Kosan's AACR Data Provides Rationale for KOS-862 (Epothilone D) Combination Clinical Trials
Wednesday March 31, 8:02 am ET
ORLANDO, Fla., March 31 /PRNewswire-FirstCall/ -- Kosan Biosciences (Nasdaq: KOSN - News) announced today at the 95th Annual Meeting of the American Association for Cancer Research in Orlando, FL, preclinical in vivo and in vitro data on the cytotoxic and antiproliferative effects of combining Kosan's lead epothilone, KOS-862 (Epothilone D) with two different standard chemotherapies. Data from these preclinical studies led to the conclusion that the clinical investigation of KOS-862 in combination with carboplatin (Paraplatin) or capecitabine (Xeloda) should be considered.
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In the study investigating KOS-862 and carboplatin ("KOS-862 (Epothilone D) and Carboplatin Demonstrate In Vitro and In Vivo Synergy Against Human NSCLC Cell Lines", Abstract # 5420), the combination therapy showed marked synergy in all the human NSCLC tumor cell lines tested in culture when KOS-862 was administered first followed by carboplatin. In the xenograft mouse model of human NSCLC tumors, the combination of KOS-862 and carboplatin demonstrated additive or synergistic effects under conditions where weight loss of the animals was well tolerated and reversible.
In the second study ("KOS-862 (Epothilone D) and 5'-Deoxy-5-fluorouridine or 5-Fluorouracil In Human Breast Cancer Cells: Marked Synergistic Antitumor Effects and Induction of Thymidine Phosphorylase Expression", Abstract # 5429) KOS-862 was evaluated in combination with 5'-deoxy-5-fluorouridine (5-DFUR, an intermediate metabolite of capecitabine, [Xeloda]) or 5-flourouracil (5-FU) in four human breast cancer cell lines. The data illustrated that both combinations resulted in broad additive or synergistic antiproliferative activity in these human tumor cell lines. The combination also produced apoptosis of the human cancer cells via several mechanisms.
According to Robert G. Johnson, Jr., M.D., Ph.D., Senior Vice President and Chief Medical Officer at Kosan Biosciences, "These preclinical combination studies demonstrated non-overlapping toxicities and improved efficacy. Combined with the knowledge of the known pharmacologic properties of the tested agents, the data provide a strong rationale for human clinical trials using KOS-862 and carboplatin or capecitabine (Xeloda)."
Early in March, Kosan announced the first of a series of several Phase Ib human clinical trials designed to evaluate KOS-862 in combination with standard chemotherapeutic regimens. In addition to the ongoing Phase Ib trial that Kosan is conducting to evaluate KOS-862 with Gemzar® (Gemcitabine HCl), Kosan, and its collaborator Roche, said they will evaluate KOS-862 in Phase Ib combination studies with Paraplatin® (carboplatin), Herceptin®, and Xeloda®. Under a global development and commercialization agreement between Kosan and Roche, Roche has the worldwide exclusive right to market and sell KOS-862 and Epothilone D analogs owned by or licensed to Kosan for the treatment of cancer, and Kosan will co-develop and has the right to co-promote its Epothilone D products in the U.S. for the treatment of cancer.
About Kosan
Kosan Biosciences has two lead product candidates: KOS-862 and 17-AAG. Both compounds are derived from an important class of natural products known as polyketides. KOS-862 is in Phase II clinical trials and is partnered with Roche in a global development and commercialization agreement. 17-AAG is being evaluated in multiple Phase I and Phase Ib clinical trials in collaboration with the National Cancer Institute. 17-AAG is a polyketide inhibitor of Hsp90 and interrupts several biological processes implicated in cancer cell growth and survival. By applying its expertise and proprietary technologies to generate polyketide analogs and by increasing the production yields of polyketides, Kosan has created a robust pipeline of potentially significant products for cancer, as well as for infectious disease and other therapeutic areas. For additional information on Kosan Biosciences, please visit the company's website at www.kosan.com |
