 My name is Jonathan LeBecchi as of this morning. Actually, I am a lifetime DAV member But I've known Matt wherever he went off to For quite a few years now. I serve four years in the Marine Corps eight years in the Army medically retired from the Army in 2009 100% permanent total for PTSD TBI and a nice fun mix of physical injuries as a lot of us have Sitting to my right is Ben Everett senior director of medical science and health outcomes for maps public benefit corporation and He'll be getting up after I talk for a few minutes part of the reason that I'm up here There we go so I deployed to Iraq in October 2005 return October 2006 and And within 60 days of returning home, I put a loaded nine millimeter to my temple and I pulled the trigger After going to a church After going to Womack Army Medical Center and begging for help when I went to Womack It was it was rather funny they Asked me if I had guns at home. I said yes They said well, we're gonna give you six Xanax don't take it all at the same time because it'll kill you When you get home on Christmas morning, and this was Christmas morning They wanted me to wake my neighbors and give all my guns to them instead of and then come back after the holiday So I went home, and I drank a bottle of vodka and I pulled out my gun That was the first of five attempts to take my life over an eight-year period and for eight years I Lived in fear. I lived in my trauma. I had nightmares every night. I couldn't sleep And I think one of the best illustrations of How bad my PTSD above and beyond when I lost hope and wanted to end my life Was actually the fourth of July before I Went through MDMA assisted therapy I was in South Carolina and anybody here from South Carolina All right, you guys all know how much they love fireworks down in South Carolina and so My neighborhood lit up literally like the fourth of July just like Baghdad just like the Lod and so I started having flashbacks and I was in my closet in my body armor with my service dog, and I thought I was in Iraq Fortunately at the my wife at the time actually took me to a VFW post um To sit with other veterans and this is where organizations and VSOs like DAV are critical in helping keep our fellow veterans alive because I know personally if any veteran is in distress and just needs to talk I will sit and I will talk with them for hours It's also why I train my service dog over here to be a therapy dog And she actually does more therapy for people than she helps me and so I realized every day that I needed help and help didn't exist Or at least I thought it didn't exist and after my fifth and final suicide attempt After I got out of hospital I had I finally got the VA to give me weekly therapy And my I'll give credit to my psychiatrist. She was great and she upheld her promise One day she came down and she's like hey I got a situation with another veteran on the inpatient floor that I need to take care of it's a critical situation If you need medication You know, I can you can sit with my intern And you can pick it up at the pharmacy But can we just meet next week? I'm like You know go take care of the other veteran and I sat with the intern And that's what changed my life Because the intern was an intern at the medical university of south carolina being an intern It's probably the first one who had read my my medical file, which is about this tall now And she slid this piece of paper across the desk and it said Google PTSD MDMA and I did and I found out that Maps public benefit corporation was doing clinical trials on an innovative therapy in Charleston MDMA assisted therapy and frankly I was like Had a lot of friends who'd use that substance and I'm like this is legal. This is a safe environment Might as well try this before I died And I went in And then I went through three sessions Eight hours each under the influence of MDMA And it starts off pretty simple They ask kindergarten questions I'm gonna guess a lot of us have gone and spoke at schools and and other places and You know, I love talking to little kids about the military and stuff like that And one of the things I do is talk about how important math is That you know every military member needs to know math Why because we got to read maps and figure out how to get it from point A to point B And they always ask the same kind of question. What was the food like? What was the weather like? Things like that and that's the kind of questions they asked And for the first time I opened up For the first time in eight years, I could open up With two specially trained therapists And work through it And how it would work I'd talk for a bit Put on eye shades and then think for a bit Then I'd talk for a bit think for a bit I can't tell you how long I talked for and I can't tell you how long I thought for because When you're under the influence of the medication time becomes a weird thing But It's the best therapy I've ever done in my entire life. I went in thinking I was going to talk about Iraq I went in thinking I was going to talk about getting blown up And I talked about everything in my life from coming home and having my now ex-wife Moving in with another person My abuse at the hands of my mother as a child Literally every traumatic event in my life. I talked about and then I went and I lived my life on my terms That was eight and a half years ago I'm one of the fortunate people on this planet who can say that I have been healed of PTSD longer than I actually