Sponsor: Gracell Biotechnologies (Shanghai) Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study of GC012F (AZD0120), a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2026 ➔ Jun 2028 | Trial primary completion date: Mar 2026 ➔ Dec 2026

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

A Study of GC012F Injection in Subjects With Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1/2 | N=118 | Not yet recruiting | Sponsor: Gracell Biotechnologies (Shanghai) Co., Ltd.

New P1/2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

An Exploratory Clinical Study of GC012F Injection for Refractory gMG (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Zhejiang University | Trial completion date: Oct 2026 ➔ Oct 2027 | Initiation date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Myasthenia Gravis

B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma. (PubMed, JAMA Oncol) - "The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

A PHASE I OPEN-LABEL SINGLE-ARM STUDY OF DUAL TARGETING BCMA AND CD19 FASTCAR-T (GC012F) AS FIRST-LINE THERAPY FOR TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED HIGH-RISK MULTIPLE MYELOMA (EHA 2024) - P1/2 | "Consistent with the previous RRMM cohort treated with GC012F, initial data from this study demonstrated thatGC012F resulted in deep and durable response in TE HR NDMM pts with a very favorable safety profile. Allthree dose groups achieved MRD negativity and 100% ORR. The promising preliminary results achieved withGC012F demonstrate the potential of CAR-T therapy in treating NDMM pts."

Clinical • P1 data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

CD19/BCMA DUAL-TARGETING FASTCAR-T GC012F FOR PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN'S LYMPHOMA: AN UPDATE (EHA 2024) - "Pts received a median of 2 prior lines(range 2 - 3) of therapy including rituximab and anthracyclines. This first-in-human trial of GC012F for the treatment of r/r DLBCL showed a manageable safety profileand promising clinical responses and a long-lasting duration of a remission. GC012F CAR-T cells weredetected in the tumor biopsies, indicating the infiltration of CAR-T cells into the tumor lesions. Overall, CD19-BCMA dual targeting CAR-T product GC012F is a promising therapy for r/r DLBCL pts and longerfollow-up is ongoing."

Clinical • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD19

A Study of GC012F, a CAR T Therapy Targeting CD19 and BCMA in Subjects With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=71 | Recruiting | Sponsor: Gracell Biopharmaceuticals, Inc. | Phase classification: P1b/2 ➔ P1/2

CAR T-Cell Therapy • Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology

CD19/BCMA dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory B-cell non-Hodgkin lymphoma: An update. (ASCO 2024) - "Ptsreceived a median of 2 prior lines (range: 2 - 3) of therapy including rituximab and anthracyclines. This first-in-human trial of GC012F for the treatment of r/r DLBCL showed a manageable safety profile and promising clinical responses and a long-lasting duration of a remission. Overall, CD19-BCMA dual targeting CAR-T product GC012F is a promising therapy for r/r DLBCL pts and longer follow-up is ongoing. Clinical trial information: ChiCTR2100047061."

Clinical • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD19

Calquence plus chemoimmunotherapy reduced the risk of disease progression or death by 27% vs. standard of care in patients with untreated mantle cell lymphoma in ECHO Phase III trial (AstraZeneca Press Release) - P1/2 | N=20 | NCT04935580 | "In an oral presentation, preliminary data was shared from an investigator-initiated trial of AstraZeneca’s first haematology cell therapy, GC012F (AZD0120), in patients with transplant-eligible high-risk, newly diagnosed multiple myeloma. Early results showed that GC012F had an overall response rate of 100%, a minimal residual disease-negative stringent complete response rate of 95%, and was well tolerated. Grade 1-2 CRS was experienced by 27% (6/22) of patients and no ICANS or neurotoxicity was observed."

P1/2 data • Multiple Myeloma

An Exploratory Clinical Study of GC012F Injection for the Treatment of Refractory Generalized Myasthenia Gravis (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Zhejiang University

New P1 trial • CNS Disorders • Myasthenia Gravis

A Dual-Targeting FasTCAR That Holds Promises in Hematological Malignancies and Auto-Immune Diseases (FOB-USA 2024) - "Key talking points include:GC012F is a FasTCAR targeting both BCMA and CD19 and has demonstrated provocative clinical efficacy and safety in myeloma and lymphoma, and is also in clinical investigation for autoimmune diseasesDual Targeting of BCMA and CD19 has strong scientific rationales for superior efficacy in various hematological malignancies and autoimmune diseases"

Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Myeloma • Oncology

Gracell Biotechnologies Acquisition Completed (GlobeNewswire) - "Gracell Biotechnologies Inc...today announced the completion of its previously announced agreement to be acquired by AstraZeneca, in accordance with the terms and conditions of the Agreement and Plan of Merger, dated as of December 23, 2023 (the 'Merger Agreement'), by and among the Company, AstraZeneca Treasury Limited, a private limited company incorporated under the laws of England and Wales ('Parent'), and Grey Wolf Merger Sub ('Merger Sub'), an exempted company with limited liability incorporated under the laws of the Cayman Islands and a wholly owned subsidiary of Parent. The acquisition was structured as a merger of Merger Sub with and into the Company with the Company surviving the merger as a wholly owned subsidiary of Parent....The Company also announced today that it has requested that trading of the ADSs on the Nasdaq Global Select Market ('Nasdaq') be suspended as of February 22, 2024 (New York Time)."

M&A • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lupus • Multiple Myeloma • Oncology • Solid Tumor • Systemic Lupus Erythematosus

Study of FasT CAR-T GC012F Injection NDMM Patients (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Shanghai Changzheng Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation