Curis, Inc., a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, has achieved the first two development milestones under its agreement with The Leukaemia & Lymphoma Society (LLS) for the development of CUDC-907, a first-in-class orally-administered small molecule drug candidate inhibitor of phosphatidylinositol-3-kinase (PI3K) and histone deacetylase (HDAC). These milestones include a preclinical development objective, as well as Curis' recent filing of an Investigational New Drug (IND) application to begin phase I clinical testing of CUDC-907 in patients.

As a result, Curis will receive $750,000 in milestone payments under the terms of its agreement with LLS.

"The completion of CUDC-907's preclinical testing and subsequent IND filing is a significant milestone in the development of this important molecule, and we look forward to initiating a phase I clinical trial in patients with relapsed or refractory lymphomas or multiple myeloma in early 2013," said Dan Passeri, Curis' president and chief executive officer. "In preclinical studies, CUDC-907 has demonstrated very potent anti-proliferation activity, and we believe that this approach of disrupting multiple signaling networks with a single-agent drug candidate holds a great deal of promise for patients with advanced cancers. The upcoming phase I dose escalation study will be extremely important for selecting a dose of CUDC-907 given orally to this specific patient population to be used for further efficacy testing.”

"We are pleased that Curis' research and development team has successfully completed the preclinical work required to advance CUDC-907 towards clinical testing in patients with lymphomas and multiple myeloma, said Richard Winneker, LLS's Senior Vice President of Research. "These patients are often in critical need of new treatment options and LLS's Therapy Acceleration Programme (TAP) has provided important capital to companies like Curis to continue advancing novel drug candidates for the treatment of blood cancers."

The phase I clinical trial is designed as a standard dose escalation study in which CUDC-907 will be orally administered to patients with relapsed or refractory lymphoma or multiple myeloma at up to four study centers in the United States. The primary objectives of the trial are to determine the maximum tolerated dose (MTD) and recommended phase II dose of oral CUDC-907.  The secondary objectives of this study are to assess safety and tolerability, to assess pharmacokinetics, to evaluate biomarker activity and to assess preliminary anti-cancer activity of CUDC-907 in this patient population.

In the absence of dose limiting toxicity, each patient will receive oral CUDC-907 once daily for a minimum of 21 days of continuous daily dosing (1 cycle), and may continue to receive additional cycles of study treatment until disease progression or other treatment discontinuation criteria are met.

CUDC-907 is a potent inhibitor of the Class I PI3K and Class I and II HDAC subtypes, the combination of which Curis scientists believe has synergistic interaction against cancer cells. CUDC-907 has demonstrated the ability to suppress multiple nodes of survival and proliferation. In addition, preclinical data have shown that CUDC-907 inhibits compensatory pathways often utilized in cancer cells during the emergence of resistance to standard of care agents and induces apoptosis in treated cancer cells.

CUDC-907 exhibits anti-proliferation activity against a broad range of cancer cell types in in vitro studies, including cell lines that exhibit reduced sensitivity to single-target PI3K inhibitors. CUDC-907's anti-proliferation activity has been demonstrated to be much more potent than that of leading PI3K inhibitors in development. CUDC-907 also inhibits tumour growth in preclinical xenograft models of blood cancers as well as solid tumours with K-RAS mutations that exhibit reduced sensitivity to known PI3K inhibitors, indicating that this compound may have broader activity than other leading PI3K inhibitors currently in clinical development.

Under the agreement, LLS will fund approximately 50 per cent of the direct costs of the development of CUDC-907, up to $4 million. Curis is currently seeking to advance the molecule into a phase I dose escalation clinical trial in patients with relapsed or refractory lymphomas or multiple myeloma in early 2013. If this study is successful, LLS has also agreed to support Curis's subsequent phase Ib or phase IIa study in one or more specific indications as well as Curis' ongoing investigation of biomarkers for CUDC-907 in these diseases.