had it And I don't go sit in an office every day One of my jobs is to go up on Capitol Hill and share my story that I'm sharing with you But in my downtime as you can see here I go to Ukraine and I provide humanitarian aid I've been shot at by Russians. I've been under artillery fire I've sat in Kiev woken up from the air raid sirens that are believe it or not the same all over the world Wait for the bangs to go off roll over go back to sleep not a single nightmare This this therapy this treatment Which is not just here take a pill It's medication in conjunction with extensive therapy to get at the root causes The drug doesn't fix you To be honest you fix you What MDMA does is it it opens your mind body and spirit to the place it needs to be So that the therapy can work so you can actually talk about it and and not have your brain betray you with a panic attack Or or shutting down emotionally or becoming too emotional It keeps you in this middle ground, which Ben's gonna talk about here in a second But I I do ask everyone in this room to pay close attention to the science because I'm just a guy standing up here I know in my heart And in my mind how effective this is and how much this will help Every veteran with PTSD As well as every civilian because well We all argue over is it 22 is it 17 is it 44? Those are numbers Another number is 130 Regardless of veteran or not 130 americans take their life each and every day in america And each one of those numbers has a name And some of those names Like dusty repass a friend of mine that I served with he took his life about a year ago We were too late for them. It's time to stop being too late and it's time to demand from The u.s. Government that they allow these treatments And now I'll hand this over to ben Yeah, john thanks so much for sharing your story john all right, um, so My talk this morning is really going to fall into really kind of two to three phases We're going to spend some time talking about PTSD. I understand everybody in this room is very familiar with PTSD But I do want to spend just a couple of minutes going over through Some of the numbers especially as they relate to to military personnel and veterans as john just alluded to We understand that suicide Risk and and rate remains entirely too high among veterans The number has come down a little bit to about 17 veterans a day in 2020 taking their own life But it's still way too many and we know that PTSD is one of the highest drivers of suicidality and veterans So we have a long way to go to bring this number down further I'm sorry. I was on the wrong slide. There you go There's the There's the the the the graph I was talking to just a second ago And this is 57 high it's 57 higher among veterans Than the civilian population So again just entirely too high a burden that we're placing on our servicemen and women Um With regard to suicidality So we understand there's a number of different things that can predispose or or lead to PTSD Including being younger Being female Being non-white lower education status and having a parent that had some kind of psychological issue as well We understand that rates of PTSD are much higher in military personnel than they are in the civilian personnel So if you look at the left here, uh, the blue bar is women and the red or excuse me the orange is men Um, and and on the far left, we're looking at at military and veterans on the right We're looking at civilians and so women do tend to have higher rates of PTSD than men But we can see among veterans The rate in men male veterans is just as high as civilian women and again military women The rate is about twice that of military men. So really entirely I want to say too high, but you know the data are with the data are just PTSD remains a very large problem among service personnel and veterans Um, and we understand that this is increased in the past two decades Largely because of the most recent wars in Iraq and Afghanistan in 2002 The rate of PTSD was 1.24 for every 1000 veterans Now that's 12 essentially 13 for every 1000 veterans We understand that combat exposure and combat trauma are among the leading causes of PTSD in the military But that's not the only cause But about one and a half to three and a half times higher compared to non-deployed or non-combat exposed veterans Fully 37 percent's over a third of veterans that retire that returned from tours in iraq and or afghanistan Qualified for a diagnosis of PTSD And this isn't just these most recent wars We understand that this has been a problem for as long as we've kept data on this going back to world war two korea Vietnam So this last step here says that the prevalence of PTSD among veterans 40 years post vietnam Was still 12.2 percent and I understand from talking to psychiatrist at the va that the highest Rate of new diagnosis of PTSD right now is actually vietnam veterans. It's not veterans Returning from iraq or afghanistan So let's dive into this a little bit more detail So now we're going to look at two different things on the left We're just looking at what types of trauma can lead to PTSD specifically in veterans All right, as I just alluded to combat trauma is is the largest single driver of PTSD There's also being in a transportation accident that can include an ied attack or some type of assault with a weapon What's not captured here? Just because we have a three highest is sexual trauma 6.2 percent Of of individuals report sexual trauma as