Viral diseases represent a major threat to global public health. AVITHRAPID aims to establish a pipeline of early stage drug candidates based on a set of small molecules whose bioactivity against various viral targets has been already shown and which can be rapidly translated into novel antiviral agents against emerging infectious diseases with pandemic potential. In addition, the consortium will conduct a Phase 2a clinical trial for a small molecule developed against Zika virus.
The AVITHRAPID research consortium comprises 18 research institutions and companies from 8 countries bringing together interdisciplinary expertise and approaches including molecular modeling, biochemical and cell-based assays, X-ray crystallography, medicinal chemistry, biophysical binding studies, ADME-Tox profiling, in vitro and in vivo PK, as well as animal disease models.
The AVITHRAPID consortium “Antiviral Therapeutics for Rapid Response Against Pandemic Infectious Diseases” is part of the Horizon Europe Framework Programme topic “Pandemic preparedness and re- sponse: Broad spectrum anti-viral therapeutics for infectious diseases with epidemic potential”, which has been launched with a budget of 50 million Euro to combat and prevent pandemics more efficiently. The AVITHRAPID project started in January 2024 with a duration of 54 months and a budget of 7.5 million EUR. The Swiss Partners in the AVITHRAPID consortium are funded by the Swiss State Secretariat for Education, Research and Innovation SERI.
Objectives
The overarching goal of AVITHRAPID is to develop novel broad-spectrum antivirals providing additional therapeutic options for current and future epidemics and pandemics based on existent substances with proven efficacy against drug targets using a rational pre-clinical drug discovery workflow.
By coordinating cutting-edge capacities and expertise already available in Europe AVITHRAPID will focus on specific objectives:
- Supporting pandemic preparedness by provision of novel approaches for the development of antivirals using sophisticated computational methods in combination with experimental validation.
- Joint development and optimization of pre-clinical candidates based on an available set of small molecules addressing various viral targets with a focus on broad-spectrum applicability
- Establish a complete pre-clinical drug discovery pipeline based on the research activities within AVITHRAPID, that allows to react rapidly in case of novel viral infections with pandemic potential.
Outcomes
The AVITHRAPID project has been fully designed to contribute to the expected outcomes of the Horizon Europe Framework Programme topic “Pandemic preparedness and response: Broad spectrum anti-viral therapeutics for infectious diseases with epidemic potential”.
These are the expected outcomes and how the AVITHRAPID Project will contribute:
1) The scientific community have an increased knowledge on viruses with epidemic potential and in particular a better understanding of different potential mechanisms of action which will directly inform the development of broad-spectrum anti-viral therapeutics for these viruses.
Contribution of AVITHRAPID: The compounds to be developed within the project allow to further study the individual targets and thereby offer the opportunity to better understand the disease-linkage and pathophysiological role of these targets and the mode of action by small molecules addressing these targets. In particular, the intention to gain atomic insight by X-ray crystallography allows to understand the detailed binding mode of the compounds and to design routes to their further optimisation. In addition, AVITHRAPID’s efforts to identify novel drug targets will provide the scientific community with further options for future treatments. All these activities contribute to improve the overall understanding of the mechanism of action of broad-spectrum antiviral compounds which is particular important for researchers in the drug discovery area.
2) The scientific and clinical communities will have access to a proven agile platform which is fit-for-purpose to support development of new anti-viral therapies for emerging (Disease X) and re-emerging infections in the context of epidemic and pandemic preparedness.
Contribution of AVITHRAPID: Besides conventional small molecule therapeutics, the research project will progresses a unique approach making use of a peptide-conjugated porphyrin ring that enables antiviral treatment beyond the blood brain barrier or the blood placenta barrier. Intended to be used as Zika virus treatment, the technique is likely to work also against other viruses. Moreover, peptide conjugation may allow to also be used with other antiviral agents providing a completely novel approach for the development of antiviral therapies.
3) The clinical communities have access to experimental broad-spectrum anti-viral candidates, based on innovative viral and host-based targeting strategies, with excellent potential against emerging or re-emerging viral infections and suitable for further clinical investigation.
Contribution of AVITHRAPID: The main ambition is the development of novel antiviral compounds with broad-spectrum applicability. The chosen strategy allows to progress various compounds towards the pre-clinical candidate status. This provides the scientific community with effective small molecules for further clinical development.
4) A diverse and robust pipeline of broad-spectrum anti-viral drug candidates is available for emerging and re-emerging viral infections, increasing therapeutic options for clinical deployment in case of an epidemic or pandemic.
Contribution of AVITHRAPID: The compounds to be developed enter the drug discovery value chain at different levels (hit, validated hit, lead, clinical candidate). These will be progressed towards pre-clinical development and one compound will undergo clinical trials. In addition, novel targets will be evaluated for their suitability to treat viral infections and it is envisaged to identify and validate hit compounds providing a broad set of bioactive small molecules with proven activity against several viruses with beneficial toxicity profile that can be further developed into novel antiviral drugs.
Exploitation
The overall goal of AVITHRAPID is to establish a community of practice comprising the infrastructure, expertise and complete range of stakeholders relevant to discover, develop and manufacture antiviral compounds. It is the ambition of AVITHRAPID to assemble and operate a complete, harmonized and accessible value chain integrating the scientific, methodological, financial, regulatory, intellectual property, production and logistics aspects as key tool for pandemic preparedness and response approach.
This includes:
- Regulatory Framework: Adressing existing barriers across the EU, with special focus on pharmaceutical incentives and legislation, marketing authorisation, HTA as well as pricing and reimbursement processes.
- Research and innovation policy: Identify major antiviral therapeutics development needs in relation to funding, including potential gaps and opportunities for joint calls. Develop innovative co-funding models, new funding streams, and/or social impact financial tools to prepare for the implementation of a (pilot) international funding call.
- Funders network: Bringing together public funders, disease-focused charities, generalist philanthropies and industry partners to share best practices, co-ordinate funding streams and promote joint calls
- Equitable access: Supporting science and policy leadership to strengthen existing and emerging innovation ecosystems that prioritize the needs of neglected populations and ensure innovations originating in low or middle income countries are integrated into international responses.
- Design of a legal entity: The foundation of a non-for-profit organization by the end will allow for further exploitation collecting all the values created in AVITHRAPID becoming a competence center and small and middle sized enterprises accelerator. This will involve establishing intellectual property, licensing and collaboration agreements, funding and operational plans and implementing a governance structure that induces transparency and trust.
- Open Science: Promoting the broadest possible sharing of research knowledge and data across the innovation lifecycle to ensure value for public investments, accelerate science, and bring solutions for patients as well as accelerate and reduce the cost of research and development
- Collaboration: Ensuring a wide external participation by organising a broad range of networking activities including all stakeholders and civil society requiring that any publication deriving from AVITHRAPID will be open access.