News

June 3, 2015

EIP Pharma announces first patient dosing in phase 2 clinical studies of a novel brain-targeted anti-inflammatory drug candidate, VX-745, for the treatment of Alzheimer’s disease (AD)

CAMBRIDGE, Mass., June 3, 2015 /PRNewswire/ — EIP Pharma LLC (www.eippharma.com) today announced that patient dosing in phase 2 clinical development of VX-745 in Alzheimer’s disease (AD) is underway.  VX-745 is an oral brain penetrant, highly selective and potent inhibitor of the alpha isoform of the protein enzyme p38 mitogen activated protein kinase (p38 MAPK alpha).

“Recent human genetic data demonstrate that inflammation is a major driver of disease in patients with symptomatic Alzheimer’s, while the science also indicates the p38 MAPK alpha mechanism could provide a novel approach to effectively treat Alzheimer’s specific inflammatory processes and their effects on neuronal function,” said John Alam, MD, Founder and CEO, EIP Pharma. “VX-745 is a highly selective antagonist of p38 MAPK alpha, achieves excellent brain drug concentrations, and has already been in the clinic.  As such, VX-745 provides today a unique opportunity to clinically evaluate the p38 MAPK alpha mechanism in patients with Alzheimer’s disease.”

Two phase 2a clinical studies are being conducted in patients with mild cognitive impairment (MCI) due to AD or mild AD:

• Study 302: “A clinical study of two doses of a selective p38 MAP kinase inhibitor, VX-745, to evaluate the effects of 12-Week oral twice-daily dosing on amyloid plaque load as assessed by Quantitative Dynamic 11C-PiB positive emission tomography (PET) amyloid scanning”. This study is being conducted at the Alzheimer’s Research Center (ARC), VU Medical Center, Amsterdam, Netherlands; with Prof. Philip Scheltens as principal investigator.

• Study 303: “A Randomized, multiple dose clinical pharmacology study of two doses of a selective p38 MAP Kinase inhibitor, VX-745, in patients with Mild Cognitive Impairment (MCI) due to Alzheimer’s disease (AD) or Mild AD”. This 6-week treatment study is being conducted at an Early Clinical Phase Unit in the Los Angeles region under an IND that was cleared in March 2015 by the Division of Neurology Products at the FDA.

“The dynamic PET scanning protocols we have developed significantly reduces the variability that is otherwise seen when measuring brain amyloid plaque levels by standard PET.  As a result, drug mechanisms that are active in reducing brain amyloid plaque load in patients would readily be identified with the use of quantitative dynamic PET scanning in clinical studies of the type we are conducting with VX-745,” said Dr. Bart N.M. van Berckel, MD, PhD, of the Nuclear Medicine & PET Research Department at the VU Medical Center.

Further information regarding these clinical trials can be obtained at www.clinicaltrials.gov.

About VX-745 and p38 MAPK alpha
VX-745¹ is an oral small molecule highly specific inhibitor of the intra-cellular enzyme p38 mitogen activated protein kinase alpha (MAPK alpha). In the brain p38 MAPK alpha regulates inflammation through effects on microglia², the major immune cell in the central nervous system (CNS). P38 MAPK alpha is also expressed in neurons, where it is involved in memory formation and synaptic plasticity³.  P38 MAPK alpha is increasingly recognized as a highly promising therapeutic target for a broad range of CNS disorders⁴, with animal data indicating that p38 MAPK alpha antagonists have the potential to rapidly improve cognitive function^{5 6}.

VX-745 readily enters the brain, with brain concentrations in pre-clinical studies being approximately two-fold higher than in peripheral blood. VX-745 was discovered by Vertex Pharmaceuticals, Inc. and previously had been clinically evaluated in non-CNS disorders.

VX-745 was licensed from Vertex in 2012 and additional pre-clinical studies were conducted to re-position it as a therapeutic for disorders of the brain.

About EIP Pharma
EIP Pharma, LLC (www.eippharma.com) is a private R&D stage CNS-focused therapeutics company based in Cambridge, Massachusetts.  The company is the owner of an issued US patent (#8,697,627, granted April 15 2014; pending worldwide) on the use of VX-745 to reduce existing brain amyloid plaque in patients.

References

1. Duffy J, et al (2011)   The discovery of VX-745: a novel and selective p38 alpha kinase inhibitor.   ACS Med Chem Lett  2, 758-763.
2. Bachstetter AD et al (2011) Microglial p38alpha MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (Abeta).  J Neuroinflammation 8, 79.
3. Correa SA, Eales KL (2012) The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. J Signal Transduct 2012, 649079
4. Yasuda S et al (2011).  P38 MAP Kinase inhibitors as potential therapeutic drugs for neural diseases. Cent Nerv Syst Agents Med Chem 11, 45-59.
5. Roy SM et al (2015) Targeting human central nervous system protein kinases:  an isoform selective p38 alpha MAPK inhibitor that attenuates disease progression in Alzheimer’s disease mouse models.  ACS Chem Neurosci, 6, 666-80
6. Alam J (2014) Effects on cognition of a selective p38 MAPK alpha inhibitor in aged rats.  Alzheimer’s & Dement 10 Supp P922