Oncology Programs
We have two oncology compounds, rhIGFBP-3 and INSM-18, in early development and both hold promise for the potential treatment for a variety of cancers. Preclinical models show that one or both treatments interact with the IGF-1 system to reduce tumor growth in models of breast, prostate, lung, colorectal and head and neck cancers. Although the oncology platform shows promise, the company's resources will be focused primarily on IPLEX™ and any further clinical trials in the oncology area are likely to be conducted either with a partner or potentially through out licensing.
Although IGF-1 is critical for normal growth and metabolism, aberrant signaling through this pathway is closely linked to the abnormal and unregulated growth of a variety of tumors. Blocking tumor-associated IGF signaling has prevented tumor growth in a variety of preclinical models. rhIGFBP-3 has demonstrated preclinical efficacy in numerous cancer indications, including breast, prostate, liver, ovarian and colon. Additionally, several lines of recent evidence, from various cell systems, have suggested that rhIGFBP-3 may play a more active, IGF-1-independent role in growth regulation of cancer cells, binding specifically with high affinity to the surface of various cell types and directly inhibiting monolayer growth of these cells in an IGF-1-independent manner. Recent independent studies have demonstrated that when IGFBP-3 is used in combination with other cancer therapies it can accentuate and even synergize the efficacy of standard cancer therapies. Paclitaxel-induced apoptosis is accentuated by rhIGFBP-3, which has been shown to sensitize cells to apoptotic signals such as irradiation and ceramides. Due to the high cost of trials in this oncology area we plan to identify a partner to co-develop rhIGFBP-3.
INSM-18 is an orally available small molecule tyrosine kinase inhibitor that has demonstrated selective inhibition of IGF-1 and human epidermal growth factor receptor (Her2/Neu). It has demonstrated anti-tumor activity in preclinical studies of breast, lung, pancreatic and prostate tumors. Two single dose Phase I clinical studies in healthy volunteers have been previously completed with INSM-18. In both studies, INSM-18 was safe and well tolerated. The University of California, San Francisco, has completed a dose-escalating Phase I/II clinical study designed to define the maximum tolerated dose of INSM-18 in patients with relapsed prostate cancer. The study consisted of a 28-day treatment period at each dose level to investigate the effect of INSM-18 on prostate-specific antigen levels. An analysis of the data collected from the study will be conducted. The results from this study will be used to design a potential Phase II clinical study which could be progressed either in collaboration with a suitable partner or through an out licensing arrangement.
