• Fighting resistant tumors with best-in-class inhibitors of casein kinase 1 (CK1)

    Fighting resistant tumors with best-in-class inhibitors of casein kinase 1 (CK1)

    CasInvent Pharma

About Us

CasInvent Pharma was established in 2020 as a spin-off of Masaryk University (MU) in cooperation with the investment partner i&i Prague, s.r.o. (Ltd). The mission of the company is to develop new therapeutic options for the treatment resistant tumors. The CasInvent platform is based on the use of proprietary, best in classhighly selective inhibitors of enzymes belonging to the Casein Kinase 1 (CK1) family that are responsible for the regulation of different cellular mechanisms leading to resistance for targeted therapies.

The CK1 inhibitors were discovered by the research groups of professors Vítězslav Bryja and Kamil Paruch at the Faculty of Science of MU, who have long-term expertise in the research areas of CK1 biology and chemistry of kinase inhibitors, respectively. CasInvent Pharma closely cooperates with these teams in advanced preclinical development of selected substances. The candidate compound is planned to enter clinical trials focused on the treatment of resistance Acute Myeloid Leukemia (AML) and solid tumor indications such as PDAC, TNBC, Melanoma or prostate cancer.

Casinvent about us

Leadership

Alexander Scheer, PhD., has more than 25 years of experience in R&D and the life science industry. Prior to joining CasInvent, he served as the CSO of Aelin Therapeutics in Belgium and before as CSO for Ertech in Lyon, France. Prior to that he was the Head of Research at Pierre Fabre in France, focused primarily on oncology and central nervous system research, and also served as a Deputy Head of Research at Pierre Fabre. At his time at Merck Serono, Dr. Scheer served as the Director, Global Research Informatics & Knowledge Management R&D and Project Leader, Neglected Diseases where, among other responsibilities, he led Merck’s program to develop drugs for neglected diseases in collaboration with the World Health Organization (WHO). At Serono, he was responsible for the selection of targets and compounds while leading the Molecular Screening and Cellular Biology department. Dr. Scheer holds anM.Sc. in Chemistry, from the University of Gottingen, and a Ph.D. in Chemistry and Biochemistry from the German Cancer Research Center in Heidelberg . He published more than 50 papers, book chapters or patents.
Vojtěch Helikar, joining CasInvent Pharma in 2021 as the Managing Director, Vojtech brings to the company over ten years of hands-on experience in international business, investments, and innovations. Former roles include Senior Consultant at the Central European Institute of Technology, Head of the Czech Trade & Investment operations in Scandinavia, Director at the Czech Trade & Investment office in Sydney, Australia, and the Investment Specialist at the Czech Investment and Business Development Agency. Vojtěch has earned his Master Degree in International Trade from the University of Economics in Prague after completing his study programs at the University of Regensburg in Germany and the University of Applied Sciences in Austria. In addition to his consulting experience, Vojtech is highly regarded for successful design and execution of partnership engagements.
Kamil Paruch, Ph.D., is associate professor of Organic Chemistry at Masaryk University. After earning his Ph.D. in organic chemistry at Columbia University (New York, USA), he worked in drug discovery (oncology) at Schering-Plough Research Institute (now Merck). After spending 13 years in the US, he returned to the Czech Republic. Since 2009, his research at Masaryk University has been focused on novel organic molecules with targeted biological activity, especially those potentially applicable in modern oncology. In particular, the team of Prof. Paruch has identified several classes of new potent and highly selective inhibitors of selected heretofore therapeutically underexplored protein kinases, including CK1 inhibitors that form the basis of the CasInvent pipeline. Practically all projects in Prof. Paruch’s laboratory are being carried out in close collaboration with leading Czech and international biologist. Noteworthy is the collaboration with Prof. Lumír Krejčí of Masaryk University in the area of identification of new inhibitors of structure-specific nucleases, which resulted in the know-how that was exclusively licensed to the innovative biotech company Artios Pharma (Cambridge, UK) and recently also to the Big Pharma company Merck KGaA (Germany). Prof. Paruch has authored 44 scientific publications and has been granted 68 international patents.
Pavlína Janovská, Ph.D. studied Molecular Biology and Genetics at Masaryk University in Brno, where she later obtained a Ph.D. in the field of Animal Physiology. During her studies, she focused on the importance of the Wnt signalling pathway in the pathogenesis of chronic lymphocytic leukemia (CLL) and described a novel molecular target for the treatment - casein kinase 1 (CK1) δ / ε. In her postdoctoral study, Dr. Janovská continues with the research on the Wnt signalling pathway and the use of CK1 inhibition for the treatment of various cancers. Dr. Janovská is an author of 15 scientific articles and 1 granted international patent. In the group of prof. Bryja, she is responsible for the development of cellular assays for studying the biological effects of CK1 inhibitors and for studies of CLL in mouse models.
David Stíbal, Ph.D., graduated with a Master's degree in Synthesis and Production of Pharmaceuticals at the University of Chemistry and Technology in Prague. During his doctoral studies at University of Neuchâtel, Switzerland, he researched the synthesis of organometallic compounds and their potential in the treatment of cancer. His postdoctoral stay in the laboratory of prof. Lippard at the Massachusetts Institute of Technology, USA, focused on the biological activity of inorganic platinum and osmium compounds with a combined anticancer and immunostimulatory effect. Afterwards, Dr. Stíbal worked for two years in industrial research at the Czech company Lach-Ner. Since 2019 he has been working in a biotechnology incubator i&i Prague as a project and investment manager. He currently works intensively on several projects in the field of drug development as well as on projects focused on chemical syntheses and drug formulation.

