Abvance’s Novel Coformulation of Insulin and Glucagon Could Revolutionize Diabetes Care
A team of scientists and physicians have discovered that insulin and glucagon, long thought solely to counteract one another as they lower or raise blood sugar levels, respectively, could actually work together for better and safer glycemic control. If Abvance’s foundational work proves out, people with diabetes who require insulin could have an easy and safe way to control their blood glucose levels more effectively without running the risk of hypoglycemia.
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A Dance, Not a Fight
“It was like watching someone be resurrected.”
David Maggs, MD, recalls the first time he saw a patient with diabetes receive treatment with glucagon to counteract dangerously low blood sugar. At the time he was a junior doctor in Kent in the UK, working in the ER. Seeing patients wheeled in the door unconscious and seizing — basically on death’s doorstep — suddenly rally with a simple injection of glucagon was an amazing clinical moment for Maggs, one that shaped his medical career.
In the years to come, first as a trainee doctor, then as an endocrinologist, Maggs came to see the enormous burden Type 1 diabetes (T1D) was for patients with the threat of hypoglycemia ever-present, “like a dark cloud hanging over their lives.” It’s a huge job balancing blood sugar on a daily basis. Too much insulin and you risk your blood sugar dropping low enough to cause a hypoglycemic event like the one above; too little and you risk long-term health consequences. Besides the health challenges, it’s a heavy emotional burden to live with diabetes — impacting spouses and children, how someone works and provides, and how someone lives a full life.
Medically speaking, two main peptides help people with T1D maintain their glycemic tightrope walk. Insulin brings blood sugar down when it is too high, and glucagon brings blood sugar back up when it drops too low. Because of their opposite functions, physicians and researchers have always considered them as adversaries, like two boxers duking it out in the ring. That’s certainly what Maggs thought, until one fateful evening in Boston when he was walking to a restaurant with Alan Cherrington, PhD, a world leader in understanding the roles of insulin and glucagon in the body.
On the way to dinner, Cherrington explained his recent animal studies to Maggs in which he put insulin and glucagon together, delivering the two peptides at the same time and at very specific molar ratios. Instead of the cage match the researchers anticipated, the two peptides actually responded dynamically to what the body needed: it wasn’t a fight, it was a dance, with each of the two peptides moving fluidly and intuitively to address rising and falling blood sugar levels. It was counter-intuitive thinking, but by the time dinner ended that night, Maggs knew he had to see what Cherrington’s research could mean for his patients with diabetes.
“The Damn Thing Works”
Fast-forward to Atlanta a couple of years later, and Maggs and Cherrington were sitting in the back room of a clinical trial unit at Atlanta Diabetes waiting to see how patients responded to receiving both peptides at once. As they sat with the clinical staff, Bruce Bode, MD, a well-respected researcher in the insulin field and a founding partner at Atlanta Diabetes where the clinical trial was being conducted, walked into the room, stunned. “The damn thing works,” Bode said.
Even now, years later, after building a company around a planned coformulated offering of insulin and glucagon, Maggs seems incredulous at what they discovered in Atlanta. The glucose levels in the subjects in the Atlanta study behaved almost exactly as predicted. While the previous assumption was that delivering insulin and glucagon at the same time would be like simultaneously slamming on the brakes and accelerator in an automobile, it turned out that the two peptides, when delivered at a precise molar ratio, worked together to regulate blood glucose. When glucose rose, insulin dominated the actions of glucagon, and when glucose fell, glucagon dominated insulin in the opposing direction. The gas and the brakes responded as necessary, together making it a much smoother and predictable ride.
Together with Cherrington and peptide chemist Soumitra Ghosh, PhD, Maggs founded Abvance Therapeutics to develop a coformulation of short acting insulin and glucagon as a kind of “smart insulin” that responds in real time to blood sugar levels. The founders approached another biotech company in 2019 for potential assistance in the coformulation work, and while that company passed on the opportunity, the then US General Manager, Steve Daly, found the Abvance data incredibly compelling, so compelling that he eventually came on board as COO in 2023.
“I’ve worked in the insulin field for a large portion of my career and this really represents a holy grail type approach when it comes to insulin — better control, less hypoglycemia risk, and cost-effective, especially compared to therapeutic options coming down the road that are targeting the same clinical benefits and likely to carry a substantial pricing premium over today’s options,” says Daly.
Because the intervention will utilize two already FDA-approved treatments, ABV100’s target product profile for dosing and handling is one that’s barely a departure from the current standard of care. For patients familiar with insulin dose determination and insulin delivery, their routine would hardly change, making adoption of ABV100 simple and straightforward. But the difference in results — in a product that unlocks an opportunity for improved glycemic control while reducing the risk and occurrence of hypoglycemia — could be enormous.
“Someone once described it as a ‘gentle insulin’ in conversation, and that really fits,” explains Daly.
Onwards and Upwards
Abvance is on the cusp of having the necessary funding to advance their solution, called ABV100, into coformulation development, large animal work, and then IND (Investigational New Drug) enablement with the FDA to move forward with testing in human subjects. Their proof-of-concept study in Atlanta, confirming that co-administering insulin and glucagon provided protection against hypoglycemia without worsening hyperglycemia, worked wonders in winning over skeptics who had long viewed the peptides as antagonists.
As they lay out the timeline and plan for eventual FDA submission, in the near term they will be refining the coformulation and experimenting with different types of insulins and glucagons in parallel. Once they have a candidate product, they plan to test it in different clinical product forms and insulin delivery modalities. Ultimately, the plan is that ABV100 will be available for patient use in vials, pens, and pumps wherever rapid-acting insulin is used today.
Even as they get into the weeds of product development, the Abvance team keeps its eyes on the patients it hopes to serve: the millions of people with insulin-requiring diabetes worldwide, who live in constant fear of hypoglycemia while simultaneously trying to prevent the long-term consequences of hyperglycemia. Daly recalls hearing a presentation from a man with T1D at a conference who had recently had his first child.
“Before the baby, he always kept his glycemic numbers under tight control to avoid future health complications, living with the daily risk and occasional occurrence of hypoglycemia. But after the birth of his child, he realized he couldn’t risk passing out from hypo with the baby in his arms, so he deliberately began under-dosing his insulin, even though he knew the possible negative consequences down the line.”
With access to the type of gentle insulin Abvance is creating with ABV100, hopefully people like that father won’t have to choose between today’s health and their future health, all by using tried and true peptides in a new way.
Our Thoughts
Daly’s description of Abvance’s first offering, ABV100, as a holy grail kind of solution rings true. It’s not every day that researchers find an approach to treatment that uses familiar components in a novel way, requiring little behavior change on the part of patients while relieving financial strain on the healthcare system. What Abvance proposes in ABV100 is a gentle form of insulin that is economical, accessible, and helps patients avoid hyper- and hypoglycemic peaks and valleys.
Although innovative treatments like glucose-responsive insulins, immune system interventions, and islet cell therapy approaches are coming down the road, they will likely come to market with significant price premiums over today’s therapeutic options. Access to these options may be very limited for many people as a result. The hope is that ABV100 can fill that gap, delivering important clinical attributes for a very large swathe of people with both T1D and T2D, their healthcare providers, and even payers, by providing an opportunity for better glycemic control with less risk and lower overall costs to the healthcare system.
The founding team behind Abvance Therapeutics is composed of top researchers and executives from the diabetes world, with an impressive set of advisors to boot. They know how to stay the course and bring their offering to fruition, and they know what’s at stake for the people they hope to serve. We’re proud to have this team as part of the StartUp Health community.
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Published: Sep 26, 2023