On July 6, 2023 Curis, Inc., (Nasdaq: CRIS), a biotechnology company focused on the development of emavusertib, an orally available small molecule triple target inhibitor (IRAK4, FLT3 and CLK) for the treatment of hematologic malignancies, reported that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold on the TakeAim Leukemia Phase 1/2 study of emavusertib (Press release, Curis, JUL 6, 2023, View Source [SID1234633077]). Further, the recommended phase 2 dose (RP2D) for emavusertib as a monotherapy has been established at 300 mg BID in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS).

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"We are pleased to announce that FDA has removed the partial clinical hold on the TakeAim Leukemia study and that we are proceeding with 300 mg BID as our RP2D. We are working with our clinical sites to enroll targeted patients with AML (patients with a FLT3 or spliceosome mutation who have received ≤ 2 prior lines of treatment). We also plan to initiate a front-line combination study of emavusertib with azacitidine and venetoclax. We believe emavusertib has the potential to be the cornerstone agent in the treatment of hematological malignancies." said James Dentzer, President and Chief Executive Officer of Curis. "In 2024, we expect to have updated data from the TakeAim Leukemia monotherapy study, clarification of a monotherapy registrational study design, and initial data from an azacitidine and venetoclax combination study."

On April 4, 2022, the Company announced that the FDA placed a partial clinical hold on the TakeAim Leukemia study. On August 30, 2022, the Company announced that the FDA notified Curis that it may resume enrollment of additional patients in the monotherapy dose finding phase of the TakeAim Leukemia study, so that the Company could enroll at least nine additional patients at the 200 mg BID dose level. On July 6, 2023, the Company announced the FDA had removed the partial clinical hold on the TakeAim Leukemia study and that the RP2D has been established at 300 mg BID.

In the TakeAim Leukemia study, as of the March 17, 2023 data cutoff for patients dosed prior to February 9, 2023, 84 patients received emavusertib monotherapy, ranging from doses of 200 mg to 500 mg BID. Significant blast count reductions have been observed across all patient groups, regardless of dose level, mutation status, or number of prior lines of treatment. Emerging from these data are two genetically-defined subpopulations of relapsed/refractory (R/R) patients who have demonstrated compelling responses in monotherapy: AML patients with FLT3 mutation and AML patients with spliceosome mutation (U2AF1 or SF3B1 mutation) who have received ≤ 2 prior lines of treatment. In these subpopulations of evaluable patients (patients whose disease has been determined to be evaluable for objective response with baseline and post-treatment marrow assessments) treated with 300 mg BID, 2 of 3 patients with a FLT3 mutation achieved a CR (Complete Response), and 2 of 3 patients with spliceosome mutation achieved a CR or CRh (Complete Response with Partial Hematologic Recovery). The duration of response for these patients ranged from 5.6 to 7.0 months.

"A significant unmet need remains for patients with AML and MDS with the majority of front-line patients relapsing with currently available treatment options," said Dr. Reinhard von Roemeling, Senior Vice President of Clinical Development of Curis. "Emavusertib has the potential to be uniquely positioned as an addition to frontline therapy in combination with standard of care and also as a monotherapy in targeted R/R patient populations."

About emavusertib (CA-4948)

Emavusertib is a triple target inhibitor (IRAK4, FLT3 and CLK). 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-κB 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.

About TakeAim Studies

TakeAim Leukemia Study (NCT04278768) – study is open for enrollment.
TakeAim Lymphoma Study (NCT03328078) – study is open for enrollment.