After noticing some coincidences, we combed through Terran Biosciences’ published patent applications to glean more about the company’s potential strategy. Here, Noah Smith1 presents our findings.
You can browse Terran Biosciences’ patent applications, just some of which are explored below, in this table.
Until recently, very little was known about Terran Biosciences outside of press releases and a small number of interviews (including one that published as this piece went to press).
However, by analysing the company’s published patent applications, both in isolation and as a portfolio, we might be able to make assumptions about the company’s broad strategy. Indeed, this year has seen many such patent application publications.
When taken together, they suggest that Terran is not interested in any particular class, family, or collection of compounds. To the contrary, it appears that the company’s interests extend across dozens of ‘classical’ and novel psychedelic compounds and families.
What’s more, much of the company’s IP portfolio appears to line-up temporally and thematically with the development plans of psychedelic drug developers across the board, as we will show in this article. Today, Terran’s IP portfolio features compounds that are competitive with, or found in the pipelines of, companies such as Delix Therapeutics, COMPASS Pathways, Transcend Therapeutics, Reunion Neurosciences, and many others. In some cases, Terran filed patent applications just days after psychedelic drug developers’ lead candidates were first divulged publicly.
Given that the company presumably lacks the immense resources needed to develop such a vast portfolio of assets, one might wonder what Terran’s strategy is. The least forgiving observer might characterise the company as a patent troll—filing on a swathe of technologies and compounds without genuine intent to develop, in the hopes of collecting revenue from licensing said IP.
In this piece, we abstain from endorsing any particular opinion about Terran’s strategy and instead opt to present and analyse pertinent and publicly-available elements of the company’s intellectual property developments.
Background
If you’re paying any attention to published patent applications in the psychedelics realm you will have noticed that Terran is on quite a tear of late. Or, rather, was on a patent-filing tear a couple of years ago, given that patent applications take 18 months to publish.
The most eagle-eyed Psychedelic Alpha reader will not be so surprised by this. Back in March and April 2022 we highlighted the company’s boasts: they claimed to have a “portfolio of over 150 patents” at the time.
Since the start of the year more than two dozen of its patent applications have published.
Terran, which describes itself as “a biotech platform company”, is yet to publicly commit to the in-house clinical development of any psychedelic lead candidates. Rather, its recently-published patent applications suggest that the company appears to be interested in, well, just about everything.
Despite its paucity of psychedelic clinical trials, Terran claims to have “one of the largest psychedelic development programs in the industry.” This development program is said to include:
“…psychedelics with a long history of human use, such as psilocybin, LSD, DOM, 2C-B, the empathogens MDMA and its derivatives (MDEA, methylone, MDAI, MBDB, MDA). Terran has also developed novel psychedelic prodrugs (psilocin, LSD, 2C-B, methylone, long-acting MDMA, orally-active DMT and 5-MeO-DMT) as well as improved psychoplastogens (non-hallucinogenic derivatives of DMT and ibogaine), and therapeutics without effects at the 5-HT2B receptor.”
As alluded to, Terran’s pipeline is not limited to psychedelics. Through licensing deals the company has also obtained rights to develop and commercialise other central nervous system (CNS) assets that fall outside of the psychedelic domain.
Yet, it remains unclear whether Terran has initiated, or will imminently initiate, a clinical development program for any of the psychedelic assets it claims. When Psychedelic Alpha asked Terran about this they reminded us that the company is currently running a Phase 1 clinical trial of idazoxan (licensed from Pierre Fabre) in healthy participants. The company also told us that it has “sponsored multiple clinical biomarker trials in the US and Canada”, and reminded us of their partnerships with Sanofi and Pierre Fabre. In the case of these in-licensed assets from Sanofi and Pierre Fabre, they’re not psychedelic; so the question stands.
Early Focus
Terran was founded in 2017, but it’s not clear that psychedelics were its focus from inception. While relatively little was known about the company until it began a slew of IP licensing deals in 2022, there are some clear indications that Terran had substantial focus outside of psychedelics.
In a 2020 interview, CEO Samuel Clark and CBO Dustin Tetzl explained that Terran “initially started with work on schizophrenia”, adding that they “decided to build a company around exciting assets licensed from different institutions”. This originally included two therapeutics and a piece of neuroimaging software, they explained. At the time, Tetzl said the company was planning to take a “late stage schizophrenia compound, TR-01 [idazoxan XR, mentioned above], forward into phase 2b.”
At the time of the interview, Tetzl explained that Terran was in the midst of a Series A raise, with capital expected to get the company “through key milestones over the next 2 years to be able to move our imaging product potentially all the way through FDA approval and early launch, as well as move […] TR-01 through the phase 2b trial”, along with some preclinical work on another asset. The company had aimed to get their neuroimaging platform on the market “in a year”.
