New cancer drugs are always going to be of interest to VCs and developments in clinical trials, such as the use of biomarkers as surrogate endpoints, could help progress therapies to market.
Glen Clack, M.D., oncology research physician at AstraZeneca (www.astra zeneca.com), described the use of two biomarkers, both collagen breakdown peptides, in bone cells in the development of a first-in-class orally active kinase inhibitor that blocks invasion of the cancer. These drugs are particularly interesting, said Dr. Clack, given the failure of MMP inhibitors.
New imaging technologies and biomarkers are incredibly helpful for proof-of-concept, said Jrg Mller, vp global clinical development, Bayer HealthCare (www.bayer.com). But, he continues, for later stages of development, we will stick with measuring tumor diameter.
He also discussed the relative advantages and disadvantages of progression free survival (PFS), a surrogate endpoint in cancer trials, compared with five-year survival. In the U.S., PFS can be used for accelerated or full-approval of an anticancer drug, but the EMA is not so keen. There is room for improvement in getting harmonization on this, he added. New modalities, such as biomarkers and imaging, are good for hypothesis generation but need more validation.
Andrew Stephens, M.D., Ph.D., director of oncology scientific affairs at OSI Pharmaceuticals (www.osip.com), also talked about the use of biomarkers in trials of Erlotinib, which is used in the treatment of non-small-cell-lung cancer. One must be cautious about interpreting small, uncontrolled trials if the endpoint is a biomarker, he cautioned.
Finally, Agamemnon Epenetos, Ph.D., CEO of Somanta (www.somanta.com), discussed the use of imaging associated with HER-2 and MUC-1, a pan-cancer marker, to select patients for cancer treatments.
The company is also looking at hypoxia, a feature of most tumor tissue that tends to create resistance to all forms of treatment. Plasma osteopontin can be used as a biomarker of hypoxia to show which patients might benefit from Prodrax, a family of hypoxia-activated pro-drugs that Somanta is developing. This approach turns the tumors strength into its weakness, explained Dr. Epenetos.
Cancer therapy is also the focus of IRL Biopharm (www.irl.cri.nz), a company making microbial toxins for chemotherapy to be used either alone or as a payload to an antibody or other conjugate. The company developed processes that allow the fermentation of marine organisms requiring high salinity that have previously been hard to exploit. Besides contract research, IRL Pharma is also creating its own library of microbial toxins.
Another New Zealand company, Pacific Edge Biotechnology (www.pacificedge biotech.com), a spinout of the University of Otaga, is developing microarray-based diagnostics and prognostic tests in bladder, gastric, and colorectal cancer. These are intended for early diagnosis, monitoring for recurrence, and screening populations.
The bladder cancer assay, based on mRNA profiling of three susceptibility genes, is currently in clinical trials in Japan. The bladder cancer test has elucidated some pathways to work on, said David Darling, CEO.
The company is currently selecting Mabs for the ELISA-based gastric cancer test and hopes to get it into the clinic within a year.