Antisense approach to scars

ENCINITAS, Calif.-In coordinated action that also included a $15.5 million Series A financing from Alta Partners, ProQuest Investments and RiverVest Venture Partners, Isis Pharmaceuticals Inc. and Excaliard Pharmaceuticals Inc. have announced a new collaboration to discover and develop antisense drugs for the local treatment of fibrotic diseases, including scarring. Isis granted Excaliard an exclusive worldwide license for the development and commercialization of certain antisense drugs not strategic to Isis. In return, Excaliard made an upfront payment to Isis in the form of equity and $1 million cash for the licensing of a particular undisclosed gene target.

Dr. Nicholas Dean, Excaliard CSO, notes that the Isis technology licensed by Excaliard has been clinically proven and that it promises multiple therapeutic opportunities in scarring, which 15-month-old Excaliard looks to commercialize over the relatively short term. Dean, who was VP of oncology and functional genomics at Isis before leaving the company 18 months ago, cites positive results in animal models of scarring and preclinical toxicology with the Isis technology as support for his optimistic outlook for early proof of concept in man and a rapid time to market. "Fibrosis represents a significant and expanding area of unmet medical need, and we believe that antisense offers unique advantages in this area for developing a completely new class of anti-fibrotic agents," he states.

Excaliard will function in most respects as a virtual pharma, Dean notes. Other than Dr. Dan Sauder, company CMO, and J. Gordon Foulkes, Ph.D., acting CEO and managing director of RiverVest Venture Partners-who co-founded Excaliard and provided the initial seed funding for the company-Excaliard will be lightly staffed and outsource almost all discovery and development work. "Our focus will be on topical application of antisense oligonucleotides where fibrosis and scarring occur," Dean summarizes.

According to Isis, during the first-generation development, substituting sulfur for oxygen allowed antisense compounds to reach trial in their initial indications, but the drug candidates had a short half-life and therefore had to be administered frequently. Now referred to as "second-generation chemistry", subtle changes have produced 10 to 15 times the potency with half-lives of two to four weeks for treatment of systemic diseases with infrequent administration.

Isis has commercialized its first antisense drug, Vitravene, and created a development pipeline of 18 drugs to treat cardiovascular, metabolic, inflammatory, cancer and neurodegenerative diseases.

"The broad applicability of our antisense technology enables us to build a substantial and diverse pipeline of antisense drugs. In order to maximize the value of this technology, a key component of our business strategy is to enter into promising partnerships that provide tremendous growth opportunities for antisense drugs in diseases that are outside our main therapeutic areas," says B. Lynne Parshall, executive VP and CFO of Isis.