Cancer Therapeutics and Diagnostics
Esther Chang, Ph.D., professor of oncology at Georgetown University Medical Center and a consultant to SynerGene Therapeutics, described the company’s work in gene-based nanotech cancer therapeutics and diagnostics. SynerGene is developing man-made, virus-like nanoparticles to target primary tumors and metastases. These particles are composed of cationic lipid shells that encapsulate various molecular therapeutics, including tumor suppressor genes, which can be used against cancer, including therapy-resistant tumors.
Attached to these nanoparticles are tumor-targeting molecules, i.e., transferrin, folic acid, or a single-chain antibody fragment, directed against the transferrin receptor, which bind to their respective receptors that are overexpressed on tumor cells. Thus, when systemically delivered, these particles zero in on both primary tumors and metastases.
“We did not originally call the treatment a nanomedicine, although it actually was. We do now,” she said.
The company performed more preclinical animal studies than it needed for the IND. “Only one relevant species is required for animal models, which are not necessarily large animals,” said Dr. Chang. The key is determining and demonstrating which species is the most relevant for your particular agent, she added. To achieve that, SynerGene conducted numerous preclinical analyses in panels of tissues from mouse, rat, dog, and two monkey species, and found that the pattern of binding of its targeting molecule was most similar between human and mouse tissues.
SynerGene is poised to begin recruiting patients for a Phase I trial for delivery of the p53 tumor suppressor gene in patients with advanced solid tumors, at the The Mary Crowley Medical Research Center, located within the Baylor University Medical Center. The company also anticipates starting a second Phase I trial delivering the RB94 gene at the M.D. Anderson Cancer Center.
SynerGene is also developing gadolinium-encapsulated diagnostic nanoparticles as an MRI contrast agent, which can detect lung cancers 5 to 10 times smaller than currently distinguishable with CT, Dr. Chang reported.
“We worked with consultants to help us meet FDA requirements,” noted Dr. Chang. The expertise of consultants, many of whom have worked at the FDA, is especially important and helpful for academic researchers. “We also had pre-pre-IND meetings early on, which I recommend as they can truly help avoid much pain and suffering. On the whole, our dealings with the FDA have gone smoothly,” she said.
Referring to biotech products in general and not just to those based on nanotechnology, G. Alexander Fleming, M.D, president and CEO of Kinexum (www.kinexum.com) and former group leader of CDER’s metabolism and endocrine drug projects, also stressed the importance of clear pre-IND communication, in light of the fact that drug development is getting harder, riskier, and more expensive. He advised companies to maximize their contact with the FDA by asking concrete and not open-ended questions and making specific proposals.