Interview with Transcend Therapeutics CEO Blake Mandell

My father's PhD advisor at Harvard was Timothy Leary, so I've always had an interest in psychedelics.  After decades in the regulatory wilderness,  psychedelic products like MDMA are now being developed to treat mental health disorders.

But if these drugs are approved there will be a new problem: patient access. The treatments generally require many hours of highly trained mental health provider time per patient. That's not going to scale.

Blake Mandell is CEO of Transcend Therapeutics, which seeks to address these challenges with a non-hallucinogenic MDMA analogue. That should mean much less need for clinical supervision of patients and should also take away patient concerns about tripping.

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Host David E. Williams is president of healthcare strategy consulting firm Health Business Group.

Episodes through March 2025 were produced by Dafna Williams.

Transcript

0:00:10 - David Williams
Companies are developing prescription versions of psychedelic drugs like psilocybin and MDMA to treat conditions including PTSD and depression. There is great promise, but also potential challenges to the healthcare system in supervising patients for hours while they trip After transcend therapeutics with a new approach that could be more practical and less expensive. Hi everyone, I'm David Williams, president of Strategy Consulting Firm Health Business Group and host of the Health Biz podcast, a weekly show where I interview top healthcare leaders about their lives and careers. My guest today is Blake Mandel, ceo and co-founder of Transcend. If you like this show, please subscribe and leave a review. 

Blake, welcome to the Health Biz podcast. Thanks so much for having me. It's a pleasure to be here. It's a great topic and, of course, when I saw BCG in your background, I had to say you know he's going to be a great guest for sure. So I want to talk about what you're doing with transcend therapeutics, but before that, and starting off, love to hear a bit about your background, your upbringing, what your childhood was like, any childhood influences that have stuck with you through your career. 

0:01:14 - Blake Mandell
Yeah, so I'm initially from the Miami Florida area and I was the first person in my family to go to college, and so my whole life dream was I want to go to college and learn and sort of have that more academic experience. And from a very young age I've always sort of thought there are two big questions in life. One of them is what's out there in space and one of them is what's in here in our minds, and I always was much interested in the second one, and so I started sort of reading psychology and philosophy in high school. Made for a bit of a strange high school experience, but it was. It was fun, and so I went off to college, I went to Brown, and while I was at Brown I had two friends died by suicide and that was sort of a turning point for me where all of this things around the mind went from being very intellectual to being very personal and I sort of said to myself well, if we can't deal with this mental health problem and this was, you know, a while ago and it's unfortunately much worse now I don't know what we at society are going to do. 

And so I thought I was going to go be an MD, phd, a researcher, some more. You know, david, we were speaking about your father, but I recognized pretty quickly that I was really fascinated with how the world worked and what was actually going on, and so that's why I, you know, went to BCG to sort of as my professional training school except they pay you, which is great, and that's working a whole bunch of different industries and from there thought maybe I could work in investing in companies that would help mental health crisis that we're experiencing, and went to a couple of venture firms, and the latter, the last one I ended up with, was a firm called Alley Corp, where I was working closely with Kevin Ryan, who's now my co-founder and chairman, and sort of from there I can get into the story, but sort of that's from where transcend was founded, got it All right. 

0:03:13 - David Williams
That's good. I'm sorry that that was. You know what happened to friends in college. Unfortunately, it's an all too common story. Not everybody is able then to actually do something about. It is what you're doing, so congratulations on that. Where does the Brown embodied neuroscience lab fit into this? I saw that, yeah. 

