Johnson & Johnson(JNJ.US) has obtained clinical approval in China for a new class 1 drug, intending to develop a treatment for multiple myeloma.

On March 31st, the official website of the China National Medical Products Administration's Center for Drug Evaluation (CDE) disclosed that the class 1 new drug JNJ-88549968 injection, submitted by Johnson & Johnson (JNJ.US), has been approved for clinical trials, with the intention of developing a treatment for myeloproliferative neoplasms. Public information indicates that this is a dual-specificity T-cell redirecting antibody targeting CALRmutCD3 being developed by Johnson & Johnson. The approval for clinical trials in China means that the product will soon undergo clinical research for the treatment of myeloproliferative neoplasms. Myeloproliferative neoplasms (MPNs) are clonal malignant hematopoietic disorders originating from the hematopoietic stem cell (HSC) region, characterized by excessive production of mature myeloid blood cells. Research has shown that mutations in JAK2, thrombopoietin receptor (MPL), and calreticulin (CALR) are phenotypic driver factors in the pathogenesis of MPNs. CALR mutation (CALRmut) is the second most common mutation in MPNs. CALRmut involves insertion or deletion mutations that cause a frame shift mutation in the last exon of the gene, leading to loss of the KDEL endoplasmic reticulum retention signal and generation of a positively charged C-terminal neoantigen composed of 36 amino acids. Due to the loss of the KDEL signal, CALRmut is not limited to the endoplasmic reticulum but transported to the cell surface through interaction with MPL, continuously activating MPL and exerting oncogenic effects. Immunotherapy involving T cells, such as dual-specific CD3 redirecting antibodies, is expected to show promising response rates in clinical settings. It is understood that JNJ-88549968 is a T-cell redirecting dual-specificity antibody targeting CALRmut, functioning to eliminate MPN clones. The mechanism of action of JNJ-88549968 involves serving as a bridge between CALRmut MPN cancer cells and T cells, inducing T cell activation in vitro and in vivo, thereby mediating T cell cytotoxicity against CALRmut cancer cells. Preclinical studies have shown that JNJ-88549968 can recognize common CALRmut epitopes in all known CALRmut types, displaying selective binding to CALRmut cell lines while showing no significant binding to wild-type CALR cells. This product can selectively activate T cells against CALRmut in vitro and induce cytotoxicity in CALRmut-modified cell lines; it can also concentration-dependently induce cytotoxicity in CALRmut CD34+ cells from patients. Cell toxicity mediated by JNJ-88549968 was observed in all tested CALRmut CD34+ cancer cells, regardless of the CALR mutation type. Researchers believe that this product has the potential to be developed as a novel dual-specificity T-cell redirecting antibody for the treatment of CALRmut MPNs.