Tryp Therapeuatics (TRYPF) Coverage Report

began to become evident, first in the patient populations where they are not approved today, and then to where they are approved (depressive disorders). More recent efforts by medium-sized biotechs, including Alkermes (ALKS; $30.65; NR) and Sage (SAGE; $43.59; NR), highlight the difficulties in trying to develop novel approaches. Meanwhile, psychedelics have begun to provide evidence from well designed and executed clinical studies that psychedelics can provide uncommonly supportive results:  MDMA in PTSD : Announced in May 2021, from a 79-patient Phase 3 conducted by the non-profit group researching psychedelics since 1986, Multidisciplinary Association for Psychedelic Studies (MAPS), researchers demonstrated that 67% of participants in the MDMA group no longer qualified for a diagnosis of PTSD, compared with 32% in the placebo group after 18 weeks, including three treatments of MDMA or placebo during once-weekly counseling sessions. The mean change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores was -24.2 and -13.9 in the MDMA and placebo groups, respectively (p<0.0001, d=.91). Transient, mild to moderate adverse events occurred more often in the MDMA group but no increase in suicidality (Nat Med. 2021 Jun;27(6):1025- 1033).  Psilocybin in MDD: Published April 15, 2021, in NEJM, a 59-patient, six-week randomized trial of 25mg psilocybin capsules vs. 10mg to 20mg Lexapro (escitalopram) demonstrated statistically equivalent results on the primary (QID- SR-16 depression score) but the -8 vs. -6 drops (p=0.17) and secondaries of response rates (70% vs. 48%), remission (57% vs. 28%), one-day change (-5.7 vs. -2.8), respectively, plus the comparable rates of adverse events generated excitement among the mental health community and brought more media attention on the prospects of a psychedelic (Engl J Med 2021;384:1402-11). Dr. Carhart-Harris (Chairs Tryp’s SAB) was lead author of this paper. o This trial followed another MDD trial of just 27 MDD patients, but psilocybin generated HAMD reductions from 22.8 to 8.0 and 8.5 after one and four weeks, respectively; plus, one-day reductions in QIDS-SR from 16.7 to 6.3 (p<0.001). Conducted at Johns Hopkins (JAMA Psychiatry. 2021;78(5):481-489). Besides the academic institutions mentioned, others with a focus on psychedelic research include the Imperial College of London, UCLA, UCSD, Harvard University, NYU and Columbia University. Given the legal impediments today and the legislative changes that will need to be modernized, schools like Harvard are starting initiatives like POPLAR (The Project on Psychedelics Law and Regulation) “…to promote evidenced-based law and policy with regard to psychedelics” (https://petrieflom.law.harvard.edu) . In terms of legislative activity, the successful changes towards cannabis have energized a variety of constituents, including:  California State Senator Scott Wiener’s SB 519, which would decriminalize psychedelics in California is passing through CA legislature procedures and expected to become law. It begins by removing ketamine from decriminalization.  Last November, Oregon voters approved a bill allowing small amounts of narcotics, LSD and MDMA for personal consumption and another bill allowing licensed providers to use psilocybin in therapeutics settings.  This summer Texas passed a bill mandating state funded research into psychedelics for the treatment of PTSD.  So far, legislators in Hawaii, Massachusetts, Vermont, Maine, Iowa, Florida, Connecticut, California, and Hawaii have sponsored legislation to decriminalize psychedelics. Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 7