Washington Editor

Like many companies that had signed research and development agreements with Dublin, Ireland-based Elan Corp. plc, Ribozyme Pharmaceuticals Inc. has been notified that its joint venture in breast cancer has concluded.

For Ribozyme (RPI), the news follows a year of ups and downs noted by a reduction in staff (from 120 to 90), possible delisting by Nasdaq and a plan to focus its research in a new direction. (See BioWorld Today, Feb. 13, 2003, and Aug. 16, 2002.)

As part of its own restructuring plan, Elan has dropped oncology programs in order to focus on neurology, pain management and autoimmune diseases. Elan and RPI were developing a ribozyme-based product called Herzyme. (See BioWorld Today, Aug. 12, 2002.)

Financially, Howard Robin, president and CEO of RPI, told BioWorld Today that no money will change hands. Instead, Elan will transfer its 19.9 percent interest in Medizyme Pharmaceuticals Ltd. (established for the development of Herzyme) to RPI in exchange for a portion of any future license fee, development revenues and royalties on commercial sales of Herzyme. If the drug never makes it to market, Robin said Ribozyme will not be responsible for payments.

Medizyme successfully completed a Phase I trial designed to evaluate Herzyme in patients with metastatic breast cancer whose tumors overexpress HER2.

Herzyme works by targeting and reducing gene expression of the epidermal growth factor receptor HER2.

Robin plans to license or partner Herzyme, mainly because the company has its eye elsewhere.

Its new area of focus is RNA interference. RNAi "silences" gene expression by deploying small interfering RNA, called siRNA, to degrade messenger RNA, which is the link between DNA and proteins.

"We see ourselves as a leader in the field of RNAi and we believe we will be the first company to demonstrate in a real way, as a real therapeutic, efficacy in animals," Robin said. "We expect to be the first company in the clinic with an RNAi compound."

RPI is using RNAi applications for research in hepatitis B and C, and macular degeneration. Robin hopes to have animal data in hepatitis B by the middle of the year.

The company's belief in RNAi has transferred into a $48 million financing agreement signed in February, pending a stockholder vote scheduled Wednesday.

RPI has agreed to sell $48 million in its stock and warrants to The Sprout Group, of New York; Venrock Associates, of New York; Oxford Bioscience Partners, of Boston; Techno Venture Management, of Munich, Germany; and Granite Global Ventures, of Menlo Park, Calif. (See BioWorld Today, Feb. 13, 2003.)

Terms would give the investors the right to appoint four designees to RPI's board, which, along with the stock ownership, would give them a controlling interest.

Wednesday, RPI shareholders will vote on the plan along with a reverse stock split.

Meanwhile, Robin says he'll appeal Nasdaq's delisting letter issued because the company failed to comply with the $1 minimum bid price and the $10 million minimum stockholders' equity requirements for continued listing. On Friday, RPI's stock (NASDAQ:RZYM) closed at 45 cents, down 3 cents.

"The appeal will take place after a hopefully favorable shareholder vote," Robin said. "Our upcoming reverse stock split plus the $48 million funding combined would put us well over Nasdaq's minimum requirement."

Elsewhere in the pipeline, RPI and Chiron Corp., of Emeryville, Calif., recently completed a Phase II trial of Angiozyme, an anti-angiogenesis drug, in metastatic colorectal cancer and are scheduled to present the data at the American Society of Clinical Oncology meeting in June. Last year the companies failed to achieve statistical significance in a Phase II trial of Angiozyme in metastatic breast cancer.

RPI discontinued a study last year of Heptazyme, also a ribozyme-based drug, after one animal in a yearlong study developed a detached retina. (See BioWorld Today, May 1, 2002.)