Editor, Rebekah Jordan, sat with Mark Bagnall, CEO of Phenomix Sciences, to understand how the company is redefining the way obesity disease is treated with precision medicine to allow for better treatment decisions and patient outcomes.
Key insights:
- Obesity is currently classed as one disease but has recently been divided into four subtypes.
- By using phenotyping to identify the obesity subtype a patient has, treatments can be personalised for patients, increasing treatment adherence, effectiveness and outcomes.
- Evidence has been published to show that treatments based on a patient’s specific phenotype results in better patient outcomes than treatments solely suggested by physicians.
In 2013, the AMA medically classified obesity as a disease. In the same year, two Mayo Clinic doctors, both GI specialists working in the field of obesity, began to work on the problem of variability in response to obesity treatments. They discovered that obesity was not one disease but at least four, each of which are mechanistically different. After several years of research, they founded Phenomix Sciences in 2020, to scale their discoveries and bring personalised medicine to the obesity field by phenotyping.
The World Health Organization says that obesity has tripled worldwide since 1975. Phenomix is working to address this issue by understanding how the disease is diagnosed, monitored and treated.
Mark explained: “If you talk to obesity specialists, the issue with obesity medicine is that for any type of treatment, that could be diets and lifestyle type treatments, through to drugs and devices and surgical techniques, there is significant variability in response. So, not everybody responds the same way.”
The National Institute of Health started a program called the Adopt Program four years ago with a goal of finding biomarkers that predict which patients will respond best to certain treatments. The program has yet to yield any insights.
Mayo Clinical researchers analysed patient behavioural, physical and biological traits in relation to obesity. They were able to determine that there are four subtypes of obesity:
Hungry brain is characterised primarily by an inability to know when to stop eating at a single meal. These individuals tend not to feel full, or at least not until way longer than others.
Hungry gut covers people who feel full on a normal size meal, but very quickly start to feel hungry again. Snacking is common in this subtype.
Emotional eating involves eating as a result of positive or negative emotions.
Slow-burn individuals share a low resting energy expenditure, often brought on by low muscle mass or minimal physical exercise.
To identify these phenotypes among patients at Mayo Clinic, each patient spends nine hours undergoing a series of tests (such as body composition scans and treadmill tests). Patients are also fed radio-labelled meals, so the speed at which food passes through the stomach can be measured with nuclear imaging.
Identifying the phenotype at Mayo Clinic is an intensive process, and Phenomix was founded to scale the process by developing a test using an individuals’ biomarkers, and determine the impact of both genetic and environmental factors of the disease.
Similar to the way precision medicine is applied to oncology, Mark stated that by predicting these obesity subtypes, you can provide the most appropriate treatment, providing better results and patient outcomes.
“Today, oncology is precision medicine based and we're learning so much about personalised medicine that we believe that eventually many diseases will be treated on some personalised basis.”
Taking all factors into account
Phenomix is initially setting out to sell saliva tests that will determine phenotypes from gene variants and biometrics.
“We've taken all of the data from Mayo Clinic, including SNP chips that gave about two and a half million gene variants per patient, metabolite and hormone data and incorporated them into our platform to develop our first test.”
Mark stated that over time, Phenomix tests will evolve and become more sophisticated, with the aim for them to become “true multi-omic tests” - accounting for all relevant biological biomarkers and digital biomarkers.
“As we move forward, our future tests will involve taking information from every corner. From questionnaires, we can look into people’s lifestyle habits. People can use apps to input the type and amount of food they are eating, as well as activity levels. And then there are other ways of identifying environmental factors. For example, looking at metabolites which are a good way of expressing how your cell is functioning partly obviously because of genetics, but partly also because of the environment. So, all of those will come into play.”
Mark continued: “Our intention is to build a robust database of information that looks at these phenotypes precisely and sees obesity through the lens of phenotypes, through the lens of precision medicine. And we think if we do that, we'll get insights that are more profound, and we'll get them faster than people who just look at obesity as one disease.”
