Elysium Basis: The Anti-Aging Pill (Updated)

Elysium Basis: The Anti-Aging Pill (Updated)

May 26

Elysium-Basics

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• Elysium Health Website
• Elysium Health on Facebook
• Elysium Health on Twitter
Wikipedia on Elysium Health

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Want To Sell An Anti-Aging Pill With No Human Testing? Make It A Supplement
By Nidhi Subbaraman
Buzz Feed
May 26, 2016

Original Link

For more than a year, New York startup Elysium Health has been selling a pill, formulated after decades of research at a famous anti-aging lab at MIT, that claims to make our aging cells healthier, leading to better energy, sleep, and memory.

According to the company, “tens of thousands” of people have bought subscriptions of about $50 a month for a daily supply of the pill, called Basis, with the expectation that they will feel healthier even as the years fly by.

But some researchers who study aging are deeply skeptical that the compounds in the pill will have any effect at all, because there is no evidence that it works in people. The company has avoided the stringent clinical testing required of pharmaceutical drugs by selling Basis as a dietary supplement.

“If it was me personally, I would like to see some data in people before I start recommending to people that they take this compound,” Matt Kaeberlein, professor of pathology at the University of Washington, told BuzzFeed News. “It’s their reputations that are on the line if this turns out not to work.”

And yet, it may be a shrewd business strategy for any product whose ingredients happen to already be a part of our diet (one of Elysium’s is found naturally in blueberries, and another is a form of vitamin B3). By marketing its pill in the loosely regulated supplement category, the investor-backed startup has bypassed the expensive, complicated, and lengthy challenge of demonstrating age-reversal to the FDA. Elysium has also dodged the question haunting the field at large: How do you prove that a person has lived longer than they otherwise would?

In an ideal world, clinical trials of Basis would have preceded sales, Thomas Südhof, a Nobel Prize winner and one of the company’s 22 high-profile scientific advisors, told BuzzFeed News.

“But I am not sure if that is realistically financeable,” Südhof said. “People who fund companies, startups, would not want to fund having a first-trial kind of approach.”

Elysium’s leaders declined to disclose their financial backers, or how much money they have raised.

Countless pills, creams, and tonics are already on the supplement market claiming to extend the human lifespan. But in the last few years, several prominent startups — like Google’s Calico, Craig Venter’s Human Longevity, and Elysium — have cropped up, aiming to take a more science-based approach to that goal.

“The anti-aging supplement space is nascent,” Michael Ringel, global topic lead of research and product development at Boston Consulting Group, told BuzzFeed News. “At the end of the day a success is something that actually helps patients and ties back to profits for the company.”

Those profits could be big. McKinsey & Company has estimated that the U.S. supplement market would be worth $30.8 billion by 2017. And 36% of those supplement customers will be 65 or older.

Elysium’s biggest group of customers are between the age of 40 and 60. “The Baby Boomer generation are perhaps the ones that hear the message most clearly because they are so young at heart — or maybe they notice they don’t manifest themselves physically in a way that mentally they feel they should,” Elysium CEO Eric Marcotulli told BuzzFeed News.

To answer its doubters — and to set a high bar for future competitors — in February Elysium began the first of a series of clinical trials of Basis, and expects to have results before the end of the year.

Anecdotal reports of the pill’s effects are intriguing: Elysium’s first customers report sleeping better, feeling more energized, and seeing their hair and nails grow faster, Marcotulli said.

But as the latest of a string of attempts by scientists to isolate an anti-aging molecule, all of which turned out to disappoint, Elysium will struggle to convince some visitors — at least until its clinical trials are complete.

“When I look over their site as a consumer I’m unconvinced about buying this stuff,” Richard Faragher, a professor of biogerontology at the University of Brighton in the U.K. told BuzzFeed News by email.

Pterostilbene, one of the two main ingredients in Basis, is also found in blueberries, Faragher noted. So why not just eat more of those, or buy cheaper supplements that also use it as an ingredient?

“I’m a pretty health conscious man, but before I bought Basis at $50 per month I would want hard evidence that taking [it] would be better for my health than other options for the same price,” he wrote.

The ingredients may be natural, but Elysium’s website reminds visitors of its product’s high-tech origins in the MIT lab of co-founder Leonard Guarente, who has been studying aging for more than three decades.

In the late 1990s, Guarente helped discover that a class of proteins called “sirtuins” adjust metabolism in ways that let worms and mice live longer. Sirtuins and the genes that made them, it seemed, were a handful of dominoes in a cascade of changes that took place in cells as they aged.