being the single driver or the largest driver of their Of trauma that led to their PTSD diagnosis Now you might look at this and say well then these numbers add up to way more than 100 percent And that's because for most patients with PTSD. It's not a single trauma It's multiple traumas like john shared a lot of times it starts in childhood It can intend it can continue into your adult life And it might not necessarily be just related to to combat trauma can be what happened at home as well So if we transition to the right again still just looking at these veterans We're going to get PTSD severity. This is PTSD Severely as rated by the cap score. So caps is the clinician administered PTSD scale It's a tool that was developed by the VA for veterans It has such a good track record of diagnosing and managing PTSD It's now the gold standard for all clinical research with PTSD But it's not really used clinically that much because it's an invasive It takes time takes about an hour to do this test But just to give you an idea This is in a percent. This is actually the score you get on this test So if you have a score of 28 to 34 That would mean you have moderate PTSD if you have a score anywhere higher than 35 That means you have severe PTSD So the three bars here are combat trauma sexual trauma and other trauma combat trauma. These patients have a score of about 69 So remember 35 Is severe PTSD. So this is almost twice the level that qualifies you for severe PTSD So we would say these patients have actually extreme PTSD the highest level of PTSD The largest PTSD symptom severity is sexual trauma So even though that's only 6.2 percent Report that that's the largest driver of their PTSD It's the highest amount of symptom burden and then other trauma is really just a catch-all of you know It could be multiple different things rolled in together So again, this just underscores that not only do veterans have higher rates of PTSD They tend to have much higher severity of PTSD once diagnosed We understand that military sexual trauma is a problem I think the VA is doing a better job now of identifying MST reporting MST MST does tend to be More in in female soldiers than male soldiers one in three women that serve reported MST One in 50 men reported MST What's interesting though is when we talk about who reports MST a third of people who report MST are men So it might not be that they had the trauma themselves. They might have witnessed it But because of chain of command didn't report it Something that made them feel uncomfortable that they witnessed So anyway one third of men reporting MST And getting back to suicidal ideation again just looking at veterans We understand that PTSD while PTSD in and of itself does increase rates of suicidality There are a lot of comorbidities that come with PTSD Especially in combat exposed veterans like john have tbi multiple other injuries that they're dealing with Chronic pain is a really big problem as is disordered sleep So veterans with PTSD have about a 50 percent higher rate of suicidality than civilians We looked at that earlier if you have sleep disturbance Or chronic pain You're actually six times higher than veterans that just have PTSD to have suicidality And we understand that again these are very common comorbidities So in terms of looking at some other comorbidities that veterans have with PTSD That might increase risk for suicidal ideation We know understand depression generalized anxiety alcohol use disorder Substance use disorders essentially a lot of times patients end up managing their symptoms with alcohol or other substances Instead of actually getting you know treatment that might actually prevent those types of things And then lastly to kind of close out this section. We understand that stigma is a really big problem For all mental health disorders So i'm going to have some civilian data here and some military data here But essentially it is the strongest predictor Stigma is the strongest predictor of help seeking behavior The more stigma you have the less likely you are to actually seek help All right, and estimated 52 to 74 of individuals as civilians with a mental disorder do not seek help We understand that this is even higher in the military 40 40 to 6 percent of military personnel who could benefit from professional treatment do not seek help Common concerns reported or my unit leadership might treat me differently I would be seen as weak or being discredited or devalued by their peers All right, we also know that military personnel report higher symptom burden and higher levels of stigma Which again potentially delays diagnosis and potential treatment And these are all compounded by perceptions that PTSD has a high economic burden, which we'll see in a second is true A negatively impacts military duty performance combat effectiveness combat readiness So in terms of the economic Impact the PTSD has to society and this is looking both at military veterans as well as general civilians This is a brand new paper. We just published Out of the tuscaloosa in birmingham veterans affairs administration late last year We understand that PTSD is a huge burden to the individuals that have PTSD As well as their friends families and caregivers But underneath that is a burden to society direct health care costs come in at 76 billion a year And direct health care cost at 36 billion per year loss of productivity at about 35 billion per year So in the civilian population, we're