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

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

Approximately 41% improved bioavailability compared with inhaled DMT

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 completed
Part C: CYB004 (dDMT) FIH
Part C: CYB004 (FIH)
Amendments to protocol
Inclusion of CYB004 FIH
Bolus + infusion
Shorter infusion duration
Flexible dose exploration
Initiated CYB004 dosing
Approximately 2000% improved bioavailability compared with orally administered DMT, which is known to
have limited to no oral bioavailability
Approximately 41% improved
bioavailability compared with
inhaled DMT
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.
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.

