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The compound, known as Chidamide in China and HBI-8000 in the US, is anovel, benzamide class histone deacetylase (HDAC) inhibitor discovered byChipscreen using a computer-aided rationale design approach.Chidamide/HBI-8000 shows promise for the treatment of a broad range ofcancers. The Phase I trial, which was initiated in China in April 2007,evaluated safety, PK, biomarker and efficacy profiles in relapsed/refractorysolid tumors and lymphomas.
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"The preclinical data, generated in both China and the US, as well as thePhase I results are very promising -- demonstrating a best in class profile,"said Mireille Gingras, PhD, CEO, HUYA Bioscience International. "The data willenable advancement of Chidamide/HBI-8000 to Phase II/III studies in China andPhase I in the US, and provides significant validation of our China/USco-development business model."
"With this exciting data in humans and continuing research efforts in ourlaboratory, we are also starting to understand better the unique propertiesand novel molecular mechanisms of action potentially associated with Chidamideas 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 thecompound worldwide outside of China, while Chipscreen maintains rights inChina. HUYA has previously received positive pre-IND comments from the FDAOncology Division for HBI-8000, including its willingness to accept bothpreclinical and clinical data generated in China as supportive information forthe opening of a US IND and initiation of a Phase I trial. Both a PhaseII/III lymphoma trial in China and a Phase I solid tumor/lymphoma trial in theUS are planned for early 2009.
Preclinical Profile and Clinical Results
Chidamide/HBI-8000 is an orally bioavailable, low nanomolar inhibitor ofcancer-associated HDACs and is one of the most potent inhibitors in thebenzamide class. It selectively inhibits tumor cell growth, relative to normalcells, with a therapeutic index of over 20-fold.
Patients received escalating oral doses of 5 to 50 mg Chidamide/HBI-8000either two or three times per week for four weeks, followed by a two weekdrug-free period for up to six cycles. PK parameters indicated significantexposure and this was validated by biomarker activity levels comparable to,but lasting longer than, most HDAC inhibitors. Chidamide/HBI-8000 producedsignificant activity in this early stage trial, with five out of twenty-fiveevaluable subjects experiencing a partial response and eleven with stabledisease. The only dose-limiting toxicities (DLTs) were gastrointestinal innature. Additional DLTs seen with other HDAC inhibitors, such as bone marrowsuppression, fatigue and QTc prolongation were not observed withChidamide/HBI-8000, supporting a best in class safety profile.
Results will be presented by Michael J. Newman, PhD, Executive VicePresident, Oncology, HUYA Bioscience International at the Cambridge HealthtechInstitute'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 howtightly DNA is wound around accessory proteins, histones. By deacetylating(removing an acetyl group from) histones, HDACs appear to promote tighterwinding of DNA around these proteins, leading to reduced access by genetranscription factors. This results in decreased expression of proteinsinvolved in cell differentiation, cell cycle arrest and apoptotic eliminationof damaged cells -- all of which contribute to the development of cancer.HDAC inhibitors are able to restore expression of tumor suppressor genes in ahighly selective manner. Treatment with HDAC inhibitors also leads,indirectly, to inhibition of the expression of angiogenesis factors, helpingto choke off the blood supply to tumors.
Although significant preclinical and clinical activity has been observedwith HDAC inhibitors, most have characteristics which may limit theirpotential for clinical success or broad applicability. In contrast,Chidamide/HBI-8000 has selectivity, potency, PK and side effect profiles thatmake it ideal for use as a stand-alone therapeutic, as well as in combinationwith 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 untappedsources of pre-clinical and clinical stage compounds for the drug developmentprocess. HUYA was one of the first companies to recognize China's potentialto help meet this need through its burgeoning biotechnology industry andworld-class talent pool. HUYA has pioneered an innovative approach -- theHUYA Integrated Co-development Model -- for partnering with Chinese researchinstitutions and pharmaceutical companies. HUYA identifies and licenses themost promising pre-clinical and clinical stage compounds in China, leveragesand extends the research efforts of its Chinese partners, and provides abridge into the Western development process and biopharma market.
Because the compounds have already been validated through a rigorousdiscovery, selection and development process in China, this model streamlinesand accelerates development in the West, while lowering risk. Moreover, thestrength of HUYA's relationships with its Chinese partners ensures acontinuous source of compounds for the future.
About HUYA
HUYA is the leader in US/China pharmaceutical co-development. With threestrategic offices in China, the broadest Chinese compound portfolio, and moreexclusive agreements with premier Chinese biotech centers than any othercompany, HUYA has pioneered the most innovative and productive approach forpharmaceutical co-development between the US and China. HUYA has jointheadquarters offices in San Diego, CA, and Shanghai. Further informationabout the company is available at http://www.huyabio.com.
About Chipscreen Biosciences
Chipscreen Biosciences is the leading Chinese biotech company specializedin the discovery and development of novel small molecule pharmaceuticals. Thecompany has utilized its proprietary chemical genomics-based discoveryplatform to successfully develop a portfolio of clinical and preclinical stageprograms in a number of therapeutic areas. Chipscreen's business strategy isto generate differentiated drug candidates across multiple therapeutic areas,then partner at the research, preclinical or early clinical stage for furtherco-development and commercialization outside China. Further information aboutthe company is available at http://www.chipscreen.com.Contact: HUYA USA: HUYA China: Shenzhen Chipscreen Biosciences, Ltd. Jan Tuttleman, PhD Ben Ni, PhD Vice President, Head of Xian-Ping LU, PhD Marketing Therapeutics President and Chief HUYA Bioscience HUYA Bioscience Scientific Officer International, LLC International, LLC Shenzhen Chipscreen (858) 798-8800 86 (21) 51323312 Biosciences, Ltd. [email protected] [email protected] 86-(755)26711889 [email protected] Website: http://www.chipscreen.com Media Contacts: Amy Berry Juliet Travis (415) 793-2258 (510) 452-3771 [email protected] [email protected]
SOURCE HUYA Bioscience International; Chipscreen Biosciences
