As psychedelic-based therapeutics gain traction in mental health, Reunion Neuroscience is at the forefront of innovation with RE104, a novel prodrug designed to offer the benefits of psilocybin with a shorter duration and improved pharmacokinetics. The company is pioneering its development in postpartum depression, a condition with significant unmet needs, while also expanding into adjustment disorder and other neuropsychiatric indications. With strong intellectual property protection through 2042 and a strategic focus on FDA-aligned clinical development, Reunion is positioning itself as a leader in next-generation psychiatric treatments. As the psychedelic industry navigates regulatory challenges and shifting investment landscapes, Reunion remains financially sound and focused on executing high-quality clinical trials. In this Q&A, Reunion Neuroscience President and CEO Greg Mayes discusses the company’s milestones, clinical strategy, and vision for reshaping mental health care, with Pharma’s Almanac’s David Alvaro, Ph.D.
David Alvaro (DA): Can you walk us through the genesis of Reunion Neuroscience?
Greg Mayes (GM): Reunion Neuroscience was officially spun out of Field Trip Health in August 2022. Field Trip had been primarily focused on operating a North American network of ketamine treatment clinics, but they decided to create a subsidiary, called Field Trip Discovery, and invest $2 million into a research initiative to develop a novel psychedelic therapeutic that could address unmet medical needs in depression and anxiety. The objective was to find a compound with a shorter duration of psychedelic effects and stronger intellectual property protection than existing psychedelics.
To lead this effort, they brought in Dr. Nathan Bryson, a seasoned chemist in pharmaceutical development, who identified 4-hydroxy-DiPT as a key component of what would become RE104. 4-hydroxy-DiPT is a compound originally synthesized and its psychedelic properties described by Dr. Alexander Shulgin — a pioneer of psychedelic drug discovery –– decades earlier. 4-hydroxy-DiPT was one of Shulgin’s favorite “shorties,” with a psychedelic trip that mimicked psilocybin but only lasted about 2–3 hours. 4-hydroxy-DiPT, however, suffered from poor absorption and variable onset of activity, as well as being quite unstable, which may explain why it never became popular as an illicit substance. Nathan saw an opportunity to transform this designer drug into a novel prodrug compound (DiPT) that could improve its absorption, pharmacokinetics, and stability while maintaining its therapeutic potential so as to be able to develop it as a pharmaceutical ingredient. Just as important, he realized this new compound could be patent protected. This work led to the creation of RE104, a new chemical entity developed as a subcutaneous injection that shares many similarities with psilocybin, but is unique in having a short psychedelic duration and a very reproducible trip profile (high and return to baseline).
Recognizing that the clinical drug development efforts were vastly different from Field Trip’s ketamine clinic business, the board decided to split the company to create Reunion Neuroscience, a standalone biotechnology company focused on psychedelic-inspired therapeutics for mental health disorders.
DA: You joined as CEO shortly after the spinout. What were your initial priorities, and how has the company evolved under your leadership?
GM: The board was looking for a leader with pharmaceutical and clinical development expertise, and, given my background, it was a great fit. I had previously founded Engaged Therapeutics, which developed a rapid treatment for seizure termination in epilepsy patients. That experience made me acutely aware of the mental health challenges that often co-occur with chronic conditions — over 80% of epilepsy patients experience mental health disorders. So, leading a company focused on advancing mental health treatments was personally meaningful to me.
When I came on board, my focus was on ensuring the success of the company’s early clinical programs. The phase I study of RE104 in healthy volunteers had just begun, and my first priority was seeing it through to completion so that we could gather strong safety and pharmacokinetic data. The next step was preparing for the Investigational New Drug application with the FDA and getting the phase II trial in postpartum depression ready for execution. Alongside these efforts, I had to ensure the company had the necessary financial and human resources to advance our programs.
