COTI-2 Is an Effective Single Agent With Low Toxicity in Multiple Xenograft Models of Human Cancers

Critical Outcome Technologies Inc. (COTI) (TSX VENTURE:COT) released a summary of animal data today clearly demonstrating that COTI-2 is an effective single agent with low toxicity in six different xenograft models of human cancers.

Generally, attempts to extrapolate from an individual animal model of human cancer to successful human drug trials have been unsuccessful. However, Voskoglou-Nomikos et al (Clinical Cancer Research, 2003) have provided evidence that where an early stage compound produces significant tumor growth inhibition in multiple xenograft models of human cancers there can be a significant correlation with that compound's Phase 2 clinical success. For that reason COTI-2, a novel AKT inhibitor, was studied in multiple xenograft models of a range of human cancers.

COTI-2, when administered at doses from 3 mg/kg to 125 mg/kg and with dosing schedules ranging from 3 times per week to 5 times per week, significantly inhibited tumor growth in multiple human cancers. These results are summarized in Table 1 below. COTI-2 is an effective single agent since doses as low as 3 mg/kg and a low dose short course of just 5 treatments given over 10 days produced significant tumor growth inhibition in different tumors. In addition, higher doses given up to 5 times per week and for longer periods produced even greater tumor growth inhibitor effects (average TGI equals 63.3% for treatments equals 19 days). COTI-2 also demonstrated low toxicity since doses up to 125 mg/kg administered for up to 36 days were well tolerated by the animals.

Table 1: A summary of the single agent activity of COTI-2 in six xenograft
models of human cancer

----------------------------------------------------------------------------
Cell     Cancer                  Dose          Tx              TGI
line       Type       Model   (mg/kg)  Route Days Schedule     (%)   p Value
----------------------------------------------------------------------------
          Small                                    3 times         less than
SHP77      Cell  Metastatic     3 - 4     IP   38      per    96.2      0.01
           Lung                                       week
         Cancer
         (SCLC)
----------------------------------------------------------------------------
                                Up to              5 times         less than
N417       SCLC       Solid        30     IP   29      per    56.8      0.05
                                                      week
----------------------------------------------------------------------------
                                Up to              5 times         less than
HT29      Colon       Solid        10     IP   48      per    54.9      0.05
                                                      week
----------------------------------------------------------------------------
                                                   3 times         less than
U87       Brain       Solid   Up to 8     IP   10      per    30.0      0.05
                                                      week
----------------------------------------------------------------------------
                                Up to              5 times         less than
U937   Leukemia       Solid        20     IP   19      per    43.8      0.13
                                                      week
----------------------------------------------------------------------------
                                Up to                 Dose
A2780   Ovarian       Solid       125     PO   36    range    64.7      0.05
                                                   finding
----------------------------------------------------------------------------
IP equals         PO equals     TGI% equals Tumor Growth           Tx equals
Intraperitoneal        Oral     Inhibition Percent                 Treatment

"We are very pleased with the significant single agent efficacy and low toxicity of COTI-2 in multiple animal models of human cancers. While traditional cancer chemotherapy is frequently limited by significant toxic side effects, it is drug candidates like COTI-2 that represent a new generation of less toxic drugs with good anti- tumor activity," said COTI President and CSO, Dr. Wayne Danter. "This data clearly supports the continued development of COTI-2 into human clinical trials. We remain focused on solidifying a licensing agreement with an organization that can assist in advancing COTI-2 forward," said COTI CEO Mr. Michael Cloutier.

About Critical Outcome Technologies Inc. (COTI)

COTI is formed around a unique computational platform technology called CHEMSAS(R), which allows for the accelerated identification, profiling and optimization of targeted small molecules potentially effective in the treatment of human diseases for which current therapy is either lacking or ineffective. Currently, six targeted libraries of lead compounds are under active development; small cell lung cancer, multiple sclerosis, HIV integrase inhibitors, acute myelogenous leukemia, colorectal cancer and Alzheimer's disease.

For further information, please visit the website at www.criticaloutcome.com.

SOURCE: Critical Outcome Technologies Inc. (COTI)

Critical Outcome Technologies Inc. (COTI)
Michael Barr
Director of Business Development and Marketing
519-858-5157
www.criticaloutcome.com

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