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With $23M, Flagship-Backed Sigilon Protects Protein-Producing Cells

Xconomy Boston — 

Companies have been trying for years, if not decades, to find a way to encapsulate cells for therapeutic use in a way that protects them from the body’s reactions. Sigilon Therapeutics, a Cambridge, MA-based biotech, announced today it has raised $23.5 million from Flagship Pioneering to take its technology to clinical trials.

The company has developed capsules that hold cells engineered to secrete therapeutic proteins, which Sigilon says can target disorders of the blood and enzymes, and possibly diabetes, too. The capsules are notable, Sigilon says, because they were developed to avoid tissue scarring and immune responses that have historically killed or disabled the cells and prevented them from delivering the therapy.

Sigilon uses a chemically altered version of a polymeric capsule—specifically an alginate, which comes from algae—that prevents the immune system from recognizing the cell in the capsule as a foreign body. This capsule also prevents fibrosis, the body’s scarring response to foreign objects. The chemical alteration was developed by co-founders Daniel Anderson, a professor of chemical engineering at MIT, and Robert Langer, the prolific MIT researcher and Xconomist.

“What’s new about our platform is that the chemistry that was used really provides an anti-fibrotic effect to the alginate, which has never been seen before,” says CEO Paul Wotton. “When you put a foreign body into someone like you or me, your body starts to attack that implant. What this chemistry does is it prevents this scar tissue from occurring.”

That approach has allowed Sigilon’s encapsulated cells to remain in animals for as long as year, according to studies the company has performed. Typically, the scarring will deprive cells of nutrients or oxygen they need to survive in about a month, Wotton says.

Sigilon was founded in 2016, but the research dates back at least a decade and was initially funded by grants from the Juvenile Diabetes Research Foundation, or JDRF, Wotton says. Langer and Anderson have both received JDRF grants that total approximately $18.8 million, according to the nonprofit’s public records, which show the initial focus was on diabetes. That has since broadened.

The capability of Sigilon’s encapsulation materials is a reason for optimism, especially given the decades researchers have spent trying to effectively deliver cell therapies, says John Wilson, an assistant professor of chemical and biological engineering at Vanderbilt University. Therapeutics developed with these methods are only as good as the cells being encapsulated, Wilson adds.

“I think it’s fair to say these materials are a big enough breakthrough to usher in a new era of optimism for these approaches, at least from the standpoint of the encapsulation device,” Wilson says. “With all the recent advances in cell engineering over the past decade, it’s exciting to see new polymers for cell encapsulation emerge that can complement these advancements.”

Cellular therapies have regained popularity in recent years by biotechs targeting developing treatments for all sorts of conditions, from makers of advanced cancer treatments to biotechs such as ViaCyte, which makes packets of stem cells that are engineered to develop into pancreatic cells for diabetics. Type 1 diabetes is a big target in cell therapy world because it destroys pancreatic beta cells, which regulate blood sugar levels in the body.

One researcher who Xconomy spoke to in San Antonio believes he has a cocktail of molecules that can stimulate the new formation of insulin-secreting beta cells. Semma Therapeutics, a Cambridge-based drug developer founded by MIT professor Douglas Melton, similarly says it can generate fully functioning beta cells from pluripotent stem cells—and potentially unlimited amounts of them.

Semma says it has its own encapsulation technology that can protect beta cells from the patient’s immune system, though it hasn’t revealed much about it. Nature wrote in 2016 that Semma may work with a University of Miami bioengineer on other encapsulation techniques.

In Sigilon’s case, the company surgically implants the encapsulated cells into a part of the abdomen near the stomach called the lesser sac. The cells in the chemically altered alginate capsule secrete the proteins from the lesser sac into the body’s bloodstream. Sigilon engineers its own proprietary cell lines to treat specific indications, with its initial focus targeting hematologic conditions, enzyme deficiencies, and endocrine disorders, according to a prepared statement.

Sigilon believes its encapsulation device has an edge over other cell therapies because it can be accessed and adjusted, even after it is implanted. That allows the number of cells that are implanted, and therefore the dosage of the treatment, to be adjusted if necessary, Wotton says.

“The big advantage for us is that you can increase the dose, decrease the dose, which you can’t do if you’ve got a standard gene therapy, where you inject the patient with a vector and hope it goes to the right place at the right quantities,” Wotton says. “It’s going to be producing that protein at a known quantity for months and probably years.”

Sigilon may expand by targeting more partnerships with companies that want to license its technology, says Douglas Cole, a managing partner at Flagship Pioneering and the chairman of Sigilon’s board of directors. That may be one way Sigilon is similar to another Flagship company, Moderna Therapeutics, which has a biological bent similar to Sigilon. Moderna develops strings of biological code, known as messenger RNA (mRNA), which it uses in patients cells to create proteins that fight diseases.

Moderna has successfully licensed its technology and spun out multiple businesses. The company has raised around $1 billion in investment and developed partnerships with companies including Merck (NYSE: MRK), AstraZeneca (NYSE: AZN), Vertex Pharmaceuticals (NASDAQ: VRTX), and Alexion Pharmaceuticals (NASDAQ: ALXN).

Even if Moderna and Sigilon have scientific similarities, Cole argues they are still different because the Sigilon’s focus on its delivery system that protects implanted cells, which deliver proteins to patients with protein deficiencies. (One publication said that Sigilon raised additional capital in 2016, and Cole says Flagship has not shown the business to other investors. Flagship is announcing the company’s launch today with the $23.5 million funding, Cole wrote in an email.)

Wotton believes Sigilon has room to grow, scientifically. He says one possibility may be trying to engineer cells to respond to biological conditions, such as lipid levels in the blood, which could encourage the cell to produce a cholesterol-reducing agent.

“I imagine within 10 years that a lot of technology will be available where you can engineer cells to respond to a specific signal, and then manufacture a protein or a drug that reflects the signal it has just received,” Wotton says. “My own personal belief is that cell therapy is coming of age now.”