In the highly competitive space of diabetes, players will look for any edge they can get. One way companies can set themselves apart is by targeting a new mechanism of action - and this is the approach that the French group Poxel (OTC:PXXLF) has taken with imeglimin, a mitochondrial bioenergetics enhancer.

Mitochondrial dysfunction has been linked with diabetes for some time, but Poxel is alone in this niche, its chief executive Thomas Kuhn believes. "We don't think there are any other products in the clinic targeting mitochondria for the treatment of type 2 diabetes," he tells EP Vantage.

This could make Poxel attractive to the bigger fish in the diabetes sector, which have been contending with US pricing pressure and slowing sales growth. And positive data from a Japanese phase IIb study of imeglimin reported last week cannot have hurt its cause ("Novo needs new blood despite earnings relief," May 4, 2017).

More energy

By targeting mitochondria, Poxel hopes to address an underlying issue in type 2 diabetes. Patients have dysfunctional mitochondria because "they usually eat too much, until they have an excess of nutrients coming into the mitochondria. On the other hand, they don't exercise as much as they should," Mr. Kuhn says.

Overall, this leads to an excess of nutrients and a low demand on energy, which creates oxidative stress that impairs mitochondrial function, according to the chief executive.

"Imeglimin restores normal functioning by increasing the capacity of the different proteins of the mitochondria to transform nutrients into energy - even in the diabetic pathological process."

Mr. Kuhn is adamant that Poxel will press on alone in Japan, where it should only need a relatively small phase III program - three trials of roughly 1,000 patients each, he estimates - to get approval. "The path to market is reasonable compared with other countries," he says. "This is something we have the experience for - we have a team in Japan that's looking after the clinical and regulatory processes."

The company plans to start phase III in the fourth quarter and hopes to submit imeglimin for Japan approval by the end of 2018. It will need more cash for this - Poxel only had 38.8 million ($42.2 million) in the bank as of the end of March 2017.

This lack of funds helps explain why development in the US and Europe has stalled in spite of promising data from a phase IIb dose-ranging trial in December 2014, which supported taking a 1,500mg dose of imeglimin monotherapy into phase III.

Mr. Kuhn admits that Poxel will need a partner to support a pivotal program here, which he believes will need to total seven trials in around 7,000 patients overall. He says the company is already in talks with potential collaborators, in parallel with discussions with the FDA and EMA about study design.

With the onerous requirement of huge trials to tease out cardiovascular risk in Europe or the US, it will take a bold partner to jump in on such a novel diabetes approach.

AMP it up

Meanwhile, Poxel has an earlier-stage diabetes asset with another novel mechanism, the direct AMP kinase activator PXL770.

According to EvaluatePharma, no AMPK activators are approved in diabetes, though Betagenon's O304 is already in phase II, putting it ahead of PXL770. There are also various projects in preclinical development.

Like imeglimin, PXL770 is designed to regulate energy - the AMPK enzyme's role is to maintain cellular energy homeostasis. "Put simply, our product will mimic the benefit of doing sport - that's the concept," says Mr. Kuhn.

However, Poxel has had a hiccup in development. It had to go back to the preclinical stage after a phase I trial found differences in the way the product was metabolised in humans versus animals. The chief executive insists that no safety worries were uncovered in the clinic, and the company hopes to start the second phase of the phase I trial in the second half of this year.

PXL770 acts directly on the liver, Mr. Kuhn says, so could also have utility in diseases such as Nash. The Nash space has garnered a lot of attention - and investment - potentially providing another avenue for Poxel to attract a partner.

But with limited resources, Poxel will not want to stretch itself too thinly. For now, the focus has to be on progressing imeglimin in diabetes.

Original post:
Poxel Takes High-Energy Approach To Diabetes - Seeking Alpha

Tawnya Galland can hold a ruler perpendicular from her hip to demonstrate how much her waistline has shrunk.

"There's a ruler less of me," she quipped.

The process began almost four years ago when a co-worker invited her to come along to a nutrition class at the YMCA. Galland figured she had nothing to lose, so she tagged along.

