Rising High: Exclusive talk with biotech company Tryp Therapeutics

Tryp CEO talks psilocybin-assisted psychotherapy, challenges, opportunities and more

In this edition of "Rising High," The Fly conducted an exclusive interview with Jim Gilligan, chief executive officer of Tryp Therapeutics (TRYPF), a clinical-stage biotech company focused on developing psilocybin-based compounds for diseases with unmet medical needs. Here are some highlights:

PSILOCYBIN-BASED TREATMENTS: Tryp Therapeutics aims to develop psilocybin-based treatments for chronic pain indications and eating disorders. The company recently announced interim results of a Phase II trial of TRP-8802, a non-proprietary 25 mg oral capsule of synthetic psilocybin, for the treatment of binge eating disorder and is working to commence a Phase IIa clinical trial with the University of Michigan to evaluate TRP-8802 for fibromyalgia. The company is also developing TRP-8803, a proprietary intravenous infusion of psilocin to potentially improve efficacy, safety and the patient experience.

“What we have elected to pursue is an IV infusion of psilocin, which is the active molecule that is derived from psilocybin,” Gilligan said. “Psilocybin needs to be converted to psilocin in the body and then that molecule is what goes into the brain and induces a psychedelic state."

He noted Tryp’s approach is an ethical pharmaceutical approach, where the drug will be administered in combination with psychotherapy in the clinic. “Folks are aware in the sector now that blood levels are quite variable following oral administration,” the CEO said. “That could mean quite simply that folks are being underdosed, some folks get the right dose, and some have been overdosed.”

That variability from a clinical development standpoint creates a large risk factor for the space, he said.

“With an IV psilocin, you could start the IV and literally dial in the patient to the psychedelic state in fifteen minutes, maintain that blood level for the prescribed period of time, and if the patient has had a very profound experience, you can extend that as long as needed to have a meaningful clinical effect,” Gilligan said. “We feel we have the optimal way to administer the drug as part of the treatment.”

PHASE II BED TRIAL: In January, Tryp announced interim results for the first five patients dosed in its Phase II STOP trial. In collaboration with the University of Florida, the STOP trial evaluated TRP-8802 in patients with binge eating disorder. Previously, Tryp reported that immediately following the post-dosing integration session and throughout the four-week period post-dosing, the first patient in the STOP trial exhibited reduced overall anxiety, reduced anxiety around food, reduced compulsion to overeat and improved self-image and confidence. Analysis of the additional four patients reinforced the initial observations.

The results demonstrated a significant reduction in the frequency of binge eating behavior for each patient as measured in multiple assessments of efficacy. Across all patients, daily binge eating episodes were reduced by an average of 80.4% from baseline during the four-week post-dosing measurement period, with all patients reporting a daily reduction in binge eating episodes of at least 60% from baseline. Four of five patients reported at least a 75% reduction in daily binge eating episodes from baseline during the four-week post-dosing measurement period. The number of daily instances of patients feeling that they had lost control over their eating were reduced by an average of 81.6% during the four-week post-dosing measurement period, with four of five patients reporting a reduction of greater than 70%. In addition, analysis of the Hospital Anxiety and Depression Scale anxiety and depression scores demonstrated improving trends related to patients’ levels of anxiety and depression.

“We were very pleased in our interim analysis to show that there was an 80% mean reduction in binge eating episodes,” Gilligan said. “One of the questions that the therapists felt was important was how many times did people feel that they lost control of their eating behavior? That was reduced by 84%, so both of those results are striking.”

He noted the company also saw durability of the response for out to sixty days.

"We did take a risk when we targeted binge eating disorders, but I think this data certainly validated us going in this direction,” the CEO said. “This tees us up so that we can use BED as one of our first patient studies where we are going to introduce TRP-8803.”

The Phase II trial results exceeded Tryp’s expectations making management believe binge eating disorder is a very attractive target for the company to advance TRP-8803, he said. “8803 will be what we bring forward into all the larger clinical studies and eventually commercialize because of the attributes,” Gilligan said, “For us, it was a resounding success. It helps us now focus our next step in binge eating on how we will use 8803 and lends credibility to our overall approach of doing small exploratory studies with 8802, followed by studies with IV psilocin.”

MGH COLLABORATION: Additionally in January, Tryp announced the signing of a letter of intent with Massachusetts General Hospital to fund and conduct a Phase 2a clinical trial investigating the effects of psilocybin-assisted psychotherapy in the treatment of patients suffering from irritable bowel syndrome. The planned study will evaluate the effect of psilocybin-assisted psychotherapy in patients with treatment-resistant IBS who experience chronic abdominal pain and other debilitating gastrointestinal symptoms. The primary efficacy endpoint of the study will be improvement in abdominal pain. The study will also explore changes in brain connectivity and responses to pain at baseline, at four weeks, six months and twelve months, post-the psychedelic session, along with numerous other secondary endpoints.

