About the Phase I Combination TrialThe Phase I clinical trial is designed as an open-label, dose escalation study in which a total of approximately 15-25 human papillomavirus negative (HPV-) locally advanced head and neck cancer patients will be treated with CUDC-101 in combination with cisplatin and radiation at four study centers in the United States. The primary objective of this study is to establish the safety, tolerability and maximum tolerated dose (MTD) of CUDC-101 in this patient population. Secondary objectives are to (i) evaluate the efficacy of CUDC-101, cisplatin and radiation therapy combination, (ii) assess the pharmacokinetics of CUDC-101, and (iii) evaluate tumor markers for response associated with CUDC-101, cisplatin and radiation activity. CUDC-101 will be administered three times per week for 8 consecutive weeks, with a beginning dose of 225 milligrams per meter 2. The MTD of CUDC-101 in a previously completed single agent Phase I clinical trial was established as 275 milligrams per meter 2. Upon determination of the MTD and assuming the otherwise successful completion of this Phase I combination trial, Curis plans to conduct a randomized Phase II two-arm clinical trial in which head and neck cancer patients will receive cisplatin and radiation plus or minus CUDC-101. It is currently expected that the Phase II study would seek to evaluate whether the addition of CUDC-101 can improve the efficacy and/or durability of cisplatin and radiation therapy in this patient population. About CUDC-101 CUDC-101 is designed as a first-in-class therapeutic to simultaneously inhibit EGFR, Her2 and HDAC. In preclinical studies, CUDC-101 demonstrated the potential to inhibit all three molecular targets resulting in the potent killing of a wide range of cancer cell lines that are representative of a variety of human cancer types, many of which have demonstrated resistance to various approved targeted agents.
Curis data suggest that CUDC-101’s mechanism of action involves the sensitization of cancer cells to EGFR and Her2 inhibition through HDAC inhibition. CUDC-101 is designed to simultaneously inhibit both EGFR and Her2 at the receptor level while inhibiting downstream HDAC activity within the cancer cells. Despite the existence of other multi-targeted inhibitors, CUDC-101 is unique in its choice of targets, which may enable a synergistic attack on multiple nodes or points in the overall cancer pathway network that are used by tumors to survive, grow, and invade surrounding tissue.Curis has completed a Phase I dose escalation clinical trial of CUDC-101 in 25 patients with advanced, refractory solid tumors and has also enrolled 45 of 50 patients in an ongoing Phase I expansion trial to test CUDC-101 in patients with specific tumor types, including breast, gastric, head and neck, liver and non-small cell lung cancers. The Phase I expansion trial is designed as an open-label study in which patients are treated with CUDC-101 at the MTD of 275 milligrams per meter 2. The primary objectives of this study are to compare the safety and tolerability of CUDC-101 in subjects with these specific advanced solid tumors when the drug is administered either on a five days per week schedule (one week on/one week off) or on a three days per week schedule (three weeks on/one week off). The safety profile observed to-date for both dosing schedules appears to be generally consistent with that observed in the Phase I dose escalation study, in which the most frequent adverse events observed were mild to moderate and included fatigue, vomiting, dyspnea (shortness of breath), pyrexia (fever), and dry skin. In addition, stable disease was observed in several patients in this study. Most notably, stable disease was observed in four patients with advanced liver cancer. Two of these patients have been treated with CUDC-101 for over six months, with one patient remaining on study after 11 months. We have also observed ongoing stable disease of greater than 10 months in an advanced breast cancer patient.
About Curis, Inc.Curis is a drug development company that is committed to leveraging its innovative signaling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer. Curis is building upon its previous experiences in targeting signaling pathways, including in the Hedgehog pathway, in its effort to develop proprietary targeted cancer programs. For more information, visit Curis' website at www.curis.com. Curis Cautionary Statement: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the potential benefit of CUDC-101 in treating locally advanced head and neck cancers and other cancers, Curis’ plans and expectations for the continued development of CUDC-101, including with respect to future studies in head and neck cancer, and the potential of CUDC-101 to effectively and therapeutically attack and disrupt cancer pathway networks . Forward-looking statements used in this press release may contain the words "believes", "expects", "anticipates", "plans", "seeks", "estimates", "assumes", "will", "may," “could” or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements including, among other things:
- CUDC-101 is a novel compound whose potential benefit as a therapeutic cancer drug is heretofore unproven. Curis may experience adverse results, delays and/or failures in its ongoing and planned clinical trials of CUDC-101. Moreover, favorable results of preclinical studies and early clinical trials of CUDC-101 may not be predictive of results that may be obtained in later trials.
- Genentech and Roche may experience adverse results, delays and/or failures in their development program under collaboration with Curis. For example, Genentech and Roche may: experience adverse or inconclusive results in their clinical trials of vismodegib, fail to achieve any development and commercialization timelines that they publicly announce with respect to vismodegib; or otherwise fail to meet applicable regulatory standards for approval of vismodegib in one or more indications.
- Curis' collaborator Debiopharm may experience adverse results, delays and/or failures in its development program under collaboration with Curis. For example, Debiopharm may not be able to successfully advance Debio 0932 through its ongoing Phase I clinical trial as planned.
- Curis may experience difficulties or delays in obtaining or maintaining required regulatory approvals for products under development both internally and through its collaborations.
- Curis may not be able to obtain or maintain the intellectual property protection necessary for the development and commercialization of drug candidates based on its technologies.
- Curis may not be able to obtain the substantial additional funding required to conduct research and development of its drug candidates.
- Curis may experience unplanned cash requirements, and may not receive additional anticipated milestone payments under its collaborations, any of which could shorten the estimated period in which Curis will have cash to fund its operations and which could also adversely affect Curis' estimated operating expenses for 2011 and beyond.
- Curis faces risks relating to its ability to enter into and maintain collaborations for development candidates under its network-targeted cancer programs, its ability to maintain its current collaborations with Genentech/Roche and Debiopharm, and the risk that any such collaborators will not perform adequately or may terminate such collaborations on short notice and/or for circumstances outside of Curis’ control.
- Curis also faces other important risks with respect to its business, operations, financial condition and future prospects generally, that are discussed in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2011 and other filings that it periodically makes with the Securities and Exchange Commission.