Joseph Grieco, VP at Tris Pharma & Liza Micioni, Sr. Director at Tris Pharma

Jesus Moreno (00:01.722)
Welcome back to Global Trials Accelerators, the podcast where we dismantle the barriers to clinical innovation. I am your host, Jesus Moreno, and today we're taking a unique approach. We're looking at the life cycle of a clinical trial through two distinct but deeply interconnected lenses, the science of clinical design and the art of clinical operations. Joining us today is a dynamic leadership duo from Trish Pharma.

a company that recently celebrated its 25th anniversary and is rapidly scaling as a powerhouse. First, we have Dr. Joseph Greco, Vice President and Head of Clinical Development Operations and ROG Safety. Dr. Greco oversees a massive portfolio of Phase I through Phase III programs and serves as the principal investigator on a 17 million NIH NIDA

founded program. Alongside him is Liza Maijani, senior director and head of clinical operations. With over 25 years of experience, Liza turns complex scientific and regulatory challenges into actionable patient-centric success stories. Joe, Liza, it is an absolute privilege to have you both on our show. Welcome.

Joseph Grieco (01:28.637)
Thank you Jesus, we're glad to be here.

Jesus Moreno (01:33.432)
It is rare to have the strategic architect of clinical program and the operational engine driving it in the same room. And that is something I'm very keen to, keen on exploring throughout our conversation. But first I would like to start with a short conversation about your individual journey. So Joe, your career spans an incredible, incredibly diverse set of

therapeutic areas from rare neurological disorders to programs in immunology and ophthalmology and even pediatric populations.

Having seen the gamut of clinical development and looking back at those driving roles, what was the defining program or trial by fire, if you will, moment in your career that fundamentally shaped your philosophy of how to build a truly data-driven clinical strategy?

Joseph Grieco (02:40.851)
Yeah, Jesus, that's a really good question. My career, as you mentioned, has been in a lot of different areas. I started in single gene disorders, and I'm now working in pain addiction, ADHD, and even narcolepsy. My interest really started with trying to figure out how we best measure results from clinical trials.

So early on in my career, I was working in Angelman syndrome, which is a single gene disorder. And one of the areas that they had a need was they didn't have any endpoints that could adequately measure the efficacy of the trials or of the drugs that we were attempting to use. And so that's how I kind of got into this, right? I recognized as an academic that we needed to be able to focus our...

efforts on developing endpoints for rare disease. And then later on, I started looking at how do we make those endpoints electronic. I also was looking at for individuals that couldn't speak because Angelman syndrome patients can't speak. I was looking at how do we measure efficacy in a patient population that can't communicate with you? And so some of those areas that we explored as a team were

things like looking at 2D gate. We used what was called a gate map to try and assess the motor function in these individuals. We also used different iPads where the individual could look and communicate through pictures. So there's a lot of different ways that we can engage with our patient populations. That's just to mention a couple.

Jesus Moreno (04:37.84)
Thank you for that. I'm keen to exploring that particular aspect of how to objectively measure biological signals when it's a self-report process on behalf of the patient. And sometimes, as you mentioned, patients are not able to communicate that, to put it into words or provide you with what they're experiencing.

I'm very interested in exploring that further. But I would like to give an opportunity to Liza to share with us about her journey. Liza, you have spent over 25 years in the trenches of clinical operations, navigating everything from early phase trials to massive late stage programs in CNS and rare disease also.

You've even built an entire clinical operation department from the ground up. The landscape of clinical trials has changed drastically over the past two and a half decades. So I'm curious to learn what is the biggest lesson you've learned early in your career about managing complex vendors and global teams that still dictates how you lead today.

Liza Micioni (06:02.574)
So I think that the biggest thing is to always remember that it's about the patients. And so that has driven me from the beginning. I started as a project administrator at a CRO more than 25 years ago, and I was...

very much an admin. I did meeting minutes and I didn't quite understand all of it. But as time went on and I started to assist in the design of trials and vendor selection and really seeing patient data, I realized it's really about the patients. And so a lot of times that's what we have to focus on. So we can change vendors, we can...

you know, pick the best of the best. But we all have to be working for the same goal. And that's to bring life changing medications to patients, preferably faster. I think in these 25 years, I

I'd like to say everything has come a long way. A lot of it has come a long way. But there are still some things that we're still doing that we were doing when I started way back when.

Jesus Moreno (07:20.974)
And please, if you find an opportunity to bring those into the conversation, I'm sure the audience would be curious to learn from your perspective which elements of the process are yet to be improved or opportunities for improvement. But before we... it's fine. This is gonna happen throughout our conversation. Please don't feel...

Liza Micioni (07:38.958)
Oh, sure. Oh, go ahead. Sorry.