0:03:33 - Blake Mandell
So I had a really fantastic mentor in college and her name was Kathy Kerr. She initially was sort of in the humanities and after she was diagnosed with multiple myeloma, got an NIH grant to have a career change into neuroscience, and so I worked with her and many of the people from the lab are still some of my closest friends and we did one of the first sort of high quality research studies with Qigong, which is a form of Tai Chi but more medically oriented, has a medical intervention for post breast cancer fatigue Many people with. So this whole thing around long COVID has actually been seen often with patients who have sort of survived different cancers, this very severe and life impairing fatigue, and so we compared it against sort of the best practices of diet and exercise and lifestyle interventions and saw that it was not inferior, which is interesting because it was much less time than all those things and with with Kathy, she was really someone to have to teach us how to challenge the establishment, but to challenge it with data and actually moving sort of into what we're doing now. I was at a conference in November of 2016. And that's actually the weekend when Kathy passed away from multiple myeloma and that weekend I happened to run into a really interesting man. 

A very special impact in my life is Roland Griffiths. He actually passed away two nights ago, but Roland was one of probably one of the longest tenured professors at Johns Hopkins. The first half of his career he was famous for the psychopharmacology of caffeine and really studying it. The latter part of his career, he was the founder of the sort of the psychedelic research center at Johns Hopkins and I sat down to dinner with him, having no idea who he was, and was told by, you know, a very sober-minded scientist that still has a lot of benefit for patients with depression. Right, this is a really pivotal weekend for me. 

Kathy passed away and I met Roland. Seven years later, I wake up every day and I'm inspired by the work that he's done and helped make possible for many, many else of us. But one of the things we're doing at Trent's End and I'll get into it a little bit later on is that we don't think that the vast majority of patients with mental health symptoms and diseases are wanting to have psychedelic experiences. Yeah, and so the whole thesis that we have is what if you could have a lot of the therapeutic benefits without the psychedelic benefits, and so we could obviously dive into that no, it sounds good. 

0:06:28 - David Williams
Well, a lot of formative experiences you know relatively early on in your life and in your career. So that is, I think you know, very powerful. You mentioned a co-founder and I want to know about you know who's your co-founder and how did that come about? 

0:06:44 - Blake Mandell
Yeah, well, there's three of us. There's myself, Kevin Ryan, who is the CEO of AlleyCorp and one of New York City's most successful serial entrepreneurs in tech and healthcare. He was the CEO of DoubleClick, which is now Google Ads Everyone's used that product at some point in their life and then he started companies ranging from MongoDB to Gilt Group, business Insider, Zola, nomad Health, and worth over $20 billion in aggregate, and he so together he and I worked on a few companies. One of them was Pearl Health, which is now an Andreessen backed company looking at a new sort of Medicare-like mechanism called. It was called direct contracting and now it's ACOs, so that company is going off into the races. 

But I'd say the majority of the time that I spent working together with Kevin, I sort of told him on day one I passion a psychiatry and there's any way we can work in that, let's do it. And he sort of said to me all right, well, you know, I've sort of been interested in this psychedelics thing for a couple years now, given he was on the board of Yale and met my other co-founder, ben, who is now the founder and director of the Yale Center for Psychedelic Research, and so he said go off and find me a company to invest in. And that was fun because I got to go out and interview the leading 50 researchers in this space back when there really were only like 50 and now there's hundreds and hundreds and hundreds become one of the major research areas in the phyto-psychiatry. And at the end of every call I asked someone, I asked someone, you know these researchers. Okay, let's assume we zoom out five, six, seven, eight years. 

We assume that psilocybin and MDMA are going to be approved. Psilocybin for treatment of depression, mdma for PTSD. What's the downside? What do you worry about? And the answer was basically a unanimous patient access. 

Yeah, so let me sort of walk through the three reasons that are getting patient access. The first one is these drugs require a lot of clinical care, and not just from any clinician but from the most highly qualified clinicians who have went through a lot of training. So MDMA, which has now finished two phased-through trials in PTSD with really fantastic results. Both the trials have been remarkably positive, with some of the most robust results ever seen in philopsychiatry. Each patient's course of treatment requires 87 hours of clinician time plus medical time, and these clinicians need 100 plus hours of time for training, which so there will be some patients who will benefit, but still millions of patients for whom this will be burdensome, given there's already a dearth of clinicians in our country. 