At the time of the spinout, Reunion was publicly traded on Nasdaq and the Toronto Stock Exchange, but as a microcap biotech, we faced significant challenges in raising capital without unfavorable dilution. In May 2023, we received an offer from MPM BioImpact, a leading Boston-based life sciences venture capital firm. They saw the potential of RE104 but advised that we transition to a private company to reset our balance sheet and eliminate the costs and distractions of being publicly traded. We finalized that transition in August 2023 and later secured a $103 million Series A financing led by MPM BioImpact and Novo Ventures, giving us a cash runway through early 2027.
Today, Reunion is in a much stronger position. We are advancing RE104 in postpartum depression, preparing for a clinical trial in adjustment disorder, and laying the groundwork for future indications. We remain focused on executing our clinical programs with quality and efficiency, knowing that success in postpartum depression could unlock broader applications for our technology.
DA: At the time of the original spinout, was the company’s broader mission and vision well-defined, or has it undergone an evolution?
GM: When I came on board, our tactical goals were clear, but the broader vision was still taking shape. RE104 was already in development, and we were the only company in the world working on a 4-hydroxy-DiPT prodrug. Other companies were developing psilocybin and 5-MeO-DMT, but we saw an opportunity to carve out a unique niche in neuropsychiatry by offering a treatment that was both safe and efficacious while also being meaningfully differentiated from existing psychedelics.
The biggest differentiator for RE104 is its shorter psychedelic experience, which our phase I study confirmed to last approximately 3.6 hours. That’s significantly shorter than psilocybin, which typically lasts six to eight hours. If you ask most people whether they’d prefer to spend a full or a half-day of treatment, they’d say a half-day — and the same logic applies to patients, providers, and payers. A shorter treatment duration means a more efficient, scalable therapy that can be better integrated into existing healthcare systems.
Beyond the product itself, one of my strongest beliefs — and something that has shaped Reunion’s long-term vision — is the critical role of intellectual property in securing investment and ensuring that innovations can be fully developed. Psychedelic drug development requires significant financial backing, and investors simply won’t commit to funding clinical trials absent robust, enforceable intellectual property protection. Without it, a competitor could copy the molecule, undercut the market, and eliminate any potential return on investment.
That lack of IP protection is one of the key reasons the cannabis industry struggled to gain traction in the pharmaceutical space. There are likely many conditions where cannabinoids could be clinically beneficial, but without strong patents, companies were unwilling to invest the money needed for rigorous clinical development and regulatory approval. The result is an industry largely dependent on anecdotal evidence rather than validated, FDA-approved indications.
At Reunion, we took a different approach. Because RE104 is a novel prodrug, we secured composition-of-matter patent protection among a suite of patents through 2042, which gives us a long runway to explore multiple indications beyond postpartum depression. We now have the opportunity to build a strong, differentiated pipeline in neuropsychiatry while also offering investors and partners the confidence that they are backing a sustainable, defensible innovation rather than an easily replicable molecule.
DA: Is RE104 functionally analogous to psilocybin in terms of its mechanism of action?
GM: While nobody fully understands the precise mechanism of action of psychedelics, we believe that RE104, like psilocybin, works through serotonin 2A receptor activation, but with a dual-phase mechanism.
The first is an acute phase, which involves default mode network inhibition — essentially reducing rigid thought patterns and allowing for greater introspection, emotional processing, and potential resolution of trauma. This phase is what enables the profound psychological experiences associated with psychedelics.
The second is a neuroplastic phase, where the compound appears to promote the growth of new neuronal spines and the regeneration of atrophied connections that may have deteriorated due to chronic conditions like depression and anxiety. These changes help establish new neural pathways, which may contribute to lasting therapeutic benefits beyond the initial psychedelic experience.
This two-phase model is how we understand RE104’s effects and how it aligns with broader research on psychedelics as both an experiential and biologically reparative treatment.
This is where the name Reunion comes from: the ability to reconnect and reignite neural connections between atrophied neurons, connections that help the patient to regain connectivity to family, loved ones, and themselves, as they used to be.
DA: Will RE104 be administered in clinics consistent with the model established for ketamine treatment?
