Celtic Pharma receives US patent for methods to treat breast, colon cancer

Celtic Pharmaceutical Holdings L.P. ("Celtic Pharma") today announced that the U.S. Patent Office has issued U.S. patent 7,816,323, for novel methods to treat breast and colon cancers using a combination therapy of Xerecept® with Avastin®.  The patent is based on in vivo data demonstrating the successful inhibition of tumor growth using a combination therapy approach. This patent was filed in April 2010, recognized as "special" based on specific criteria of the Patent and Trademark Office, and therefore expedited and issued on October 19, 2010.

Xerecept is a synthetic version of the natural peptide hormone Corticotrophin Releasing Factor. Celtic Pharma has been pursuing Xerecept's clinical development as a treatment for edema associated with cerebral tumors.  In trials to date, Xerecept has demonstrated that its use enables significant reductions or elimination of corticosteroid dosing in cerebral tumor patients, and that patients tolerate chronic daily Xerecept dosing over several years without significant side effect issues.

Celtic Pharma and its co-investigators first presented the results from Xerecept administered in combination with Avastin against both breast and colon cancers at the Annual Meeting of the American Association of Cancer Research (AACR) in April, 2010.  The data showed both synergistic activity between the two molecules and potentiation of Avastin by Xerecept.

"Celtic Pharma believes that Xerecept continues to show great promise as an important addition to the therapeutic options in clinical oncology," said Stephen Evans-Freke and John Mayo, Managing General Partners of Celtic Pharma.  "We are committed to ensuring the potential of Xerecept is realized, both in its application for the treatment of cerebral edema and in this exciting new opportunity as a potential oncology drug in major solid tumor types."

Dr. Jerry Posner, Former Chair of Neuro-Oncology at Memorial Sloan-Kettering Cancer Center commented, "The emerging data from the combination of Xerecept and Avastin is an important development that strongly suggests the need for evaluation of this combination treatment in patients.  Combination therapies are an important part of modern anticancer therapy.  The use of rational combinations of targeted, mechanism-based treatments offers the clinical oncologist the promise of more potent therapeutic options for addressing the multifaceted complexity of cancer."

Celtic Pharma is actively exploring clinical trial strategies to assess combination treatments of Xerecept with Avastin in order to validate these important preclinical findings in a clinical setting, and is also considering the potential for exploring Xerecept in combination with other leading cancer therapies. Celtic Pharma is in productive discussions with the U.S. Food and Drug Administration (FDA) in regards to the design of a registrational study evaluating objectively the clinical benefit associated with reductions in steroid dosing that may be achieved with the use of Xerecept in both primary and metastatic brain tumor patients. Celtic Pharma is also currently evaluating Xerecept in a pediatric trial for patients requiring high doses of corticosteroids to control their cerebral edema, with resulting heavy burdens of steroid-related symptoms.

Preclinical Studies

Several preclinical studies using implanted solid tumor (breast and colon) human xenografts into nude mice, as well as both pediatric and adult human brain tumor xenografts, were evaluated when treated with Xerecept® alone and in combination with Avastin®.  All of these particular models demonstrated statistically significant tumor regression and prolongation of survival following combination treatment with Xerecept and Avastin, compared to Xerecept or Avastin alone.

Specifically, in the human breast model, both Xerecept and Avastin by themselves produced similar antitumor effects; however, when Xerecept was combined with Avastin, the antitumor effect was significantly increased (p<0.001). The enhanced combination effect was statistically different (p<0.03) than either result associated with the monotherapies.  In the human colon xenograft model, Xerecept was not active alone against this tumor model while Avastin produced a significant tumor growth delay compared to the vehicle-treated control.  However, the combination therapy of Xerecept plus Avastin significantly increased the overall survival of animals when compared to treatment with vehicle (p<0.001) or Avastin alone (p<0.01).  In the high grade pediatric glioblastoma model, Xerecept demonstrated activity by itself and the combination of Xerecept with Avastin was significantly better than Xerecept or Avastin alone.  These preclinical findings demonstrate that Xerecept has the ability to potentiate or provide a synergistic enhancement of the antitumor effects of Avastin in these various models.