A few years later, David Sinclair, who worked as a post-doctoral researcher in Guarente’s lab, showed that resveratrol, a molecule found in foods such as red wine, was able to enhance the work of sirtuins in obese mice and keep them healthier for longer. Sinclair created a company, Sirtris Pharmaceuticals, to develop drugs targeted at age-related diseases like diabetes, and Guarente became one of its scientific advisors.

GlaxoSmithKline bought the company for a staggering $720 million, only to shutter the effort after trials in people failed to yield results. Although resveratrol’s role in reversing aging is still in question, a $30 million market for the compound as a supplement continues to thrive.

Guarente got another chance at commercial success when approached by Marcotulli — a Harvard Business School graduate with no scientific training — with an open-ended pitch about starting a company based on health-boosting compounds derived from food, supplements sometimes called “nutraceuticals.”

“I said, there’s a lot happening recently,” Guarente recollected. “So if there was a way to structure a company around that wisely, I think it could do very well, and it could also do good.”

One of the two ingredients in Basis, pterostilbene, is a form of resveratrol – a more effective avatar, Guarente said. The other ingredient is nicotinamide riboside, which enters the body and turns into NAD, a molecule that participates in cell metabolism. Other labs have shown that boosting NAD in aging mice helps sirtuins perform better.

“The take-home message is that NAD levels decrease with aging, and if they can be restored with precursor the old animals enjoy better health,” Guarente said.

But sirtuin studies across the board have been inconsistent. “There’s a fairly public and well-known controversy around sirtuins,” João Pedro de Magalhães, an aging researcher at the University of Liverpool in the U.K., told BuzzFeed News. (In 2014 and in 2016, Guarente retracted two papers that investigated the role of sirtuins.)

In the last decade, other labs have uncovered dozens of other anti-aging candidates — genes, cells, drugs — that have kept mice, yeast, and worms alive for much longer than usual. Kaeberlein is more convinced about evidence from other such avenues: the diabetes drug, metformin, for example, or from the immunosuppressant drug rapamycin. But those drugs, unlike resveratrol, pterostilbene, and nicotinamide riboside, are heavily regulated by the FDA.

Elysium’s first trial hopes to enroll 120 adults between the ages of 60 and 80, receiving either a regular dose, a double dose, and no dose at all. A variety of health indicators will be measured over eight weeks — such as blood pressure, heart-rate, balance — most of which Guarente expects to be tempered by Basis-activated sirtuins. The trial will also look for increased NAD levels in the blood, an indication that Basis is acting as expected.

“It’s asking a lot to see something in two months, but we’re hopeful,” Guarente said.

Despite his misgivings about the approach, Magalhães also sees the upside to launching an investor-backed startup as a fast-track to payoff. “If I discovered a drug that I was convinced could work in people, and I could sell it as a supplement, maybe I would do the same thing,” he said.

The one thing that researchers seem to agree on is this: The FDA has a blind spot when it comes to regulating drugs that affect the aging process.

Based on the biology of the molecules, said Kaeberlein of the University of Washington, “there’s no scientific reason for not regulating [Basis] and regulating other classes of molecules that the FDA regulates — there’s no justification for that.”

But how to properly design trials for anti-aging drugs is still something of a puzzle. A fundamental hurdle is that such trials could span, at the very least, the length of a person’s life.

Researchers who are testing promising life-extenders will also confront unique ethical quandaries. For example, a drug that helps some people live longer could shorten the lives of otherwise healthy others, Andrew Dillin and Celine Riera of the University of California, Berkeley, noted in a paper published in Nature Medicine last year.

But because age is the primary risk factor for major killers, including cancer, heart disease, and diabetes, the reward could be well worth the wander through the fog.

“If you retard it a little bit, like you can do in animal models already, it will have an unprecedented health and medical impact,” Magalhães said.

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One Of The World’s Top Aging Researchers Has A Pill To Keep You Feeling Young
By Jessica Leber
fastcoexist.com
February 3, 2015

Original Link

Elysium Health hasn’t discovered the fountain of youth, but their new supplement — with the backing of some of the world’s foremost authorities on aging — could change how you get older.

Say someone came up to you selling a dietary supplement — a pill that you take once a day — that could boost your energy, improve your body’s ability to repair its DNA, and keep you healthier as you get older.

It might sound like a scam, or more likely just another in a sea of confusing, undifferentiated claims that make up the $20 billion dollar supplement industry.

