Aminex Therapeutics, Inc. 

PRODUCT DEVELOPMENT STRATEGY

Cancer is the second most common cause of death in the western world. According to the American Cancer Society, approximately 560,000 cancer-related deaths were projected to occur and 1.4 million new cases were projected to be diagnosed in the U.S. during 2008 (1). Demographic trends and improved screening are expected to increase the rate of cancer diagnoses, as 85 percent of cancers occur in the over-55 year old population. The National Cancer Institute estimates that the median age of cancer patients at death was 73, and the overall cost of cancer in the U.S. during 2007 was $219 billion.

1. Head and Neck - Squamous Cell Carcinoma - The company intends to file an IND application with the FDA in the second quarter of 2010 for use of PDT against HNSCC.  The American Cancer Society estimated that the number of new cases of HNSCC reported in 2008 was 35,310 resulting in 7,590 deaths (1).  The Company has reported success in treating this disease using a mouse model of SCC with details provided in several scientific articles (2, 3).

2. Melanoma - Several reported and ongoing chemopreventative clinical studies are testing the efficacy of DFMO against skin cancers (4-6).  An estimated 62,480 new cases resulting in 8,420 deaths from melanoma in 2008 were predicted by the American Cancer Society for the United States (1). 

3. Colon Cancer - A recent groundbreaking study demonstrated the efficacy of oral DFMO for the chemoprevention of the re-occurance colon cancer (7).  In this placebo-controlled clinical trial of combination difluoromethylornithine and sulindac (a nonsteroidal anti-inflammatory drug), it was found that the 3-year treatment was associated with a 70% reduction of recurrence of all adenomas, and over a 90% reduction of recurrence of advanced and/or multiple adenomas, without evidence of serious toxicities. This proof-of-principle trial indicates that targeting polyamine synthesis and inflammation allowed prevention of this disease.  Furthermore, it highlights the potential that combination use of a biosynthesis inhibitor and polyamine transport inhibitor holds for treatment of this disease.  The American Cancer Society estimated 108,070 new cases of colon cancer were expected in 2008 which were projected to result in 49,960 deaths (1).

REFERENCES

(1) American Cancer Society. Cancer Facts & Figures 2008. Atlanta: American Cancer Society; 2008.
(2) Chen, Y.; Weeks, R. S.; Burns, M. R.; Boorman, D. W.; Klein-Szanto, A.; and O'Brien, T. G. Combination therapy with 2-difluoromethylornithine and a polyamine transport inhibitor against murine squamous cell carcinoma. Int. J. Cancer 2006, 118, 2344-2349.
(3) Burns, M.R.; Graminski, G.F.; Weeks, R.S.; Chen, Y.; O’Brien, T.G. Lipophilic lysine-spermine Conjugates are potent polyamine transport inhibitors for use in combination with a polyamine biosynthesis inhibitor. J. Med. Chem. 2009, 52 (7), 1983-1993.
(4) Einspahr, J.G.; Nelson, M.A.; Saboda, K.; Warneke, J.; Bowden, G.T.; Alberts, D.S. Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer. Clin. Cancer Res. 2002, 8(1), 149-55.
(5) Alberts, D.S.; Dorr, R.T.; Einspahr, J.G.; Aickin, M.; Saboda, K.; Xu, M.J.; Peng, Y.M.; Goldman, R.; Foote, J.A.; Warneke, J.A.; Salasche, S.; Roe, D.J.; Bowden, G.T. Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine. Cancer Epidemiol Biomarkers Prev. 2000, 9(12), 1281-6.
(6) see ClinicalTrials.gov (Trial Identifiers: 1. NCT00601640; 2. NCT00021294; 3. NCT00005884; 4. NCT00204789).
(7) Meyskens, F.L. Jr; McLaren, C.E.; Pelot, D.; Fujikawa-Brooks, S.; Carpenter, P.M.; Hawk, E.; Kelloff, G.; Lawson, M.J.; Kidao, J.; McCracken, J.; Albers, C.G.; Ahnen, D.J.; Turgeon, D.K.; Goldschmid, S.; Lance, P.; Hagedorn, C.H.; Gillen, D.L.; Gerner, E.W. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila Pa), 2008, 1(1), 32-8.