Johnson & Johnson's Class 1 New Drug JNJ-88549968 Receives IND Approval in China for Myeloproliferative Neoplasms

Intelligent Finance APP learned on March 31 that the official website of the Center for Drug Evaluation (CDE) under the China National Medical Products Administration disclosed that Johnson & Johnson's (JNJ.US) Class 1 new drug, JNJ-88549968 injection, has been approved for clinical trials. It is intended to be developed for the treatment of myeloproliferative neoplasms. Public information shows that this is a bispecific T-cell redirection antibody targeting CALRmut×CD3 currently being researched by Johnson & Johnson. The product’s recent clinical approval in China indicates that it will soon commence clinical research targeting myeloproliferative neoplasms.

Myeloproliferative Neoplasms (MPNs) are clonal malignant hematological disorders originating in the hematopoietic stem cell (HSC) compartment, characterized by the overproduction of mature myeloid blood cells.

Studies have shown that mutations in JAK2, thrombopoietin receptor (MPL), and calreticulin (CALR) are phenotypic drivers in the pathogenesis of MPN. CALR mutations (CALRmut) are the second most common mutations in MPN. CALRmut are insertions or deletions that cause a frameshift in the last exon of the gene, leading to the loss of the KDEL endoplasmic reticulum retention motif and generating a new positively charged C-terminal neoantigen composed of 36 amino acids. Due to the loss of the KDEL motif, CALRmut is not confined to the endoplasmic reticulum but is transported to the cell surface through interaction with MPL, thereby continuously activating MPL and exerting oncogenic effects. T-cell-engaged immunotherapy, such as bispecific CD3 redirection antibodies, is expected to show promising response rates in clinical settings.

It is reported that JNJ-88549968 is a T-cell redirecting bispecific antibody targeting CALRmut, which functions by eliminating MPN clones. The mechanism of action of JNJ-88549968 is to act as a bridge between CALRmut MPN cancer cells and T-cells, inducing T-cell activation both in vitro and in vivo, thereby mediating the cytotoxicity of T-cells against CALRmut cancer cells.

Preclinical studies have shown that JNJ-88549968 can recognize the CALRmut epitope common to all known CALRmut types, demonstrating selective binding to CALRmut cell lines with no significant binding to CALR wild-type cells. The product can achieve selective T-cell activation against CALRmut in vitro and exhibits cytotoxicity against cell lines engineered with CALRmut; it can induce concentration-dependent cytotoxicity in patient-derived CALRmut CD34+ cells. JNJ-88549968-mediated cytotoxicity was observed in all tested CALRmut CD34+ cancer cells, and this effect was independent of the CALR mutation type. Researchers believe that this product has the potential to be developed into a novel bispecific T-cell redirecting antibody for the treatment of CALRmut MPN.