We are happy to share that the invention "Use of marimastat for preventing and/or treating epileptogenesis" has been granted patents in several jurisdictions: Europe (EP3982945), Japan (JP7507798), Hong Kong (HK40065314) and China (CN113993512B). Furthermore, the Australian Government IP Australia has issued a decision on granting a patent which soon will be in force.

The inventors are: Prof. Leszek Kaczmarek, PhD DSc; Barbara Pijet-Binkiewicz, PhD; Anna Konopka PhD; Emilia Rejmak-Kozicka, PhD.

Patent claims non-obvious indication for the known compound and is rooted in the research results on the role of MMP-9 enzyme in the process of epileptogenesis, by Prof. Leszek Kaczmarek and his team at the Laboratory of Neurobiology, Center of Excellence for Neural Plasticity and Brain Disorders BRAINCITY, Nencki Institute.  Direct evidence supporting the invention was established i.a. in collaboration with Dr. Anna Konopka at University of Warsaw (Pijet at al. 2020). Patent rights portfolio was licensed out to Pikralida Sp. z o. o., R&D clinical stage company, which is responsible for further product development based on the invention.

Epilepsy, a chronic neurological condition characterized by recurrent seizures, arises from transient dysfunction in the brain due to sudden and excessive bioelectrical discharges in nerve cells. Presently, approximately 30% of epilepsy cases lack a cure, necessitating ongoing pharmacotherapy to manage symptoms. These seizures and continuous medication usage impose significant limitations on the professional and social lives of those affected. Epilepsy commonly arises as a complication following traumatic brain injury or stroke, yet there are currently no drugs available to prevent its development.

MMP-9 inhibitor named PKL-021, based on the invention, is a small molecule, currently developed by Pikralida, exhibiting potent activity and favorable drug-like properties. Its exceptional characteristics position it as a promising candidate for a groundbreaking therapeutic solution aimed at preventing post-traumatic and post-stroke epilepsy. Pikralida’s team has completed I phase clinical trial of an investigational medicinal product containing the active substance PKL-021 (more info here).

Research building blocks that led to the invention were funded by several sources:

• 2007-2010 MNiSW Polish-German funding “The role of matrix-metalloproteinases in the developing brain and in developmental brain injury syndromes?”
• 2008-2011 Polish-Norwegian funding “Aberrant synaptic plasticity in epilepsy,”
• 2013-2016 ERANET Neuron “Proteolytic remodeling of the extracellular matrix in aberrant synaptic plasticity underlying epilepsy evoked by traumatic brain injury”
• 2013-2017 7 PR UE ITN EXTRABRAIN “Extracellular brain proteolysis in neuronal plasticity and neuropsychiatric disorders”
• 2015-2017 PBS Narodowe Centrum Badań i Rozwoju (NCBiR) “Inhibitory MMP-9 jako nowy lek blokujący rozwój padaczki”
• 2015-2019 Horizon 2020 ITN ECMED “Extracellular matrix in prognostication and treatment of epileptogenesis”
• 2019 FNP International Research Agenda “Center of Excellence for Neural Plasticity and Brain Disorders BRAINCITY”