The second is that MDMA and not as much as I have been, but certainly MDMA is contraindicated for patients who are concurrently on the most commonly prescribed drugs in psychiatry SSRIs, things like Prozac, where weaning patients off these drugs can be quite difficult and many clinicians are not comfortable doing so. And the third one, which will sort of be a little funny to you, but within this sort of like subfield of psychiatry where people are interested in psychedelics, is actually most patients in clinicians would rather not do a psychedelic drug if they could get the same exact therapeutic outcomes without the psychedelic experience. 

0:10:15 - David Williams
It sounds like pretty well laid out and also I can tell you a BCG background, because in consulting there's always three things you know. Sometimes they'll say there's these two and then, if you forget the third, say well, there's a third, but it kind of types into the second or so on. So that sounds good. We were talking before the show of my dad's PhD in social psychology from Harvard and Timothy Leary was his faculty advisor and it's interesting when you hear about this isn't exactly the same. But when someone's going and let's say they're getting painkillers after they've had some procedure, it's like and people say, well, that must be fun. And they're like you know they're not looking for fun, they're looking for impact. 

And to tie together a couple of the things that you said, well, first of all, someone's got a moderately successful approach to depression. They're on a medication. It's taken them a while to ramp up. They've got some sort of result. They don't want to be weaned off of it then for something that sounds scary and might be scary and they might not get it and might not work. So I can definitely see that the appeal if you look at it from the perspective of a patient and then, of course, as a clinician who doesn't have so many hours, why that could be successful. So it's a great idea to have it, but I mean, how do you achieve it? 

0:11:26 - Blake Mandell
Well, first I think it's one of the things I learned from Kevin is people, people, people. So there's three co-founders and I was very short on the third. Once again, the BCG were all three and his name is Benjamin Kelmendi. He's a psychiatrist on faculty at Yale and he was the first person since 1967 from when probably your dad was working with Timothy Leary to receive funding from the National Institute of Health to study psychedelics clinically. So he really is. He's broken the barrier for a lot of other researchers who have now been getting initial grants, and so his expertise in helping to navigate through these three weaknesses of psychedelics and also bringing out what is the strength of psychedelics, also within the historical context of psychiatry. 

In the key strength here there are two. I'm not gonna give you three, I'm just gonna give you two. So the first one is that in psychiatry there are a variety of translational models that are used. That means you do things to animals and assume that those will translate the patients, but for the vast majority of the time they don't have the type of fidelity and translation to patients that fields like rare disease and cancer do, where in rare disease, if you figure out there's a genetic issue with the patient and you can figure out a way to change that exact genetic issue. The patient oftentimes gets better, which is fantastic. 

But in psychiatry these are much more heterogeneous, difficult to define diseases, at least biologically, and so in the field of psychiatry, oftentimes advances in the field are spurred by clinical anecdotes. It's not clinical trials, but just you give a drug to a patient, you see something happens. It might be something different, and it's great because then you learn something, I mean. One example that people find funny is Viagra was not initially intended for that effect, but it was meant to be deal with blood pressure. 

0:13:20 - David Williams
But patients had certain side effects and that's where they developed it for, and so and I think Blake would happen in that particular trial is that, you know, it's the end of the trial and they couldn't get the patients to give back their extra medication, which is usually not an issue, and so it took some probing to figure out what was happening. Oh, was that really what happened? Yeah, that's how they had the idea. 

0:13:43 - Blake Mandell
Yeah, oh, I had no idea, wow. And so one of the interesting things here is when you look at this field like psilocybin was not invented five years ago, mdma was not invented five years ago you know these drugs have been used for thousands of years for psilocybin and for decades for MDMA and there were therapists working underground not until local trials again working with these drugs and you know many patients and clinicians had had these anecdotal reports and anecdotal cases of drugs having efficacy. So that's the first thing we want to look. We value human data over animal data to translate to patients. 

