JAK2 inhibitors (JAK2i) are the standard treatment for myelofibrosis (MF), offering symptom relief and reducing spleen size. However, all FDA-approved JAK2i are type I inhibitors, which fail to eliminate the mutant MPN clone, leading many patients to treatment discontinuation.
Using C-X-C chemokine receptor type 4 (CXCR4) antagonists as cell mobilization agents has resulted in some FDA approved agents, such as Plerixafor, for hematopoietic stem cell transplantation and neutropenia. Oral cell mobilizers could result in using them in conditions such as sickle-cell disease (SCD) and chronic neutropenia. Emory University has developed and presented data for their CXCR4 antagonist EMU-116.
Most patients with myelodysplastic syndrome (MDS) exhibit variable degrees of anemia due to impaired erythropoiesis. Ameliorating anemia and reducing the dependence on transfusion may enhance the quality of life of these patients and improve their survival rates.
Modex Therapeutics Inc. has developed MDX-2003, a first-in-class tetraspecific T-cell engager targeting CD19 and CD20 on B cells, while co-engaging CD3 and CD28 on T cells.
Researchers from Aera Therapeutics Inc. reported the preclinical profile of AERA-109, a novel, targeted in vivo CAR T therapy designed to treat B-cell-mediated autoimmune diseases.
Sumitomo Pharma Co. Ltd. is developing the Menin (MEN1)-myeloid/lymphoid or mixed-lineage leukemia (MLL) interaction inhibitor DSP-5336 (enzomenib) for the treatment of MLL-rearranged acute myeloid leukemia.
Antibodies targeting CD269 and GPRC5D have shown unprecedented clinical efficacy in the treatment of multiple myeloma (MM), but many patients still develop progressive disease. It was hypothesized that dual-targeting T-cell immunotherapies might improve the efficacy by addressing the difficulty of heterogenous target expression and preventing resistance development due to antigen escape.
Apollo Therapeutics Ltd. has developed APL-4098, a small-molecule general control nonderepressible 2 (GCN2) inhibitor for the potential treatment of AML.
Astrazeneca plc has provided data for their CD22-targeting antibody-drug conjugate (ADC) AZD-4512 under development for the treatment of B-cell malignancies, which still have significant rates of disease resistance and relapse, as well as treatment-related toxicities.
Amphista Therapeutics Ltd. has developed and presented data for AMX-883, a novel orally bioavailable bromodomain-containing protein 9 (BRD9) degradation inducer for acute myeloid leukemia (AML)
treatment.
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