Sam Altman's longevity company is testing an extra-strength Alzheimer's drug after disappointing trial results

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Sam Altman's longevity company is testing an extra-strength Alzheimer's drug after disappointing trial results

Hilary Brueck

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joe founder — Joe Betts-LaCroix is the CEO of Retro Biosciences, a longevity biotech company backed by Sam Altman.
Retro Biosciences

The Sam Altman-funded longevity startup Retro Biosciences is testing a longevity pill that the company hopes could one day fight dementia. First, however, they need to figure out the right dose.

The pill, called RTR 242, is designed to jump-start key cellular recycling processes in the body, which stall as we get older, and get especially clogged up in people with neurodegenerative diseases, including Alzheimer's and Parkinson's.

RTR 242 has already been in clinical trials in Australia for several months, a bullish attempt to beat the longevity-focused competition in Silicon Valley.

Things are going well, Retro CEO Joe Betts LaCroix told me, when I showed up at the company's bustling office in Redwood City. No major side effects, no safety signals. But that presents a challenge: Retro scientists can't pinpoint the dose at which they'll get the best results: enough medication to be potent, but without severe side effects.

"It's sort of like a curse and a blessing for us, in that it makes it a little bit hard to measure that 'Yay; it's doing the thing,'" Betts-LaCroix said.

So, Retro is adding two new cohorts to their safety trial, the CEO told Business Insider in an exclusive interview. They're increasing total enrollment in their Phase 1 trial by more than 42%, from 76 to 108 participants.

"Hopefully, at some point, we will at least get headaches or something," Betts-LaCroix said of the drug's potential side effects.

For Betts-LaCroix, who lost his father to Alzheimer's earlier this year, the quest for a longevity drug is also deeply personal.

"You make it into your 90s and then, damn. It comes along and strips your personhood out right from under you," he said of the disease.

If the trial is successful, it could pave the way for Altman's longevity startup to edge ahead in the schoolyard competition among Silicon Valley billionaires: Who can deliver a moonshot longevity drug first?

A billionaire's race for the first longevity drug

autophagy drug — RTR-242 is a drug designed to improve brain aging. So far, it's only been tested in healthy volunteers.
Retro Biosciences

At Retro, about 90 people are quietly working on a very ambitious goal: adding 10 healthy years onto our lifespans.

The lean biotech company, with offices built initially from shipping containers, is arguably ahead of its competition. So far, other Bay Area longevity startups, including the Bezos-backed longevity project Altos Labs and the Founders Fund-backed New Limit, have not announced any human-stage clinical trials.

Internally, there are different ideas brewing at the Sam Altman-backed company about exactly how best to tackle aging. Some of the most far-out initiatives involve using a new Food and Drug Administration-compliant blood cell manufacturing lab, intended to treat blood disorders and central nervous system (CNS) conditions. It has just been completed in the warehouses that used to serve as the company's makeshift first offices.

In the near term, though, the company's ambitions are a classic biotech play to develop, test, and patent a new drug. Retro Biosciences is safety-testing RTR-242, the pill the company hopes could one day help treat Alzheimer's by triggering the brain to clear out leftover junk.

Here's how it works: RTR 242 is designed to restore old lysosomes, which are a critical recycling center inside our cells. Lysosomes use acid to break down old, junky proteins into usable parts again, during the final stages of an important cellular cleanup process called autophagy. Lysosomal cleaning power often wanes as we age, a cellular performance issue that's tightly tied to biological aging, age-related diseases, and inflammation.

Retro's drug aims to restore the acidity of creaky old lysosomes, so they can recycle cellular trash into usable treasure more efficiently again. It's a promising idea that several biotech startups are exploring, but it hasn't proven successful clinically yet.

Paul Robbins, a biochemist and longevity researcher at the University of Minnesota, who is not involved in the Retro trial, called the lysosome an "interesting target," especially for cognitive decline and dementia.

"If they're not seeing toxicity, that's great," Robbins told Business Insider. But, he hesitates to give the trial a standing ovation, without knowing yet exactly how the drug works (the company is cagey on those details) and whether it works in people with dementia.

Because the drug is initially being tested out in healthy volunteers, ages 18 to 65, it's hard to know exactly how well it will ultimately perform in older adults suffering from cognitive decline.

"There are other ways to stimulate autophagy," Robbins said. "We'll have to see if this is the right way or not."

A new cellular cleanup strategy to fight Parkinson's and Alzheimer's

Retro isn't the only company targeting lysosomes for brain health. Lysoway Therapeutics, a Boston-based biotech company developing lysosome-targeting drugs, began its first-in-human clinical trial in Australia in May aimed at treating neurodegenerative diseases, including Alzheimer's and Parkinson's, with major support from The Michael J. Fox Foundation for Parkinson's Research.

That same month, Chicago-based Vanqua Bio released promising results from a Phase 1B safety trial of a lysosome-targeting drug for Parkinson's, showing both tolerability and target engagement, meaning the drug appears safe and effective for treating Parkinson's but will need to advance into Phase 2 to prove it.

Betts-LaCroix wouldn't say where or when his company will be ready to move into Phase 2, the real proving ground for RTR-242, when it will be tested in older people with Alzheimer's. First, he wants to see what emerges from testing the two higher doses in healthy volunteers.

"Nobody understands the disease very well, but it's definitely a hallmark of Alzheimer's that the autophagy is inhibited or stalled," he said. "Something that's a fresh take on the disease from a therapeutic perspective has, in my opinion, a lot higher probability of success than something people have been hammering away at hundreds of times without success."

Sam Altman's longevity company is testing an extra-strength Alzheimer's drug after disappointing trial results