The second thing is one thing that was really exciting about psilocybin and MDMA, even linking back to ketamine, which has now approved the SNS enantiomers Ascata means for Vata by Janssen for treatment resistance and depression has actually came out of sort of the Yale group and Ben has worked with a lot of those people as mentors at Yale is this thing called neuroplasticity, which is a very vague term, but basically it means that there is sort of a new induction of like new things happening in the brain. And I'm very vague because there are multiple ways of measuring neuroplasticity. You can do neurogenesis, new cells, then dritric remodeling, where neurons basically connect to new neurons. The short term is neurons that fire together wires together, so that you fired new neurons and that leads to new things. And this has been highly correlated to therapeutic outcomes in ketamine, psilocybin, mdma, and these are all rapid acting drugs with neuroplasticity. 

One interesting thing as well is with SSRIs they take six to eight weeks to have a therapeutic benefit in patients for whom get a benefit, and this also correlates with neuroplasticity. It just isn't rapid acting and so, once again, so just to summarize, the first thing is clinical anecdotes and the second is neuroplasticity. And so we went out looking across hundreds and hundreds of drugs for what would solve these three challenges but also check these two things that we're looking for. We landed on this drug called methylene, and that's what we've primarily focused on to date. We've had to sort of walk into what it is and who our team is and whatnot, but I thought that the story of sort of figuring out it's sort of very consultant-like, like what are the difficulties you want to avoid, what are the checks you want to hit and how do you look at drugs across that criteria? 

0:16:14 - David Williams
That sounds good. I remember, as you're saying, in psychiatry or neurology there are these kind of anecdotal effects because when you look at the clinical trials, a lot of times they're using these measures that are actually just usually for screening or something and it's very hard to actually see anything going on and never mind. It's just not a very good understanding. So you might have a good drug and it doesn't. 

0:16:35 - Blake Mandell
I also want to share another just quick anecdote and then, we'll move on. So the first antidepressant was found accidentally. They gave a drug to patients and saw that their mood improved. And also, the first anti-psychotic was believed to be testing for some type of we would now call it anesthesia, but that's not the word they were using back then and they found that the patients had effects that they thought might be beneficial in patients with schizophrenia. And they did, and so really the whole field of psychopharmacology has started from these anecdotes. 

0:17:09 - David Williams
Yeah, the one that I remember that was a very strong one was more than an anecdote, it was a scientific paper, but they were talking about psilocybin and they were talking about people who'd had an experience with it 20 or 30 years ago and most of them reported that it was one of the one or two most profound experiences of their life. So it's like a very I remember reading that and I'm sure I don't have exactly accurate, but it's like, wow, they're really something. 

0:17:35 - Blake Mandell
I think you're totally right. Yeah, most patients found it in the top three, or if not the top five, most important experience of their life, up with getting married and having a child. 

0:17:44 - David Williams
So let's go, let's actually jump ahead and say, like, assume you succeed. So I was trained in economics. So they'd say you know, it's like you're stuck in a hole and you have this canned food and what do you do? And the economist says, you know, assume a can opener. So let's assume that you're successful in all the clinical development and all that. 

What's the potential impact on the US healthcare delivery system? I heard one thing that was relatively clear, which is that more patients should have access, because no way you can get, you know, 87 hours of time in order to, you know, have this therapy done by some, you know, some leading clinician, and also there's the people that will be scared of it and so on and so forth. We'll talk about that. But beyond that, a lot of what comes into primary care are people that actually at root causes depression, and that's actually a big reason why we have so much trouble with primary care access is because you've got patients that are there actually for something that's not really primary physical care. Is the ambition that big? Can you actually have an impact? You know, even more broadly than what you had suggested. 