But let’s say that someone is MIT’s Lenny Guarente, one of the world’s leading scientists in the field of aging research. And he’s being advised by five Nobel Prize winners and two dozen other top researchers in their fields. You might pay a little more attention.

THE SCIENTIST AND THE STARTUP

Cofounding a supplement company seems an unlikely career move for someone like Guarente, a man who is one of the most well-respected scientists in his field. (“It is a departure,” Guarente admits). Mostly, for him, getting involved in Elysium Health is a decision born out of opportunity and frustration. The opportunity is the chance to make a difference by translating findings in the booming field of aging research directly to consumers today. The frustration is that doing this has taken so long in the first place.

“My biggest hope is that we can make available to people something that is currently unavailable, and that it will have a positive impact on their health,” Guarente says.

Elysium Health actually had its beginnings in conversations between its other two, younger cofounders, Eric Marcotulli and Dan Alminana, who were then tech investors and gym buddies. Even though they’re both quite health-conscious, they knew they couldn’t halt the march of aging and all the ailments that come with it. Far more than diet or anything else people can control, the biggest risk factor for many of the diseases that kill us — including diabetes, cancer, and cardiovascular disease — is simply getting older.

Marcotulli knew something about the market opportunity too, which has also lately attracted the likes of Google (with its Calico Labs project) and other SIlicon Valley investors. He had studied the story of a company called Sirtris Pharmaceuticals, which in the mid-2000s was working to take resveratrol, the natural anti-aging compound found in red wine, and alter it into a more potent form that could be patented and developed into a medical drug. In 2008, Sirtris — founded by Guarente’s former postdoc David Sinclair — was acquired by the drugmaker GlaxoSmithKline for a jaw-dropping $720 million.

“The fundamental question was: Are there other natural products out there that could be meaningful? I think resveratrol was the first, and I was thinking there’s maybe the potential for many others,” Marcotulli remembers thinking as he studied the story while in business school.

The two started cold-calling scientists involved in aging research and were surprised how many were enthusiastic about the idea, including Guarente. The FDA doesn’t recognize aging itself as a condition, so, instead, companies like Sirtris and GSK are are taking scientific findings about how we age and translating them into drugs that treat specific age-related diseases. The issue is that the clinical trials involved in doing this can take more than a decade, and even then that is no guarantee a drug will be approved. The result has been that, though scientists have made major strides in understanding how and why we age and demonstrating that this aging can be delayed, they’ve so far seen few results in translating their work to help people.

The two entrepreneurs wanted to take a very different approach than the drug makers: sell only unaltered natural products, which generally aren’t patented and don’t need FDA approval, and create new kinds of supplements that make no claim to treat a specific disease but promote general wellness instead.

“If there’s a benefit that can be had now, then I think it doesn’t make sense to wait a decade or more until some derivative [from a drug company] becomes available—though I’m not saying that’s not a good thing to do too” says Guarente.

The three cofounders have been taking the company’s first product, a pill they are calling BASIS, for the last three to five months. Through its website, Elysium Health will sell a one-month supply to consumers for $60, or $50 with a monthly subscription.

BOOSTING NAD

The theory behind the pill is built on work first pioneered in Guarente’s lab on sirtuins, a group of enzymes involved in cell metabolism and energy production that are common to a wide range of living organisms. Researchers have found that boosting the activity of sirtuins, which is sometimes done by calorie restriction diets, can extend lifespan of yeasts, worms, mice, and other animals. Efforts to develop a drug that can have the same effect, without the lack of calories, have been going on for the last two decades, including at Sirtris and GlaxoSmithKline. There are also natural compounds that elevate sirtuins — one is resveratrol, which is already sold as a dietary supplement today. Another is called NAD.

NAD — Nicotinamide adenine dinucleotide — is one of the most compelling bits of chemistry related to aging. Its presence in the body is directly correlated with the passage of time: An elderly man will have about half the levels of NAD is his body as a young person. There’s no amount of healthy eating or exercise that can stop the decline. But in a scientific paper published in 2013 that generated headlines about “reversing aging,” Harvard’s Sinclair showed that after a week of giving two-year-old mice a boost of NAD, their tissues looked more like six-month-old mice.

Elysium’s pill is an attempt to replicate that process naturally in humans. It contains the building blocks of NAD, so the body can easily absorb the smaller molecules and synthesize its own. The pill also contains pterostilbene, a compound, that is a close relative of resveratrol, but which Guarente says is potentially more potent and effective.

