SOUTH SAN FRANCISCO — The market for acne treatments is simultaneously oversaturated and sorely lacking. There are the mainstays, of course — the Proactivs and Clean & Clears of the skin care world. There are the new kids on the block, the Glossier zit sticks and K-beauty toners and manuka honey face masks. And there are the solutions that require a trip to the dermatologist, like generic Accutane and antibiotics.
But there could one day be a new option in the acne treatment arsenal: microscopic bacteria and viruses.
As scientists uncover more details about the skin microbiome, small startups and beauty giants alike are exploring how the trillions of microorganisms on and in our bodies could be used to treat a range of skin conditions, either by battling the bad bugs or bolstering the good ones. But as businesses launch new efforts to investigate that idea, they face an existential question: Are they a beauty company, a biotech company, or somewhere in between?
A clear illustration of that choice can be found in Johnson & Johnson’s tech incubator in South San Francisco, where two companies are both betting that influencing the skin microbiome could lead to clearer skin. One, Naked Biome, is using a specific strain of bacteria — plucked from the pore strips of people with healthy skin — to tamp down acne. That company is running clinical trials and, if all goes successfully, plans to apply for approval as a drug.
Its neighbor, a company called Ellis Day, has created a cocktail of three phages — viruses that kill bacteria — that it says can help improve the appearance of “blemish-prone skin.” Ellis Day is going straight to consumers with its serum.
Whatever path companies take to market, scientists caution one thing is clear: There are still far more scientific questions about the skin microbiome than there are answers.
“We really are still at the early stages,” said Julie Segre, the head of the microbial genomics section of the National Human Genome Research Institute at the National Institutes of Health.
A scientific bet on bacteria pulled from pore strips
Naked Biome’s particular strain of bacteria was pulled from a pile of Biore pore strips, ripped from the faces of partygoers at a happy hour in 2016 at an accelerator for genomics startups. The guests — who were all also trying to get companies off the ground — were happy to offer up their skin for sampling.
“We’re just going to swab and take some strips, and you can go about and have your cocktails,” Dr. Emma Taylor, founder of Naked Biome and a dermatologist, recalled telling the group. She meticulously assessed each person’s skin, taking notes on every bump and blemish, hoping to glean more insights into the differences in the microbial makeup of healthy skin and acne-prone skin.
The company sequenced the bugs from healthy skin and pinpointed a single bacterial strain they’ve since advanced into clinical trials. They’re currently running a Phase 1 trial in which people are applying the product to their face every day for 11 weeks, after a week of using benzoyl peroxide.
The bacterium is delivered in a single-use pad that’s similar to the old-school Stridex pads loaded with salicylic acid. They come in a vacuum-sealed pack and are stored in the freezer to keep the bacteria happy until it’s time for a user to swipe it across their face. Naked Biome is trying to limit the other products people are using to control the results, but are still letting people use sunscreen and makeup like they normally would to see how the product would fare in a somewhat real-world setting.
“We’re trying to make it integrate into their normal routine, recognizing that our bugs may die along the way with some of the products that they’re using,” she said.
And while the primary objective is to make sure the product is safe, they’re also looking at lesion counts for early signs that the strain is successfully treating acne. They are expecting that data this month.
It’ll be years before the company has enough evidence to take to the FDA for approval, but Naked Biome believes it’s worth the wait to see whether the treatment is truly effective and safe. Taylor said she believes the microbiome has the potential to be as “paradigm-shifting” for inflammatory conditions like acne as immunotherapy has been for cancer care. But that’s if — and only if — it’s approached the right way, she said.
“Getting buy-in from the scientific community is going to be in the long run much better, because this will then be, we hope, a drug that has been appropriately validated scientifically vetted,” she said.
‘These are all questions we’re scratching the surface of’
Vetting a new acne treatment isn’t simple. Skin conditions are notoriously difficult to study. There aren’t good animal models for acne, there are persistent problems with the accuracy of bacterial counts, and there’s a notable placebo effect.
And adding the microbiome into the mix only complicates the equation. It’s tricky to get a live look at the community of microbes crawling on the skin — and even more difficult to see what happens in the moment a new microbe is added. Naked Biome is turning to its trusty strips to see if its bacteria is getting inside hair follicles. But they still don’t know what’s happening in the time between when a participant uses the pad, when a skin sample is collected, and when that sample gets to the lab.
“They were nice and happy in a little cold vacuum-sealed pack. Suddenly you warm it up and put it on someone’s skin,” Taylor explained. “Are they still alive after application, or are they just dying, like it’s this mass Armageddon, after putting them into a new environment?”