GM: The administration of RE104 will be very similar to what we’re currently doing in our clinical trials, and I expect it will resemble the existing model for esketamine (SPRAVATO) treatment. Right now, there are over 5,000 specialized treatment centers across the country administering SPRAVATO, and these clinics provide a well-established infrastructure for psychedelic-assisted therapies. Since the FDA will almost certainly impose Risk Evaluation and Mitigation Strategy (REMS) requirements on these molecules — at least in the near term — RE104 will need to be administered in a controlled setting with healthcare professionals closely monitoring the process.
By the time we bring RE104 to market, likely in late 2028 or early 2029, I anticipate that this infrastructure will have further evolved and matured. But even today, the foundation is strong, and we believe Reunion is well-positioned as a fast follower in this space.
In terms of the patient experience, the treatment will take place in a dedicated dosing room within a certified facility, and the patient will receive a subcutaneous injection administered by a healthcare professional. During the experience, they will likely wear blindfolds and listen to curated music in a carefully designed set and setting to ensure comfort and therapeutic effectiveness. Trained psychedelic monitors, who are healthcare professionals, will oversee the session, with medical doctors and nurses available on-site in case any support is needed. After the experience, patients will remain under observation for a period of time before discharge.
Psychiatrists will play a key role in referring appropriate patients to these specialized treatment centers, but RE104 is designed to expand — not replace — existing neuropsychiatric treatment options. The reality is that the toolkit for treating neuropsychiatric conditions remains quite limited, and the introduction of psychedelic-based treatments offers a much-needed new option. In some cases, RE104 could even be used as a first-line treatment, while in others, it may be integrated into a broader therapeutic plan.
I also don’t see FDA regulations as a major roadblock. Psychedelic treatments will require structured administration, but there are already established reimbursement codes for SPRAVATO and other treatments, which provide a framework for insurance coverage. As long as companies build within these existing regulatory and reimbursement structures, access to these therapies should be feasible.
DA: Can you expand a bit on the burden of disease of postpartum depression and current need for better treatments?
GM: Postpartum depression affects one in five perinatal individuals during pregnancy or up to one year after childbirth. It’s a significant and growing issue, with suicide and overdose being the leading causes of maternal morbidity. In fact, 80% of maternal deaths in the first postpartum year are due to mental illness, with suicide as the leading cause. Diagnoses of PPD have nearly doubled over the past decade, rising from 9.4% in 2010 to 19% in 2021, and today, around 500,000 women are diagnosed with postpartum depression each year in the U.S. alone.
Postpartum depression is an episodic and acute condition, meaning that a single-dose treatment has the potential to put a woman into remission. That’s why we believe RE104 is a perfect fit for this indication. Unlike chronic mental health conditions that require long-term maintenance therapy, postpartum depression is time-sensitive — patients need relief immediately, not weeks or months down the road. The patient population is also non-refractory, meaning that response rates can be higher compared with treatment-resistant depression or other forms of refractory depressive disorders.
We also saw a clear opportunity to be the only company in the United States developing a psychedelic therapy for postpartum depression. That gives us valuable white space to advance our clinical program efficiently, conducting a focused phase II proof-of-concept study with fewer patients and sites while still addressing a huge unmet medical need. If we demonstrate success in postpartum depression, it could set the stage for expansion into other depressive disorders, making this an incredibly important study for us.
DA: How does RE104 compare to other treatment options currently on the market?
GM: There’s only one other product currently approved by the FDA for postpartum depression — Zurzuvae. While it was an important step forward, it has several significant limitations. It requires daily oral dosing for 14 days, followed by a seven-day washout period before women can return to breastfeeding. That means women would have to stop breastfeeding for a full 21 days, which is a major barrier for many new mothers. It also comes with a black box warning for sedation, requiring patients to take it after 8:00 p.m. each night, they need to remember to take it every day, and avoid driving for 12 hours after each dose.
Beyond Zurzuvae, the standard treatment for postpartum depression is traditional antidepressants, typically SSRIs. These medications only work for about 30% of patients and can take six to eight weeks to show meaningful improvement. For a woman suffering from severe postpartum depression, waiting two months to see if a treatment works — knowing there’s only a one-in-three chance it will — is not a viable option.
