Therapeutics Development Coalition offers hope

In August, READDI and its collaborators made the case for a Therapeutics Development Coalition in the pages of PLOS Global Public Health.

“The COVID-19 pandemic starkly highlighted the underdeveloped and poorly coordinated pipeline of safe, effective, fit-for-purpose, and affordable therapeutics for diseases with pandemic potential,” the authors wrote.

In the following Q&A, READDI Co-founder and Scientific Adviser Nat Moorman, who has been instrumental in helping shape the Coalition, discusses its purpose and current priorities.

How urgent is the need for antivirals?

The need is quite urgent. There’s currently a major epidemic of dengue virus. There’s an outbreak of Marburg virus. Bird flu is spilling over to mammals, including humans. And there have been several other viral outbreaks this year. The pace is not slowing. If anything, it’s accelerating. For almost all these viruses, we don’t have any effective antiviral therapies.

COVID-19 showed us that we need antiviral drugs to treat sick patients and keep them from getting sicker, filling hospitals to capacity and dying. During the year before we had vaccines, we saw the consequences of not having those antiviral therapies ready on the first day of an outbreak.

How will the Therapeutics Development Coalition help solve this problem?

Given that there are at least eight families of viruses with epidemic and pandemic potential, there’s a tremendous amount of work to be done. Members of the Coalition can work together to move therapies forward into the clinic so that we have a chance to be prepared.

The Coalition lets folks who are enthusiastic about their research see how their efforts fit into the larger, concerted effort. It also lets them connect with people who can help them, be it with reagents, expertise, funding or something else.

A central role for the Coalition is to align people around the needs — the gaps — and then make sure everyone is working toward the same goals and filling unique spaces rather than duplicating efforts.

READDI is collaborating on the Coalition with some of the world’s largest public health organizations — the WHO, Unitaid, DNDi and others. What does READDI bring to the group?

READDI brings a singular focus on the development of those therapeutics. Many of those groups are involved in the important work of how we prepare and respond in the case of an outbreak. READDI is focused on making the actual therapeutics. Our work links the intentions and the planning with the medicines the world needs.

What are the current priorities for the Therapeutics Development Coalition?

There are three main priorities: building preclinical and clinical development teams for each virus family of pandemic and epidemic concern; creating a virtual data hub for sharing resources; and launching projects that develop new therapeutics.

What role will the development teams play?

We’ve noticed a disconnect between the different stages of antiviral development, particularly in the preclinical space, which is the most pressing space now. People at the earliest stages don’t always consider or operate in the later stages of development. That can lead to costly missteps. So, we’re building preclinical and clinical development teams for each virus family. They will create strategies to help developers consider all the downstream points in their development programs. We want to make sure folks in the earliest stage discovery efforts are thinking about the requirements for preclinical testing and eventual clinical development right from the start.

How about the virtual data hub?

The purpose of the hub is to enable people across the preclinical pipeline to do their work more efficiently and more effectively. We’ll do that by making visible the reagents, data and resources from the researchers working in this space. For example, if you’re interested in developing an antiviral for a target, you’re going to need an assay to measure the target’s activity. If somebody else has already made that assay, there’s no point in you duplicating that effort.

There’s a barrier to entry in terms of generating the tools you need for discovery and development. We can significantly lower that barrier by sharing resources. We hope to encourage participation, particularly from places where resources may be less abundant.

A lot of the information on the hub will be useful in a pre-competitive space. Fundamentally, at least on the academic side, that’s the way this works. When my lab takes funding from, say, the NIH, we have an obligation to publish that data and to make those resources available. The hub will be an even more effective way to share resources.

What’s the purpose of the projects?

The projects are where the actual work to develop antiviral therapeutics takes place. The projects are the whole point. The idea is to have projects that are filling the gaps identified by the preclinical development teams. The initial projects are designed to move promising therapies forward and fill the pipeline to account for the attrition that’s inherent in the process of developing therapeutics.

You have to start somewhere, and you have to start now. There are sick people today who need antiviral therapies. And we know more viruses will emerge in the coming years. This isn’t a theoretical situation. We really don’t have a choice.

There is an impression that cost is a barrier to progress. Is that impression accurate?

The two landscape analyses conducted by READDI and the INTREPID Alliance [a consortium of biopharmaceutical companies focused on pandemic response] reveal the same point — that there’s a big gap in the early-stage development of antiviral therapeutics. Right now, there’s nothing to put into clinical development for most viruses, so we need to focus on those earlier stages. Those initial efforts can happen for a fraction of the cost of the later clinical development.

None of the three currently approved COVID-19 drugs — molnupiravir, remdesivir and Paxlovid — started from scratch when the pandemic began. Developers built off work that had been done ahead of time. Paxlovid started as a lead compound that had been shelved at the end of the original SARS outbreak in 2003. It took longer to get to patients because they had to do all the preclinical development. They did it in an amazingly accelerated timeline, and it’s been a real game changer. But imagine if you had a pill like Paxlovid in January of 2020 instead of two years later. Thousands, if not millions, of lives may have been saved, and much of the hospital overcrowding and many of the shutdowns could have been avoided.

We need to do the discovery and development work now for all families of pandemic and epidemic concern. The Coalition approach will help us get there.