surovatamig (AZD0486) / AstraZeneca - LARVOL DELTA

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

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

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

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

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

Soundtrack-E: A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=276 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2031 ➔ Feb 2028 | Trial primary completion date: Apr 2031 ➔ Feb 2028

Monotherapy • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

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 (SIE 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...In DL1/DL2, no treatment discontinuations due to AZD0486-related AEs occurred. 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 • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma

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

New P3 trial • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

New Targets and Drugs on the Horizon in Chronic Lymphocytic Leukemia (SOHO 2025) - P1, P1/2 | "12 Treatment planning for patients with " double refractory " CLL — CLL that is resistant to a covalent BTKi and venetoclax — is a relatively novel but emerging scenario in the clinic...Noncovalent (Reversible) BTK Inhibitors In the BRUIN-321 phase 3 randomized trial of pirtobrutinib monotherapy versus the control arm of the investigator's choice between idealisib plus rituximab or bendamustine plus rituximab, pirtobrutinib had improved PFS (14 vs 8.7 months, Hazard ratio [HR] 0.54, P = 0.0002) and a superior time to next treatment or death compared to the control arm (24 vs 10.9 months, HR 0.37, P < 0.0001)...Nemtabrutinib is another noncovalent BTKi under clinical investigation, demonstrating an overall response rate (ORR) of 36.4% in CLL patients in the phase 1 study (n = 22 patients)...23,24 Thus far, data for three orally administered BTK degraders — NX-2127, NX-5948 and BGB-16673 23–25— have been presented, and there are ongoing clinical..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Oncology • CD20 • PRKCB • PRKCH • ROR1

Novel Immunotherapy Combinations in Indolent Lymphoma (SOHO 2025) - P1/2, P2, P3 | "The MITHIC-FL1 Table Overview of BsAb combination studies in patients with FL Trial /NCT Phase Treatment setting Number of patients Description Outcomes CRS Median follow-up EPCORE NHL-2, Arm 2 NCT04663347 Phase 1b/2 Relapse/ refractory 111 subcutaneous epcoritamab with R² ORR: 96% CR: 87% Grade 1 – 2: 46% Grade 3: 2% 25.3 months EPCORE FL1 NCT05409066 Phase 3 Relapse/ refractory 500 subcutaneous epcoritamab with R² vs R² NA NA Jan 2030 27 Grade 1 – 2: 25% (mostly grade 1) NA NCT04246086 Phase 1b Relapse/ refractory mosunetuzumab plus lenalidomide ORR: 92%; CR- 77% CELESTIMO NCT04712097 Phase 3 Relapse/ refractory 400 NA NA mosunetuzumab plus lenalidomide vs rituximab plus lenalidomide NA NCT06453044 Phase 2 NA March 2028 Relapse/ refractory 41 mosunetuzumab and polatuzumab vedotin NA NCT04077723 Phase 1 subgroup englumafusp alfa combined with glofitamab ORR: 91% CR: 80% Relapse/ refractory 134 pts total , 24 in the iNHL Grade 1 – 2: 63%..."

Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology

Soundtrack-E: A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=276 | Recruiting | Sponsor: AstraZeneca | N=180 ➔ 276

Enrollment change • Monotherapy • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

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 (SOHO 2025) - P1, P1/2 | "Complete remission (CR)/CR with incomplete recovery (CRi) rate was 46% (6/13); 83% (5/6) were MRD-negative including 1/4 double-exposed to blinatumomab and CAR-T. In DL2, 8/11 (73%) had ≥1 CRS event during SUD (n = 2 G2) and 2 had CRS (n = 1 G2) at TD; tocilizumab was used in 4 patients... Preliminary results from SYRUS suggest AZD0486 is active and well tolerated in patients with R/R B-ALL. This trial is sponsored by AstraZeneca. Accepted at the EHA Annual Congress."

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

Safety and Efficacy of AZD0486, a CD19 × CD3 T-Cell Engager, in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (SOHO 2025) - P1 | "In patients with 2SUD (n = 54), CRS occurred in 44% (all grade ≤2) and 20% received tocilizumab; ICANS occurred in 17% (grade 3, 3%). AZD0486 at TDs ≥2.4 mg showed promising efficacy and manageable safety. TDs up to 25 mg have not exceeded MTD. Dose escalation is ongoing."

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