CEO: Yotam Nisemblat
ProteKt Therapeutics is a biopharmaceutical company aiming to develop potent and selective oral inhibitors of the kinase PKR for the treatment of neurodegenerative and neuroinflammatory diseases. The company was originally financed by a syndicate of Takeda Pharmaceutical Company through its venture group Takeda Ventures Inc., OrbiMed Israel Partners, Johnson & Johnson Innovation – JJDC, RMGP and the Israel Innovation Authority (IIA), and has operated since December 2015 in the FutuRx biotech incubator in Ness Ziona, Israel. In November 2019, ProteKt raised 4.1 M USD in a series A round, when two new investors joined – Fonds de solidarité FTQ and Bukwang Pharmaceutical.
There are no disease modifying treatments for neurodegenerative diseases, including Alzheimer’s disease (AD), and most of the available treatments are symptomatic and focuses on single mechanistic process of the disease. Inhibition of the enzyme PKR offers a unique approach that provides multimodal solution to the multifactorial mechanism of neurodegeneration, and provides a potential to modify the progress of these diseases, while improving cognition. PKR inhibition by small molecule can lead to a disease-modifying effect through its anti-inflammatory effect, anti-apoptotic effect, by reducing Tau phosphorylation and Aβ production, providing an attractive multimodal novel mechanism to treat AD. In addition, PKR inhibition improves protein synthesis, and this can promote learning-related neuronal modifications, thus enhancing long-term memory.
PKR overactivation is found in various neurodegenerative diseases, such as AD, Mild Cognitive Impairment (MCI), Huntington’s disease, traumatic brain injury (TBI) and Parkinson’s disease. PKR activation induces neuroinflammation via the NFkB and inflammasome pathways and induces apoptosis via the FADD-Caspase-8 pathway. PKR activation leads to Tau phosphorylation either directly or via GSK3β, contributing to AD pathology. PKR activation also leads to overproduction Aβ via activation of BACE1. Therefore, inhibition of PKR can reduce neuroinflammation, apoptosis and AD pathology and create a disease-modifying effect.
In addition, ProteKt Therapeutics’ mechanism propose an innovative approach for enhancement of the protein translation process needed for memory consolidation. ProteKt Therapeutics is pioneering the enhancement of memory by inhibiting PKR, which inhibits the translation process. This mechanism may be used for potential cognitive enhancement in various neurodegenerative diseases such as MCI, traumatic brain injury and other cognitive disorders such as AD. Long-term, but not short-term, memory depends on protein synthesis. In aging and disease states, which leads to a chronic cellular stress, neurons respond by inhibiting the rate of protein translation, a protective cellular mechanism called Integrated Stress Response (ISR) and that can negatively affect neuronal and cognitive function. The overall rate of protein synthesis is controlled by eIF2α, a key protein in the translation machinery. In performing this role, unphosphorylated eIF2α promotes general protein translation. Activation of PKR upon cellular stress, leads to eIF2α phosphorylation and consequent inhibition of protein synthesis. Thus, an effective PKR inhibitor will stimulate higher levels of protein translation, which should enhance memory consolidation and may rescue cognitive decline in neurodegenerative diseases.
The PKR inhibition mechanism is a multimodal solution for multifactorial neurodegenerative diseases and therefore, it may have a better outcome in patients.
The therapeutic potential of PKR inhibition is large, and includes neurodegenerative diseases, neuroinflammatory diseases, metabolic diseases, and cancer, and this offers the possibility to create a pipeline of treatments for various diseases. ProteKt aims to treat early-stage AD patients as a proof of concept of the technology. AD is a chronic neurodegenerative disease and the most common form of dementia. It has no current cure and only treatments for symptoms of AD are available. These patients are treated with drugs for dementia pathologies with only slight if any improvement. AD prevalence worldwide is estimated at 32.7M in 2018 and this number is predicted to grow to 44.5M by the year 2028. Global sales are expected to grow from $2.2B in 2018 to $12.9B in 2028 (GlobalData AD Report, May 2020), creating a huge market with unmet medical need that strives for novel disease-modifying approaches of treatment.
The Company is comprised of individuals with vast experience in the biotech industry, as well as academic leaders in the fields of neuroscience and computational chemistry.
Tetsuyuki Maruyama: Chairperson of the Board
An independent pharmaceutical and biotech consultant. He previously held faculty positions at the University of Minnesota and Cardiff University where he focused on the neurobiology of learning and memory. Tetsu then held leadership positions in CNS drug discovery for Merck Sharp and Dohme in the UK and for GlaxoSmithKline in Singapore before becoming SVP of Drug Discovery at Takeda. In 2016 he joined the Dementia Discovery Fund as Chief Scientist, a position he held until the end of 2019. Tetsu is on the Boards of a number of privately held biotech companies and non-profits.
Yotam Nisemblat: CEO
MSc from Tel-Aviv University in Neurobiology with specialization in Alzheimer’s disease and MBA from The Interdisciplinary Center in Herzliya. Ten years of industry experiences in drug development and research, mainly in the field of CNS-related disorder. Former Drug Development Director at BioLineRx.
Prof. Kobi Rosenblum: Inventor
Professor of molecular and cellular mechanisms underlying learning and memory, University of Haifa, Israel; PhD in neurobiology with more than two decades of experience in applied neuroscience research and development.