Cybin CYB004 (DMT) GAD Phase 2 Trial

Executive Summary

Cybin will announce the results of a phase 2 study in GAD for CYB004 (DMT) in Q2/mid 2025. Based on the general success of other psychedelics in mood disorders and the similarity in the MOA, it is likely the trial will be successful. DMT has already demonstrated excellent results in depression. I am looking at buying the May $7.5 calls or the August $10 calls to play this catalyst.

Background Information

GAD Overview

Generalized Anxiety Disorder

Generalized Anxiety Disorder (GAD) is a chronic mental health condition characterized by excessive, persistent worry or anxiety about various aspects of everyday life, even when there's little or no reason to worry. It affects adults and children and can significantly impair daily functioning, relationships, and overall well-being.

Symptoms:

• Excessive worry: Difficult to control, occurs more days than not, and lasts for at least six months.

• Multiple domains: Worry is not limited to a single issue

• Physical symptoms:

  • Restlessness or feeling “on edge”

  • Fatigue

  • Difficulty concentrating

  • Irritability

  • Muscle tension

  • Sleep disturbances (e.g., trouble falling or staying asleep)

The prevalence of the disease is about 3% of the US population. It often begins in adolescence or early adulthood and fluctuates throughout life.

Development History for Prescription and Advanced Therapies

Treatment for GAD falls into two categories: psychological and pharmacological. Psychological treatment is often either CBT, DBT, or acceptance and commitment therapy. FDA-approved pharmacological treatment falls under four classes of medication: SSRIs, SNRIs, azapirones, and benzodiazepines.

Examples of SSRIs:

·         Paroxetine

·         Escitalopram

·         Fluoxetine

·         Fluvoxamine

Examples of SNRIs:

·         Venlafaxine

·         Duloxetine

Examples of Azapiriones:

·         Buspirone

Examples of Benzodiazepines:

·         Alprazolam

·         Lorazepam

·         Clonazepam

Sometimes, atypical antipsychotics, anticonvulsants, and beta-blockers can be used off-label in the treatment of GAD. Occasionally, MAOIs can be used in the treatment of GAD.

For some, these treatments are very effective. However, very few see complete symptom resolution, and the disease often requires long-term management.

There are many molecules currently being tested in the treatment of GAD that appear promising:

Psychedelics:

·         LSD (MindMed)

·         CYB004 (Cybin)

·         Psilocybin (many companies)

Other Small molecules:

·         Soclenicant

·         Ulotaront

·         Tulodesvenlafaxine

The trials into the psychedelics appear promising. In their phase 2b, MindMed showed a 65% clinical response rate and a 48% remission rate at 12 weeks without psychotherapy for LSD. These are impressive numbers, especially relative to current treatments on the market. The trials of psilocybin in depression and anxiety have shown great success thus far. In phase 2, Incannex Healthcare showed that 44% of participants experienced at least a 50% reduction in anxiety. 27% achieved complete remission.

CYB004

​CYB004 is a proprietary, deuterated form of N,N-dimethyltryptamine (DMT). Deuteration enhances the molecule's stability and bioavailability, potentially offering a more controlled and sustained therapeutic effect than traditional DMT.​ CYB004 functions as a serotonin 5-HT₂A receptor agonist, similar to psilocybin and LSD, inducing psychedelic effects that may help alleviate anxiety symptoms.

Disease/MOA Interaction

The etiology of GAD is complex, and psychiatric diseases are not well understood from a biologocial perspective. However, it is clear the neurotransmitters norepinephrine, serotonin, dopamine, GABA, and possibly glutamate are at least implicated due to the success of benzodiazepines, MAOIs, and SSRIs. It has been hypothesized that the increase in neuroplasticity as a result of the increased levels of these neurotransmitters is at least partially responsible for the improvement in symptoms in the case of MAOIs and SSRIs. DMT is a strong agonist of the 5HT-2A receptor and induces an increased state of neuroplasticity following admission.

CYB004 (DMT) Discussion

Given the general success of psychedelics in the treatment of mood disorders and the similarity of the MOA for DMT, it is likely this trial meets its primary endpoint. My only concern with the use of psychedelics is the adverse effect profile. There are anecdotal reports of these drugs triggering worse mental states, including psychotic breaks.

Conclusion

The upcoming readout of CYB004 in GAD will likely be positive. I have some concerns about the adverse effect profile. However, humans have been using psychedelics for a long time. The general efficacy of these compounds relative to existing treatments leads me to believe most, if not all these compounds get approved for mood disorders. I am long August $10 calls and some common stock.