Rising High: Exclusive talk with biotech company Tryp Therapeutics

In this edition of “Rising High,” The Fly conducted an exclusive interview with Jim Gilligan, Chief Scientific Officer, and Peter Molloy, Chief Business Officer, of Tryp Therapeutics (TRYPF), a clinical-stage biotech company focused on developing intravenous-infused psilocin for diseases with unmet medical needs. Here are some highlights:

PSILOCYBIN-BASED TREATMENTS: Tryp aims to develop novel formulations for the administration of psilocin in combination with psychotherapy to treat diseases. The company’s lead program, TRP-8803, is a proprietary formulation of IV-infused psilocin designed to alleviate the shortcomings of oral psilocybin. Tryp has completed a Phase 2a clinical trial for the treatment of Binge Eating Disorder at the University of Florida and has started a Phase 2a clinical trial with the University of Michigan for the treatment of fibromyalgia. The company is also preparing to initiate a Phase 2a clinical trial with Massachusetts General Hospital for the treatment of abdominal pain related to irritable bowel syndrome. Each of these studies are utilizing TRP-8802, a synthetic, oral psilocybin, to demonstrate efficacy. “We have been advancing those core programs, but the thing we have been spending most of our recent time on is moving forward the IV-infused psilocin study,” Gilligan said. “We were looking at different sites where we could move this program forward quickly and we evaluated a number of areas in Canada, the UK and Australia.”

The company ultimately decided that Australia afforded Tryp several distinct opportunities, he said. “Just from a clinical perspective, there is an ease of performing the study and of course, there is the 43% corporate rebate on the cost,” the CSO said. “That in and of itself was attractive and then through our board and one of our founders, it also became apparent Australia had a conducive environment from a financial and a corporate growth perspective.”

He noted Tryp has decided to establish the company as a legal corporate entity in the country as the Therapeutic Goods Administration wants to facilitate psychedelic research. “That environment is more conducive to conduct of clinical studies and the beauty of Australia is that the Food and Drug Administration will accept the data,” Gilligan said. “We can go through and create significant data sets that we can use not only in Australia, but in Europe or the U.S. Our goals remain the same: to advance IV psilocin, to fortify our position in our unique areas, but to also position the company in a business environment where we can meet our financial growth needs.”

EXOPHARM AGREEMENT: In December, Tryp announced an arrangement agreement with Exopharm, pursuant to which Exopharm will acquire all the issued and outstanding common shares of Tryp in consideration of 4.52 ordinary shares of Exopharm for each Tryp share. The agreement represents a aggregate transaction value of approximately $12.8M. The majority of directors of the combined entity will be appointed by Tryp, and Tryp’s clinical programs and development strategy will remain as the foundation of the entity. The combined company is expected to relist on the Australian Securities Exchange in Q1. “Tryp will be the largest part of the combined entity, so you could look at it as a reverse takeover in that sense,” Molloy said. “We will also be the majority of the board as well, so we are the decision makers, and Tryp’s programs will be the focus of that company.”

Tryp decided to enter into the agreement as the company was at a pivotal point where it needed further investment, he said. “The Canadian Stock Exchange just hasn’t been supportive of small biotech, where in Australia there is a great interest in the psychedelics movement,” the CBO said. “The TGA has rescheduled psilocybin and MDMA and provided a path for psychiatrists to prescribe it for two specific indications, and there is a lot of investor interest in Australia for this.”

He added Exopharm presented a good merger opportunity as the company has cash on the balance sheet, a supportive shareholder base and experienced directors who will be staying onboard. “It was a good fit for us, and we are excited about what it means for the acceleration of the company,” Molloy said.

PHASE 2A BED TRIAL: Tryp recently completed a Phase 2a clinical trial for the treatment of Binge Eating Disorder at the University of Florida, which demonstrated an average reduction in binge eating episodes of greater than 80%. “This was very rewarding for us because we elected to go down a path not well trodden,” Gilligan said. “We elected to look at areas of indications that were distinct from some of the other companies and the first that we ventured into was eating disorders.”

He said there was no guarantee that the company would see a beneficial effect, but Tryp management was confident from a clinical and scientific perspective. “We were very, very pleased with the results that we have seen,” the CSO said. “It fits in with some of the results from other studies looking at psilocybin-assisted therapy, where you see the drug helps with behavioral modification. It not only has a benefit on the primary indication, but you also see improvements in anxiety and depression scores.”

