Conforma Therapeutics Corp. raised $11 million more to advance its pipeline of small-molecule oncology drugs designed to target heat-shock protein 90 (Hsp90).

The funding represents the final tranche of the company's Series C round, bringing the total raised to about $41.5 million. Conforma completed the first tranche in 2003, raising about $30 million. (See BioWorld Today, Sept. 19, 2003.)

Since beginning operations in 2001, the San-Diego based company has raised a total of $58 million, said Lawrence Fritz, president and CEO of Conforma. He added that the recent investment should "allow us to go well into 2006."

Based on technology developed at the Memorial Sloan-Kettering Cancer Center in New York, Conforma's main focus is centered on Hsp90, described as a family of molecular "chaperones" that control protein shape and affect key signaling molecules involved in the growth and survival of tumor cells. The company's lead product, CNF1010, given intravenously, is in Phase I trials, and Conforma hopes to start the product in Phase II testing by the end of the year.

A second cancer product, CNF2024, is an oral formulation set to enter the clinic during the third quarter. Both of those "attack the chaperone target Hsp90," Fritz said, adding that the chaperones act as catalysts in cells to control and promote protein folding, and "in the case of Hsp90, can also direct protein degradation."

Heat-shock proteins have been visible lately, with Vancouver, British Columbia-based OncoGenex Technologies Inc. saying last week it planned to begin clinical trials in 2006 of OGX-427, a second-generation antisense drug, to target Hsp27, which is overexpressed in tumors. Also Stressgen Biotechnologies Corp. announced a restructuring plan to direct more of its resources toward its lead product, HspE7, which combines the immunostimulatory abilities of heat-shock proteins with recombinant technology. Victoria, British Columbia-based Stressgen expects to begin a pivotal trial later this year in a human papillomavirus-related disease. (See BioWorld Today, April 27, 2005, and April 29, 2005.)

For Conforma, Fritz noted that the "client" proteins - the cellular proteins that are chaperoned by Hsp90 - include "some of the most commonly deregulated signaling molecules in cancer."

He added that Hsp90 primarily served as a chaperone for HER2, the androgen receptor and mutant signaling proteins such as BCR-ABL, all of which are "very well-validated cancer-promoting molecules."

Both CNF1010 and CNF2024 are designed to interact with the Hsp90 proteins and "convert the chaperone from a machine that normally folds those signals into one that degrades those signals," Fritz said. For instance, the drugs can direct a tumor cell to attack HER2, and "not just inhibit HER2, but actually degrade it and eliminate it from the cell."

While CNF1010 is a form of the geldanamycin derivative 17-AAG, Conforma's CNF2024 is a totally synthetic compound. The company is working on other applications involving the Hsp90 target outside oncology, including autoimmune, inflammatory and central nervous system diseases.

"We also have some programs that have branched out, based on chemistry done with Hsp90," Fritz said. "Those have brought us into some additional areas in oncology.

The financing round was supported by the company's major investors, including Domain Associates, of Laguna Niguel, Calif.; Lilly Bioventures, of Indianapolis; Novo A/S, of Bagsvaerd, Denmark; RBC Capital Partners, of Toronto; RiverVest Venture Partners, of St. Louis; S.R. One Ltd., of West Conshohocken, Pa.; and San Diego-based firms Forward Ventures, Inglewood Ventures and ProQuest Investments.