The private company has been backed by the likes of Noetic Fund and Valhalla Ventures, as well as one of Christian Angermayer’s venture firms, Presight Capital. Angermayer’s fund invested an undisclosed amount in Terran around about 2019, just after he co-founded atai Life Sciences.
Licensing Deals
Since the beginning of 2021, Terran has inked a number of deals to build out its intellectual property portfolio, including:
- A deal with the University of Maryland, Baltimore announced on March 8th, 2022 that covered a portfolio of patents and data from UMB.
- Three days later, the company announced that it had acquired a CNS IP portfolio from Concert Therapeutics. The deal included rights to “deuterated compounds” that Terran described as “next-generation therapeutics with applications across several different psychiatric and neurological conditions.”
- Shortly thereafter, the company shared news of its third licensing deal, this time with Columbia University. Through the agreement, Terran obtained “exclusive rights to develop and commercialize Columbia’s proprietary CNS biomarker software platform and patent portfolio.”
- Then, on April 13, 2022, Terran announced that it had acquired Blumentech’s patent portfolio which covered “multiple groundbreaking discoveries by the late Dr. Jordi Riba Serrano, a renown ethnopharmacologist and pioneer of psychedelics research.”
- Terran subsequently announced its fifth and final licensing deal of 2022 with the global pharmaceutical company Sanofi. Through the agreement, the company gained “exclusive rights to develop and commercialize two late-stage CNS pipeline assets.”
- More recently, Terran announced that it had entered into its first licensing deal of 2023 with Pierre Fabre Médicament S.A.S to support its development of idazoxan XR as a treatment for schizophrenia.
Based on limited publicly available information and the abridged timeline above, Terran’s focus appears to centre around constructing a wide-reaching IP portfolio via licensing agreements, patent filings, and litigation.
The company painted a different picture, however, telling us that they “intend to develop these assets through clinical studies with the goal of eventual regulatory approval and commercialization.” Based on the sheer breadth of patents the company has filed, as we will explore below, that might be a tall ask.
COMPASS Pathways Litigation
On August 5, 2022, the quasi-stealth company made headlines when it filed a lawsuit (PDF) against COMPASS Pathways claiming that, under the guise of a potential collaboration, the industry leader had “milked” Scott Thompson, Terran’s advisor and partner at the University of Maryland, Baltimore (UMB), “for all the information it could about his confidential research” on the use of a 5-HT2A antagonist to attenuate psilocybin’s subjective effects.
Three years prior, in August 2019, Thompson filed a provisional patent application covering the concomitant use of the drugs; a patent that Terran, through its 2021 deal with UMB, has rights over. However, in the suit Terran claimed that COMPASS used confidential information, gained through conversations with Thompson that were protected by NDA, to include similar methods in patent applications of its own around the same time.
Through its agreement with UMB, Terran gained “an exclusive license” to the aforementioned “Psilocybin Trade Secrets” covering the use of a 5-HT2A antagonist alongside psilocybin. Accordingly, the company claims to have a “first and primary right to prosecute and control any action for misappropriation of the Psilocybin Trade Secrets”.
The lawsuit seeks injunctive relief and damages.These legal remedies include measures to prevent COMPASS from using or disclosing the trade secrets and requiring the company to hand over documents and information that would elucidate “how the trade secrets were utilised or transmitted with and beyond Compass”
However, Terran also sought an order that would compel COMPASS to assign to Terran “any rights to patent applications or other intellectual property that incorporates the Psilocybin Trade Secrets.”
“… requiring Defendants to assign to Terran any rights to patents, patent applications, or other intellectual property that incorporates the Psilocybin Trade Secrets or to correct inventorship on any patents or patent applications that incorporate the Psilocybin Trade Secrets”
Should Terran be successful, COMPASS could be required to sign over at least six of its published patent families2, and the patents that issue therefrom (potentially, dozens).
While the lawsuit is still ongoing, COMPASS has recently filed a motion to dismiss Terran’s complaint, claiming that “the Court lacks personal jurisdiction over Compass” and that “even after ten months and three different complaints, Plaintiffs still fail to make a prima facie showing that Maryland has either general or specific jurisdiction over Compass”. Terran recently responded, requesting that the COMPASS motion be dismissed “in its entirety.”
Nevertheless, Terran’s requests for legal remedies and damages might obscure a more practical objective in the process. As discussed in our August 2022 coverage:
“A more cynical observer might wonder if this alleged misappropriation of trade secrets might be the impetus for a fishing expedition of sorts. If Terran convinces the Judge to compel Compass to turn over sensitive documents and plans, and make corporate representatives available for deposition testimony, they might come away with intelligence worth more than any straightforward monetary award. Of course, this is pure speculation.”
