Bob Geho refers to himself as a "liver evangelist" when it comes to improving diabetes care. That's because he's on a holy mission to get insulin to be better absorbed in the bodies of PWDs (people with diabetes), using nanotechnology targetting that organ.
The 50-year-old from Cleveland, OH, also happens to live with type 1 himself, diagnosed during college in the early 90s. That was a life-changing moment that shifted not only how he thought about his own health, but also set him on a career path in medical science that his father had paved before him.
Today, he is CEO of Cleveland-based startup Diasome Pharmaceuticals, developing nanotechnology known as HDV (short for Hepatocyte Directed Vesicles), that would be injected as an insulin add-on or swallowed as a pill. It would attach to insulin, causing the medication to be better absorbed into the liver's metabolic cells (rather than the muscles or fat) before being released back into the bloodstream.
In short, this liver-targeted compound could be a game-changer for how insulin works -- because while the medication obviously saves lives, getting the dosing right is a huge challenge, fraught with guess-work and risks. It is well-known that injected insulin doesn't work fast enough in the body, so Diasome's product could be a revolutionary fix.
"The revolution that has to happen, and that I view us as vanguard of, is a need for this kind of (more precise and predictable) insulin therapy," Geho says. "It's not generally well understood either in the pharmaceutical industry or in routine clinical practice why insulin doesn't work in the liver like it should, and we think this would dramatically change the day-to-day of insulin therapy. We want to turn this whole thing upside-down."
Father and Son Tackle Diabetes Research
Geho never dreamed he would follow in the footsteps of his famous medical researcher father, Dr. W. Blair Geho. His dad entered medical school in the early 60s and was taken under the wing of the great pharmacologist Dr. Earl Sutherland Jr., who won a Nobel prize in 1971 for his work on protein chemistry and was part of the team that identified "the mystery protein of glucagon" in the 70s.
Studying under Sutherland, the elder Geho learned the foundation of knowledge that he'd go on to use in developing liver-specific insulin years later. Geho joined Procter & Gamble in the 60s and helped build the company's Research Division, which his son says gave him more insight into the body's chemical process than those working directly in Pharma because of P&G's research on Crest toothpaste, that delved into bone metabolism. While at P&G, Blair Geho also led the development of Didronel, the first bisphosphonate drug approved for human use, and Osteoscan, the first bone imaging agent.
Blair Geho didn't have any personal connection to diabetes, other than family members with type 2, but his research led him down the path of liver-specific insulin. In the early 90s, he would go on to found the tech-startup SDG Inc. in Cleveland as a way to continue his work developing techniques to improve insulin delivery in diabetics.
Right around that time in the early 90s, his son Bob was studying music and planning to become an orchestra conductor (following graduate business school, which he went into as a "fallback" in case music didn't materialize). But a routine physical led to a type 1 diagnosis, and the first call after seeing his own doctor was to his father. From that point on, diabetes became his world -- personally and professionally. It's now been 26 years.
"My father was just starting SDG and continuing his odyssey of creating an insulin therapy device, so I went there and got my feet wet... the rest, as they say, is history," Geho says. "I jumped ship from the music world and got very intrigued by (my father's) mindset and that kind of diabetes research."
The two have been on a joint path ever since, at the helm of several startups all aiming at the same goal: to get this HDV oral and injection insulin therapy through the research phases and onto the market. The 1994-created SDG holding tech company is now in its 25th year, and the father-son team also jointly founded Diasome Pharmaceuticals, now in its 15th year. After a down-period in which they've been quietly working on the science as well as funding, Bob Geho stepped back in as CEO and Director of Diasome a few years ago and his father now serves as Chief Science Officer.
Their mission hasn't changed, and Geho tells us they're getting closer than ever before.
The Concept Behind Diasome
Really, the concept of HDV tech (Hepatocyte Directed Vesicles) is pretty simple to understand: making insulin work in your body the way it should, as it does in those without diabetes.
As Geho puts it: "Why can we inject twice as much insulin as a healthy, non-diabetic, but still have high blood glucose levels? Because insulin doesn't work the way it should in the body."
This illustrates the need for therapy beyond just getting the insulin into our bodies, he says.
In those without diabetes, food triggers insulin from the pancreas but it first goes into the liver, where about 65% of the glucose is stored. But for us PWDs, the subcutaneous insulin we take is used first by fat and muscle cells and not the liver. So when we're taking insulin at the time of a meal, instead of the liver storing as much as two-thirds of the glucose we eat, almost all of it goes through the liver and into the blood. Only the hepatocytes in the liver can both store and then release the glucose, but that's not what happens with the insulin we're using.
