Over the past few months the psychedelic community has seen a flurry of new IP published from the biotech company Terran Biosciences, so Microdose organized a Q&A with Terran’s founder and CEO, Dr. Sam Clark, MD PhD, to learn more about the company and their recent discoveries that are starting to make waves in the space.
See highlights from our Q&A below.
Could you tell us a little about your background and the impetus behind founding Terran?
I’ve always been passionate about neuroscience, and focused my research on novel neural mechanisms during my undergraduate years at MIT and during my MD/PhD years at Columbia University. I also had several close family members who struggled with mental illness, and wanted to do everything I could to make an impact in this space, so founded Terran Biosciences in 2017 to develop novel therapeutics for patients suffering from these devastating illnesses.
Can you tell us more about how you develop drugs and IP at Terran?
Terran is a true platform company, with many CNS assets in active development across several verticals at the company. As such we’ve developed a central team to guide the portfolio but also have dedicated teams for each program working to ensure their success. We also have a robust drug discovery program, one of the largest in the space.
For example, last year we had over 40 chemists working full time across medicinal chemistry, solid state chemistry, and GMP manufacturing. We also have a veteran clinical development team and are currently running a multisite clinical trial in over 100 subjects (NCT05727189). We have applied our team’s prodrug expertise to promising psychedelic compounds, with very encouraging results, and our CMC team has worked diligently to characterize salts and polymorphs to determine if forms exist that are stable and able to be manufactured at scale. We have since continued to expand our pipeline through both in-licensing and partnerships and through the development of novel compounds from our own in-house drug design engine.
Can you talk more about these partnerships?
We’ve been lucky to partner with a wide range of great biopharma companies, including Sanofi, for two late stage clinical CNS assets, and Pierre Fabre, for a late stage clinical asset for schizophrenia. We also sponsor research and/or do licensing deals with a number of academic institutions including Columbia University, University of Ottawa, McGill University, University of Maryland, Virginia Commonwealth University, and several institutions in Spain like Fundació Institut de Recerca de l’Hospital de La Santa Creu i Sant Pau (FIRHSCSP), Universidad Autónoma de Madrid (UAM), State Agency Consejo Superior de Investigaciones Cientificas M.P (CSIC), and Consorcio Centro de Investigación Biomédica en Red (CIBER).
Can you highlight for us some of the breakthroughs in psychedelics you’ve unveiled recently?
Over the course of this year, we’ve published a number of discoveries including the first orally-active DMT and 5-MeO-DMT, long acting MDMA, the first new salts and polymorphs of psilocybin and 2C-B, enantiomerically pure and stable isotope labeled versions of a number of empathogens, full characterization of LSD and its analogs ALD-52 and 1P-LSD, and novel psychoplastogens based on DMT and ibogaine.
With so many potential options, how do you go about choosing which psychedelic compounds to develop?
First, in order to have the best chance of success, we search the published literature to identify compounds with histories of therapeutic human use. However, many of these compounds had not been optimized for clinical use. We noticed there was an opportunity to conduct the important chemistry and discovery work to improve their profiles, make them developable and ultimately FDA-approvable as therapeutic options for patients. So over the past few years we’ve prioritized the compounds we think have the most promising profiles and potential for maximum benefit to patients.
Neurological and psychiatric diseases are incredibly diverse, as are the patients who suffer from them, and they need as many therapeutic options as possible. Through our teams’ recent breakthroughs we’ve clearly demonstrated that Terran is intently devoted and uniquely qualified to develop these compounds. We don’t want to wait around simply hoping that someone else will do it, and so have taken the first steps in developing unique “right sized” therapies that are as diverse as the diseases they may treat.
How does your development strategy differ from that of other companies working on similar compounds?
The psychedelic therapeutic space is indeed quite crowded, with over 100 companies claiming to be working on some form of a psychedelic or empathogen, including a majority of these working on psilocybin or its analogs, and many others claiming to be working on DMT, MDMA, LSD, and ibogaine etc. It’s simply a function of the industry and the history of these compounds that there would be multiple companies working on similar compounds.