spending about 20 000 per patient per year to treat PTSD And frankly, we're not having very good outcomes And the military were spending 26 000 per veteran per year to treat PTSD and again No innovation in this field. We're using the same things that we've been using for quite some time And frankly, they're just not that effective as shown by the graph here So the VA recommends that it does the american psychological Association first line treatment for PTSD should be psychotherapy therapy counseling, right? Only a third of patients actually receive that All right, less than a quarter receive some type of prescription therapy Usually an SSRI like paxil or zoloft They go along with that 44 of veterans patients get a combination of these two treatments But when we look at these drugs, there's only two drugs that actually have an indication to treat PTSD Zoloft and paxil were Approved in the mid 2000s and frankly, they're just not very effective They have a lot of unwanted side effects associated with them All these other drugs that are used to treat PTSD are used off-label Another core issue here is all of these drugs. They just treat symptoms They do not plow the patient that has PTSD to understand and try and reconcile or resolve the underlying trauma That led to and continues to to be a problem for their PTSD So when we look at the right, we can see that even if you get combination therapy the best You know what we consider now gold standard therapy for PTSD Less than half of patients actually are met from their PTSD 56 of patients remain unrecovered. All right, this is for a number of reasons psychotherapy can be difficult to access You're supposed to get eight sessions. It can be very difficult to get eight sessions It can be difficult to get eight sessions with the same therapist We understand that there's a lot of burnout a lot of turnover in these things High dropout rates essentially for this type of therapy to work You have to relive the trauma over and over again until it's not a stigma to you anymore A lot of people simply cannot do that And as I indicated with the drugs a lot of the drugs have unwanted side effects They just don't work that well the effect sizes. We call the effect size how A measure of how well the treatment works are really pretty low Require chronic daily use and essentially just treating symptoms. So it's just take this pill for the rest of your life And hopefully you'll feel a little bit better All right, so changing gears and trying to set up, you know, why we wanted to study MDMA to treat PTSD Well, we understand there's a number of changes In the in the mind when a patient has PTSD So the amygdala I call that our lizard brain. So it's a very ancient part of the brain at the core of the brain That's where we have our fight or flight Um System and that's where we house Fear and in patients with PTSD their amygdala is is overactive. So they have enhanced fear learning It can be very problematic in the hippocampus. That's where our memories are supposed to be stored For appropriate storage and access later on and the prefrontal cortex is the front of our brain That's where we kind of reconcile all this. We have a lot of emotion The way that we Just deal with everyday life So all of these things are disordered in patients with PTSD And one of the things that's unique about MDMA and why we feel like this treatment modality is especially effective for patients with trauma Is that it actually treats all three of these areas it imports Changes in the brain to where it shuts down blood flow where it reduces blood flow to the amygdala So that you don't have this heightened fear response So that you're actually able to access the memories in your hippocampus And as john mentioned a lot of times veterans I'm going through this will you know not just talk about their combat related Issues but we'll remember things that happen in childhood Um that you know, maybe they didn't even realize that they had experienced these feelings will come up And appropriately we also have an increase in blood flow to the prefrontal cortex So that now patients are able to reconcile appropriately Get these memories where they're supposed to be and and be at peace with those memories All right, so Transition now to talk about MDMA assisted therapy and individuals to PTSD So to date we've completed two phase three trials So that's what's required by the food and drug administration or the FDA to seek a new drug Approval we'll go through that in a little bit later. I'm not only going to cover I'm going to give you a little timeline that gives you an idea of how much research we've done And then I'll talk about our first phase three trial To date so you can see here. We've done a number of phase one. That's kind of the first time you study An agent and people we did six phase two studies That resulted in an MDMA assisted therapy being labeled as a breakthrough therapy designation by FDA It's very unusual to get breakthrough therapy designation less than five percent of new therapies Actually get this rating from the FDA. You have to apply for it's very unusual So we're very proud of that and I think it just shows how promising this potential therapy is We've completed both of our phase three studies The first phase three study was started in 2018 closed down in 2020 Was published late last year and then our second phase three study closed finished late last year We had top line results Presented at a major