• Highly Potent and SelectiveInhibitors of CK1 Kinases

    Highly Potent and Selective
    Inhibitors of CK1 Kinases

    for the Treatment of Leukaemias,
    Lymphomas and Solid Tumors

    CasInvent Pharma

About Us

The company 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 of selected malignancies. The CasInvent technology is based on the use of proprietary highly selective inhibitors of enzymes belonging to the Casein Kinase 1 (CK1) family that are responsible for the migration of leukemia cells into lymphoid organs.

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 Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML).

Casinvent about us

Our Team

Managing Director

Vojtěch Helikar 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. Throughout his career, Vojtech established and ran CzechTrade & the Investment office in Sydney, Australia, and afterwards was posted to manage the CzechTrade office in Stockholm, Sweden. After his return to the Czech Republic in 2019, Vojtech engaged with the Central European Institute of Technology as a Senior Consultant looking after the Technology Transfer and as well as relations with the corporate sector.

Board of Directors

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 42 scientific publications and has been granted 62 international patents.
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 synthesis and drug formulation.
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.

Project Team

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 42 scientific publications and has been granted 62 international patents.
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.
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.
Jana Daňková, M.Sc., MBA, graduated with a master's degree in Biology at the Faculty of Science of Masaryk University and subsequently obtained M.Sc. and MBA degrees at Nottingham Trent University / Brno International Business School. She worked in multinational pharmaceutical companies Eli Lilly and Novartis in sales positions for more than 12 years. Since 2015, she has been working as a Business Development Manager at the Technology Transfer Office at Masaryk University. She is mainly in charge of developing strategies for intellectual property commercialization, negotiating cooperation with the application partners and concluding licensing contracts.
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.

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 chronic lymphocytic leukemia (CLL), and CK1 α for acute myeloid leukemia (AML).

The development of the proprietary CK1 inhibitors is based on our studies of CLL biology. CLL is a lymphoproliferative malignancy with highly heterogeneous disease course and unclear pathogenesis. Our research of pathological cell signaling in CLL has been focused on regulators of cell migration and interaction of the leukemic cells with their protective microenvironment, which often enables survival of tumor cells, disease progression and therapy evasion. We discovered that targeting of CK1 δ and ε kinases alone in CLL cells is sufficient to block the leukemic cell migration and the microenvironmental interactions and delay the disease progression in mice. Importantly, when combined with standard CLL treatment (ibrutinib, potent inhibitor of B cell receptor signaling), CK1 inhibition provided the benefit of stronger, synergistic effects in vitro and stronger response to therapy in vivo in the used animal model of CLL.

Targeting of the kinase CK1 α has been also recently recognized as an attractive therapeutic strategy for the treatment of AML and myelodysplastic syndrome (MDS). 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

Selectivity and Potency of Lead Compounds

The lead compound MU1630 was designed to efficiently target selected CK1 isoforms. Chosen out of a series of >300 compounds, MU1630 exhibits exceptional selectivity to CK1, combined with favorable PK and safety profiles. The kinome trees (on the left) show the improvement of the kinase selectivity from PF-670462 (left), which served as a model compound for the studies of the therapeutic effects of CK1 inhibition on hematological malignancies, to the novel patent-protected lead compound MU1630 (right). 

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 250 compounds were 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 I (CK1). Our main development program is focused on drug candidate MU1630 for the treatment of Accute Myeloid Leukemia (AML). Concurrently, CasInvent is developing the molecule MU1630 as a potential treatment for CLL. Both programs are in the preclinical stage of development. 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 candidate to the clinical phase Ib.

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