Pfizer Inc (NEW YORK, NY) and Adolor Corp (EXTON, Pennsylvania), a leader in the area of novel, opioid receptor-targeted therapeutics, announced an exclusive worldwide collaboration to develop and commercialize delta opioid (DOP) receptor agonist candidates, ADL5859 and ADL5747, for the treatment of pain. DOP receptor agonists have the potential to treat a wide range of inflammatory, neuropathic, and acute pain conditions, without some of the complicating side effects of traditional mu agonists including lower incidences of respiratory depression and constipation, and a lower potential for dependence/abuse.

The companies will form a joint steering committee to guide the development and commercialization of products resulting from the collaboration. Adolor will be responsible for IND filings and clinical evaluation through phase IIa, at which point, Pfizer will undertake the completion of development, regulatory approval, and commercialization for each compound on a worldwide basis.

Under the terms of the agreement, Pfizer and Adolor will share revenues and expenses in the US on a 60/40 basis. Outside the US, Pfizer will fund development activities and, on commercialization, Adolor will receive royalties on Pfizer's net sales. Adolor will receive an upfront, nonrefundable payment of $30 million, plus $1.9 million reimbursement for prior phase II development costs. Adolor may also receive payments up to $232.5 million upon achieving development and regulatory milestones for its DOP compounds. More than 50% of these milestones may be earned prior to regulatory approval of the compounds; the first milestone payment may be earned on commencement of phase IIb clinical studies.

ADL5859 is in phase IIa development exploring its analgesic efficacy in inflammatory pain associated with rheumatoid arthritis and acute postdental surgery pain. Additional programs are planned to evaluate the compound in patients with osteoarthritis and diabetic peripheral neuropathy. Results to date indicate that it is a potent, selective DOP agonist with favorable physicochemical properties. It has shown activity in preclinical models of inflammatory, incisional, and neuropathic pain, with acceptable safety and toxicology profiles. In phase I clinical studies, ADL5859 was readily absorbed when given orally. It appears to be well tolerated in humans.

Adolor expects to begin phase I clinical testing of ADL5747 in the first quarter of 2008. These DOP agents would be first-in-class as there are none currently approved by the US FDA.

Today, all marketed opioid analgesic drugs interact with the mu subtype of opioid receptors in the brain and spinal cord. Activation of these mu opioid receptors in the central nervous system with opioid analgesics, such as morphine, is very effective in reducing pain perception. Despite the significant clinical benefit of these drugs, the use of morphine-like opioid analgesics is limited by their abuse potential as well as the incidence of serious side effects such as sedation, decreased respiratory function, seizure, and gastrointestinal complications including postoperative ileus and opioid bowel dysfunction.

One of three opioid receptors, the DOP receptor has potential utility in a variety of indications, in addition to the modulation of pain. DOP agonists are thought to modulate other biological processes that may manifest themselves in disease states or conditions such as cardioprotection, overactive bladder, and depression.