anselamimab (CAEL-101) / AstraZeneca - LARVOL DELTA

Safety and tolerability of anselamimab in participants with light chain amyloidosis: Results from a phase 2 study. (PubMed, Eur J Cancer) - P2 | "Anselamimab was well tolerated. Most common TEAEs were consistent with AL amyloidosis or anti-PCD therapy."

Journal • P2 data • Amyloidosis • Hematological Disorders

Phase 3 Randomized Trial of Anselamimab Demonstrates Improvement in All-Cause Mortality in ? Light Chain Amyloidosis (IMS 2026) - P3 | " Alongside anti-PCD therapy with CyBorD (daratumumab was permitted) newly diagnosed patients with European modification of Mayo stage IIIa or IIIb AL amyloidosis were randomized 2:1 to receive anselamimab (1000 mg/m 2 ) or placebo (normal saline) IV every 7 days for 4 weeks followed by every 14 days for the remainder of the blinded study (18 months after the last participant enrolled). Anselamimab, a κ light chain–directed anti-fibril monoclonal antibody used alongside anti-plasma cell dyscrasia therapy, offers a first-in-class, new therapeutic option for patients with newly diagnosed κ AL amyloidosis."

Clinical • P3 data • Amyloidosis • Cardiovascular

SAFETY AND TOLERABILITY OF CAEL-101, AN ANTI-AMYLOID MONOCLONAL ANTIBODY, COMBINED WITH ANTI-PLASMA CELL DYSCRASIA THERAPY IN PATIENTS WITH LIGHT-CHAIN AMYLOIDOSIS: 18-MONTH RESULTS OF A PHASE 2 STUDY (EHA 2023) - P2 | "Aims: To present safety, tolerability, and biomarker data for 18 months of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Currently enrolled patients have been treated for ≥18 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs were mild to moderate."

Clinical • P2 data • Amyloidosis • Heart Failure • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • NPPB

Effect of Anselamimab on Cardiac Structure and Function in Patients With Light Chain Amyloidosis: Insights From the CARES Clinical Trials. (PubMed, Circulation) - No abstract available

Journal • Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Updated OS of patients with AL amyloidosis after CAEL-101. (ASCO 2023) - P1a/1b | "Patients with relapsed/refractory AL amyloidosis who received a low cumulative amount of the novel anti-amyloid CAEL-101 in a phase 1a/1b study had lengthy overall and progression-free survival compared to historical controls. Patterns of organ progression after initial response may reflect intrinsic differences in organ vulnerability. The CAEL101-301 and CAEL101-302 phase 3 clinical trials are underway to confirm these findings."

Clinical • Amyloidosis • Cardiovascular • Hematological Disorders • Transplantation • Venous Thromboembolism

Erratum: Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials. (PubMed, J Clin Oncol) - No abstract available

Journal • Amyloidosis

1F10, a λ Light Chain Amyloid-Specific Monoclonal Antibody for Targeted Therapy of AL Amyloidosis. (PubMed, Blood) - "Amyloid-targeting monoclonal antibodies birtamimab and anselamimab were developed and tested for active AL amyloid clearance; however, they failed to meet the primary endpoint in Phase 3 trials, presumably due to insufficient binding affinity for l LC amyloid, which occurs in ~80% of patients. Importantly, 1F10 demonstrates robust in vivo activity, significantly accelerating the resolution of l amyloid fibrils in an AL amyloidoma mouse model. Together, these findings establish 1F10 antibody as a promising subtype-specific immunotherapeutic candidate for targeting l LC amyloid, addressing a critical unmet need for the majority of patients with AL amyloidosis."

Journal • Amyloidosis

PHASE 3 RANDOMIZED TRIAL OF ANSELAMIMAB DEMONSTRATES IMPROVEMENT IN ALL-CAUSE MORTALITY IN Κ LIGHT-CHAIN AMYLOIDOSIS (EHA 2026) - P3 | "Methods Alongside anti-PCD therapy with CyBorD (daratumumab was permitted) newly diagnosed patients with European modification of Mayo stage IIIa or IIIb AL amyloidosis were randomized 2:1 to receive anselamimab (1000 mg/m 2 ) or placebo (normal saline) IV every 7 days for 4 weeks followed by every 14 days for the remainder of the blinded study (18 months after the last participant enrolled). Kaplan-Meier curve of time to all-cause mortality in patients with ? isotype AL amyloidosis."

Clinical • P3 data • Amyloidosis • Cardiovascular

ANSELAMIMAB TARGETS BOTH CYTOTOXIC SOLUBLE PREFIBRILLAR SPECIES AND INSOLUBLE FIBRILS OF LIGHT CHAIN AMYLOIDOSIS (EHA 2026) - "We further characterized its MoA, demonstrating the engagement of myeloid cells in removing insoluble fibrils in a whole blood system. These findings suggest that anselamimab targets misfolded amyloid protein at multiple steps of fibril formation, potentially impacting both early and late stages of AL amyloidosis pathogenesis."

