Tryp Therapeuatics (TRYPF) Coverage Report

MARKET REVIEW – Eating disorders Three of Tryp’s six target indications include eating disorders, as described here, along with the rationale for psilocybin and its novel mechanism of action for these conditions. Eating disorders. Eating disorders are characterized by various disruptions to otherwise common and healthy eating patterns, often including disruptive behaviors that manifest in problems with weight control. Eating disorders coincide with a person’s mental and physical well-being (Lancet 2020; 395: 899–911). These various disorders are associated with co-morbidities, such as, metabolic disorders, obesity, and psychiatric conditions. There are several types of eating disorders, but TRYP is focusing on binge eating disorder (BED), hypothalamic obesity (HO), and Prader-Willi syndrome (PWS). Tryp’s clinical development plans in eating disorders. Tryp is collaborating with Dr. Jennifer Miller of the University of Florida as the Principal Investigator for a Phase 2a open-label, exploratory clinical study to investigate TRP-8802 in binge eating disorder, hypothalamic obesity, and Prader-Willi syndrome. The Phase 2a clinical trial will be a single trial of a total of 10 patients. Finalization of the trial design is underway with plans to initiate patient dosing in 4Q21. Interim data readouts are expected in 1H22 that will be used for their IND submissions for Ph2b studies with Tryp’s proprietary TRP-8803. The three eating disorders Tryp is pursuing with TRP-8803 include:  Binge eating is characterized by frequent episodes of eating large quantities of food followed by excessive feelings of guilt and distress. Current standard of care is focused on psychotherapy, possibly including Vyvanse (lisdexamfetamine dimesylate), which is the first FDA-approved medication to treat moderate to severe binge-eating disorder as well as its approval to treat attention-deficit hyperactivity disorder (ADHD). Since the drug is a stimulant, it has a high abuse liability (Schedule II). Vyvanse is not well tolerated, with 36% reporting a dry mouth and 20% having insomnia (Drugs@FDA). Other medications such as anti-depressants and anti- convulsants are also used to treat binge eating-related symptoms.  Hypothalamic obesity is caused due to damage to the hypothalamus. The damage can be due to surgical removal of brain tumor, head trauma or swelling in the brain. The hypothalamus is a region in the brain that plays an important role in the endocrine system and plays a role in regulating many important functions of the body, among them being appetite and body weight. There are currently no FDA-approved therapies.  Prader-Willi syndrome is an eating disorder due to a genetic disorder. Defect on chromosome 15 disrupts hypothalamic function, resulting in constant sense of hunger with never feeling full (hyperphagia). Symptoms can start early in childhood and features can remain throughout life. Some examples include, underdeveloped sex organs, cognitive impairment, abnormalities in growth, behavioral and speech troubles. There are no approved therapies, and we are not aware of any therapies with positive clinical results. While Rhythm Pharmaceuticals (RYTM: $12.48; Neutral) is targeting rare genetic obesities it has not stated it plans to test Imcivree (setmelanotide, MC4 receptor pathway) in PWS. Eating orders have been shown to have overlapping brain pathways with the DMN and ECN (Exhibit 17). These networks are highly interactive, with modulation of activity in the insula. Changes in functional connectivity within and between these networks are proposed to underlie the impact of psilocybin to generate cognitive flexibility in eating disorders. Neuroimaging studies have shown psilocybin increases in the connectivity between the DMN and other resting state networks and increased coactivation between DMN and other task-positive networks (Front Neurosci. 2020; 14: 43). This the enhanced cognitive flexibility has been shown to being driven by the activation of the 5-HT 2A receptor (Psychol Med. 46: 1379). Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 24