Tryp Therapeuatics (TRYPF) Coverage Report

mushrooms (psilocybin) had the lowest harm score of the 20 drugs tested, with an overall harm score 12-fold lower than alcohol. Psilocybin’s score on a potential to cause harm to others is near zero. In terms of causing harm to oneself, psilocybin mushrooms scored ~six-fold lower than heroin, crack, and methamphetamine (Lancet. 2010; 376(9752): 1558). In our view, psilocybin differs from high abuse potential drugs like stimulants and opioids and has a low abuse liability which should support its role in treating neurological disorders. Exhibit 15: Drugs ordered by their overall harm scores “Advisory Council on the Misuse of Drugs (the UK Govt committee on drug misuse). A panel of drug- harm experts was convened to establish scores for 20 representative drugs that are relevant to the UK, and which span the range of potential harms”. Source: Lancet. 2010; 376(9752): 1558  Psilocybin toxicity. Psilocybin’s LD 50 is 280 and 285 mg/kg for rats and mice, respectively. In humans, the effective dose is >1,000-fold less than the lethal dose. Psilocybin has minimal potential to cause respiratory depression or other cardiovascular issues that are associated with other drugs of abuse such as opioids (Neuropharmacology. 2018 Nov;142: 143). According to a study to assess the concentration-QTc relationship of psilocybin/psilocin, there is a limited potential of QT prolongation following a 25 mg oral psilocybin dose (Clin Pharmacol Drug Dev. 2021; 10(1): 78). There has been one case of overdose reported so far, but it was from an individual who had received a heart transplant ten years earlier and died of a cardiac arrest two-to-three hours after psilocybin administration. A mouse study has also reported that psilocybin administration does not cause causes chromosome breaking (Neuropharmacology. 2018 Nov;142: 143).  Psilocybin’s tolerance and physical dependence. Tolerance has been reported to the psychological and physiological effects of psilocybin. However, physical dependence and withdrawal have not been found (Neuropharmacology. 2018 Nov;142: 143). Cross-tolerance between psilocybin and LSD has been demonstrated.  Psilocybin’s subjective effects. These are a hallmark features of hallucinogens and subjective effects for psilocybin can begin within seconds of administration. In a within-subjects single-blind design study, 15 healthy volunteers with prior experience with psychedelics received a bolus infusion of 10 ml of saline in one magnetoencephalography (MEG) session and 2 mg of psilocybin in 10 ml of saline in a second session. When tested fifteen minutes post treatment, participants have demonstrated a difference in a 23-item questionnaire scoring for distinct aspects of their subjective effects, as shown in Exhibit 16 (J Neurosci. 2013; 33(38): 15171). Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 22