This is, of course, speculation. But, as we explore below, Terran’s recent pattern of behaviour certainly suggests that the company is indeed bent on capturing as much of the broadly psychedelics-related intellectual property landscape it can.
Planting a Thicket: Terran’s Broad Patent Strategy
Starting in autumn 2021, Terran began filing an extensive series of provisional patent applications covering a broad array of psychedelic compounds and their prodrugs. In the last seven weeks of 2021 alone, the company filed more than sixty psychedelics-related provisional patent applications. Terran continued to file applications into the new year.
While the majority of these early provisionals were prophetic, lacking supporting data, these filings allowed Terran to secure relatively early priority dates for a wide array of compounds, setting a foundation for the company’s eventual PCTs3.
In H1’22 the company appears to have narrowed its focus on a smaller selection of compounds for which it generated data that was subsequently included in follow-on provisional applications. Between January 6th and April 26th, 2022, Terran filed more than fifty additional provisional applications, the majority of which included supporting data for specific compounds of interest.
To date, over 30 of Terran’s PCT applications have been published, encompassing more than 150 provisional applications.
Throughout this article we demonstrate how Terran’s provisional patent filing timelines and the increasingly narrow compounds claimed therein are often strikingly congruent with the timelines of other psychedelic companies’ public disclosures.
Psychedelic Alpha has received private communication from a number of individuals that are concerned about the company’s apparent strategy, comparing it to that of rent seeking, with one using the metaphor of setting up toll booths for other drug developers to pass through.
Others have told us that the company has all the hallmarks of a patent troll.
Terran told us that they “strongly disagree” with this characterisation, pointing us to “important scientific breakthroughs and contributions to the field.” To elucidate this point, the company pointed us to a number of press releases describing these developments, many of which are discussed substantively in this piece.
Whether this intersection between Terran’s IP portfolio and other psychedelic drug developers’ activity is deliberate or not is for you, the reader, to decide. Here, we simply present the facts.
First we look at how these similarities play out with more well-known psychedelic candidates and companies. Later, we take a look at how some of Terran’s other patent filings have claimed novel psychedelics, namely psychoplastogens.
As such, while the company’s broad patenting efforts intersect with the foci of dozens of companies in the space, below are examples of some of what look to be more targeted efforts by Terran.
Salty Psilocybin Competition – COMPASS, Continued…
Since Terran first filed its lawsuit against COMPASS in August 2022, competition between the pair over IP has not simmered down.
It’s worth noting that this broad competition over psilocybin-related IP is certainly not unique to COMPASS and Terran. Dozens of companies have, over recent years, engaged in a concerted effort to capture their slice of the psilocybin intellectual property landscape.
The resurgence in interest in psilocybin as a therapeutic drug candidate motivated companies interested in commercialising the compound to not only identify an optimal form of psilocybin for use in humans, but also to identify patentable preparations of the drug that could guarantee a period of defensibility in order to recoup R&D outlay.
As Sherwood et al. note, “some 50 years after Sandoz production, re-evaluation of psilocybin as a pharmaceutical tool has driven efforts such as contemporary commercial-scale production, systematic physical characterization of the crystalline active pharmaceutical ingredient (API), as well as attempts to block manufacturing of psilocybin through patent protection” (2021).
An important element of drug development “is determining which specific solid form of an active pharmaceutical ingredient (API) should be selected for scale-up, formulation activities, and clinical trials” (Aitipamula et al., 2012). APIs can take on a diverse range of solid forms (visualised in the schematic below), and “finding the optimal solid form is important to intellectual property, processing, enabling drug discovery and is key to obtaining regulatory approval” (ibid.).
Accordingly, all companies pursuing IP protection over preparations and uses of psilocybin (and APIs thereof) are faced with a highly-competitive landscape characterised by a large number of entrants vying for a limited number of formulations and drug applications.
Perhaps demonstrating this crowded landscape and limited numbers of forms, an investigation published by Sherwood et al. (2021) found that Hydrate A, Polymorph A, and Polymorph B were the three most commonly identified crystalline forms of psilocybin in a batch of 24 psilocybin samples produced between 1963 and 2021.
Since 2021, COMPASS Pathways has been granted a number of patents claiming both the crystalline Polymorph A and Hydrate A forms of psilocybin. The granting of COMPASS’s patents has provided the company with a considerable—and controversial—commercial advantage over its competitors, given that it holds patents covering two of the three most commonly identified forms of psilocybin.
However, on May 19, 2023, Terran announced the publication of its PCT patent application claiming “what may be the first new salts, co-crystals, and polymorphs of psilocybin in history.”
Through what the company describes as “one of the most rigorous evaluations of psilocybin to date”, Terran purports to have created “a number of novel salt forms of psilocybin.” The creation of salt forms of psilocybin is something the company claims many experts previously believed was not possible.