RE104 offers a completely different approach. It’s designed to be rapid, effective, and administered in a single session. A one-and-done treatment could be life-changing for women struggling with postpartum depression, allowing them to quickly regain a sense of normalcy and return to their families and daily lives without prolonged suffering. If data from our phase I studies are confirmed in the ongoing lactation study, we will be able to show that the drug washes out rapidly as well, and so mothers could return to breastfeeding with very little to no risk of transferring drug to their child. Bonding through breastfeeding is very important to both the mother’s wellbeing, as well as for the child’s ultimate development trajectory.
Beyond the direct clinical benefits, we also see a growing shift in societal attitudes toward mental health and psychedelics. More patient advocacy groups are actively raising awareness and pushing for better screening and treatment options for postpartum depression. Right now, many women have very little follow-up care — in most cases, their last visit with an OB/GYN is six weeks after delivery, and then they’re on their own. Screening is inconsistent, and 50–70% of maternal mental health disorders go undiagnosed, while 75% of diagnosed cases go untreated.
I truly believe that stigma around psychedelic medicine will disappear within the next five years. We’re already seeing a shift with younger generations, particularly Gen Z, where mental health care is openly discussed, and therapy is widely accepted. For postpartum depression, where there’s such an urgent need for fast and effective treatment, I believe women will increasingly see psychedelic therapy as a powerful and legitimate option — a treatment that could help them quickly reconnect with their lives, their families, and their sense of self.
DA: How broadly do you see RE104’s potential across the family of depressive disorders and beyond? Do you have any preliminary data suggesting it could be extended to additional indications?
GM: In our phase I study in healthy volunteers, we demonstrated that RE104 has a strong safety profile, with side effects similar to psilocybin — mostly limited to mild, “day-of” symptoms like nausea and headache, which resolve quickly. The study also provided early indications that RE104 has a reproducible pharmacokinetic (PK) profile and a pharmacodynamic (PD) effect, suggesting it could offer therapeutic efficacy similar to psilocybin. While that’s promising, we’re now in phase II proof-of-concept studies to validate its effectiveness.
Our RECONNECT study, the 36-site, 72-patient phase II trial for postpartum depression, is a major milestone for the company. We intentionally named it “RECONNECT” because it reflects the goal of the treatment — helping women with postpartum depression reconnect with themselves, their families, and the world around them. More than half of the study is already enrolled, and we expect topline data in the second half of this year. The results from this study will be a key catalyst in determining how broadly we can expand RE104’s applications.
DA: Beyond postpartum depression, what additional indications are you exploring?
GM: From the beginning, we’ve seen the potential to extend RE104 into other areas of neuropsychiatry, and we’ve already laid the groundwork for our second major clinical program: adjustment disorder, a stress-related mental health condition that develops in response to a significant life stressor, such as a medical diagnosis, loss, or major life change, and causes marked distress or impairment.
The psychedelic renaissance in clinical research really began in the early 2000s when investigators at major academic centers explored the use of psychedelics in cancer patients. These patients often experience severe depression and anxiety directly linked to their diagnosis, and in five separate phase II trials, psilocybin demonstrated remarkable efficacy in helping them process their condition and significantly improve their mental health. While these were not registrational studies — meaning they weren’t structured for FDA approval — their results were compelling.
We recognized the strength of this data and approached the FDA early on about developing a trial in cancer-related psychiatric distress. The agency provided clear guidance that while the concept was valuable, the proper clinical indication wasn’t well-defined. However, adjustment disorder — a DSM-5-recognized condition — fit precisely within the scope of what we were aiming to treat.
Adjustment disorder is a unique and underappreciated diagnosis. It is distinct from major depressive disorder, treatment-resistant depression, or generalized anxiety — it’s a specific response to a major life event. Despite being a well-recognized psychiatric condition, there has never been an FDA-approved treatment for adjustment disorder, making it a huge unmet medical need.
