surovatamig (AZD0486) / AstraZeneca - LARVOL DELTA

Surovatamig: Data from P2 SOUNDTRACK-B trial (NCT06526793) for B-cell NHL/FL/DLBCL in 2027 (AstraZeneca) - FY 2025 Results: Data from P1/2 SYRUS trial (NCT06137118) for r/r B-ALL in 2027

P1/2 data • P2 data • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Surovatamig: Data from P1/2 SOUNDTRACK-E trial (NCT06564038) for B-cell NHL/FL/DLBCL in H2 2026 (AstraZeneca) - FY 2025 Results: Data from P1/2 trial (NCT04594642) for r/r B-cell NHL in H2 2026

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

Surovatamig: Data from P3 SOUNDTRACK-D2 trial (NCT07215585) in elderly patients with B-cell non-Hodgkin lymphoma/DLBCL post 2027 (AstraZeneca) - FY 2025 Results: Data from P3 SOUNDTRACK-F1 trial (NCT06549595) for previously untreated follicular lymphoma post 2027

P3 data • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

SAFETY AND EFFICACY OF AZD0486 IN ADOLESCENT AND ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: EARLY RESULTS FROM THE PHASE 1/2 SYRUS STUDY (EHA 2025) - P1, P1/2 | "Rate of complete remission (CR) or CR with incomplete recovery (CRi) was 46% (6/13); 83% (5/6) were MRD negative (MRDneg) including 1 of 4 pts double-exposed to blinatumomab and CAR-T. In DL2, 8/11 (73%) pts had ≥1 CRS event during SUD (2 G2) and 2 pts had CRS (1 G2) at TD; tocilizumab was used in 4 pts... Preliminary results from SYRUS suggest AZD0486 is active and well tolerated in pts with R/R B-ALL."

Clinical • IO biomarker • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SOUNDTRACK-E: A phase 1/2, open-label, multicenter study to evaluate the safety and efficacy of AZD0486 monotherapy or combination therapy in patients with mature B-cell malignancies. (ASCO 2025) - P1, P1/2 | "Substudy 1 evaluates SC AZD0486 in R/R CLL/small lymphocytic lymphoma and includes a monotherapy cohort (1A; ≥2 prior lines of therapy [pLOT] with Bruton tyrosine kinase inhibitor exposure) and a cohort that receives combination with acalabrutinib (1B; ≥1 pLOT)...In substudy 3, R-CHOP is administered once every 3 weeks for 6 cycles...Secondary objectives include efficacy endpoints, pharmacokinetics, and immunogenicity. Enrollment opened in October 2024."

Clinical • Combination therapy • Monotherapy • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Diffuse Large B Cell Lymphoma • Epilepsy • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Escalating Doses of AZD0486, a Novel CD19xCD3 T-Cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma (ASH 2024) - P1 | "Median prior lines of therapy was 3 (range 2–12), 18 (38%) pts received prior lenalidomide–based therapy, 7 (15%) pts received prior chimeric antigen receptor T-cell therapy (CAR-T), and 4 (9%) received prior CD20 TCE therapy. The exposure-response analysis supports the target dose of 7.2 mg. Further studies of AZD0486 are planned as monotherapy and in combination regimens."

Clinical • Minimal residual disease • Residual disease • Diabetes • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

SAFETY AND EFFICACY OF AZD0486, a CD19xCD3 T-CELL ENGAGER, IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P1 | "In pts who received 2SUD (n = 54), CRS occurred in 44% of pts, all low grade (G1/G2, 41%/4%), and 20% received tocilizumab; ICANS occurred in 17% of pts (G3, 3%). AZD0486 at TDs ≥ 2.4 mg showed promising efficacy and manageable safety in pts with R/R DLBCL. Target doses up to 25 mg have been tested without exceeding MTD. Dose escalation is ongoing."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HIGH COMPLETE RESPONSE RATE WITH TNB-486, A NOVEL CD19XCD3 T-CELL ENGAGER, IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: INTERIM RESULTS FROM AN ONGOING PHASE 1 STUDY (EHA 2023) - P1 | "TNB-486 induces high complete remission rates during early phase dose escalation. With limited follow-up, responses appear durable in heavily pretreated FL pts, with a manageable safety profile. Dose escalation is ongoing to identify the RP2D."

Clinical • P1 data • Bone Marrow Transplantation • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • Transplantation • CD19 • CD20

T-cell engaging antibodies for B-cell lymphomas. (PubMed, Semin Hematol) - "This review focused on 4 CD20 × CD3 BsAbs, as well as surovatamig, a CD19 × CD3 BsAb currently under investigation that has demonstrated promising efficacy against relapsed/refractory B-cell lymphomas. All 4 CD20 × CD3 BsAbs are approved as third-line and beyond therapies: mosunetuzumab for follicular lymphoma (FL), glofitamab for diffuse large B-cell lymphoma (DLBCL), and epcoritamab and odronextamab for both FL and DLBCL (the latter in European Union only)...Multiple studies are currently evaluating these agents in both the relapsed/refractory and frontline settings, either as monotherapy or in combination with other agents. This review summarizes the efficacy and safety of each agent across B-cell lymphoma subtypes, along with their dosing schedules and CRS mitigation strategies."

