Psychedelic: Exclusive talk with biopharma company Reunion Neuroscience

In this edition of “Psychedelic”, The Fly conducted an exclusive interview with Greg Mayes, President and Chief Executive Officer, Mark Pollack, Chief Medical Officer, Nathan Bryson, Chief Science Officer and Mark Theeuwes, Chief Operating Officer, at Reunion Neuroscience, a biopharmaceutical company committed to revolutionizing the treatment of mental health disorders through next-generation psychedelic-inspired therapeutic solutions. Here are some highlights:

PSYCHEDELIC DRUG DEVELOPMENT: Reunion, a clinical-stage company that became private in 2023, is actively investigating the use of its lead product candidate, RE104, in postpartum depression, PPD, and adjustment disorder, AjD, as well as in additional neuropsychiatric indications where there remains a significant unmet need.

“Reunion remains the only drug developer of 4-hydroxy-DiPT prodrug in the world,” President and CEO Greg Mayes said. “That is the cornerstone of our growth strategy moving forward in terms of trying to maximize the value and the impact of what that drug could bring to the world. We believe it is fast-acting, has rapid onset and can be highly differentiated to other psychedelic drug therapeutics. With that background, we intend to take the product into areas of high unmet medical need where there are not adequate remedies.”

The compound, which has been developed as a subcutaneous injectable, is easy to use, reasonably short in terms of duration and reproducible in its pharmacokinetics, CSO Nathan Bryson said.

“In the case of mothers or other patients, they only have to stay in the clinic for about a half of a day,” he said. “As a subcutaneous injectable, the drug is very simple to administer and it also gives the shortest, fastest routes for the drug to get into the system and get out of the system.”

The CSO added that the reproducible pharmacokinetics in terms of psychedelic experience allows clinicians monitoring a patient to know the trajectory of the psychedelic trip, including the maximum concentration of the plasma, which corresponds to maximum effect.

“That allows practitioners to be present for the patient, if needed, at the right time,” he said. “Additionally, this is a brand-new chemical entity, which means that we have intellectual property. It won’t be genericized right away, so we have a certain amount of time to develop our molecule, get it to market, develop the indication space, make sure we can meet the needs of as many patients as possible and become a profitable company.”

RECONNECT PHASE 2 TRIAL: In August, Reunion announced topline results from its RECONNECT Phase 2 clinical trial evaluating RE104 in adult female patients with moderate-to-severe PPD. COO Mark Theeuwes said Reunion chose to focus on PPD after evaluating the target product profile the company was hoping to achieve and seeing what was currently available in the market.

“There is Zurzuvae/zuranolone, brexanolone, that was recently removed from the market, and SSRIs,” he said. “Certainly, something that you could provide a single dose of, and which could offer a significant amount of relief would be ideal in this space. Ultimately, we looked at this population, which is a typically non-refractory population, meaning that these moms haven’t tried a bunch of things, and what happens with a non-refractory population is you tend to see a bigger effect. Obviously if you look at our results, you saw an enormous effect.”

As PPD is an acute indication and does not require repeat dosing, the company’s assumption was that treatment could be done with a single dose, the COO said.

“We were able to prove that the moms stayed healthy throughout the entire 28 days,” he said. “When you look at the entire package and how we started the company, what we anticipated our target product profile to be, which ended up by and large happening, could really be a paradigm shift in how mothers could be treated in this space.”

RECONNECT met its primary endpoint with a single 30mg subcutaneous dose of RE104 demonstrating a statistically significant reduction from baseline of 23.0 points in the Montgomery-Åsberg Depression Rating Scale total score on Day 7, as compared to a reduction of 17.2 points in patients treated in the active control arm with a 1.5mg dose of RE104. Clinically meaningful reductions in MADRS were observed for RE104 30mg on the first day following administration and maintained through the Day 28 follow-up. 77.1% of patients treated with RE104 30mg demonstrated a response to therapy at Day 7, as compared to 61.6% of patients who received active control. 71.4% of patients treated with RE104 30mg were in remission at Day 7, as compared to 41% of patients who received Active Control. Both response and remission rates were maintained through the Day 28 follow-up.