0:18:46 - Blake Mandell
So first we are developing methadone, which we call a non-hallucinogenic rapid acting neuroplastogen for PTSD. We're in a trial in patients right now and we can sort of share on when that'll be done and we'll have some data to present. But we're also going to pursue patients who are suffering from depression and patients who are suffering from anxiety as well. Actually, on our leadership team, the person who leads our clinical development led the clinical development of one of the most reasonably approved drugs for depression from I and D, which is the first study through NDA, which is, you know, new drug approval. So we have a lot of expertise in our team and so our goal really is to develop, you know, a drug that can benefit patients across diagnoses. We don't envision methylene being used in primary care settings because a patient would need to come into a clinic to receive a dose, so primary care setting may not be the best setting. There's one interesting trend that the occurring right now that we think lines up really well with these novel treatments for mental health, and that's called interventional psychiatry. So traditionally, psychiatry is psychopharmacology, which means you go see a psychiatrist for 15 minutes. They say you know, try some Zoloft. To come back, say either it works or didn't, and they'll give you a different thing to try if not. But interventional psychiatry is as it sounds your psychiatrists are doing interventions with patients. This can range from things, as you know, as old as ECT, electroconvulsive therapy, to newer things like TMS transmagnetic cranial stimulation Transcranial magnetic stimulation to new things like ketamine clinics, which is where ketamine is used off label. Generic ketamine is used off label for patients, oftentimes IV or in a shot. Im Well, even ranging to now Sravada, which is, which was approved in 2019 for treat resistant depression. It's intranasal S ketamine and it's now at a $600 million run rate. 

Janssen's fastest growing product grew over 90% year over year where a patient comes into a doctor's office and they they need to be medically supervised and they take the drug and then they go home and they do this a couple times a week for a while. And with our program, a patient will come into a doctor's office, have a medically supervised dose, come back a week, a week later and do that for three or four weeks. And you know, obviously it depends on the data, but our goal is that a patient would then be able to have a response or even go into remission from their disease and come back many months later for the, for the sort of following course treatment. But but the whole thesis isn't that this is a everyday treatment or twice week treatment forever. It's an episodic treatment. So when the patient is sort of suffering from the disease, they come in and get a course treatment and then they go off and live their lives where they want to and then maybe, if it comes back, they'd come and do it again. 

0:21:41 - David Williams
Got it, so it will have. The impact on primary care is more indirect. I wasn't necessarily suggesting that it would be, but it should take off if someone's going to kind of this pathway instead of coming to primary care with something like a stomach ache or something. Yeah, they can't really be treated. 

0:21:55 - Blake Mandell
So interventional psychiatry is growing really, really rapidly. I don't have exact numbers we're sort of working on that right now it's not super clear but it's more than doubled in the last decade the number of sort of clinics that are doing this, and we expect to continue doubling as there become new treatments available that work well in an interventional setting. And so there are obviously two ways that a patient gets into an interventional psychiatry. They're normal, they're sort of traditional psychiatrists could recommend them or their primary care doc would recommend them, and so we see this becoming a larger and larger part of psychiatry, just like in many other parts of healthcare. There are sort of outpatient oncology clinics, there are outpatient infusion clinics for various diseases, so this is sort of becoming more and more a part of psychiatry. 

0:22:44 - David Williams
Got it. Talk about the PTSD trial. What is the design of that, how big is it and what's the? What's the path to approval from here? 

0:22:52 - Blake Mandell
Yeah. So right now we're in a phase two trial in patients with PTSD. All the patients in our trial actually have severe PTSD according to the sort of standard PTSD endpoint that's accepted by the FDA. We've split up the trials in two different parts. The first part is we call it part A and it's open label, meaning that all patients are receiving drug. We do this to make sure that we're seeing a safety and efficacy profile that allows us to feel comfortable, sort of locking a database and doing a randomized control trial. That's the third line, placebo control, which is part B. So we've now finished enrollment for part A of 14 patients. We'll be presenting that data in December and over the next couple of months we'll be starting the randomized control trial part of it. But hopefully you know we expect that to take 12 to 18 months depending on how you define the end of the trial. 

