Listening to Cannabis; MindMed Update; Manufacturing Questions and more
MindMed Update
MindMed Concludes Phase 1 dosing of 18-MC:
“Mind Medicine… has concluded dosing in a Phase 1 Single Ascending Dose (SAD) study of 18-MC. The dosing of 18-MC was well tolerated in humans and will help advance planning for a Phase 2a clinical trial in opioid addiction… The study tested doses ranging from 4mg to 16mg twice a day and all participants were evaluated for pharmacokinetics and safety… MindMed plans to begin the Phase 2a study of 18-MC in opioid addiction by the end of this year.”
It is important to note that Phase 1 studies are conducted with healthy volunteers, not the target population.
A Phase 2 trial for opioid addiction will pose two challenges: recruitment and drop out rates.
A paper from 2018 in the journal Addiction noted:
“Many addiction trials have also reported problems achieving their target sample sizes or taking longer to recruit than planned 10, 11, 12, 13, 14. According to one review, fewer than 45 of every 100 potential participants in drug dependence RCTs were actually eligible, consented and did not drop out immediately after randomization 12.”
The authors of this paper concluded:
“Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment.”
One way that MindMed and others undertaking clinical trials with this patient population might extend an olive branch and contribute to the psychedelic ecosystem is sharing what they learn from their experience in the recruitment and maintenance of conducting trials with this population.
Such disclosure would not compromise IP concerns while still contributing to a robust and resilient psychedelic medicine field.
Small Pharma
Last week, in a post about the different DMT drug development projects and their various routes of administration, I failed to include Small Pharma. This UK company has partnered with Imperial College London and appears to be targeting intravenous administration. Please excuse the omission.
All Eyes on England
Strident efforts are officially underway to reclassify psychedelics as Schedule 2 drugs to ease restrictions on psilocybin research in England.
The Synthesis Struggles
Presumably, the first generation of psychedelic medicine will consist of agents that are no longer under patent protection, assuming all goes well with MAPS, Usona, and COMPASS.
This is a challenging domain to wrap my head around.
Typically a company that stewards a new drug through clinical trials will have developed synthesis and formulation processes that are part of their Intellectual Property strategy. Once the drug gets FDA approval, the manufacturer has a period of market exclusivity. After the patent expires, generic manufacturers will then enter the market to offer off-label versions.
What is confusing about how this will play out in psychedelic medicine is that the first generation psychedelics combine products that have been in the public domain for years with psychotherapy— how this affects prescribing practices is unclear.
MAPS' approach to generating data will give them a window of market exclusivity as a manufacturer of MDMA. Presumably, the same goes for Usona and COMPASS.
So I don't understand the rationale for a company like a Mindset to announce that they have filed a patent for a "groundbreaking psilocybin synthesis" process.
CEO James Lanthier in the Press Release:
“Access to high quality, low-cost, psilocybin is essential to the medical psychedelic market; as the range of clinical trials, academic studies, and innovative businesses entering the medical psychedelic market grows, demand for psilocybin will increase exponentially. We believe that our innovative synthesis process will enable the widespread adoption of Mindset’s standard psilocybin.”
I think where I am jumping the tracks and what is challenging to conceptualize is that patents are typically leveraged to maintain pricing power (high prices); however, the opposite can also be true.
If any readers can help me better understand this dynamic, I would love to hear from you.
Listening to Cannabis
There's the running theme that psychedelics are not cannabis 2.0.
There are two ways of conceiving of this:
Represented by the development of MDMA, Psilocybin, and others to be FDA approved pharmaceuticals, (a route that cannabis never really had the chance to go down due to the bizarre and arcane restrictions around studying cannabis).
The other is in how to approach decriminalization and legalization efforts with the lessons from cannabis legalization in mind.
The details of cannabis legalization are beyond my understanding as they are different from state to state and country to country. Still, one theme that concerns many psychedelic decriminalization activists is the unnecessary complexity, regulations, licenses, restrictions, and required costs built into cannabis regulations imposed limitations on who could participate.
