KappaMab / HaemaLogiX - LARVOL DELTA

Novel Therapeutic Targets Kappa Myeloma Antigen (KMA) and Lambda Myeloma Antigen (LMA) Are Expressed on Malignant Plasma Cells from Patients with Plasma Cell Dyscrasias but Not on Normal Plasma Cells (IMS 2025) - "Their expression on a broad range of plasma cell dyscrasias (PCDs) and normal tissues has not been fully documented. Antibodies to KMA and LMA (KappaMab and LambdaMab) and other antibodies were used to compare the expression of KMA, LMA, B cell maturation antigen (BCMA), CD56 and SLAMF7 on bone marrow PCs from patients with a range of PCDs... KMA and LMA were only expressed on clonal but not on normal PCs. Antigen expression was independent of the Ig subtype, the number of bone marrow PCs and the Ig and FLC serum concentrations. In some cases of MM, the frequency and density of antigen expression increased as MM evolved."

Clinical • IO biomarker • Amyloidosis • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Plasmacytoma • Smoldering Multiple Myeloma • NCAM1 • SLAMF7

Expression of Kappa Myeloma Antigen (KMA) and Lambda Myeloma Antigen (LMA) on Malignant but Not Normal Plasma Cells Offers Novel Therapeutic Targets for Patients With Myeloma, Amyloidosis and Other Plasma Cell Dyscrasias. (PubMed, Clin Lymphoma Myeloma Leuk) - "The broad and selective expression of KMA and LMA on malignant PCs and the high antigen density highlight the potential of these as valuable targets for immunotherapies in a variety of PCDs including AL-amyloidosis."

IO biomarker • Journal • Amyloidosis • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Plasmacytoma • NCAM1 • SLAMF7

NOVEL ANTIGENS LMA AND KMA ARE EXPRESSED ON BONE MARROW PLASMA CELLS FROM PATIENTS WITH AL AMYLOIDOSIS BUT THEY ARE NOT DETECTED ON NORMAL PLASMA CELLS (EHA 2024) - "We investigated 3 human monoclonal antibodies (Mabs) – 2 LambdaMabs and 1 KappaMab – that bind to cell-membrane-bound antigens called lambda myeloma antigen (LMA) and kappa myeloma antigen (KMA). LMA or KMA were detected in all samples from daratumumab-treated patients. In addition, KMA or LMA wereexpressed on PCs on all samples and their expression was generally higher than for BCMA. The 10B3LambdaMab was better than the 7F11 LambdaMab at detecting LMA."

Clinical • IO biomarker • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology • ANXA5 • NCAM1 • PTPRC • SDC1

Changes in immune cell populations following KappaMab, lenalidomide and low-dose dexamethasone treatment in multiple myeloma. (PubMed, Clin Transl Immunology) - "These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells."

Immune cell • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8

A Novel CAR-T cell therapy targeting kappa myeloma antigen for the treatment of multiple myeloma (IMW 2023) - "Chimeric Antigen Receptor (CAR)-T cell therapy has recently entered the standard of care for relapsed and refractory MM, following the recent FDA-approval of two CAR-T cell products, ide-cel® and cilta-cel®, which target the B cell maturation antigen (BCMA)...The monoclonal antibody, KappaMab (MDX-1097), binds to a conformational epitope on KMA, and has been assessed in phase I, IIa and IIb clinical trials in relapse refractory myeloma patients... Our data demonstrates that anti-KMA CAR-T cell therapy is a novel and potent treatment ready to enter a phase I clinical trial for patients with multiple myeloma."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • IFNG

Novel antigens LMA and KMA are expressed on malignant bone marrow plasma cells from patients at all stages of multiple myeloma and in other plasma cell dyscrasias (IMW 2023) - "KappaMab (formerly MDX-1097) clinical trials have confirmed that normal leukocytes are not depleted by the antibody with no on-target off-tumour effects1-3, and preclinical KMA.CAR T cell data has confirmed the antibody specificity4. KMA or LMA are expressed on PCs at all stages of MM, and all plasmacytomas and AL patient samples. The increased Ag densities of both KMA and LMA compared to BCMA on RRMM BM PCs indicates antigen persistence on a treatment resistant clone. The combination of increased and persistent antigen density and the specificity of these therapeutic antibodies could provide a significant benefit in the treatment of myeloma and PCDs.1."

