Aiming to advance its molecular-chaperone therapy for cancer, Conforma Therapeutics Corp. closed a $30 million private placement of Series C stock.

"We expect this round will last somewhere between two and three years," said Lawrence Fritz, president and CEO of San Diego-based Conforma.

The company is developing drugs directed to the heat shock protein 90 (HSP90) family of cellular chaperones that control protein conformations, including those of key signaling molecules in cancer.

Fritz founded the privately held company in 1999, basing its platform - first named HALT - on heat shock protein technology licensed from the Memorial Sloan-Kettering Cancer Center in New York. (See BioWorld Today, May 10, 2001.)

"It's all related to heat shock proteins," Fritz said. "There were specific analogues that fell within the HALT technology, and we've gone beyond that to other classes of compounds."

The chaperone approach is based on molecular conjugates between HSP90-binding molecules and pharmacological ligands. Two classes of natural products have been shown to bind with high affinity into the adenosine triphosphate-binding pocket of HSP90: bacterially derived benzoquinone ansamycins and the fungal metabolite radicicol.

The ansamycins include herbimycin A and geldanamycin - both first noted to have weak antibiotic activity but later shown to reverse transformation of cells by the v-src oncogene. They also degrade a set of signaling molecules that includes steroid receptors and several receptor tyrosine kinases.

"We think there's the opportunity for broad efficacy," said Fritz, since "essentially all tumor cells we've looked at are dependent" on the discovered mechanism.

"There are likely to be specific cancers that are more sensitive," he said.

Conforma's lead ansamycin product, CNF1010, is in preclinical work and the company expects to file an investigational new drug application in the first half of next year and start Phase I trials.

"We think there are going to be certain molecularly defined cancers where there's a good chance for single-agent compounds" developed by way of the HSP approach, Fritz said. "But, as with most compounds, physicians are going to look for ways to combine them in cocktails with other drugs."

Preclinical data have already suggested "strong synergies [between the HSP drugs] with various other, already used compounds," he added. "That's why there's been so much excitement in new mechanisms with reasons to think they will augment the activity of compounds that work by other mechanisms."

The HSP technology might also have applications against inflammatory illness, viruses and central nervous system disorders, Conforma said.

Behind the ansamycin product in the pipeline are "totally synthetic compounds designed to interact with various members of the HSP90 family," Fritz told BioWorld Today. "We made some very striking progress and we expect to be in the clinic in the not wildly distant future."

The round was led by S.R. One Ltd., of West Conshohocken, Pa., and included new investors Lilly BioVentures, of Indianapolis; Novo A/S, of Bagsvaerd, Denmark; RBC Capital Partners, of Toronto; and RiverVest Venture Partners, of St. Louis.

Also participating were existing investors Domain Associates of Princeton, N.J.; ProQuest Investments, also of Princeton; Forward Ventures, of San Diego; and Inglewood Ventures, also of San Diego.