Anybody paying attention to these guys anymore? They've burned an awful lot of $$ going in reverse.
Curis Selects First Development Candidate from its Targeted Cancer Drug Development Platform
Wednesday March 14, 8:17 am ET
- A proprietary small molecule multi-target inhibitor, CUDC-101 is being developed to target EGFR and another clinically validated cancer target -
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Curis, Inc. (NASDAQ:CRIS - News), a drug development company focused on novel targeted medicines primarily for cancer treatment, today announced that it has selected the first development candidate from its Targeted Cancer Drug Development Platform. Curis is seeking to use this platform to discover and develop a portfolio of small molecule multi-target inhibitors against a wide range of cancer types. For each drug program, compounds are being designed by covalently linking two active drug components, or pharmacophores. Each pharmacophore targets at least one distinct clinically validated cancer target, where Target A remains constant throughout all programs currently under development at Curis, and Target B is a different clinically validated or promising cancer target that varies between programs. Specific Target A-Target B pharmacophore combinations define each of the several drug programs that are currently under development. Curis has filed several patent applications covering its multi-target inhibitor programs.
CUDC-101 is a multi-target small molecule where the first active drug component is designed to inhibit Target A and the second active drug component is designed to inhibit Target B, which is the Epidermal Growth Factor Receptor (EGFR). Curis has determined not to disclose Target A for proprietary reasons. Curis plans to initiate IND-enabling preclinical drug development activities shortly and, assuming the successful completion of such preclinical studies, expects to file an IND application with the FDA in late 2007 or early 2008.
Cancers for which various EGFR inhibitors have been approved in the U.S. for treatment include non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and head and neck cancer. These cancers represent a serious healthcare challenge. For example, the American Cancer Society estimates that there will be 213,000 new cases of lung cancer in the U.S. in 2007, of which 87% will be non-small cell lung cancer. For colorectal cancer, it is estimated that there were 149,000 new cases of and 55,000 deaths in the U.S. in 2006. Pancreatic cancer is one of the most aggressive cancers, with an estimated 34,000 new cases and 32,000 deaths in 2006. We believe that the development of effective therapies that treat any of these cancers better than the current standard would represent a significant commercial opportunity to Curis. In addition to FDA approved indications, EGFR inhibitors are being tested in other significant cancers, such as breast cancer (215,000 new cases in 2006).
"Our selection of CUDC-101 as a development candidate is an important milestone in our ongoing efforts to develop a pipeline of drug development programs," said Daniel Passeri, Curis' President and Chief Executive Officer. "We believe that the emergence of CUDC-101 as a development candidate demonstrates our ability to effectively conduct preclinical activities through development candidate selection on small molecule cancer drug candidates. We are working to add clinical development and regulatory capacities as we seek to progress CUDC-101 and other potential future candidates from our Targeted Cancer Drug Development Platform to IND application filing and into human clinical testing. As we seek to progress the development of CUDC-101 towards an IND filing, we are also seeking a corporate collaborator for this drug candidate that will have the potential to provide Curis with significant involvement in at least the early stages of clinical testing. Our current plan is to retain the rights to a majority of our other multi-target programs for further proprietary development."
About CUDC-101
In order to qualify CUDC-101 as a development candidate, Curis designed and evaluated a number of compounds within the current class of EGFR-Target A candidates. The decision to advance CUDC-101 into development candidate status was based upon CUDC-101 fulfilling key preclinical criteria generally considered necessary for such advancement. These criteria include good potency against the specific molecular targets, multiple demonstrations of in vitro antiproliferation and apoptosis-inducing activities, in vivo efficacy in preclinical animal models, and early safety assessment. Curis believes that CUDC-101, if ultimately approved, may have the potential to offer a number of important improvements over the currently available single pharmacophore EGFR or Target A drugs. A summary of key data from Curis' preclinical studies is as follows:
Potency. In in vitro enzymatic potency assays, CUDC-101 inhibited EGFR activity (Target B) up to 20-fold higher and Target A activity up to 10-fold higher when compared with FDA approved comparator small molecules for each respective activity.
In vitro antiproliferation and apoptosis. In in vitro studies using various cancer cell lines, CUDC-101 displayed higher anti-proliferation activity when compared to a combination of FDA approved EGFR and Target A inhibitors. The evaluation included 4 breast cancer cell lines, 6 pancreatic cancer cell lines, 8 non-small cell lung cancer cell lines, as well as other cancer cell lines. Many of the cancer cell lines tested are insensitive or resistant to EGFR and/or Target A inhibitors alone. In these in vitro studies, CUDC-101's antiproliferation activity was 2 to 20-fold greater than a combination of EGFR inhibitor and Target A inhibitor reference compounds. Thus, Curis believes that CUDC-101 has the potential, if approved, to have broader anticancer activity and to be more potent than such EGFR or Target A inhibitors in combination. In other in vitro studies, CUDC-101 also induced apoptosis, or programmed cell death, in cancer cell lines.
In vivo efficacy in preclinical animal models. CUDC-101 demonstrated tumor growth inhibition or regression in a number of xenograft preclinical animal models using representative cell lines selected from the in vitro studies. In addition, in a series of pharmacokinetics and pharmacodynamic studies in xenograft preclinical animal models, CUDC-101 penetrated into the tumor tissues, down-regulated EGFR activity, reduced proliferation, and induced apoptosis, which mirrors our earlier in vitro findings and which Curis believes is indicative of a targeted mechanism of action.
Safety assessment. Early in vitro safety assessment studies evaluated CUDC-101 against a standard panel of molecular targets considered clinically relevant for potential adverse effects, including enzymes, receptors, transporters and ion channels. These assays also included CYP450 inhibition (for assessing liver metabolism and potential drug-drug interactions), hERG ion channel inhibition (for assessing potential induction of cardiac arrhythmia), and kinase selectivity. The compound appears to be well tolerated in preclinical animal in vivo studies. |
