Adolor Corp. plans to take its lead topical peripheral opiate analgesicinto human trials with a recently completed $9.6 million privatefinancing.
The privately held Malvern, Pa., company's lead technology istargeted toward opiate receptors on peripheral tissues, such as skin.During the inflammation cascade a sheath around the nerve endingsswells and opens. New opiate receptors then are created, migrate tothe area and are expressed at nerve endings, said Adolor Presidentand CEO John Farrar.
"If you stimulate those receptors you can mediate a substantialanalgesic effect," Farrar said. The lead compound, ADL 2-1294,initially will be developed to reduce pain associated with burns, but isapplicable to other painful conditions on or near the skin surface thatare associated with inflammation.
Opiate analgesics, such as morphine, stimulate receptors within thecentral nervous system. The advantages of Adolor's compound are itsability as act as a potent opiate agonist without crossing the blood-brain barrier (BBB). And, Farrar said, it can't be metabolized intosomething that can cross the barrier. Therefore the analgesic wouldn'tbe held to the same strict standards as narcotics, and would havereduced side effects because the brain receptors are not activated.
Adolor intends to file an investigational new drug application laterthis year to begin studies of the topical formulation for burns, whichis an inflammatory pain condition with easily available models and alarge market opportunity. Pain associated with abrasions andcontusions are among other potential indications.
Farrar said human studies have shown small doses of morphine (notenough to get into the brain) in joints have had profound analgesiceffect in arthroscopic knee surgery. That also was shown in cornealabrasions and third molar extractions, he said. Anecdotally, morphinehas worked for sunburn, Farrar said.
Behind that program Adolor is using proprietary chemistry todevelop orally active kappa-specific compounds that aremetabolically stable, don't cross the BBB and are more effective thannon-steroidal anti-inflammatories in treating rheumatoid arthritispain. If successful, those agonists would be the first opiate analgesicsto address the pain of chronic inflammatory disease, Farrar said.
An early stage effort at Adolor is a directed screening program thatuses cloned opiate receptors to find specific compounds. In a separateprogram Adolor is looking at an opiate receptor-based approach toimmunosuppression. The company ultimately wants to developcentral opiate analgesics.
Adolor was formed in 1994 and has rights to several technologies inthe area of opiate receptors. Initial technology was brought in by theUniversity of Chicago in the area of cloned opiate receptors. Thecompany also has patents and applications on compounds that reactwith the receptors, novel uses of existing compounds, and opiatereceptor-reactive compound collections comprising more than 25,000structures.
The company secured its first financing of $1.5 million in November1994 from Arch Venture Partners, the development arm of theUniversity of Chicago; Falcon Technology Partners, of Devon, Pa.;and Weiss, Peck & Greer Venture Partners, of San Francisco.
TL Ventures, of Wayne, Pa., led the $9.6 million financing round.Alta California Partners, of San Francisco and OneLiberty Ventures,of Boston, also participated, as did the founding investors, companyofficials and other individuals. n
-- Jim Shrine
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