A pain product developed by Rinat Neuroscience Corp. came full circle on Tuesday with the announcement of a co-development and joint commercialization agreement with Genentech Inc.

South San Francisco-based Genentech was responsible for the early technology that Rinat later licensed and humanized to create RI 624, an anti-nerve growth factor antibody that blocks NGF from binding to its target.

Now that technology is back in Genentech's hands, after the company exercised its option for the worldwide rights. Genentech and Palo Alto, Calif.-based Rinat will share all costs and profits of the Phase I product. Rinat also will receive up-front payments and an equity investment from Genentech.

"Less than 2 percent of the biotech/big pharma deals are profit-sharing deals," said David Pritchard, Rinat's chief business officer. "Most of those deals are done after Phase II, so it's unusual for a company of our size to get one of these deals."

Pritchard would not disclose the percentage of profits that each company will share, but he did say the up-front payment is $20 million and the equity investment is "minor."

"One of the other things I'm excited about is there's a financing vehicle as part of the deal that helps fund our portion of the costs," he told BioWorld Today.

While RI 624 will be developed in a variety of pain indications, Genentech expects to focus mainly on cancer pain. The company originally cloned the NGF target in 1983. Privately held Rinat was founded in 2001 when Genentech made a strategic decision to focus on other programs and granted Rinat broad licenses to its key neuroscience assets. (See BioWorld Today, Nov. 7, 2001.)

"There's three key focuses to our business: oncology, immunology and angiogenic disorders. This latest agreement helps support our aim in oncology," said Caroline Pecquet, Genentech's associate director of corporate communications. "We aim to be the No. 1 U.S. oncology company in sales by 2010."

Pecquet said it is too early to discuss the market potential or development timelines for RI 624, which is Rinat's first clinical product. Pritchard said the companies will conduct Phase I and Phase I/II trials over the next one to two years, evaluating the product in several pain indications. With Genentech's acute care and hospital sales force, the product also could be marketed outside of cancer pain.

"One particular area that this drug might be used is for surgeries, such as appendectomies," Pritchard said.

The current Phase I trial is evaluating RI 624 in osteoarthritis of the knee. While Rinat has been studying an intravenous version of the product, the company hopes to develop a subcutaneous, self-injected version, as well. RI 624 is at least five years away from reaching the market, Pritchard said.

"We do not have a sales force at this point in time," he said, "but we do have co-promotion provisions," and Rinat would build its own sales force, if the drug gets approved.

RI 624 works by inhibiting NGF, making it distinct from all approved drugs for pain. In animal models, it has shown equal or better efficacy than opiates or non-steroidal anti-inflammatory drugs, and demonstrated a significantly longer half-life of two to three weeks as compared to a half-life of hours to days for other pain therapeutics.

"Antibodies traditionally have lower side effects," Pritchard said. "The hope would be to have an efficacious drug with lower side effects."

NGF is a member of the protein family called neurotrophins. It plays a role in the growth of certain sensory neurons. The inhibition of NGF might help in treating pain since injury and inflammation induce the synthesis and stimulate the release of NGF.

The need for new pain drugs is considerable, as opioids and morphine can be addictive. Rush Limbaugh's addiction to Oxycontin and the removal from the market last month of Whitehouse Station, N.J.-based Merck & Co. Inc.'s painkiller Vioxx have only stressed the need for new pain drugs even more, Pritchard said. Vioxx, a COX-2 inhibitor, was removed after clinical data showed an increased risk of heart attack and stroke in patients taking the drug for 18 months or more.

"I think it's safe to say there are just classes and categories of pain that people find they just don't have the relief that they need," Pritchard said.

Genentech's stock (NYSE:DNA) dropped $1.02 on Tuesday, to close at $49.30.