Curis Announces Initiation of Phase 1 Trial of CA-4948, a Small Molecule Inhibitor of IRAK4 Kinase in Patients with Lymphoma

LEXINGTON, Mass., Jan. 17, 2018 /PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer, today announced initiation of patient dosing in a Phase 1 trial of CA-4948, an orally available small molecule inhibitor of the IRAK4 kinase, for treatment of patients with lymphoma. CA-4948 was discovered at Aurigene and is the second licensed program from the Curis-Aurigene collaboration to enter the clinic. 

The Phase 1 study is designed to evaluate the safety, tolerability, and pharmacokinetic profile of CA-4948; identify any dose-limiting toxicities; and establish the recommended Phase 2 dose for the treatment of patients with lymphomas. The dose escalation stage of the trial will enroll patients with relapsed/refractory non-Hodgkin's lymphoma, and the expansion stage will focus on specific populations of patients with lymphomas harboring alterations in the MYD88 gene or Toll-like receptor (TLR) signaling pathway.

"We are pleased to announce the advancement of our clinical pipeline with the initiation of the Phase 1 trial for this selective IRAK kinase inhibitor in patients with lymphomas," commented Ali Fattaey, Ph.D., Curis's president and CEO. "Given the prevalence of activating mutations in the MYD88 gene and the TLR pathway, IRAK4 represents a significant target for the precision treatment of patients with different hematologic malignancies. In addition to its preclinical anti-tumor activity in MYD88-mutated lymphomas, we have observed encouraging effects of CA-4948 in animal models of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) as well as non-oncology inflammatory disease models. We look forward to working with our partner Aurigene to develop CA-4948 and  explore clinical opportunities for these conditions in the near future."

"We are excited to have enrolled the first patient in this lymphoma clinical trial and look forward to further investigating CA-4948 as a potential new treatment option for patients with hematologic malignancies," said Mathew Lunning, DO, University of Nebraska Medical Center, an investigator for the study.

"We are delighted with our collaboration that has led to the advancement of the second program into the clinic, an IRAK4 targeting molecule that came out of Aurigene's discovery efforts over many years," said CSN Murthy, Aurigene's CEO. "Our investment into Curis exhibits our belief and commitment for this program and beyond as we work with Curis to focus our collective resources to advance exciting drug candidates."

About CA-4948, a Small-Molecule Inhibitor of IRAK4 Kinase

Innate immune responses orchestrated through Toll-like receptors are important mediators of the body's initial defense against infections, while their dysregulation is associated with certain inflammatory conditions. Toll-like receptor signaling through the adaptor protein MYD88 results in the activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression. MYD88 gene mutations occur in approximately 30 percent of activated B-cell subtype of diffuse large B-cell lymphomas (DLBCL)^1,2 and in over 90 percent of cases of the B-cell malignancy Waldenstrom's macroglobulinemia (WM).³ IRAK4 has been validated as a target in DLBCL and WM disease setting, and its inhibition by CA-4948 has been shown to provide potent in vivo anti-tumor activity in animal models.^4,5 IRAK4 inhibitors are also in clinical testing for treatment of patients with rheumatoid arthritis.

¹Nature. 2011; 470(7332):115–119
²Immunology and Cell Biology. 2011; 89(6):659–660
³N Engl J Med. 2012; 367(9):826–833
⁴Cancer Res. 2017; 77(13 Suppl): Abstract 1168
⁵Blood. 2015;126(23):4004–4004

About Curis

Curis is a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, including CUDC-907, which is being investigated in clinical studies in patients with lymphomas and solid tumors. Curis is also engaged in a broad collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule dual antagonists of PD1 and VISTA, including PDL1/VISTA antagonist CA-170, and oral small molecule dual antagonists of PD1 and TIM3, including PDL1/TIM3 antagonist CA-327, as well as to molecules designed to inhibit the IRAK4 kinase, including CA-4948. CA-170 is currently undergoing testing in a Phase 1 trial in patients with advanced solid tumors and lymphomas. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. For more information, visit Curis's website at www.curis.com.

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SOURCE Curis, Inc.