April’s announcement that insulin maker Eli Lilly would invest up to $473 million in Sigilon Therapeutics and the cell encapsulation technology the Cambridge, Mass., biotech company is developing was big news in the type 1 diabetes space. We’ve been following this encapsulation technology since I met with Arturo Vegas in 2015, when he was a chemistry post doc at MIT working with Robert Langer and Daniel Anderson at the Koch Institute for Integrative Cancer Research. (In the lab, Vegas and his colleagues tested almost 800 different versions of an alginate material, and found one in particular that seemed to work particularly well: the material protected beta cells in an immunocompetent mouse for the six months, the length of the study; and, when empty capsules made of the material were placed in the abdomen of a non-human primate, the monkey’s immune system basically left them alone for more than 6 months, whereas capsules made of most of the other materials they tested were soon encased in a fibrous gunk. In a more recent test, encapsulated beta cells remained clean after four months inside a primate.) Last year, Sigilon licensed the material from MIT for $23 million, but with the Lilly deal Sigilon will be specifically focused on developing and testing insulin-producing beta cells in the lab, and using the material, now named Afibromer, to protect them from type 1 diabetes’ autoimmune attack. The goal of that product would be to replace the beta cells of someone with type 1—meaning a patient could regulate their own blood sugar, without insulin injections. “Imagine how transformative this could be,” says Vegas. “I keep on coming back to that—this will really change the way people with type 1 diabetes live.”
As Paul Wotton, Sigilon’s CEO, explained it to me, his company will be managing the work until it gets to the point of filing an Investigational New Drug (IND) application with the FDA, at which point Lilly will take over, and design the testing of the product on real patients. Before the deal with Lilly, Sigilon was already working on developing the encapsulation technology to protect cells for patients with hemophilia (a disease that prevents blood from clotting), so the company will have established a timeline in terms of testing the material and going to the FDA for approval. “It’s a good example, I think, of how creative corporate development can actually make things happen more quickly. We’re using our skills; Lilly is using theirs. Without giving confidential information away, I do believe we’ll be in the clinic within a few years—that’s what the current timeline is,” says Wotton.
Part of the work will involve translating induced pluripotent stem cells (iPS) into beta cells that can sense fluctuating glucose levels and respond. As Vegas points out, though, the steps to do this were outlined in 2014 (in a paper published in Cell by Douglas Melton, Felicia Pagliuca, Jeffrey Millman, Mads Gurtler and several other scientists). “Once the know-how is there, it’s just about applying it,” says Vegas. It’s the encapsulation technology licensed from MIT that’s “really the advantage,” says Wotton. “No one else has this ability to hide things from the immune system.” The chemical modification that Vegas and his team discovered at MIT seems to have a profound effect on whether or not the immune system can detect what’s encapsulated inside the material. Wotton narrated two moving graphics for me, showing what happens when alginate beads are placed in mice; the beads in the first image were encapsulated in the material developed at MIT; the beads in the second image were not. “With the beads that are coated, using this technology, you can see macrophages swimming up to the surface, and they sort of sniff it and they turn around and go away. But if you use the same polymer without the chemistry from MIT on it, the macrophages will swim up and it will stick. And then, as soon as one of them is stuck, some of its friends show up, and all of a sudden there’s a macrophage party going on at the implant. You don’t see that with this chemistry.”
As has been written here and elsewhere, creating a functional beta cell, encapsulated from the body’s attack, is the holy grail of diabetes research. And that’s part of the reason why this deal, involving a new encapsulation technology and a significant investment from an insulin manufacturer with its eye on the future, has received such attention. Both Vegas and Wotton emphasized to me the speed of this process, while acknowledging that progress can’t come fast enough for those affected by type 1. “This takes time of course,” says Vegas. “But this project was started in 2008; in scientific terms we are moving at breakneck speed.” Wotton expressed a similar point of view: “I know that if you’re a patient with any dread disease, one day is too many days. But this is a rapid development, and everything just seems to be coming together now. We’ve got this technology; we’ve got the ability to convert these IPS cells into beta cells using a process that’s quite well defined. And now we’ve got to put it together and execute it. And we’ve got the money and the focus to do it.”