Earlier this month China-based Contract Research Organization (CRO) WuXi Biologics started commercial production at the company’s new Current Good Manufacturing Practice (cGMP)-approved DP3 bulk and preparation facility.
The new facility will, following a strategic partnership between WuXi Biologics and Novocodex Biopharmaceuticals, a subsidiary of Zhejiang Medicine, be used for the manufacturing of antibody-drug conjugates (ADCs), including Phase III and commercial-scale production of ARX788, an ADC designed to targets HER2 over-expressing tumors including breast, gastric, colon, pancreatic and ovarian cancers.
“We’re quite excited to [start commercial production and] and expand [our] integrated biologics conjugation solution center, which will further enhance our technical capabilities and manufacturing capacities in the fast-growing bioconjugation field,” noted Zhisheng (Chris) Chen, Ph.D., Chief Executive Officer of WuXi Biologics.
“With the strength of our ONE-stop service platform covering antibody, bioconjugation drug substance and drug product, WuXi Biologics will continue enabling our global partners to develop exciting ADCs to benefit cancer patients worldwide,” Chen added.
ARX788 is based on a next-generation ADC technology platform developed by Ambrx, a privately-held clinical stage biopharmaceutical company, in which a HER2 specific monoclonal antibody is site-specifically conjugated with Amberstatin269, a potent cytotoxic tubulin inhibitor.
In preclinical models, ARX788 has demonstrated an improved efficacy and safety profile relative to currently available HER2 targeting antibody-drug conjugates. These studies have also demonstrated that ARX788 is effective in controlling xenograft tumors. Result from safety studies in rodents and non-human primates have demonstrated that the investigational drug is well tolerated at doses significantly higher than the doses required to demonstrate efficacy.
Based on an agreement signed in June 2013, Novocodex and Ambrx, jointly develop and commercialize ARX788, which included joint clinical trials in Australia, the United States, and China.
Cutting edge facility
WuXi Biologics’ new DP3 facility is equipped with cutting-edge isolators and single-use production technology, giving the company the ability to handle Occupational Exposure Band (OEB) 5 raw materials as well as production of photosensitive oxygen sensitive products.
OEB 5 compounds include active pharmaceutical ingredients (APIs) that are highly potent (therapeutic doses less than 0.5 mg/day), have significant adverse effects at low doses (life-threatening, irreversible, or severe sensitizers) or may be genotoxic, carcinogenic, or have reproductive effects at relevant doses. The compounds typically have occupational exposure limits (OEL) less than 1 μg/m3.
The expected annual production capacity of WuXi Biologics’ DP3 facility is 100 kilogram of antibody-drug conjugates and 500,000 bottles of lyophilized preparation.
There are currently more than 20 ADCs being developed by WuXi Biologics. To date, WuXi Biologics has successfully advanced 11 ADCs projects to Investigational New Drug (IND) filing.
Based on the agreement with Novocodex, WuXi Biologics will be responsible for the manufacturing of clinical samples for the Phase III study of ARX788, as well as process characterization and verification research, and large-scale commercial production.
A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression – NCT02512237
A Dose-escalation Study of ARX788, IV Administered in Subjects With Advanced Cancers With HER2 Expression – NCT03255070