psychological conference earlier this year and we're expecting that paper to be published In the next four to six weeks. Hopefully all right So we use the exact same protocol and both of our phase three clinical registry studies of the FDA So you'll bear with me. There's a lot going on on this slide. So I'm going to spend a couple of minutes Kind of be orienting everybody to exactly what the what the treatment might look like all right, so Essentially if a patient is deemed eligible to go in they have to have a diagnosis for PTSD They can't have known cardiovascular disease a number of things and they're randomized one to one in a double blind manner So the patient doesn't know what they're getting the prescribing psychiatrist doesn't know what they're getting and the therapists don't know What treatment they're getting Every patients get the exact same level and amount of therapy The only thing that changes is are they getting active mdma or placebo? So the patient meets with a therapy team. So two different therapists. These are highly trained therapists trauma focused therapists They meet with these people for three times to understand What's the nature of your trauma get to know each other to develop some kind of therapeutic alliance? And then also a lot of informed consent. Hey, if you get the mdma, this is what the experience might feel like This is what we hope to accomplish through this process After those three sessions the patients start three separate essentially one-month treatment cycles So you can see the dark blue circle indicates the dark blue triangle Indicates the the days the patient actually takes the mdma So the patient takes mdma these sessions last about six to eight hours as john said and you're in a room With two therapists the entire time So it's not like hey go take some mdma and sit in a room by yourself You're in a room with therapists to help you Manage the experience talk and and understand what you're going through Following that the patients then meet with the same therapy team Three separate times for these integration sessions. Now these sessions only last 90 minutes But essentially you talk through Not under the influence of mdma You know, what your memories were what you went through what you experienced and as you get to the last one You want to start setting up? All right. This is what we want to accomplish in our next session Okay Primary endpoint for our study was looking at that caps the clinician administered ptsd scale Um, essentially what their treatment burden was what their what their severity of their their ptsd was as this cap score We also looked at Comorbid depression Functionalities of how functional a patient is after this therapy Um Let's see if there's anything I missed. I think that's about it So this takes about 14 weeks total. So we consider this an acute treatment. It's not a chronic treatment It's here take a pill every day for the rest of your life. We hope you get better All right, so in terms of patient care characteristics mean age was about 40 Consistent with what we understand about ptsd two-thirds female 77 white You see the duration of ptsd in this first study was 11 years The highest was 50 years vietnam veteran baseline cap scores 44 so remember 35 is your cut point for severe. So these patients had severe to extreme ptsd Their sds. That's a measure of of how functional they are with seven That's pretty severe means these patients are having trouble holding down a job Interacting with their peers getting out of bed in the morning 21 had the dissociative subtype of ptsd This is an especially I'm going to say severe type of ptsd, but it's very difficult to treat This is where a patient literally just doesn't feel like themselves. They feel like a shell of themselves 18 percent were veterans 91 had major depression disorder 92 had a lifetime history of suicidal ideation and 32 had lifetime suicidal behavior All right, so very severe ptsd patients. So Let's look at the data All right, so this is that primary endpoint looking at their caps five score So the top blue line is patients who receive placebo with intensive therapy All right, you can see that these patients had a 14 point drop in their caps five score It's a really really good drop in their caps five score just by getting Very effective therapy in a controlled environment. However, the patients got mdma assisted therapy Did much much better a 24 percent or excuse me a 24 point drop in their caps five score so just to put this in In in in uh in context a drop of 11 points in your caps five score Indicates clinically significant improvement. So these patients are doing much better This is a very highly statistically significant and clinically relevant Decreased in their pts score and I mentioned effect size earlier. You can see here. That's that d the effect size is 0.91 That's a measure of just how well we think this this therapy works and that indicates that we think this therapy works really really well Excuse me All right, moving on this is looking at that sds. This is that Excuse me Measure of functionality Again, you can see in the top that's placebo assisted therapy these patients had a improvement in their in their Functionality score, but again the patients that got mdma assisted therapy had a much higher improvement Or a much better improvement in their functionality score And this measure a four point change is considered clinically relevant So it didn't quite reach that