Compass Pathways and Definium Near Regulatory Milestones as Psychedelics Field Approaches Commercial Reality
Key Insights
Compass Pathways is planning multiple Phase III data readouts this quarter for its psilocybin-based therapy COMP360 in treatment-resistant depression (search), with regulatory filing expected by Q3 2025.
Definium (search) is preparing three Phase III data drops for its LSD-based MM120 in generalized anxiety disorder (search) and major depressive disorder (search), representing a potential "tipping point" for the psychedelics space.
Both companies are positioned to become the first FDA-approved "classic psychedelics" following the 2024 rejection of Lykos Therapeutics (search)' MDMA-based therapy for PTSD.
The psychedelics industry stands at a pivotal moment as two leading companies prepare to file for regulatory approval, potentially transforming the field from experimental therapy to commercial reality. Compass Pathways and Definium (search) are nearing critical Phase III data readouts that could establish the first FDA-approved classic psychedelic treatments.
"This is a very big year for psychedelics," H.C. Wainwright analyst Patrick Trucchio told BioSpace. "It's the biggest year from a clinical data standpoint," since the firm began covering Compass in 2018.
Compass Pathways Prepares Multiple Phase III Readouts
Compass is planning multiple readouts this quarter for COMP360, its psilocybin-based therapy for treatment-resistant depression (search) (TRD). The company will release 26-week results from the Phase III COMP005 trial, full data from Part A of COMP005, and full data from Part B of the parallel Phase III COMP006 trial, according to Steve Levine, the company's chief patient officer.
What the FDA is most interested in seeing from the 26-week COMP005 readout is the safety of potentially retreating patients up to 12 weeks, Levine explained. Trucchio said Compass is "very likely" to file for approval of COMP360 by the third quarter of this year.
A recent investor and key opinion leader event held by Compass reframed the opportunity "from a theoretical commercial debate to an executable launch scenario," H.C. Wainwright noted. "Overall sentiment from providers was notably enthusiastic and proactive," with multiple KOLs characterizing COMP360 as "a rare, field-defining innovation."
The company has also received FDA acceptance of an Investigational New Drug application for a late-stage trial of COMP360 in post-traumatic stress disorder (search), expanding its potential therapeutic applications.
Definium's LSD-Based Therapy Shows Promise
Three upcoming Phase III data drops from Definium (search)—formerly MindMed (search)—for its LSD-based MM120 in generalized anxiety disorder (search) and major depressive disorder (search) could be a "potential psychedelic space tipping point," according to RBC Capital Markets. Trucchio predicted that Definium would follow Compass in filing for approval, with MM120 likely to receive regulatory submission after COMP360.
"So by 2027, that's a reality that MM120 and COMP360 are probably going to be approved," Trucchio predicted.
Overcoming Previous Setbacks
The psychedelics sector is still regrouping from the FDA's August 2024 rejection of an MDMA-assisted therapy for post-traumatic stress disorder (search) from Lykos—now Resilient Therapeutics (search). However, details from the complete response letter published in September 2025 made clear that the rejection was primarily focused on Resilient's trial design rather than the psychedelics field overall.
Compass and Definium (search), along with other psychedelic players in the depression space, are now gearing up to claim the title that Lykos once sought—the first FDA-approved "classic psychedelic."
Differentiation from Existing Treatments
Johnson & Johnson's Spravato, an inhaled esketamine treatment approved for TRD in 2019, has primed the infrastructure for future psychedelics-based therapies. However, J&J has previously stated it does not consider Spravato to be a classic psychedelic due to differences in both mechanism and psychedelic experience.
While classic psychedelics activate the 5-HT2A receptors (search), esketamine hits the NMDA receptor (search), resulting in a less profound dissociative effect. During its investor event, Compass reiterated that from a payer perspective, COMP360's single-session 6-week efficacy already represents a differentiated value proposition compared to Spravato's approximately 10 administrations over the same timeframe.
Regulatory and Commercial Challenges Ahead
Despite the promising outlook, several challenges remain for the psychedelics field. Trucchio cautioned that psychedelics may experience delays during launch because the Drug Enforcement Administration will have to reschedule psilocybin and LSD, which are both currently classified as Schedule 1 drugs.
Following an FDA approval, the DEA would have 90 days to make a determination of rescheduling, followed by individual state decisions. Levine noted that "about half" of U.S. states have trigger laws that "essentially automatically follow federal guidance."
Given these regulatory complexities, Trucchio said that even if Compass were to submit an NDA following the 26-week data this quarter, a fourth-quarter 2027 launch would be "optimistic."
Infrastructure Development and Market Preparation
Compass has begun preparing for commercial launch through strategic partnerships. The company announced a collaboration with Radial Health (search), a mental health company developing a network of clinics across the U.S. that provide treatments including transcranial magnetic stimulation and esketamine while seeking insurance reimbursements.
"We're proud to collaborate with Compass to help ensure that its innovative, science-based treatment, if approved, reaches patients," Radial's CEO and co-founder John Capecelatro stated.
Managing Expectations
When Compass announced 6-week data from the Phase III COMP005 trial in June 2025, the reaction from Wall Street was muted. While the trial hit its primary endpoint, the 3.6-point reduction on a key depression scale paled in comparison to Phase II data that showed a 12-point drop over the same time period.
"Typically, in Phase II to Phase III in neuropsychiatry, you come down on the primary endpoint," as later-stage trials comprise a broader sample with a higher number of enrolled patients, Trucchio explained. The subdued response may also be due to early academic trials showing remission rates of over 85% in TRD, creating elevated expectations.
"Unfortunately, because that high bar was created, I think there's this idea that these are miracle drugs, they're going to cure everyone of their depression. That's not what this is," Trucchio cautioned.
With multiple late-stage data readouts and regulatory catalysts expected in 2026, H.C. Wainwright believes the psychedelics coverage is "well positioned to transition from 'speculative' clinical validation to large-scale market launch."