“Harvard MGH sought us out,” the CEO said. “It wasn’t like we were sitting there saying we should go after IBS, they actually came to us.” He said the school looked at different companies within the space and noticed Tryp’s FDA success, in-house drug development expertise and previous collaborative relationships with different institutions. 

“They educated us into why they felt psilocybin-assisted psychotherapy would be a benefit for their patients,” Gilligan said.  “They mentioned to us that actually about 35% of people with IBS also have fibromyalgia and went into deeper science on the brain-gut access.” The body has a whole system of feedback between the gut and the brain with the predominant neurotransmitter being serotonin, he said, the receptor which Tryp has been targeting in the brain. “Of course, we would be targeting receptors in the GI, and there’s another whole series of clinical and scientific pieces of information that suggest it would be a benefit,” the CEO said. “The primary interest here is that many of these patients have chronic abdominal tenderness and pain and it’s disruptive to their lives. We’ll really focus on this abdominal pain."

PHASE 2A FIBROMYALGIA STUDY: In December, Tryp noted it was preparing for a Phase 2a trial using TRP-8802 to evaluate psilocybin-assisted therapy among patients with fibromyalgia, in partnership with the University of Michigan, expected to commence in the first half of 2023.

“We received a letter from the FDA that we could proceed with that study at the end of December of last year and we literally just received the final paperwork from the Michigan DEA this week,” Gilligan said. “The problem with these timelines is the DEA.” He said the company is in discussions with researchers currently on whether a refresher course in psychotherapy is necessary following the delay. “They’re eager to get started so if I had to go down to Vegas and bet, I think they’ll start absolutely Q1 this year,” the CEO said. “They just sort of have to dust off the cobwebs and line everything up.”

He added like the binge eating study, Tryp is looking for a signal to determine the potential for TRP-8803 in fibromyalgia.

“We’ll be looking at pain scales and also changes in sleep,” Gilligan said. “A lot of people with fibromyalgia have problems sleeping and they also have anxiety and depression, so we’ll be looking at the same constellation of endpoints. The most important thing will be, not just attention to pain, but the patient’s relationship to that pain and their functionality. We’re optimistic that we’ll see a positive response. “

He noted Tryp gave a single infusion of psilocybin to a fibromyalgia preclinical model at the University of Michigan and saw a statistically significant decrease in pain that existed out for 28 days.

“We saw a robust response and given our understanding of the disease, our expectation is to see a benefit in this patient population,” the CEO said.

TRP-8803: In October, Tryp announced that the World Intellectual Property Organization published their international patent application covering the intravenous administration of psilocybin and psilocin. The PCT application, titled “Improved Methods For The Use of Psychedelics” expands and strengthens the IP related to the company’s development of TRP-8803.

“For me, the first benefit is I don’t have to say to people anymore, ‘We have this secret sauce and it’s awesome. Trust me,’” Gilligan said. “We can actually explain to people what we are doing.”

He added the initial review of the patent application found several claims both novel and inventive.

“That speaks volumes for the fact that it gives a high likelihood that these claims will issue and in particular, because we had a fair amount of actual data in our patent application that supported claims,” the CEO said. “That’s very, very encouraging. In addition, we continue to file provisional patents in unique indications. We now have provisional patents to cover IBS, fibromyalgia and binge eating.”

Tryp has been taking steps to advance its proprietary TRP-8803 programs into clinic and has made 8803 the company’s top priority, he said.

“Initially we believed that since in the body you convert psilocybin to psilocin, we would be able to use a lot of data that has historically been used to allow people to use psilocybin in the clinic,” Gilligan said. “The FDA took a conservative position, which we understand, as we’re changing the route of administration to IV and giving a different molecule. Although that was tremendous for us on the IP front and gave us a very strong patent position, we ended up having to do a series of bridging toxicology studies.”

He said Tryp took considerable time and resources, close to $1M in funds, to complete those studies, which turned up no safety signals.

“Traditionally, if I have a brand-new chemical entity that has never been administered to humans, you do what is called an ascending dose study,” the CEO said. “In our case, we know what the circulating levels of psilocin are following administration and in order to move forward more quickly, we decided that we would do those first in healthy volunteer studies outside of the U.S. Certain countries like the UK, Canada, and Australia make it much easier to perform those initial studies.”