“We were very pleased to see that we had a positive study that met the primary outcome point,” said CMO Mark Pollack. “These women with PPD had significant improvement in their depressive and related symptoms compared to the control group. One of the most striking findings was not just that it was better compared to control, but that 70% of these women were in remission rapidly after taking the drug. They were not just better, but essentially well and that really is ultimately the goal of treatment.”

When looking at PPD, Reunion was not just thinking about the moms, but the fact that those affected moms have trouble caring for their babies in the way that they would like, he said.

“We assessed those mothers with an instrument called the Barkin Index of Maternal Functioning, which asked how they are doing in the day-to-day management of the babies and the nature of the relationship,” the CMO said. “There too, we saw really substantial improvement for our treated patients. It implies we are not just helping the moms, which is of course critical, but it has a downstream positive effect on the babies and their development.”

Additionally, the drug was generally well-tolerated and displayed a fast onset of activity that tended to wear off quickly with patients ready to go home in about four hours, he said.

“We will be able to get women home relatively quickly back to their families and clinicians will be able to provide access to care by being able to see more patients in a given time period,” Pollack said.

NEXT STEPS: Reunion remains on track for commencement of a Phase 3 program in PPD in 2026, Mayes said.

“We’ll be going to the FDA with the results of this study and plans going forward, so we can optimize our next set of studies,” Pollack said. “Given the robust response in this Phase 2 study, we’re optimistic that we are going to see positive results in our Phase 3 study, which will likely be larger and will probably include a placebo. We may be looking at intermediate doses as well to make some sense of dose response relationships.”

CLINICAL LACTATION STUDY: Along with RECONNECT study results, Reunion announced initial data from its clinical lactation study. Preliminary results from the study suggest that the total amount of metabolites observed in the breastmilk represents less than 0.1% of the 30mg RE104 administered to the mother, an order of magnitude below the level that might potentially cause risk to the infant. Reunion believes these results suggest that mothers who wish to return to breastfeeding following RE104 treatment may be able to do so with limited interruption.

“What we observed was that essentially the drug was getting to what I consider not clinically relevant concentrations in a very, very short period of time,” Bryson said. “It’s possible that we may be able to get mothers back to breastfeeding in a very limited span of time, probably hours versus days to get back to breastfeeding their infant. This is going to add to the overall efficacy of the drug and improves the real utility of this drug in PPD.”

AJD: Reunion is also evaluating RE104 as a potential treatment for AjD in cancer and expects to initiate the REKINDLE Phase 2 trial in Q3.

“The return of psychedelics to be considered as therapeutics for people with mental health issues was to a large extent stimulated by findings that started to emerge over the last decade or so, in which patients who had cancers or other life-threatening illnesses were given psychedelics,” Pollack said. “They were seen to have a gratifying response, a sense of improvement in their mood, a lack of depression and a sense of acceptance and peace. Those findings really extenuated general interest in psychedelics.”

He noted there are a significant number of patients with serious medical illnesses like cancer, who are having adjustment difficulties or having depression and anxiety related to their diagnosis.

“There is evidence that psychedelics may have a role to play,” the CMO said. “We think this disorder is an area where we can have a big positive impact in terms of improving and helping affected individuals. What we would like to show in the study is that in treating individuals who are having depression or elevated difficulties adjusting to their medical illness, we can demonstrate a significant improvement in their mood, their functioning and their sense of peace and comfort.”

NON-PSYCHEDELIC RE245: Reunion has also advanced lead candidate RE245, a discovery-stage, non-psychedelic asset, for application in chronic treatment paradigms and plans to file an Investigational New Drug application in 2026.

“Psychedelics require patients to go into a clinic and be monitored for a certain amount of time,” Bryson said. “Being able to take away the psychedelic effects means we could have drugs that can be taken at home by patients, resulting in a lot more convenience.”

