Addrenex Pharmaceuticals Inc., founded 18 months ago to develop a sustained-release formulation of clonidine, recently complemented that program with additional compounds aimed at the adrenergic system, which is believed to play a role in a wide range of diseases, from hypertension to post-traumatic stress disorder.
Earlier this month, the start-up firm in-licensed a library of nearly 400 compounds from UNeMed Corp., the technology transfer arm of the University of Nebraska Medical Center. Those compounds target adrenergic receptors, or docking sites on cells that react with the hormone adrenaline and hormone/neurotransmitter noradrenaline.
Both of those are secreted by adrenergic pathways and are "active throughout the body and centralized in the brain," said Moise Khayrallah, CEO and co-founder of Research Triangle Park, N.C.-based Addrenex. "When the adrenergic system gets dysfunctional, [it] can contribute to a wide range of medical conditions."
Compounds from the University of Nebraska specifically target alpha-2 adrenergic receptors, which have been implicated in hypertension, attention deficit hyperactivity disorder (ADHD), postmenopausal symptoms, pain, aggression, sleep disorders and PTSD, Khayrallah said. "We'll be working on determining which compounds specifically target those receptors," with plans to move those compounds into preclinical and clinical development.
"We want to try and bring at least one of the compounds we licensed from the University of Nebraska into the clinic by the end" of 2008, he told BioWorld Today, adding that the goal "should be feasible" given that two of the compounds already have been tested in the clinic in nasal decongestion and migraine.
Under the terms of the licensing agreement, Addrenex agreed to pay milestones and future royalties on any product sales. Specific terms were not disclosed.
With the addition of the university's portfolio, the company hopes to "come at the adrenergic pathway from a variety of angles," Khayrallah said, adding that it "fits well" with the company's work to date on Clonicel, a sustained-release version of clonidine developed by Addrenex co-founder Joseph Horacek.
Clonidine is a direct-acting adrenergic agonist that is approved for hypertension, though it's also used off-label for ADHD. "It's been useful" in that indication, Khayrallah said, but side effects, such as drowsiness, lightheadedness, dizziness and constipation, tend to limit its usage.
Horacek, a board-certified physician in neurology and psychiatry who runs a Charlotte, N.C.-based practice primarily treating children, developed the extended-release formulation "that is just as useful, but also safer," Khayrallah said.
Addrenex intends to develop Clonicel for both hypertension and ADHD. Since clonidine already is approved for hypertension, the company will make short work of filing a new drug application in that indication, expected in 2008, with approval coming in "late 2008 or early 2009," Khayrallah said.
In October, the company started a Phase III trial of Clonicel in ADHD, "and we're getting ready to launch a second Phase III," he said.
To date, funding for Clonicel work has come from the company's seed/angel investments of $700,000, plus a $6 million payment from Atlanta-based Sciele Pharma Inc., which licensed marketing rights to the product in July. In that deal Sciele also will pay up to an additional $11 million in milestones, plus royalties on product sales.
"So we've made quite a bit of progress with limited funding," Khayrallah said of Addrenex, which has "tried to stay small and nimble," with four full-time employees and roughly a dozen contract or part-time employees.
"We will need to raise funds" to support work on the newly in-licensed compounds, either from partnerships or other sources, he said, adding that we "would prefer the partnership route."
Addrenex has no plans to expand into the commercialization arena at this time, choosing instead to hand over marketing rights to bigger firms.
"Our aim is to stay a development-stage company," Khayrallah said. "That's where our expertise lies."