Indigo Pharmaceuticals Inc. jumped headfirst into cardiovascular drug development by licensing INDI-702 (previously NM-702) from Nissan Chemical Industries Ltd. and Taisho Pharmaceutical Co. Ltd.

In exchange for an undisclosed up-front fee, development milestone payments and royalties, New York-based Indigo gained exclusive worldwide rights to INDI-702 except in Japan, South Korea, China and Taiwan. In those countries, Nissan and Taisho, both of Tokyo, will continue ongoing Phase II trials with the drug (known in Japan as NT-702) and manage subsequent development and commercialization efforts.

INDI-702 is an orally active, dual-inhibitor of phosphodiesterase III and thromboxane A2 synthetase. Indigo initially will develop the drug for intermittent claudication caused by arteriosclerosis obliterans, a hallmark of peripheral artery disease that affects about 6 million Americans. Intermittent claudication is transient pain that usually occurs during exercise when blood flow through occluded peripheral arteries cannot meet the body's needs.

"These patients are very compromised in terms of quality of life," said Indigo President and CEO Carol Ann Satler. "They are effectively robbed of their mobility."

The only drug currently approved in the U.S. to treat intermittent claudication is Pletal (cilostazol, Otsuka America Pharmaceutical Inc.). It, too, is a phosphodiesterase III inhibitor, and it is contraindicated in patients with congestive heart failure. Valentis Inc. tried to get around that contraindication by developing the poloxamer VLTS 934, but it was discontinued after a failed Phase IIb trial. (See BioWorld Today, July 12, 2006.)

Satler said Indigo will try to differentiate INDI-702 from Pletal based on quality of life. While the phosphodiesterase inhibition in both drugs provides vasodilation, the thromboxane A2 synthetase inhibition in INDI-702 adds an antiplatelet effect. Satler added that antiplatelet agents are often prescribed in that patient population, although they do not specifically address intermittent claudication.

In a randomized, double-blind, placebo-controlled Phase II trial conducted in the U.S. by Nissan and Taisho, INDI-702 significantly (p=0.004) increased peak walking time on a treadmill compared to placebo.

The drug also improved physical component, physical functioning, walking distance and stair climbing quality-of-life scores. INDI-702 generally was well-tolerated with adverse events typical of vasodilators.

Based on the data, Indigo plans to initiate Phase III trials with INDI-702 in the first half of 2008. The Phase III program likely will include three parallel trials enrolling about 2,000 patients in the U.S., Canada and Europe. Like the Phase II trial, the Phase III studies will focus on both walking time and quality of life. If all goes well, Satler predicted the drug could be filed in the U.S. and Europe in 2010 and potentially launched with a partner by 2011.

In Japan, Nissan and Taisho are studying INDI-702/NT-702 in additional indications, including asthma, stroke and intermittent claudication caused by spinal canal stenosis. In the asthma space, MediciNova Inc.'s Phase III drug MN-001 also inhibits thromboxane A2 and phosphodiesterases III and IV, among other inflammatory mechanisms.

Satler said Indigo eventually will look at INDI-702 in other indications as well. The company also is building its pipeline through the acquisition of late preclinical and clinical cardiovascular drugs, and Satler said they hope to identify another candidate "in the next month."

Indigo also will pursue financing in the coming weeks, initially from high-net worth individual investors and later from institutional investors. Company-builder Paramount BioSciences LLC provided the initial funding for the licensure of INDI-702 by holding company Milford Sound Sciences Inc. Satler changed the name to Indigo when she came on board last month because she wanted "something people could remember easily and spell easily."

For now, the Indigo team consists solely of Satler, who previously worked with the Sanofi-Aventis Group on cardiovascular drug development, including the antiplatelet blockbuster Plavix (clopidogrel). She plans to bring on four additional employees within the next week to focus on clinical, medical, regulatory and manufacturing issues. In the interim, Paramount's team is providing the fledgling company with support.