-Intravenous (“IV”) CYB004 demonstrated robust and rapid-onset psychedelic effects at lower doses compared to native DMT, suggesting potential as a short-acting, scalable treatment –

– Intramuscular (“IM”) dosing of SPL028 produced robust, short-duration psychedelic effects in the majority of participants –

– Both IV and IM routes were safe and well-tolerated, with potential for IM administration to provide more convenient, patient-friendly dosing –

– Combined Phase 1 results for deuterated DMT program support progression to a Phase 2 study in Generalized Anxiety Disorder (“GAD”) in Q1 2024 –

– Patent portfolio includes 40 granted patents and over 170 pending applications, with 25 granted patents directly related to the deuterated DMT program –

Cybin Inc. (NYSE American:CYBN) (NEO:CYBN) (“Cybin” or the “Company”), a clinical-stage biopharmaceutical company committed to revolutionizing mental healthcare by developing new and innovative psychedelic-based treatment options, today announced positive safety, pharmacokinetic (“PK”) and pharmacodynamic (“PD”) data from its Phase 1 studies of CYB004 (IV) and SPL028 (IV and IM) in healthy volunteers. CYB004 and SPL028 are proprietary deuterated DMT molecules within the Company’s DMT program in development for the treatment of generalized anxiety disorder.

Results from the Phase 1 studies in the CYB004 and SPL028 programs demonstrated PK and PD profiles with the potential to bridge data across these molecules, and the PK profiles for both molecules demonstrated concentrations in the effective range. Both IV (CYB004 and SPL028) and IM (SPL028) administration routes were safe and well-tolerated, with potential for IM dosing to provide a more convenient dosing method for patients when compared to IV infusion. IM dosing of SPL028 produced robust psychedelic effects lasting a short duration in the majority of subjects, a finding that supports IM administration as a well-tolerated and effective dosing method that is highly scalable.

“The positive data from our Phase 1 studies of CYB004 and SPL028 are highly encouraging with the combined data from these studies enabling us to prioritize our 2024 development plan for our deuterated DMT program. Importantly, these are the first-in-human studies of deuterated DMT in healthy participants. We are pleased that both the IV and IM administrations produced robust psychedelic effects and were safe and well-tolerated. We are especially encouraged that the IM route produced psychedelic effects in the majority of subjects, with a short-duration psychedelic experience from a single administration of SPL028. These results for IM dosing of deuterated DMT are highly promising and will help inform dosing in future clinical trials, saving time and resources by eliminating the need for further formulation studies of other methods such as subcutaneous dosing.”

-Doug Drysdale, Chief Executive Officer of Cybin

“The completion of our Phase 1 CYB004 and SPL028 studies represents a significant milestone in the clinical advancement of our deuterated DMT program. From these studies, we identified a dose that resulted in strong psychedelic effects, was well-tolerated and we believe will result in therapeutic efficacy. Collectively, these positive results will inform a more targeted approach and support an accelerated path to a Phase 2 deuterated DMT study in GAD in early 2024.”

-Amir Inamdar, Chief Medical Officer of Cybin

Phase 1 CYB004 Topline Results

The objective of the Phase 1 CYB004 study was to evaluate the safety, PK, and PD of escalating doses of DMT and CYB004 in healthy participants. This was a three-part study, consisting of Part A (90-minute IV DMT infusion) in 39 participants, Part B (IV DMT bolus + infusion) in 12 participants, and Part C (IV CYB004 bolus ± infusion) in 24 participants.

CYB004 was well-tolerated with no serious adverse events, and the majority of adverse events were mild to moderate and self-limiting. The Phase 1 study’s robust dataset on safety, tolerability and PK/PD provided important dosing information allowing the Company to advance its deuterated DMT program into patients in a Phase 2 GAD study in Q1 2024.

Study highlights:

  • Escalating doses of DMT IV infusion over 90 minutes were well-tolerated
  • Robust psychedelic effects were produced, and the intensity of effects was related to the rate at which the peak concentration was achieved.
  • Deuteration of DMT, as with CYB004, resulted in stronger psychedelic effects at lower plasma concentrations, compared with native DMT.
  • These psychedelic effects were rapid in onset when administered as an IV bolus over 5 minutes and persisted for about 40 minutes after the bolus without the need for an extended infusion.
  • This short duration of effects has the potential for CYB004 to be a scalable treatment that can be delivered in a shorter period of time compared with longer acting psychedelics.

Phase 1 IV/IM SPL028 Topline Results

The Company today also announced the completion of dosing in a Phase 1 study evaluating IV and IM doses of SPL028 (deuterated DMT) in healthy participants. The objective of this study was to evaluate the safety, PK, and PD of escalating doses of SPL028 in healthy participants. This was a two-part study, consisting of Part 1 (IV vs IM cross-over dosing in 16 psychedelic-experienced healthy participants) and Part 2 (single IV or IM doses of SPL028 in 22 healthy participants with little-to-no psychedelic experience).

IV and IM SPL028 demonstrated a favorable safety and tolerability profile. No serious adverse events were observed, and the majority of adverse events were mild to moderate and self-limiting. Furthermore, the study identified an IM dose of SPL028 that resulted in a breakthrough psychedelic experience, with a total duration ranging from 55 to 120 minutes.

Phase 1 Data Summary: CYB004 and SPL028

  • IV and IM routes both safe and well-tolerated
  • CYB004 and SPL028 demonstrated similar PK and PD profiles which allows bridging of data across molecules
  • PK profiles for both molecules demonstrated concentrations in the effective range
  • IM dosing of SPL028 produced robust psychedelic effects lasting a short duration in the majority of subjects

“With these important deuterated DMT datasets in hand, as well as the recently announced positive findings from our Phase 2 study of CYB003, our deuterated psilocybin analog in development for the treatment of Major Depressive Disorder, we are well positioned to advance both programs as we pursue our goal of creating safe and effective treatments for multiple mental health disorders,” concluded Drysdale.

About Cybin

Cybin is a clinical-stage biopharmaceutical company on a mission to create safe and effective psychedelic-based therapeutics to address the large unmet need for new and innovative treatment options for people who suffer from mental health conditions.

Cybin’s goal of revolutionizing mental healthcare is supported by a network of world-class partners and internationally recognized scientists aimed at progressing proprietary drug discovery platforms, innovative drug delivery systems, and novel formulation approaches and treatment regimens. The Company is currently developing CYB003, a proprietary deuterated psilocybin analog for the treatment of major depressive disorder and CYB004, a proprietary deuterated DMT molecule for generalized anxiety disorder and has a research pipeline of investigational psychedelic-based compounds.

Headquartered in Canada and founded in 2019, Cybin is operational in Canada, the United States, the United Kingdom, the Netherlands and Ireland. For company updates and to learn more about Cybin, visit www.cybin.com or follow the team on X, LinkedIn, YouTube and Instagram.