READDI expertise guides 100 Days Mission Therapeutics Roadmap

By READDI, February 15, 2024 — READDI played a leading role in creating the recently launched 100 Days Mission Therapeutics Roadmap, an important new tool to help the world prepare for future catastrophic viral outbreaks.

The Roadmap and the 100 Days Mission’s Third Implementation Report were released by the London-based International Pandemic Preparedness Secretariat (IPPS) during an event at the Accademia dei Lincei in Rome on January 24.

In the year leading up to the release, READDI CEO James Rosen and READDI Co-founder and Scientific Adviser Dr. Nat Moorman met regularly with other academic and industry experts convened by the IPPS to identify key issues, set goals and establish ways of collaborating to rapidly meet those goals. The pair shared valuable insights, including virology expertise, timelines and budget projections, from their experience planning READDI’s own way forward.

Given the Implementation Report’s top news — that the R&D pipeline for drugs to treat pathogens with pandemic potential is bare — the 100DM Therapeutics Roadmap lands at an especially critical moment. It lays out three strategic visions:

1. Ensure sustained funding throughout the drug development lifecycle.
2. Develop at least two Phase-2 ready therapeutic candidates against each of the identified viral pathogen families.
3. Develop programmable platforms or technologies capable of speeding up the availability of new or enhanced therapeutics in case of a pandemic — and be able to rapidly and safely apply them to treat “Disease X.”

These visions mirror those of READDI, a nonprofit biotechnology company working in the public interest with a singular focus: to make antiviral drugs available to everyone who needs them, when they need them, where they need them in the event of a viral outbreak.

“READDI has been incredibly impressed with the work of the IPPS,” says READDI CEO James Rosen. “We were grateful for the opportunity to provide leadership in the creation of the Therapeutics Roadmap and are pleased to see that the approach READDI began taking more than four years ago has now been adopted by the global community.”

Creating READDI and its way forward

No one knew what SARS-CoV-2 was when it first emerged in 2019, and no one knows which virus will emerge next. Or when. But virologists agree that the arrival of novel viruses for which humans will have no immune response is inevitable.

This quandary consumed a trio of UNC-Chapel Hill virologists well before SARS-CoV-2 began wreaking havoc around the world.

After the emergence of the coronaviruses SARS (2002) and MERS (2012), the scientists watched in frustration as antiviral research faded. “Everybody recognized the potential devastation SARS and MERS could cause, but the outbreaks were contained. Life moved on, including the funding and the interest,” says Moorman.

Moorman and his colleagues felt a similar helplessness when outbreaks from a handful of high-risk viral families — chikungunya (alphavirus), zika and dengue (flaviviruses), ebola (filovirus) — left disease, birth defects, long-term disability and death in their wake.

In response, the scientists founded READDI, with its focus on preparedness and equitable global access. Their approach? To develop oral therapeutics that are shelf stable, portable, easy to distribute and uncoupled from cold chains, so that treatment courses can be initiated at home soon after infection.

READDI’s antivirals are meant as a frontline defense, says Rosen. “Anything that requires you to have the sequence of a virus before you can start creating a drug, like monoclonal antibodies or vaccines, is too late to prevent the millions of illnesses and fatalities that can occur within months of an outbreak. And if it’s too expensive to manufacture for most of the world, must be delivered by IV or requires refrigeration, you’re not creating an equitably accessible product.”

A roadmap — even for unknown ‘destinations’

READDI’s approach is elegant and clear: to develop small molecule therapeutics (pills) that reduce viral disease, hospitalization and death. The approach also identifies routes to as-yet-unknown “destinations” — in other words, killer viruses that have not yet emerged to threaten humans.

Most antiviral drug discovery efforts target specific existing pathogens, such as SARS-CoV-2 or, say, the four distinct serotypes of dengue. READDI, on the other hand, is developing antivirals that work broadly against many (ideally all) of the viruses in a given virus family. How? By exploiting the Achilles’ heel of viruses, the fact that they cluster in families that evolved from common ancestors. READDI’s scientists identify and target conserved factors that all viruses in a family need to replicate.

This “one drug, many bugs” solution makes the drugs highly likely to work against future related viruses — even those that do not yet exist.

Planning: start to finish

An early READDI step was to commission a comprehensive antiviral landscape assessment for the top virus families of pandemic concern. That created a starting line for each virus family.

“The urgency of the 100 Days Mission Implementation Report is not overblown,” says Rosen. “From our assessment, we saw right away which virus families have been completely neglected. Knowing where the gaps are helped inform where to focus our drug discovery and development efforts moving forward.”

In mapping the path forward, READDI first estimated hit-to-lead attrition rates after modeling the probability of technical success. To establish budget projections, READDI used estimates from its own research experience, including costs of running screens and conducting medicinal chemistry. Or they bid work out to industry partners.

To reach its goal, READDI is advancing a diverse portfolio of broad-spectrum, small molecule antiviral assets focused on five virus families — alphaviruses, coronaviruses, filoviruses, flaviviruses and paramyxoviruses — with plans to add two more families when funding allows.

“READDI has the expertise, including a global community of more than 200 researchers and industry partners, and the ability to rapidly scale up,” says Rosen. “We know where we want to go. What we need to get there is spelled out in the first strategic vision of the 100 Days Mission Therapeutics Roadmap: sustainable funding throughout the development lifecycle.”