3:08 PM
Aug 23, 2018
 |  BC Innovations  |  Product R&D

Sweet switch

How Ziylo’s glucose sensors could help Novo make the smartest insulin

Novo Nordisk A/S is betting Ziylo Ltd.’s glucose-responsive compounds can unlock development of smart insulins that are a step up for diabetes therapy. Unlike the competitors, which mostly act when blood glucose is high, Ziylo’s chemistry can also shut off insulin when glucose levels are low, removing the risk of hypoglycemia.

Novo’s acquisition of the U.K. biotech, announced last week, is evidence the pharma is following through on its commitment to move away from insulins that only offer incremental improvements and focus instead on more disruptive technologies (see ).

Ziylo’s platform is still at an early stage, but Novo thinks it has the potential to achieve a major goal in diabetes -- making a hypoglycemia-proof insulin therapy.

Standard insulin therapies require vigilant attention to dosing. If the molecules persist for too long, they can stimulate excessive glucose uptake into tissues, resulting in dangerously low levels of blood glucose.

Companies have long sought alternatives that take responsibility for avoiding hypoglycemia out of patients’ hands by emulating insulin’s homeostatic regulation, which couples its activity to high blood glucose levels. Such a product could increase safety and convenience, and fine-tune efficacy.

The leading approach involves smart devices, which are closed-loop pumps that continuously monitor glucose and automatically deliver insulin when needed. Drug developers are seeking pharmacological solutions as well, via smart insulins that are intrinsically capable of sensing high glucose. But none of the former, and few of the latter, contain a mechanism for stopping insulin signaling when glucose levels fall.

Two other pharmas have put stakes in the ground for glucose-responsive insulin therapies through M&A, though both deals have yet to bear fruit.

In 2010, Merck & Co. Inc. acquired SmartCells Inc.’s SmartInsulin technology, a polymer that releases insulin in response to changing glucose levels, in a deal valued at up to $500 million. Merck took the technology into the clinic via Phase I studies of the compound MK-2640, but discontinued the program in 2016 due to lack of efficacy. According to spokesperson Pamela Eisele, Merck is advancing a backup compound that is in early development.

Companies have long sought alternatives that take responsibility for avoiding hypoglycemia out of patients’ hands.

In 2016, Eli Lilly and Co. acquired Glycostasis Inc. for a different type of smart insulin depot. The biotech has a protein-based system that both releases insulin at high blood glucose levels and sequesters it when the levels fall. Deal terms were not disclosed, and Lilly has not yet published data on the program. Lilly spokesperson Nicole Hebert said the pharma has ongoing work in this area that includes the Glycostasis technology, and is open to additional partnerships.

Sanofi also has invested in glucose-responsive insulins through co-funding early stage work in the space with JDRF.

Novo had been working on the problem internally, developing...

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