Tryp Therapeuatics (TRYPF) Coverage Report

Exhibit 18: Psychedelics’ neurobiological and psychological characteristics Source: Psychological Medicine. 2016; 46: 1379 MARKET REVIEW – Chronic pain Three of Tryp’s six target indications include chronic pain disorders, as described here, along with the rationale for psilocybin and its novel mechanism of action for these conditions. TRP-8802/03 in chronic pain. Chronic pain is defined as pain that persists or recurs for more than three months. It is further subdivided into two categories: 1) Chronic primary pain is when pain is caused by a disease, such as fibromyalgia, or nonspecific low-back pain. 2) Chronic secondary pain is when pain secondary to an underlying disease, such as chronic cancer-related pain, chronic neuropathic pain, chronic posttraumatic and postsurgical pain (Pain. 2019: 160(1): 19). Chronic pain can impact the quality of daily life, affect workday and social activities. In addition, it can also affect mental health, cognitive processing, cardiovascular health etc. Chronic pain affects 50 million adults, or one in every five American adults (Pain. 2021; Apr 2. doi: 10.1097/j.pain.0000000000002291). The estimated U.S. cost of chronic pain management is >$600 billion, which is higher than for cancer, diabetes, and cardiovascular diseases (J Pain. 2012; 13(8): 715). In chronic pain, TRYP is focused on the following indications: Psilocybin in chronic pain disorders. The primary mechanism of action of psychedelic compounds is the activation of the 5-HT receptors. Upon activation of these receptors several downstream pathways are modulated leading to the upregulation of several genes that are involved in synaptic plasticity. Clearly, this is a very distinct approach than deployed by opioid receptor agonists. Receptor activation with certain psychedelics can also lead to the inhibition of tumor necrosis factor α (TNF-α)-mediated inflammatory pathways. Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 26