BOSTON, Oct. 23 /PRNewswire/ -- CHI -- Chipscreen Biosciences (Chipscreen) and HUYA Bioscience International (HUYA) today described the preclinical profile and outcome of a Phase I trial with Chidamide/HBI-8000, carried out in China by Chipscreen Biosciences, Ltd. of Shenzhen. The clinical trial produced best in class pharmacokinetics (PK), biomarker and safety profiles, and demonstrated activity against T-lymphoma and other tumor types.
The compound, known as Chidamide in China and HBI-8000 in the US, is a novel, benzamide class histone deacetylase (HDAC) inhibitor discovered by Chipscreen using a computer-aided rationale design approach. Chidamide/HBI-8000 shows promise for the treatment of a broad range of cancers. The Phase I trial, which was initiated in China in April 2007, evaluated safety, PK, biomarker and efficacy profiles in relapsed/refractory solid tumors and lymphomas.
"The preclinical data, generated in both China and the US, as well as the Phase I results are very promising -- demonstrating a best in class profile," said Mireille Gingras, PhD, CEO, HUYA Bioscience International. "The data will enable advancement of Chidamide/HBI-8000 to Phase II/III studies in China and Phase I in the US, and provides significant validation of our China/US co-development business model."
"With this exciting data in humans and continuing research efforts in our laboratory, we are also starting to understand better the unique properties and novel molecular mechanisms of action potentially associated with Chidamide as well as certain subtypes of the HDAC family," said Xian-Ping LU, PhD, President and Chief Scientific Officer of Chipscreen Biosciences.
HUYA holds exclusive development and commercialization rights to the compound worldwide outside of China, while Chipscreen maintains rights in China. HUYA has previously received positive pre-IND comments from the FDA Oncology Division for HBI-8000, including its willingness to accept both preclinical and clinical data generated in China as supportive information for the opening of a US IND and initiation of a Phase I trial. Both a Phase II/III lymphoma trial in China and a Phase I solid tumor/lymphoma trial in the US are planned for early 2009.
Preclinical Profile and Clinical Results
Chidamide/HBI-8000 is an orally bioavailable, low nanomolar inhibitor of cancer-associated HDACs and is one of the most potent inhibitors in the benzamide class. It selectively inhibits tumor cell growth, relative to normal cells, with a therapeutic index of over 20-fold.
Patients received escalating oral doses of 5 to 50 mg Chidamide/HBI-8000 either two or three times per week for four weeks, followed by a two week drug-free period for up to six cycles. PK parameters indicated significant exposure and this was validated by biomarker activity levels comparable to, but lasting longer than, most HDAC inhibitors. Chidamide/HBI-8000 produced significant activity in this early stage trial, with five out of twenty-five evaluable subjects experiencing a partial response and eleven with stable disease. The only dose-limiting toxicities (DLTs) were gastrointestinal in nature. Additional DLTs seen with other HDAC inhibitors, such as bone marrow suppression, fatigue and QTc prolongation were not observed with Chidamide/HBI-8000, supporting a best in class safety profile.
Results will be presented by Michael J. Newman, PhD, Executive Vice President, Oncology, HUYA Bioscience International at the Cambridge Healthtech Institute's annual conference on HDAC inhibitors, Thursday, October 23.
About HDACs and HDAC inhibitors
HDAC inhibitors, a new class of cancer drugs, work by controlling how tightly DNA is wound around accessory proteins, histones. By deacetylating (removing an acetyl group from) histones, HDACs appear to promote tighter winding of DNA around these proteins, leading to reduced access by gene transcription factors. This results in decreased expression of proteins involved in cell differentiation, cell cycle arrest and apoptotic elimination of damaged cells -- all of which contribute to the development of cancer. HDAC inhibitors are able to restore expression of tumor suppressor genes in a highly selective manner. Treatment with HDAC inhibitors also leads, indirectly, to inhibition of the expression of angiogenesis factors, helping to choke off the blood supply to tumors.
Although significant preclinical and clinical activity has been observed with HDAC inhibitors, most have characteristics which may limit their potential for clinical success or broad applicability. In contrast, Chidamide/HBI-8000 has selectivity, potency, PK and side effect profiles that make it ideal for use as a stand-alone therapeutic, as well as in combination with a wide variety of marketed anti-tumor agents.
HUYA's Integrated Co-development Model (ICM)
The global pharmaceutical industry faces a pressing need for new untapped sources of pre-clinical and clinical stage compounds for the drug development process. HUYA was one of the first companies to recognize China's potential to help meet this need through its burgeoning biotechnology industry and world-class talent pool. HUYA has pioneered an innovative approach -- the HUYA Integrated Co-development Model -- for partnering with Chinese research institutions and pharmaceutical companies. HUYA identifies and licenses the most promising pre-clinical and clinical stage compounds in China, leverages and extends the research efforts of its Chinese partners, and provides a bridge into the Western development process and biopharma market.
Because the compounds have already been validated through a rigorous discovery, selection and development process in China, this model streamlines and accelerates development in the West, while lowering risk. Moreover, the strength of HUYA's relationships with its Chinese partners ensures a continuous source of compounds for the future.
HUYA is the leader in US/China pharmaceutical co-development. With three strategic offices in China, the broadest Chinese compound portfolio, and more exclusive agreements with premier Chinese biotech centers than any other company, HUYA has pioneered the most innovative and productive approach for pharmaceutical co-development between the US and China. HUYA has joint headquarters offices in San Diego, CA, and Shanghai. Further information about the company is available at http://www.huyabio.com.
About Chipscreen Biosciences
Chipscreen Biosciences is the leading Chinese biotech company specialized in the discovery and development of novel small molecule pharmaceuticals. The company has utilized its proprietary chemical genomics-based discovery platform to successfully develop a portfolio of clinical and preclinical stage programs in a number of therapeutic areas. Chipscreen's business strategy is to generate differentiated drug candidates across multiple therapeutic areas, then partner at the research, preclinical or early clinical stage for further co-development and commercialization outside China. Further information about the company is available at http://www.chipscreen.com.
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