Curis, Inc. announced initial combination study data from its Take Aim Lymphoma trial including 5 primary CNS lymphoma (PCNSL) patients. As of October 12th, the Take Aim Lymphoma trial has enrolled and treated 19 Non-Hodgkin Lymphoma (NHL) patients, with a combination of emavusertib and ibrutinib; with emavusertib doses ranging from 100 mg to 300 mg BID. The initial data reveal encouraging efficacy, demonstrating multiple objective responses in both BTK-naive and BTK-experienced patients.

Patients with PCNSL who had a history of failed BTKi therapy showed a particularly noteworthy response: 3 out of 5 evaluable PCNSL patients achieved a Complete Response (CR), with durability ranging from 0.3 - 8.9 months. These data underscore the potential of emavusertib to re-sensitize patients to BTKi therapy, marking a significant advancement in Non-HodgkinLymphoma treatment. Emavusertib is a small molecule IRAK4 inhibitor.

IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-?B protein complex. Preclinical studies targeting IRAK1/4 in combination with FLT3 have demonstrated the ability to overcome the adaptive resistance incurred when targeting FLT3 alone.

Further, emavusertib has shown anti-tumor activity across a broad range of hematologic malignancies including monotherapy activity in patient-derived xenografts and synergy with both azacitidine and venetoclax.