The $101 million XPRIZE Healthspan has just announced its Finalists – 20 teams that lead the pack, competing to claim its Grand Prize when judging happens around 2030. All Finalists are now commencing clinical trials to attempt to produce evidence of longevity benefit in humans. 10 of the 20 Finalists have been selected to receive Milestone 2 Awards of US$1 million each.

The organisers hope the Grand Prize will find treatments that improve performance in three domains – muscle, immunity and cognition – by the equivalent of 10 or more years. Competitors who show the biggest improvement could net as much as $81 million if they reach the ‘stretch goal’ of a 20-year improvement across all three measures.

The twenty shortlisted teams run the gamut from offering stem cell infusions, to gene therapies, to exercise plus supplements (a list of the Finalists is available at the end of the article). Some of the therapies are early in their scientific journey, while some boast more substantive existing evidence (e.g., exercise is one of the best-studied things you can do for your health and is known to impact all of the domains being tested).

At the Longevity Initiative, we believe prizes are one of the most effective, but underused tools to efficiently test different hypotheses and fund those with the best emerging evidence. 

We therefore spoke with XPRIZE Healthspan Executive Director Dr Jamie Justice about the Finalists, and what this latest phase of the competition means for the Prize and longevity science overall.

The Interview

We were curious how the competition had weighed existing scientific evidence against more practical factors like the ability to run a trial in time for the prize deadline. Perhaps unsurprisingly, the ability to run a trial by a deadline was the base criterion in the semi finals. The judges primarily assessed teams’ abilities to get regulatory approvals, recruit human subjects, and deploy in an accelerated fashion. Beyond that gating criterion, the organisers aimed to ensure a balance of innovation, approach, evidence, accessibility and scalability.

As longevity therapeutics should be affordable for all, we asked first how accessibility was prioritised. Dr Justice told us that while some of the Finalists’ therapies may be expensive or hard to get at present, others were not. She cited telemedicine approaches with repurposed and generic drugs or nutraceuticals.

Accessibility is connected to regulatory considerations. While regulations, for instance on gene therapy, can thwart clinical trials in major markets such as the USA (and therefore could limit access during the trial in the USA or cause late availability of a potential intervention even after approvals in other markets), the competition’s uniform and transparent standard meant that wherever in the world they are conducted, trials could be compared head-to-head. The evidence that would emerge was approach-neutral: it could support approaches currently thought either relatively safe or relatively high-risk and high-reward. 

This openness to unconventional regulatory approaches should give a therapy an opportunity to get a foothold, scale, then lower its eventual price tag and expand access.  However, as we frequently see with other therapies, exclusion from the currently dominant US market can considerably impact pricing. This exclusion is a roadbump to scaling that many biotechs in the past have struggled to overcome.

The trials, she notes, will also generate evidence on real-world practicality – what the therapies cost to deliver, and whether people stick with them – the numbers on which any claim about access ultimately rests. Until then, she suggests, talk of affordability in either direction is speculation. Dr Justice was confident that the Finalist cohort had a diversity of approaches which helped build the evidentiary base on accessibility.

We then got to talk about the data the Finalists were producing:

The LI: Two of the teams are combining exercise with supplements or longevity drugs. How can we distinguish the effect of the exercise versus the medicines? Will they be required to run a (literally!) active exercise-only control arm? Has XPRIZE considered running its own exercise-only controls?

Dr Jamie Justice: Our population is ageing and what we need are effective solutions to close the gap between healthspan and lifespan. We do not need to become dogmatic about how trials are usually structured. The goal of XPRIZE Healthspan is to determine whether an intervention meaningfully improves function in people – not necessarily to isolate the contribution of every individual component of a combination therapy. Combination approaches are common in medicine, and many teams are testing them.

All teams must have a control group, so we know that the treatment effect is not by chance. We don’t mandate an exercise-only control, but we will not allow teams to tell trial participants to stop exercising or limit their activity levels. If exercise is in the intervention protocol, teams must at least provide their controls something like the WHO physical activity guidelines. 

That said, Judges did review teams with exercise-only interventions and, based on data, they were not convinced that this approach would demonstrate the range of effects necessary to win. Through alignment with lead academics, referent data on potential effects of exercise-only interventions will be available for post-hoc comparison.

If a combination approach proves successful, future studies can prize the elements apart.

We wanted to know about the data: will it be made available after 2030? We surmised that the control arms of trials might be especially valuable, as it will be data on how this biomarker performs in diverse populations, ageing normally.

Dr Justice agreed that the unique dataset generated by the Finalists will be a lasting contribution of XPRIZE Healthspan. The results from the control arms in particular will be one of the largest standardized datasets relating to healthspan collected under uniform protocols and schedules. 

Teams will collect standardized measurements of muscle function, cognition, immune health, and related biomarkers, in adults aged 55-90 followed over one year using common protocols. These data should help scientists better understand healthy ageing, evaluate biomarkers, and compare therapeutics.

Indeed, a well-known challenge of trials for healthspan is the time required to pass to actually test if people live longer and healthier and the large numbers of participants. One thing that would be very useful for the field is a ‘surrogate endpoint’ which could be measured more quickly in a smaller group could prove that a therapy works, saving time and money in testing. The paradigmatic example is in heart disease, where many regulators will accept a lowering of LDL cholesterol as sufficient evidence to approve a new treatment, and will test the impact on heart disease after it is on the market.

