Small Cell Lung Cancer
The Need
Lung Cancer is the world’s most frequently occurring cancer and often has no effective treatment. The World Health Organization (WHO) states that there are 1.2 million new cases diagnosed annually and 1 million people die from lung cancer each year. WHO also reports that worldwide more people die each year from lung cancer than from any other cancer.
Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. Thus, there are approximately 240,000 new cases of SCLC each year. Those with limited SCLC who receive chemotherapy have a 2-year survival rate of 20-30% and a 5-year survival rate of 10-15%.
People with advanced SCLC have average survival duration of 6-9 months. Our SCLC library represents a viable opportunity to address this important therapeutic need and the large worldwide market for an orally effective and nontoxic treatment for SCLC.
Our Solution
COTI has developed a targeted library of 10 highly effective small molecules with low toxicity. Three compounds within this SCLC library have completed in vitro and animal testing. Our lead compound COTI-2 is a novel, easily synthesized small molecule originally designed and optimized for oral treatment of SCLC. COTI-2 has shown highly promising preclinical results indicating:
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Inhibition of Akt/PKB phosphorylation in cancer cells resulting in apoptosis or programmed cell death.
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Excellent in vitro activity in several human cancer cell lines including SCLC.
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In vitro activity at very low nanomolar dose levels in 4 aggressive human brain cancer cell lines.
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Low acute toxicity in escalating dosing according to standard test protocols. Examination of tissues and organs from treated animals demonstrated no drug induced abnormalities.
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Repeated doses with COTI-2 have not produced any evidence of emerging in vitro
resistance in human SCLC. In comparison, repeated treatment with current SCLC drugs Cisplatin and Paclitaxel does produce resistance compared with parental cell lines.
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Excellent in vitro efficacy in human SCLC lines with known resistance to both Cisplatin and Paclitaxel.
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Good in vitro metabolic stability in a human liver microsomal enzyme system with effective drug retention.
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Significant in vivo activity/growth inhibition in an athymic mouse model of human SCLC compared with Cisplatin and Paclitaxel.
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Significant in vivo activity/growth inhibition in 2 other separate athymic mouse models of human SCLC.
Based on these encouraging preclinical results COTI is moving forward immediately with its plans to complete the necessary animal pharmacokinetic and toxicity testing (i.e. PK/Tox testing) required for the submission of an Investigational New Drug (IND) application to Health Canada.
The balance of the SCLC Library consists of 2 additional scaffolds and 7 molecules. Preclinical development of the next two SCLC compounds is in progress.
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