INTREPID Alliance updated review of antiviral compounds in clinical and preclinical development for fourteen priority viruses of pandemic potential

In support of the G7’s recommended 100 Days Mission and the International Pandemic Preparedness Secretariat (IPPS), which seeks the “development of at least two ‘Phase 2 ready’ therapeutic candidates against the identified viral pathogen families of greatest pandemic potential,”¹ the INTREPID Alliance committed in July 2023 to conduct a global landscape assessment of antiviral compound R&D. The landscape analysis intends to aid in the identification of clinical (e.g., Phase 2/3 ready) and preclinical antivirals aligned with the 100 Days Mission and highlight gaps in the pipeline.

INTREPID released the first four editions of the landscape analysis in January 2024, April 2024, October 2024, and April 2025. These updates were based on non-confidential information and provided the initial summary of the clinical and preclinical phase antiviral compounds across 13 viral families of pandemic potential.^2,3,4 Clinical compounds were classified as noted in the updated definitions below.⁴ Preclinical compounds were classified as previously described.⁴

The Antiviral Clinical and Preclinical Development Landscape – 5^th Edition begins our scheduled reports with emphases on the changes in compound classification since the previous edition. In view of the evolving state of global viral disease threats, INTREPID evaluates the list of viral families to include in our landscape on an ongoing basis. Informed by the World Health Organization list of priority diseases,⁵ the 5th Edition Antiviral Landscape evaluates 14 viral families of pandemic potential, adding Phenuiviridae to the analysis.

Today’s release of the interactive version of the 5^th edition of the Antiviral Clinical Development Pipeline complements the previously downloadable version of the Landscape published on May 12, 2026, and inclusive of data from December 2024 to January 2026. The landscape shows all compounds categorized by phase of clinical development, viral disease indication, viral target, developer, and approval status. Novel unapproved compounds in clinical development are classified as either Promising, Watch & Wait, Investigational Antiviral-Indication Expansion, or Investigational Antiviral-Indication Expansion Preclinical Exploratory.

With this release being the 5^th edition of our landscape, we have reviewed the current data with a longitudinal perspective relative to the previous editions over the past 2 years. Some, but limited, progress was noted in a few areas which are detailed below:

Clinical Compounds

• The number of investigational clinical compounds under evaluation has remained relatively stable for COVID-19 and Non-COVID-19 viral disease indications.
  • This is reflective of clinical development where compounds advance from preclinical into clinical development and replace either some compounds that have dropped out of development or others that may have advanced to regulatory approval.
• 5 of 12 clinical phase compounds categorized by the INTREPID Alliance as Promising have advanced forward in development:
  • 3 Promising achieved regulatory approval for Influenza.
  • 2 Promising moved from Phase 2 to Phase 3.

Preclinical Compounds

• A marked 2.3-fold increase in preclinical compounds for Non-COVID-19 activity is noted since 3^rd Edition.
  • This reflects a shift in early phase antiviral drug discovery activity and perhaps funding, as is evidenced by these also including 15 new preclinical compounds from the U.S. NIAID-funded AViDD Centers.

Broad-Spectrum Antivirals

• Indication Expansion (IE) evaluations exploring potential broad-spectrum activity against Non–COVID-19 viral diseases have grown over time.
  • The increase in potential indication expansions with approved or investigational compounds shows expanding efforts to explore broad-spectrum potential of antivirals with existing clinical experience.

While the incremental progress noted may be encouraging, significant gaps still remain:

• Three of the 14 viral families have no clinical or preclinical evaluations: Adenoviridae, Hantaviridae, and Peribunyaviridae.
• Only 8 viral disease indications are in clinical evaluation across 6 of the 14 viral families.
• The majority of the Promising and Watch & Wait clinical compounds are under evaluation for COVID-19 and Influenza.
  • There is still a gap in phase-2-ready Non-COVID-19/Non-Influenza antivirals

Evaluation of potential indication expansions of existing clinical phase or approved antivirals is the quickest way to assess potential clinical utility for possible broad-spectrum activity. These compounds already have previous safety, tolerability, dosing, and efficacy data from preclinical and clinical studies. It should be noted that while discovery and development of new chemical entities with possible broad-spectrum activity requires many years, such efforts should also occur in parallel.

A systematic assessment of antiviral activity in vitro and/or in preclinical in vivo efficacy models, where available, can support informed decision making when the need arises for rapid access to antivirals for use in treatment of an emerging outbreak or a different viral disease than the one(s) currently evaluated.

The importance of such an approach is highlighted by recent outbreaks with Hantavirus and Ebola-Bundibugyo virus. With Hantavirus for example, there are currently no approved antivirals for treatment of hantavirus infection and, based on publicly available information since the 1^st Edition of the INTREPID landscape in January 2024, no ongoing preclinical or clinical compound evaluations of new or unapproved antivirals have been noted.

For Bundibugyo virus (BDBV) and other filoviruses (e.g., Zaire Ebola virus (EBOV), Sudan virus (SUDV), Marburg virus (MARV) and Ravn virus (RAVV)), the current filovirus antiviral landscape highlights the urgent need for broad-spectrum antivirals with activity across viruses within a given viral family; this is applicable not only to the filovirus family, but also to other families such as flaviviruses, paramyxoviruses, bunyaviruses and others. Filoviridae is one of the fourteen viral families included in the INTREPID Alliance antiviral landscape that relies on publicly available information based on the efforts of our scientific advisors and our collaborators at Airfinity. While monoclonal antibodies for the treatment of and vaccines for the prevention of EBOV infection are approved, there are currently no approved direct-acting antivirals for treatment of orthoebolavirus or orthomarburgvirus infection.

Our longitudinal analysis of the antiviral R&D landscape highlights the persisting urgent need to strengthen our outbreak readiness by addressing R&D gaps through funding and policymaking with a focus on known as well as emerging viral diseases with potential to cause outbreaks on a major scale, including a global pandemic. Given attrition rates and time required to progress new compounds through the various stages of antiviral R&D, together with the routine uncertainties that come with preclinical candidates, a coordinated and systematic approach to advancing preclinical and clinical phase antivirals is merited.

The 5^th Edition landscape and interactive pipeline are based on evaluation of non-confidential information as of January 2026. Going forward, these INTREPID landscape reports will be updated as resources allow.