FT-104: A Goldilocks Molecule? Field Trip Patent Application Reveals Nature of Company’s Lead Candidate

Like many psychedelics companies, Field Trip has sought to diversify itself across a number of different business areas (or, ‘value chain’ locations). As such, while many view the company as primarily operating in the clinics space, Field Trip has been keen to point to its drug development efforts, too.

Recap: What’s FT-104?

These drug development efforts are housed in Field Trip’s Discovery unit, with FT-104 being the first molecule under development. 

Field Trip has previously described FT-104 as a prodrug of a synthetic 5-HT2A agonist, with a binding affinity similar to that of psilocybin. However, the company claimed that FT-104 should be expected to produce a “reliably shorter duration of psychoactivity” than psilocybin, in the region of 2-3 hours.

In September, the company announced treatment resistant depression (TRD) and postpartum depression (PPD) as lead indications for FT-104, the former of which is the focus of COMPASS Pathways’ drug development efforts, among others. 

Despite these qualitative claims about FT-104, which led to some educated guesses, little was known about it. That all changed yesterday.

Patent Filing Reveals Nature of FT-104

Last week, many people woke up on Christmas morning to unwrap gifts, presumably finding a welcomed gift inside. That’s not always the case, though: sometimes what lies beneath the festive wrapping paper and tacky plastic bow is a gift that comes as a surprise, or one that’s distasteful or unwanted. 

In the case of Christmas, this anticipation is an annual affair. For patent nerds, however, every Thursday approximates this experience as patent applications publish on the USPTO’s web portal. When these applications publish, it’s often the first time we get to fully unwrap the box and see inside (at risk of stretching this tenuous metaphor far beyond its utility: perhaps you can imagine companies discussing their patent filings prior to publication as being similar to a situation where someone tells you, broadly, what gift they have acquired for you. You have a general idea, and you may even be able to pick up the wrapped gift and give it a shake in an attempt to verify their claims. But, it’s not until you unwrap that gift that you can see every detail).

Yesterday’s ‘drop’ was a little thin on the psychedelics front, with Psilocybin Alpha’s eagle-eyed editor-at-large Graham Pechenik sharing a number of U.S. filings of note. Field Trip’s filing, however, lifts the shroud of secrecy from FT-104.

In a patent application titled Tryptamine Prodrugs, Field Trip claims prodrugs of a number of tryptamines and isotryptamines, with the primary focus being 4-HO-DiPT.

While the application doesn’t mention FT-104 anywhere, Pechenik correctly deduced that the molecule was, indeed, the subject of the filing. This was confirmed when Founder Ronan Levy tweeted on the matter a number of hours later.

The patent application itself covers use in treatment (of mental disorders including depression) of 4-HO-DiPT prodrugs, including via subcutaneous injection or oral tablet administration. 

See Graham Pechenik’s thread for more information on the patent filing and 4-HO-DiPT, including a number of figures from the filing. 

What’s 4-HO-DiPT?

As aforementioned, Field Trips’ Ronan Levy confirmed that FT-104 refers to a prodrug of 4-HO-DiPT via Twitter: “It’s a more soluble form of 4-HO-DIPT, one of Shulgin’s favourite tryptamines.”

Levy went on to quote Shulgin, who said of 4-HO-DiPT: “I truly doubt that there is another psychedelic drug, anywhere, that can match this one for speed, for intensity, for brevity, and sensitive to dose.”

We won’t get too into the chemistry of this synthetic psychedelic, but it’s worth noting that its subjective effects are reportedly similar to those of other serotonergic psychedelics like psilocybin and LSD. That’s not surprising, given that it’s a tryptamine and a homologue of psilocin. 

As alluded to, what differentiates 4-HO-DiPT, and presumably FT-104, is the brevity of the subjective effects it induces.

This fits into a broader trend we’re seeing whereby psychedelic drug developers are seeking to identify and develop shorter-acting psychedelics.

The primary motivation for this is to allow psychedelic-assisted therapy to become more congruent with the current standard of care for mental health disorders, which often includes talking therapy sessions that last for around an hour and are spread across a number of months or years.

Psychedelic-assisted therapies, meanwhile, can take the better part of a full day, which is cost- and labour-intensive, and is perhaps more akin to a procedure (such as a surgery) than traditional psychotherapy.

Noticing this potential benefit of 4-HO-DiPT, in TiHKAL Shulgin wrote:

“To be on a trip and then to be back pretty much in two hours and really baseline in another hour? Most unusual. If there will ever be an acceptance of drugs such as these, in a psychotherapeutic context, a short duration is of extreme value to both the patient & the therapist.”

A 2-3 hour trip is certainly not as short-acting as the drugs under development by other companies (like GH Research who are looking at 5-MeO-DMT, for example), or as the ketamine therapy currently administered by Field Trip at its clinics.

As such, FT-104 might represent a middle ground (or, “just right,” as Goldilocks exclaimed) between the lengthy, but apparently effective, psilocybin- and MDMA-assisted therapies and a new wave of incredibly short-acting (or even non-hallucinogenic entirely) psychedelics. 

But, it’s not all rosy. Psychedelics of the DiPT class exert their effects in a primarily aural way, with some reporting that music can become less harmonious and more dissonant. We wonder how this might affect the decisions Field Trip might eventually make around set and setting in its clinics, should FT-104 make it that far. Music playlists are carefully curated in psychedelic-assisted therapy, so these aural distortions may add another layer of consideration to this process.

Writing in TiHKAL, Shulgin also reported that 4-HO-DiPT had a tendency to induce tremors. 

Interestingly, 4-HO-DiPT is not scheduled at the federal level in the U.S. (though at least one state, Florida, has scheduled the substance), though DiPT-based psychedelics could be construed as analogs of 5-MeO-DiPT which would criminalise possession, purchase or sale of the drug under the Federal Analog Act.

Regarding patentability, we’d note that Field Trip filed its application “Track One” and is receiving prioritized examination. Hence, although the U.S. non-provisional application was only filed on July 30, 2021, it’s already received one substantive office action, to which Field Trip has already replied (the U.S. prosecution documents are available here). After amending the claims to exclude certain unsubstituted compounds alleged to be in the prior art, it appears that at least some claims to FT-104 will be allowed. We also note that another Field Trip application, claiming the benefit of a different U.S. provisional application, and filed on October 1, 2021, is currently pending in Canada: CA3132847, entitled “Rapid-Acting Hallucinogenic Compositions and Methods”, and said to cover “rapid-acting formulations of hallucinogenic drugs that contain excipients which modify pharmacokinetics”.

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TL;DR: The shroud of mystery surrounding Field Trip’s FT-104 molecule is finally lifted. We now know that FT-104 is a prodrug of 4-HO-DiPT, a tryptamine that Shulgin spoke highly of. Importantly, 4-HO-DiPT has a relatively short duration of action at around 2-3 hours, which might make it more attractive (or, manageable) for use as a catalyst to psychotherapy.