With an approach described as "assisted suicide for cancer cells," Denver-based start-up ApopLogic Pharmaceuticals LLC was formed earlier this year to develop and commercialize technology that emerged from the University of Colorado.

Like the name suggests, the company targets apoptotic pathways found in tumor cells and proliferating lymphocytes using technology that emerged from its seven scientific founders and members of the University of Colorado Cancer Center. Initially brought together "to capitalize on one technology," said Founder, President and CEO Richard Duke, the company now has an early stage development pipeline led by two preclinical compounds, both of which are about a year away from entering the clinic.

To date, ApopLogic has raised close to $1 million, including $800,000 in SBIR funds and another $100,000 from UC's proof-of-concept investment program. Most recently, the company received a $10,000 Venture Showcase Award at the Colorado BioScience Association meeting.

Those funds are supporting early efforts, and the company hopes to secure a commitment from the National Cancer Institute for toxicology studies and manufacturing of its lead product, Breceptin, a neuropeptide growth factor receptor antagonist to target a range of cancers.

Though Breceptin is the most advanced, it actually was the availability of a Fas ligand-based therapy, Fasaret, that led to the creation of ApopLogic.

"I've always had a tremendous interest in working on things that induce apoptosis," said Duke, who along with Don Bellgrau, previously founded GlobeImmune Inc., also of Denver. At the time it was formed, GlobeImmune licensed two technologies from UC: a recombinant yeast-based platform that has yielded several clinical compounds and a Fas ligand technology it licensed to Sandoz GmbH, later acquired by Basel, Switzerland-based Novartis AG.

Not a high priority to Novartis after the merger, the Fas ligand program was handed back to GlobeImmune in 2003, but by that time, it no longer fit into GlobeImmune's business strategy. The program then returned to its original developers at UC.

"The university asked us if we'd like to have it," said Duke, who had stepped down from his position as president and CEO of GlobeImmune in 2002, though he still remains actively involved in the firm's progress. Then once "we got the technology back, we started to think about putting together a company."

But first they needed some proof that the compound would work against cancer, especially since it failed completely in early studies in transplant rejection, the indication for which Novartis had licensed it.

Duke and Bellgrau enlisted the help of veterinary scientist Jaime Modiano, who decided to test a DNA-encoding Fas ligand in dogs with oral melanoma, rather than using the traditional approach of injecting tumor cells into mice. The results showed that a single injection directly into the tumor demonstrated significant shrinkage in seven days in four of five animals, Duke said.

From there, the founders applied for the SBIR grant to conduct a Phase I study of the Fasaret in dogs with osteosarcoma, a tumor type closely related to human cancer.

"The company really started with the application for that grant," Duke said.

The addition of Breceptin came about when Duke approached Paul Bunn, a lung cancer expert with UC's cancer center, about joining ApopLogic's scientific advisory board.

"He informed me that the university had some other technology of interest," he told BioWorld Today, "so I went to the technology transfer office and discovered what has now become our lead program."

Breceptin is aimed at targeting bradykinin, a peptide that is expressed prominently on lung cancer cells. By targeting the bradykinin receptor, the hope is to induce apoptosis.

ApopLogic is hoping that NCI will assist in toxicology and manufacturing work for Breceptin to allow the company time to raise a seed venture capital round to begin clinical studies. Beyond that, the firm likely will seek a modest Series A.

"We're looking to keep our cash flow low," Duke said, adding that company, which right now consists only of its founders, plans to contract out research, manufacturing and toxicology work.

"It's difficult for start-ups these days," he said, "because a Phase I trial is just not worth that much anymore" to investors, who are putting most of their money into later-stage firms.

"If we can get the NCI [to help], we'd have a little bit of cushion for bringing in some money," Duke said. "We're hopeful that we can bring in some high-quality investors."

In addition to Duke and Bellgrau, the company's founders include Bunn, Modiano, Daniel Chan, Lajos Gera and John Stewart.