XPRIZE Healthspan’s functional outcome panel is a surrogate endpoint. Moreover, these outcomes are close to what people actually care about every day: being fitter, with better immunity and brain function. Could this be something future longevity trials might target? We asked Dr Justice.

The LI: Have you spoken with FDA or any other regulators about the idea of adopting these tests as a ‘surrogate endpoint’ for longevity clinical trials?

Dr Jamie Justice: Yes, at the Reagan-Udall Foundation for the FDA, where we held a full day workshop. The event focused on regulatory pathways for the development of drugs, biologics, and devices. I discussed promising frameworks across phases II to III and tackled a critical gap: ageing remains largely absent from formal regulatory recognition as a therapeutic target. Our next goal is to convene an international workgroup and patient voices to align on clinical outcome assessments and evidence necessary for gerotherapeutic development. Then, the Finals trials will help establish some of the basic trial evidence needed to evaluate biomarkers for qualification. 

In the competition itself, trials are conducted globally, teams follow the local regulatory requirements for safety and monitoring. This is helping establish a higher standard for clinical validation.  

I also saw the Montana Experimental Therapy Review Board (ETRB) as an opportunity to help build a transparent and scientifically rigorous process for Montana’s expanded right-to-try legislation. I wanted to help ensure that the field advances with rigor, accountability, and thoughtful evaluation to protect patients and advance meaningful innovation.

The LI: Finally, let’s game out some victory scenarios. It’s 2030 and… It’s quite plausible that one of the exercise-plus-something-simple teams wins. What does that mean for how close we are to medical treatments with broad effects on healthspan?

Dr Jamie Justice: If a team combining exercise with something simple – such as a nutritional supplement or an existing drug – were to win, that would be exciting. It would suggest one of the most effective ways to improve healthspan involves interventions that are already widely available, affordable, and scalable.

It wouldn’t mean we’ve “solved” ageing or discovered a single magic bullet but that a practical combination can meaningfully improve healthspan across multiple functions. That kind of result could be translated into practice quickly, opening the door to even greater advances in future.

The LI: It’s 2030 and… Discretionary late registration stays open until July 2027. Could a pharma company notice functional improvements in some participants in, say, a GLP-1 trial, pay $100k to enter a trial they were planning to do anyway, and win $81 million?

Dr Jamie Justice: The competition is open to any eligible team that meets the requirements of the Competition Guidelines, regardless of whether they are an academic institution, startup, non-profit, or pharmaceutical company. 

Teams must design and conduct their trials to satisfy the competition’s specific requirements and also demonstrate proof-of-concept studies generating preliminary data in humans.

If any organisation develops a therapeutic that meets those standards, it would be eligible to compete pending Judge approval. This rewards generation of rigorous clinical evidence.

And by all means – if a company is running a trial and they think they have a therapeutic that can win, they are encouraged to enter. But we must warn that demonstrating an IMPROVEMENT in muscle, cognitive, and immune function equivalent to declines seen in 10- and up to 20-years of natural ageing is not trivial. This kind of moonshot may not be suited for off-the-shelf medicine and requires bold action. 

The LI: It’s 2030 and… No-one wins! A ten-year reversal across three domains is a bold target. What is XPRIZE Healthspan’s legacy, and does the door stay open for someone to net $81 million in 2031 or beyond?

Dr Jamie Justice: We anticipate awarding the best team to surpass the pre-determined thresholds (10-year threshold = $61M; 15-year threshold = $71M, 20-year threshold = $81M), but XPRIZE will defer to the independent Judging Panel for all final adjudication of the Grand Prize Winner or Winners. This applies both in the unlikely event of a tie or of a failure of all teams to achieve the thresholds set for awarding.

But, if the Judging Panel reviews all evidence collected by 2030 and they collectively vote that none of the teams should be named ‘Best Team’ – because no team achieved a breakthrough of sufficient effect across muscle, cognitive, and immune function – then the Judges may recommend XPRIZE not to award any amount of the Prize Purses and the remaining money will be returned to the competition Sponsor(s) in 2030. This, for us, would be the only true failure, but we truly believe our teams will push the field beyond its current limits.

We wish Dr Jamie Justice and the Finalists good luck, and look forward to the results in 2030

Whatever happens, XPRIZE Healthspan should leave the field with something valuable. The obvious hope is that one or more teams meet the Prize’s ambitious thresholds and demonstrate meaningful restoration of muscle, cognitive and immune function in older adults. That would be a landmark result for longevity science.

But even if no team wins, the competition will generate something very valuable: standardised, comparable human data across a diverse range of interventions. By the time it reports, this might be the first ITP-style comparative evidence base in humans and across intervention classes. It should help identify which approaches deserve further investment, improve our understanding of how ageing-related functional measures change over time, and potentially inform how future gerotherapeutics are evaluated. As legacies go, this might outlast the winnings.

This is also the value of ambitious prizes: they set a concrete goal, bring different approaches into competition, and force promising ideas into rigorous human testing.