West Coast Editor

About a week after disclosing a successful Phase I safety trial with its non-absorbed phosphate binder, ILY101, Ilypsa Inc. has signed a potential $92 million deal with Astellas Pharma Inc., which will market the drug in Japan.

Under the terms, Ilypsa gets $22 million up front and the remainder in milestone payments "spread evenly" throughout the development life of the product, said Gerrit Klaerner, vice president of business and corporate development for Santa Clara, Calif.-based Ilypsa. Klaerner, a co-founder of the company, was instrumental in making the deal with Tokyo-based Astellas.

"It was a very deliberate strategic decision to seek a Japanese partner," he said, and called Phase I "a good value-inflection point for this particular product."

Targeting hyperphosphatemia, or abnormally high blood concentrations of phosphorus often found in dialysis patients, the metal-free polymer, ILY101, binds phosphorous in the gastrointestinal tract. If high phosphorous levels are allowed to persist, they interact with blood calcium or parathyroid hormones, making patients more prone to calcium deposits in soft tissues such as the coronary arteries, thus boosting the risk of ischemic heart disease. In phosphate binders, Klaerner said, there are two worlds, metal and non-metal, and for decades physicians have been "mindful of loading more metal into the patient" through the use of metal-based drugs.

The Ilypsa drug's mechanism of action is similar to that of an approved, non-metal newsmaker - Cambridge, Mass.-based Genzyme Corp.'s Renagel (sevelamer hydrochloride), cleared by the FDA in 1998 for patients with end-stage renal disease on hemodialysis. Renagel sold $118.7 million in the first quarter of this year.

Jay Shepard, president and CEO of Ilypsa, said his company hopes to achieve advantages over Renagel on "a number of fronts," such as fewer doses and improved tolerability, but future clinical work will determine more precisely what those benefits might be.

From the same Genzyme platform are WelChol (colesevelam hydrochloride), approved and partnered with Sankyo Pharma Inc., of Tokyo, for cholesterol, and tolevamer, a non-absorbed polymer therapy in development to treat C. difficile-associated diarrhea. Ilypsa has ILY103, a C. difficile toxin binder, at the lead-optimization stage.

Also in the phosphate binder space is Fosrenol, approved in fall 2004, from Shire Pharmaceuticals Group plc, of Basingstoke, UK. Fosrenol is a carbonate salt of the rare-earth metal lanthanum. (See BioWorld Today, Oct. 28, 2004.)

Ilypsa's discovery platform involves a high-throughput screening system created by Symyx Technologies Inc., of which Ilypsa - which has raised $46 million since its inception in May 2003 - is a spinout. Ilypsa first was called Symyx Therapeutics Inc., and changed its name in 2004.

"We had a strong cash position before the [Astellas] deal," Shepard said, estimating that Ilypsa has adequate money "in the short and medium term" to move its drug candidates along. Next in the pipeline, "about a year behind" ILY101, is a potassium binder, ILY105. That product "could have a very similar partnering strategy" to the phosphate binder, which Ilypsa plans to market independently in the U.S., he said. Then comes ILY102, a sodium binder, then ILY104 for metabolic disease, and then ILY103.

"For these last three products, we're still examining partnering possibilities," Shepard said.