Preparing for future pandemic: outputs and progress resulting from a European Commission (EC) sponsored workshop in November 2022

While Covid-19 is no longer deemed to be a pandemic, the risk of future pandemics remains. Application of lessons learned during our collective recent experience is vital to being in a stronger position to handle this situation again.

Members of the CARE consortium were among the participants of a workshop held a year ago, organized by the EC’s Directorate-General for Research and Innovation (DG-RTD) and the European Health Emergency Preparedness and Response Authority (HERA) to explore the opportunities and challenges of providing globally available broad spectrum antiviral therapeutics as a tool for pandemic preparedness.

Given the evolving and unpredictable nature of the coronavirus, the delegates of the workshop recommended inclusion of broad-spectrum antiviral therapeutics as a key tool of pandemic preparedness. The workshop which was set up with input from Dr. Ed Schmidt and Prof. Eric Snijder (LUMC), and Johan Neyts (KUL) from CARE was also attended by Marnix Van Loock (Janssen).

Why broad spectrum antiviral therapeutics?

Broad-spectrum antiviral therapeutics in cocktail or combination formats to limit drug resistance, can potentially target broader viral families or groupings in an initial outbreak, crucially buying time for more targeted therapies to be developed and tested in parallel, by containing the spread of the (novel) virus in the early stages and limiting the impact of the pandemic on the health system. The reassurance of knowing there is a swift therapeutic response to an arising future epidemic is important for society, having experienced the impact Covid-19 had on so many lives and economies globally.

Key recommendations from the workshop

To make this a reality requires measures to support rapid global drug development including effective collaborations though global and harmonized research infrastructures, adequate and flexible manufacturing capacities, fast and efficient global clinical trials, clear regulatory frameworks for broad spectrum antivirals (as current regulatory pathways only provide approval for a specific viral disease) and sufficient and flexible funding.

In this context, public-private partnerships such as CARE are an important tool to mobilize the expertise needed in an emergency response and to enable sustainable funding. Moreover, the importance of basic research to understand pathogens was highlighted as it is the foundation for the research done in response to an epidemic or a pandemic.

Since the workshop took place almost 12 months ago, a new series of calls for proposals was launched by HERA on broad-spectrum antivirals with various projects being approved in 2023. One of them is the Panviprep consortium, which will start on 1 January 2024 and in which all eight partners of the SCORE consortium (who are also all CARE partners) together with seven additional partners, will develop antiviral drugs against a range of pandemic viral threats.

How does this relate to CARE?

 CARE is heavily involved in broad-spectrum antiviral development as part of its preparedness track. These recommendations lend weight to the ongoing antiviral discovery and preclinical work being undertaken today in CARE across numerous work packages.

For more information

November 2022 meeting outputs: https://op.europa.eu/s/y449

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