Hey everyone,

Thank you for being a reader for so long. We're expanding our coverage, and today's a first for us: a whole edition built around one theme, Longevity, instead of our usual mix.

Let us know what you think of this edition, and whether you'd want to see more longevity-exclusive editions from us, in the poll below.

If you're reading this, thanks for giving it a shot with us.

The VACCINE FOR CANCER: A Personalized Cancer Vaccine Just Passed Its Most Major Test

This week, Merck and Moderna revealed that their experimental cancer vaccine, known as intismeran autogene (or V940 or mRNA-4157), achieved its primary endpoints in a Phase 3 trial for high-risk melanoma.

That sentence is a gross understatement of the events that transpired.

This is the first and only time ever a customized cancer vaccine has been tested in a randomized, late-stage trial and actually worked. This idea has been pursued for decades by scientists, and now there's real evidence it might be working for the first time.

Building a vaccine out of your own tumor

It begins once the melanoma is excised through surgery. Scientists compare the DNA of the tumor against that of the patient to find mistakes, errors in genetic code that are unique to each individual cancer, things that create proteins so out-of-whack they have no parallels inside the body.

Those abnormal proteins become a fingerprint of the tumor. Using the same mRNA technology that is behind Covid shots, researchers then build a vaccine to train the immune system to recognize those specific fingerprints. The vaccine gives the immune system a target, what it can attack, while Merck's immunotherapy drug Keytruda works alongside it, removing a natural brake that normally stops immune cells from attacking, giving those cells permission to fire.

The numbers no one has ever seen

INTerpath-001, the trial enrolled 1,137 patients with resected stage IIB to IV melanoma. Patients received the vaccine plus Keytruda, or just Keytruda alone, for approximately one year. The combination beat Keytruda alone on both key endpoints: how long did it take for the cancer to come back, and when did it spread elsewhere in the body.

Merck and Moderna haven't put an exact number on it yet, delaying that information for a forthcoming medical conference, but have touted the results as "statistically significant and clinically meaningful." Data previously presented from a more early-phase trial on the same combination showed a 49% reduction in the risk of recurrence or death at five years.

This becomes one of the largest results in cancer in years, if its Phase 3 numbers land anywhere near there. Aside from the tiredness, injection site pain and chills previously seen in earlier trials, no new safety concerns were identified.

Why this trial specifically matters

Melanoma accounts for only about one percent of skin cancers but the vast majority in terms of causing deaths from skin cancer, and most recurrences happen within a two or three-year window after initial treatment, exactly the span in which this vaccine is aimed. The result calls for "truly this next phase in immunotherapy," Karen Knudsen, CEO of the Parker Institute for Cancer Immunotherapy said.

Moderna's shares jumped on the news, which is significant considering the past year has seen a shifting focus toward cancer research as friction with federal vaccine regulators over its Covid- and flu shots had put the brakes on this part of the business.

Now Merck and Moderna plan to take these results to regulators, and if the full data passes muster, melanoma could be only the tip of the iceberg. A similar personalized approach is already being trialed in lung, bladder and kidney cancer on the theory that if you can teach the immune system to recognize one tumor's fingerprint it should be able to learn anyone's as well.

Velma Long and Dorothy Boggess became friends in 1917, over WWII. They're both still here, and Boggess starts every morning the same way: she plugs in a boom box, hits play on the Cha Cha Slide, and dances in her kitchen with a hand on the counter. Her mug reads "109 and fabulous." Nobody funded a lab for this. Worth sitting with before the money section below.

👉 The test half the industry relies on just got checked

Half the longevity industry measures success with "biological age" tests, DNA methylation clocks that claim to tell you how fast you're actually aging. A new Nature Medicine paper ran the first real stress test on whether these clocks behave the way a genuine clinical measurement should, moving when there's real benefit, staying flat when there isn't. It's the unglamorous paper nobody in this space wants to talk about, and possibly the most important one here.

👉 Which Anti-Aging Ideas Actually Work?

That's the question XPRIZE Healthspan exists to answer, because right now almost nobody can. The competition's own director admits submissions range "from legitimate, rigorously developed approaches to more fantastical schemes," with no easy way to tell which is which from the outside. So instead of taking anyone's word for it, XPRIZE is making teams prove it. Ten finalists just won $1 million each to show, in real human trials, that their approach can restore a decade of lost muscle strength, cognition, or immune function in people aged 50 to 80, within 12 months.

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