CYBIN INC.

About the Deuterated Dimethyltryptamine Program

The Company’s proprietary deuterated dimethyltryptamine (“dDMT”) program CYB004 is being developed as an intermittent treatment with the potential for less invasive, more convenient and patient-friendly dosing methods for the potential treatment of GAD. A single intramuscular (“IM”) dose is expected to result in acute psychedelic effects lasting an average of 90 minutes.

Cybin has leveraged clinical data from its completed DMT and dDMT trials, which collectively form one of the most advanced and extensive DMT/dDMT data portfolio in the psychedelic drug development sector, to inform and optimize the development of the CYB004 program. To date, Cybin has completed five clinical trials across four molecules: CYB004 (IV dDMT), SPL028 (IV/IM dDMT), SPL026 (IV/IM DMT), and DMT, demonstrating proof-of-concept in potentially treating depression, supporting the development of dDMT for the potential treatment of anxiety disorders, and providing important dosing insights.

Key findings from these completed studies are as follows:

•Phase 2a safety and efficacy data for SPL026 (IV DMT) in 34 participants with MDD, demonstrating a clinically relevant and statistically significant reduction in depression symptoms at two weeks after dosing (-7.4 point difference in MADRS between SPL026 and placebo). Durable antidepressant response and remission rates were observed at six months. Among participants who had achieved remission within three months with SPL026, 64% sustained remission to six months.

•Phase 1 study evaluating IM SPL026 supporting IM administration for patient-friendly dosing. The study demonstrated that IM DMT is well-tolerated and generates a breakthrough psychedelic experience lasting approximately 45 minutes.

•Phase 1 study evaluating IM SPL028 supporting IM administration for patient-friendly dosing. The completed Phase 1 study of IV/IM SPL028 in healthy volunteers showed that SPL028 is safe and well-tolerated, and demonstrated that IM dosing of SPL028 produced robust psychedelic effects lasting a short duration (average approximately 90 minutes) in the majority of subjects.

•Phase 1b study evaluating the safety and efficacy of SPL026 in conjunction with selective serotonin reuptake inhibitors (“SSRIs”) in 17 participants with MDD, demonstrating no relevant drug-drug interactions, a favorable safety profile and enhanced efficacy when SPL026 was administered with SSRIs, and a 92% remission rate at 4 weeks in the DMT + SSRI combination cohort (n=12).

•Phase 1 results for IV CYB004 demonstrated robust and rapid-onset psychedelic effects at lower doses compared to native DMT, suggesting potential as a short-acting, scalable treatment.

Exploratory analysis of the Phase 2a and Phase 1b data for SPL026 also shows significant improvements in symptoms of anxiety, as measured using the State Trait Anxiety Inventory – Trait version (STAI-T), with a 23 point improvement from baseline at the two week endpoint, in the DMT+ SSRI combination group.

The Company is currently advancing CYB004, a deuterated version of DMT, for the potential treatment of GAD. DMT activates the serotonin 5-HT 2A receptor, which is believed to mediate the potential therapeutic effects of DMT. In its regular form, DMT is an unstable molecule rapidly metabolized in the body, which significantly reduces its bioavailability. CYB004, as a deuterated molecule, has the potential to overcome the therapeutic limitations of native DMT. To date, CYB004 has demonstrated robust and rapid-onset psychedelic effects at lower doses compared to native DMT, suggesting potential as a short-acting, scalable treatment. Additionally, learnings from Phase 1 studies of IM SPL028 have supported IM administration as a viable dosing method for deuterated DMT, suggesting the potential for CYB004 to offer more convenient and patient-friendly dosing methods.

CYB004 is secured by a U.S. composition of matter patent with protection through 2041. The patent covers a range of deuteration forms of DMT and protects CYB004 as a putative new chemical entity.

On June 7, 2022, the Company announced it had entered into an agreement to acquire a Phase 1 DMT study (the “Asset Acquisition”) from Entheon Biomedical Corp. (“Entheon”) to accelerate the clinical development path for CYB004. On July 11, 2022, the Company announced that the Asset Acquisition was completed. The Phase 1 study, previously identified as EBRX-101 and now named CYB004-E, was conducted in the Netherlands. Entheon acted as external consultants to the Company for approximately 10 months after the Asset Acquisition.

On January 12, 2023, the Company announced that it has selected GAD as the target indication for its proprietary deuterated DMT molecule, CYB004.