The company plans to focus on the loading dose and the maintenance dose in the initial studies to allow for a broad range of both drug exposure and duration data to support use in future patient studies, he said.

“We’ll go up to two hours and share that data with the FDA,” Gilligan said. “Here is the starting dose, the maintenance dose, the duration and the safety profile. By having the data from outside the U.S. it is no longer theoretical and that would allow us to proceed directly with that data into patient studies.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic space, the CEO pointed to the Schedule I listing of psilocybin and psilocin under the Controlled Substances Act.

“It’s a hugely difficult barrier to overcome especially when it is not only federal, but state-to-state,” he said. “I think that’s one of the biggest challenges. At the national phase the DEA has been more consistent, you can count on a response in six to eight weeks. The wild part is at the state level.”

Gilligan also cited the need for adequate investment to support programs in the biotech sector as another obstacle for the industry.

“As more and more positive data becomes available, it is going to require additional clinical studies, and additional clinical studies will require additional funding resources,” he said. “All of that needs to go hand in hand, but clearly reducing the complexity of being able to perform FDA-approved clinical studies will be significant.”

OPPORTUNITIES: As the psychedelic industry develops and matures, the CEO noted there are several companies advancing programs in the space as it gains more and more credibility amid emerging positive critical data.

“Tryp on its side is opening up a wide range of opportunities in nociplastic pain between phantom limb, fibromyalgia and complex regional pain syndrome,” he said. “When we look at binge eating, there’s also an opportunity in the broader range of obesity.”

Gilligan cited learnings from collaborators that showed after three of four years, a large sum of people who have had gastric bypass surgery start to gain the weight back.

“They restricted caloric input by physical limitations but haven’t changed their behavior,” he said. “We do believe that our approach has a clinical benefit to those outside of just binge eating. And if you look at pain, a third of fibromyalgia patients resort to opioid use. Opioid use is a tremendous problem, so the ability to reduce opioid use is tremendous. The potential in this field is enormous.”

OTHER CANNABIS/PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Acreage (ACRHF), Akerna (KERN), Aleafia (ALEAF), Atai Life Sciences (ATAI), Awakn Life Sciences (AWKNF), Audacious (AUSAF), Aurora Cannabis (ACB), Ayr Wellness (AYRWF), BC Craft (CRFTF), Body and Mind (BMMJ), CanaFarma (CNFHF), Cannara Biotech (LOVFF), Canopy Growth (CGC), RIV Capital (CNPOF), Chicago Atlantic (REFI), Columbia Care (CCHWF), Compass Pathways (CMPS), CordovaCann (LVRLF), Clever Leaves (CLVR), Cresco Labs (CRLBF), Cronos Group (CRON), CV Sciences (CVSI), Curaleaf (CURLF), CURE Pharmaceutical (CURR), Delic Holdings (DELCF), Delta 9 (DLTNF), Entourage Health (ETRGF), Fire & Flower (FFLWF), Flora Growth (FLGC), FluroTech (FLURF), General Cannabis (CANN), Goodness Growth (GDNSF), Greenlane (GNLN), Green Thumb (GTBIF), GrowGeneration (GRWG), Harborside (HBORF), Hemp (HEMP), HEXO (HEXO), High Tide (HITI), Innovative Industrial Properties (IIPR), IM Cannabis (IMCC), India Globalization Capital (IGC), Indiva (NDVAF), InterCure (INCR), Wellbeing Digital (KONEF), Khiron Life Sciences (KHRNF), Lowell Farms (LOWLF), Lotus Ventures (LTTSF), MediPharm (MEDIF), MedMen (MMNFF), MJardin Group (MJARF), Neptune Wellness (NEPT), NewLake Capital (NLCP), Thermic Science (ENDO), Organigram (OGI), Planet 13 (PLNHF), Relmada (RLMD), RYAH Group (RYAHF), Sproutly (SRUTF), Stem Holdings (STMH), Small Pharma (DMTTF), Skye Biosciences (SKYE), Sundial Growers (SNDL), Sunniva (SNNVF), TerrAscend (TRSSF), Tetra Bio-Pharma (TBPMF), Tilray (TLRY), Trulieve (TCNNF), Valens (VLNCF), Verano Holdings (VRNOF), Village Farms (VFF), Wesana Health (WSNAF), Zynerba (ZYNE) and 4Front Ventures (FFNTF).

Keywords: cannabis, stocks, cultivation, legalization, CBD, THC, psychedelics, ketamine, psilocybin, LSD, MDMA, psilocin