Interview: Phenomix' Mark Bagnall and obesity's four different phenotypes

Not only that, but according to GlobalData report Obesity: Seven Market Drug Forecast and Market Analysis, the obesity market is expected to grow at a compound annual growth rate of 31.3% during the forecast period, reaching $31.7 billion. The growth will be across the seven major markets, known as the 7MM, and include the US, France, Germany, Italy, Spain, the UK, and Japan.

An increase in the obese population and the number of therapies with promising efficacies and longer duration of action are both significant reasons for the growth.

Mark Bagnall is CEO at Phenomix Sciences, Inc., and joined Outsourcing Pharma for a discussion on how the company has discovered a test that determines that obesity can be categorized into four different diseases that all require different treatments. These are referred to as phenotypes.

As a Brit, Mark found himself in California just as the biotech industry was taking off and he spent time working on several start-ups, many of them in chronic diseases. Five or six years ago he ended up with an entity called Health2047 that the American Medical Association put together to invest in big health issues before moving to Phenomix. 

“I came in to look for interesting ideas for them to invest in and through a friend found the Mayo Clinic where I met Dr Andres Acosta and he told me about this idea that you could categorize obesity into classes. This was fundamental precision medicine that would improve a patient’s outcome. Having been around chronic diseases a long, long time ago, the puzzle to me was, why were we still not tackling obesity? It is such a cause of all these other conditions, and it seemed like we’d all looked the other way with obesity and now had to deal with the enormous consequences of not having dealt with the underlying problem,” he says.

Phenomix then studied nearly 1,000 patients and found that obesity can be categorized as four different diseases, requiring different treatments. They are referred to as obesity phenotypes – hungry brain, hungry gut, emotional hunger, and slow burn.

Obesity phenotyping empowers providers to use precision medicine to individualize treatment and was shown to double​ ​the amount of weight lost.

Bagnall says he found it fascinating to hear someone who understood it at a fine granular level and was able to demonstrate that if you knew the subtypes of obesity, you would get better patient outcomes.

“He started ten years of studies, and this was all happening before these new drugs got launched and found that there was a problem of variability in response to treatments which is well-known and has been well-documented. Not all diets work for the same people the same way not all drugs work the same way.”

This prompted the launch of Phenomix two years ago so that all the research done at Mayo Clinic including the ten years of clinical studies using machine learning, AI etc to look for associations in a person’s biomarkers and principally their genetics.  

Bagnall continued: “It was a chance to look for those patterns and see how those associations were associated with the subtypes. And that was the basis of our company launching its MyPhenome​ tests for hungry gut and hungry brain biomarkers. Hungry gut which is patients who snack between meals and the best drug for that is something like Ozempic or Wegovy. The hungry brain is people who have a really hard time feeling full, so they eat a lot in a single meal and the best drug for that is Qsymia and then there's emotional eating, the best drug for that is Contrave, and then slow burn, which is when a lot of people think they have just got bad metabolism.”  

There are no drugs for that other than very effective exercise routines but there are drugs in development. The company is working on the other two and Bagnall says it has ‘some really neat data.’

The data shows if you use the test and you find out you fall into the hungry brain category and start taking Qysemia you can achieve the same weight loss as you would if you had an operation, so 20% total body weight loss.

“It works and this is exactly what you would expect precision medicine to do. We can identify the patients who respond to the treatment and then two things happen. They get better, faster. And the other thing is we don't waste money on expensive drugs. So the patient benefits and the healthcare system benefits.

“We launched six months ago, and it is taking off. We have decided that we will launch the test first to obesity specialists, people who understand the disease as we want their feedback. We're getting good interest in this. But it is that kind of opportunity to introduce precision medicine to obesity. It's done such a great job in oncology, and it has now been introduced to another disease. We've just benefited on some level by the fact that suddenly obesity went from something nobody talks about to the craze of Ozempic and everything has gone nuts.”

Bagnall said that everyone who has a medical or science background working in the field knows there’s no silver bullet – but that everyone who has marketed products for obesity has insisted they do have it.

He said: “When you take in all the advertizing, they all have the silver bullet ‘if you just use our program, everything will be solved. Interestingly, the makers of Ozempic don't say that, but the people who take Ozempic then take to TikTok to talk about it say that because I think that is just human nature. People want the silver bullet.”

He said Novo Nordisk has done the planet a big favor by introducing Wegovy because it acknowledges that obesity is a clinical problem.

“Obesity, that's what’s happened, so the favor that Novo has done by introducing an effective drug is to emphasize the point that this is a disease and needs to be treated as such in a clinical fashion in a clinical setting.

“It's been a huge favor that has now heightened the sense that this a disease, not a not a consumer-based problem. That benefits us because we're launching a product that is based on a ton of clinical evidence and can help make that choice. So now we were in what we're attempting to do in a very, very short period, is go from consumer base to clinical base to procurement, to consumer base to medicine to precision medicine. Right, and that was the process in oncology in a couple of decades, and we're going to attempt to do that and two years. That's incredible.”

He worked in his first diabetes-focused company 20-plus years ago and says that everyone working with diabetes knew a significant proportion of patients suffering from that disease were doing so because of being overweight or obese.

He said: “It's such an overwhelming problem. You just don't know where to start to tackle it. There's a sad part and that is tackling it because it is going to cost money. I mean, tackling it is going to cost money. I think we're now at a point where we're beginning to see tools being developed. There are many other interesting pharmaceutical company products in development.

“There's a lot of shame put on patients. You eat too much you shouldn't, you don't have self-control. You're lazy, you don't get out and exercise and that's why patients are here sadly, one of the things that drew me to working on this with our founder is the story he tells of people who come to his office, who go through this process of understanding that phenotype and people who have gone through program after program year after year, who had been told constantly if only you stick with a program you would do better if only you would have portion control, you would do better. This kind of pounding on for their feelings and then coming into office going through these tests that he did for them and be able to say you know what? We know it's the hungry gut phenotype, we know you have this genetic issue 20% of other people who suffer from obesity have this.”

Bagnall believes that for patients realizing they hadn’t been failing and that this was just a disease just like any other lifted the burden for them.

He added: “I think this is part of the great thing - here is where we get to change the conversation. It was just too convenient for the healthcare system to tell people it was their fault because then everybody could move on. The payers didn't have to pay. The physicians didn't have to think about it. The pharmaceutical companies didn't have to develop drugs for it. Nobody had the system needed to care for people if it was their fault.

“We are talking to other entities, including drug companies, and doing studies over time, where we see over one year, two years, five years, the fluctuations in levels of metabolites, levels of hormones, fluctuations in mental state, asking how they feel, how often they exercise and then look at that, with patients who are taking the drugs who are partaking in all the exercise programs, and then measuring that over time.

“There's so much research still to be done. It's fun because we know we have a roadmap because of what they have done. We know where the road is going to go but there's still a lot of research to do. Our test already knows that there are differences between men and women in terms of how we do our cut-offs, etc. We know there are some age differences too. There's quite an exciting area to explore. It's a little daunting, but cool because where were we with oncology in 1990, think of all the trillions of dollars invested in oncology since 1990. We just need to catch up.”