FDA Grants Cybin Breakthrough Therapy Status For Major Depression Psilocybin Therapy, Company Announces Positive Clinical Data & Canadian $150M Private Placement

Clinical-stage psychedelics biopharma company Cybin Inc. CYBN announced that the Food and Drug Administration has granted Breakthrough Therapy designation to CYB003, its proprietary deuterated psilocybin analog targeting the adjunctive treatment of Major Depressive Disorder (MDD.) 

The news follows the same granted designation to MindMed's MNMD LSD-derived treatment for Generalized Anxiety Disorder (GAD.) 

Further, it makes the group of psychedelic-based treatments for mental health conditions that have in recent years received such status granted by the U.S. federal agency five therapies total: the mentioned two, plus MAPS' MDMA-assisted therapy for PTSD treatment and Compass Pathways' CMPS psilocybin therapy targeting Treatment-Resistant Depression (TRD.) 

Designation’s Enabling Features

Breakthrough Therapy designation provides an expedited review pathway, with fast-track program features as well as increased access to FDA guidance and discussion on the therapy's development program including trial design and expedited manufacturing development strategy, with the potential to significantly reduce drug development timelines.

It is granted to drug candidates that target serious conditions and demonstrate substantial improvement on a clinically significant endpoint as compared to available therapies.

Supported by the positive topline results from Cybin's Phase 2 study of CYB003 in MDD, the company says the designation acknowledges the significant unmet medical need for more effective treatments of MDD and supports CYB003's potential for significant improvements over existing therapies. If approved by the FDA, it would be the first known adjunctive psychedelic-based therapeutic for the treatment of MDD. 

CEO Doug Drysdale stated that the designation underscores CYB003's potential "to fill a gap in the treatment landscape for MDD" and also "serves to expedite and de-risk" the company's drug development program going forward. 

"This designation provides for a streamlined review process and enhanced engagement with the FDA. With the robust durability data from our Phase 2 study in hand, we are ready to move forward expeditiously. We are grateful for the opportunity to accelerate the development and regulatory review process that this designation affords, as we prepare to advance CYB003 toward a Phase 3 pivotal trial around mid-year," Drysdale concluded.

Sustained Therapeutic Results At Four Months

Cybin also announced that its Phase 2 trial of CYB003 in MDD demonstrated "robust and sustained improvement" in depression symptoms at four months, and 75% of participants receiving two doses of 16mg achieved remission and no longer showed signs of depression.

As reported by the company, positive four-month efficacy data for CYB003 includes:

• "Robust and sustained" improvements in depression symptoms, with two doses of 12 mg or 16 mg of CYB003 (22 mean reduction points from baseline in the MADRS* total score.) 
• About 75% of patients were responders (50% or more improvement in MADRS scores) following two doses of 16mg.
• 60% of patients on 12 mg and 75% on 16 mg were in remission from depression following 2 doses (MADRS score of 10 or less.)
• CYB003 was well tolerated with no drug-related serious adverse events, only mild or moderate, and no incidents of suicidal ideation or behavior nor discontinuations due to adverse events.

*The MADRS is a 10-item, clinician-administered scale designed to measure overall severity of depressive symptoms. Broadly used in clinical trials and accepted by regulatory authorities worldwide as a measure of symptoms of depression, it includes items ranging from sadness of mood, reduction in sleep and appetite, to difficulties in concentration, anhedonia, and negative and suicidal thoughts scored from 0 to 6, giving a total score ranging from 0 to 60. 

Typical score ranges for severity are 0-6 normal; 7-19 mild; 20-34 moderate; and >34 severe depression. In the CYB003 study, mean baseline total scores on the MADRS were 31.4 to 33.7 in the active group and 30.8 in the placebo group.

Cybin's chief medical officer Amir Inamdar stated that the sustained reduction in depression symptoms at the four-month mark after just two doses of CYB003 "is a critical milestone, which demonstrates the durability of the response," following rapid improvement in symptoms. 

"It is truly remarkable that at four months the participants experienced a sustained reduction and incremental improvement in depression symptoms," Drysdale said. "Impressively, the mean reduction from baseline in the MADRS total score was approximately 22 points at 4 months (compared to a mean reduction of 14 points vs. placebo and 17 points from baseline at 3 weeks). This is highly encouraging, especially for patients who have not responded to existing treatment options." 

Inamdar views these results as paving the way for a change in the treatment paradigm for MDD: "Unlike currently approved adjunctive treatments which require chronic, daily dosing, CYB003 allows for intermittent dosing without the challenges of withdrawing patients from their existing medications," he concluded.

Canadian $150M Oversubscribed Private Placement

In parallel to the exciting clinical program news, Cybin additionally announced a proposed private placement of 348,837,210 common shares in its capital at a unit price of $0.43 -an about 17% premium to the 10-day volume weighted average trading price on the NYSE exchange,- for expected aggregate gross proceeds of $150 million.

Net proceeds will be used for certain Phase 3 drug development activities for CYB003, working capital and general corporate purposes.

The oversubscribed private placement is being led by Deep Track Capital and includes participation from RA Capital Management, Avidity Partners, Acorn Bioventures and Altium Capital among other institutional investors.

With Bloom Burton Securities Inc. acting as the lead agent, the placement is expected to close on or about March 19, 2024, following approval of Cboe Canada and NYSE American LLC as well as other met conditions.

In the U.S., the shares will be offered on a private placement basis pursuant to exemptions from the registration requirements of the Securities Act. The securities have not been registered under the U.S. Securities Act, and may not be offered or sold within the U.S. or to, or for the account or benefit of, U.S. persons absent registration or an applicable exemption.

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