The results reaffirm Tryp’s strategy of identifying areas where psilocybin-assisted therapy would have a benefit and then using that information to transition to TRP-8803, he said. “As we go forward, we think that these results certainly justify us now exploring the benefits of IV-infused psilocin in this patient population,” Gilligan said. “It has reinforced our strategy and we’re just hoping that we see similar results in both the fibromyalgia and the IBS study.”

PHASE 2A FIBROMYALGIA STUDY: The company also recently started a Phase 2a clinical trial with the University of Michigan for the treatment of fibromyalgia. “We went through the FDA process, received a notice of allowance to proceed and received the DEA approval,” the CSO said. “The study is progressing, and I think after the holidays, we’ll be making some announcements with respect to that program.”

He said the company’s expectation for the study is to see an improvement in pain scores, but also an improvement in anxiety and depression scores. “Our confidence is fairly high,” Gilligan said. “We did do some preclinical work in this area with the IV infusion and demonstrated a significant reduction in pain in preclinical models of fibromyalgia. We’re cautiously optimistic and after the holidays, we’ll have some updates.”

PHASE 2A IBS TRIAL: Tryp is also preparing to initiate a Phase 2a clinical trial with Massachusetts General Hospital for the treatment of abdominal pain and visceral tenderness in patients suffering from IBS. “We received the notice of allowance from FDA, successfully completed ethics review and now we are in the process of obtaining the DEA license so that we can ship the clinical trial material to MGH,” the CSO said. “The folks have been trained there so that they’re ready. It’s going pretty well and we’re planning to hopefully get the DEA license in Q1 and initiate that study.”

The primary endpoint in the IBS study is improvement in abdominal pain and visceral tenderness, he said. “What’s interesting about some of these patients is that when GI specialists look and the inflammation has decreased, from a GI perspective there has been improvement, yet patients still have this ongoing pain and discomfort,” Gilligan said. “It fits a little bit into this nociplastic pain model and as we have discussed, there is the gut/brain access where the signaling from the brain to the gut back and forth is predominantly handled through serotonin receptors. We think there is a sound scientific rationale for using this approach in this patient population.”

TRP-8803: TRP-8803 is the company’s proprietary formulation of IV-infused psilocin designed to overcome the limitations of orally administered psilocybin, including high patient variability in terms of drug blood levels and long duration of treatment. “We did a canvas of where an ideal area might be to perform these first-into-human studies and we selected Australia,” the CSO said. “We’ve selected a site, located in Adelaide, and they have an outstanding Phase I unit. Our plan is to administer IV psilocin to optimize both the dose and the infusion rate.”

People have predicted that a certain dose over a certain infusion period should achieve a certain blood level, but Gilligan noted that is currently hypothetical. “The other thing is no one has really performed a definitive study to correlate blood levels to a psychedelic state, so that is what we will be doing,” he said. “In the interest of safety, we start at a low dose. We have what is called the loading dose, we give a certain dose to achieve and hold that blood level, and then we slow down the infusion rate to maintain that blood level up to a couple of hours.”

Tryp will be analyzing a patient’s brain activity with real time EEG measurements as well as having them recount their experience in the study, the CSO said. “That is going to give us the opportunity to identify what the exact dose needs to be and what the infusion rates need to be for each of the three blood levels that we’re targeting,” he said. “By the end of the study, we’ll have a good understanding of what doses and infusion rates you need to achieve a range of blood levels. Once we have that, we have the foundational information we need to advance into patient populations, and we’ll know exactly what dose and infusion rates we want to bring into certain indications.”

The approach also enables Tryp to bolster its ability to answer scientific clinical questions, Gilligan said. “For example, people say, ‘You’re doing this binge eating study, but what if you are going to target patients that have a higher BMI, would it be a higher dose?'” he said. “With our approach, we can take a cohort of three or four obese patients, give them a dose and determine whether or not the blood levels are the same or whether it needs to be adjusted. It really gives us the ability to customize our approach for different indications.”

MAPS NDA: The Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation recently submitted a New Drug Application to the FDA for MDMA-assisted therapy for post-traumatic stress disorder. “All ships rise with a rising tide,” Gilligan said. “The filing demonstrates that there is a utility for these types of drugs and I think many of the logistical issues associated with psychedelic assisted therapy will now start to be addressed.”

Those issues include clarity around commercialization and building the psychotherapy foundations necessary for these treatments, he said. “It’s a positive step that will help the companies that are still in development,” the CSO said. “That’s important for us and a benefit for the industry.”

