Companies are currently selecting final HER2/neu antibodies to move into the clinic.
A cancer antibody collaboration between YM Biosciences and the National Research Council of Canada’s Biotechnology Research Institute (NRC-BRI) has yielded new HER2 antibodies. The partners claim that these candidates could be safer than existing antibody-based drugs such Herceptin® (trastuzumab; Genentech/Roche).
The new candidates have been designed to bind to HER2/neu on cancer cells but, in contrast to Herceptin, only minimally bind to HER2 on healthy cardiac cells. This is expected to result in reduced collateral cardiac toxicity, says David Allan, YM’s chairman and CEO.
YM and the NRC-BRI are currently selecting a lead candidate to be taken into full development.
The organizations are co-funding and collaborating on a multitarget, parallel-discovery research project focused on exploiting YM’s IntelliMab™ technology. The aim is to develop a new generation of antibodies that target cancer-associated cell surface receptors but with reduced toxicity.
Dependent on the target, the resulting antibodies may also represent ideal candidates for delivering toxins to cancer cells, Allan claims. “The improved specificity of these anti-HER2 antibodies makes them amenable to conjugation with highly potent toxins, which would permit the selected IntelliMab anti-HER2-neu conjugate antibody to be an important competitor to trastuzumab-DM1 (Genentech/Immunogen).”
YM’s lead antibody drug is nimotuzumab, which is being developed to compete against the established class of EGFR-targeting drugs. It is designed to reduce the incidence of grade 4 radiation dermatitis or grade 3/4 acneform rash. These conditions are severe and dose-limiting side-effects observed with all other antibodies and small molecules targeting the EGF tyrosine kinase signaling pathway, YM states.
Nimotuzumab has been approved for marketing in 23 countries including Brazil, India, China, Argentina, and Indonesia. The antibody is also undergoing Phase II and III trials globally in multiple indications including non-small-cell lung cancer, pediatric and adult glioma, esophageal cancer, pancreatic cancer, gastric cancer, as well as head and neck cancer.
During August YM’s U.S. subsidiary received a license from the U.S. Department of the Treasury’s Office of Foreign Assets Control (OFAC) to develop nimotuzumab for patients with solid tumors in the U.S. “This license from OFAC to develop nimotuzumab in any cancer indication is a major step forward in our U.S. development program and will allow us to immediately discuss our IND submissions with the FDA to include U.S. patients in our randomized, double-blinded lung cancer and brain metastases trials,” notes David Allan. “Our development plans may also include extending some of the Phase III trials being conducted worldwide into the U.S.”
Then in October YM BioSciences proposed to acquire Australia-based Cytopia. YM expects the takeover to allow it to start clinical trials of nimotuzumab in Australia (subject to regulatory clearance) and supply nimotuzumab to individual patients in the country through a special access scheme that has already been launched.
Cytopia’s lead products are CYT997, a novel vascular disrupting agent currently in Phase II trials, and CYT387, a novel, orally active JAK2 inhibitor that recently received clearance from the FDA to commence a Phase I trial in myeloproliferative disorders.
