OK fantastic, I believe we are live and running.Welcome to our first content panel for psychedelic capital, so we’re going to be discussing clinical trials and real world evidence today.

On re from the Conscious Fund will be moderating should his Maltese and Wi-Fi allow an we are joined by Malcolm Barrett Johnson, Matthew Johnson and Andrew Pendrill.

We almost have 3 Johnson’s in the room.Gentlemen, thank you. For joining us very much appreciate you and I’m looking forward to the discussion.

Thank you.

She had we have five Johnsons.Otherwise he’s got this severe medical problem.How I’m so to begin with,I think that probably the easiest thing is if you could all just give a brief introduction and also maybe talk about the companies that you work for.And then I’m going to kick things off and start firing questions.

So Andrew, if we could start with you, please. Thank you thank you alright Andrew Pendrell on the CEO of a of delicate rank.I guess our profile is my Delica we’re a spin out from Imperial College London.The founders Robin Carhartt Harris.Effectively we’re trying to capture data out there perspective in the wild data of the psychedelic use and trying to leverage that data for a for credit.

Thank you very much Matthew.

Alright, so I’m a I’m a professor at Johns Hopkins University School of Medicine,Department of Psychiatry and Behavioral Sciences.I’m one of the leaders of our nominal Center for psychedelic and consciousness research at Hopkins.I’ve been doing clinical research with psychedelics for 17 years now.Since 2004 have published on any number of things in both.

Healthy, normal zanin clinical trial.So mystical experience change in personality.Openness treatment of cancer patients depression anxiety within cancer patients.Treatment of people with major depressive disorder.I developed the notion of treating people for nicotine dependence so helping with smoking cessation with psilocybin.

All of this, by the way,with psilocybin, although I’ve also worked with some other psychedelic compounds and.Yeah, uh, and also uh and barking.Currently on work to treat opioid,use disorder and PTSD with psilocybin and also treating chronic pain with LSD.

Some other things, but that about that.That’s a good. Yeah, that’s enough.It’s a good idea, but Malcolm.

Thank you Matthew is fascinating.I’m Malcolm about Johnson and Chief Medical Officer Velvet Labs.I’m in egotist, by training and medical doctor,still am used to work for them.Hi in London. Are you still in clinical trials division for the UK government?

At one point on the medical side Albert lamps is based in Canada.It’s Canadian based company but Barbie searches European focused at the moment we got a number of research centers coming online in London and Manchester.Learning big centres in the UK and we’re really focusing on anxiety and oncology patients and this is very unmet need in the UK and actually indeed worldwide.It addresses two UK government focuses which is effectively the anxiety and and urological of aspects which are the absolute fascinating and important and also the aspect of looking atNYU entities in this space in oncology.

So we’re very. We’ve had an amazing run in the last year.We’ve got an amazing team on board with a very very good Advisory Board,so I’m very lucky to work with you.And thank you very much indeed for asking us to to take part tonight.

Pleasant, Pleasant, so let’s dive into this I guess.In order to frame the question,I would ask everyone to look at this very much an investor,almost an emense perspective, and Andrew if we could start with you,could you talk a little bit about the typical prognosis for a clinical trial?

So how long does it take?What is the kind of average costs?

What is it? What is a typical clinical trial look like that uses a traditional pathway?Or perhaps the the obvious one there is Robin’s recent study,published in the New England Journal of Medicine.Which is intentionally was was with two to be 60 patients,but one dropped out. You end up with 59 patients in the study.

The cost was broadly about a million a million bucks.To give you a sense of it and the time period which event when you define the start of a clinical trial.Of course you know, for if we actually talking about from patient recruitment to patient patient completion and then when does the trial truly end?’cause then there’s always follow up periods,but you know, I think you can easily talk about sort of 6 to 12 months being being a very you know normal structure for a in terms of timeperiod. And yeah. Yeah, that they tend not to be that complicated,but but highly costly.

Unpack that trial gone alright?Let’s say that you had a drug under development that you got all the way through to phase three and the drug was on the market.

What kind of time frame are we talking about for that problem games?Sorry, that’s a typically that typically they take 8 to 10 years as a rough idea.Patent. Would be 20 years,so yeah, that was your sense of it.There’s a lot of speculation.

