Could XPRIZE Healthspan deliver the ‘holy grail’ for longevity science?

Dr Jamie Justice on how the $101m competition can deliver a lasting legacy to the longevity field and it’s not about the prize money.

Yesterday’s launch of XPRIZE Healthspan has kicked off a seven-year, $101 million race to find therapeutics capable of reversing the effects of aging. To many, this may sound like the stuff of science fiction, but huge progress has been made in recent years showing that aging, while clearly a complex, multifactorial process, is a process that can be therapeutically mediated

Despite all this progress, there are still no approved regulatory pathways to show whether therapeutics designed to extend healthspan and longevity actually work in humans. XPRIZE Healthspan was created to incentivize rigorous testing of these therapeutics and hopefully provide the answer to the question: can we restore function lost to aging in humans?

Longevity.Technology: The launch of XPRIZE Healthspan has everyone talking about aging, healthspan and longevity – which is already a good thing for the field. But how did the competition come together, how will it work in practice, and what are some of the challenges it faces over the next seven years? We caught up with XPRIZE Healthspan’s executive director Dr Jamie Justice to find out.

A gerontology professor at Wake Forest University, Justice is a renowned academic in the field of aging science. She has dedicated her career to research that advances the hypothesis that by targeting the basic biology of aging the incidence of multiple age-related diseases can be delayed or prevented. Which is presumably why XPRIZE founder Peter Diamandis approached her to head up what is the largest ever competition of its kind.

Could XPRIZE Healthspan deliver the ‘holy grail’ for longevity science?
Jamie Justice and Peter Diamandis discuss the launch of XPRIZE Healthspan at the the Global Healthspan Summit in Riyadh, Saudi Arabia.

“Throughout my career, I’ve been trying to test interventions going from preclinical to clinical translation – small proof of concepts, senolytics, dietary lifestyle interventions and so on,” says Justice, who also serves on the executive committee for the targeting aging with metformin (TAME) trial. “This is my stomping ground – this is what I do. And I know the heartbreak and the barriers all too well – eight years on, and there’s still no TAME trial in the field.”

No regulatory pathway for longevity

The challenges facing longevity and healthspan therapeutic development are well understood. Developing and testing therapeutics even for well-characterized clinical diseases like cancer and cardiovascular disease is arduous, with 12-17 years from research and development to regulatory approval for clinical use. There is no regulatory pathway (yet) for therapeutics that target biological aging, so there are still no standard pathways to judge the effects of therapeutics to counteract aging itself.

“It’s a heartbreaking thing building a translational geroscience network, trying to pull people together, get resources together, get people steering in the same direction,” says Justice. “We’ve tried to do it with federal funding, with philanthropic funding, and through other means. But there’s no buy-in – you don’t have the power to really make change on the regulatory side, because everybody’s doing their own thing. I’ve seen this, I’ve worked in it.”

These concerns were also front of mind for Diamandis, whose vision for XPRIZE Healthspan was to change the paradigm for therapeutics targeting aging.

“Peter came out of left field with a completely different approach to the problem,” recalls Justice. “Instead of prospective funding, if we dangle a big ass carrot out there, we actually have the power to bring people together to start the conversation that’s needed to make change. That was the goal, and that’s what brought me to XPRIZE.”

XPRIZE Healthspan offers $101m prize for successful longevity therapeutic
Peter Diamandis announces XPRIZE Healthspan with Hevolution CEO Mehmood Kahn.

The road to victory

While the prize purse of $101 million is certainly headline-grabbing, the real story is the scale of the competition. Hundreds of teams from around the world are expected to apply over the next two years, at which point 40 of the registered teams will be selected by the judging panel to receive a $250,000 award to support their on-going work.

“In the grand scheme of things, $250,000 is not a lot, but the teams can use that to at least seed proof of concept studies in humans, if they’re not already there,” says Justice.  “If these are novel therapeutics, they’re going to need to do target engagement, they’re going to have to figure out dosing and administration – can you get your regulatory paperwork, can you administer to humans, do you have the resources you need to go into a one-year trial?”

By that time, Justice expects that most of the 40 teams selected will probably already be involved in trials of some sort, potentially for a specific disease indication.

“Those that are, would probably have a biomarker signal that looks like it’s going in the direction of change, and at least have enough of a safety signal to give us a go for additional testing,” she says. “This could be an easy add-on to an existing trial, as long as it fits within the frameworks that we’ve developed.”

In another year or two, the judges will select the top 10 teams from the 40, who will each receive a further award of $1 million to continue their work.

“That is definitely not enough to run a one-year trial, but it is the seed money to do so,” says Justice. “And then they’ll have to test their therapeutic. As long as it’s safe, we’re hands off. They’ll have one year of baseline testing and follow up, and we’ll be tracking everything they do – we’ll have common data management systems, measurements of function pre and post supported by biomarkers, supported by safety considerations, accessibility, and adherence.”

Functional improvement is key

The ultimate winners of XPRIZE Healthspan will be able to demonstrate that their therapy restores function by 20 years (minimum 10 years), across three key domains: muscle, cognitive, and immune function.

“This is key for the longevity field – our framework is about functional improvement,” says Justice. “We’re focusing on function, because we’re asking teams to show improvement, which is very different than something like the TAME trial, which is looking at prevention. We have a ‘menu’ of possible measures that people can use under the three domains of muscle, cognitive and immune function. We want teams to have a strong signal and show that they’ve made change in a meaningful way across all three domains.”

From a therapeutic perspective, Justice expects applying teams will represent a huge variety of differing approaches.

“There are so many opportunities – it could be a new drug or a repurposed drug, it could be alone or in combination, or it could be a device, a supplement, a biologic, a vaccine, or a gene or stem cell therapy,” says Justice. “And there are any number lifestyle approaches – it could be dietary, there are some great fasting mimicking diets out there, and other things that are very testable, very provable, or a combination of approaches.”

Longevity’s holy grail?

Given the tight timeframes involved, it may seem that the competition is stacked towards a repurposed drug or a new combination of repurposed drugs, but Justice says XPRIZE also wants to drive innovation.

“In fact, innovation is going to be a judged criteria for qualifying submissions,” she says. “You’re going to need to hit all three systems, so we expect a lot of combination approaches. But we can’t have any bias, we’ll let people test whatever they’re going to test – we just set up the framework, and we need to make real solutions.”

At the end of the day, Justice believes the real winner of XPRIZE will be the field of aging science itself.

“I think the real value and impact of the prize is not going to be any single trial or crowning a winner, I think it’s actually going to be the value that is going to come from actually combining all those datasets,” she says. “If we get everybody on the same data platform, so we can merge the data at the end, you could start to envision some meta-analyses, where we can look to see whether a biomarker is a mediator of a response. As somebody who’s worked in biomarker validation and development for trials before coming into this, that’s the holy grail.”

“Until now, we didn’t have gerotherapeutic trials – there hasn’t been a way to actually get to those surrogate biomarkers. And it’s such a deep need, and this competition is a great opportunity to give back to science. It’s why I joined. This is my field – and I think we could really make an impact.”