In what may be a nod to designing around COMPASS IP, Terran positioned its (ostensibly) novel work as something that, “would likely remove potential barriers to development across the ecosystem, enable the development of new formulations, provide expanded options to researchers, and accelerate the timeline of bringing this important compound to patients.”
While different crystalline (polymorphic) forms of the same drugs are considered by the FDA to be the same API, “[p]er the current regulatory scheme, different salt forms of the same active moiety are considered different APIs.”
Accordingly, the company has stated it believes that these discoveries could “allow the widespread development and commercialization of these new forms of psilocybin”.
However, there is no clear indication that Terran has any intention of developing or commercialising these psilocybin salts itself. It might be more likely that the company will focus on supplying psilocybin to investigators and sponsors and licensing its intellectual property.
Terran’s patent applications don’t appear to only target its more notable competitor, COMPASS. Rather, Terran is casting a much wider net.
4-HO a No-Go? Reunion, Mindset, CaaMTech
As discussed in a recent bulletin that served as a prelude to this analysis, one of Terran’s latest PCTs provides an overt example of the company attempting to patent another psychedelic drug developer’s clinical-stage compounds.
On December 30, 2021, a patent application from Reunion Neuroscience (formerly Field Trip Health) was published, lifting the veil on Reunion’s lead candidate: RE104. Prior to this reveal little was known about the specific compound Reunion had set its sights on, beyond vague company descriptions.
On the same day the PCT was published, Psychedelic Alpha Editor-at-Large and Calyx Law patent attorney Graham Pechenik deduced that RE104 was in fact a prodrug of 4-HO-DiPT. However, some uncertainty remained regarding the precise form of the prodrug Reunion was developing, given that the company’s application included claims covering both “4-hemiglutarate & 4-hemisuccinate of 4-HO-DiPT”.
Just one week later, on January 6, 2022, Terran filed four provisional patent applications describing prophetic examples of the 4-HO-DiPT prodrugs 4-hemiglutarate and 4-hemisuccinate, and methods of screening salts and polymorphs of the compounds. Terran would later file two follow-on provisional applications that included supporting screening data and claims focused only on solid forms of 4-HO-DiPT hemiglutarate HCl, the precise formulation Reunion is developing.
Terran’s refined focus on the 4-hemiglutarate prodrug may very well be the result of some careful sleuthing. On January 11, 2022, not long after Terran had filed its early provisionals, Field Trip (now Reunion) published a press release that outlined its “preferred prodrug” as being an “endogenous, natural compound glutaric acid as a hemi-ester.” Even the company’s chosen name, Isoprocin Glutarate, pointed to its prodrug of choice.
It is perhaps of little surprise, then, that Terran’s ultimate PCT claimed only solid forms of 4-HO-DiPT hemiglutarate HCl. Through its ostensibly novel, inventive, and industrially applicable claimed solid forms, Terran may very well have secured IP that will block Reunion from using specific crystalline polymorphs of its own lead candidate.
However, the impact of Terran’s recently uncovered efforts may also be felt by Mindset Pharma, who—through strategic efforts of their own—managed to obtain a claim to 4-HO-DiPT hemiglutarate as well.
Additionally, private drug discovery company CaaMTech previously published on its work synthesising “two new prodrugs of 4-HO-DiPT”. In its September 2022 press release, CaaMTech claimed that its work represented “the first crystal structures reported for any 4-substituted DiPT compound, the first solvates of 4-glutarato-N,N-diisopropyltryptamine, and the first crystalline material reported for any form of 4-glutarato-N,N-diisopropyltryptamine.”
Presumably, CaaMTech had hoped to secure the intellectual property necessary to licence out the fruits of its discovery work. However, given that a patent application is yet to publish covering these 4-HO-DiPT prodrugs, it may be the case that Terran has scooped CaaMTech, too.
Moats Around Methylone — Transcend Therapeutics
In late 2021, Terran filed a series of prophetic provisional patent applications covering a family of MDMA-related compounds including, but not limited to, MDMA, MDAI, MDE, MBDB, and methylone.
As aforementioned, around mid-2022 Terran began filing follow-on provisional applications that included screening data the company had generated on a smaller selection of compounds. Methylone, unlike the majority of the MDMA-related compounds it had previously filed on, was included in these more narrow follow-on efforts.
After filing several additional methylone follow-on provisionals between February 18 and September 27, 2022, Terran assembled and filed its eventual PCT (WO2023/081403) claiming “novel deuterated forms, enantiomerically pure forms, as well as novel salts, polymorphs, and co-crystals of racemic methylone, R-methylone and S-methylone.”
In light of the company’s initial focus on a plethora of MDxx compounds, one might wonder what the impetus for prioritising its data generating efforts on methylone could have been. After all, it’s an empathogen that, despite being first synthesised and patented by Peyton Jacob and Alexander ‘Sasha’ Shulgin in 1996 (WO1996/039133), had gained very little overt commercial or academic interest as a therapeutic.
