Skip to main content
Published January 24, 2024

INTREPID Alliance review of antiviral compounds in clinical development for twelve priority viruses of pandemic potential

The Antiviral Clinical Development Landscape

In support of the G7’s recommended 100 Days Mission and the International Pandemic Preparedness Secretariat, which, in today’s released annual report, seeks the “development of at least two ‘Phase 2 ready’ therapeutic candidates against the identified viral pathogen families of greatest pandemic potential.” The INTREPID Alliance committed in July 2023 to conduct a global landscape assessment of antiviral compound R&D from which a listing of promising preclinical and a listing of promising Phase 2 ready clinical compounds will be derived. The intent of the landscape analysis is to aid identification of clinical (e.g., Phase 2/3 ready) and preclinical antivirals aligned with the 100 Days Mission and to highlight research gaps. Today, we are releasing the first phase of the landscape: the Antiviral Clinical Development Landscape. It will be updated quarterly.

Scientific review and initial triage of a global R&D database of antivirals,i as of November 16, 2023, targeting 12 viral families of pandemic potential revealed there are 61 unique compounds targeting 80 indications for 9 of 12 priority viral families.ii Of the 61 compounds, 19 are approved by stringent authority or other national regulatory authorities, 26 compounds are undergoing clinical development from Phase 1-3. The remaining 16 of the 61 compounds are undergoing further information gathering by the INTREPID Alliance.

Developers and Sponsors of Clinical Phase Compounds

Our analysis found that the biopharmaceutical industry (both large and small companies), represents nearly 88 percent of the global antiviral clinical developers. Academia represents nearly 8 percent, contract research organizations represent 3 percent and government approximately 2 percent.

Interactive Antiviral Clinical Development Pipeline

In the interactive pipeline below, compounds are reported by phase of clinical development, viral disease indication, viral target, developer and whether approved, in development, paused or undergoing further information gathering.


Icon Approved S.A.
Icon Approved O.N.A.
Icon Ongoing
Icon Paused
Icon Undergoing Validation
Icon
  • Icon

    Approved by Stringent Authority

  • Icon

    Approved by Other National Authorities

  • icon

    Ongoing: Currently in clinical development

  • icon

    Paused: Program discontinued for business priorities or no public disclosure of on-going studies.

  • icon

    Undergoing Validation: Intrepid seeking additional information

Phase 1 (20)

Phase 2 (23)

Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon

Phase 3 (11)

Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon

Phase 4 (4)

Icon
Icon
Icon
Icon

Approved (22)

Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon
Icon

Indication Legend

Chapare hemorrhagic fever
COVID-19
Crimean Congo hemorrhagic fever
Dengue
Ebola
Japanese encephalitis
Hendra virus
Human Adenovirus A-G
Influenza
Lassa fever
Polio
Rhinovirus

To improve our listing, developers are invited to submit non-confidential information on their compound candidates.

Viral Families, Indications and Phase of Development

The majority of clinical phase antiviral compound/indications are targeting coronaviruses (SARS-CoV-2) and orthomyxoviruses (Influenza) and other indications under development or approved include Human Adenovirus, Lassa fever, Chapare hemorrhagic fever, Ebola, Dengue, Japanese encephalitis, Crimean Congo hemorrhagic fever, Hendra virus, Rhinovirus, and Polio. Viral families representing gaps in clinical development are Hantaviridae, Peribunyaviridae, and Togaviridae.

View Now

Antiviral Mechanisms/Targets

Replication (n=31), protease (n=19), and entry inhibitors (n=17) predominate the antiviral mechanisms/targets in clinical development or approved antivirals. Assembly/Release (n=7), ribavirin (n=4), and combination viral target approaches (n=2) represent the remaining mechanisms/targets of the clinical development or approved antiviral pipeline.