We're actually seeing insights that other people are not seeing, which feels exciting.”
The treatment algorithm: precision with phenotyping
“While you may have hungry brain phenotype, from time to time there may be emotional issues that exacerbate that, which need to be recognised, understood and treated. And so, what we’re thinking about, as our tests evolve, is what does that mean for the treatment algorithm,” said Mark.
Phenomix’s founders recently conducted a study on lifestyle and diet interventions showing that you could tailor lifestyle and diet interventions for each of the phenotypes. It’s important to note that, although individuals may share the same phenotype, the course of treatment may not be the same. For example, there will be some patients who have a ‘hungry gut’ phenotype that may require a diet intervention only. However, for others with the same phenotype, a diet intervention may not be enough and so, they may need to be treated with a new GLP-1 drug.
Mark related the analysis of the potential of these therapeutic interventions as a four-by-four matrix. “On one side, we determine which phenotype you fit into. On the other side, we look to identify your potential treatment options: whether you need diet and lifestyle and intervention, - which would include counselling - whether you need a drug, a device, or surgery on top. And I think if we're successful, in the end, we're going to help people make the right decision.”
Of course, there is individual treatment effectiveness, side effects and cost factors that all need to be considered before a treatment can be explored.
The good news is that the notion that phenotyping has an effect on treatment effectiveness is already being proven through clinical evidence.
One of Mayo’s most recent studies was published in the Journal of Obesity 2021. In the study, around a third of patients (84) out of 312 patients were given drugs based on their phenotype. The remaining two-thirds (228) were assigned drugs based on whatever their physician decided was best for them. The results identified that the patients who were assigned drugs according to their phenotype lost, on average, twice as much weight as the patients who were just randomly given drugs.
“This really emphasises the ‘one size doesn't fit all’ theory, which really hammered home to us,” said Mark.
Read EPM's interview with Phenomix's co-founder to learn how phenotyping can pave the way for successful obesity treatment.
Leveraging the power of collaborations
Phenomix’s first test is a high-complexity sequencing test, requiring data from about 6,000 gene variants. Phenomix needed to partner with a lab that could facilitate this – which is where Kailos Genetics comes in.
Kailos can analyse saliva samples against 6,000 gene variants that are required for the test. The test includes additional biometrics that are gathered directly from the physician. The mix is then entered into Phenomix’s predictive algorithm, which can identify whether a patient has hungry gut - of which the treatment would be a GLP-1 and a specific diet.
On the topic of their recent partnership, Mark commented: “We already knew the lab director at Kailos Genetics. Kailos Genetics is part of Hudson Alpha Institute, which is one of the top sequencing institutes in the country. Friends of mine have been associated with them for years, and their chief scientific officer, Dr. Richard Myers, and so it was just natural for us to go to somebody like that, knowing we could get reliable, reproducible, high-quality results, as we launch our first test.”
Following this, Mark stated Phenomix is currently doing a biobanking study with Mayo Clinic and is in communication with other large institutions about potential biobanking opportunities. Additionally, Phenomix is talking to pharmaceutical companies and device manufacturers about collaborating on obesity phenotyping.
“I think if we're going to solve obesity, we need a lot of folks all coming together. Both in the spirit of competition, but also to move the field forward and get to that level of sophistication that is already present in the field of oncology.”
Changing the world
Mark emphasised that there is no guidance today on which treatment to offer when a patient with obesity shows up at a doctor’s office. He said that Phenomix has plans to change this. Rather than a trial-and-error approach to treatments, Phenomix’s test will get the right treatment for each patient the first time around.
“We would like to bring science to the treatment decision.” Mark explained that this health problem is only getting more common, but by introducing precision medicine into the obesity space, everyone could benefit.
“When you can really help people who are suffering, that’s meaningful work. Everyone wins. You are getting better. Your physician feels better about it. The healthcare system performs better, and your pocketbook is better too.”