CYB004

CYB004
Deuterated Dimethyltryptamine (dDMT)

Cybin is developing CYB004 for the treatment of Anxiety Disorders, specifically Generalized Anxiety Disorder (GAD). CYB004, a deuterated dimethyltryptamine (dDMT), has been shown to exert its psychedelic effects by activating the 5-HT2A receptor.

In its regular form, DMT is an unstable molecule rapidly metabolized in the body, which significantly reduces its bioavailability. CYB004 has the potential to overcome the limitations of DMT.

Cybin has been granted a composition of matter patent from the USPTO that covers new chemical entity claims for CYB004 until 2041.

The World Intellectual Property Organization WIPO has published an international patent application for Cybin covering inhalation delivery methods for multiple psychedelic molecules that are currently being researched and developed by the company as well as other psychedelic molecules that may be developed in the future.

CYB004 Demonstrates Positive Preclinical Results

In preclinical studies, CYB004 has demonstrated an improved bioavailability and pharmacokinetic profile in comparison to DMT when administered via intravenous and inhaled routes. These studies also demonstrated that IV CYB004 had a longer duration of effect compared to DMT indicating the potential to extend the therapeutic window and provide better dose optimization.

Improved Bioavailability = potential for lower dosing and reduced side effects
Modified Duration = improved therapeutic window
Deuteration = potential for less invasive dosing methods for patients

CYB004 Demonstrates Promising Preclinical Results

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Approximately 2000% improved bioavailability compared with orally administered DMT, which is known to have limited to no oral bioavailability

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Approximately 41% improved bioavailability compared with inhaled DMT

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Approximately 300% longer duration of effect when compared to IV DMT, indicating potential to extend therapeutic window

Developing CYB004 as a Potentially More Viable Treatment Option for Anxiety Disorders

Cybin is currently conducting one of the largest Phase 1 DMT clinical trials to date. This 3-part Phase 1 trial is designed to evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of DMT and CYB004 in healthy volunteers.

CYB004E Study Design Overview

Part A: DMT SAD

Part A: DMT (Single Ascending Dose)

Acquired study in smokers

Single Ascending Dose

90-minute infusion

4 cohorts completed

Part B: DMT

Part B: DMT (Bolus + Infusion)

Amendments to protocol:

Non-smokers only

Change to bolus + infusion

Shorter infusion duration

Flexible dose exploration

Dosing Initiated

Part C: CYB004 (dDMT) FIH

Part C: CYB004 (FIH)

Amendments to protocol

Inclusion of CYB004 FIH

Bolus + infusion

Shorter infusion duration

Flexible dose exploration

1 %

Approximately 2000% improved bioavailability compared with orally administered DMT, which is known to
have limited to no oral bioavailability

1 %

Approximately 41% improved
bioavailability compared with
inhaled DMT

1 %

Approximately 300% longer
duration of effect when compared
with IV DMT, indicating potential to
extend therapeutic window

Rapid onset of effect and similar low variability equivalent to IV DMT

Improved Bioavailability = potential for lower dosing and reduced side effects
Modified Duration = improved therapeutic window (IV DMT at ~6-10 minutes v. CYB004 at ~30 minutes)
Inhalation Delivery = less invasive option for patients than IV

Note: Expectations for the potential benefits of CYB004 are based on preclinical data.

Data from Part A of the Phase 1 trial suggest DMT was well-tolerated within
evaluated dose range, with dose-related increases in both exposure and PD/behavioral effects
Data from Parts B and C will be used to build a robust PK/PD model to support dose optimization for future clinical studies

Scientific Rationale

DMT has agonistic actions on a range of 5-HT receptors

Efficacy demonstrated in a range of observational and
real-world studies in depression, anxiety and substance use disorders

As a deuterated molecule, CYB004 improves upon the bioavailability of DMT that may offer less invasive and more convenient dosing methods

Program Development

Cybin is currently conducting the largest Phase 1 DMT clinical study to date. This adaptive, randomized, double-blind, placebo-controlled, single ascending dose study is designed to evaluate the safety, pharmacokinetics and pharmacodynamics of a target-controlled intravenous infusion of DMT in 50 healthy volunteers who smoke tobacco. The Phase 1 study is being conducted in the Netherlands at the Centre for Human Drug Research (CHDR) and is expected to potentially yield essential safety and dosing data and provide the foundation for additional research on the therapeutic potential of DMT.

The primary objectives of the study are to: Evaluate the safety of increasing doses of a single dose continuous DMT infusion over 90 minutes; Characterize the PK of a single dose DMT administered continuously over 90 minutes; Characterize the PD of a single dose DMT administered continuously over 90 minutes; and Establish the minimum DMT dose required to produce a psychedelic effect.