Entropy Neurodynamics, GH Research and Helus Pharma are taking different approaches to a shared challenge: developing psychedelic medicines that can be delivered and managed within clinical practice.
Psychedelic drug development is moving beyond the question of whether these compounds can produce meaningful changes in mental health. For biotechnology companies, another challenge is becoming increasingly important: how to deliver a psychedelic treatment in a way that clinicians can manage, patients can tolerate and healthcare systems can accommodate.
That is shaping the development strategies of several clinical-stage companies, including Australia’s Entropy Neurodynamics, Ireland’s GH Research and Helus Pharma, formerly Cybin. Their programmes differ in their pharmacology and delivery methods, but each is exploring ways to make the treatment experience more predictable or the intervention more practical.
Entropy is developing intravenous psilocin, GH Research is pursuing inhaled and intravenous mebufotenin, and Helus is advancing an oral deuterated psilocin analogue through Phase 3. Meanwhile, Eli Lilly’s acquisition of AtaiBeckley has brought additional psychedelic-derived drug programmes into the portfolio of a major pharmaceutical company.
Entropy is building its programme around intravenous psilocin
Melbourne-based Entropy Neurodynamics (ASX: ENP) is developing TRP-8803, a proprietary intravenous formulation of psilocin, the active metabolite of psilocybin.
The rationale for intravenous administration is the ability to adjust drug delivery during a treatment session. Unlike an oral formulation, which is administered as a fixed dose and takes time to produce its effects, an infusion gives clinicians more direct control over the amount of drug being administered and the timing of its delivery.
Entropy is investigating whether that control can improve the practical management of psychedelic-assisted treatment, including the onset, intensity and duration of the experience. These remain development objectives rather than established advantages over oral psilocybin.
The programme is progressing across several indications, including binge eating disorder and major depressive disorder. In September, Entropy reported that all participants in the first cohort of its Phase 2 binge-eating-disorder study had improved, with half achieving remission at 12 weeks. The company is continuing the study, with further results expected from its second cohort in the fourth quarter of 2026. These early findings are encouraging for the programme, but the small cohort means they should not be interpreted as evidence of efficacy at a broader population level.
Entropy has also advanced TRP-8803 towards US development in depression and secured manufacturing arrangements intended to support the programme’s progression into larger clinical studies. Its strategy places the infusion process itself at the centre of the product, rather than treating the drug formulation and the clinical experience as separate considerations.
GH Research is pursuing short-duration psychedelic treatments
GH Research (NASDAQ: GHRS) is investigating mebufotenin, also known as 5-MeO-DMT, through its lead candidate GH001, an inhaled formulation being developed for treatment-resistant depression.
The programme is built around a different pharmacological and delivery profile from Entropy’s psilocin infusion. GH Research is pursuing an inhaled treatment with a relatively brief psychedelic experience, potentially reducing the time patients spend undergoing the acute effects of treatment.
GH Research has completed a randomised, double-blind, placebo-controlled Phase 2b study of GH001 in treatment-resistant depression and has been preparing its pivotal development programme. It has also developed a proprietary aerosol delivery device, making the delivery technology an important part of the candidate’s development.
The company is also advancing GH002, an intravenous formulation of mebufotenin, with early clinical development intended to establish its safety and pharmacological profile.
The comparison with Entropy is particularly relevant at the level of clinical delivery. Both companies are exploring how formulation and administration can influence the treatment session, but the compounds themselves are different. Their respective programmes will need to demonstrate that the intended practical benefits translate into acceptable safety, clinical outcomes and workable treatment protocols.
For GH Research, the next major development milestones will help establish whether its inhaled approach can progress through pivotal trials and towards regulatory review.
Helus is modifying the molecule rather than relying on infusion
Helus Pharma (NASDAQ: HELP; Cboe Canada: HELP), previously known as Cybin, is taking a different approach with HLP003, an oral deuterated serotonergic agonist being developed as an adjunctive treatment for major depressive disorder.