Also, because Terran has been focused on development, we haven’t typically announced much of our work until after our patents actually publish. Since there is a lag time of 18 months from filing a provisional patent until it publishes as a PCT, many of our innovations you see publishing this year were first filed in 2021. During this lag time we have seen other companies publicly stake a claim to similar assets in their own pipelines.
Besides the scale of our operation itself, we differentiate ourselves at Terran by creating a comprehensive and optimized development package for these therapeutic candidates, which includes a salt and polymorph screen to identify the most stable form for GMP manufacturing and development, deuterated analogs and prodrugs to improve the PK, and novel “designer” derivatives with optimized binding to enable version 2.0 of the compound. Our different teams have been working diligently in parallel to innovate across this large pipeline of therapeutics and steadily advance their development.
You’ve mentioned salts and polymorphs quite a bit – why is this so important to you and why do you perform such extensive screening?
It’s actually standard practice to perform this type of screening prior to GMP manufacturing in order to identify the most stable form for scale up and formulation. In fact, the FDA usually requires demonstrated control of the polymorph to ensure any commercial product will have consistency from batch to batch.
One of the hurdles facing psychedelic drug development is that many of the early studies performed at academic institutions use salts and polymorphs of the compounds that have not been standardized or optimized for regulatory development. So in order to develop optimized psychedelic therapeutics suitable for the large-scale production needed to bring a therapeutic candidate through clinical studies, we perform the same salt and polymorph screens that we apply to all of our clinical candidate compounds. We believe this is essential for eventually bringing these drugs to market and demonstrates our commitment to these medicines and the psychedelic ecosystem as a whole.
Does the discovery of a new salt and polymorph or a new prodrug allow you to accelerate development of these compounds in any way?
In short, yes. While Terran may not be the first company to win FDA approval for psilocybin or MDMA, we 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 (typically 5 years after initial approval). We believe this approach would allow for further market expansion to those in need and help improve accessibility for patients.
Empathogens are a topic of much conversation recently as MAPS is preparing their filing for the potential FDA approval of MDMA. We noticed from some recent press you’re also working in the empathogen space, could you clarify what you’re working on?
Given its long history of use and clear efficacy, Terran chose MDMA as our primary empathogen to study. To enable a successful development program we performed an extensive salt and polymorph screen in order to identify the form that would be most suitable for large scale GMP manufacturing. This resulted in new forms such as MDMA hemifumarate which we believe has advantages over other salt forms. Additionally, the classic MDMA molecule is known to have a short half-life which often necessitates a booster dose during psychotherapy, so we looked to improve upon this and designed long-acting prodrugs of MDMA.
We also looked for other empathogens that may have other advantages beyond MDMA and identified several with extensive human use, including MDA, MDEA, MBDB, MDAI, methylone, and ethylone. Since these molecules have different reported subjective effects they could potentially be targeted to different mental illnesses. We believe that patients should have access to a variety of different options.
Is Terran considering collaborating with other companies in the space?
Collaboration is central to our mission here at Terran, and through our work we want to make sure to help buoy up the ecosystem in any way possible as we all work to find solutions for the mental health crisis. While we are currently developing our own lead compounds in house and intend to do so through FDA and EMA approval and commercialization, there are some molecules that may benefit from co-development synergies or other types of licensing or collaborations. It’s important to note that we aren’t just licensing patents but have 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. We’re a firm believer in “a rising tides lifts all boats,” and our door is always open to prospective partners.
Thanks so much Sam, for this special look “under the hood” at your pipeline and process at Terran. It’s great to learn a little more and nice to hear about your optimism for the road ahead. What else can we expect from Terran in the coming months?
Our chemistry and discovery engines are still firing, our development team is gearing up for additional clinical studies, and our business development team is forging new partnerships and collaborations with academic labs and biopharma companies. We look forward to unveiling some exciting updates soon, so stay tuned!
For more on Terran, check out Terran Biosciences Announces Licensing Deal with Pierre Fabre for Idazoxan; Completes Development Milestones
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