Merck is acquiring Afferent Pharmaceuticals — including its therapeutic candidates targeting the P2X3 receptor, now in clinical testing for neurogenic conditions that include chronic respiratory diseases — under a definitive agreement announced by the two companies.
A lead investigational drug developed by Afferent, AF-219, is under evaluation in a Phase 2b dose-escalating study (NCT02349425) for the treatment of refractory chronic cough, and in a separate Phase 2 trial (NCT02502097) in patients with idiopathic pulmonary fibrosis (IPF) with persistent cough. AF-219 is a selective, non-narcotic, orally administered P2X3 antagonist. A separate P2X3 antagonist, AF-130, is also in clinical testing.
Under the agreement, a Merck subsidiary will acquire all Afferent outstanding stock for an upfront cash payment of $500 million. The company’s shareholders may receive up to an additional $750 million if certain clinical development and commercial milestones are achieved for certain candidates, including AF-219.
“Afferent has pioneered the clinical development of novel investigational candidates selectively targeting the P2X3 receptor, an exciting area of research,” Dr. Roger M. Perlmutter, president of Merck Research Laboratories, said in a press release. “We look forward to advancing these innovative molecules for patients with conditions like chronic cough, an area of significant unmet medical need.”
P2X3 receptors are thought to be crucial in the sensitization of specific sensory nerves, especially C-fiber afferents. These nerves activate and become sensitized under disease conditions mediated by a common cellular signal, ATP, when released in high concentrations due to the cellular distress that follows an injury or infection. Afferent’s compounds are engineered to selectively block activation of ATP signaling in P2X3 channels, potentially reducing sensory signs and symptoms.
Afferent presented data from a first cohort of patients in the dose-escalation study at the 2016 American Thoracic Society (ATS) International Conference, and data from a lower-dose second cohort is to be discussed at a future scientific meeting.
“This achievement is a reflection of the talent and hard work of the experienced Afferent team in advancing the science of P2X3 receptors and the clinical development of our novel therapeutic candidates,” said Kathleen Sereda Glaub, CEO of Afferent. “We are very pleased to enter into this agreement given Merck’s reputation for maximizing opportunities around novel mechanisms. This agreement with Merck creates significant value for Afferent shareholders while enhancing the potential of our portfolio to provide meaningful benefits to patients globally.”
Chronic cough, defined as a cough lasting for more than eight weeks, is estimated to affect around 10% of adults in the U.S. It often is the result of an underlying condition, but 20% to 40% of people with chronic cough are exceptions. Chronic cough currently has no approved treatments.