Clinical • IO biomarker • Amyloidosis • Hematological Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Plasmacytoma • NCAM1 • PTPRC • SDC1 • SLAMF7 • TNFRSF17

HaemaLogiX to study higher dose of KappaMab in Phase IIb trial (Clinical Trials Arena) - "Australian biotech HaemaLogiX is planning to initiate another Phase IIb trial with a higher dose of KappaMab in patients with multiple myeloma, chief scientific officer Rosanne Dunn told Clinical Trials Arena. The company expects to initiate the trial early next year."

New P2b trial • Hematological Malignancies • Multiple Myeloma • Oncology

HaemaLogiX Announces Positive Final Results from KappaMab Combination Phase IIb Myeloma Trial (PRNewswire) - P2b | N=60 | "HaemaLogiX...announced positive final results from a Phase IIb clinical study of its monoclonal antibody KappaMab in combination with lenalidomide and dexamethasone in kappa-type multiple myeloma patients who had relapsed or become refractory to other treatment options....A statistically significant overall response rate (ORR) of 83% and clinical benefit rate (CBR) of 93% in KappaMab + lenalidomide / dexamethasone (Case) was achieved compared to the matched Control cohort of lenalidomide + dexamethasone alone (ORR = 45%)."

P2b data • Hematological Malignancies • Multiple Myeloma • Oncology

A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16). (PubMed, Br J Haematol) - "Both single-agent KM and KM-Rd regimens were well tolerated, with the KM-Rd safety profile similar to patients given only Rd in other clinical settings. Based on the excellent safety profile and significant efficacy, further clinical trials escalating the KM dose and pairing KM with other standard-of-care treatments are planned."

Journal • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

KAPPA MYELOMA ANTIGEN (KMA) AND LAMBDA MYELOMA ANTIGEN (LMA) ARE EXPRESSED ON B CELL MALIGNANCIES AND ARE PROMISING NOVEL TARGETS ON MALIGNANT PLASMA CELLS (ICML 2023) - "KappaMab is a therapeutic antibody that specifically targets KMA and a phase IIb study in combination with lenalidomide and dexamethasone has recently been completed. Although there are smaller numbers of samples from other B cell malignancies such as lymphoplasmacytoid, amyloidosis and BLPDs, we have demonstrated that KMA or LMA are expressed on malignant BM PCs. In the myeloma cases, the antigen density of both KMA and LMA was increased compared to BCMA on RRMM BM PCs, which suggests a clonal advantage of KMA and LMA expressing plasma cells that are resistant to standard of care treatments. These data suggest that KappaMab and LambdaMabs have therapeutic potential in RRMM where the combination of high antigen density and restriction of the target antigen to the malignant subpopulation of PCs may confer clinical benefit by retaining normal plasma cells following treatment."

IO biomarker • Hematological Malignancies • Lymphoma • Oncology • NCAM1 • PTPRC • SDC1 • SLAMF7 • TNFRSF17

Cellular immunotherapy targeting kappa myeloma antigen for the treatment of multiple myeloma (AACR 2023) - "Chimeric Antigen Receptor (CAR)-T cell therapy has recently entered the standard of care for relapsed and refractory MM, following the recent FDA-approval of two CAR-T cell products, ide-cel® and cilta-cel®, which target the B cell maturation antigen (BCMA)...The monoclonal antibody, KappaMab (MDX-1097), binds to a conformational epitope on KMA, and has been assessed in phase I, IIa and IIb clinical trials in relapse refractory myeloma patients (1)...We successfully generated human anti-KMA CAR-T cells with high and stable CAR expression and a predominately memory T cell phenotype...(1) Spencer et al. Blood Cancer Journal (2019) 9:58"

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • IFNG

Novel Antigens LMA and Kma Are Expressed on Malignant Bone Marrow Plasma Cells from Patients with Relapsed Refractory Multiple Myeloma and Plasma Cell Dyscrasias (ASH 2022) - "KMA and LMA expression is independent of serum Ig and FLC levels and % marrow plasma cells. These data show that KappaMab and LambdaMab have therapeutic potential in the treatment of myeloma patients, especially in the setting of relapsed refractory disease where the combination of high antigen density and restriction of the target antigen to the malignant subpopulation of plasma cells will confer valuable clinical benefit."

