CA-4948 Phase 1 Promising To Treat Acute Myeloid Leukemia and Myelodysplastic Syndromes

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Curis Inc has reported their CA-4948 treatment has shown an overall tumor decrease of >20% from baseline. Downstream pharmacodynamic markers of IRAK4 are being actively evaluated and Molecular characteristics including cell-of-origin will be presented.

What Is Going On?

Curis Inc is a biotechnology company with a focus on creating therapeutics for the treatment of cancer. One of their most recent and most publicized of these is the CA-4948 which is a novel, small molecule IRAK4 kinase inhibitor used to treat patients with acute myeloid leukemia ( AML ) as well as high-risk myelodsplastic syndroms ( MDS ) with spliceosome mutations including SF3B1 and U2AF1.

Okay… What Does That Mean?

The company has produced a treatment that has shown promise to reduce the size of certain tumors. This success has opened the door to additional possibilities to further increase those who can be positively impacted as well as the efficiency of the treatment.

Dr. Starczynowski, Dr. Verma, and their colleagues showed that IRAK4-L, the oncogenic long isoform of IRAK-4, is expressed as a result of specific spliceosome mutations common in AML and MDS. Further, they demonstrated that it potentially impacts over 50% of the AML/MDS population. We quickly worked with our clinical investigators and the U.S. Food and Drug Administration (FDA) to design a study of CA-4948, our first-in-class IRAK4 inhibitor, in this population. We are pleased to announce today, just six months later, that we have initiated this new study and successfully dosed our first patient. The initial dose in this study is 200mg twice-daily (BID) which, based on our preclinical models, we believe may be a therapeutic dose level. As a result, we expect to report initial efficacy data by the end of the year.

James Dentzer, President and Chief Executive Officer of Curis

Originally announced in July of 2020, that the initial patients received the Phase 1 trial for evaluating CA-4948, just a few months later and they have reports of more than 20% reduction in the size of the tumor.

The long isoform of IRAK4, itself the result of specific genetic mutations, was recently discovered to be a driver of disease in over half the population of patients with AML and MDS. With CA-4948, we may now have a single drug that can directly target a key driver of disease in these patients. We are delighted to be a lead clinical site in the study of this novel new drug.”

Dr. Guillermo Garcia-Manero, Chief, Section of Myelodysplastic Syndromes at the University of Texas MD Anderson Cancer Center

About CA-4948 Phase 1 Clinical Trial

Phase 1 trial is listed as an open-label, dose escalation study designed to evaluate the safety of the new treatment. The primary objective being focused on what the maximum dose can be and then recommending Phase 2 doses of CA-4948 while adhering to dose-limiting toxicities ( DLT ).

What this means is that there will be a minimum of three patients who will be enrolled at each level starting with 200 mg BID. This dose has already been determined safe and is being used as the control. Each cycle will be 28 days in length and repeated as long as there are no toxicity levels identified. This data is expected to be completed by fourth quarter 2020.

Clinical trial: NCT03328078.

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