It was fortuitous. The nutrition class they attended was the Diabetes Prevention Program, a joint project between St. Vincent Healthcare and the YMCA.

Heavy and not very active, Galland was pre-diabetic, and she likely would have ended up with type 2 diabetes had she not followed her friend to the class and begun to change her life.

"We give people some broad guidelines," said Bev McHugh, the YMCA's registered dietitian and lifestyle coach for the diabetes prevention program.

In the class, she teaches participants about the importance of diet and exercise, helps them to create food journals where they track everything they eat and talks to them about the importance of finding balance in their lives. And then a relatively intensive exercise portion kicks in after the first month.

In other words, she said, she gives them some tools and teaches participants how to use them. But it's those in the class who have to make it work.

"To sustain a healthy lifestyle, people have to take ownership," McHugh said.

Galland was on board from the start, although she admits when she learned there was an exercise component she got a little nervous. She was all too aware of what it would look like for someone her size to saunter into a fitness center.

"Walking into a gym can be overwhelming," she said. "But you're all starting pretty much at the same level. So that was the benefit to doing it in a group."

And rather than starting straight out on exercise equipment, Galland was able to use the pool and work out in a water aerobics class.

"When you weigh as much as a linebacker, your joints don't like the land classes," she said with a laugh.

The biggest surprise was that she enjoyed it. She meticulously kept up her food diary, exercised multiple times a week and eventually lost 44 inches from her waistline.

These days, she's doing a spin class three times a week, a two-hour swim class twice a week and one group aerobics class on Saturdays. She finds genuine pleasure from the workouts, saying they're as good for her head as they are for her heart.

"I'm not happy when I haven't made it to the gym," she said.

McHugh talks to her class about the myriad ways there are to mark success. It's not just about pounds lost or physical endurance gained.

"There's many measures of progress," she said.

Most important, she said, is giving class participants tools that will help them keep in place the lifestyle changes they make when they finish the course.

McHugh likes to tell her class that she can't motivate them but that she can help them find their motivation.

ForGalland, that motivation comes from a desire not to lose the progress she's made and from the positive changes she's experienced in her life. Her mood has improved along with her health. She's more energetic throughout the day, and she has more confidence.

"I don't want to go backwards," she said. "It scares me to go backwards."

The diabetes prevention program lasts a year. It starts with 16 weekly classes, then moves to classes every other week. Then, for the last six months of the class, participants meet once a month. Through it all, there's the exercise regimen.

The best way to prevent diabetes is to improve diet and get active, McHugh said. Those improvements can be charted through weight loss.

"The goal of the program is moderate weight loss," she said, which is defined as a 5 percent to 10 percent loss from a person's starting weight.

Galland has dropped 103 pounds over the last three years, and she's happy with the balance she's struck in her life. Had she tried to do this 10 years ago, she wouldn't have been able to pull it off. Her life simply wasn't in the right place at the time.

"You have to find that place in your life when it'll work," she said. "I'm content with where I'm at."

View original post here:
'I don't want to go backwards': Woman beats diabetes before she gets it with help of YMCA class - Billings Gazette

By Savannah Edgens Special to The Ledger

A group of University of Florida health researchers has found a way to expand andpreserve certain cord-blood cells, which could prove to be a treatment for Type I diabetes.

The findings involved regulatory cells known as T-cells, which are white blood cells thatsupport the immune system and protect against diabetes and other autoimmune diseases. Theresearch revealed that the T-cells can be frozen, then multiplied in a laboratory.

This is an incremental step forward on our long pathway toward our ultimate goal ofpreventing and reversing Type I, said Dr. Michael Haller, professor and chief of pediatricendocrinology at the UF College of Medicine.

People with Type I diabetes likely have an imbalance in two types of T-cells: regulatoryand effecter, Haller said. If a person doesnt have enough regulatory T-cells or the regulatorycells arent doing their job, then it allows the effecter cells to take over. The regulatory cellsthen attack the effecter cells.

