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July 1, 2004
Kinex Achieves Significant R&D Milestones
Over a period of just 4 months (February-May, 2004), and with a very modest expenditure of funds, Kinex has made very significant progress toward the goal of selecting a drug candidate for progression to an IND and human studies. A group of 260 novel compounds were tested for their ability to inhibit the growth of a human colon cancer cell line (KM-12 cell line) and human lung cancer cell lines (H460 and A549 cell lines). These molecules were designed as improvements and extensions of the molecules that were part of the original business plan. The studies were done at the Southern Research Institute (SRI) in Birmingham, Alabama and at the Roswell Park Cancer Institute (RPCI) in Buffalo, N.Y.
The first major milestone achieved in this four-month period was that two of the novel compounds, KX1-136b and KX-305, both inhibited the growth of colon cancer cells at concentrations below 100 nanomolar. This represents an increase in potency of more than 50-fold over the early prototype compounds. More importantly, inhibition of tumor growth is also occurring in a concentration range that should be found in plasma after reasonable oral doses of drug. The human lung cancer cell lines H460 and A549 were also inhibited with similar potency.
The next step was to re-synthesize both drug candidates in quantities sufficient to test them in animals, and this too has been completed. KX1-136b and KX-305 are now both being tested in mice in a 3-part study at RPCI. The first part of the study was to determine the highest dose of each drug that could be tested in mice without producing any toxicity or significant weight loss. This part has been completed and represents the achievement of the second major milestone i.e.both drug candidates are safe, as were the earlier prototypes, and can now be tested for their effect on human tumor (colon) growth in immunocompromised (SCID) mice. Based on the positive results already obtained in a pilot study in these mice, it is highly likely that these drugs will effectively inhibit tumor growth when tested in a larger study.
The third part of the study involves measurement of the levels of each drug candidate in the blood and in the tumor. This data will be obtained at the same time that the drug’s effectiveness in blocking tumor growth is measured. These data will then allow us to determine whether either or both of these candidates should be developed further, and what types of improvements should be designed into the next series of compounds to be made, if needed. The chemical structures of KX1-136b and KX-305 are such that improvements can be easily made if needed.
Inhibition of human tumor growth in mice by new and novel types of drugs is considered a major milestone by venture capitalists and other large investors when determining their interest in new companies. Reaching this milestone, without the toxicity seen using current anti-cancer drugs, is a major advance and achievement and should place Kinex in a very strong position for attracting additional capital to further develop its Src kinase inhibitors and other R&D programs.