Big insulin maker Eli Lilly is stepping into islet cell encapsulation, marking its first foray into a type of research that could bring about a new era of treating and potentially curing type 1 diabetes.

In early April, the Indianapolis-based Pharma giant announced a new collaboration with biopharm startup Sigilon Therapeutics in Cambridge, MA, to develop implantable mini-capsules containing insulin-making islet cells that would go into a person's abdomen -- lasting for at least a year without the need for immunosuppressant medications!

This is the first time Lilly has moved into the diabetes cure research space, although it's been involved in cure research for a variety of other health conditions -- countering lingering doubt that Big Pharma really wants to cure diseases that bring them so much profit.

“The cure for diabetes is high on our agenda, it just comes down to figuring out the right time and project to jump in with," says Dr. Ruth Gimeno, Eli Lilly's VP of Diabetes and Metabolic Research in Indianapolis. “This represents a unique combination of where we are in the islet stem cell space, as it’s ripe for cell-based therapies, and finding encapsulation technology that doesn’t require immunosuppressants. Putting the two together and starting a program in that area... it just seemed like the right time to do this.”

This work with Sigilon could in fact represent a major step forward in islet cell transplantation, if they are indeed able to eliminate the body's negative immune system response to implanted and encapsulated cells. Doing away with that huge hurdle would be a significant milestone.

All the work is in pre-clinical stages now and still years from even getting to human studies. But the promise of Sigilon's technology along with Lilly's substantial stake in this makes it quite intriguing, even at this early stage.

 

Sigilon's Afibromer Technology

So what exactly is Sigilon's technology all about?

The Boston area startup itself is only about a year old, a spin-off from life science innovation firm Flagship Pioneering that unveiled Sigilon in mid-2017 with $23.5 million in capital funding from both JDRF and the Helmsley Trust.

Known as Afibromer technology, Sigilon's platform is combines cell engineering and a new class of proprietary implantable biomaterials. Those biomaterials can be crafted into tiny microsphere capsules -- about the size of little beads -- that will not trigger an immune fibrosis response in a person's body, so immunosuppressant drugs wouldn't be needed.

These bead-like capsules would be implanted into the peritoneal cavity (in the abdomen between the inner organs) with a short surgical procedure, something that could take place in a doctor's office. From there, we're told that "therapeutic molecules produced by cells within the microsphere capsules would be secreted into the body and enter circulation," with the implants remaining in place.

In other words: the glucose-responsive cells inside these microsphere capsules would be invisible to the immune system and able to do their job managing glucose levels with insulin or glucagon as needed -- and Sigilon says the implants could last at least a year, if not longer, before needing to be replaced.

Of course, we've yet to see any human results... In early data published in 2016, the Sigilon Afibromer tech worked in lab mice for 174 days. And Sigilon's people tell us other studies show they've lasted for a year, and could potentially survive for multiple years if they find the correct cell line. But there is of course no guarantee what will materialize in human trials.

Sigilon's work originated with research by Dr. Robert Langer and Dr. Daniel Anderson, both from MIT and Boston's Children Hospital, who co-founded Sigilon; and the company has quite the list of accomplished collaborators, including Dr. Jose Oberholzer, well-known for his many years of islet transplantation work at the University of Illinois at Chicago.

For JDRF's part, they're banking on Sigilon's potential to do away with required immunosuppressants -- which could open a whole new chapter in diabetes cure research.

"For the past decade, we’ve supported research... to make beta cell replacement a widely available option for people with T1. We’re excited that Eli Lilly and Sigilon Therapeutics are developing new encapsulated cell therapies with potential to restore insulin production and look forward to the benefits their collaboration will have to the diabetes community," says JDRF Chief Mission Officer Aaron Kowalski, a longtime type 1 himself.

 

Different from Other Islet Encapsulation Tech?

OK, this may sound familiar because others are also exploring islet cell encapsulation technology along the same lines.

Two of the most news-making approaches are from the Diabetes Research Institute in Florida, with its BioHub that has already been transplanted into people with diabetes, and ViaCyte's Encaptra device that's currently undergoing human trials. Both of those also encapsulate islet cells and, to a varying degree, allow for someone with diabetes to produce their own insulin again and basically be "diabetes free" for a period of time. Interestingly, ViaCyte also recently announced a over 200 new patents for its proprietary encapsulation tech.

