The faces behind the CARE work-packages – WP1

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It is no surprise that it is designed in a comprehensive, yet agile, structure to fulfill the 37 partners’ shared key goals: (1) to identify therapeutics for the current pandemic, (2) to identify antiviral therapies for future outbreaks and (3) to increase the understanding of the pathophysiology of COVID-19. In a set-up of eight work-packages (WPs), the scientists and management at CARE carry out the project activities that have so far resulted in valuable learnings about the COVID-19 and how it might be defeated.  

In this monthly series, we go behind the scenes through brief interviews with the leadership of each of the eight CARE work-packages to hear insights on what makes their work so special, as well as their challenges and hopes.  

WP1 – Anti-coronavirus drug discovery in phenotypic virus-cell-based assays 

The CARE work-package 1 (WP1) dedicates its efforts to identify small molecule therapeutic candidates against the current SARS-CoV-2 and potentially other variants of concern using the infectious virus. For this, the CARE scientists take a close look at how the virus can be inhibited in cell culture using drugs that could potentially qualify for repurposing, small molecule libraries and biologicals. The leads of WP1, Ellen van Damme (Janssen) and Pieter Leyssen (KU Leuven) share their view on the work in WP1 of the CARE project. 

What makes the work at CARE special for you and your WP team?  

Ellen: The CARE Consortium has enabled us to pull together experts from across Europe and bring the best minds together to mount an international answer to the challenges that the COVID-19 pandemic presents. By working together and rapidly exchanging information and knowledge, the whole is greater than the sum of its parts. Moreover, our collaboration has given rise to an armamentarium of assays already deployed to benefit consortium academic and industrial partners and beyond. 

How has the collaboration within your team developed over the past year?  

Pieter: During the intense fight against COVID, collaborations have turned into friendships and long-lasting working relationships, which is important to be prepared for future research challenges. 

What has surprised you about working in the CARE project?  

Ellen: Although viruses continue to surprise us with their ingenuity and provide us with challenges, science has come to the point that we can mount a multidisciplinary answer to respond to a pandemic with unseen speed. And yet, the virus keeps taking us by surprise, for example, with the emergence of new variants. 

CARE paper published in Science Translational Medicine: New cell-free assay 

A CARE research team developed a cell-free assay to quantify neutralizing antibody responses. Neutralizing antibody responses to SARS-CoV-2 are usually assessed using cell-based assays requiring live virus. These assays are time-consuming and necessitate additional biosafety precautions, thus limiting their clinical use. The new cell-free assay can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and it can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.

To learn more, read the paper in Science Translational Medicine: A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma

CARE paper published in Circulation: Mechanisms of SARS-CoV-2 with regards to endothelial cells

The CARE scientists investigated if the coronavirus infects and damages endothelial cells directly by viral infection or indirectly via neighborhood effects, circulating mediators and immune mechanisms. Endothelial cells build a cell layer that lines blood vessels and regulates exchanges between the blood circulation and surrounding tissues. The generated data indicates that endothelial damage reported in severely ill patients with COVID-19 is more likely secondary to infection of neighboring cells and/or other mechanisms, including immune cells, platelets and complement activation, and circulating proinflammatory cytokines. These findings have implications for therapeutic approaches to tackle vascular damage in severe COVID-19 disease.

To learn more, read the paper in Circulation: Lack of Evidence of Angiotensin-Converting Enzyme 2 Expression and Replicative Infection by SARS-CoV-2 in Human Endothelial Cells

One Year of CARE Against COVID-19 / Interview Part 3 /

On March 11, 2020 the novel coronavirus outbreak has been declared a pandemic. To combat the virus, multiple approaches are needed including therapeutic options that help those who are infected and those who are not able to be vaccinated or do not develop a strong immune response. In addition, there is a need for therapeutic approaches that help preparing for future outbreaks. Less than a month later, on April 1, 2020 the CARE consortium was formed to collaborate under as a public-private partnership to address these challenges as Europe’s largest research initiative in the fight against SARS-CoV-2 funded by the Innovative Medicines Initiative (IMI). 

In this three-part interview series, the members of the CARE Executive Committee reflect on the first of five years of CARE, answering questions like:  

• How was the team able to set up a consortium of 37 partners in a record time? 
• How can a project of this size make notable progress albeit not working together face-to-face?  
• How can CARE help to develop relevant therapeutic options?  

Professor Yves Lévy as the academic coordinator, Marnix Van Loock as the EFPIA project leader and Kumar Singh Saikatendu as the project co-leader provided answers and insights below. 

Part 3 – FINDING SOLUTIONS: A two-pronged strategy to develop relevant assets 

CARE is a five-year project with the aspiration to discover and develop several new and effective medicines and follows a two-fold strategy: a shorter-term emergency response track through drug repurposing as well as on a longer-term track for the discovery of new therapeutic candidates to prepare for the current and future outbreaks. 

What does it mean for you to be in a project progressing these two tracks simultaneously and where do they stand? 

Marnix van Loock: Right from the start of the CARE consortium, our ambitions have been clear: to identify opportunities that support the imminent relief for COVID-19 patients during the current pandemic which has recently been complicated with the identification of the variants of concern; and to prepare for the future. Within CARE, we screened the compound libraries of our partners with the aim to find candidates for repurposing. Unfortunately, these efforts did not yield any clinical candidates. However, the antibody development is already showing promising results with highly potent SARS-CoV-2 neutralizing antibodies.  

Yves Lévy: It’s important to highlight that we treat both tracks with the same commitment as there are strong links between the emergency response and the long-term strategy. The findings in the fight against the current pandemic benefit the track for the future pandemic preparedness. 

