surovatamig (AZD0486) / AstraZeneca - LARVOL DELTA

Selective T-Cell Engagement for Deep B-Cell Depletion in Primary Membranous Nephropathy (pMN): Scientific Rationale and Trial Design for CLEAR-AbKD (KIDNEY WEEK 2026) - "Current therapies for high-risk disease (e.g. cyclophosphamide, calcineurin inhibitors, or anti-CD20 antibodies) can induce remission but are limited by toxicity, incomplete B cell depletion, and frequent relapse. By eliminating circulating, tissue-resident, and anti-CD20-refractory B cell clones, surovatamig may achieve deeper and more durable remission while reducing cumulative immunosuppression. The CLEAR-AbKD trial will provide initial data on the feasibility, safety, and immunological impact of this approach in pMN."

Glomerulonephritis • Immunology • Infectious Disease • Nephrology • Renal Disease

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

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

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

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

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

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

SOUNDTRACK-B: Surovatamig (AZD0486) as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Nov 2027 ➔ Apr 2028

Monotherapy • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

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

SYRUS: AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P1/2 | N=255 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2027 ➔ Sep 2028 | Trial primary completion date: Nov 2026 ➔ Feb 2028

Monotherapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19

RAZOR: A Randomised Phase 3 Study Comparing a New Drug (Surovatamig) With Standard Radiotherapy With or Without Rituximab in Adults With Limited Stage Nodal Follicular Lymphoma (clinicaltrials.gov) - P3 | N=138 | Not yet recruiting | Sponsor: Australasian Leukaemia and Lymphoma Group

New P3 trial • Follicular Lymphoma • Hematological Malignancies • 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=408 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Feb 2028 ➔ Jun 2029

Monotherapy • 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 • CD19

SYRUS: AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P1/2 | N=236 | Suspended | Sponsor: AstraZeneca | Recruiting ➔ Suspended

Monotherapy • Trial suspension • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19

SOUNDTRACK-D2: AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL (clinicaltrials.gov) - P3 | N=420 | Sponsor: AstraZeneca

Trial initiation date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SOUNDTRACK-B: Surovatamig (AZD0486) as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2029 ➔ Oct 2032 | Trial primary completion date: Mar 2027 ➔ Nov 2027

Monotherapy • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

SUROVATAMIG (AZD0486) PLUS RITUXIMAB IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL): INITIAL SAFETY DATA FROM THE PHASE 3 SOUNDTRACK-F1 TRIAL (EHA 2026) - P3 | "Summary/Conclusion Surovatamig in combination with rituximab showed deep responses and manageable safety and tolerability at both dose levels, with comparable TEAEs and no discontinuations. These results supported selection of 7.2 mg as the RP3D; the phase 3 trial is ongoing."

Clinical • P3 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Musculoskeletal Pain

D7400C00006: A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=226 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SOUNDTRACK-F1: Early Deep Responses and Manageable Safety With Surovatamig + Rituximab in Frontline FL (OncoDaily) - "Safety was broadly comparable across both dose levels, with no treatment discontinuations attributed to adverse events. The most common toxicities were infusion-related reactions, fatigue, myalgia, and cytopenias. Infections were frequent but largely low grade....Deep responses were observed across both dose levels: CR rates reached 82% in the 2.4 mg cohort and 95% in the 7.2 mg cohort; ORR of 96% and 100%; PFS remained high in both cohorts, with relatively few progression events observed at the time of analysis. Similarly, DOR analyses suggested sustained remissions, though follow-up remains limited....Among evaluable patients, MRD negativity was achieved in 75% of patients receiving 2.4 mg vs 100%. Conversion to MRD negativity frequently occurred early during treatment, with many patients achieving undetectable disease by the end of induction."

P3 data • Follicular Lymphoma

MODULE 5: Other Novel Strategies for CLL (ASCO 2026) - "Supported by This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP and Eli Lilly. Biological rationale for the evaluation of CAR T-cell therapy in CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early antitumor activity and safety data with bispecific antibodies for R/R CLL and CLL with Richter's syndrome Rationale for the design of the ongoing Phase III SOUNDTRACK-C1 study of the CD19 x CD3 bispecific T-cell engager surovatamig as consolidation therapy for patients with IGHV-unmutated CLL Preliminary data with and ongoing Phase III trials of other promising novel agents and strategies, such as sonrotoclax and BTK degraders, for patients with CLL"

IO biomarker • Chronic Lymphocytic Leukemia • Richter's Syndrome

SOUNDTRACK-C1: Surovatamig as Consolidation Therapy in Participants With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated Immunoglobulin Heavy Chain Variable (IGHV) (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2033 ➔ Apr 2032 | Trial primary completion date: Nov 2032 ➔ Aug 2031

Enrollment open • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH

SYRUS: AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P1/2 | N=236 | Recruiting | Sponsor: AstraZeneca | N=163 ➔ 236

Enrollment change • Monotherapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19

SOUNDTRACK-D2: AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: AstraZeneca

Trial initiation date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell 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 | Recruiting | Sponsor: AstraZeneca

Trial initiation date • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

CLEAR-AbKD: A Study to Assess the Effect of Surovatamig in Adult Participants With Antibody-mediated Kidney Disease (clinicaltrials.gov) - P2 | N=43 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Glomerulonephritis • Nephrology • Renal Disease