If we can shift the balance by giving more regulatory T-cells that are either morefunctional or more potent, then we might be able to reverse the primary cause of autoimmunediseases, Haller said.

The next step will be to conduct clinical trials, Haller said. The clinical trials will involvegrowing the cells from stored cord blood, then injecting the cells back into patients. Funding isthe biggest thing keeping the research team from conducting the trials. The clinical trials willcost $1 million to $1.5 million, Haller said.

The regulatory cells are not insulin-producing cells, Haller said. They will not replacedamaged pancreas cells. The goal is to fix the immune problem. The expansion of T-cells, Haller said, could also be used to help a number of other autoimmune diseases.

Cell therapy is a living drug, and it is very different from a pill a person might take, saidTodd Brusko, associate professor of pathology at the UF College of Medicine. It is somethingyour body has developed over time as a way to control immune responses.

I think whats really unique about our approach, Brusko said, is that we areharnessing the bodys own systems to control immune responses, and using those to interferewith this disease process.

Patients with Type I diabetes have some kind of underlying autoimmune disease, Bruskosaid. Even if they received a new pancreas, the body would recognize it as foreign, and thebody would attack it. This was the goal of the research, he said, to fix the underlying issue.

Diabetes is a devastating disease for families, Brusko said. Its a family disease becauseit impacts every aspect of a persons life. They have to worry about how high or low their bloodsugar will be when they go to sleep at night.

If you can imagine a very young child being woken up in the middle of the night to havetheir blood sugar checked, that can be incredibly stressful for a family, Brusko said. This issomething that is 24/7.

Link:
UF Health diabetes researchers multiply T-cells - News Chief

Local scientists have worked for decades to develop technology that could cure diabetes. Consultant John Mills (left), Bri Bintz, Moses Goddard, Chris Thanos. Photography by James Jones.

Leonard Thompson was fourteen years old and near death when he helped make medical history. It was 1922, and though what became known as diabetes dated back to ancient times the Chinese called it sugar urine disease the only treatment for the illness at the time was the starvation diet.

Thompson weighed sixty-five pounds when he was admitted to Toronto General Hospital. A young surgeon named Dr. Frederick Banting convinced his father to let him inject his son with a new drug he was testing in dogs called insulin. Thompsons health improved dramatically, and news of the medical miracle made the front pages of newspapers around the globe. The next year, the drug manufacturer Eli Lilly began making insulin to treat diabetes.

But though the technology for treating the disease has improved over time, for an estimated three million Americans many of them children a diagnosis of type 1 diabetes remains a life sentence. They manage it by monitoring their blood sugar throughout the day and administering insulin. But severe complications later in life can include heart disease, blindness, nerve damage and even amputation. The disease costs an estimated $15 billion a year to treat.

Thats why researchers and investors have long considered finding a way to transplant cells that could regulate insulin without getting rejected by the immune system, a holy grail. Scientists in Rhode Island are among those who have been working on and off for decades on achieving it.

About three years ago, Harvards Stem Cell Institute announced a major breakthrough in the fight against diabetes. The institutes co-founder, Dr. Doug Melton, and a team of scientists said that using embryonic stem cells, they were able to develop islets clusters of pancreatic cells that house beta cells and produce insulin in a healthy pancreas.

The transplantable tissue, which they tested in mice, opened the door to a potential treatment that would enable diabetics to once again naturally regulate their own blood sugar. It was gratifying to know that we could do something that we always thought was possible, Melton said at the time, but many people felt it wouldnt work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now Im really energized.

Melton had dedicated himself to finding a cure for the disease more than twenty-five years before, when his then-infant son, Sam, and then later his daughter, Emma, were diagnosed with type 1 diabetes. While the cause of type 1 diabetes isnt known, genetics are believed to play a role.

With venture capitalist Robert Millman, Melton founded a startup called Semma Therapeutics named for Sam and Emma to develop the technology for an artificial pancreas and bring it to market. It attracted nearly $50 million in investment from Millmans firm MPM Capital, medical companies Novartis and Medtronic and later, the California Stem Cell Association.

