FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | 1 PHYSIOLOGY OF TASTE

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | SECTIONSECTION TITLESLIDE# 1Understanding Taste4 & 5 & 6 2Five Distinct Tastes7 3The Taste Spectrum8 4How Palatability Affects Medication Adherence9 & 10 Table of Contents 2

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | Understanding Taste Taste is a chemical sense which provides important information on the chemical composition of food. It is one of the body’s mechanisms developed to recognize foods needed for nutritional value as well as a natural defense mechanism helping to identify harmful substances. For example, bitter flavors are more commonly associated with natural toxins whereas sweet tastes are associated with energy rich foods needed for survival. Flavor, is created when additional senses such as sight and smell are included into the experience. 3

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | Understanding Taste Taste buds are located on the papillae on the tongue. The average adult has approximately 10,000 taste buds. Many taste buds lie along the walls of the papillae. Isolated ones also are present on the palate, the pharynx, and the epiglottis. Taste buds are comprised of taste cells with taste nerves interwoven between. When taste cells are stimulated, the taste nerves depolarize and send taste signals to the brain, including the hypothalamus, the thalamus, and the gustatory part of the sensory cortex - the "taste center", where the signals are interpreted. The thalamus acts like a relay station, shunting the data onto appropriate cortical areas for processing (Please refer to the diagrams depicted on the next slide). When taste is combined with the sense of smell, flavor is perceived by the brain. 4

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | Understanding Taste 5

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | Five Distinct Tastes Five distinct tastes can be detected: 1. Sweet- provides a recognition of energy rich nutrients. 2. Salty - allows modulating the diet for electrolyte balance. 3. Sour- typically indicates the presence of acids and allows for the detection of when foods may be spoiled. 4.Bitter- allows sensing of diverse natural toxins. 5.More recently a fifth taste has been recognized known as Umami or savory. It is the taste of amino acids (e.g. meat broth or aged cheese). Many diagrams present “taste-zones” however it is now believed that while there are differences to taste sensitivity around the tongue, the different tastes are perceived in any area taste buds exist. Presence and density of taste buds may vary by individual 6

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | The Taste Spectrum It is estimated that 25% of the population are super-tasters indicating a higher density of taste-buds and increased sensitivity to certain tastes. Women are more likely to be super-tasters. Normal tasters make up 50% of the population. Non-tasters make up the remaining 25%. Non-tasters are less affected by strong flavors. Research indicates a decline in the number and change in the shape of taste buds with age. Despite these age-related changes, it is not clear the degree to which this affects taste sensation. Age related decline in taste is more often correlated to co-morbidities affecting smell, which in turn can impact an individual’s sensitivity to taste. Additionally, certain disease states, medications, dental work, as well as cultural or environmental factors may influence taste sensitivity and preference. 7

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | The literature supports taste as being a significant factor in adherence and recognizes that this issue should be considered when selecting medications, especially among pediatric patients. The chemical structure of a medication determines not only the pharmacological efficacy of a drug, but the bitter taste as well. As mentioned before, the rejection of bitter flavors is part of basic biology. Bitter flavors are most commonly associated with natural toxins and poisons, therefore rejection of such tastes is thought to have evolved to protect the consumer from harm. This issue further highlights the role taste plays in medication adherence among children. Parent reports reiterate that medication with poor taste is a viable barrier to administering medications 8 How Palatability Affects Medication Adherence

FLAVORx Inc, 9475 Gerwig Lane, Columbia, MD | | H How Palatability Affects Medication Adherence Approximately 350 million liquid medications are dispensed in the U.S. each year, many of which are associated with poor palatability. While companies recognize palatability issues with medication administration, often only one flavor per formulation is manufactured. This is primarily due to Research and Development costs as well as production costs. Having the ability to customize the flavor of medications after- market, to mask unpleasant taste and/or meet patient preferences, may improve adherence. 9