CEO: Yotam Nisemblat
ProteKt Therapeutics is a biopharmaceutical company aiming to develop a drug for enhancing long-term memory of those suffering from Alzheimer’s disease (AD) and mild cognitive impairment (MCI). 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 3.6 M USD in a series A round, when two new investors joined – Fonds de solidarité FTQ and Bukwang Pharmaceutical. There are no marketed drugs for enhancing memory in AD and MCI and the pharmacological treatment is limited in its effect and in time. Inhibition of the enzyme PKR offers a unique approach for improving memory consolidation, as supported by a strong and growing body of preclinical and human evidence. A PKR inhibitor (PKRi) small molecule provides an attractive and novel mechanism for modulating protein synthesis that can promote learning-related neuronal modifications, thus enhancing long-term memory. In addition, inhibition of PKR can lead to a disease-modifying effect through it anti-inflammatory and anti-apoptotic effects, providing an attractive multimodal novel mechanism to treat AD. ProteKt-Tx aims to identify and develop a potent and selective oral PKRi for the treatment of cognitive disorders such as AD and MCI, for which there are significant unmet medical need.
ProteKt-Tx has an innovative approach for targeted enhancement of the protein translation process needed for memory consolidation. ProteKt-Tx is pioneering the enhancement of memory by targeting PKR, an enzyme that inhibits the translation process. This mechanism may be used for potential therapy in MCI as well as traumatic brain injury and other cognitive disorders such as Alzheimer’s disease (AD). Long-term, but not short-term, memory depends on protein synthesis. In aging, which is also considered a chronic metabolic stress, neurons respond by inhibiting the rate of protein translation, a protective cellular mechanism 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, a Ser/Thr kinase, upon cellular stress, leads to eIF2α phosphorylation and consequent inhibition of protein synthesis. Thus, an effective PKRi will stimulates higher levels of protein translation, which should enhance memory consolidation and may rescue AD/MCI/ aging effects. In addition, PKR activation induces neuroinflammation via the NFkB and inflammasome pathways and induces apoptosis via the FADD-Caspase-8 pathway and therefore, inhibition of PKR can reduce neuroinflammation and apoptosis and create a disease-modifying effect. The PKRi mechanism is a multimodal solution for a multifactorial disease and therefore it may have a better outcome in patients.
MCI is an intermediate state between the regular cognitive decline that occurs with normal aging and the onset of dementia as in AD. Most diagnosed MCI patients are over age 60 and experience moderate but significant and measurable decline in cognitive functions including language, judgement, memory and mental skills, but not dementia. 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. MCI prevalence worldwide is estimated at 80 million, and the MCI market for treatment may be ~$4B in 2023 (estimated from GlobalData AD and MCI Report, 2015). AD prevalence worldwide is estimated at 26.6M (Brookmeyer et al., 2006) and this number is predicted to grow fourfold to 106.8 million by the year 2050. Global sales are expected to grow to ~$13.3B in 2023 (GlobalData AD Report, 2016).
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.