I mean, if you gotta trust Institute Delta out some numbers as to what they estimate the cost of from zero to hero as it were.For a friend, clinical development and roughly be throwing about a billion dollars per person for clinical entity as a rough idea.So not cheap and slow I guess would be the the two very basic conclusions from that.

Now Malcolm, you’re working with a very different protocol,famously actually just used for the development of a lot of covid vaccine work.And what is the difference in essence,between real-world evidence and a traditional clinical trial?

Thanks Honeywell. Affectively, a clinical trial is we,we know, from randomized control trials.You have a number of lines of inquiry affectively have patients in maybe one arm,two arms or three arms or four.When you’re meeting the, you’re looking at your product or the experimental products against maybe standard of care or against other standards of care together with another product.

So you comparing one against the other in your basically doing statistics on him to see whether one is over is actually more efficacious than another or even more safethan other. Collecting that data over,they are very short time actually considering or it could be quite long as Andrew said,but it’s normally quite a short here that I’m generally speaking.But what are you also got?

You’ve actually got a very controlled number of patients within it.He might have 60 like and resubmit the study from the other day where you may have 1000,but is still quite a low number.And when you’re dealing with patients who are very varied in the way they metabolize substances or in terms of their genomic structure as well,it doesn’t really capture the horse.

Data and So what will what evidences and we were data capture is is basically you must take all comers within the study.So you’re basically putting the substance in to population which is pre ordained and you’re looking at it in real time and you’re collecting the data as it’s being treatingas. You’re treating patients in the setting,which would be normally the setting in which they’re being treated.That’s good because it means you got a much greater number of patients.

Quite often you don’t have to follow the patients in terms of trying to.For some in a Secondly,you’ve got a much wider genomic structure,so you can see a very wide range of patients.And Thirdly, you’ve got a an ability to actually catch a safety data,which is difficult. Actually on such a wide range of patients in a randomized control trial,you do catch it, but normally you have to wait till the phase four or when they actually comes after license,and so it’s a very good structure to go into all that evidence.

So it’s effectively more realistic.It is a shorter path between the development of the drug and a patient getting there, and I would imagine a much cheaper exercise compared to the sort of billion dollar hundreds of 1,000,000 in terms of our traditional clinical trial.It is it’s extremely expensive to use medicines nowadays.And Andrew you actually write it costs billions to do so and.Is this very, very difficult actually?Do and you could have an incredibly clever team and great number of people working on it.

We would evidence to some extent,avoids most of that, and it’s a big advantage over RCT’s.

Thank you Matthew. Just from very broad perspective.Does it frustrate the scientific community that developing these substances is so difficult and that the if you have a patient population with an urgent needs there actually there isn’t?Except for protocols like Real world Evidence there is this very lengthly delay before you’re able to actually benefit that patient population even if you’ve stumbled across.A wonder drug Aurora. You’re highly effective intervention does that frustrate sort of scientists as much as it frustrates lenza capitalist?I think you may be muted.

It’s Matthew. In fact, I’m sure Mr yeah,there we go. Thank you.So two directions with that one I think.You know, uh?You know, compared to a whole lot of psychedelic,you know fans out there,you know, we absolutely need,you know, we need these regulatory bodies to vet these medications as well as all other medications for safety and efficacy.

And so we need to move through.You know, these, you know,registration trials, I mean most of the research I conducted earlier phase,you know, not necessarily. Within I towards approval,although some of the things I’ve worked on are now getting to that.

Phase and other entities frankly have moved in into.You know those upper phase trials based on work that that my colleagues and I have done.So, you know, deep appreciation for the FDA,the, the EMA and an equivalent bodies and what they do and the necessities of clinical trials.On the other hand, particularly for certain disorders,I think of the work with cancer so.

We did the largest trial at Hopkins with with cancer patients,treating them with psilocybin cancer patients with substantial depression and anxiety didn’t necessarily have to be terminal,but a good number were terminal and often that’s a hard assessment to make,and that’s a kind of a moving target in terms of the state of cancer treatment,but. In your gosh, I’m,you know, often contacted by people that say they run across the study that we published now.