As part of Reunion’s non-psychedelic research, the company built a whole library of molecules, found certain safety aspects and designed RE245, the CSO said.

“The idea is that you can have a non-scheduled take home medication that is safe and effective,” he said. “You’re getting back to a novel, classical therapeutic and it could have a significant amount of uptake. We also designed certain safety features into it so that it could be potentially administered every day and we’re looking to take this drug down the path of treating more chronic indications in the neurological space. We are currently in the throes of preclinical assessment of the molecule to build our safety package that we would present to the FDA toward the end of 2026, so we can do some initial studies in humans in 2027.”

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act including MDMA, psilocybin and DMT, but Mayes said he believes scheduling will be overcome with the development and FDA approval of psychedelic therapeutics that have gone through the appropriate safety and efficacy studies.

“I think just like any other medication, these drugs will go through the proper channels to demonstrate safety and efficacy, will get put on the market with reimbursement and patients will open up to it,” Bryson added. “There’s a general acceptance in the population that these drugs can be effective and safe over time and that’s going to increase usage and help more people.”

TRUMP ADMINISTRATION: In the 2024 election, Donald Trump was elected president and in subsequent months, several of his administration’s appointees have made positive remarks regarding psychedelics.

“We welcome the positive and open mind that the new administration has for psychedelic drug development,” Mayes said. “The situation has gone from good to great because prior to the Trump administration, the FDA promulgated in 2023, the clinical trial guidance for psychedelic drug development. When you combine the clinical trial guidance, the FDA’s openness to consider it and now the administration that came in 2025, you have a nice opportunity for us, if we can sustain safe and efficacious molecules, to see the approval of psychedelic therapeutics in the coming years.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic biopharma space, the CEO said he believes limited infrastructure is a big challenge as it makes it very difficult to run clinical trials.

“There are not that many clinical trial sites in the U.S. that are fully trained and have the capacity to run multiple trials,” he said. “For this sector to really maximize its opportunity, one of the challenges is to have more clinical trial sites up and running that are willing to and trained in how to run psychedelic trials.”

OPPORTUNITIES: As the psychedelic biopharma industry develops and matures, Mayes said Reunion is excited to take its data into other indications as well as move its PPD program forward.

“We now have proof of concept data that suggests that we have an active drug that can help not only women with PPD, but potentially cases with other mental health disorders that are not being treated right now,” he said.

Bryson added there is not only a growing acceptance in the patient population, but also amongst big pharma, which could offer opportunities in the near future.

“They’re starting to dip their toe into the space,” he said. “If you want to get the maximum expansion of these drugs into the market and reach the greatest number of patients, we need those big pharma muscles to get out there, do the sales and marketing that needs to be done and make this the giant success that we think it can be.”

“The regulatory environment has improved, clinical trials have read out with some positivity, and investors investing in psychedelic companies is on the rise,” Mayes said. “These companies are now more investable than they ever been and, in some cases, derisked to a certain degree because the data that has been generated.”

PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Algernon Pharmaceuticals (AGNPF), Allied Corp. (ALID), atai Life Sciences (ATAI), BetterLife (BETRF), Bright Minds Biosciences (DRUG), Compass Pathways (CMPS), Clearmind (CMND), Cybin (CYBN), Enveric Biosciences (ENVB), Filament Health (FLHLF), GH Research (GHRS), Incannex (IXHL), Mind Medicine (MNMD), MIRA Pharmaceuticals (MIRA), Numinus Wellness (NUMIF), NRx Pharmaceuticals (NRXP), Pasithea Therapeutics (KTTA), PharmAla (MDXXF), PharmaTher (PHRRF), Psyence Biomedical (PBM), Psyence Group (PSYGF), Relmada Therapeutics (RLMD), Revive Therapeutics (RVVTF), SciSparc (SPRC), Seelos Therapeutics (SEEL) and Silo Pharma (SILO).