Amyloidosis • CASP3 • CASP7

Phase 3 randomized trial to evaluate the impact of anselamimab on all-cause mortality in κ light-chain amyloidosis. (ASCO 2026) - P3 | " Alongside anti-PCD therapy with CyBorD (daratumumab was permitted) newly diagnosed patients with European modification of Mayo stage IIIa or IIIb AL amyloidosis were randomized 2:1 to receive anselamimab (1000 mg/m2) or placebo (normal saline) IV every 7 days for 4 weeks followed by every 14 days for the remainder of the blinded study (18 months after the last participant enrolled). Anselamimab, a κ light chain–directed anti-fibril monoclonal antibody used alongside standard of care chemotherapy, offers a first-in-class, new therapeutic option for patients with newly diagnosed κ AL amyloidosis. Summary of primary efficacy endpoints."

Clinical • P3 data • Amyloidosis • Cardiovascular • Rare Diseases

Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials. (PubMed, J Clin Oncol) - "Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype."

Journal • Amyloidosis • Cardiomyopathy • Cardiovascular

A Pilot Study of Anselamimab in Patients With AL Amyloidoma and Measurable Tissue Involvement (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Stanford University

New P1 trial • Amyloidosis

CARES Phase III clinical programme did not meet primary endpoint in overall light chain amyloidosis population, however, demonstrated anselamimab as potential first anti-fibril therapy in kappa light chain amyloidosis (AstraZeneca Press Release) - "In a prespecified subgroup analysis of patients with kappa predominant light chain isotype, anselamimab improved survival by 62%, measured by ACM (hazard ratio 0.38; 95% confidence interval [CI] 0.17, 0.86; nominal p=0.012), and reduced the frequency of CVH by 71% (incidence risk ratio 0.29; 95% CI 0.10, 0.87; nominal p=0.028), compared to placebo in the subgroup with kappa AL amyoidosis....Results published in the Journal of Clinical Oncology and will be presented at 2026 American Society of Clinical Oncology Annual Meeting."

P3 data • Amyloidosis

AstraZeneca to showcase Phase III data in liver, breast and bladder cancers and potential first-in-class rare disease therapy at ASCO 2026 (AstraZeneca Press Release) - "EMERALD-3 late-breaking presentation will showcase benefit of Imfinzi and Imjudo in early liver cancer; Phase III data from SERENA-6, DESTINY-Breast09 and TROPION-Breast02 span all three major subtypes of metastatic breast cancer; CARES Phase III results will demonstrate highly clinically meaningful benefit of anti-fibril therapy, anselamimab, for kappa light chain amyloidosis"

Late-breaking abstract • P3 data • Amyloidosis • Hepatocellular Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer

Dysregulated proteasome proteostasis acts as a driver of light chain amyloidosis (ASH 2025) - "Nine of the 14 patients were enrolled in the CAEL-101 study with standard of care Daratumumab+Cyclophosphamide+Borezomib+Dexamethasone plus 1:1 randomized 1:1 to also receive CAEL-101, an amyloid-eating antibody, vs placebo. This finding is consistent with previous report that IGLL5 could be a potential signature mutation in AL.Here we report that loss of function mutation in E3 ubiquitin ligase HERC1 HECT domain may allow the exit of toxic IgLC from the plasma cells and hence created an aberrant proteasomal proteostasis. This mutation causing decoupling of proteasome from ER-stress providing new insights for early-stage biomarkers and therapeutic targets in AL."

Tumor mutational burden • Amyloidosis • Hematological Malignancies • Leukemia • Targeted Protein Degradation • HERC1 • IGLL5 • TMB

Harnessing phagocytes for amyloid clearance: Development of a novel bispecific phagocyte engager (LC Fibril x CD64) for AL amyloidosis (ASH 2025) - "Anselamimab (ch11-1F4, CAEL101) is an AL amyloid fibril-specificantibody promoting amyloid clearance via antibody-dependent phagocytosis through binding to Fcreceptor (FcR) on phagocyte (Ashfaque et al., 2025)...In contrast, BiPEinduced significantly enhanced phagocytosis that remained unaffected by Fc blocker or IgG competition.Similar results with primary human phagocytes supported BiPE's superior Fc-independent recruitmentand amyloid clearance, resistant to serum IgG interference.ConclusionWe developed a bispecific antibody (LC fibril × CD64) that harnesses phagocytes via Fc-independentbinding, which is resistant to IgG competition. By overcoming a key limitation of traditional antibodies,this approach enhances amyloid clearance and offers strong therapeutic potential for AL amyloidosis,including those on concurrent monoclonal antibody therapies."

