Five years after licensing its first compounds from Novo Nordisk A/S, Sapphire Therapeutics Inc. entered another deal with the Danish firm for worldwide rights to ipamorelin, a small-molecule ghrelin mimetic in development for postoperative ileus.

Financial terms were not disclosed, but Bill Polvino, executive vice president of Sapphire, called the agreement a "long-awaited consummation of the relationship" between the companies.

Bridgewater, N.J.-based Sapphire was founded to develop compounds targeting the ghrelin pathway for metabolic and cancer indications. In its first licensing deal with Novo Nordisk in May 2001, the company picked up a portfolio of ghrelin mimetics and since has advanced the lead molecule, RC-1291, into Phase II studies in cancer anorexia/cachexia syndrome.

Ipamorelin was not included in the 2001 transaction, but it's a compound "we have really liked for some time," Polvino told BioWorld Today. "We're delighted that we got the opportunity to in-license it. It really rounds out" the company's ghrelin mimetic portfolio.

Ipamorelin, a synthetic growth hormone secretagogue, is designed to be administered via intravenous injection to stimulate gastrointestinal motility. The molecule binds to GHS receptors, which are found in high density throughout the gastrointestinal tract, and mimics the effect of ghrelin, which studies have shown helps promote gastric emptying.

The product also appears to have a sustained half-life in humans, and in Phase I studies showed good safety and tolerability data.

Sapphire intends to begin a Phase II study of ipamorelin early next year in patients with postoperative ileus, a condition involving the temporary disruption of gastrointestinal motility following surgery. In most cases, the only existing treatment involves keeping patients hospitalized and on I.V. fluids until motility is restored.

"This really is a sizeable unmet medical need," Polvino said. Ipamorelin is intended as an "acute, short-term treatment to speed recovery and get patients out of the hospital sooner."

In the postoperative ileus space, ipamorelin joins several other drugs in development, including Exton, Pa.-based Adolor Corp.'s Entereg (alvimopan), which received an approvable letter in 2005, and methylnaltrexone, from Tarrytown, N.Y.-based Progenics Pharmaceuticals Inc., which is readying for a Phase III trial.

Depending on results from further trials in postoperative ileus, Sapphire likely will consider testing ipamorelin in chronic indications, as well.

"We look at postoperative ileus as a prototype disorder of slow GI motility," Polvino said. "There are several other conditions where that mechanism of action may be beneficial, such as diabetic gastroparesis," a condition that slows the stomach's ability to empty. For now, Sapphire intends to develop the product "as if we're going to take it to the market ourselves," he said, though "we may seek a suitable partner at the appropriate point in development."

Meanwhile, Sapphire expects to report results from its Phase II trial of RC-1291 in cancer anorexia/cachexia "around the start of the new year," Polvino said, and pending positive results, might take that product into other related wasting indications.

RC-1291 is an oral, small-molecule ghrelin mimetic designed to be administered once daily. It has received fast-track designation from the FDA.