Critical Outcome Technologies Inc announced positive test results from a series of animal experiments carried out at a prominent Canadian cancer research facility with COTI-2 as a single agent against an aggressive strain of triple negative human breast cancer (TNBC); MDA-MB-231-luc.

The significance of this development is that TNBC is a difficult-to-treat cancer subtype that does not have an approved standard-of-care and does not respond to current hormone-based and targeted therapies. TNBC is a very aggressive cancer, with higher rates of metastases and poorer survival rates than other breast cancer subtypes.

In this particular study, animals were divided into three study groups: Group 1 (Control) animals received vehicle only (no treatment), Group 2 (Pretreatment) animals received oral COTI-2 (200 mg/kg) daily for 5 days prior to tumour implantation and daily for 5 days/week for the duration of the study and Group 3 (Conventional) group received oral COTI-2 daily for 5 days/week once tumours had reached 100- 200 cubic mm starting on day 21 and for the remainder of the study.

The following results provide strong supportive evidence for the continued evaluation of COTI-2 for the treatment of breast cancer, including HER-2/neu and ER/PR negative disease - Control Group: Tumours grew quickly and reached maximum size by day 38 of the study. Pretreatment Group: Marked tumour growth inhibition (78.0%, p<0.001) compared to the Control Group at day 38 of the study. Conventional Group: Significant tumour growth inhibition (56.8%, p<0.005) compared to the Control Group at day 38 of the study (after only 13 doses of COTI-2). None of the study groups had any evidence of metastatic disease spread using whole body fluorescent imaging. Tumour growth inhibition in the Pretreatment Group was significantly greater than in the Conventional Group (78.0% vs. 56.8%, p=0.01). Treatment with oral COTI-2 as a single agent was well tolerated with no treatment deaths or
observable toxicity over the duration of the study.

"We chose to study this particular model of human breast cancer because it exemplifies an aggressive form of the disease that accounts for about 20% of all breast cancers. Moreover, we wanted to explore recent scientific data indicating that the PI3K/AKT/mTOR pathway is activated in TNBC. We were pleased to see impressive efficacy shown in this study," said Dr. Wayne Danter, president and CSO of COTI. "TNBC responds poorly to commonly used targeted therapies. There are high relapse rates following traditional therapies and as a result there is a clear unmet medical need. Drugs that we have previously studied in combination with COTI-2 like gemcitabine, doxorubicin and various taxols have demonstrated clear evidence of combination benefit and low toxicity in several other models of human cancers. Taken together these results are encouraging and support further evaluation of COTI-2 in combination with other agents like taxols for the potential effective treatment of triple negative breast cancer," said Dr Danter.

"We are delighted with these new scientific results which provide evidence to support the commercial development of COTI-2 in breast cancer," said Michael Cloutier, CEO of COTI. "We look forward to sharing this promising new data with parties who have expressed a licensing interest in COTI-2."

COTI-2 is a novel small molecule that acts by inhibition of Akt/PKB (Protein kinase B) phosphorylation that leads to caspase-9 activation in cancer cells resulting in apoptosis or programmed cell death.

COTI is formed around a unique computational platform technology called Chemsas, which allows for accelerated identification and optimization of targeted small molecules potentially effective in the treatment of human diseases for which current therapy is either lacking or ineffective.