View Now

Methodology: Global Database and INTREPID’s Triage

The INTREPID Alliance triaged a global antiviral R&D database using stringent inclusion and exclusion criteria to arrive at the Antiviral Clinical Development Landscape. The database was licensed from Airfinity, a predictive health intelligence and data analytics firm, who monitors preclinical and clinical development of diverse compounds against 12 viral families that pose the greatest risk of pandemic potential. Airfinity sources clinical stage candidates from global trial repositories, such as those from NIH, WHO, and other national-level repositories including the US, UK, China, India, etc., as well as media/press releases, biopharmaceutical pipeline websites, preprints and peer-reviewed publications by keyword matching and scraping. The information about preclinical candidates is also sourced from publications and biopharmaceutical pipeline websites through keyword matching and scraping. Some compounds are also added based on data presented at conferences (e.g., ICAR, ECCMID) attended by Airfinity analysts. Historic approvals are collected from government websites (and other available sources) with the earliest approvals collected from 1980. After scraping and import of the data, compounds are manually checked and annotated by Airfinity subject matter experts and analysts to ensure all associated data points are accurate and up to date. The information from Airfinity is updated monthly.

Data are generally categorized by compound, developer or sponsor, antiviral mechanism of action/target, viral family, viral disease (e.g., indication) and phase of development. Compounds that are already commercially available for 1 or more indications are further classified by the type of regulatory authority granting the approval per stringent authority (S.A.) or other national authority (O.N.A.). As of November 16, 2023, the Airfinity database identified 687 diverse compound/indications for the 12 priority viral families of pandemic potential; 387 were preclinical and 300 were in the clinical phase of development and/or approved by a global regulatory authority.

INTREPID Alliance Inclusion and Exclusion Criteria

A triage, using inclusion and exclusion criteria, of the clinical phase and approved compound/indications identified 61 distinct antiviral compounds associated with 80 compound/indications, as reported above. Consistent with INTREPID’s mission of advancing small molecule antiviral development, compounds included were small molecules, peptides, and RNA-based compounds with known direct antiviral mechanisms of action, in vitro/in vivo activity, first-in-human (FIH) single ascending dose vs. multiple asending dose data completed and no major safety signals observed. Compounds excluded from our analysis were antibodies, antibiotics and other anti-infectives, cell-based therapy, HIV or HCV-specific antivirals, host targets (including immunomodulators), natural products/nutraceuticals/herbals and vaccines.


Next Steps

Later this year, we will publish a list of promising Phase 2 ready candidates that can be quickly deployed as antiviral drugs derived from this landscape. We will also release a list of preclinical stage compounds that may have utility against 12 viral families identified by the INTREPID Alliance as having potential to result in a pandemic. The preclinical listing will be derived from a soon-to-be-released preclinical global landscape.

Our 2024 Deliverables

  • Initial Clinical Triage - January 24
  • Promising Clinical Compounds - February
  • Initial Preclinical Triage - May
  • Promising Preclinical Compounds - June
  • Updated Quarterly

INTREPID will offer advice and consultation to help accelerate the selected antiviral compounds that have the strongest potential to positively alter the course of future pandemics. In addition, the INTREPID Alliance engages reactively with academic and biotech entities to understand their ongoing activity; compounds and compound/indications identified through this mechanism will be added in future iterations of the antiviral landscape.

Treatments are considered an integral part of any effective pandemic response, with antivirals playing an important role in saving lives. INTREPID will also engage with policymakers and public health bodies to ensure that antivirals are incentivized and integrated appropriately into global and local efforts to be better prepared against future pandemics.


i Compounds included small molecules, peptides, and RNA-based compounds with known direct antiviral mechanisms of action, in vitro/in vivo activity, first-in-human (FIH) single ascending dose vs. multiple ascending dose data completed and no major safety signals observed.
ii 12 priority viral families identified by the INTREPID Alliance Scientific Working Group using the NIH/NIAID priority viral family list; World Health Organization priority disease areas; and Airfinity database of antivirals.