There is one notable exception, though. Around the time that Terran began filing its earliest provisional patent applications in 2021, a private biotech company by the name of Transcend Therapeutics was being formed by Blake Mandell, Kevin Ryan, and Benjamin Kelmendi.
While Transcend remained in stealth for well over a year after its founding, the company’s early focus on developing methylone as a treatment for PTSD was revealed publicly when it announced a Series A financing in February 2023. The company’s $40 million round, which closed in the midst of a depressed fundraising environment, was presumably the culmination of many months of investor solicitation—perhaps a year or so.
The timelines for Transcend’s founding, incubation, and fundraising efforts appear to roughly coincide with Terran’s refined focus on generating supporting data for its methylone applications as opposed to some of the other MDxx molecules that it had previously filed on. Might Terran have caught wind of Transcend’s interest in methylone while the company remained in stealth?
Transcend did file a patent application (WO2023/015154) covering methylone with an earlier priority date than Terran’s PCT. Subsequently, on July 25, 2023, a newly-granted Transcend patent was issued by the USPTO. Accordingly, it looks as though the private company has begun to secure IP over its lead drug candidate.
However, its claims extended only to methods of using the drug in the treatment of various psychiatric and neurological disorders and dose ranges. By contrast, Terran’s PCT captures a sweeping list of solid forms of methylone—“composition of matter” protection that’s often viewed as being stronger. And potentially, one of those solid forms may be the most desirable form to take through development.
Accordingly, Terran’s claims over methylone could eventually cloud at least some of the commercial viability of Transcend’s lead candidate. Unless, of course, they could secure a licence agreement from the (potential) patent holder.
R-MDMA Draws a Crowd — MindMed & atai
Among Terran’s gamut of early provisionals were applications covering solid forms of MDMA and its enantiomers, R- and S-MDMA. While Terran’s apparent interest in MDMA is certainly not uncommon among drug developers operating in the industry, its patenting efforts once again coincide neatly with actions taken by other companies.
Since its founding, psychedelic drug developer MindMed has largely focused on LSD. However, on October 26, 2021, the company announced that it would be expanding its drug development pipeline to include the MDMA enantiomer, R-MDMA, with a focus on developing the drug as a treatment for symptoms of Autism Spectrum Disorder (ASD). (See our earlier coverage.)
Prior to its announcement, on May 5, 2021 MindMed filed a provisional patent application covering “compositions and methods for providing safer treatment with enantiomers of MDMA and MDA.” The company’s PCT (WO2022/235530) would be filed a year later.
On November 18, 2021, just a few weeks after MindMed publicly announced its intent to develop R(-)-MDMA, Terran filed a provisional patent application covering various solid forms of the very same MDMA enantiomer. Terran’s complete PCT (WO2023/092044) was filed roughly a year later claiming solid forms of MDMA and both its enantiomers.
While Terran’s pursuit of IP covering MDMA enantiomers appears to be closely linked (temporally, at least) with its competitor’s pipeline expansion, MindMed’s R-MDMA is not the only MDMA enantiomer-based development program that Terran’s patent strategy might have muddied.
atai Life Sciences, like MindMed, has disclosed its development of MDMA-related candidates. Through its wholly-owned subsidiary, EmpathBio, atai is working to develop a compound the company vaguely describes as an “MDMA derivative” for post-traumatic stress disorder (PTSD).
However, an evaluation of the company’s patent portfolio suggests that this lead candidate, EMP-01, is R-MDMA; the same enantiomer that MindMed expanded its pipeline to include. In fact, since late 2021, atai has filed a number of PCTs (e.g. WO2023/129958 & WO2023/056472) covering salts and solid forms, processes for preparation, and uses of R-MDMA.
Once again it would appear that Terran has attempted to lay partial claim to an already crowded intellectual property space.
***
With dozens of patent applications now published across more than 30 patent families, it seems apparent that Terran is determined to capture as much intellectual property as it can. In addition to those companies and compounds mentioned above, Terran’s patent filings appear to at least partially overlap with the development programs of other companies such as Ceruvia Lifesciences, Clearmind Medicine, PharmAla, BrightMinds Biosciences, and others. Its IP portfolio now includes claims over preparations of further compounds such as LSD, DMT, 5-MeO-DMT, 2-Bromo-LSD, ALD-52, DOI, 2C-B, and many more. As such, the candidates of many other psychedelic drug developers are contained within Terran’s applications.
Though Terran tells us that it intends to develop its assets through to approval and commercialisation, the resources needed to achieve this across such a comprehensive pipeline of drugs would be colossal. As such, one might once again assume that the predominant strategy is to attempt to licence out the majority of IP it accumulates.
