Intervene Immune puts thymus regeneration back in the spotlight

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With its immune-restoring TRIIM platform in the XPRIZE Healthspan semifinals, the company says the body ‘still remembers how to be young’.

Continuing our exploration of the XPRIZE Healthspan Top 40 in partnership with our friends at TimePie, we head to California to meet Intervene Immune, where a once-overlooked organ is being treated as a longevity linchpin. With thymus regeneration, immune restoration and unexpected functional gains now in the mix, the team is arguing that aging may be less destiny than design problem.

Some longevity breakthroughs arrive with fireworks; others arrive with data, discipline and a slightly unfashionable organ that most of us stop thinking about after high school biology. Intervene Immune belongs firmly to the second category. Founded around the work of cryobiologist-turned-thymus-regenerator Dr Greg Fahy, the company has been named a semifinalist in the XPRIZE Healthspan competition, advancing in a global field of more than 600 teams.

The recognition matters because XPRIZE forces teams to show function, not just biomarkers – muscle, cognition and immune performance, with ten years of rejuvenation compressed into twelve months. Intervene Immune’s bet is that immune aging is not merely inevitable, but modifiable, and that thymus regeneration can help unwind immunosenescence using tools already sitting in our clinical cupboards.

Longevity.Technology: The longevity world loves novelty – shiny gene editors, exotic vectors, sleek partial reprogramming pipelines – but TRIIM is, in many ways, stubbornly pragmatic. Growth hormone has decades of use; metformin is practically the patron saint of off-label aging curiosity; DHEA has long occupied that awkward borderland between endocrinology and wellness culture. And yet the biology is anything but simple. The thymus is not merely an immune accessory, it is a master regulator of immune competence; rejuvenate it and you may be shifting inflammation, resilience and cancer surveillance, as well as the downstream ability to respond to everything from viruses to vaccines.

XPRIZE, meanwhile, is a forcing function – less romance, more measurable reality. It demands functional change in a year, a timeframe that is uncomfortably short for many interventions but arguably well-suited to systems already primed to respond; Intervene Immune believes it is in that category, and its early data suggests as much. The field has learned to be hopeful and hard-nosed in equal measure; extraordinary claims are not banned, but they are required to pay rent in the currency of reproducibility.

On making it to the XPRIZE semifinals

Cofounder, CEO and CTO of Intervene Immune Robert (Bobby) Brooke, says the company didn’t take advancement for granted – not with universities, major institutions and high-profile biotechs in the race. But when the announcement came, the team’s reaction was straightforward: elation.

Brooke says that while they had confidence in their work’s clinical signals, the team had no certainty about how those results would compare to competitors until the cut was made. XPRIZE recognition, he adds, has proven to be an unexpected crowd-pleaser: Intervene Immune hasn’t pursued it as a publicity campaign, but whenever it is mentioned during talks, the response is immediate. “It’s a wonderful validation of our approach,” says Brooke.

From cryobiology to thymus regeneration

Dr Greg Fahy, Brooke explains, has been interested in both cryopreservation and aging for most of his life. The limiting factor was not conviction, but capacity – until the two met in the early 2010s through a longevity discussion group in Los Angeles. Brooke offered support, and with that partnership the company was formed around a plan Fahy had carried for years: reverse immune aging and autoimmune disease by regenerating the thymus.

“Greg’s entry into clinical aging research was not a transformation of his interests, but a transformation of his reach,” Brooke explains. The TRIIM protocol began as Fahy’s own self-experimentation, then expanded into a pilot clinical study – the Stanford-based TRIIM trial.

The story also loops back to Fahy’s earlier cryopreservation work. If the thymus can be regenerated and immune tolerance improved, Brooke suggests, it may help create conditions in which organ transplants can be accepted without rejection – a future where organs sit in banks awaiting recipients, and immune systems can be reconditioned to meet them.

“We realize more than ever how critical preserving the immune system is for human longevity: without it, all other systems will inevitably fail,” Brooke says. “And we’re uniquely positioned to address it with treatments we have available today, which makes us all the more determined to move forward.”

Why TRIIM is a cocktail, not a single drug

Intervene Immune’s starting point, Brooke explains, was an animal finding that old rats could regenerate thymic tissue when exposed to persistent growth hormone signaling, with a broader reversal of immune aging. The promise was enormous; so was the catch. Growth hormone can be diabetogenic, and metabolic dysfunction is not exactly the side dish anyone wants with their longevity intervention.

Fahy’s early work involved self-experimentation and an attempt to neutralize that risk. DHEA, another hormone abundant in youth but dwindling with age, appeared to block growth hormone’s diabetogenic effect, and metformin was added to further support insulin sensitivity.

“It turns out that both DHEA and metformin have independent antiaging effects beyond controlling insulin,” Brooke says. “So combining them with the antiaging effects of growth hormone – to regrow the thymus without inducing a diabetes-like state – has proven to be a particularly powerful intervention.”

The safety moment – and the surprise that followed

Brooke describes the team’s confidence as something that arrived in stages. First came the need to show the metabolic counterbalance held up beyond Fahy. Then came safety, particularly cancer risk – with growth hormone driving IGF-1, and reports suggesting lifelong high IGF-1 exposure could increase prostate cancer risk.

Instead, Brooke says, established cancer-risk metrics moved in the opposite direction. “Miraculously, cancer risk based on established metrics actually fell quite substantially – and that was our second sign that the treatment might be both workable and safe,” he says.

“The risks were very much on our minds at the start: would it work at all, and would it be safe? It really wasn’t until the trial was over and all the results were in that we knew the answers.”