Advisory

Radoslav Trautmann, Ph.D., MBA, studied Materials Chemistry at the Faculty of Chemistry of the Brno University of Technology, where he subsequently obtained a Ph.D. in the field of Macromolecular Chemistry. During his doctoral studies, he started working for the startup company ADM, a.s., which deals with the development and production of materials for dentistry. In the company, he was initially responsible for the development and certification of new products but later focused mainly on managing the company's distribution network, training end customers and business partners, preparing business strategies for individual countries and finding new business partners. In 2015, he started working as a business development manager at Technology Transfer Office at Masaryk University, where he currently works as a head of the transfer department and a deputy director. The main activity of the Technology Transfer Department is the protection of MUNI's intellectual property and its subsequent application in practice in the form of further scientific cooperation or as a cooperation with private entities. In 2017, Dr. Trautmann completed studies at the University of St. Francis, Joliet, USA / Brno University of Technology, Faculty of Business and Management and obtained his MBA degree.

Scientific Advisory

Vítězslav Bryja, Ph.D., is a professor of Animal Physiology at Masaryk University. He earned his degrees at Masaryk University (Master in Molecular biology and genetics), and Charles University in Prague (Ph.D. in Neurosciences). Subsequently, he worked as a postdoctoral researcher at the Department of Molecular Biochemistry and Biophysics at Karolinska Institute, Sweden. Upon his return to the Czech Republic, he has worked in the Laboratory of Cytokinetics at the Institute of Biophysics of Academy of Sciences of the Czech Republic and at the Department of Experimental Biology of Faculty of Sciences, Masaryk University where he established his research group in 2007. Prof. Bryja´s main research interest is to understand the cell signalling cascades with focus on the Wnt signalling pathway in the context of cancer cells and design of novel candidate therapeutic approaches. Specifically, his research aims to introduce the new CK1 inhibitors into the treatment of chronic lymphocytic leukemia and other cancer types. Prof. Bryja is an author of 118 scientific publications and an inventor of 4 granted international patents.
Uwe Knippschild, PhD, is Professor in the Department of General and Visceral Surgery at the Center for Surgery at Ulm University Hospital. He studied biology at the University of Cologne, completed his dissertation at the Heinrich-Pette-Institute for Experimental Virology in Hamburg and received his doctorate from the University of Ulm in 1992. Subsequently, he continued his postdoctoral work at the Heinrich-Pette-Institute for Experimental Virology in Hamburg and then at the Biomedical Research Center in Dundee, Scotland in the area of signal transduction with a focus on p53 and CK1. From 1998 to 2002 he established his own research group at the Heinrich-Pette-Institute as group leader. From 2002 until now, he has been doing research at the Department of General and Visceral Surgery, serving as laboratory director until 2021 and as research director since 2021. Since then, his research activities have focused on the characterition of changes in signal transduction pathways of various tumor entities thereby identifying novel targets for drug development, and validating CK1 isoform- specific inhibitors and biologically active peptides in vitro and in animal models. Other foci of his research are obesity and its influence on tissue regeneration after induction of trauma. In total, Prof. Knippschild has published 141 papers in internationally renowned journals.
Peter has about 35 years of industry experience in medicinal chemistry and drug discovery starting his professional career at Sandoz/Novartis. For many years, he headed the Chemistry Department at the Novartis Institutes for BioMedical Research in Vienna, Austria. Since 2008, he is Managing Director at the Lead Discovery Center GmbH in Dortmund, Germany, a translational incubator operating at the interface of academia and industry; since 2019, he is also Managing Director of the Khanu Management GmbH in Dortmund and the wings4innovation GmbH in Vienna, Austria, both acting for KHAN Technology Transfer Fund I GmbH & Co KG, a financing vehicle to translate excellent basic research into professional drug development and commercialization. 
Peter is member of several international scientific advisory boards and serves as advisor to private and public funding bodies. He is (co)author of more than 80 peer-reviewed publications and more than 25 patent applications, referee to various journals, and holds a Dr. degree in organic chemistry from the TU Wien, Austria.
Dr. Gibbs is a Consultant at JBG Pharma Consulting where he specializes in Oncology and Pharmacology R&D. Jay currently uses his broad knowledge of cancer biology/drug development, his large network of collaborators, and his understanding of the interfaces between industry, academia, and non-profit foundations to support clients in the bio-pharmaceutical industry. He is also an Adjunct Professor in the Department of Biochemistry and Molecular Medicine at George Washington University School of Medicine and Health Sciences. Dr. Gibbs received his Ph.D. in Pharmacology from the University of Virginia followed by postdoctoral studies on the ras oncogene with Edward Scolnick at Merck Research Laboratories. Jay’s extensive pharmaceutical career was at Merck and AstraZeneca where he did cancer research and drug development. He led projects at all stages of development: target identification/validation, med chem supported drug discovery, drug candidate identification/IND filing, and phase I project team guidance (farnesyltransferase L-778,123, VEGFR inhibitor, c-Met MK-2461, AZD6244 + MK-2206 phase I, and selumetinib for NF1). He also has deep experience in leading external alliances and licensing efforts. He previously was also an Adjunct Professor of Pharmacology at the University of Pennsylvania School of Medicine. Dr. Gibbs is co-inventor on five U.S. issued patents and an author of 128 research articles, book chapters, and review articles.
David Virshup, M.D., is Director of the Program in Cancer and Stem Cell Biology (CSCB) and Professor at the Duke-NUS Medical School in Singapore, and is jointly appointed as Professor of Pediatrics at Duke University in North Carolina. Dr. Virshup received his M.D. and research training at Johns Hopkins University and established his first independent laboratory at the University of Utah. He joined Duke-NUS in Singapore in 2007. His research has focused on signal transduction, with an emphasis on the role of protein phosphorylation in Wnt signaling and circadian rhythms. He laboratory cloned CK1ε as well as the B56 family of Protein Phosphatase 2A regulators. In Singapore, his studies of how CK1 phosphorylates the PERIOD proteins led to the phosphoswitch model controlling circadian clock speed. His work in Wnt signaling led to development of a small molecule inhibitor of Wnt secretion, ETC-159. Prof. Virshup has been elected to several honorific societies including the American Society for Clinical Investigation (ASCI), the American Association for the Advancement of Science (AAAS) and the Association of American Physicians (AAP).