The FDA was highly supportive of us pursuing this path. They recognized the clinical value and encouraged us to become a leader in this space. As a result, we are launching our phase II adjustment disorder study — the REKINDLE Study — later this year. We will be presenting a trial-in-progress poster at the Anxiety and Depression Association of America (ADAA) conference on April 5, formally signaling our expansion into this area. This study will focus primarily on cancer patients but will also include patients with other serious medical illnesses that can trigger adjustment disorder.
DA: Does Reunion plan to expand beyond these two indications?
GM: Absolutely. If we see positive data in postpartum depression, we believe there’s a strong rationale to expand into additional neuropsychiatric conditions, including generalized anxiety disorder (GAD), major depressive disorder (MDD), and treatment-resistant depression (TRD) — some of the largest and most established areas in mental health drug development.
We see RE104 as a pipeline within a product — a single compound with the potential to treat multiple, distinct psychiatric conditions. That’s possible because of the underlying mechanism of action, which we believe could be beneficial across a spectrum of mood and anxiety-related disorders.
Beyond RE104, we also have a preclinical asset, RE245, which represents the next evolution of our platform. RE245 is a non-psychedelic serotonergic neuroplastogen designed to provide therapeutic mental health benefits without inducing hallucinations. The goal is to create an oral 5-HT2A agonist that can offer the neuroplastic benefits of psychedelics without the experiential effects, potentially making it suitable for chronic outpatient use. This is an ambitious area of research; many companies are trying to develop non-hallucinogenic psychedelics, but nobody has fully proven the concept yet. Still, our chief scientific officer, Dr. Nathan Bryson, who led the development of RE104, is now driving this project forward. While still in early development, RE245 could represent the future of serotonergic neuroplasticity-based treatments.
DA: What’s the long-term vision for Reunion Neuroscience?
GM: Our longer-term future hinges on delivering in 2025. This year is about execution and quality — completing our trial successfully, meeting regulatory expectations, and establishing ourselves as a leader in psychedelic-inspired neuropsychiatry.
Beyond Reunion, 2025 is shaping up to be a big year for the entire neuropsychiatric field. Multiple companies — including us — are reaching key data readouts that could reshape investor interest in the sector. There was some negativity in 2024, including a notable FDA rejection of MDMA-assisted therapy for posttraumatic stress disorder, but that may have been the result of those trials being planned before the FDA released their 2023 clinical trial guidance on psychedelic drug development.
Reunion is much more strongly positioned for success. We launched our phase II study in the fall of 2023, after incorporating extensive FDA feedback to ensure alignment with the latest regulatory expectations. We’re not navigating uncharted territory — we’re following a clear regulatory roadmap, developing RE104 as a pure-play, small molecule therapeutic that meets the highest clinical and regulatory standards.
That’s the advantage of being a fast follower: we’re building on the lessons learned by early developers, leveraging the FDA’s playbook, and ensuring that when we bring RE104 to market, it has a clear, evidence-based path forward. The next year is all about delivering on that vision, and we’re very excited for what’s ahead.
At the same time, our vision goes beyond RECONNECT. We’re launching our second clinical program, REKINDLE, for adjustment disorder, and if we see positive data in postpartum depression, our next move will be a third clinical program in a larger psychiatric indication, such as MDD, TRD, or GAD.
What truly sets us apart is intellectual property. Many psychedelic drug developers are trying to bring products to market, but without strong IP protection, attracting investment is nearly impossible. RE104 has composition-of-matter patent protection through 2042, giving us a long runway to expand into multiple indications and build a differentiated, sustainable company.
We’re not just developing one drug — we’re developing a new class of psychiatric treatments that have the potential to reshape mental health care.
Learn more about the RECONNECT phase II clinical trial for postpartum depression.
Postpartum depression can leave you feeling lost, but there is hope for relief. Join us in a research study to learn whether a novel investigational treatment can improve symptoms of PPD in women like you — with a single dose. If you qualify, you’ll receive support every step of the way, including compensation for your time.