Tryp Therapeuatics (TRYPF) Coverage Report

In addition to these molecular mechanisms, psychedelics are known to affect changes in the brain functional connectivity which can contribute to its analgesic effect. There is clinical evidence to support the role of psychedelics for the treatment of different pain states such as PLP, cluster headaches, and cancer, ischemic, or neuropathic pain. Fibromyalgia (FM). Fibromyalgia is a chronic and widespread musculoskeletal pain characterized by consistent fatigue, sleep disturbances, psychiatric disorders, hypersensitivity to pain, and cognitive impairments. Worldwide prevalence is 2 to 4% with females showing twice as much of a prevalence rate (Lancet. 2021; 397(10289): 2098. At roughly four million Americans, fibromyalgia is Tryp’s largest target patient group. It is also one of the most untreatable pain conditions today. Exhibit 19: Hypothesized interplay between potential pathogenic mechanisms and nociplastic alterations in fibromyalgia Source: Nat Rev Rheumatol. 2020;16(11): 645  FM-driven pain is described as nociplastic, which is “…pain arising from altered nociception, despite no evidence of tissue damage causing the activation of nociceptors or evidence of disease or lesions of the somatosensory system causing the pain”. The pathophysiology is being investigated, but so far, the known factors are related to genetic predisposition, stressful events, and a disruption between central and peripheral neural mechanisms. Exhibit 19 shows a hypothesized demonstration of how these mechanisms come into play.  Not surprisingly, the diagnosis of FM is difficult due to the lack of nociceptive, observable pain, the divergent symptoms, lack of biomarkers, and differing opinions on the diagnostic criteria. Diagnosis typically occurs from a mix of clinical assessments, including patient’s history, physical examination, X-rays, and blood work. Treatment is individualized following trial and error, including exercise, pharmacotherapy, psychotherapy, and patient education, (Nat Rev Rheumatol. 2020;16(11): 645).  Existing treatments for fibromyalgia (Lyrica [pregabalin], Cymbalta [duloxetine], and Savella [milnacipran]) are flawed with limited efficacy, side effects, and poor patient adherence (only 10%). Almost a third of patients take opioids even though they are not efficacious for FM increasing their risk of addiction and overdose (Pain Manag. 2016 May;6(4):347-55; J Clin Rheumatol. 2021 Aug Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 27