Tryp Therapeuatics (TRYPF) Coverage Report

Exhibit 17: Overlapping 5-HT pathways in AN, ECN and DMN dlPFC = dorsolateral prefrontal cortex; Ins = insula; pACC = perirenal anterior cingulate cortex; PCC = posterior cingulate cortex; PPC = posterior parietal cortex; vmPFC = ventromedial prefrontal cortex; vStr = ventral striatum; Source: Front Neurosci. 2020; 14: 43 Scientists looking into eating disorders are discovering that these disorders are related to disturbances in functional connectivity between neural networks in the brain. Their research has found that there are abnormalities within the neural networks that are both different and overlapping between the eating disorders. There are three main networks: default mode network (DMN); executive control network (ECN); and salience network (SN) that play a role in emotional and environmental processing, reward, and food processing (Brain Behav . 2019; 9: e01207, Sc Rep. 5:10964).  Default mode network (DMN): The DMN consists of several connecting brain regions. This network shows lower levels of activity when an individual is involved in a particular task like paying attention, but higher levels of activity when they are active but not focused on a specific mental exercise. Studies support the role of increased DMN activity in obese individuals.  Executive control network (ECN): The ECN is involved during cognitive tasks that require externally directed attention. It is also involved in inhibitory processes such as the cessation of eating.  Salience network (SN): The SN is involved in emotional arousal, food, and reward processing. This network activated by a salient stimulus. Psilocybin in eating disorders. It is important to note that the exact mechanisms related to psilocybin’s actions in altering resting state networks is still not fully understood. Due to these neurobiological actions, it is believed that psilocybin provides a break from extreme and inappropriate degree of internal focus on eating disorder patterns so the individual can shift towards developing new patterns that focus on contextual balance that is not dictated by eating disorder thoughts and urges. Exhibit 18 provides a more detailed description on how psychedelics make this happen. These therapeutic effects are a combination of the drug in addition to the assisted psychotherapy sessions. Individuals with binge eating disorders have shown insufficiencies related to problem- solving, cognitive flexibility, and working memory (Braz J Psychiatry. 32(4): 381). Given these changes in the functional connectivity in the brain, psilocybin is being tested in the treatment of eating disorders given its ability to alter serotonin signaling and cognitive inflexibility. Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 25