Precision Medicine for Obesity As clinicians treating obesity are acutely aware, identifying effective treatments for obesity often involves trial and error. Outcomes with current interventions (including medications, endoscopy, and surgery) are highly variable because of the underlying heterogeneity and complexity of the disease. However, emerging research from Mayo Clinic has recently defined four underlying phenotypes of obesity which can be determined from a fasting blood sample, and clinically applied to help select the most effective treatments.

Obesity classification based on pathophysiology In 509 patients with obesity vs. normal body weight controls, research has identified several obesity phenotypes1,2. Phenotypes were established with an unsupervised machine learning approach using gold standard measures of obesity pathophysiology.

Clinical application of phenotyping at Mayo Clinic: 2X more weight-loss Clinical experience at Mayo Clinic Weight Management Center shows that a phenotype guided approach (n=55) results in a higher percentage of responders and total body weight loss (TBWL) compared to non-phenotype guided (standard of care) approach (n=175) when patients are treated with FDA-approved obesity pharmacotherapy.

0%

10%

20%

30%

40%

50%

60%

70%

80%

>3% TBWL(month 3)

>10% TBWL(month 6)

>15% TBWL(month 12)

Patie

nts

(%)

Treatment RespondersNon-Phenotype GuidedPhenotype-Guided

-6,7

-13,4

-20

-15

-10

-5

0

0 3 6 9 12

TBW

L (%

)

Time (months)

Total Body Weight Loss (%)

Non-Phenotype Guided

Phenotype-Guided

1Acosta A , Camilleri, et al., Gastroenterology. 2015 2Camilleri M and Acosta A., Gastrointest Endosc. 2015

Biomarker assessment of obesity phenotypes PhenoTest is a fasting, “multi-omics” blood test which measures a combination of genes, metabolites, proteins, and hormones in the body that are related to obesity. Together, these biomarkers can be used to identify the obesity phenotype with sensitivity and specificity >90% using a proprietary AI-driven algorithm developed and exclusively licensed from Mayo Clinic. How it works

Easy-to-interpret results to guide weight-loss interventions • CLIA laboratory test • Targeted analysis of:

o Genomics o Metabolomics o Proteins/hormones

• Report includes: o Predicted phenotype composition o Annotated treatment considerations o Analytical test results

• Web-based portal facilitates ordering and report delivery

Ready to learn more? J We are currently enrolling select clinics in our early access program. To receive the latest news from Phenomix (including availability of the test) or for more information about the program, please e-mail info@phenomixsciences.com.

We are here to revolutionize the treatment of obesity by guiding ‘the right intervention for the right patient’

info@phenomixsciences.com 1-877-673-0981

PATI

ENT

Name Sex Date of Birth

SPEC

IMEN

Collection Date Specimen ID

PRO

VID

ER Institution/Account Name

Jane Doe Female 08/11/87 10/10/18 1001011000001 Uptown Obesity Clinic Patient ID Height Weight Collection Time Report Type Provider Name

10-259-0472 5 ft 6 in 200 lbs 08:57 AM Original Dr. James Smith Fasting Status Age BMI Received Date Report Date Client ID

Unknown 31 32 10/11/18 10/12/18 093295

15%

50%

30%

5%

Predicted Phenotype Composition

Slow Burn

Emotional Hunger

Hungry Gut

Hungry Brain

ABOUT OBESITY PHENOTYPES

HUNGRY BRAIN

The brain’s inability to determine when a meal is over is the main cause of obesity with this phenotype, which is also known as abnormal satiation or fullness. Abnormal satiation has been characterized by increased calorie intake during meal periods using ad libitum buffet meals and nutrient drink feeding paradigm tests. Presence of certain satiation-related gene variants and/or low levels of certain metabolites predict the satiation/hungry brain obesity phenotype. Along with implementing strategies to limit intake during meals, some weight-loss interventions work by targeting neurotransmitters that are related to brain-gut signaling and may prove effective in treating a dominant satiation phenotype.

HUNGRY GUT

Feeling hungry sooner or in periods between meals is frequently caused by the stomach and gut sending empty signals to the brain; this is also known as abnormal satiety. Abnormal satiety has been characterized by rapid gastric emptying after meals as measured with scintigraphy imaging techniques or by visual analog scores for satiety after a standard meal. Patients with a dominant satiety/hungry gut phenotype will return to a state of hunger between meals faster than other phenotypes. Presence of certain satiety-related gene variants and/or low levels of certain metabolites may be used to predict the hungry gut phenotype. Some weight loss-interventions work by targeting the early satiety signals and may prove effective in treating a dominant satiety phenotype.

Seeking food as a reaction to negative or positive emotions, or as a coping mechanism can be defined as emotional hunger. Emotional hunger has been characterized by high levels of cravings, anxiety, and depression as measured with tools such as the Three Eating Factor Questionnaire or the Hospital Anxiety Depression Scale (HADS). Presence of certain gene variants and/or high levels of certain metabolites may be used to predict the emotional hunger obesity phenotype. Cognitive therapy and medications that address some of the underlying emotions or psychological conditions may be helpful and lead to weight-loss for patients with this phenotype.

EMOTIONAL HUNGER

SLOW BURN

With this phenotype, the base metabolic rate is lower than normal; this is also known as abnormal energy expenditure. The slow burn phenotype has been characterized clinically by low muscle mass and abnormal resting energy expenditure (metabolic rate) as measured by indirect calorimetry. Presence of certain gene variants and/or low levels of certain metabolites may be used to predict the slow burn phenotype. Increasing physical activity may prove to be the most effective weight-loss strategy for patients presenting with a dominant slow burn obesity phenotype.

Patient ID: 10-259-0472 Patient Name: Jane Doe DOB: 08/11/1987 Page 1/3

Predicted Phenotype: Dominant: Emotional Hunger (50%)Secondary: Hungry Gut (30%)

Treatment Considerations: Treatment plan oriented around counseling to reduce emotional and stress eating. Consider medication such as naltrexone-bupropion, if appropriate, to help quell emotional or reward-based eating between healthy meals.