Jesus Moreno (07:50.309)
the need to let me keep going. If you have something you want to share, that's completely fine. But before we move on in our conversation, I would also like to explore

As you work together from the clinical perspective and the legit execution perspective, how your past experiences shaped your view of each other's role. Joe, as a clinical scientist, what is the biggest misconception development teams have about operations?

Joseph Grieco (08:33.193)
That's an interesting question. I'm not sure that there is a misconception. I think that sometimes we get in the way of each other or perhaps there's an ego that's involved. What I mean by that is early on in my career, I think that I thought that the science person was the most important on the team. Typically when we have the science person or the MD is typically leading that team.

you come in with a bit of arrogance. And I think that very quickly I realized that my best friend, the people that were looking out for me, the people that were going to allow our clinical trial to remain within compliance, remain patient focused, were our operations individuals. And so very, very quickly in my career, I figured out that they should be my best friend.

And instead of being egotistical, instead of being legalistic, my attitude changed toward them as a close colleague and confidant where I go to them for their advice. I go to them for their experiences and try and build that into the protocols and the science that I want to conduct.

Jesus Moreno (09:52.751)
Wonderful. you for that. And Liza, I similar question as an operation leader. What do you wish clinical strategists or clinical strategy teams rather understood better before handing a protocol to the operation team?

Liza Micioni (10:12.942)
So that is a very good question. So I think all different clinical development scientists have different levels of knowledge when it comes to operations. I think it's important that operations is involved during the protocol development because what looks good on paper may not actually work when it makes it to the clinic.

So, and luckily, since I've been in a lot of small biotech and pharma companies, our teams were so small that we worked really close together. And so there really wasn't the opportunity for clinical development to write a protocol on their own and hand it to me later. I've always sort of been involved in that. Although I do hear that it happens at larger companies sometimes that they just write the protocol and then hand it to operations and hope it'll work.

So I have been lucky enough in my career that I've been involved because I think it's important that operations has some input into the way this study is going to be conducted.

Joseph Grieco (11:19.763)
Yeah, I'd like to add there, you know, for us at Tris, we do really try hard to have a multifunctional overview of the protocol development phase. What I mean by that is our scientists will conceptualize something in the format of a synopsis typically, and that's really when we start to engage all the other functions, whether that's the regulatory affairs folks.

Jesus Moreno (11:21.606)
you

Joseph Grieco (11:46.281)
We really focus on operations because ultimately if they're not able to conduct the protocol and we have a lot of protocol deviations, clearly that affects the endpoints that we're trying to measure. But I think to Liza's point, it's really important to get a strong multifunctional input on your protocol designs very early before you even spend the money or the time and effort to build out the protocol in total.

Jesus Moreno (12:19.174)
That's excellent.

Would you say that there's a particular way to approaching this conversation that's been helpful within the team, or is it more of a let us do our due diligence and then we'll bring that to the team, we'll discuss and then the operations team goes on their own and brainstorms and brings back the, like whatever developments or insights they have to the table and then you guys come together and.

and land on a decision. What I mean by this is, is it a mix of individual work that then comes together in a conversation or is it more of a let's sit down and build this together simultaneously?

Joseph Grieco (13:11.411)
So as the leader of the group, I like to think that we sit down and build this together, but I'm going to turn over to Liza and let her answer.

Liza Micioni (13:19.48)
So I was actually gonna give the same answer. think at Trois we're very good at coming together as a group to discuss protocol design and strategy and operations kind of all at the same time. My past experience I've also done the same. I spent a lot of nights in a conference room, hashing out study design and the new protocols and it was important for me to be in the room, not.

from the science standpoint, but just to make sure that the protocol is able to be operationalized.

Jesus Moreno (13:54.618)
That's wonderful.

Joseph Grieco (13:54.727)
Yeah, there's a, there's a lot of things in clinical protocols that from a scientific perspective, we would love to capture, you know, and, as a scientist, I'm always trying to maximize the protocol to get as much data out of it as I possibly can. but there are a lot of times where, you know, Liza will, will rein me in and she'll be like, Joe, did you think about how many blood draws need to be done all at the same time, for instance, or did you think about what they're doing on the site?

at the site in terms of moving the patient from one room to another or weighing them at the same time you say that you need a PK sample. So, you know, there's a lot of that, but that's not even to mention the amount of time that things take. For instance, one of Liza and her team's roles is to manage our timeline and manage our budget. So, you know, if I add an arm to a study or if I add an endpoint to a study,

It could have some really big downstream implications in terms of cost and timeline. And Liza is always really good about saying, hey, you know, we can do it, but it is going to have these implications downstream.

Jesus Moreno (15:02.854)
Hmm.

Jesus Moreno (15:06.992)
So it's the key here in this conversation, I take it is the going into those potential alternative roads or alternative tracks with eyes wide open, understanding what the trade-offs are and being able to decide whether they're justifiable or not.