Rather than relying on an infusion to control administration, Helus is developing a modified molecule intended to produce a therapeutic effect through its pharmacological properties. HLP003 has received FDA Breakthrough Therapy Designation and is being evaluated in the company’s Phase 3 PARADIGM programme.
The programme includes APPROACH, a pivotal study comparing two doses of HLP003 with placebo, and EMBRACE, a second pivotal study with multiple dose arms. Helus has reported that APPROACH completed enrolment of 223 participants, with topline results expected in the fourth quarter of 2026. The company is also conducting EXTEND, a long-term extension study designed to collect additional information on safety, durability and potential redosing.
Helus is also developing HLP004, an intramuscular serotonergic agonist candidate for generalised anxiety disorder. Its development adds another formulation and indication to the company’s pipeline, although the evidence from this programme should be considered separately from the Phase 3 work on HLP003.
The distinction between Helus and the other companies is important. Its principal development proposition is molecular, whereas Entropy’s is centred on infusion control and GH Research’s lead programme combines a different psychedelic compound with inhaled administration.
Lilly’s acquisition of AtaiBeckley brings another delivery platform into big pharma
The acquisition of AtaiBeckley by Eli Lilly adds another set of psychedelic-derived medicines to the development portfolios of established pharmaceutical companies.
Announced in July and completed on 11 September 2026, the transaction involved approximately US$2.8 billion in upfront aggregate equity value, with additional contingent payments linked to development and regulatory milestones. AtaiBeckley is now a wholly owned Lilly subsidiary.
AtaiBeckley’s lead programme, BPL-003, is a nasal formulation of mebufotenin benzoate being developed for treatment-resistant depression. The company has also been advancing VLS-01, a proprietary oral transmucosal DMT formulation, through clinical development.
The acquisition places two additional delivery approaches alongside Lilly’s existing neuroscience capabilities: nasal administration of a rapid-acting psychedelic-derived compound and an oral transmucosal formulation of DMT.
For the wider sector, the transaction is a significant commercial development, although it does not establish that these treatments will ultimately receive approval or achieve widespread adoption. Lilly’s investment gives the programmes access to the resources of a large pharmaceutical company, while their clinical and regulatory prospects remain to be demonstrated.
It also gives the psychedelic medicine sector a concrete example of a large pharmaceutical company acquiring an entire clinical-stage platform rather than pursuing development solely through smaller-company partnerships.
The commercial challenge is becoming a delivery problem
The differences between these programmes are substantial, but they share a development question: what combination of molecule, formulation and treatment protocol can produce a clinically useful intervention without creating an impractical burden for patients and providers?
For Entropy, the central proposition is that an infusion can give clinicians greater control over drug administration. For GH Research, the focus is on an inhaled compound with a short-duration psychedelic experience, alongside an intravenous programme. Helus is testing whether a modified oral compound can deliver its intended therapeutic effects as an adjunct to existing antidepressant treatment.
These are distinct hypotheses, and their clinical results cannot be compared directly. The compounds, patient populations, dosing protocols and trial designs differ, while none of the programmes has yet established an approved commercial product.
There is also a practical distinction between controlling the pharmacological experience and simplifying the overall treatment. A shorter drug effect may reduce the time required for acute monitoring, for example, but patients may still require preparation, clinical supervision, psychological support and follow-up. Intravenous administration may offer dosing flexibility while introducing additional equipment, staffing and monitoring requirements.
Those trade-offs will matter when companies begin making the case for adoption beyond specialist research settings. Clinical efficacy is only one part of the eventual commercial proposition; manufacturing, safety, treatment duration, staffing requirements and reimbursement will also influence whether a product can become part of routine care.
For Entropy, GH Research and Helus, the coming clinical readouts will provide more information about their respective approaches. Lilly’s acquisition of AtaiBeckley adds a further dimension: the potential for established pharmaceutical companies to invest in the development of these technologies at scale.
The competitive landscape is therefore taking shape around more than the psychedelic molecule itself. How a treatment is formulated, administered and incorporated into clinical practice is becoming an increasingly important part of its development.
