NJA-730, NapaJen's lead therapeutic compound is an anti-CD40 oligo complexed with SPG for the treatment of acute Graft versus Host Disease (aGvHD) in Hematological Cancer Patients undergoing Stem Cell Transplantations. Clinical trials are expected in 2018.
NapaJen™ DDS Advantage
NapaJen's oligonucleotide-SPG complex uses the dectin-1 receptor to specifically target immature dendritic cells (not antigen exposed) to inhibit the CD40 protein production which is critical in dendritic cell semi-maturation, hence allowing for tolerance. NapaJen's approach is distinct from other anti-CD40 drugs since it does not disrupt CD40 expression in B-cells and spares overall immune homeostasis.
Results of nonclinical pharmacology studies of NJA-730 collectively indicate that the in vivo efficacious dose of a mouse- orthologous anti-CD40 oligonucleotide is 100- to 1000-fold lower than that reported from other oligonucleotide drugs targeting similar cell types; making it likely that NapaJen's approach will preserve patient quality of life by reducing side effects.
About Hematopoietic Stem, Cell Transplantations and GvHD:
A common treatment for refractory hematological cancers (those not responding to existing therapeutics) involves ablative treatment with high levels of chemotherapy or radiation which has the potential to kill cancer cells along with the immune cells of the patient. A hematopoietic stem cell transplantation (HSCT) from a "matched" donor is typically used after the ablative treatment to restore immune function and to provide immune surveillance against any residual cancer in the form of a graft versus leukemia (GVL) effect.
The foundation for this treatment was created when more than 40 years ago Thomas and colleagues at the Fred Hutchinson Cancer Center showed that patients with refractory acute leukemia could be cured with a combination of high-dose myeloablative chemoradiotherapy and the allogeneic graft-versus-leukemia (GVL; also referred to as Graft versus Disease) effect provided by an infusion of HLA-compatible bone marrow from a sibling donor. However, the majority of patients with leukemia do not have an HLA-compatible related donor. Hence, many patients have faced serious complications or death caused by alloreactive T cell mediated GvHD (graft versus host disease), a syndrome in which donor cells recognize and launch an attack against host tissues primarily involving the skin, mucosa, gastrointestinal tract, liver and lungs. Although traditionally HSCT has been used as a second line of treatment recently experts have been debating over the use of HSCT as a first-line of treatment for many hematological disorders. The risk of GvHD has limited the broader applications of HSCT where it has the potential to not only cure a wider range of hematological cancers but also treat autoimmune diseases, immunologic deficiencies such as AIDS and facilitate transplant tolerance.