but it trended in that direction. It was still better than placebo assisted therapy And then lastly looking at depression again about 91 92 of these patients had comorbid major depression So we're not giving these patients any medicine to specifically address Their depression but going through this we can see very Very significant decreases in depression and again the therapy by itself works pretty well But mdma assisted therapy works that much better in addressing the patient's comorbid depression Put this all into context. What's this really mean? All right 88 percent of patients who received mdma assisted therapy Noted a clinically significant improvement in their symptoms 88 percent It's just a remarkable remarkable Change in the patient's symptom burden. All right, so that's the efficacy. How well it works. Well, what about safety? We always have to manage safety or balance safety with with therapies advocacy Well, what you can see here is mdma does essentially what we expect it to do Patients who received mdma Can report muscle tightness decrease in appetite some nausea that tends to be transient right when the medication starts to kick in They can sweat. They can feel cold. So kind of those cold sweats Pupil dilation Restlessness they can clench the jaw a little bit No cardiac Excuse me nine cardiac chest pain was uh reported enough in a couple of patients. So these things are all higher than placebo but importantly these all um, we say respond Spontaneously so essentially by the end of the day all these things have gone back to normal There's no special intervention that's required. It's not like okay You started having this problem So I had to administer some type of medication to address that they all revolve Spontaneously and in terms of looking at what we call serious adverse events This is like did someone have a heart attack or a stroke? In the trial with someone hospitalized not a single patient that got mdma assisted therapy had a serious adverse event There were two participants in placebo that did have three serious adverse events Both patients issues were related to suicidality One patient ended up self administering or excuse me self admitting themselves to the hospital Because they were having some suicidal ideation In terms of other adverse events of special interest So these are things that uh in collaboration with the fda. We decided we needed to take a close hard look at Because mdma does activate the sympathetic nervous system means it can increase your heart rate make your blood pressure a little bit higher We wanted to look at some of these things specifically the no cardiac events No new arrhythmias like atrial fibrillation And as noted in the trial no increase in abuse potential All right, all right. So to bring this to a close here I want to talk a little bit about who we are as a as a company so maps pvc is the maps public benefit corporation So, you know, a lot of people say what is a public benefit corporation before I started looking at coming to work for the company I'd never heard of a public benefit corporation Well on the left in the dark blue we have our traditional not-for-profit like a 501c3 like dav is These are Organizations that have tax exempt status. They operate for charity. They do not make a profit. They're not obligated necessarily to be Transparent because they don't have shareholders per se on the right is your traditional for-profit company These can be privately or publicly held. They pay taxes. They operate for profit But they can spend their money however they want and often this is just done as as returns to shareholders and dividends or things like that So in the middle is a public benefit corporation So that's what maps says a public benefit corporation is allowed to operate for profit. We do pay taxes But we spend our profit on a specific A specific benefit and for us for public benefit What we're really interested in is mental health and being innovative in the way that mental health is is diagnosed Talked about in terms of reducing stigma and ultimately treated In these patients. We're obligated to be transparent with our process or our progress and We are allowed to have shareholders Or stocks so in terms of where we are in terms of you know getting this potential treatment to veterans You can see here that we're on track. All right, we've done both of our phase three clinical trials We anticipate applying to the fda for a new drug application later this year And hopefully this will be on the market sometime next year So coming to va centers near you So with that i'll bring us to a close So we talked about a couple of things today one is that ptsd remains a very large unmet need in veterans It contributes to suicidality. It can be associated with a large burden to individuals their caregivers and society MDMA assisted therapy is a potential first in class treatment That we hope can really revolutionize the way that ptsd is treated As i just indicated we've completed both of our phase three studies Demonstrated significant clinically relevant improvement ptsd measures as well as comorbid depression We have a potential to treat 1.6 million patients with ptsd by 2032 And this combination modality again, it's not just taking a drug. It is drug in combination with therapy So with that i'll thank you for your attention this morning And john and i'd be happy to take any questions. There's a mic at the front of the room if anybody wants to come up