CARE External Newsletter – December 2023
The new issue of our biannual newsletter is out. In this edition, we share the EC sponsored recommendations about pandemic preparedness and we introduce 2 CARE partners, i.e., Iktos, a SME, and LUMC, an academic organisation.
Read the Newsletter here: CARE External Newsletter – December 2023
Published in Journal of infection: a new potent, broad-spectrum antibody isolated
The CARE partner Centre Hospitalier Universitaire Vaudois (CHUV) isolated a broad-spectrum monoclonal antibody (mAb), named P4J15, which showed neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages, against which all authorized therapeutic mAbs have become almost completely ineffective.
The collaboration within CARE with the Vaccine Research Institute (Inserm-VRI, France), the French Alternative Energies and Atomic Energy Commission (CEA) and KU Leuven (KUL, Belgium) led to an extended characterisation of P4J15 both in vitro and in vivo. This mAb provides exceptional levels of protection against infection in vivo.
P4J15 is a Class 1 mAb that shares ∼93% of its buried surface area with the ACE2 contact region and thus exerts its potent neutralizing activity against all current SARS-CoV-2 variants by blocking ACE2 receptor binding. As a result, this mAb provides exceptional levels of protection against infection in vivo.
The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations who are unable to mount a strong protection after vaccination.
To learn more, click here: Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys.
Introducing Iktos – a CARE SME organisation
Iktos was founded in 2016 by Yann Gaston-Mathé, Quentin Perron and Nicolas Do Huu, to develop an innovative and user-friendly technology platform for deep learning-based de novo drug design, leveraging a proprietary algorithm developed by Quentin and Nicolas
Iktos is an innovative company specializing in the development of artificial intelligence (AI) solutions applied to chemical research, more specifically medicinal chemistry and new drug design. These solutions foster productivity improvement in small molecule discovery, which in turn enable major productivity gains in upstream pharmaceutical R&D.
Iktos’ de novo design algorithm is based on deep generative models with reinforcement learning. It designs novel and easy to make compounds, optimized to meet a given multi-objective blueprint, with unprecedented speed, performance, and diversity.
Why did Iktos choose to get involved in CARE?
Iktos joined the CARE consortium in 2022 because it was a great opportunity to firstly be able to contribute to the research and development of effective therapies for Covid-19 patients, and secondly, to become part of a consortium of great companies and organizations known for their excellence in drug discovery and to collaborate with all of them.
What has Iktos delivered for CARE?
Iktos’ CARE objective was to discover potent SARS-CoV-2 antivirals through target-based and phenotypic-based drug discovery approaches, within the scope of Work Package 3. Iktos successfully employed a target-based approach, harnessing their Structure-Based AI technology, to design diverse and novel chemical structures. Iktos’s AI platform generated approximately 142 compounds with excellent synthetic accessibility. They further optimized the synthetic accessibility to expedite Drug Metabolism and Toxicology Assessment (DMTA) cycles, leading to the discovery of a compound with a remarkable pIC50 value of 5.47. In addition, through a phenotypic approach, they set target parameters and rewards for their AI-driven generation, enabling the proposal of novel scaffolds and the exploration of a broader chemical space. Iktos’s AI retrosynthesis tool ensured the security of synthetic accessibility, thus contributing to efficient DMTA cycles.
For more information about the different work packages, please click here
What benefits has Iktos enjoyed through participating in CARE?
Iktos experienced valuable interactions with pharma, mid-pharma and biotech collaborators, along with cutting-edge science to identify promising drug candidates.
In addition to Yann and Quentin, the Iktos team in WP3 includes
Introducing Ai-biopharma – a CARE SME organisation
Ai-biopharma was set up in 2018 by Dr Cyril B. Dousson. It is a Biopharma company which specializes in research into medicinal chemistry of preclinical drug candidates, based in France.
Ai-biopharma is an early-stage small molecule drug discovery company advancing its antiviral programmes based on a proprietary Chemoinformatic and Artificial Intelligence platform. To support the design and accelerate the discovery effort of new preclinical candidate drugs, the company has developed in-silico solutions of chemoinformatics, molecular modelling, docking, data analysis, Structure Activity Relationship (SAR), proprietary database software and also an artificial intelligence platform.