Beyond the clocks

The 2019 Aging Cell paper drew attention for showing epigenetic age reversal in humans [1]. Brooke says the team was startled by the magnitude of the results. “They were the first evidence that aging reversal based on multiple established global aging clocks could be achieved in any organism – and in this case, in humans,” he says. “We were floored.”

But the clocks were not the original mission. TRIIM was designed to address immunological aging, and Brooke points to immune markers that supported the central claim. One was a reduction in PD-1-positive CD8 T cells, a subset implicated in blunted cytotoxic function and a target of major cancer immunotherapies.

“Knocking them down is the object of two multi-billion-dollar anti-cancer drugs,” Brooke says, “but we obtained positive results simply by making the immune system younger.”

Still, the most direct validation came from the basics: naïve T cells. Restoring the thymus should increase naïve T cell output; seeing that signal helped shape the next phase of work in TRIIM-X and beyond.

XPRIZE and the functional question

XPRIZE Healthspan has a useful habit of stripping away comforting ambiguity. Biomarkers are welcome, but the competition is built around function – muscle, cognition and immune performance, improved enough to resemble a ten-year reversal.

Brooke says interim TRIIM-X results have been encouraging, particularly in VO₂max, lower-limb strength and immune measures. The team has also tried to quantify the gains by comparing them to the years it took those same parameters to decline before the trial by the amount gained during the trial – an approach that frames improvement in the language of aging itself.

“Significant rollbacks were achieved on this basis over one year of treatment,” Brooke says.

Early analyses compared each participant with themselves before treatment, but the control question is now being addressed through untreated control data and a crossover study design, allowing treated and untreated outcomes to be compared within the same individuals.

One result, Brooke says, is already clear: epigenetic aging reversal does not occur in controls.

Why the immune system might influence strength and cognition

Intervene Immune argues that restoring immune function may also enhance muscle and brain outcomes – partly because growth hormone has known effects in those domains. Brooke notes that growth hormone alone doesn’t reliably increase skeletal muscle strength, even if it makes muscle larger; in their experience, the combination appears to enable strength gains more consistently.

Cognition, he adds, is similarly plausible. Growth hormone has been shown to improve cognitive function, and DHEA adds its own neurological logic. It is produced in the brain and has been described as a neurosteroid, with reported effects on memory, mood and emotion.

What comes next – and what could stand in the way

TRIIM-X is still ongoing, Brooke says, with additional groups launched recently, so full publication will take time. Funding remains a priority, both to expand trials and develop improved versions of the protocol; but Brooke suggests Intervene Immune is in an unusual position for a longevity biotech, holding broad patent coverage and the ability to market internationally at small scale, potentially supporting revenue streams earlier than most platforms.

Beyond science, Brooke sees three main hurdles: regulation, manufacturing and physician usability. Public acceptance, he says, already appears strong. Regulatory pathways may be comparatively favorable, given the long histories of the cocktail’s components and existing approvals for immune deficiency states. Manufacturing is always a challenge for biologics at scale, but protein production is mature and scalable, and the company is building internal capacity.

The immediate obstacle, Brooke argues, is complexity. Intervene Immune is developing a dosing system designed to be relatively foolproof for doctors, and expects to build an AI assistant to support implementation as sufficient data accumulates.

A final message

Intervene Immune’s closing sentiment is less biotech slogan and more biological provocation. “No matter how old you may be, your body still remembers how to be young,” Brooke says.

That knowledge, he argues, becomes dormant in the genome with age, but it is not erased. With the scientific and business communities now pressing forward with vigor, Brooke finishes on a note of optimism.

“The future may be brighter than you have imagined,” he says, “and in some respects, that brighter future is already at hand. But stay tuned; the best is yet to come.”

Photograph courtesy of Intervene Immune. Photograph shows Intervene Immune co-founders Dr Greg Fahy (center) and Robert Brooke (left), with three TRIIM-X clinical trial volunteers.

[1] https://pubmed.ncbi.nlm.nih.gov/31496122/

LTUI: 2225

Intervene Immune

Longevity level(s):

  • Level 6: Aging disease prevention therapeutics
    Therapeutic interventions that control aging drivers to prevent aging diseases from occurring, like the current wave of GLP-1 agonists that prevent type 2 diabetes through metabolic interventions that also are proving effective in mitigating cardiovascular and neurological diseases.
  • Level 7: Targeted aging disease reversal
    Therapeutic interventions that stop or reverse age-related damage in specific organs (organ specific / tissue specific / localized reversal) or for age-related diseases including technologies like partial cellular reprogramming.
  • Level 8: Systemic aging reversal
    Therapeutic interventions that stop or reverse age-related damage throughout the whole body system at a cellular level. Including technologies such as mitochondrial transplant, senotherapeutics and partial cellular reprogramming.

Overview

Intervene Immune is a clinical-stage biopharmaceutical company focused on reversing age-related immune system decline through thymus regeneration. The company develops personalized combination treatment regimens designed to restore thymic tissue function and combat immunosenescence, a hallmark of aging. Intervene Immune's therapeutic approach targets the fundamental biology of immune aging by employing existing pharmaceutical agents in novel combinations to rejuvenate immune competence. The company's mission centers on translating discoveries in immune system aging into clinical interventions that extend healthspan and reduce age-related disease susceptibility.

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Eleanor Garth

Editor

Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

With a keen interest in all things geroscience, Eleanor covers the biological mechanisms of aging, highlighting how interventions – from nutritional strategies to advanced therapeutics – can influence the aging process at a cellular level. She also investigates the broader implications of aging research, including the integration of longevity science into healthcare strategy and the expanding wellness economy. Her work (hopefully) provides insights into how these developments are shaping the emerging landscape of healthspan optimization and age-related innovation.

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