But Sigilon says its Afibromer technology is different in that:

  • it only uses human stem cells from adult donors
  • there's no need for immunosuppressant drugs (!)
  • it's cost effective and scalable (though specifics on that are TBD)

"We believe that over time, as we have seen in other areas of diabetes care, the best solution for patients will be as much about the delivery mechanism of the product as the therapeutic molecule utilized (insulin)," says Rich Allen, a spokesman for Sigilon. "We also believe that the Sigilon encapsulation technology offers a strategic advantage to islet cell therapy per se in its ability to avoid foreign body response and enable long-term cell survival and function."   

In terms of their pipeline, Sigilon tells us the startup has an internal goal to first pursue its blood disorders program in 2019, and then move into the clinical trials for this islet cell program as soon as possible after that.

Once that happens, Lilly will take over the later phases of clinical R&D to prepare for regulatory approval, which is at best several years down the road. Lilly would then have exclusive rights to market and sell this product/procedure worldwide, once approved by the FDA.

 

Lilly's Interest in a Diabetes Cure

For many in the Diabetes Community, Eli Lilly isn't the first organization that comes to mind when you think of those pursing a diabetes cure. Insulin manufacturing is usually top of mind, probably followed by some level of fist-clenching over skyrocketing prices and inaccessibility. You might even remember how Lilly's now putting its foot into the D-tech space, announcing in late 2017 its plan to develop an insulin pump and smart insulin pen down the road.

Now we can add D-Cure related science to that list, too.

“While cell encapsulation research is new, Lilly has targeted both cures and maintenance therapies across various disease states during our history,” said Greg Kueterman, communications director for Lilly Diabetes. “The pathway has often followed the disease and the emerging science around it."

We're told this Lilly-Sigilon collaboration was in the works for months before it was finally announced in early April, and that a meeting taking place during the big JP Morgan Healthcare Conference in January helped solidify the deal.

It's also worth pointing out that in January 2018, Dr. David Moller left his role as Eli Lilly's VP of business development in emerging technologies and innovation to become Chief Scientific Officer at Sigilon -- a move that probably also played into this how collaboration came together when it did.

Yes, and a big chunk of cash is connected to this deal: Sigilon will get $63 million up front, along with an undisclosed equity investment from Lilly and up to $410 million in milestone payments over the course of the collaboration.

Dr. Gimeno at Lilly says the initial lead for this deal came from Lilly Cambridge Innovation Center, which she says is exactly the point of establishing that new innovation center. And working with Sigilon made perfect sense, given what they bring to the table. There will be a joint Lilly-Sigilon steering committee overseeing this project as it progresses.

“This is part of our strategy in looking toward the external environment. It’s impossible to develop everything yourself, and so I see a lot of value in these collaborations,” she said.

With Sigilon's expertise in T1-focused cell therapies combined with the immunosuppression workaround, Gimeno says she's excited about the possibilties -- both from the Lilly research side, as well as from her personal POV as aunt to a niece living with type 1 diabetes.

 

Hope versus Hype

Lilly certainly isn't the first Pharma company to step into the diabetes cure arena, as others -- including direct competitors in the insulin and diabetes drug space -- have done so in the past.

For example, Janssen Pharmaceuticals announced a few years ago its Disease Interception Accelerator (DIA) aimed at studying T1D and eventually curing the condition. A quick Google search will bring up many other projects, including Novo's use of stem cells and Sanofi's interest in beta cell regeneration as examples of ongoing cure-related research projects.

What all of these have in common is that they're futuristic visions right now, with no guarantee that they'll pan out to meet their lofty cure goals.

Of course, whenever diabetes cure research comes up, there's also the talk of conspiracy. Yes, some people believe there's an active plot by Pharma (and maybe even the FDA and big national nonprofits?) to suppress a cure in the interest of preserving cash flow.

Others point out that's just nonsense, as a cure itself could be quite profitable, while also saving lives.

The big hope is that any "cure" -- biological or technological -- will be affordable and accessible to all who need it. But like so much in this realm, we'll just have to wait and see.