But its a very competitive landscape. Other companies are also working on the creation of artificial pancreases, including California-based VitaCite, which already has clinical trials scheduled.

In addition to creating the islets, scientists also have to figure out a way to keep a persons immune system from rejecting them. Thats where the scientists and clinicians in Rhode Island come in. Using a method called encapsulated cell technology (ECT), they are developing a semi-permeable membrane to house the islets that will allow oxygen and glucose to diffuse through it, but that the patients body wont reject.

Trying to make that work has occupied scientists in Rhode Island and around the world for more than three decades. In 2015, Semma recruited some of the most prominent people working in ECT in Rhode Island Dr. Moses Goddard, Christopher Thanos, John Mills and Briannan Bintz to develop the technology for Meltons islets. Over the next few years, they plan to get approval from the Food and Drug Administration for clinical trials with the hope that one day, surgeons can implant healthy new tissue that can regulate insulin in diabetic patients.

But despite the excitement about the prospect of developing a way to potentially cure type 1 diabetes, those involved acknowledge that if it were easy, it would have happened long ago. The public definitely doesnt appreciate that much of science is a failure, Melton told MIT Technology Review last year.

One of the pioneers in the development of the method that could change the treatment of diabetes was a transplant from Switzerland named Dr. Pierre Galletti. An internationally known scientist, Galletti was the first dean of biology and medicine at Brown University and one of the founders of its medical school.

Galletti worked to develop synthetic solutions for failing organs. He also had an entrepreneurial streak. Galletti published the first really significant paper on ECT in the journal Science in 1973, and it caused a big splash, Goddard recalls.

Galletti advanced the idea that ECT could be used to help treat type 1 diabetes. In healthy people, islets in the pancreas create insulin and secrete it into the blood stream. But in people with type 1 diabetes, the bodys immune system destroys the insulin-producing beta cells. And when they dont make enough insulin, glucose builds up in the blood.

The idea behind ECT was that scientists could use beta cells from another source at the time Galletti was using pigs and put them in an envelope designed to protect them from a persons immune system, then transplant the cells into the pancreas. And the membrane should be porous enough that blood sugar could diffuse through it and affect the beta cells, and the beta cells could respond with insulin.

Galletti performed the first experiment with ECT on a human in 1983, in what Goddard describes as the good old days/bad old days of medicine. The patient was a French nephrologist with type 1 diabetes who was in end-stage kidney failure. Galletti worked with a French endocrine surgeon who extracted islets from an islet tumor. The nephrologist already had an access shunt for dialysis, so Gallettis lab at Brown built a device with the islets that could be plugged into the shunt.

The doctors took the nephrologist off insulin. He enjoyed a proper French meal with several courses and wine as the doctors measured his blood sugar and treated his diabetes for twenty-four hours.

That was the kind of thing you did as experiments back in the day, says Goddard, who was a protege of Gallettis, along with Patrick Aebischer. Aebischer had earned degrees in medicine and neuroscience in Switzerland before coming to Brown. Goddard, a descendant of the founder of Rhode Island Hospital, had earned undergraduate and medical degrees from Brown. They also recruited a mechanical mind named John Mills.

Meanwhile, some companies were already making commercial versions of membranes to encapsulate cells for a variety of medical purposes. Goddard and Aebischer were consulting for a company that was manufacturing membranes for dialysis cartridges when they realized they could make their own.

The company had maintained that creating the membranes was an extremely complex process that required great expertise and hundreds of employees, Goddard recalls. One day, he and Aebischer had a meeting at the company to discuss the diameter of the membranes they were looking for. A junior employee took them on a tour, and Goddard and Aebischer were allowed to see where the membranes were being made. It was a small room for controlled experiments and they couldnt see the actual process. But Goddard and Aebischer were convinced that it couldnt be too hard to figure out how to make their own membranes.

Patrick dove into the patent literature and figured out what they did, Goddard says. We replicated it and really mastered it.

Originally posted here:
Will Rhode Island Win the Race to Cure Diabetes? - Rhode Island Monthly