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Finding the right channel
CAMBRIDGE, U.K.—An agency of the British government has awarded £1.4 million ($2.3 million) to Xention to support the preclinical development of the biopharmaceutical company’s treatment for atrial fibrillation (AF). The Technology Strategy Board, an agency dedicated to accelerating economic growth by stimulating business-led innovation, is directing its Biomedical Catalyst funding award toward Xention’s IKACh channel blockers, which target key ion channels playing a role in the condition.
“There was a very rigorous review process, and we’re very excited that the board recognized the quality of our program and the promise IKACh represents as a new target for atrial fibrillation,” Tim Brears, Xention’s CEO, tells DDNews. “There’s been very little innovation in this area and we think there’s great potential.”
Individuals with AF experience an irregular and often rapid heart rate. Although not typically life-threatening on its own, the condition often causes poor blood flow to the body and can lead to blood clots, stroke, heart failure and other heart-related complications. The American Heart Association reports that 2.7 million Americans live with AF. Around 1 percent of the healthcare budget of Western European and North American countries is spent on the management of AF, according to Xention.
Xention’s IKACh inhibitors represent one of two approaches in the company’s pipeline that are focused on the treatment of AF by targeting key ion channels. In patients with atrial fibrillation, IKACh activity is increased in the atria, and this abnormal activity can contribute to AF. Inhibition of IKACh is expected to halt and prevent the recurrence of the condition. Xention also expects this approach to provide a more targeted and safer therapy than the currently available anti-arrhythmic drugs for AF.
Xention has identified a series of potent and selective modulators of IKACh that also appear differentiated from other IKACh inhibitors in their activity on human atrial tissue from AF patients. The company is preparing to advance some of these modulators through its pipeline toward the clinic.
The funding award will support Xention’s progression of one IKACh inhibitor through a full preclinical development program while the company also undergoes the manufacturing activities needed for subsequent clinical development. If successful, the co-funded research will lead to the clinical evaluation of a therapy for patients with AF.
“Most other agents that seek to restore sinus rhythm in the heart, which is what we’re trying to do, block multiple ion channels, whereas the approach we’re taking is to block just a single channel,” says Brears. “Our expectation is that this approach, if successful, will provide a much safer way of intervening and restoring sinus rhythm.”
In addition to its IKACh program, Xention and Servier Laboratories are conducting clinical studies of XEN-D0103, a modulator of IKur, another cardiac potassium channel thought to be important in AF. Xention recently granted an option to Servier to develop and commercialize XEN-D0103 in all territories except the United States and Japan. Xention has moved another potent and selective antagonist of IKur further along the pipeline. XEN-D0101 has already been assessed in a Phase 1 study that used extensive cardiovascular safety monitoring to establish the safety of modulating the Kv1.5 target. XEN-D0103 is reportedly more potent and more selective than XEN-D0101.
Brears anticipates that the commercial and therapuetic potential for Xention’s approach to treating AF, if successful, could be extremely significant. “There’s a consensus among experts that the next step in treating AF is the development of single-channel blockers,” he says.