Tryp Therapeuatics (TRYPF) Coverage Report

Psychedelic drugs have been used for thousands of years for spiritual and religious purposes. While the history does not dictate that every psychedelic company will successfully develop an FDA approved treatment, in our view the history of psychedelics does favor the outcome for the industry as a whole. Here, we review their use from the most historical to the most recent. According to archaeologists, evidence from fossils suggest humans have consumed psychedelics for more than 10,000 years (Economic Botany. Vol. 57, No. 3 (Autumn, 2003), pp. 295-323; U Victoria, Reist, Ancient Peoples and Psychoactive Plants). Psychedelics were believed to be a part of ritual ceremonies across a variety of disconnected cultures, including cave paintings of mushrooms from Algeria almost 5,000 years ago and Mesoamerican Mayan “mushroom stones” around 2,600 B.C. throughout Mexico through 250 A.D. Scientific research into psychedelic mushrooms began in the mid-1800’s. While German scientist Arthur Heffter is widely credited with first isolating mescaline from the peyote cactus it was really a team effort from various European and American scientists that spanned ~50 years (Monatshefte für Chemie - Chemical Monthly volume 150, 941–947, 2019). In 1938, Sandoz chemist Albert Hofmann synthesized LSD (lysergic acid diethylamide). He resynthesized LSD five years later, absorbing LSD via his fingertips to serendipitously discover its hallucinogenic effects (MAPS Newsletter, Volume 6 Number 3 Summer 1996). In 1947, Sandoz first launched LSD in European countries as Delysid to treat various psychiatric conditions and in 1949 it was launched in the U.S. to treat neurosis, alcoholism and to spark creativity (Isis. 1997 Mar;88(1):87-110). In 1958, Hofmann isolated the active component of psilocybin (psilocybe) and discovered it was a shorter acting alternative to LSD (Neuropharmacology 142 (2018) 143e166). Sandoz marketed across Europe and the U.S. primarily for depression and anxiety as Indocybin until discontinuing its sale in 1966. During this period of the 1950-1960s there was a surge in psychedelic research with ~1,000 scientific papers and reports generating data on ~40,000 subjects. However, due to the association of these drugs with counterculture, plus the misuse and recreational experimentation of their effects, the research and sale of psychedelics was virtually eliminated. With the Controlled Substances Act of 1970 in the US, and similar regulations and restrictions in other countries, psychedelics were declared as dangerous substances with no potential therapeutic benefit (Trends Pharmacol Sci. 2017 Nov;38(11):992-1005. doi: 10.1016/j.tips.2017.08.003; Nat Rev Neurosci. 2020 Nov;21(11):611-624). In the US, Schedule I drugs are highly restricted, and their possession is criminalized. This put a big hindrance on scientific research, with companion restrictions across Europe also. Exhibit 5: Psychedelic research timeline Sources: Trends Pharmacol Sci. 2017 Nov;38(11):992-1005. doi: 10.1016/j.tips.2017.08.003 Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 11