Tryp Therapeuatics (TRYPF) Coverage Report

However, in the 1980’s there were public signs that psychedelic research began to return, mainly in academic settings, which leveraged improved tools to understand mechanism of action, target engagement and animal models. These discoveries were on a small scale what we have today, which is an environment where there is a partnership between many academic centers and companies focused on generating prescription treatments. Today’s renaissance in psychedelic research includes programs ranging from early-stage drug discovery to formulation optimization to late clinical studies. This space is now being eagerly watched by scientists, pharma, investors, and patients for whom these drugs are providing unprecedented, life-changing effects. We believe June 2018’s FDA approval of GW Pharmaceuticals’ (JAZZ; $135.26; NR) Epidiolex (oral CBD solution) as a treatment for two rare epileptic disorders supported the renewed interest in psychedelics. More so, Jazz’s announced acquisition on February 3, 2021, of GW likely supported the view of psychedelic investors that what happened to CBD (become mainstream) can happen with psychedelics. SCIENTIFIC BACKGROUND What are psychedelics? The term “psychedelic” is derived from ancient Greek words psychē ("soul") and dēloun ("to reveal"). Psychedelics generate altered visual and auditory perceptions of reality, but also a substantially different state of consciousness. Hallucinogens are a type of drug that disconnects one’s awareness of their current surroundings as well as their own long-term memories and long-term feelings. The psychedelics can be divided into four classes based on their pharmacological profiles and chemical structures (Exp Clin Psychopharmacol 2016; 24:229–268), including classic psychedelics, empathogens/entactogens, dissociatives and atypical hallucinogens. Classic psychedelics. A class of hallucinogenic drugs with a primary effect via serotonin 2A receptor agonism, including psilocin (psilocybin mushrooms), mescaline (found in peyote, a cactus), LSD (ergot fungi), and DMT (psilocybin mushrooms). Classic psychedelics are further broken down to include  Tryptamines: The classic psychedelics share their core structure with the neurotransmitter 5-HT and modulate multiple targets, including 5-HT receptors, monoamine transporters, and trace-amine-associated receptors. Tryptamines include the synthetic ergoline LSD and the plant-derived indoleamine psilocybin. o LSD: This popular, illicit hallucinogenic psychedelic is distinct from other psychedelics in that it binds with sub micromolar affinity to the α1 adrenergic and has affinity for the D 1–3 dopaminergic receptors and has the greatest affinity for the 5-HT2 A receptor. The difference in dose amounts between psilocybin and LSD is dramatic, as LSD is 10 to 100 times more potent than psilocybin at the 5-HT1 A and 5-HT2 receptors and more potent at α adrenergic and dopaminergic receptors. Visual perceptions from LSD are driven by an increased functional connectivity in the visual cortex. As found in the within the default mode network (DMN), there is a reduced connectivity between the parahippocampus (hippocampal gyrus) and the retrosplenial cortex. o Psilocybin: Meanwhile, this classic psychedelic is a more potent inhibitor of the serotonin transporter (Eur Neuropsychopharmacol 2016; 26:1327–1337).  Phenethylamines: Phenethylamines are stimulant, entactogenic, and hallucinogenic substances (Dis Mon. 2014 Mar;60(3):110-32). This type of classic psychedelic also includes popular, illicit hallucinogens, such as MDMA “Ecstasy” and mescaline (peyote cactus seeds). These drugs act as a serotonin agonist to release dopamine and norepinephrine (Neuropharmacology. 2018 Nov; 142:116). Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 12