Molloy agreed, stating the filing is a huge step for the psychedelic sector. “It is just going to broaden the conversation on psychedelics to make it a household topic,” he said. “The narrative is going shift. It is really positive having this out there and it’s going to lead to a significant uptick in patient acceptance when it becomes normalized to have this type of treatment.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic space, Gilligan pointed to the current scheduling of psilocybin as Schedule I under the Controlled Substances Act. “From a Tryp perspective, where we were looking to advance our programs into clinic and to potentially launch our studies here in the states, the current scheduling and the impact of requiring a DEA license created a challenge,” he said. “To be fair the DEA isn’t usually accustomed to reviewing clinical protocols. I’m hoping that there is some movement in Congress and there’s some recognition of the clinical benefits of these molecules. “

Molloy added another issue facing the sector is the traditional biotechnology business model. “There’s a well-trodden business model for biotech where you simply progress a drug to proof-of-concept and then you out license it to major pharma,” he said. “They have got the sales and marketing infrastructure to build a bigger revenue opportunity. We just don’t know quite how well that is going to work out. How far will biotech have to take it? Will pharma want to come in at all? Alot of that is going to change now that we have MAPS and over the next two years, we’re going to get a lot more clarity. But that lack of clarity on the business model has been a hindrance to getting the big institutional investors to come in.”

OPPORTUNITIES: As the psychedelic industry develops and matures, the CSO said Tryp is most excited about conducting the TRP-8803 study and developing that asset. “That gives us the ability to then look at how we can advance 8803 into these indications,” he said. “From our perspective, as the field advances and more academic and company research demonstrates clinical utility of psilocybin-based therapies that opens the door for 8803. Our internal feeling is that 8803 will be applicable in any indication where psilocybin-assisted therapy has proven to be a benefit.”

Gilligan said throughout Tryp’s operations, the company has developed a better understanding of mechanism of action, process, and drug administration. “The entire field is learning and advancing,” he said, “I do believe that our data will advance the field significantly with a better understanding of the relationship between blood levels and psychedelic states as well as what blood levels are needed to treat different indications. The better we understand things, the broader acceptability we’ll get from patients at large.”

CANNABIS/PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Aleafia Health (ALEAF), Acreage (ACRHF), Atai Life Sciences (ATAI), Audacious (AUSAF), Aurora Cannabis (ACB), Avant Brands (AVTBF), Ayr Wellness (AYRWF), Awakn Life Sciences (AWKNF), Body and Mind (BMMJ), BZAM (BZAMF), Cannara Biotech (LOVFF), Canopy Growth (CGC), Chicago Atlantic (REFI), Clearmind (CMND), Clever Leaves (CLVR), CordovaCann (LVRLF), Cresco Labs (CRLBF), Cronos Group (CRON), Columbia Care (CCHWF), Compass Pathways (CMPS), CURE Pharmaceutical (CURR), Curaleaf (CURLF), CV Sciences (CVSI), Cybin (CYBN), Delic Holdings (DELCF), Delta 9 (DLTNF), Entourage Health (ETRGF), Enveric Biosciences (ENVB), Fire & Flower (FFLWF), Flora Growth (FLGC), General Cannabis (CANN), Goodness Growth (GDNSF), Greenlane (GNLN), Green Thumb (GTBIF), GrowGeneration (GRWG), Hemp (HEMP), High Tide (HITI), India Globalization Capital (IGC), Indiva (NDVAF), Innovative Industrial Properties (IIPR), InterCure (INCR), IM Cannabis (IMCC), Wellbeing Digital (KONEF), Khiron Life Sciences (KHRNF), Lowell Farms (LOWLF), Lotus Ventures (LTTSF), Lucy Scientific Discovery (LSDI), MediPharm (MEDIF), MedMen (MMNFF), MindMed (MNMD), NewLake Capital (NLCP), Numinus (NUMIF), Organigram (OGI), Planet 13 (PLNHF), Reunion Neuroscience (REUN), Revitalist (RVLWF), RIV Capital (CNPOF), Relmada (RLMD), RYAH Group (RYAHF), Safe Harbor Financial (SHFS), Small Pharma (DMTTF), SNDL (SNDL), Sproutly (SRUTF), Skye Biosciences (SKYE), Stem Holdings (STMH), Sunniva (SNNVF), TerrAscend (TRSSF), Tetra Bio-Pharma (TBPMF), Tilray (TLRY), Trulieve (TCNNF), Tryp Therapeutics (TRYPF), Verano (VRNOF), Village Farms (VFF), Wesana Health (WSNAF), Zynerba (ZYNE) and 4Front Ventures (FFNTF).