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Calando Inks Deal with NCI to Develop Cancer Drugs; Deal Does Not Mark First Pipeline Program


Calando Pharmaceuticals said this week that it has established a collaboration with the National Cancer Institute to develop RNAi-based treatments for a form of pediatric cancer.

The program, however, is not the company's first formal drug-development program, which has yet to be announced, according to Calando CEO John Petrovich.

Calando said it will work with the NCI's pediatric oncology branch to develop treatments for neuroblastoma, a malignancy that forms in the nerve tissues of the adrenal glands, neck, chest, or spinal cord. It often develops during early childhood, usually in children younger than 5 years, according to the NCI.

According to the company, the partnership, which is expected to last three years, will involve "preclinical research and its translation into human clinical trials." The partners will share responsibilities for development of the various therapeutics.

Petrovich told RNAi News this week that the NCI approached the company about forming the collaboration following a presentation of in vivo data showing that Calando's delivery technology could be used to deliver siRNAs, with anti-tumor effect, in a mouse model of Ewing's sarcoma. The data were presented at the annual meeting of the American Association of Cancer Research last year.

"The idea is that we're basically providing the delivery system and the expertise … and [the NCI] is going to do a lot of the animal work and preclinical work, and ultimately this could extend up to doing clinical trials."

The technology comprises a linear, cyclodextrin-containing polycation that is able to bind to the anionic backbone of an siRNA. When mixed together, the polymer and siRNA self-assemble into nanoparticles, roughly 50 nanometers in diameter, which are protected from nuclease degradation in blood serum.

According to Calando, the cyclodextrin in the polymer allows stabilizing agents to be attached to the surface of the particles. These agents have terminal adamantane groups that form inclusion complexes with cyclodextrin and contain polyethylene glycol, which prevents aggregation while preventing degradation. Additionally, ligands to cell-surface receptors can be covalently attached to the adamantane-PEG modifier, which allows the particles to be targeted to tissues of interest.

The AACR session at which Calando's data were presented, was attended by Javed Khan, chief of the oncogenomics section of NCI's pediatric oncology branch, Petrovich said. "He saw it and they called us and invited us to speak with them," he said. Neuroblastoma "was a program [the NCI] picked and wanted to advance. It seemed like an interesting target for us, as well."

Thus far, the NCI and Calando have signed a letter of intent to a cooperative research and development agreement, allowing the partners to begin work while the actual agreement is finalized. Petrovich said that he expects the CRADA to be formally in place within about six months.

"The idea is that we're basically providing the delivery system and the expertise … and [the NCI] is going to do a lot of the animal work and preclinical work, and ultimately this could extend up to doing clinical trials," he said. Petrovich added that Calando is in discussions with a number of companies about making the siRNAs for the NCI collaboration.

He declined to specify the targets for the RNAi drugs being developed under the collaboration.

As for what will become of any drug candidates developed by Calando and the NCI, Petrovich said that the CRADA will provide the company with a "right of first negotiation to license" any intellectual property resulting from the partnership.

Starting a Start-Up

At about one year old, Calando is still in the process of setting itself up as a drug developer — and this process includes defining its pipeline, Petrovich said.

The neuroblastoma project "is not the one we're doing on our own," he said. "We're still keeping that [one] under wraps. We're still doing preliminary work and haven't announced it yet." He added that the company plans to disclose further details about its pipeline "some time by the summer."

Petrovich did state that Calando's first pipeline program would most likely be in oncology, given the background of the company's founders, which include Mark Davis, a California Institute of Technology researcher who is also a member of the experimental therapeutics program of the Comprehensive Cancer Center at the City of Hope.

Meanwhile, the company has fully ramped up operations at facilities in Duarte, Calif., leased from the City of Hope, Petrovich said, although the company is planning to begin the search for a bigger space within about six months. "We're going to stay in the area, though, because it behooves us … to be proximate to the City of Hope and CalTech."

Petrovich also said that Calando continues to search for an industry partner, after having failed to meet a previously disclosed timeline of signing a deal in 2005 (see RNAi News, 4/29/2005).

"If something had happened we would have announced it," he said, adding that "we're talking to people all the time."

Petrovich declined to provide a new timeline, noting that partnership discussions "take their own course."

— Doug Macron ([email protected])

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