PF-05251749 complements the company’s pipeline of potential disease-modifying therapies for Alzheimer’s and Parkinson’s diseases.
Biogen has agreed to acquire from Pfizer PF-05251749, a novel CNS-penetrant small molecule inhibitor of casein kinase 1 (CK1), for the potential treatment of patients with behavioral and neurological symptoms across various psychiatric and neurological diseases.
In particular, Biogen plans to develop the Phase I asset for the treatment of Sundowning in Alzheimer’s disease (AD) and Irregular Sleep Wake Rhythm Disorder (ISWRD) in Parkinson’s disease (PD). The purchase will include an upfront payment of $75 million with up to $635 million in potential additional development and commercialization milestone payments, as well as tiered royalties in the high single digits to sub-teens.
“This asset is highly complementary to our existing pipeline of potential disease-modifying therapies in Alzheimer’s and Parkinson’s diseases,” said Alfred Sandrock Jr., Executive Vice President, Research and Development and Chief Medical Officer at Biogen. “Many patients with Alzheimer’s and Parkinson’s suffer from debilitating sleep disorders and agitation, and we believe that the regulation of the circadian rhythm may hold promise in addressing these challenging behavioral and neurological symptoms.”
CK1 is a key regulator of the ‘central clock,’ the suprachiasmatic nucleus of the hypothalamus, that controls circadian rhythm and impacts nearly all vital physiology and metabolism. The disruption of circadian rhythm is associated with various psychiatric and neurological diseases, including certain important symptoms of AD and PD.
Sundowning is a symptom that impacts 20% or more of AD patients who become confused, anxious, aggressive, agitated or restless later in the day. ISWRD is a circadian rhythm disorder where patients experience fragmented nighttime sleep leading to daytime sleepiness, severe fatigue and difficulty with activities of daily living.
It is one of the non-motor symptoms of PD, and usually increases in frequency over the course of the disease and disability progression. Biogen will explore the potential of PF-05251749 to improve behavioral disturbances of Sundowning in AD by correcting circadian rhythm, as well as its potential to treat symptoms of ISWRD to improve daytime wakefulness, sleep quality, behavior and daily function.
PF-05251749 has previously demonstrated an acceptable safety profile and proof of mechanism in a Phase Ia clinical study. Biogen aims to initiate a Phase Ib study in Q4 2020.