Joseph Grieco (15:37.001)
Yeah, I mean, I would describe it as having a second pair of eyes. but you know, Liza has a team of people, right? And so it's not just a second pair of eyes. It's a third and fourth pair of eyes too. Um, I think that again, we have to, we really need to, as scientists and leaders be open to what the people around you are saying, right? And make it and create a space and environment in which they're not afraid to speak up and tell you.

if there's something that they see could be challenging.

Jesus Moreno (16:11.02)
Of course. Well, I would like to maybe zoom out and take a look at the rather clinical landscape. The central nervous system space is notoriously difficult because so much of the data relies on subject reporting. And Joe, you hinted at this previously. So I'm curious to learn from your background.

In rare cognitive diseases, I understand that rare cognitive diseases values lean high impact trial design. How is the integration of digital health and objective biomarkers such as, let's say, AI enhanced eye tracking help to reduce the noise and the subjectivity in the CNS

trial data set shortening and does this even help shorten the clinical trial timeline?

Joseph Grieco (17:21.523)
Yeah, you know, there's a lot of available devices out there. There are meetings just full where you can talk to vendor after vendor of people who are developing new either wearables or systems to track movement, like you pointed out, eye movement, to basically create a human fingerprint, right?

I think that the challenge for me on the science side, one of my roles in the development program is to move the program forward to ultimately an NDA application and approval. And I think the challenge on my side of that is really in the regulatory space and the validation of the device or the endpoint. Going back to my experience in Angelman syndrome, for instance,

It took a large amount of money and time to develop what is now a global Angelman syndrome scale. But we're talking about years of development and trying to convince FDA that this is a valid measure, especially because it's somewhat subjective. To your point, I think that FDA is more accepting of these objective measures. I mentioned that we used a gate mat to record

the walking or the ambulatory ability of patients. While the FDA loved the idea, they were again unsure on how valid that was. And remember when you are taking a drug to the FDA, they're looking for a particular concept of interest or multiple concepts of interest that you are addressing with your medication. So.

If I am looking at gait, for instance, then my approved label is likely going to be for the treatment of ataxia in Angelman syndrome, for instance. So I say all of that to say that, you know, we can employ a lot of different electronic types of endpoints, but I'm not sure that the FDA is quite there.

Joseph Grieco (19:38.619)
and very certain about the validity of those endpoints. And I do believe that, at least in my experience, they allowed them as supporting evidence, but not necessarily evidence on their own.

I don't know, Liza, do you have experience in that space?

Liza Micioni (19:57.334)
and not a ton to add to that, no.

Jesus Moreno (20:02.479)
But I'm sure you do have something to say about how these technologies might impact the operational side of things. And maybe you can share with us, Liza, some of the biggest operational hurdles you faced and how do emerging patient-centric technologies have helped you solve them in the implementation of a clinical trial?

Liza Micioni (20:32.077)
So I think we really need to think about what we're asking patients to do during the study, aside from all the visits and the travel to the site and any assessments while they're there. What are we then giving them technology-wise that we're asking them to do at home on top of what they're doing when they come into the sites? And so I think it also often depends on the patient.

For example, my father had a flip phone until about two years ago. And so if it's an older population in your study, giving everyone or asking them to download an app on a phone that they may not have may not work.

you know, sometimes I think, I think we want all of our studies and all the patients in the studies to fit in one box. And sometimes I think we need to be a little more flexible. And so, you know, maybe we have technology for some of the patients, they can download the app and they can enter the data and we can have it electronically. But then maybe we have some, patients who either won't or refuse to, or just don't want to deal with walking around with a cell

phone that they need to do it on paper and we enter that data a different way.

I think we try really hard to say this is what we're using on a study. But the longer I've done this, the more I've realized that why do we need to make everyone fit in the same box? I think there's no reason, you know, just like some sites have certain technologies, if one has technology A and one has technology B, why can't I use both? If the ultimate goal is the same and the outcome is the same from either one, why can't I let them

Liza Micioni (22:20.408)
use the ones they already have. And so those are things that I've been looking into for future studies and, you know, trying to, you know, we try to meet patients where they are. I think it's important to also meet sites where they are and not give everyone new technology that they then have to start over on every study that they do. Because I'm not the only study they're doing, obviously.

Joseph Grieco (22:45.725)
Yeah, Jesus, I just would like to add to that, you know, anytime that there is a difference in the patient population, like Liza is describing, there's a layer of validity that needs to be assessed as well. And so if you are completing something on a paper source versus an electronic source, we've always validated from paper to electronic, but we also have to do the validation, know, interest subject validation as well or interest.

instrument validation as well. So I just would call that out that it's challenging sometimes to put two different tools, I guess, in a research program when they're measuring the same thing. The other thing I'd like to add is there was an experience of mine where we had some fairly low compliance in our phase two in terms of getting people to fill out

a lot of the questionnaires. It was a very heavy questionnaire-based program. And one of the things that we did implement and saw improvement in terms of compliance completing the questionnaires was gamification of questionnaires. There are several companies out there now that offer either a BYOD app type of device where they can put your questionnaires within their gamification program or app.

it gives people things like gems and cookies or whatever, you know, as they complete those things, they get to see on screen. within this particular program, for instance, as they gained gems, they were able to buy with those gems avatars and kind of deck out, so to speak, their environment within the game system.

