31 Mar Complix and VIB Publish Pioneering Study on Cell-Penetrating Alphabodies in Science Advances
Publication highlights for the first time a cell-penetrating protein drug with high affinity target binding, exquisite specificity, and extended half-life in vivo
Transformative, “membrane crossing” CPAB technology designed to address multiple challenging intracellular disease targets
Hasselt, March 31, 2021 – Complix, a biopharmaceutical company developing a pipeline of transformative Alphabody therapeutics announces the publication in Science Advances of the results from a joint, multidisciplinary study with Belgian life sciences research Institute VIB and Ghent University. The proof-of-concept study demonstrates the potential of Cell-Penetrating Alphabodies™ (CPABs) to efficiently penetrate the cancer cell membrane, disrupt an intracellular protein-protein interface, and cause an anti-tumor effect upon in vivo administration in relevant xenograft models.
The article by Pannecoucke et al. can be accessed by clicking here.
CPABs are a revolutionary class of small proteins that have been designed to overcome the limitations of conventional antibodies and small molecules through combining the specific potency of biologics with the cell-penetrating capacity and stability of small molecules. Data available show that CPABs have the potential to address a wide range of disease targets, particularly intracellular targets, that are difficult for current therapies to reach.
The study, published in Science Advances, demonstrates that CPABs can be designed to efficiently penetrate the cell membrane, disrupt an intracellular protein-protein interface, and carry an albumin-binding moiety to extend their serum half-life to therapeutically relevant levels. The unique combination of these three features in a single protein scaffold is without precedent. In this publication a CPAB was engineered against MCL-1, an intracellular protein target in cancer.
The findings from this study provide strong proof of concept for the use of CPABs against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics.
Dr. Ignace Lasters, CTO of Complix, commented:
“We are pleased to see the publication of this important study, which is a clear validation of our platform and highlights the potential of CPABs to directly address intracellular drug targets in oncology. Reaching the intracellular space has been a critical limiting factor in broadening the therapeutic potential of current biologicals such as monoclonal antibodies. This proof-of-concept study clearly demonstrates the potential of CPABs as a transformative, “membrane crossing” technology to address a variety of cutting-edge and challenging intracellular disease targets. This holds the promise for the creation of an entirely novel class of therapeutics with applications in oncology and beyond.”
Prof. Savvas Savvides, Group leader at VIB Center for Inflammation Research, and Professor of Structural Biology at Ghent University, said:
“Our study clearly extends the currently charted protein-based drug-targeting landscape by targeting the well-known intracellular drug target MCL–1, a protein upregulated in multiple tumor types and correlated with therapy resistance. It is very exciting and rewarding to see how our longstanding collaboration with Complix has matured to provide the essential knowledge needed to tackle such a major and important challenge in the design of novel therapeutics.”
Erwin Pannecoucke, Maaike Van Trimpont, Johan Desmet, Tim Pieters, Lindy Reunes, Lisa Demoen, Marnik Vuylsteke, Stefan Loverix, Karen Vandenbroucke, Philippe Alard, Paula Henderikx, Sabrina Deroo, Franky Baatz, Eric Lorent, Sophie Thiolloy, Klaartje Somers, Yvonne McGrath, Pieter Van Vlierberghe, Ignace Lasters, Savvas N. Savvides. Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting. Science Advances, 26 March 2021: Vol. 7, no. 13.
Complix is a biopharmaceutical company using its unique AlphabodyTM platform to develop a pipeline of transformative, “membrane crossing” therapeutics against a number of cutting-edge and challenging disease targets that play an important role in oncology, autoimmunity and viral diseases.
In addition to crossing cellular membranes, Alphabodies have the potential to cross the blood brain barrier to address CNS diseases and to be delivered orally given their ability to cross the gut wall.
Complix is developing Cell Penetrating Alphabodies (CPABs) that can address disease targets present in the cytosol or in the nucleus of human cells. CPABs act with great specificity and high affinity on targets that are considered “intractable” by current drug formats, such as antibodies or small chemicals. CPABs are also equipped with half-life extension motifs, so that they stay in circulation for sufficient time to ensure optimal biodistribution in peripheral tissues to reach the cells where their target is located. As a pioneer in intracellular targeting, Complix aims to develop a collection of first-in-class therapeutics with the potential to cure severe diseases with high unmet medical need.
Alphabodies also provide an ideal scaffold to design potent inhibitors of viral entry. Complix believes that its research could yield broadly cross-reactive anti-viral compounds with both prophylactic and therapeutic efficacy against SARS-CoV-2 as well as future emerging coronavirus variants or mutants.
Complix has established a strong intellectual property position protecting the Alphabody platform and its emerging product portfolio through the filing of multiple patent applications. The company is led by an experienced management team with a track record of success in the biotech industry and is backed by a syndicate of experienced life sciences investors, through which it has raised close to US$ 40 million to date.
VIB is an entrepreneurial research institute in life sciences located in Flanders, Belgium. VIB’s basic research leads to new and innovative insights into normal and pathological life processes. It unites the expertise of all its collaborators and research groups in a single institute, firmly based on its close partnership with 5 Flemish universities (Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University) and supported by a solid funding programme from the Flemish government. VIB has an excellent track record on translating basic scientific results into pharmaceutical, agricultural and industrial applications. Since its foundation in 1996, VIB has created 27 start-up companies, now employing over 900 people. More information: www.vib.be
About Ghent University
After more than twenty years of uninterrupted growth, Ghent University is now one of the most important institutions of higher education and research in the Low Countries. Ghent University yearly attracts over 41,000 students, with a foreign student population of over 2,200 EU and non-EU citizens. Ghent University offers a broad range of study programs in all academic and scientific fields. With a view to cooperation in research and community service, numerous research groups, centers and institutes have been founded over the years. For more information www.UGent.be
Dr. Mark Vaeck, Chief Executive Officer
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Elisabeth Stes, External relations Manager
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Prof. Savvas Savvides, Leading Scientist
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