Investors

Our Science

Target: Casein kinase 1 (CK1)

  • Serine/threonine kinases
  • Isoforms α, γ1, γ2, γ3, δ and ε – different expression levels in different pathogeneses
  • Implicated in cancer, AD, sleep disorders, obesity, opioid addiction

Goal: Development of highly potent and selective inhibitors of CK1

The small-molecule inhibitors developed by CasInvent Pharma are designed to target with high selectivity and activity individual isoforms of serine-threonine kinases from the Casein kinase 1 (CK1) family. In our research, we have focused on the isoforms CK1 δ, ε as therapeutic targets for the treatment of resistance in melanoma, TNBC and pancreatic cancer, and CK1 α for the treatment of acute myeloid leukemia (AML), with special focus on venetoclax resistance.

The development of the proprietary CK1 inhibitors is based on our studies.

Melanoma is a malignant neoplasm characterized by the uncontrolled growth of pigment-producing cells. Our investigation into the pathological cell signaling in melanoma has primarily concentrated on the regulators influencing cell migration and the interactions of melanoma cells with their surrounding microenvironment. This microenvironmental interaction often facilitates tumor cell survival, disease advancement, and evasion of therapeutic interventions.

Our findings revealed that selectively targeting CK1 δ and ε kinases in melanoma cells alone effectively impedes the migratory capacity of the malignant cells and disrupts their interactions with the protective microenvironment, leading to a significant delay in disease progression in murine models. Notably, the combination of CK1 inhibition with standard melanoma treatment, such as BRAF inhibitors, yielded enhanced, synergistic effects in vitro and a more robust therapeutic response in vivo in our established animal model of melanoma.

Targeting of the kinase CK1 α has been also recently recognized as an attractive therapeutic strategy for the treatment of AML . Similarly, in the realm of AML biology, this hematologic malignancy is marked by highly heterogeneous disease courses and an unclear pathogenesis. Our exploration of the pathological cell signaling in AML has predominantly focused on regulators governing cell migration and the interactions between leukemic cells and their supportive microenvironment. This microenvironmental support often contributes to the survival of tumor cells, disease progression, and resistance to therapeutic interventions. However, most of the published studies have used small-molecule inhibitors with low potency and poor kinase selectivity. Our recently identified series of molecules contains potent and highly selective inhibitors of CK1 α, with minimal off-target effects at therapeutic doses.

Casinvent our science

Background

  • Research based on the activity of Pfizer compound PF-670462 on CK1
  • New proprietary (patent pending) pharmacophores developed and optimized
  • Developed compounds have better properties (selectivity, potency) than PF-670462

To date, more than 450 compounds have been prepared and tested:

  • Small-molecule inhibitors (M < 400)
  • ClogP = 2.0 - 4.5
  • Efficient & modular synthesis, compounds can be rapidly prepared in gram quantities
  • Well water soluble, compounds can be formulated as salts
Casinvent our science Selectivity and Potency of Lead Compounds

Pipeline

CasInvent Pharma is developing selective small molecule inhibitors of casein kinase 1(CK1). Other indications in the field of oncology are being studied, using the lead candidate as well as other molecules in our portfolio. CasInvent intends to advance its lead candidates to the clinical phase Ib.

The IP is subject to the exclusive sublicenceable worldwide license from the Masaryk University.

Publications