Shots:
- GH001, an inhaled formulation of mebufotenin, is emerging as a highly differentiated therapy for treatment-resistant depression, delivering ultra-rapid and profound symptom improvement – patients come to the clinic depressed and many leave in remission already on the same day. Long term, in a Phase 2b trial, 73% of patients who completed six months were in remission—substantially higher than the ~11% rates typically seen with third- or fourth-line oral antidepressants.
- Early-stage studies in postpartum depression and bipolar disorder reinforce GH001’s broader neuropsychiatric potential. In a Phase 2a trial in postpartum depression—an area of profound unmet need and frequent underdiagnosis—all 10 treated patients achieved remission.
- GH Research is advancing GH001 within established psychiatric care models that already support novel treatments such as Spravato. The therapy’s ultra-rapid onset (within seconds), brief psychoactive duration (~11 minutes on average), and short overall clinic visit (patients typically discharge-ready within one hour from last dose), may support real-world scalability and patient access as development progresses.
Saurabh: Today I’m speaking with Dr. Velichka “Villy” Valcheva, CEO of GH Research, about the company’s work in neurological disorders, with a focus on treatment-resistant depression. To start, could you briefly introduce yourself and tell us about GH Research?
Villy: Of course. I’m Villy Valcheva, CEO of GH Research, and I’m also a physician. My background has always centered on innovative treatments, particularly in areas of high unmet medical need. Over the past 15 years, I’ve had the opportunity to help bring several transformative therapies to patients and families, which has been deeply meaningful to me.
GH Research is an Ireland-based, clinical-stage biotechnology company founded in 2018. We are focused on developing novel treatments for psychiatric disorders, starting with depression. We currently have two proprietary product candidates, GH001 and GH002. GH001, our most advanced program, is being developed for treatment-resistant depression, though we have also conducted proof-of-concept studies in other indications.
We chose neuropsychiatry because mental health has become one of the most pressing challenges in modern society. Millions of people live with psychiatric conditions. In the U.S. alone, data from 2023 shows that 13 million people seriously considered suicide, with one death occurring every 11 minutes. Roughly 90% of these cases are linked to psychiatric conditions, most commonly depression.
Despite this, neuropsychiatry has lagged behind other fields – such as oncology or cardiovascular medicine – in terms of innovation. As a result, patients are often cycled through multiple lines of treatment, with diminishing efficacy and increasing side effects. That gap is what GH Research aims to address.
GH001 differs from traditional antidepressants in a key way: it has a truly rapid onset of action, with patients achieving remission very quickly.
Saurabh: Let’s discuss your early-stage trials in bipolar disorder and postpartum depression. What have you seen so far?
Villy: We’ve conducted early-stage trials in both bipolar disorder and postpartum depression, and the results have been consistent with what we observed in treatment-resistant depression. Patients experienced rapid improvement and entered remission quickly.
These are areas of significant unmet need. Postpartum depression, in particular, is often underdiagnosed due to stigma, and many women hesitate to seek care. Importantly, untreated postpartum depression affects not just the mother but also the child, with potentially serious long-term consequences.
In our Phase 2 postpartum depression study, all 10 patients achieved remission. The average MADRS reduction was 35 points. For comparison, traditional antidepressants typically achieve reductions of around 3 to 4 points.
Saurabh: That’s quite striking. GH001 is described as having a rapid onset and a short psychoactive window. If approved, how scalable is this treatment in real-world clinical settings?
Villy: To answer that, it helps to briefly explain what GH001 is and the data we’ve generated so far. GH001 is inhaled mebufotenin, also known as 5-MeO-DMT.
To date, we’ve completed six clinical trials involving 175 healthy volunteers and patients. Most recently, we completed a Phase 2b randomized, double-blind, placebo-controlled trial in 81 patients with treatment-resistant depression, with six months of follow-up.
The topline results were presented by Professor Michael Thase at the ASCP Congress. The study met its primary endpoint, showing a statistically significant 15.5-point improvement in MADRS scores versus placebo by Day 8. We also met all secondary endpoints, including improvements in anxiety, global disease severity, and quality of life. GH001 was well tolerated.
At six months, 73% of patients who completed the trial were in remission with infrequent treatments – on average 4 in 6 months. To put that in context, remission rates for patients on third or fourth-line oral antidepressants are typically around 11% or lower. This is a very promising outcome.