What if you have a few years ago and it took us a long time to run that study?You know my husband is dying of pancreatic cancer.Who’s doing this work now?Well, no ones really picked up.We couldn’t get any funding to continue that work.

You know, no ones really.There are some, you know,entities that have shown some interest,but.Nothing is happening as far as I know,keepcheckingclinicaltrials.gov. Maybe something’s happening in a few years and it’s like,you know, my husband has a few months to live,you know. And it’s just heartbreaking.

And so I’m a big fan.For example, of what Canada has allowed the compassionate use,and I’m less familiar with their regulations.It’s it. Do US has the.This possibility, but my impression is that it’s a.

It’s a more difficult landscape,so you know Canada has already allowed cancer patients to be administered psilocybin.I believe in the form of psilocybin mushrooms.Based on the early work you know with the idea like hey,like these people, don’t. I mean,given that the record we know a lot like,physiologically, psilocybin is very safe.

There are risks, and those are largely behavioral psychiatric.Then you can address those through screening and monitoring and preparation,but with those in place,it just seems it does seem absolutely frustrating and horrific that people with the disorder like that can’t be treated.You know more immediately given what we know at the state of the science.

Yes, it’s a terrible balancing act between the need for safety and the patients need for.The most rapid possible access to treatment,and so yeah, very difficult kind of tip to mitigate basin Andrew,just on the subject of cost.Do you think that medicines in some ways have become too expensive to develop?

And do you think that is inhibiting the development of beneficial therapies generally?

I think I think you need a robust process.I think you need rigor in that process.I think there’s things that FDA and an approval authority should do too.See additional data to ensure efficacy and safety,’cause that’s that’s ultimately the primary concern,and I think that’s where real world real world evidence can come in and and and maybe help help those approving authorities understand what they’re dealing with.

So yeah, I think I think there’s options out there and it’s just it’s just getting that data and presenting it to to those regulatory authorities and getting them.Then be more and more comfortable with it.

Thank you so welcome you about to say something.

I’m just saying saying they agree and you know I think they have become too expensive and I think we’re in a very difficult position globally.Psychedelics and all other medicines actually because.We’ve reached a point now where science is actually advancing so quickly generally that we can’t actually treat all the patients with the medicines we got available to us.There’s only a limited number of patients,within reason with which you can treat as any limited amount of money.

We’re very lucky because at this point in time,we’ve got so much science available to us and it is getting too expensive.We have to find other ways of treating patients.We have to find other ways of doing research.If we don’t, we’re going to lose out enormously.

So I completely agree, and I think it is too expensive and I think this way of looking at what evidence is very valuable.Looking at the regulatory structure.The making actually structure is now changing.Its changing for one good reason.It’s been changed for a long time actually,but the devices we’ve had an awful pandemic we’ve got at the moment.

We’ve seen this with the vaccines are vaccines have been actually the biggest trial we’ve ever had over what evidence is exactly what we did.We actually tested it out on real populations in real time against a real disease,and we’ve shown it works.So Astra Zeneca did that.Pfizer did that Nova Vax have done it,and it’s an incredibly important lesson for the regulators and the regulators have suddenly waking up and thinking,wow. We can do it differently when we can look at efficacy day,safety, more time and look at safety.

Thank you, I’m just I’m gonna ask this place of Matthew and Andrew.This is a kind of.Picking up something that Matthew said a moment ago,which is that you did this very valuable early word.And nobody picked it up and ran with it.

Could you elaborate on the reasons why that might happen in academia and that something promising that clearly has a commercial output at the end of it is just notpicked up on him? Why does that happen?

Well, in the case of our work with cancer.Which which actually you know a lot of people miss this,but that that is the most advanced finding in the area for psilocybin,with with three published randomized clinical trials of various sizes but three double blind studies suggesting you know safety and efficacy and large reductions in depression and anxiety and incancer patients. But in that particular case,the reason.

One when we finished that work a few years ago,like there was very little commercial interest in in in this area.It’s like this is all ballooned out of nowhere,you know. And it was,you know. So at that time that didn’t exist,the the couple of entities that were exploring things chose to go with major depressive disorder,which in a way is a subset of some of our people.

