CPF and Cardiff University announce study of tefinostat

LONDON—CRT Pioneer Fund (CPF) has announced an investment of up to £2.8 million from the CRT Pioneer Fund to progress the development of tefinostat for the treatment of chronic myelomonocytic leukemia (CMML). As a result of this funding, the Phase 2 MONOCLE study for the treatment of CMML has been initiated and the first patient has been recruited.

Dr. Robert James, a managing partner for Sixth Element Capital and manager of the CPF, commented: “We believe tefinostat has great potential in treating chronic myelomonocytic leukemia and has the possibility for rapid market authorization in a very well-defined patient population where there is a significant clinical need and little in development. The start of the Phase 2 trial is a significant milestone, and our funding will help drive forward this potential new treatment to approval in the next few years. There are also other potential uses for the compound which we are exploring, but commencing the MONOCLE study is a great step forward. MONOCLE has been driven by the work of Dr. Knapper, and we very much look forward to working with him and his colleagues to develop tefinostat with the hope of bringing a successful treatment to CMML patients.”

James tells DDNews the MONOCLE study got its moniker from the study title: “A Phase 2 study of the monocyte-targeted histone deacetylase inhibitor tefinostat (CHR-2845) in chronic myelomonocytic leukemia (CMML),” which was shortened to MONOCLE.

CMML is a very poorly treated orphan disease with a high unmet medical need. There are currently more than 4,000 diagnosed patients in the seven major pharmaceutical markets per annum, and it affects the elderly, who cannot tolerate aggressive chemotherapy treatments. Allogeneic stem cell transplant is a potentially curative treatment, but this is only possible in a small minority of younger, healthier patients.

Dr. Alasdair Rankin, director of research at U.K-based Bloodwise (formerly Leukaemia & Lymphoma Research), said, “The outlook for CMML patients is currently extremely poor, with an approximate 20-percent five-year relative survival rate. Traditional chemotherapy-based treatments are unsuitable for the majority of older patients. Early results for tefinostat have been promising, and we are delighted to be supporting the next stage in what we hope will bring a new and urgently needed treatment option to patients.”

CMML is a disease caused by the over-production of monocytes. Tefinostat is a highly potent, innovative oral HDAC (histone deacetylase) inhibitor that selectively targets macrophages and monocytes—central cells of the innate immune system. Tefinostat has successfully completed a Phase 1 study with promising signs that it could treat CMML patients.

James explains that CPF acquired tefinostat from Chroma Therapeutics in 2013. “[Dr.] Steve Knapper proposed the idea of testing tefinostat in CMML patients, where there was a very strong preclinical rationale to support the idea that it may have activity in those patients, as well as a strong clinical need. CPF was very excited to support the study, as it is a very focused study and could generate very exciting clinical data that will support the future development of the compound.”

The Phase 2 MONOCLE study will be led by Knapper as principal investigator. Knapper is also a clinical reader from the Institute of Cancer & Genetics at Cardiff University and is generously supported by charitable funding from Bloodwise. The trial will be managed by the Centre for Trials Research at Cardiff University and aims to determine the tolerability and safety of the tefinostat compound. The multicenter, single-arm study—which will bring in many of the United Kingdom’s leading key opinion leaders in treating CMML—will initially recruit 19 patients, with the potential to increase to 40 based on results. There are currently no other CMML-specific studies being held in the U.K.

“We are very excited to be in a position to commence the MONOCLE study which will, for the first time, allow us to assess the effects of tefinostat, a monocyte-directed therapeutic agent, in patients with this often-neglected hematological malignancy,” said Knapper. “Hospital sites across the United Kingdom will be open for recruiting patients into the trial. I am extremely grateful to our funders Bloodwise and the CRT Pioneer Fund for making this study possible.”

In addition to its potential use with CMML, “Tefinostat has potential to be used in hepatocellular carcinoma and in immuno-oncology settings as, through its unique mechanism of action, it has been shown to specifically modulate cytokine production in macrophages and monocytes,” says James. “The current goal for tefinostat is to further develop it for CMML. A positive readout in this [Phase 2] study would lead to a larger registration study being run, either financed by CPF or a partner. Such a study would, we hope, centrally involve Cardiff University.”