Journal • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Pre-clinical evaluation of surovatamig (AZD0486) in comparison to CD20xCD3 bispecific antibodies (ASH 2025) - "We conductedcomprehensive preclinical comparisons between Surovatamig and FDA-approved CD20×CD3 bispecifics(mosunetuzumab, epcoritamab, and glofitamab) to evaluate relative efficacy and safety profiles.MethodsComparative analyses were performed using in vitro assays to evaluate T-cell activation, cytokine release,and cytotoxicity against B-cell tumor lines. Similarprofiles were observed across other cytokines evaluated (e.g. IL-10, IL-2, IL-17A).ConclusionsThese findings demonstrate that Surovatamig's unique low-affinity CD3 binding delivers effective anti-tumor activity while significantly reducing CRS-associated cytokine in preclinical models. This favorableprofile positions Surovatamig as a promising therapeutic candidate with potential to expand thetherapeutic window and improve tolerability for patients with B-cell related pathologies, supporting itsadvancement into clinical investigation."

Preclinical • Diffuse Large B Cell Lymphoma • CD20 • IL10 • IL17A • IL2 • IL6 • TNFA

ASSURO: Study Evaluating Safety, Tolerability, PK/PD of Surovatamig in Adult RA or SLE Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

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

Surovatamig (AZD0486), a CD19xCD3 T-cell engager (TCE), demonstrates high rate of minimal residual disease (MRD)–Negative complete responses in Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including in patients who previously progressed on CD20 TCE and CD19 CAR T-cell therapies (ASH 2025) - P1 | "The median number of pLOT was 3(range, 2–13), with 28 (26%), 17 (16%), and 29 (27%) pts having received 3, 4, and ≥5 pLOT, respectively.Forty-four (42%) pts had previously received CD19 CAR T, 25 (24%) polatuzumab vedotin, 16 (15%) CD20TCE, and 9 (8%) other non–CAR T CD19-directed therapies. Surovatamig is active in pts with heavily pretreated DLBCL, including those who receivedprior CD20 TCEs and CD19 CAR T. Responses appear to be target dose–dependent up to 25 mg, which issupported by exposure–response analysis. Higher target doses were not associated with greater clinicallyrelevant toxicity."

CAR T-Cell Therapy • Clinical • Minimal residual disease • Residual disease • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Thrombocytopenia • CD20

Three-year follow-up of the Phase 1 first-in-human study investigating surovatamig, a novel CD19xCD3 T-cell engager, in patients with Relapsed/Refractory (R/R) follicular lymphoma (FL) (ASH 2025) - P1, P2, P3 | "Fifty-five (90%) pts had prioralkylator therapy, 37 (61%) had prior R-CHOP, 26 (43%) had prior lenalidomide-based therapy, 7 (11%)had prior CAR T, and 5 (8%) had prior CD20 TCE therapy. Surovatamig treatment is well tolerated and results in a high CR rate that is durable in ptswith heavily pretreated R/R FL, including those with prior exposure to CD19 CAR T or CD20 TCEs. A phase2 study of surovatamig monotherapy in pts with FL and ≥2 pLOT (NCT06526793) and a phase 3 studyinvestigating surovatamig in combination with rituximab in pts with treatment-naive FL are underway(NCT06549595)."

Clinical • First-in-human • P1 data • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases

SOUNDTRACK-B: A phase 2 single-arm study to evaluate the efficacy and safety of surovatamig (AZD0486) in relapsed or refractory B-cell non-Hodgkin lymphoma (ASH 2025) - P1, P2 | "Secondary endpoints include duration of response, CR rate, MRD-negative CR rate, andsafety. Enrollment in module 1 (R/R FL) began in November 2024."

Clinical • P2 data • B Cell Lymphoma • Cardiovascular • CNS Disorders • Diffuse Large B Cell Lymphoma • Epilepsy • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

Safety and efficacy of surovatamig (AZD0486) in adolescent and adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL): Updated Results from the Phase 1/2 SYRUS study (ASH 2025) - P1/2 | "Among pts receiving TD of 15 mg, ORR was 88% in pts with prior blinatumomab tx, 73% inpts with prior CAR-T, 86% in double-exposed pts (prior blinatumomab and CAR-T), and 86% in triple-exposed pts (double-exposed + prior inotuzumab ozogamacin). Surovatamig up to a TD of 15 mg is well tolerated in pts with R/R B-ALL. SUD 0.09/0.27/1.0 mgmitigates the incidence and severity of CRS and ICANS. The 15-mg TD showed the highest efficacy,including in pts with prior CD19-targeted therapy and with EMD."