Clinical • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Infectious Disease • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Transplantation • NCAM1 • PTPRC • SDC1 • SLAMF7 • TNFRSF17

[VIRTUAL] Extracellular RNA: An emerging biomarker for therapeutic monitoring in multiple myeloma (IMW 2021) - "We also performed droplet digital PCR (ddPCR) for exRNA transcripts of candidate biomarkers of lenalidomide (LEN) response in a “test cohort” of samples collected at study entry (baseline) and after five days of LEN treatment (C1D5) in a phase 1b trial of azacitidine in combination with LEN and dexamethasone (DEX) for patients with RR MM (ROAR trial; n= 24 patients). A “validation cohort” was obtained from a phase IIb trial of KappaMab in combination with LEN and DEX in RR MM (KappaMab trial; n=39 patients) at screening and C1D5... The data presented here provide the first demonstration of the utility of exRNA for biomarker identification and therapeutic monitoring. It provides the foundation for further exploration and development of exRNA testing as a potentially simple, non-invasive, repeatable strategy in MM."

Biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • IKZF3

"#HaemaLogiX and #Lonza Collaborate to Manufacture #KappaMab a #MultipleMyeloma Drug Candidate https://t.co/SWJbVQuALW" (@1stOncology)

Hematological Malignancies • Multiple Myeloma • Oncology

HaemaLogiX and Lonza Collaborate to Manufacture KappaMab, a Multiple Myeloma Drug Candidate (PRNewswire) - "HaemaLogiX Ltd...and Lonza...have entered into an agreement to manufacture the next clinical batch (cGMP) of HaemaLogiX's lead multiple myeloma drug candidate, KappaMab....'We look forward to taking KappaMab back into the clinic alongside standard of care, and this Lonza agreement is an important step toward providing the drug product for our upcoming trial'....The drug product will then be used in Australian-based clinical trials, currently scheduled to begin in late 2022."

Licensing / partnership • New trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Novel B Cell Antigen Designated Lambda Myeloma Antigen (LMA) Has Been Identified Using Two Fully Human Monoclonal Antibodies (Mabs) That Bind to Similar Epitopes on Plasma Cells from Patients with Plasma Cell Dyscrasias (ASH 2021) - "Introduction: The novel kappa (κ) myeloma antigen (KMA) has been described and a specific monoclonal antibody KappaMab (formerly MDX-1097) developed which is currently in a Phase IIb clinical trial... These studies used mostly myeloma samples and a small number of other plasma cell dyscrasias. Nevertheless expression of KMA and LMA was identified on PCs across the spectrum of disease. Within the treated patient cohort the antigen density of KMA or LMA was higher than that of BCMA and implies there is an enrichment of these novel antigens in relapsed refractory myeloma."

Clinical • IO biomarker • Amyloidosis • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Plasmacytoma • Waldenstrom Macroglobulinemia • NCAM1 • PTPRC • SDC1 • TNFRSF17

CAR T-cells targeting the kappa myeloma antigen for the treatment of multiple myeloma (AACR 2018) - "...The monoclonal antibody KappaMab (kMAb-previously-MDX-1097) binds to a unique conformational epitope on the Kappa Myeloma Antigen (KMA)...Our in vitro data indicates that the KM.CAR T-cell is likely to be effective in kappa restricted myeloma patients. In vivo testing of these CAR T-cells in a Rag2-/- myeloma mouse model system is currently underway."

CAR T-Cell Therapy • IO Biomarker • PD(L)-1 Biomarker • Leukemia • Lymphoma • Multiple Myeloma

A preliminary study of the anti-κ myeloma antigen monoclonal antibody KappaMab (MDX-1097) in pretreated patients with κ-restricted multiple myeloma. (PubMed, Blood Cancer J) - No abstract available

Clinical • Journal