0:23:53 - David Williams
The funding environment for startup companies at least, like biotech companies, has been pretty challenging. So, early stage in development, what are you seeing in terms of the funding environment and how does that either relate to what you're doing or you're an exception to it? 

0:24:10 - Blake Mandell
I think, from what I've seen, investors are really going back to the fundamentals that existed before 2019. So on one hand, it's you know, worse than last, worse than two years ago, but it's not that bad that if you have good fundamentals and by that I mean you have interesting mechanism you can demonstrate safety, you have intellectual property, you're going after a big indication and obviously, at the end of the day, if you have efficacy in that indication, if you have those things, I think it's you know you can raise money. But biotech went up a lot in COVID, as we saw, as we as a society saw what amazing things you know pharmaceuticals can do for our world with the COVID vaccines and it's just come down from then. But so there are. There are companies who are are struggling, but the companies who have good data and strong teams and strong intellectual property, they continue to move forward. 

0:25:12 - David Williams
One of the things that I think may be in your favor is that I notice some investors, now that they're taking more sober view, are looking at kind of, if you are successful, what's the practicalities of rolling it out. And you see that with like cell and gene therapy, they say, all right, well, gets approved. Now how is it actually going to be administered? But a lot of the value proposition of what you're doing is actually that this is going to be something that, where there can be uptake within the health care delivery system, yeah, I mean, we're focused on access from day one. 

0:25:38 - Blake Mandell
Right, we have a wonderful, wonderful team who works tirelessly day in and day out to move our lead drug, Methylone we call it Transcend to a one sort of forward in each stage of development. And let's say, years from now. We got to approve a patient couldn't use it, It'd be a waste. Frank, I mean, this is where we're working day in and day out to help patients at the end of the day, not just to do great science, which we also do Blake, my last question for you is whether you've read any good books lately, anything that you might recommend? 

Yeah, there's actually a book I finished about a month ago and it's pretty dark book but it was probably the best book I read all year. It's called the Best Minds by Jonathan Rosen. He writes about his childhood best friend named Michael Lauder, who was brilliant. They grew up in New Rochelle and both of them went to Yale undergrad and sort of towards the end of your undergrad, michael began to sort of exhibit strange behaviors. Turns out it's schizophrenia and he was very ill and you know it goes. It goes through Michael's life going to Yale Law School and being very sick and Michael was famous in the 90s. Unfortunately, he murdered his fiancee and their unborn baby, believing that, you know, she was not the real fiancee. 

It's like a long story, but the way that Jonathan writes the book he's also worked on other other books and he's a novelist and writes nonfiction it's really beautiful writing and I think it really illuminates, from the perspective of someone who loves their childhood best friend, the pain that untreated mental illness or I would even say poorly treated mental illness, insufficiently treated mental illness causes not just the individual but really the whole circle of people around them who care and love them, and it makes me feel, you know, even more enthused to develop treatments for patients with PTSD, who today have only true approved treatments, both of which are SSRIs that were approved previously for depression. And so you know there's 12 million patients a year with PTSD and two approved drugs, and over 60% of these patients don't end up having sort of adequate responses that last. So it really struck a struck a nerve and I would highly recommend the book. 

0:28:12 - David Williams
I think we've shared more than the typical number of dark stories as part of this podcast, but they're all for a good reason that you're actually addressing and I appreciate that very much. So. Blake Mandel, CEO and co-founder of Transcend, thank you so much for joining me today on the Health Biz podcast. You've been listening to the Health Biz podcast with me, David Williams, president of Health Business Group. I conduct in-depth interviews with leaders in healthcare, business and policy. If you like what you hear, go ahead and subscribe on your favorite service. While you're at it, go ahead and subscribe on your second and third favorite services as well. There's more good stuff to come and you won't want to miss an episode. If your organization is seeking strategy consulting services in healthcare, check out our website, healthbusinessgroupcom.