Clinical • IO biomarker • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia

SOUNDTRACK-F1: A phase 3, randomized, open-label study of surovatamig (AZD0486) plus rituximab versus chemotherapy plus rituximab in patients with previously untreated follicular lymphoma (ASH 2025) - P3 | "In the phase 3 portion, patients will be randomized 1:1:1 toarms A, B, or C. Patients in arm A will receive surovatamig at the RP3D target dose plus rituximab for 7cycles; those in arm B will receive the same therapy as arm A followed by 17 cycles of surovatamigmonotherapy for patients who achieved PR or CR after the first 7 cycles; and patients in arm C will receivea preselected choice of chemoimmunotherapy (R-CHOP [rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone], R-CVP [rituximab-cyclophosphamide-vincristine-prednisone], or BR[bendamustine-rituximab]) followed by rituximab maintenance for patients achieving PR or CR withinduction chemoimmunotherapy (arm C). The keysecondary endpoint is overall survival. Minimal residual disease and safety will also be assessed.Enrollment in the study is ongoing."

Clinical • P3 data • B Cell Lymphoma • Cardiovascular • CNS Disorders • CNS Lymphoma • Epilepsy • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

AstraZeneca advances haematology and cell therapy ambition with largest-ever presence at ASH (AstraZeneca Press Release) - "Investigational T-cell engager, surovatamig, and CAR T-cell therapy, AZD0120, will show potential with initial data across multiple blood cancers; New results will showcase benefit of Calquence in patients with mantle cell lymphoma and chronic lymphocytic leukaemia."

Clinical data • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma

SOUNDTRACK-D2: AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T–Naive and CAR-T–Exposed Patients (ASH 2024) - P1 | "Additionally, 31 (61%) pts previously received chimeric antigen receptor T-cell therapy (CAR-T), 14 (28%) pts previously received polatuzumab vedotin, 4 (8%) received prior CD20 TCE therapy, and 3 (6%) received other CD19-directed therapies; 20 (39%) pts were refractory to last line of therapy. At target doses evaluated, AZD0486 was well tolerated, with 2SUD mitigating CRS and ICANS events. Dose escalation is ongoing."

Clinical • First-in-human • P1 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Double Step-up Dosing (2SUD) Regimen Mitigates Severe Icans and CRS While Maintaining High Efficacy in Subjects with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (NHL) Treated with AZD0486, a Novel CD19xCD3 T-Cell Engager (TCE): Updated Safety and Efficacy Data from the Ongoing First-in-Human (FIH) Phase 1 Trial (ASH 2023) - P1 | "AZD0486 (formerly TNB-486) is an active treatment in patients with advanced R/R B-NHL and has a predictable safety profile characterized by mainly low-grade AEs and fully transient and reversible CRS/ICANS events. The 2 SUD schedule reduced the overall rate of low grade CRS and ICANS (Grade 1-2) and abrogated Grade 3 events further improving the risk/benefit profile of AZD0486. Dose escalation is ongoing to identify the RP2D."

Clinical • First-in-human • P1 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CXCL8 • IL10 • IL6 • TNFA

AstraZeneca (AZN, Financial) has received orphan drug designation from the FDA for surovatamig, targeting acute lymphocytic leukemia. (Gurufocus)

Orphan drug • Acute Lymphocytic Leukemia

Exposure-Response Analysis and Quantitative Systems Pharmacology Modeling for Optimal RP2D Selection of AZD0486 in Follicular Lymphoma Patients (ASH 2024) - P1 | "The ER analysis of ICANS or CRS also confirmed the comparable safety profile with 2SUD at target doses of 2.4 to 7.2 mg. Overall, the comprehensive analysis package supported the benefit vs risk at the dose of 0.27/1.0/7.2 mg in r/r pts with FL."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Surovatamig: Data from P1/2 SOUNDTRACK-E trial (NCT06564038) for mature B-cell malignancies in H2 2026 (AstraZeneca) - Q3 2025 Results: Data from P1 trial (NCT04594642) for r/r B-cell NHL in H2 2026

P1 data • P1/2 data • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Large B Cell Lymphoma • Mantle Cell Lymphoma • Oncology • Small Lymphocytic Lymphoma

Surovatamig: Data from P3 SOUNDTRACK-F1 trial (NCT06549595) for previously untreated follicular lymphoma post 2026 (AstraZeneca) - Q3 2025 Results: Data from P2 SOUNDTRACK-B trial (NCT06526793) for B-cell NHL/FL/DLBCL post 2026

P2 data • P3 data • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Oncology

"SAFETY AND EFFICACY OF AZD0486 IN ADOLESCENT AND ADULT PATIENTS WITH R/R B-CELL ALL: EARLY RESULTS FROM THE PHASE 1/2 SYRUS STUDY" (DGHO 2025) - P1, P1/2 | "In DL1, 4 of 13 (31%) pts developed CRS during SUD (2 G2) and 4 developed CRS at TD (1 G2); tocilizumab was used in 4 pts...Rate of complete remission (CR) or CR with incomplete recovery (CRi) was 46% (6/13); 83% (5/6) were MRD negative including 1 of 4 pts double-exposed to blinatumomab and CAR-T... Preliminary results from SYRUS suggest AZD0486 is active and well tolerated in pts with R/R B-ALL."

Clinical • IO biomarker • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia