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Triple Boston biotech launch includes Kaleido, LifeMine, and Disarm Therapeutics

Start-ups aim to modulate the microbiome, trawl fungal genomes for drugs, and prevent axon degeneration

by Ryan Cross
September 21, 2017 | A version of this story appeared in Volume 95, Issue 38

Credit: Kaleido Biosciences
Kaleido scientists are testing polysaccharides that modulate microbiome health.
A photo of gloved hands holding a petri dish.
Credit: Kaleido Biosciences
Kaleido scientists are testing polysaccharides that modulate microbiome health.

A trio of Cambridge, Mass.-based biotech start-ups unveiled themselves last week, all boasting impressive first rounds of financing.

Leading the pack was Flagship Pioneering-funded Kaleido Biosciences, which is designing orally available compounds to modulate the human microbiome, improve health, and treat disease.

Founded in 2015, the start-up remained in stealth mode within Flagship VentureLabs until its Sept. 18 emergence with $65 million in series A and B funding, more than 60 employees, and 100-some patent applications.

Newly positioned at Kaleido’s helm is Mike Bonney, former CEO of antibiotics developer Cubist Pharmaceuticals, which Merck & Co. purchased for $9.5 billion in 2014. That acquisition led to an exodus of several antibiotics experts from Cubist to Kaleido, including Jared Silverman, Kaleido’s first employee and previous vice president of discovery biology at Cubist.

“We’re creating a new category of chemistries that are the opposite of antibiotics,” says Flagship Pioneering partner Geoff Von Maltzahn. Kaleido views the microbiome as an organ that needs healing, not killing, he says.

During the past two-and-a-half years, Kaleido amassed a library of glycans (which includes oligosaccharides and polysaccharides) and began testing them on human gut microbiome assays designed to reflect healthy and diseased human bowels. “Other microbiome companies focus on the bugs-as-drugs approach,” in which microbes themselves provide treatment, Von Maltzahn says. Kaleido’s goal is to “drug the bugs” and improve microbial community health.

The precise reasons why different glycans modify the microbiome remains hazy, but “the concept is very well established,” says microbiologist Eric Martens, who studies the topic at the University of Michigan. “Every time you eat food, you are changing your microbiome based on your diet.”

Kaleido is seeking to uncover relationships between various glycans and microbiome health. “How this is all happening, we don’t have that clarity yet,” Bonney says. “But we do have the reproducibility,” with specific compounds producing predictable changes in the microbiome.

Kaleido’s pipeline includes compounds for several conditions, with an initial focus on urea cycle disorders, or “anywhere that hyperammonemia, or too much ammonia in the blood, is a problem,” Bonney says. The firm is also advancing compounds to cut toxins in chronic kidney disease, eradicate pathogens, and reduce mucus membrane damage in the gut caused by chemotherapy.

Kaleido aims to launch four human studies this fall and 20 over the next 18 months, although these won’t necessarily take the form of traditional clinical trials. “We’ve been able to get a lot of info from humans outside of an IND,” or Investigational New Drug Application, Bonney says, because many of the firm’s compounds are generally recognized as safe by the U.S. Food & Drug Administration. “We already have multiple IND candidates for a fraction of the cost that most companies would spend on their first IND.”

Von Maltzahn hopes that the antibiotics expertise of former Cubist employees will help quickly develop compounds that translate well from petri dish to humans.

Also receiving sizable funding is fungal genome mining start-up LifeMine Therapeutics. A $55 million series A funding round led by WuXi Healthcare Ventures launched the company with Harvard University chemical biologist Gregory Verdine as CEO. Verdine previously cofounded and served as CEO at Warp Drive Bio, which similarly trawls microbial genomes in search of gene clusters that produce natural products.

Launching with $30 million in series A funding from Atlas Venture, Lighthouse Ventures, and AbbVie Ventures is neurology-driven Disarm Therapeutics. Disarm plans to design small-molecule inhibitors of a protein called SARM1, recently implicated in axon degeneration. Potential SARM1 inhibitor applications include multiple sclerosis and amyotrophic lateral sclerosis.


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