While much of the company’s early filing efforts concentrated on what are sometimes referred to as ‘first’ or ‘second generation’ psychedelics, Terran has also taken to filing patents on novel compounds being discovered and developed by researchers and companies—i.e., compounds that exist exclusively in the pipelines of other drug developers. In this sense, Terran’s IP thicket might be extending well beyond the shortlist of compounds and companies mentioned thus far.
Tripping up the Trip Skippers? Terran Files on Delix’s Psychoplastogens
One example of the apparent expansion in Terran’s IP remit is its filing on versions of Delix Therapeutics’ novel ‘psychoplastogens’, which have been the subject of significant investor attention in the past few years.
Delix is a private company that’s largely based on the work of David Olson’s lab at UC Davis. The lab’s research substantially revolves around the discovery and development of modified psychedelics4 which it hopes will prove non-hallucinogenic but therapeutic. Olson coined the term “psychoplastogen” to refer to these trip-skipping drugs in a nod to the proposed mechanism of action, neuroplasticity.
The lab and its spin-out company, Delix, hope that these non-hallucinogenic drug candidates would have greater commercial viability by reducing or eliminating the need for supervision and allowing them to be prescribed to populations who might otherwise be contraindicated to psychedelic-based therapeutics. These would effectively be take-home drugs.
The company has raised over $100m in pursuit of this goal and appears to be developing a library of psychoplastogens, with two lead candidates identified: AAZ-A-154 (“AAZ”, or DLX-001) and Tabernanthalog (“TBG”, or DLX-007). Delix-affiliated researchers have published prominent preclinical studies on these compounds since 2020.
Recently, Delix advanced AAZ into a Phase 1 trial, marking the first in-human studies of this so-called psychoplastogen class of drugs.
However, recently published patent applications from Terran suggest that Delix may now face some competition over its novel work. Here, we look at both tabernanthalog and AAZ.
Tabernanthalog (DLX-007)
Tabernanthalog is perhaps the most well-known psychoplastogen to emerge from David Olson’s lab. The compound, which now appears to be a prominent fixture of Delix’s pipeline, is a novel, purportedly non-hallucinogenic analog of ibogaine.
TBG first appeared in the literature in December 2020 when Olson et al. published an article titled, A non-hallucinogenic psychedelic analogue with therapeutic potential. Subsequent publications suggest that—in animal models—TBG shows promise as a treatment for substance use disorders, depression, and other neurodegenerative disorders.
The compound’s therapeutic potential attracted the attention of NIDA, who directed more than $1.6 million towards research into the compound in 2022, and will continue funding the research being led by Jamie Peters until June 2025.
Naturally, Olson and his startup have filed a number of patents covering preparations and uses of the psychoplastogen.
But, it’s not alone. Recently-published patent applications reveal that Terran is also pursuing intellectual property rights over the psychoplastogen developed by David Olson and his team.
Most notable is Terran’s recently published PCT, Salt and Solid Forms of Tabernanthalog (WO2023/092045), in which the company claims various forms and methods of using of tabernanthalog, some of which the company described as having “at least one improved property.”
TBG is also referenced in another of Terran’s published applications (WO2023/077125) claiming isotopologues of tabernanthalog. In its application, Terran claims that “compounds such as tabernanthalog do not have the drug-like pharmacokinetic and pharmacodynamic properties to support their wider use in the clinical treatment of brain disorders.”
Accordingly, the company once again posits that through deuterium or tritium enrichment, for example, its disclosed TBG isotopologues can benefit from “improved characteristics.” However, a considerable number of Terran’s examined claims in each of the PCTs were found to lack both novelty or an inventive step by the examiner, due largely to prior art produced by Olson and colleagues.
Nevertheless, there are still dozens of claims covering ostensibly novel versions of the psychoplastogen that are yet to be examined, many of which are supported by screening data produced by the company.
As a result, Terran may very well secure a claim over some iterations of tabernanthalog.
We asked Terran what prompted them to become interested in tabernanthalog. They pointed us to an interview in Microdose that was published as this piece went to press, and provided a link to a company press release. While the press release repeatedly describes the compounds as “novel”, it’s hard not to reach the conclusion that the company was inspired by reading the work of Delix and its affiliated researchers.
AAZ-A-154 (DLX-001)
While TBG may be Delix’s more well-known candidate, it’s not Terran’s only target. In fact, the company is also pursuing patent claims on Delix’s current lead drug candidate, DLX-001.
This lesser-known compound, also referred to AAZ-A-154, was first referenced in David Olson’s April 2021 publication, Psychedelic-inspired drug discovery using an engineered biosensor. Based on Delix’s pipeline, DLX-001 appears to be another non-hallucinogenic compound inspired by the structural scaffolds of MDMA and 5-MeO-DMT.