The CARE project is navigating a changing landscape and accordingly the strategy includes finding solutions for coronavirus variants. How do the new coronavirus variants impact the work and strategic orientation of CARE? 

Yves Lévy: The CARE consortium follows a very reactive approach and includes the variants of concern in its research, for example by testing the SARS-CoV-2 neutralizing antibodies against these variants. 

Marnix van Loock: The evolving SARS-CoV-2 landscape is indeed very high on the agenda of the CARE partners. We proactively incorporate this aspect into the project’s strategy to guarantee that the assets in development stay relevant. For this, we brought all leaders of the work packages together to discuss and outline the impact of the variants of concern and defined strategies accordingly. Actually, the emergence of the coronavirus variants increases the importance of CARE’s work! 

The CARE Executive Committee wishes to express its gratitude towards each member of the CARE consortium appreciating their enthusiasm, scientific passion, drive and willingness to collaborate that build the heart of CARE – a heart that is beating vividly due to everyone’s time and effort. 

– Sarah Soetbeer  

This is the last part of the three-part interview with the CARE Executive Committee. Please find the other parts here. 

One Year of CARE Against COVID-19 / Interview Part 2 /

On March 11, 2020 the novel coronavirus outbreak has been declared a pandemic. To combat the virus, multiple approaches are needed including therapeutic options that help those who are infected and those who are not able to be vaccinated or do not develop a strong immune response. In addition, there is a need for therapeutic approaches that help preparing for future outbreaks. Less than a month later, on April 1, 2020 the CARE consortium was formed to collaborate under as a public-private partnership to address these challenges as Europe’s largest research initiative in the fight against SARS-CoV-2 funded by the Innovative Medicines Initiative (IMI). 

In this three-part interview series, the members of the CARE Executive Committee reflect on the first of five years of CARE, answering questions like:  

• How was the team able to set up a consortium of 37 partners in a record time? 
• How can a project of this size make notable progress albeit not working together face-to-face?  
• How can CARE help to develop relevant therapeutic options?  

Professor Yves Lévy as the academic coordinator, Marnix Van Loock as the EFPIA project leader and Kumar Singh Saikatendu as the project co-leader provided answers and insights below. 

Part 2 – WORKING TOGETHER: Professional collaborations becoming friendships 

CARE is an initiative uniting scientists from academia, research centers, SMEs, EFPIA members and IMI2 Associated Partners in the fight against the coronavirus. In other words, it brings together a multi-disciplinary team with deep scientific knowledge, technical expertise and a strong commitment to jointly develop solutions at a fast pace. Within this framework, the CARE Executive Committee ensures scientific co-ordination and collaboration across the consortium and overall coordination and management of the project. 

After one year of working together, how do you complement each other’s expertise in the Executive Committee? 

Marnix van Loock: Our team combines different track records bringing relevant and complementary experience to the (virtual) table that cover the key aspects of our efforts. The respect and trust between us three, which was there from the start, enables us to have open, honest and thorough discussions on leading and coordinating CARE, combined with the opportunity to just pick up the phone and call each other whenever required. Also, we should not forget the critical role of the project management office colleagues supporting us in orchestrating and implementing all the efforts. 

Yves Lévy: Indeed, the trust and confidence between Marnix, Kumar and myself was there immediately and quickly led to a working environment with a very good spirit, and a smooth and flexible way of communicating. This professional collaboration is turning into a friendship! 

How do you enable and keep up the collaborative spirit across this large initiative of 37 partners while collaboration mostly takes place virtually? 

Kumar Singh Saikatendu: At an overarching level, I think there are two key enablers of any successful partnership. The first one is operational – where logistical issues such as questions around funding, compounds or material shipment are sorted out quickly. The second one is about the scientific part – where research hurdles such as assay throughput, library creation or compound progression are smoothened effectively. The IMI CARE consortium demonstrated that despite the large size and multi-party nature of our partnership, these two enablers were handled successfully in the first year and lay the foundation to deliver the much-needed medicines. 

Yves Lévy: And on a working level, there are from my point of view two main factors as well which enable this collaborative spirit. Firstly, we have created a meeting structure that enables a rapid exchange and alignment between the eight different CARE work packages. Secondly, Marnix, Kumar and myself as members of the Executive Committee are committed to offer a high degree of availability to our CARE partners and leaders of the work packages to provide advice and discuss any matters. 

Marnix van Loock: Although everything is remote and done mostly from home, we recognize that we are in the same ‘lockdown’ situation and being there for each other is the cornerstone of this success. I agree with Yves, that alignment across the different work packages is key. Although we must admit, we look forward to the time when the circumstances will allow us to meet each other face to face and celebrate this story of trusting and close collaboration. 

What are your aspirations in collaborating with other IMI2 projects or third parties? 

Yves Lévy: The first year of CARE was all about the huge task of setting up and implementing this big project and enabling research progress to find solutions for COVID-19 patients as quickly as possible. At the same time 7 more IMI2 funded projects against different aspects of COVID-19 have been started. We are working to collaborate across these projects to foster the development of solutions to the pandemic even more. 

Marnix van Loock: We are keen on building synergies and ensuring the maximization of opportunities to accelerate the development of antiviral assets, like potentially implementing diagnostic tools that were developed by other projects into our clinical trials, which will enable optimized execution of our trials. 

Kumar Singh Saikatendu: And even beyond, CARE aspires to deliver effective medicines and to position them for clinical development. I hope as we deliver these clinical candidates, other global scientific organizations step up and participate as funders and by advancing these molecules into clinical development and beyond, for example through support in manufacturing, regulatory steps or clinical trial logistics.  

This is the second part of the three-part interview with the CARE Executive Committee. Please find the other parts here.