Selecta Takes Nanotech to Gene Therapy, Celiac With New Deals

Xconomy Boston — 

Selecta Biosciences looks to have found two new potential niches for its nanoparticle technology.

The Watertown, MA-based company is announcing two deals this morning. First, Selecta said that Sanofi has chosen to license a potential immunotherapy treatment for celiac disease, the allergic disorder that renders people unable to digest gluten. Sanofi got the option as part of a 2012 deal between the two companies, and its decision today means that Selecta could ultimately get $300 million in payouts if the drug progresses.

In a second deal, with France’s Genethon, Selecta is attempting to address a looming potential problem with gene therapy—its staying power. Selecta aims to use its custom-built nanoparticles to stop a patient’s immune system from neutralizing a gene therapy after it’s delivered.

The two companies will first work on therapies for three muscular dystrophies and metabolic diseases of the liver in children (Selecta isn’t saying which ones specifically). Those therapies are delivered via what are known as adeno-associated viruses, or AAVs, the most commonly used “viral vectors”—gene therapy delivery tools. When used in gene therapy, AAVs burrow into cells and produce a protein that patients are lacking. But those transfected cells can alert the immune system, which can send antibodies to shut them down, and the patient doesn’t receive enough, if any, of the necessary protein.

It’s unclear how significant this potential waning effect is. In certain studies in hemophilia, for instance, AAV gene therapy has lasted for several years (and in dogs, a decade), but recently an AAV gene therapy for a form of inherited blindness was shown to be wearing off after a few years. Thus, despite all the progress that’s been made in gene therapy, it’s not really known how long these therapies will last.

Selecta believes its technology, what it calls a “Synthetic Vaccine Particle” platform, might help. It’s a method of producing vaccines from biodegradable, polymer nanoparticles that can be custom-built to have the same size and shape of specific viruses. As I wrote in December, Selecta originally planned to use this technology to develop vaccines. But the company has since focused on using its technology to tell the immune system to call off an unwanted attack—creating what’s called “antigen-specific tolerance.”

Selecta is trying to use this potential benefit in a variety of ways, like warding off the immune response against biologic drugs. Its lead program, for example, is a modified form of pegsiticase, a gout drug that had problems with immune reactions that limited its use. Selecta believes it’s effectively fixed those problems. Called SEL-212, the drug will begin clinical trials “in the next weeks,” CEO Werner Cautreels says, and serve as a test case for Selecta’s technology. But Selecta is diversifying its efforts as well, which is where these two deals come in.

In the case of celiac, the body misidentifies fragments of the protein gluten (found in barley, wheat and rye), and attacks and damages the gut. The field is crowded with experimental celiac therapies, because the disorder has no FDA approved treatments. The only remedy is to avoid gluten. Companies like Alvine Pharmaceuticals and Alba Therapeutics are developing treatments that would be taken in tandem with a gluten-free diet. A Lebanon, NJ, startup called Celimmune formed and licensed an old Amgen drug to try as a celiac treatment. And ImmusanT of Cambridge, MA, is testing an immunotherapy meant to work like an allergy shot, which would teach the body to tolerate gluten.

Like ImmusanT, Selecta wants to use an immunotherapy to induce tolerance. Cautreels says Selecta’s approach is different in that it’s trying to develop a “very short term” vaccine that would essentially tell the body to “ignore” gluten, rather than teaching it to tolerate the protein over time. The potential benefit—which hasn’t been proven yet— is that Selecta’s therapy, Cautreels says, might react quicker and be “much less variable from one patient to the other.” Still, Selecta is well behind: Cautreels estimates Selecta is “a couple of years” away from testing a celiac product in humans. ImmusanT said late last year that it’s gearing up for a Phase 2 proof-of-concept study.

Selecta is getting an upfront payment as part of the Sanofi deal, but Cautreels wouldn’t disclose how much. Sanofi will also cover research and development costs, while Selecta stands to get milestone payments and royalties if the deal ever leads to a marketed product.