As alluded to above, in May 2023 Delix advanced this candidate into an early Phase 1 trial, marking what appears to be the first time a novel psychoplastogen has been studied in humans (in a clinical trial setting, at least). Just over one month after initiating its inaugural study, the company announced that it had completed dosing in its first patient cohort with some promising early results.
On February 2, 2020, roughly three years before initiating this clinical study, Olson filed a PCT (WO2020/176597) covering AAZ-A-154. The company’s ensuing US patent application was published on October 28, 2021 and ultimately issued as US 11,254,640 near the beginning of 2022.
By this point, there are no prizes for guessing what happens next.
Around two weeks after Olson’s US patent application published, Terran filed its first two prophetic provisional applications covering different preparations of the (R)-1-(5-Methoxy-1H-Indol-1-YL)-N,N-Dimethylpropan-2-Amine compound. The company would eventually file two follow-on provisionals with supporting screening data, before submitting a complete PCT (WO2023/091974) on November 16, 2022 claiming numerous iterations of Delix’s novel work.
Acquiring IP
As the company was working behind the scenes filing provisionals and assembling PCTs, Terran was also focused on strategically buying up existing intellectual property to add to its growing portfolio. In fact, the company’s licensing deals, outlined at the beginning of this article, provided the general public with some of the first, albeit limited, insights into the stealth company’s development.
Some of these early pursuits of pre-existing IP appear to have been concentrated on capturing a large share of the 5-HT2A antagonist IP landscape; an early area of interest for several companies hoping to identify ways to improve the clinical, logistical and commercial viability of therapeutics based on longer-acting classical psychedelics.
Given Terran’s pattern of attempting to secure IP around competitors’ endeavours, the move to acquire patents covering compounds of interest like ketanserin looks to have been one of Terran’s earliest public pursuits of blocking IP. The company has since filed a PCT (WO2023/129976) of its own covering salt and other solid forms of ketanserin, presumably in an effort to extend its reach over the ‘trip neutraliser’.
A Shotgun Approach?
Terran’s patent portfolio, which consists of more than 150 provisional applications, quickly started to take shape in late 2021 when the company began rapidly filing dozens of provisionals covering hundreds of prophetic examples of an extensive array of psychedelic compounds.
Despite this early shotgun approach, thereafter Terran refined its IP data generating efforts to target a smaller assortment of the compounds included in its earlier prophetic applications. In doing so, the company started to produce the data needed to support its claims to compositions and preparations of some of the compounds included in its earlier provisionals.
While many of the compounds claimed in Terran’s early provisionals were never supported with follow-on data, they were nevertheless grouped together and filed as PCTs.
However, many of those PCTs which were subsequently supported by compound screening data clearly overlap with the development programs of other companies operating in the industry. One might speculate that Terran has been keeping close tabs on the pipelines of competitors operating across the sector.
In several instances, as detailed above, once the nature of a company’s lead candidate had been revealed, Terran was quick to file provisional patent applications covering solid forms of those candidates and iterations thereupon.
Terran’s End Game
To our knowledge, Terran—in its sixth year of operation—is yet to advance a single psychedelic drug candidate through clinical trials, nor has it publicly committed to a specific clinical development pursuit in the psychedelic space.
As such, one might assume that Terran is primarily interested in striking licensing agreements for its psychedelic compounds, either voluntarily from those interested in developing certain compounds or through compelling existing developers with assets in development to licence Terran’s competing and blocking IP.
Companies that find the compounds in their development programs captured by any of Terran’s patents might now be at a crossroads: with Terran’s tollbooth set up in one direction, while the other road might be characterised by freedom to operate uncertainty.
One way forward for companies looking to maintain clear freedom to operate is to pivot to a new form of the drug that’s clear of Terran’s tollbooth. But pursuing this avenue might mean completing requisite bridging studies in order to demonstrate that the alternative candidate is pharmaceutically and biologically equivalent. Bridging to an alternative form might also entail redoing Chemistry, Manufacturing, and Controls (CMC).
Not only would this solution require a developer to commit additional financial resources to their development program, it would also delay an already lengthy drug development process; in turn, chewing away at any existing patent life and diminishing future revenues.
Terran, meanwhile, might stand ready to negotiate a licensing agreement with such a company that would allow for continued development without the need for backtracking. While the terms of such an agreement could cost a company a considerable sum, it may be the case that, over the life of the product, licensing makes the most commercial sense.
Licensing agreements might not only come from companies who have found themselves outmanoeuvred by Terran, though. In light of the company’s apparent efforts to patent competitors’ compounds, any granted IP might be attractive to companies looking to bring common molecules to market as competitive alternatives to those already in development.
