Eli Lilly will partner with Sigilon Therapeutics to develop encapsulated cell therapies as treatments for type 1 diabetes, through a collaboration that could generate up to $473 million-plus for the year-old startup, the companies said today.

Based in Cambridge, MA, privately held Sigilon focuses on discovering and developing “living therapeutics” through its Afibromer™ technology product platform. Afibromer stands for “afibrotic polymers which do not trigger a fibrotic response.”

“Insulin-dependent diabetes is a very compelling application of our Afibromer technology, with the challenge of providing dynamic protein delivery in response to specific conditions in the body,” Sigilon states on its website. “This requires a complex clinical development strategy that is best handled with an industry partner where together we can leverage the significant resources required for success.”

Sigilon plans to create proprietary products consisting of induced pluripotent stem cells, engineered into differentiated insulin-producing pancreatic ß-cells and encapsulated using Sigilon's Afibromer technology. The goal of these products, Lilly and Sigilon said, will be to restore insulin production over sustained periods, without triggering an immune reaction.

“We are excited to be collaborating with, and investing in, Sigilon as they seek to develop encapsulated cell therapies, a potentially disruptive technology that could result in meaningful clinical advancements for chronic diseases such as type 1 diabetes,” Daniel Skovronsky, M.D., Ph.D., SVP for clinical and product development and incoming president of Lilly Research Labs, said in a statement.

Dr. Skovronsky will lead Lilly Research Labs as of June 1, succeeding Jan Lundberg, Ph.D., who will retire after overseeing the development of 20 new treatments in 10 years. The R&D leadership shuffle followed the appointment of David A. Ricks last year to succeed John C. Lechleiter, Ph.D., as chairman and CEO.


Diabetes Legacy

Lilly is a diabetes pioneer. It launched the first commercially available insulin product for diabetes control in humans in 1923, and in 1982 won FDA approval for Humulin®, the first marketed human healthcare product derived from recombinant DNA (rDNA) technology. In announcing fourth-quarter and full-year 2017 results on January 31, Ricks said diabetes was among core therapeutic areas for which Lilly expects progress this year in developing new treatments, along with cancer, immunologic disorders, neurodegeneration, and pain.

In December 2017, Lilly launched a clinical trial (NCT03367390) to assess the functionality and safety of its “Connected Diabetes Ecosystem” automated insulin delivery (AID) system in type 1 diabetes—namely a hybrid closed-loop platform consisting of an insulin pump with a dedicated controller, dosing algorithm and continuous glucose monitor. The study was completed as of March 15.

According to Lilly, AID is one of two platforms in development for the Ecosystem. The other is an integrated insulin management system combining a connected insulin pen with glucose-sensing technologies and software applications to deliver personalized insulin dose recommendations.

Lilly’s diabetes pipeline is headed by four Phase III programs, two of them focused on treating type 1 diabetes. One is BI10773 (empagliflozin), a small-molecule sodium glucose co-transporter-2 (SGLT 2) inhibitor being co-developed with Boehringer Ingelheim. The other is LY900014 (ultra-rapid lispro), a novel formulation containing locally acting excipients to accelerate insulin lispro absorption, under study for types 1 and 2 diabetes.

Sigilon’s pipeline includes a diabetes candidate in early preclinical development, Sig-002.

Between 2015 and last year, Daniel G. Anderson, Ph.D., of MIT’s David H. Koch Institute for Integrative Cancer Research led researchers in studies that showed promise for the Afibromer platform. Research leading to the discovery of Afibromer biomaterials was funded by grants from JDRF International and the Leona M. Helmsley and Harry B. Helmsley Charitable Trust, and conducted by researchers led by Dr. Anderson and Robert Langer, Sc.D., of MIT and Boston Children's Hospital.


“Allogenic Cell Factories”

“This holds the promise for the creation of state-of-the-art allogeneic cell factories to be transplanted into patients, without the need for immune suppression,” added Sigilon CEO Paul Wotton, Ph.D. “Our cell engineering and delivery system-based platform may allow us to program and control dynamic protein delivery for the long-term treatment of debilitating diseases.”

Sigilon says its Afibromer technology is designed to enable a new category of therapeutic, encapsulated cell therapeutics that do not require immunosuppression. While implanted cells have shown the ability to produce desired therapeutic proteins, the company notes, genetically dissimilar cells can be attacked and destroyed by the immune system, even if the cells are encapsulated within biomaterials.

Cells encapsulated in Afibromer-coated capsules are designed to be invisible to the immune system and thus not trigger fibrosis.

“Our therapeutic platform combines an engineered cell line with our novel polymer chemistry to create a durable, biologically active cell implant,” Sigilon states on its website. “Our proprietary cells are engineered to secrete therapeutic proteins and, in combination with our Afibromer technology, these implanted cells are hidden from the immune system, and levels of the missing protein in the body can be restored for long periods of time following a single intervention.”

According to Sigilon, the Afibromer platform offers “extremely broad” potential to treat numerous illnesses as well as numerous advantages over traditional biologics—including improved outcomes over current standard-of-care, safe and reversible therapeutic modality, restored protein levels at a constant rate, the potential for years of therapy without redosing or frequent injection/infusion, and a rapid preclinical timeline and favorable regulatory pathway.

Lilly will receive from Sigilon an exclusive worldwide license to its Afibromer technology for islet cell encapsulation. Sigilon has agreed to oversee all development activities and costs related to the collaboration until submission of an Investigational New Drug (IND) application. After an IND is submitted, Lilly will be responsible for all clinical development and commercialization activities and costs related to the collaboration, the companies said.

In return, Lilly agreed to pay Sigilon $63 million upfront, an undisclosed equity investment, and up to $410 million in payments tied to achieving development and commercialization milestones. Sigilon is also eligible to receive from Lilly double-digit tiered royalties on future product sales should the collaboration yield a commercially successful product.

Sigilon was launched last year by Flagship Pioneering (formerly Flagship Ventures)—a firm that creates and supports, as well as funds, life science companies—with $23.5 million in capital. Flagship Pioneering’s managing partner, Doug Cole, M.D., is chairman of Sigilon’s board.

Lilly said it will incur an acquired in-process research and development charge against earnings of approximately 5 cents per share in the second quarter—with the pharma’s earnings per share (EPS) guidance for 2018 expected to shrink by the amount of the charge. Lilly has given investors guidance for 2018 of GAAP EPS ranging from $4.39 to $4.49.

There will be no change to the company's non-GAAP EPS guidance, which is between $4.81 and $4.91, Lilly added.






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