Allen Steiner, a cannabis consultant, and drug reform activists wrote a piece in Chacruna that provides some background worth noting:
"Steve DeAngelo explained how the original language intended for the 2016 ballot was changed dramatically when Sean Parker, the key financial backer for Prop 64, fired the Drug Policy Alliance (DPA), who had worked with stakeholders across the cannabis industry to develop language for the initiative. Parker then replaced DPA with an outside consultant who made compromises that advocates never would have allowed. Within its 62 pages, this new version of Prop 64 mandated local control, high taxation, heavy regulation, and packaging requirements that rival the pharmaceutical industry. All of this (and more) led to huge barriers to entry that prevented a majority of traditional cannabis operators from participating in the newly legal market."
In February, I wondered why to Decriminalize Nature Oakland would even dabble with commerce. Why not create a web of local prioritization efforts to build momentum, garner support, and data to support federal (real) decriminalization?
The proposed framework they announced last week is creative and could be effective in avoiding monetization plant medicine products. But, does such a proposal bring attention to shamans, guides, and participants that increase their exposure to state or federal punishment?
News and Headlines
Breaking: LSD Chemist William Leonard Pickard to be Released From Prison
Are magic mushroom edibles Canada's next drug trend?
Thanks as always for reading and connecting. Until next time.
Zach
Reminder about our New Project
In the last few months, we've seen a wave of psychedelic companies form, and some have even gone public with no viable business plans whatsoever.
On the other hand, thoughtful, pragmatic, and experienced psychedelic people who will be putting their hat in the ring with drug development, clinical infrastructure, drug discovery projects are quietly putting together their teams, strategizing, and fundraising.
At the same time, there are individuals with the business, legal, financial, pharmaceutical, and FDA compliance experience who are passionate about psychedelics and want to be involved with this movement but reluctant to offer their services to dubious actors.
The Trip Report readership has grown to a size where I think I can help connect these two parties.
If your psychedelic project is in need of expertise in any of the above areas
OR
you have professional experience in any of the above areas and you are looking for a psychedelic project
please send me an email (thetripreport@protonmail.com) and we’ll see if we can make meaningful connections.
On the topic of trials in participants with substance use disorders, it would not be surprising for MindMed to hire a CRO with experience in these populations to run the trial. In that case, MindMed would learn very little. No matter what they do, their knowledge will be small compared to groups that have worked on this area for years. So this isn't esoteric knowledge that only MindMed would have. NIDA puts significant money into treatment trials and maintaining this expertise. Much of the success in recruitment depends on small details like reducing time between contact with participants (eg, if someone contacts you expressing interest, bring them in the next day or two, not the next month), helping with transportation once they're in the study, and having a thoughtful approach to reimbursement. Finally, you're plausibly optimizing on cost per completed participant not on dropout rate. If someone is high risk of dropping out, you want it to happen as early and inexpensively as possible.
The motivations for applying for a patent on psilocybin synthesis presumably include protecting your ability to manufacture, specifically having legal ammo for litigation against other manufacturers. That is, it help you to be able to countersue if you're sued. Also, patent applications (no matter how improbable) make you seem valuable to investors, which young companies desperately need to do. I don't know MindSet's strategy, but it sounds like they are saying they want to supply active pharmaceutical ingredients for investigator-initiated clinical trials as an early income stream. This manufacturing capability could then position them to release a generic psilocybin medicine in 8 or 9 years or whenever exclusivity expires for any FDA-approved products. And they'll be positioned for supplying material for consumer products if/when/where that becomes legal.
Hi Zach,
In regards to some of your musings re Mindset Pharma and others looking to create revenue streams from production of non patentable compounds - From my understanding the potential goldmine is in finding the cheapest way to produce something like psilocybin. In the rub lies in the fact some methods may be exponentially cheaper. Examples that spring to mind would be Octarine Bio and CB Therapeutics. Both are looking to develop proprietary biosynthesis methods using genetically modified microorganisms like yeast. If successful batch fermentation of GM yeast could produce a far higher yield at a far lower cost than methods using direct organic chemistry synthesis or distillation from mycological sources, essentially blowing their competitors out of the water with their ability to provide low cost compound. The IP would then lie in the creation of a specific GMO used in the biosynthesis method and/or the enzymes involved. These novel biosynthesis processes could also then be potentially piggyback production of other novel (read patentable) psychedelics as a future source of growth for which ever company has the IP.
Not sure if this what you were wondering about but hope it's helpful!
Cheers,
Finnebar
(My views are informed by a Medical Degree with a previous BSc in Molecular Biology & Statistics).