Think of it like the "streetlight effect" -- where someone is standing under a street light at night looking for their keys or a dropped coin, blocks away from where they actually dropped it; someone asks why they're not searching closer to where it was dropped, and the searcher responds: "Better light here." That is the equivalent of what's happening with HDV and insulin, Geho says; the Liver is the darkness and insulin just doesn't get there to work effectively. Rather, it's just going to where the light is and PWDs are left hoping it works.
Geho points to recent outcomes data from the Jaeb Center and T1D Exchange
While their HDV tech is undergoing clinical trials, the vision for a product prototype could involve a few different options:
- Diasome could market HDV for patients to add into the vial or pen they are using in increments of 20 nanometers. The HDV nanoparticles would attach to the insulin and allow a certain portion of it, when injected into the body, to go into the PWD's liver. Nothing about the insulin structure would change, so it's simply an add-on for the life-sustaining meds we already use each day.
- That HDV solution could be sold right in the package with existing insulin products, for patients to add to their pens, vials or pump cartridges when ready. But it's more likely to be sold as a separate product, since insulin developers may not be keen to coupling it with their products.
- Or if partnerships did materialize with insulin manufacturers Lilly, Novo and Sanofi, there could be a way to add the HDV into those insulin products during the production process, as an ingredient making their insulins more effective.
- Diasome is also developing an oral capsule form, which contains five units of the HDV insulin molecules.
"It's almost an alarmingly simple idea," Geho says. "No one else in the insulin world is looking at a liver-targeted meal-time insulin therapy, and that leaves Diasome out in front -- possibly on its own."
A Big Insulin Oversight?
As a type 1 himself, Geho is grateful for the insulins we have today, but certainly not content.
"Now, I love being able to inject 15 minutes before a meal, rather than longer times before that. I appreciate that and love what these companies are giving us to do that. But it's a terrible product from a day-to-day aspect. You really couldn't design a worse product. That's the reason we exist, to change that and develop a tech that allows our insulin to understand glucose metabolism."
Geho even says that new, faster injectable insulins -- including Novo's faster-acting Fiasp -- face the same challenge because they won't solve the issue of going into the liver. Inhaled insulin like Afrezza is a bit of a different animal, because it goes into the lungs rather than the liver, he says.
But he can't quite understand why this liver pathway has been all but ignored to date.
"At a certain level, people should be outraged because the insulin companies aren't telling us this story," Geho says. "Every high school student learns that the liver stores glucose, but for some reason the Pharma insulin-makers don't seem to realize that. It's puzzling."
While Pharma giants Lilly and Novo have abandoned their own liver-targeted insulin therapies, there continues to be quite a bit of interest in the area of research, he says.
JDRF Support of Insulin and Liver Studies
So why hasn't Diasome moved along faster in the past five years? Geho points out that there has been quite a bit of change and "expanded thinking" in the insulin world. This has been helped along by JDRF's T1DFund, founded in 2015 to narrow the gap between scientific advancements and commercial solutions.
In 2017, that investment fund took on Diasome's research as one of its projects, which has kickstarted their clinical studies in recent years. Part of that also involves looking Beyond A1C in clinical research, so that other outcomes such as reduced hypoglycemia and Time In Range (TIR) will also be examined as they develop this HDV insulin therapy.
"We are trying to be as forward-thinking as possible," Geho tells us.
To date, Diasome has completed three human clinical studies of its HDV nanotech in PWDs with type 1:
- Its Phase 2 “Good to Great” double-blinded, multi-center study that compared injected HDV added to rapid acting insulin (lispro) versus lispro alone in 42 patients with baseline A1C levels between 6.9% and 7.9% over six weeks of dosing.
- Its Phase 2 "Insulin Pump” double-blinded crossover study that compared injected HDV added to lispro versus lispro alone in seven subjects on continuous subcutaneous insulin infusion over three weeks.
- Its Phase 2b “InSulin Liver Effect” (ISLE-1) double-blinded, multi-center study that included 176 patients and compared injected HDV added to lispro versus lispro alone over six months of dosing.
Going forward, more research is on tap and already underway:
- The first type 1 PWD has been enrolled in a Phase 2 clinical trial known as "OPTI-1 study," which looks at dosing guidance for HDV injections. It's a six-month study started in March 2019, and is expected to enroll 60 people. Here is a news release on that study.
- If everything goes as planned, Diasome expects to work with FDA in 2019 to finalize Phase 3 clinical trial protocols, and those could begin in early 2020. If so, he hopes to have HDV additives to market by 2022.
The science and concept are very intriguing, as well as the mission: to make every unit of insulin work better with the body’s normal metabolic system -- making all insulins more effective and much safer. It sure will be interesting to watch Diasome and this HDV therapy move forward!
Oh, and does Geho still have any music in his life?
He laughs, and tells us all four of his kids play piano but for the most part music is now a strictly personal way to help clear his head when needed. The main orchestra he's conducting these days is all about insulin therapy, and the hope is that it turns out to be for the Diabetes Community what Mozart was to the music world.