Elysium explicitly wants to avoid the charlatan feel of the countless “anti-aging” products on the market today. It isn’t selling the pill as a key to a longer life or to preventing any particular disease, since there isn’t any evidence the pill will do that. A press release the company put out with its launch hardly mentions aging at all. (Another reason is they want to appeal to young people too, who don’t necessarily care about aging, but may want to feel healthier and more energetic). Instead, the founders talks about enhancing basic biological functions: improving DNA repair, cellular detoxification, energy production, and protein function.

“We have no interest in being an anti-aging company and extending lifespan,” says Marcotulli. “For us this is about increasing healthspan, not lifespan.”

THE FUTURE OF DIETARY SUPPLEMENTS

There is a downside to the model: They can’t patent their work. Some companies already sell supplements for each of the two ingredients in BASIS, and others could copy Elysium as soon as it releases its next products. That’s where Elysium’s business model — and its scientific superstars — come in.

The company aims to be very different type of dietary supplement company — the founders cite the hip, design savvy consumer brands Warby Parker, Oscar Health, Harry’s, and Nest as their role models. (Warby Parker co-CEO Dave Gilboa and one of its early investors, Kal Vepuri, are angel investors in Elysium. Martin Lotti, creative director for Nike’s soccer division, is a strategic advisor.)

“Our vision and mission is to bring scientifically validated natural health products to market through these traditional retail channels,” says Marcotulli. “But it also takes the best aspects of the pharmaceutical model — the R&D focus, clinical rigor, and following these consumers over time.”

Its products will only be sold on its website, where Elysium can control more nuanced messaging than on store shelves. Branding, trust, and scientific expertise are what the team hopes differentiates them from the faceless companies that line Whole Foods’ shelves. At the most basic level, that means trust that the pill contains what it says it contains, but also beyond that, trust that it is doing a person any good.

Elysium assures the ingredients in its products will all be pure, and it will do its own safety testing, as well as test for a basic level of efficacy. Already, says Guarente, it has tested BASIS at a range of doses for safety and to assure that NAD levels in the body actually increase from taking its pill. Over time, the team hopes to also collect data back from customers to start demonstrating some of the longer-term benefits over months and eventually years.

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, says Elysium has a good business idea based on sound science and an impressive team. As someone who is not involved in the company, his one fear is that if something went wrong with a top scientist like Guarente’s name attached, it might set back the whole field of research. Though not required by the FDA, he urges the company to go above and beyond in all of its testing. “People are going to overuse it, and I’m sure if you have too much of it, it could have some effect we can’t predict,” he says.

For Elysium’s next products, which might touch on other areas such as brain health or musculoskeletal health, it will start to tap into the expertise of the formidable list of more than 30 scientific advisors signed on — everyone from Eric Kandel, a brain scientist who received the 2000 Nobel Prize in medicine to Tom Sudhof, a cellular physiologist at Stanford who received the prize in 2013. Eventually, it hopes to expand this network of scientific expertise further to as many scientists that want to get involved.

If anything, Elysium might make more people aware that aging is becoming something that we may one day treat.

“There has been an explosion of science in the field of aging. And I think the public doesn’t really realize how far aging research has come. We have a lot of ideas about the mechanisms of aging, and tons and tons of pathways that can be optimized, tweaked, or activated to possibly extend lifespan,” says Stanford University aging researcher Stuart Kim, who is on Elysium’s scientific advisory team. “I think the public is probably about 30 years behind our thinking about aging. It’s as if we thought about cancer in the way we did in 1960.”

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The Anti-Aging Pill
By Karen Weintraub
Technology Review
February 3, 2015

Original Link

An anti-aging startup hopes to elude the U.S. Food and Drug Administration and death at the same time.

The company, Elysium Health, says it will be turning chemicals that lengthen the lives of mice and worms in the laboratory into over-the-counter vitamin pills that people can take to combat aging.

The startup is being founded by Leonard Guarente, an MIT biologist who is 62 (“unfortunately,” he says) and who’s convinced that the process of aging can be slowed by tweaking the body’s metabolism.

The problem, Guarente says, is that it’s nearly impossible to prove, in any reasonable time frame, that drugs that extend the lifespan of animals can do the same in people; such an experiment could take decades. That’s why Guarente says he decided to take the unconventional route of packaging cutting-edge lab research as so-called nutraceuticals, which don’t require clinical trials or approval by the FDA.

This means there’s no guarantee that Elysium’s first product, a blue pill called Basis that is going on sale this week, will actually keep you young. The product contains a chemical precursor to nicotinamide adenine dinucleotide, or NAD, a compound that cells use to carry out metabolic reactions like releasing energy from glucose. The compound is believed cause some effects similar to a diet that is severely short on calories—a proven way to make a mouse live longer.