Qualified for that we actually used.There is no DSM or ICD category for site cancer related distress,I predict in the future the science actually supports.A nominal disorder such as that,but nonetheless it’s not a recognized disorder now,so we allowed people with with a large a preset number of potential psychiatric disorders with the Attribution that it was because of their cancer that all involved anxiety andor depressive symptoms to be in that study.

So only a subset were major depressive disorder patients,but entities. Essentially you could you can view.You know this is a subset of the larger,you know depression, and frankly,you know folks that you know whether the interest is in helping people or the interest is in an money,or both.

You know, would you rather treat you know potentially 10%of the population? Or you know something like that.You know in terms of people with major depressive disorder or would rather treat,I don’t know what it is,but it’s you know, relatively speaking,extremely small. You know portion of the population with cancer related.

You know psychiatric distress, so you know the evidence keeps moving along that for depression,things are looking really depression itself outside of cancer is looking really promising as well,so maybe that’s a that’s a good bet and the idea is that hey,you know, maybe if this is approved for depression,a good number of those cancer patients who would qualify for this type of treatment.

So I think I think it was that in the case of of cancer,but there’s actually, I think now interest and we’ll see what happens.But as of pretty recently interest in really all of the therapeutic indications that we’ve we’ve explored or published,or you know, currently working on.

Maybe if I don’t mind me asking you a follow-up question so effectively,I mean, there’s a. Clearly there’s a commercial decision being made by the by the by the industry,and if we’re sitting here saying which I which clearly you are that if you know N stage anxiety is a subset of MDD and usona are seeking MDD approvaland FDA pathway to that,then I guess ultimately they would.

You would get some conclusion or some access for that for that patient population,

right? Is that fair?Yes, yes yes potentially so you know like that would be a part of the larger population that would qualify,but again, you know how about the people that are showing anxiety symptoms but not depressive symptoms and don’t qualify for major depressive disorder.And again, this I think there’s a science to support it,but there is an unrecognized syndrome that isn’t quite the same thing as major depressive disorders and quite the sitting certainly not generalized anxiety disorder.

You could argue it’s an adjustment disorder,but even that’s sort of a square peg and round hole.So hopefully a good number.I don’t know exactly how many,but hopefully a good number of those people.

But then it I do think it was more of a of a gamble.I mean at the time we didn’t have as much evidence as we we do now.For major depressive disorder and my bed is still long term that.In terms of effect size,an robustness that is good as the depression stuff is.

I’m guessing the cancer treatment stuff is just still the best bet.I mean from having worked with patients of all these types,it’s just like.Nothing works for everyone but relatively speaking.Gosh, it’s a Gimme, I mean a good psilocybin session.

So directly addresses this. The psychological symptoms that people go through at the end of life and an for some patients with major depressive disorder.It just seems there’s this constitutional.Issue you’re dealing with that where.Even with a great session it.It you know those old patterns kind of can bounce back,and again, I think we’re seeing some great promise there.

But, well, I still think cancer is kind of.If you had to name one disorder that is kind of just custom fit for psilocybin treatment,cancer is probably at the top of the list.

I and I would just add to that that I mean my my Delica which is the the website and that we’re building,and I guess the digital solution that we’re trying to bring to market.We want to capture all that data we want to understand what’s going on and guide and help those that you know there’s end stage anxieties and fears.I think we can do it and I think once we build up that data set,I think we can go to authorities and at one point it out to them and there’s you know I mean.

There’s an awful lot of people in America who have taken a psychedelic.I mean, 2020. Nineteen. I think it was 6.2 million people.A lot of those people.Clearly I’m doing it for,you know, self development. You know Wellness,Wellness efforts, and I suspect there’s a ton of people in there who are doing it for that for the end stage.

Anxiety. And by the way, Matthew, I spent a lot of time looking their studies,

and they’re really impressive. So well done in along the line.Thank you. In along the lines of what you’re saying.I’ve LED a number of projects more in the addictions area.Kind of based on the smoking cessation work I’ve done where?I first started probing. I kept getting these stories when present the data.

