AZD0486 / Ancora Biotech, AstraZeneca - LARVOL DELTA

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 Disorders • 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. (ASCO 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 • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • 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

D7400C00006: A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=317 | Recruiting | Sponsor: AstraZeneca | N=231 ➔ 317 | Trial completion date: Jan 2027 ➔ Apr 2028 | Trial primary completion date: Jan 2027 ➔ Apr 2028

Enrollment change • Trial completion date • Trial primary completion date • 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

SAFETY AND EFFICACY OF AZD0486, A CD19XCD3 T-CELL ENGAGER, IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (EHA 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 • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • 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 (EHA 2025) - P1, P1/2 | "Substudy 1 evaluates SC AZD0486 in R/R chronic lymphocytic leukemia (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... SOUNDTRACK-E will evaluate the safety and efficacy of AZD0486 as monotherapy or in combination with other anticancer agents for pts with B-cell malignancies. This study is the first to evaluate SC AZD0486, and the first to evaluate AZD0486 in CLL."

Clinical • Combination therapy • Monotherapy • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • 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

SOUNDTRACK-F1: A Study of AZD0486 Plus Rituximab in Previously Untreated Follicular Lymphoma Patients (clinicaltrials.gov) - P3 | N=1015 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2035 ➔ Nov 2031 | Trial primary completion date: Apr 2031 ➔ Nov 2031

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Safety and Efficacy of AZD0486, a CD19xCD3 T–cell Engager, in Relapsed or Refractory Diffuse Large B–cell Lymphoma (ICML 2025) - No abstract available

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

The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma. (PubMed, Expert Opin Investig Drugs) - "AZD0486 results in high complete response rates with low incidence of high grade immune-mediated toxicity compared to alternative TCE therapies. Importantly, it remains active in patients with lymphomas that have lost CD20 expression, an important mechanism of treatment failure following CD20 targeting TCEs."

Journal • Review • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s 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=180 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2024 ➔ Jan 2025

Enrollment open • Monotherapy • Trial initiation 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

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 • 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

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

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

D7400C00006: A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=231 | Recruiting | Sponsor: AstraZeneca | N=116 ➔ 231

Enrollment change • 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

AstraZeneca showcases strength of haematology portfolio and pipeline at ASH 2024 (AstraZeneca Press Release) - P1 | N=116 | NCT04594642 | Sponosr: AstraZeneca | "Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486...Phase I results demonstrate high response rates, with a 96% overall response rate, 85% complete response rate and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above. Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL). Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule."

P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma

AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2027 ➔ Jun 2027 | Trial primary completion date: Jan 2026 ➔ Jun 2026

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

AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

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

A Study of AZD0486 Plus Rituximab in Previously Untreated Follicular Lymphoma Patients (clinicaltrials.gov) - P3 | N=1005 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

A Study of AZD0486 Plus Rituximab in Previously Untreated Follicular Lymphoma Patients (clinicaltrials.gov) - P3 | N=1005 | Not yet recruiting | Sponsor: AstraZeneca

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=180 | Not yet recruiting | Sponsor: AstraZeneca

Combination therapy • Monotherapy • New P1/2 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: AstraZeneca

Monotherapy • New P2 trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

D7400C00006: A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=116 | Recruiting | Sponsor: AstraZeneca | N=206 ➔ 116

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

AZD0486, A NOVEL CD19XCD3 T-CELL ENGAGER, SHOWS DURABLE RESPONSES IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: UPDATE ON EFFICACY AND SAFETY (EHA 2024) - P1 | "AZD0486 is active and well tolerated with 2SUD mitigating CRS and ICANS events in pts with R/R FL. Durableresponses were observed with long-term follow-up of up to 31 mo. Later-phase studies of AZD0486 asmonotherapy and in combination regimens are planned."

Clinical • Cardiovascular • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

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 | N=206 | NCT04594642 | Sponsor: AstraZeneca | "Results from the ongoing Phase I, dose-escalation trial of AZD0486, a novel CD19xCD3 T cell engager, showed durable responses in patients with heavily pretreated relapsed/refractory follicular lymphoma with a median follow up of 11 months. Complete response rates of 84% were seen at doses of AZD0486 of 2.4 mg and above. Data also showed how cytokine release syndrome (CRS) events were effectively mitigated by the double step-up dosing schedule and no immune effector cell-associated neurotoxicity syndrome (ICANS) events were observed."

P1 data • Follicular Lymphoma

D7400C00006: A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=206 | Recruiting | Sponsor: AstraZeneca | N=116 ➔ 206

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