Amyloidosis • Hematological Malignancies

Development of a high-affinity antibody specific to the predominant λ light chain amyloid subtype for AL amyloidosis immunotherapy (ASH 2025) - P3 | "Such mixed resultsare not unexpected: birtamimab was developed against serum amyloid A and anselamimab against κ LCamyloid, but 80% of AL amyloidosis cases involve λ LCs. Ch1F10 mAb also showed significantly higher phagocytic activity than ch11-1F4mAb against λ6 Wil amyloid using human THP-1 macrophages (P<0.0001, one-way ANOVA).CONCLUSIONSWe developed the novel λ-light chain specific monoclonal antibody 1F10, which demonstrated high-affinity binding and clearance activity. Given the current lack of efficient fibril targeting therapies for thismajority patient population, the 1F10 mAb represents a promising candidate for advancing subtype-specific precision immunotherapy in AL amyloidosis."

Amyloidosis

Cael-101 Enhances the Clearance of Light Chain Fibrils and Intermediate Aggregates By Phagocytosis (ASH 2023) - "The phagocytotic activity is further enhanced in the presence of complement. In addition, for the first time we demonstrated that CAEL-101 was able to phagocytose intermediate soluble light chain aggregates, known precursors of amyloid fibril formation."

Amyloidosis • GLI2

Safety and Tolerability of Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study (ASH 2023) - P2, P3 | "Aims: To present safety, tolerability, and biomarker data after 110 weeks of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Patients in this analysis have been treated for ≥24 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs (85%) were mild to moderate."

Clinical • P2 data • Amyloidosis • Anemia • Cardiomyopathy • Cardiovascular • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Insomnia • Multiple Myeloma • Oncology • Pulmonary Disease • Respiratory Diseases • Sleep Disorder • NPPB

Development of Anti-Amyloid 11-1F4- CAR Phagocytes for Treatment of AL Amyloidosis (ASH 2024) - "Anselamimab (11-1F4, CAEL-101) is an AL amyloid fibril specific monoclonal antibody currently being tested in phase 3 clinical trials, which triggers amyloid clearance via phagocytosis...Conclusions We developed first-in-class anti-amyloidosis human CAR macrophages using CD34+ hematopoietic stem cells and confirmed their amyloid-targeting activities both in vitro and in vivo. Our data suggest that anti-AL amyloid CAR macrophages could be a promising novel cell therapy for AL amyloidosis."

Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology • CD14 • CD33 • CD34 • CSF1 • PTPRC • SIRPA

Development of anti-AL amyloidosis CAR Phagocyte Therapy (IMS 2025) - "CAEL-101(c11-1F4), a fibril-specific monoclonal antibody in Phase 3A/B trials, promotes amyloid clearance via phagocytosis. However, the use of anti-CD38 antibodies in AL amyloidosis treatment and the recent failure of Birtamimab raised concerns that antibody-dependent phagocytosis for amyloid clearance may be impaired by high serum levels of anti-CD38 antibodies competing for Fc receptor binding... We developed the first-in-class anti-AL amyloidosis CAR phagocytes using CD34+ cells and confirmed their amyloid-targeting activities both in vitro and in vivo. By bypassing serum IgG Fc competition, CAR phagocytes represent a promising novel cell therapy for AL amyloidosis."

IO biomarker • Amyloidosis • CD14 • CD34 • CD68 • CD86 • CSF1 • ITGAX • MRC1

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (CARES) (clinicaltrials.gov) - P3 | N=281 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Sep 2027 ➔ Apr 2027

Trial completion date • Amyloidosis

Update on CARES Phase III clinical programme of anselamimab in light chain amyloidosis (AstraZeneca Press Release) - P3 | N=125 | CARES (NCT04504825) | P3 | N=281 | CARES (NCT04512235) | Sponsor: Alexion Pharmaceuticals, Inc | "High-level results from the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase III clinical programme showed that anselamimab, a light chain depleter antibody, did not achieve statistical significance for the primary endpoint compared to placebo in patients with Mayo stages IIIa and IIIb light chain (AL) amyloidosis. The primary endpoint was defined as a hierarchical combination of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalisations (CVH). All patients in the clinical programme received background standard of care for plasma cell dyscrasia. Anselamimab showed highly clinically meaningful improvement in time to ACM and frequency of CVH in a prespecified subgroup of patients, compared to placebo...Anselamimab was well tolerated, with the majority of events balanced between the anselamimab treatment arm and the placebo arm."

P3 data • Amyloidosis

Long term follow-up of patients with AL amyloidosis treated on a phase 1 trial of CAEL-101. (PubMed, Blood Adv) - No abstract available

Journal • P1 data • Amyloidosis

COMPLEMENT AND AMYLOID SIGNATURE PROTEIN UPREGULATION IN POST- TREATMENT AL AMYLOID PROTEOMES PROVIDES NOVEL INSIGHTS INTO DISEASE BIOLOGY (EHA 2025) - "This is the first study to examine treatment related proteomic changes in AL amyloidosis. The upregulation of complement proteins in the post-treatment samples of responders suggests complement activation plays a role in amyloid plaque removal but may also represent a mechanism of tissue toxicity. The reduction in immunoglobulin proteins in the residual amyloid plaques of responders may have therapeutic implications, as both birtamimab and anselamimab target misfolded immunoglobulin light chains which are be less abundant following therapy."

Amyloidosis • APOE • IGKC • VTN