By Randall Osborne

Taking aim with its enzyme-replacement therapy at a rare but potentially fatal disease that strikes children, BioMarin Pharmaceutical Inc. raised $10 million in a round of private financing.

The two-year-old company with 12 employees, based in Novato, Calif., is on the fast track toward a new drug application for its treatment of mucopolysaccharidosis (MPS) I, which is one of seven similar diseases, said John Klock, president of BioMarin.

"What the FDA has done, which is quite unusual, is allowed us to do Phase I, II and III [trials] all in one," Klock said. "We're looking at approval this year."

The trials in 10 patients began last December. BioMarin's enzyme drug also has been granted orphan status by the FDA, giving the company market exclusivity, Klock said.

BioMarin's financing consisted of $5 million from BB BioVentures LP, of Cambridge, Mass. Other participants were Glyko Biomedical Ltd., which owns a 40 percent stake in BioMarin and is located in the same city; and Grosvenor Capital, of Washington.

BB BioVentures is a pure technology fund. Its general partner is a joint venture between MPM Capital LP and its affiliate, Venture Asset Management (VAM) LLC, also of Cambridge; and Bellevue Asset Management, of Zug, Switzerland. Late last year, VAM raised $200 million, more than half of it from Europe, to fund BB BioVentures. (See BioWorld Today, Dec. 18, 1997, p. 1.)

With its MPS I drug, BioMarin hopes to duplicate the success of Genzyme Corp., which earns more than $300 million annually from sales of its enzyme treatment for Gaucher's disease, Klock said. Cambridge, Mass.-based Genzyme sells Cerezyme (recombinant glucocerebrosidase) and Ceredase, the natural version of the enzyme, derived from human placenta.

Like Gaucher's disease — which is characterized by liver and spleen enlargement, with bone weakening — MPS I is rare. Patients "can't break down sugar chains," Klock said. The condition causes carbohydrate materials to build up in all parts of the body. Symptoms of MPS I include enlargement of the liver and spleen, skeletal deformity, vision impairment, stunted growth, hearing loss and fluid on the brain.

MPS I is a genetic disease that afflicts more than 1,000 patients, primarily children, in the developed world. "It's not as common as some diseases, but Genzyme does well treating 1,500 patients," Klock said.

"Each patient has a little different variant of the problem," Klock said. Each [of the seven varieties of MPS] is rare, but one in 50 people carries the genetic predisposition for one of them."

The most severe form of MPS I is Hurler's syndrome, which is crippling and fatal.

BioMarin chose enzyme-replacement therapy and MPS I as its areas of research "based on time-to-market, primarily, and risk factors," Klock said.

"We wanted a technical area where other people weren't working," he said. "We also wanted an area where the technology was not so leading edge, like gene therapy or genomics. We used conventional recombinant DNA technology to do everything."

Enzyme deficiencies, Klock said, "are all around us," playing a part in diseases such as cystic fibrosis, hemophilia, emphysema and heart disease. "All the blood-clotting proteins are enzymes." Brain chemicals related to enzymes are involved in depression, he added.

"Gene therapy has got a lot of buzz, but it's not going to work, not in my lifetime," Klock said. "You can't express enough enzyme. You get the gene in, you get it working and you infect people with the virus, but it's very complicated."

As an example, he cited bone marrow transplants, in which the first part of the procedure — placing the genes — cannot ensure the enzymes will be adequately expressed for a successful operation.

Goal Focused On Getting To Market

BioMarin will limit its scope at first, Klock said.

"Enzymes that control inflammation, we're certainly going after," he said. "And enzymes involved in activating sperm." The company has products in clinical development for fungal infections, burn and wound care, and male infertility.

"We're simply trying to mine this field and come up with [drugs] that are unique and have killer applications," Klock said. "For our first few products, we wanted to look at getting approvals quickly."

Quickness is the name of the game, he added, for the sake of MPS I patients as well as for BioMarin's balance sheet.

"Many of these children use up their families' health-insurance caps, $1 million, during their short lives," he said, adding that enzyme therapy "won't result in an instant cure, but more likely will alter the quality of life and enable the children to grow."

The company may attack adult forms of the disease later. Meanwhile, the trial time for MPS I will be short. "If it's going to work, it will work right away," Klock said. "In dog models, it worked in several weeks."

Glyko, of which Klock also is president, developed carbohydrate analysis systems based on its Fluorophore-Assisted Carbohydrate Electrophoresis (FACE) system, which includes recombinant enzymes, chemicals, imaging and software.

The company currently is working to develop a more advanced version of the company's diagnostic test system for inborn errors of metabolism in children, or lysosomal storage diseases, which include at least 35 diseases such as Tay-Sachs and Gaucher's. *