Tryp Therapeuatics (TRYPF) Coverage Report

MARKET OPPORTUNITY Currently, Tryp is planning to conduct six Phase 2a proof-of-concept studies with non- proprietary psilocybin, TRP-8802. The company intends to complete the formulation work for TRP-8803 prior to the start of the Phase 2b’s in the indications where 25mg synthetic psilocybin capsules generated insightful improvements to patients. The following summarizes the market opportunity for TRP-8803. Fibromyalgia (FM). The worldwide prevalence of FM is 2–4% and stable, with females twice as likely as males to have FM (Lancet. 2021; 397(10289): 2098). In the U.S., the rate of FM is roughly half the global rate. For the ~four million Americans with FM (www.cdc.gov/arthritis/basics/fibromyalgia.htm) there are three approved FM drugs (Lyrica [pregabalin], Cymbalta [duloxetine], and Savella [milnacipran]). However, there is considerable lack of benefit from these drugs, as physicians continue to rely on opioids (~27%, per J Clin Rheumatol. 2021 Aug 1;27(5):187-193) despite a large meta-analysis finding, “…no evidence from clinical trials that opioids are effective for the treatment of FM” (Mayo Clin Proc. 2016 May;91(5):640-8). Among Tryp’s six potential indications, FM is by far the largest in terms of patient populations. Phantom Limb Pain (PLP). The number of people with PLP has increased dramatically over the past 25 years, along with the increasing rates of obesity. In 1996, there were an estimated 1.6M with amputations (Vital Health Stat 10 1999;(200):1-203), increasing 25% over nine years to a 2.0 estimate in 2005 (Arch Phys Med Rehabil Vol 89, March 2008). While the amputees from the wars in Iraq and Afghanistan may appear to have contributed to the increase, the ~1,700 limb amputations from those wars were not material (Front Neurol. 2018;9:153). Rather, we attribute the increase to the increasing rates of obesity, diabetes, and peripheral arterial disease (PAD). We estimate there are 2.0 to 2.5M amputated Americans today and 1.75M to 2.2M suffering from PLP, with various degrees of pain, from occasional sensations to constantly excruciating. However, we may be underestimating PLP prevalence. Studies suggest we are approaching 12M Americans with peripheral arterial disease (PAD), with 15-20% undergoing amputations, or ~2M PAD amputees (Arterioscler Thromb Vasc Biol. 2020;40:1808–1817). Between 2000 and 2010, while PAD diagnoses rose 13% annually in the U.S., growth rates in low- to middle-income countries were twice that rate. Not all amputees experience PLP, with estimates ranging from 64% based on a meta- analysis of papers between 1980 and 2019 (PLoS One. 2020; 15(10): e0240431) to 82% based on a meta-analysis of papers between 2014 and 2019 (Eur J Pain. 2021 Jan;25(1):23-38). The lifetime prevalence for PLP is 76%–87%. The severity of PLP can vary between amputees (J Clin Invest. 2018; 128: 2168) and the prevalence of PLP from lower limb amputations are higher than those of upper limbs (Int J Rehabil Res. 2010 Sep;33(3):279-82). Men have twice the rate of amputations, with 88% coming from those >45 years old (www.acl.gov’s Amputee Coalition). Complex regional pain syndrome (CRPS). We believe there are ~112,000 Americans (0.03%) with CRPS based on epidemiologists’ review of the Nationwide Inpatient Sample database of 20% of U.S. hospital stays, including 22,533 patients discharged with a diagnosis of CRPS (J Clin Anesth. 2017 Jun;39:34-37). Women have CRPS at roughly twice the rate of men, with a mean age of 50.7 and ~five diagnosed comorbidities (Pain Physician. 2017 Feb;20(2):E257-E268). Per a review of ~6.6M ICD-9 codes from 2000 to 2012, the most common comorbidity was pain back, at ~75% (Pain Physician. 2017 Feb;20(2):E257-E268). Since most CRPS treatments are generic, the average cost to treat CRPS is ~$1,500 annually (Neuromodulation. 2018 Jul;21(5):423-430). Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 32