In terms of scalability, there is already precedent. Spravato, an intranasal treatment for treatment-resistant depression, is approved and delivered through approximately 6,000 clinics across the U.S. These clinics are already equipped to administer novel psychiatric treatments. We believe GH001 could fit into a similar clinical model in the future.
Saurabh: Why did you choose the inhaled route rather than intranasal or oral delivery?
Villy: We selected the inhaled route as best for developing GH001 as the lungs have an enormous surface area – roughly half the size of a tennis court – which allows the compound to reach the brain within seconds. This provides an ultra-rapid onset of action, which was a key design goal.
Patients typically enter the psychoactive phase within seconds, and importantly, that phase is very short. In our Phase 2b study, the average duration was about 11 minutes. Patients are generally discharge-ready within an hour of their last dose. This short duration is critical for real-world scalability and clinic workflow.
Saurabh: Beyond depression, what are GH Research’s plans for other indications?
Villy: The potential for GH001 in neuropsychiatry is significant. There are millions of patients with treatment-resistant depression in the U.S. and Europe alone, and existing treatment options are limited.
In addition to postpartum depression and bipolar disorder, data from the broader psychedelic field suggests potential efficacy in conditions such as anxiety disorders, PTSD, alcohol use disorder, and substance use disorders. Over time, we believe GH001 could play a meaningful role across multiple psychiatric indications. Our current focus though is on TRD!
Saurabh: Shifting gears a bit – how do you spend your time outside of work?
Villy: Being a CEO doesn’t leave much free time, but I’ve found a balance. I dedicate early mornings – around 5 or 6 a.m. – to exercise and the gym, which helps me stay focused and productive. When I do have time off, I love traveling with my family. I’m very family-oriented and enjoy nature and the sea. For now, my routine is largely work, fitness, and staying healthy.
Saurabh: Coming back to GH001 – Are there plans to combine it with digital health tools or AI-enabled technologies?
Villy: Our immediate focus is clinical development. The next step is a pivotal Phase 3 program to support regulatory approval. That’s where our full attention is today.
That said, digital health tools are already part of the broader mental health landscape—apps for mood support, wearables for tracking symptoms, and more. My long-term vision is that patients in remission could use wearables to detect early signs of relapse, allowing them to seek treatment before symptoms return.
In our six-month data, patients required an average of four treatments, which aligns well with this concept of proactive, maintenance-based care.
Saurabh: Are you open to partnerships or licensing discussions?
Villy: At this stage, we are fully focused on development. GH Research is publicly traded on NASDAQ and well funded. Following our Phase 2b results, we successfully raised additional capital, giving us the resources needed to advance the program.
We believe we have strong internal expertise and insights from our development work, and our priority is executing the next phase successfully. We’ll see what the future brings.
Saurabh: With growing awareness around mental health, what do you see as the biggest responsibilities and opportunities for companies like GH Research?
Villy: Awareness has increased significantly, and stigma related to mental health conditions is gradually decreasing, though it still exists. Our responsibility is to persevere and deliver GH001 to patients who need it. That includes outstanding execution of our global pivotal program, training physicians, building infrastructure, educating clinicians, and ensuring reimbursement access once approved.
As for the opportunity, it’s deeply personal. There isn’t a single person I speak to who doesn’t know someone affected by depression or another psychiatric condition. Being able to say that we helped change the treatment paradigm – and improved the lives of patients and families – is the greatest opportunity of all.
Saurabh: Sounds like GH001 could be a life-changing option. Do you have any final thoughts you’d like to share?
Villy: I hope this conversation highlights the renewed innovation happening in neuropsychiatry. It’s becoming an increasingly important and attractive field for clinicians, researchers, investors, and patients alike.
Most importantly, I hope it gives hope to people living with treatment-resistant depression – that new options are coming, and that we are working tirelessly to bring them forward.
About the Author:
Velichka Valcheva
Dr. Velichka (Villy) Valcheva is the Chief Executive Officer at GH Research. Previously she served in a number of global leadership roles in biotech and pharmaceutical companies such as Albireo, Ipsen and Sanofi. Dr. Valcheva holds a medical degree from Medical University Plovdiv Bulgaria, as well as an MSc in Pharmaceutical Medicine from Trinity College Dublin.
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