Elysium’s approach to the anti-aging market represents a change of strategy for Guarente. He was previously involved with Sirtris Pharmaceuticals, a high-profile biotechnology startup that studied resveratrol, an anti-aging compound found in red wine that it hoped would help patients with diabetes. That company was bought by drug giant GlaxoSmithKline, but early trials failed to pan out.

This time, Guarente says, the idea is to market anti-aging molecules as a dietary supplement and follow up with clients over time with surveys and post-marketing studies. Guarente is founding the company along with Eric Marcotulli, a former venture capitalist and technology executive who will be CEO, and Dan Alminana, chief operating officer.

The company says it will follow strict pharmaceutical-quality production standards and make the supplements available solely through its website, for $60 for a 30-day supply or $50 per month with an ongoing subscription.

“You have high-end prescription drugs up here, which are expensive,” says Guarente, gesturing upward. “And you have the nutraceuticals down there, which are a pig in a poke — you don’t know what you’re getting and you don’t know a lot about the science behind them. There’s this vast space in between that could be filled in a way that’s useful for health maintenance.”

An anti-aging pill with an ivory-tower pedigree could prove profitable. The $30 billion supplements market is growing at about 7 percent a year overall, Alminana says, and at twice that rate for online sales.

Elysium declined to name its investors, but it has some high-level endorsements. Its board includes Daniel Fabricant, former director of the FDA’s division of dietary supplements and now CEO of the Natural Products Association, a trade association. The company also has five Nobel Prize winners advising it including neuroscientist Eric Kandel, biologist Thomas Südhof, origin-of-life theorist Jack Szostak, and the 2013 laureate in chemistry Martin Karplus.

Karplus, now an emeritus professor at Harvard, said in a telephone interview that he was turning 85 this year and had asked the company to send him a supply of Basis as soon as it’s available. “I want to remind myself whether I really want to take it or not,” says Karplus.

Scientists have shown they can reliably extend the life of laboratory mice by feeding them less, a process known as “caloric restriction.” That process seems to be mediated by biological molecules called sirtuins. NAD is important because it’s a chemical that sirtuins need to do their work and is also involved in other aspects of a cell’s metabolism. In worms, mice, and people, NAD levels fall with age, says Guarente, so the idea is to increase levels of the molecule.

“NAD replacement is one of the most exciting things happening in the biology of aging,” says Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, who has coauthored scientific papers with Guarente but is not involved in Elysium. “The frustration in our field is that we have shown we can target aging, but the FDA does not [recognize it] as an indication.”

Other experts said while NAD may decline with age, there is limited evidence that aging can be affected by restoring or increasing NAD levels. “There is enough evidence to be excited, but not completely compelling evidence,” said Brian K. Kennedy, CEO of the California-based Buck Institute for Research on Aging.

Guarente says Elysium’s pill includes a precursor to NAD, called nicotinamide riboside, which the body can transform into NAD and put to use. In addition, the pill contains pterostilbene, an antioxidant that Guarente says stimulates sirtuins in a different way. Both ingredients can already be found in specialty vitamins. “We expect a synergistic effect [from] combining them,” he says.

Guarente says Elysium plans to gradually add to its product line with other compounds shown in academic labs to extend the healthy lifespan of worms, mice, or other animals. The company will do preliminary testing to make sure the products are not toxic but will not follow the arduous FDA approval process. Vitamins and supplements can be sold over the counter as long as they contain ingredients known to be safe and don’t make overly specific health claims.

Marcotulli says the company has some anecdotal evidence that Elysium’s pills make a difference. “For older demographics, we’ve heard really interesting feedback related to levels of energy. It’s very, very useful and restorative,” he says. And he takes the pills himself. “When I don’t have a supply, I feel actually fuzzy,” he said. “It’s become a staple of my routine.”

Guarente also says he takes Basis every day, along with 250 mg of resveratrol, the red-wine compound. Guarente also exercises — though not, he says, as often as he should.

He says it doesn’t trouble him that he sees no obvious benefits yet from his supplement regimen. Too many studies in the anti-aging field, he says, are too short-term to show real benefits. Or else they study people who are already unhealthy. “I think that’s the way it would be if something is really acting to slow your progression into decrepitude — you’re not going to notice that,” Guarente says.

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RELATED LINKS:

Pulse on Aging & Anti-Aging
• Rethinking Buddhism: A New Way To View Suffering

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