If the bacteria are living and thriving on the skin, that raises a whole new crop of questions, experts said.
“When we give someone a drug, we understand what the half-life of that drug is. [With a bug,] do we want it to stay there? Does it matter if it stays there?” said Segre, of the NHGRI.
Not all strains of bacteria behave the same way. Some develop antibiotic resistance. Some have an easier time colonizing the skin than others — and are harder to get rid of. It’s not clear what, exactly, needs to happen for a new strain of bacteria to become a permanent part of a person’s microbiome, and it’s not clear whether there are long-term consequences if that does happen.
To be clear, many of the products found in medicine cabinets likely also affect the microbes on our skin. Cleansers do away with the day’s dirt, while face scrubs might tamp down bacteria that’s driving inflammation.
“When you put on a cream, you probably think you’re moisturizing your skin, but I think you’re feeding your microbial garden,” Segre said. But for the most part, skin care products you can pick up at the store haven’t been studied to see if they permanently change the skin microbiome. That’s one of the issues that Naked Biome and other companies are grappling with as they look toward FDA approval in the coming years.
“These are all questions that we’re just scratching the surface of right now,” Taylor said. “There’s a lot more that has to be done to answer [them].”
A phage cocktail promises to make ‘blemish-prone skin’ look better
Answering all of those questions — or even some of them — will take years. In the meantime, other skin care companies are marching to the market with products that promise to give your skin microbiome a boost.
One of those companies, Ellis Day, is launching a serum later this year that’s made with a cocktail of three phages. The teeny viruses can infect bacteria and replicate inside them, killing it from the inside. Like microbes, our skin and our environments are already crawling with phages that peacefully coexist with us. Ellis Day found two of its three phages on the skin, and another “in nature” in the Bay Area. The company is betting the blend can clear up skin by combating several different strains of bacteria that can cause acne.
“This is a radically new approach to treating acne. … This is the way nature gets rid of the bad bacteria,” said Carole Christopher, the chief executive officer of Ellis Day.
The company ran a small study with 20 women who used the serum every night for three months. Christopher said that study found that people using the serum had a greater reduction in the number of blemishes on their face than those who didn’t, though that data hasn’t been published in a peer-reviewed journal.
The team at Ellis Day talked with the FDA and regulatory consultants about the best path to take to the market. They considered going ahead as an over-the-counter product, but that would mean they would need to include an ingredient on the FDA’s list of ingredients cleared for over-the-counter drugs, like acne heavy-hitters such as salicylic acid or benzoyl peroxide. They didn’t want to do that.
“Our concern was consumers, who are very savvy now about ingredients, would look at the label and say, ‘Oh, it’s got salicylic acid, it’s the same old thing,’” Christopher said.
So instead, Ellis Day will market its phage product — a watery serum housed in an opaque glass bottle with a special stopper to keep air out — as a cosmetic. That means the company has to tread lightly with its claims. They aren’t treating acne — they’re “changing the appearance of blemish-prone skin.”
But Christopher is betting that consumers will be willing to try it, largely because it’s different than the charcoal scrubs, zit sticks, and clay masks they’ve tried in the past. Taking a page from the glossy beauty brands that have found success on Instagram, Ellis Day plans to use “micro-influencers” on social media to drum up more interest. Their target audience is millennial women between 25 and 30, who are more likely to have two key characteristics: skin issues and disposable income. A bottle of the serum, which lasts for two months, will cost a cool $85.
There are already plans to launch a cleanser and moisturizer next year. And while the company will start selling on its own website, Christopher is hopeful that Ellis Day will soon earn a coveted spot on the shelves of brick-and-mortar beauty stores.
“Sephora would be the best fit, I think, because they handle premium-priced brands. And they also handle new technologies pretty well,” Christopher said.
Outside experts said there aren’t safety concerns with phages, given that they’re found naturally on the skin. But there are still questions about how well phages in general would work to treat acne.
“They still are microorganisms that need to be studied rigorously before being sold to consumers. … I don’t like the idea of phages being sold essentially as nutraceuticals without adequate testing,” said Dr. Robert Schooley, the co-director of the Center for Innovative Phage Applications and Therapeutics at the University of California, San Diego.
As scientists continue to study the microbiome, they’re gleaning new insight into the intricate interactions happening between bacteria on and in our bodies. But Segre said it will take much more research to understand how to best harness the microbiome for new types of medical treatments.
“You might think that the last few years have really been an acceleration of the fundamental knowledge gained about the skin microbiome,” Segre said. “I am going to argue that we need additional basic research to realize [its] potential.”