One such example might be salt form alternatives to COMPASS’s crystalline polymorphic psilocybin. By developing patentable salt preparations of psilocybin that can be approved as independent APIs, Terran has potentially patented a portfolio of competitive alternatives to the crystalline psilocybin API that may one day be approved. Whether they decide to develop these in-house or out-licence is yet to be seen.
In cases such as this, interest might also come from companies facing the prospect of having new competitors eat away at their market share. Thus, Terran might also be able to market its IP to developers seeking to keep their target markets free of competitive alternatives, generics, or competing programs.
For example, if COMPASS Pathways sought to monopolise the market for psilocybin further it could, in theory, investigate licensing salt form IP from Terran that would effectively enable it to block competitors from developing any viable alternative salt forms of psilocybin.
While the strategies discussed above might prove lucrative for Terran if pursued (and, assuming that companies in the space have the resources to engage in licences on terms attractive to Terran), they could also stifle innovation and accessibility by disincentivizing early drug development or aiding further monopolisation and staving off generic entry5.
In particular, their recently published PCT on solid forms of 4-HO-DiPT hemiglutarate might have complicated the IP landscape for that candidate to such a degree that licensing costs for an interested fourth party could prove to be prohibitive, given that Reunion, Mindset, and Terran all now have—to varying degrees—claims to the 4-HO-DiPT prodrug.
What’s more, it’s unlikely that Terran will be able to pursue claims to all of the many laundry lists of compounds, combinations, compositions, and methods disclosed in their applications, especially where only supported by prophetic examples. In total, Terran’s published provisionals and PCT applications total around 12,000 and 10,000 pages of disclosure, respectively.
However, all of that disclosure is now prior art to others, making it more challenging for others to protect those now-disclosed forms and compounds. While this could certainly impede further innovation, it could also, in theory, increase the value of the compounds Terran may eventually hold claims over, as the company—even without securing patents—has effectively limited the latitude of others who seek to work with similar alternatives.
Closing Thoughts
While already expansive, Terran’s patent portfolio continues to grow (reminder: you can explore the company’s other published applications in our tracker). In fact, just as this report went to press, two new PCT applications were published. Accordingly, while the recent unveiling of Terran’s applications have helped shed light on the company’s IP strategy, and allow for speculation as to its commercial strategy, the true extent of its growing patent portfolio remains unclear. As a result it may be that Terran has, for many months now, had its sights set on IP that competes with a slew of drug developers not yet able to be included in this present analysis.
Time will reveal which of Terran’s applications and their constituent claims continue to be pursued, and which survive and pass through further examination. Until this point, when the company’s portfolio crystallises, we are left to speculate on the implications of Terran’s IP activity.
Terran maintains—both in response to our request for comment as well as in a recent interview—that it is not in the business of “just licensing patents”. Rather, Terran’s Clark points out that it has “entire datasets available accompanying these patents which could potentially save enormous costs and years of work, accelerating the development of novel therapies for patients in need.” The logic presumably follows that the additional cost to a drug developer in potentially having to shell out for a licence from Terran might be offset by an easier path through the drug development and commercialisation process.
What’s not given much attention, however, is the fact that many psychedelic drug developers could have explored and pursued solid forms and related IP without Terran’s intervention. In fact, it’s probable that many were already doing this.
In some senses, it’s reminiscent of the animosity directed towards COMPASS Pathways when it emerged it had filed solid form IP on psilocybin, potentially blocking other ongoing drug development. The nonprofit Usona Institute, for example, was working extensively with psilocybin, too. But they had chosen not to file patent applications on those solid forms—despite having performed their own “polymorph screen involving over 150 solvent and non-solvent based screening experiments,” the results of which they published in February 2020.
“We’re a firm believer in ‘a rising tide lifts all boats,’ and our door is always open to prospective partners,” Clark said in an interview earlier this week. But what if the tide was coming in anyway?
One might also ask why Terran would repeatedly wade into crowded waters, targeting compounds that are subject to existing IP claims (in some cases, from multiple parties) and found in the pipelines of other companies. In many cases, if Terran sought to develop and commercialise the candidates claimed in its own IP portfolio, it would need to hope that others’ doors were open, too.
- With thanks to our Editor-at-Large, Graham Pechenik, for review.
- WO2023114097, WO2023086252, WO2022207746, WO2020212952, WO2020212948, and WO2020212951.
- Through the Patent Cooperation Treaty (PCT) system, inventors are able to file a single international patent application that then allows them to simultaneously seek patent protection across 157 PCT contracting states.
- i.e., new chemical entities that are structurally related to known psychedelics.
- In an interview that published as this piece went to press, Terran CEO Sam Clark noted that the company “could pursue the 505(b)(2) approval pathway that would allow us to leverage existing data to bring our own novel salts and polymorphs or prodrugs to the market as soon as FDA marketing exclusivity expires”. Clark said that this could also improve accessibility for patients.