The company is developing, in its laboratories, innovative drug candidates for certain viral diseases, including Hepatitis B and SARS-CoV-2.
Why did Ai-biopharma choose to get involved in CARE?
Ai-biopharma decided to get involved with CARE based on its founding team’s extensive antiviral expertise. They believed that direct acting antivirals such as polymerase inhibitors would be the best answer to SARS-CoV-2 viral replication and variants coverage.
What has Ai-biopharma delivered for CARE?
Ai-biopharma’s achievements in CARE include the screening of a selected Direct Antivirals library (Work Package 1), the in silico screening against NSP12 of large in house virtual libraries designed for polymerase inhibition (Work Package 2), selection of potential hits from the screening (Work Package 2) and confirmation of four hit series of polymerase-like inhibitors. These series are currently advancing to move to the potential selection of a lead candidate (Work Package 3).
For more information about the different work packages, please click here.
In addition to Dr. Dousson, the Ai-biopharma team includes
Introducing Leiden University Medical Center – a CARE academic organisation
The LUMC has a long history and has its origins in the 16th century when in 1575, following a year-long siege, William of Orange granted Leiden the right to have a university. The university started with 3 faculties: Law, Theology and Medicine.
In 1996, the Leiden University Medical Center (LUMC) emerged from the collaboration between the Leiden University Hospital and the Faculty of Medicine of Leiden University.
Today, it is a centre of medical innovation that aims to improve patient care through scientific research. It trains doctors and biomedical researchers to contribute to this. In addition to general patient care, the LUMC offers specialist treatments that may only be performed in a limited number of medical centres. The LUMC distinguishes itself in particular as a referral center for complex medical questions for which there are no ready-made answers. As of 2024, all fundamental, translational and clinical research related to pathogens and infectious diseases will be integrated in the new Leiden University Center of Infectious Diseases (LUCID). This month, LUMC is opening a new Biosafety Level 3 (BSL-3) research facility, including two units to be used for studies on SARS-CoV-2 and other pathogenic coronaviruses.
The LUMC has 3 social spearheads: oncology, regenerative medicine and population health. These spearheads relate to important issues in society and medicine. Approximately 7000 people work at LUMC today.
Why did the LUMC choose to get involved in CARE?
The LUMC molecular virology team has a >30-year track record in studying the biology of coronaviruses, including a number of previous projects in antiviral drug research. LUMC decided to get involved with CARE because of the need to establish an international response to the rapidly developing SARS-CoV-2 pandemic, thus facilitating scientific collaboration and the sharing of expertise and toolboxes. Moreover, since February 2020, LUMC was coordinating the EU-funded SCORE project to target SARS-CoV-2, and its eight partners thus became a sub-network within CARE. This enabled the rapid exchange of knowledge, technologies, reagents, and candidate antiviral drugs between the two projects.
What has the LUMC delivered for CARE?
The LUMC’s achievements in CARE include many aspects in Work Packages (WP) 1, 2, 5, 6, 7 and 8 (For more information information about the different work packages, please click here.). LUMC developed assays and reagents in WP1 and 2 to better define coronavirus drug targets, and characterize and select antiviral compounds developed by other partners. Such studies into the mechanism-of-action of CARE’s drug candidates continue to constitute the bulk of LUMC’s contribution. Furthermore, LUMC performed “omics” studies in WP5, established animal models and performed preclinical studies on candidate antivirals in WP6; performed dual-transcriptomics studies in WP7; and organized a European Medicines Agency (EMA) meeting to obtain advice on combinational treatments for immune-compromised patients in WP8.
The LUMC CARE team currently includes:
Montse Bárcena, Nina de Beijer, Jonna Bloeme, Brenda Bontes, Jutte de Vries, Mirjam Groenewold, Sytze Jorritsma, Marjolein Kikkert, Marissa Linger, Kees Mourik, Sebe Myeni, Ana Roque, Anna Roukens, Ed Schmidt, Eric Snijder, Thijs Steijaert, Ali Tas, Emmely Treffers, Martijn van Hemert, Peter van Veelen, Patrick Wanningen, and Jessika Zevenhoven.