Sometimes people would come up quietly and say after a talk and they say hey,that happened to me and so does it say it happened 20 years ago or 30 years ago.And so I said, let’s do a survey of that and see just to kind of get it out there and so found you know thousands of people.That said, yeah, they quit smoking because they’re usually looking just a party on a psychedelic LSD or psilocybin.And so then we launched surveys for alcohol for cocaine,methamphetamine, cannabis. We’ve like public.

Opioids we’ve published results from all of it.Doesn’t prove it works necessarily,but it’s really compelling. You know,you know data, and then I’m not an expert in terms of how data like what you’re working on,how that interfaces with the you know evolving regulatory,what will be acceptable, but I had to say it’s extremely complementary and if it is 1 signal,that seems like something’s going on out there,even under sub optimal conditions.

In most cases, will Matthews,

who’s supporting data so thank you.It’s so they’re in very important because.You can’t really put a regulatory dossier in to get a license unless you got the backup.Unless you understand how it works and why group of patients so that what you’ve done is is really very valuable to everybody.So thank you and I think you’re right about oncology,particularly because if we’re looking at anxiety,which we’re doing at the moment,it’s about 1.2 million patients in the UK alone.

That’s a huge number of patients,and as we were saying before,you know to put a study together with that number patients or even thinking you got a population you can treat with.That would be nigh impossible.So you’re absolutely right about the cancer bit.

Thank you.If you actually generated this huge amounts of audience questions and I’m gonna.Three them as quickly as possible.I’ll start with you, Andrew.Where research is being done on paraphrasing this question slightly.

We’ve seen a lot of research on what you might call the classic psychedelic compounds.The six or eight compounds that everybody talks about.Is there anything inherent in the clinical trial or the real world evidence process?That makes it easier to work with known compounds rather than something rarer or a new synthetic.Is the reason that we’re seeing a lot of work something to do with regulations,

or is it just with starting with the stuff that’s known verse?I think there’s an element of,you know you start at the start right?But but what I would say too,is we’re looking to capture data where our objective is to be psychedelic agnostic.

So if you want to put in your five me O DMT data in their,specify what it is, would love to hear about it,tell us how it works,tell it, tell us why it why it should work with you.Again, that data is incredibly valuable,so but yeah, I think you know,I think it’s it’s really as simple as that.

I mean, I yeah, it’s just again a sort of sense.Full coherent approach, right?

Some people have said that regulators will favor compounds with.Simply more of a history,more data, more known and kind of touch points.Then something completely new to them is that.

Do you think that’s a fair comment?I think that I think the any regulator cares about the safety and that’s why the clinical trial process for to go from that zero to hero status you youstart with safety. That’s what phase one is all about,and so you need to have that data set to assure safety before you go any further.So that does make sense.

Thank you Anne Malcolm, very quick one for you.And what is the difference between global approaches to real-world evidence?So it are certain countries more favorably predisposed towards there isn’t a global approach.Others that right now. Yeah,

it’s a great question. I would say that at the moment,so I’m not pushing the UK because I’m sitting in London.The moment is actually the most open to it,only because we’ve had more experience of it.But there also it does depend on the.

Regulate his point of view is some of the regulators,like the EMEA is still struggling a little bit with wilwood evidence they haven’t had as much experience.So unless you got expenses are regulated by used to be a licensing assessor myself in the Regulatory agency,it’s very difficult in terms of America.The FDA are very open to this.

There’s now crossovers between IMB Hi,the NBA and the FDA.An indeed the Australian authorities are too.We seeing a lot of evidence also in.South America, they’re very open to this sort of study,so it’s varying. But what I would say is that it’s getting a lot better.

People really looking at this and thinking,actually, I don’t want to be left behind as a regulator.I want to be up at the top table,and I think even with Brexit in the UK,the Europeans are looking at UK and thinking all day.

No, I don’t want to get them to get away with this,so they’re coming down that line too,so I’m hopeful, but I would say the UK is probably the most open at the moment,

together with the FDA.So I hate to break it to you guys,but we are running up against time.We’re running late on our next panel.I’m sure this panel could go on for hours.

There’s a lot of fascinating coverage and information,and we genuinely appreciate you guys coming on to discuss.

Patrick, thank you my pleasure.Thank you all. Thank you thank you.

Come on.