Merck & Co. will acquire Afferent Pharmaceuticals for up to $1.25 billion, the companies said today, in a deal that expands the pharma giant’s pipeline with candidates for treating neurogenic conditions.
Afferent specializes in developing drugs designed to treat common, poorly managed, neurogenic conditions by selectively blocking P2X3 receptors.
The company’s lead investigational candidate, AF-219, is a selective, nonnarcotic, orally administered P2X3 antagonist designed to target the mechanism by which certain nerve fibers become hypersensitized and can lead to chronic and debilitating symptoms—such as chronic cough, defined as a cough lasting more than 8 weeks.
AF-219 is now under study in a Phase IIb clinical trial in patients with refractory, chronic cough, as well as in a Phase II trial in idiopathic pulmonary fibrosis (IPF) with cough—with a Phase III trial anticipated to begin in early 2017.
At the 2016 American Thoracic Society (ATS) International Conference, held May 13–18 in San Francisco, Afferent presented data showing that AF-219 significantly reduced cough frequency compared to placebo in the first cohort of a Phase IIb dose-escalation clinical trial in patients with chronic cough. At the lowest dose of 50 mg twice daily, Afferent said last month, nearly half of patients had at least a 50% reduction in cough frequency and 35% of patients had at least a 70% reduction in cough frequency.
Results from the second cohort, which is examining doses as low as 7.5 mg twice daily, are expected to be presented at a future scientific congress, Merck and Afferent said. They did not say when that was set to occur; last month Afferent said such a presentation was expected in the second half of this year.
Another selective P2X3 antagonist under development by Afferent is AF-130, which is designed to block P2X3 in the carotid body, with the goal of controlling hyperreactivity and thus blood pressure.
A Phase I study of AF-130 was launched in December 2015 to assess the safety, tolerability, and pharmacokinetics of single ascending doses and, in a second cohort, multiple ascending doses of AF-130 administered to healthy subjects.
AF-130 is set to advance to Phase II trials in nonrespiratory conditions. Afferent has said it intends to evaluate AF-130 in multiple conditions, including treatment-resistant hypertension, and potentially in heart failure, migraine, and visceral pain.
P2X3 receptors are believed to play a key role in the sensitization of certain sensory nerves, notably C-fiber afferents. The nerves become activated and sensitized under pathological conditions mediated by a common cellular signal, adenosine triphosphate (ATP), when it is released in high concentrations due to cellular distress following injury or infection. Afferent’s compounds are designed to block ATP activation of P2X3 channels selectively.
“We look forward to advancing these innovative molecules for patients with conditions like chronic cough, an area of significant unmet medical need,” Roger M. Perlmutter, M.D., Ph.D., president, Merck Research Laboratories, said in a statement.
Through a subsidiary, Merck will acquire all outstanding stock of Afferent in exchange for $500 million cash upfront. Afferent shareholders will be eligible to receive up to an additional $750 million tied to achieving clinical development and commercial milestones for multiple indications and candidates, including AF-219.
Merck and Afferent said they expect to complete the acquisition in the third quarter. The deal is subject to expiration of the waiting period under the Hart–Scott–Rodino Antitrust Improvements Act and other customary conditions.
Headquartered in San Mateo, CA, privately held Afferent was co-founded by Anthony Ford, Ph.D., a former vp of research at Roche who initiated and drove the P2X3 program for a decade until Roche exclusively licensed its P2X3 program to Afferent in 2009. He is now Afferent’s CSO. Other founders included Pappas Ventures, Third Rock Ventures, Domain Associates, New Leaf Venture Partners, and Roche Ventures.
Last year, Afferent completed a $55 million Series C financing intended to fund the advancement of AF-219 for pathologic cough, including cough in IPF patients, as well as advancement of AF-130 into clinical phases for cardiovascular and other diseases. The financing was led by Fidelity Management & Research, with participation from other crossover funds Jennison Associates (on behalf of certain clients), New Leaf Ventures, Partner Fund Management, Redmile Group, Tekla Healthcare Investors, and Tekla Life.