CARE embarks on an unprecedented mission to get ready for coming COVID-19 waves and new coronavirus outbreaks
The world needs to prepare for a future wherein waves of COVID-19 and other coronavirus outbreaks become part of the landscape. Apart from studying the potential of existing drugs to treat COVID-19 in the short-term, the CARE consortium are working on preparing for a better response to outbreaks that will inevitably occur much further down the road.
“We are aiming to get a deep understanding of the virus,” says Professor Yves Lévy, Executive Director of the VRI-Inserm and CARE coordinator. “In the mid-term we aspire to come up with better treatments that will definitely still be needed following a first wave. In the long-term, CARE also aspires to build a foundation for better response to future coronaviral threats, which is an emerging topic.”
CARE is among the first initiatives to go after such a large, holistic and future-proof response to the outbreak. It’s also the largest of the scientific research initiatives being supported by IMI in the fight against COVID-19.
“We have three key parts: repurposing existing compounds to have candidates or potential therapeutics in clinical testing within 18 months; discovery of small molecule treatments directed against viral proteases (36 months to clinic); and discovery of antibodies directed against the spike protein, with a view to going to clinic within 36 months.”
Of the antibodies, says CARE project leader Dr Marnix Van Loock, Senior Scientific Director and R&D Lead of Emerging Pathogens, Global Public Health, Janssen Pharmaceutica NV, “They have not just the potential to treat the disease, but also to prevent it, because antibodies could be given to family members or peers of people who have tested positive, in order to prevent infection, or to elderly people who may not be able to achieve sufficient vaccine immune responses. They could also play a role if vaccines are not as effective as hoped.”
CARE researchers will try to identify markers contributing to host immune responses to COVID-19 infection and their correlations with clinical outcomes. They will assess ADME (absorption, distribution, metabolism, and excretion), potency and safety, and carry out pharmacokinetic and pharmacodynamic modelling of therapeutic candidates through in-vitro and animal models.
Not without challenges
According to CARE co-lead Dr Kumar Saikatendu, Director, Global Research Externalization, Takeda, “Despite being positioned for success, the team sees a few challenges; conducting clinical trials once molecules are ready in three years may be a challenge if the virus disappears from the general population, making patient recruitment difficult.”
“Also, while SARS-CoV-2 is from a known coronavirus family, it is unique in infectivity and physiopathology. It will be necessary to understand this from multiple scientific fronts in order to adapt treatment strategies. This is especially true if drugs are required to be effective against future variants of the coronavirus,” added Dr Saikatendu.
The consortium plans to screen more than 600,000 compounds from more than ten different and diverse small molecule compound libraries. The teams are working on advanced compounds for repositioning, and screening a larger set of compounds based on their potential to inhibit key viral targets that interfere with the viral replication in host cells.
“The goal is to quickly identify the first candidates that show activity as single agents or in combination to enable synergistic effects on the potency, while also covering escape mutations that may appear over time. This will ensure preparedness for potential coronavirus outbreaks in the future.”
The consortium’s 37 globally-renowned academic institutions, research organisations and pharmaceutical companies are creating a network of laboratories, clinical centres, data and knowledge repositories that will act as a leading coronavirus knowledge hub in Europe.
The consortium have fielded more than 400 requests to explore collaboration opportunities. They are committed to the FAIR (findable, accessible, interoperable, reusable) principles of open science and will disseminate scientific results through open access platforms, peer-reviewed journals, relevant conferences, meetings, workshops, and project events. The consortium will also communicate with the EVAGLOBAL H2020 consortium, and has committed to collaborating with the other funded COVID-19 projects to ensure the acceleration of effective therapies.
“CARE is spearheading an unprecedented level of open science and collaboration across industry and academia, setting new standards for the future of pharma R&D,” added Dr van Loock. “This, and the pan-European and globally-networked approach, are a features I do not see elsewhere.”
CARE is coordinated by Inserm-VRI, Janssen and Takeda.