And so there are opportunities to bring these kinds of things into the clinical trial space to encourage people to be compliant with the questionnaires and complete them. And I think the last thing I would say is I really, experience with BYOD or bring your own device, that is my preference because people to Liza's point, some might not have the device that we need and we can always issue somebody that, but

Joseph Grieco (25:06.385)
Somebody, I can't remember the research, I think off the top of my head is something like we check our phones 150 or 200 times a day, something like that. So if somebody has their own device in their hand, it's likely that they're going to see a message from our research app or whatever we are using to collect saying, hey, you need to fill out this form. And it keeps us from having gaps in that data.

Jesus Moreno (25:33.837)
Excellent. And I love that you both have pointed at something that's, let's call it real world, meaning the complexities of the real world are such that even a collaborative designed protocol sometimes fails to meet those complexities. And in the CNS trial space,

those factors of the real world rarely match one to one to the perfect ideal scenario where the protocol is thought of. And I'm curious to understand when trials hit a sudden operational roadblock, say an emerging technology as the ones that you've been describing is not integrating correctly into the protocol and

the endpoints are not being met. How does the tension between the strategy wanting to preserve the original data integrity and the operations needing to pivot to something that actually works place out? How does that conversation go behind closed doors and what are some of those compromises that both the strategy and operations teams

can leverage to come to a solution.

Joseph Grieco (27:06.172)
Liza, you want to go first?

Liza Micioni (27:07.694)
So I think in all of my experience doing operations and in recent trials that we have conducted, we made sure that we were collecting the endpoint, whether it was electronic or on paper. And that was...

fully discussed with all of the sites. in the event that there was a technology failure, because we all think that it's always going to work and it doesn't always work, they would at least be able to still capture the data. So they would capture it on paper source and we would make sure that it got into the electronic data. I think it's somewhat technology related, but a few years ago when the Ukraine war started,

It kind of goes back to the pandemic, those things that we didn't really expect.

that you mentioned the word pivot and I actually wear a bracelet that says pivot because it's one of my words that doesn't come off my wrist. And it's something that we constantly have to do because you wake up one morning and the world shut down for the pandemic. then Ukraine was getting attacked and we had sites in Ukraine at the time that had active patients. And so

It's something that we do in clinical operations. It's the most rewarding, but sometimes the hardest industry because we have to deal with real life in so many different situations on a day-to-day basis.

Joseph Grieco (28:48.167)
Yeah, I would say that I lean on the operations people to be creative. We always, I think that we go into the study understanding that at the very least, the primary endpoint is to be protected at all costs. You know, obviously, patient safety is first, but if we're talking strictly about the technical aspects of program, the primary endpoint is why we are doing the trial.

And in our operations folks, they are very good at understanding all the little details as to what can affect that primary endpoint. Pivot is a great word. I'm reminded of who was it Ross on friends when they were moving the couch up the stairs and it just wasn't fitting, right? Same kind of thing. We do have to move couches sometimes up stairs.

And fortunately, there are people on the ground, our CRO partners, our site staff that also understand and have received the appropriate training where they can also come up with ideas and say, hey, listen, we weren't able to record it that particular way or using that particular mechanism, but we can implement this mitigation instead.

Jesus Moreno (30:12.354)
Wonderful. Yeah, teamwork is essential to push this efforts across the finish line. And I'm curious to learn also in those initial conversations when you're deciding on the primary objectives of the study, how relevant is the conversation about geography as

Liza mentioned you guys were running some trials in Ukraine. well, looking at the global stage offers more opportunity, maybe shorter timelines, maybe lower costs at equally, at equal levels of data quality. But from the strategic and operational point of view,

How do you guys look at different geographies and evaluate whether they're a good fit for a particular clinical trial or not?

Joseph Grieco (31:22.921)
I mean, I would say that for me, it starts with the overall clinical development plan and the strategy for approval. I think that that's kind of where it comes from first, right? If we are going to be filing in the US, obviously, we're always gonna do our clinical trials and at least in part here in the US. But there is a large consideration to how other regulatory agencies are going to evaluate your data. And...

the need that they have, what kinds of treatment arms are they going to be looking for? What is their end point for their populations of people? Because let's face it, every country treats the same indication differently, right? We're in the pain space, for instance. The EMA has very different requirements for chronic pain indications than the US does because their patients are treated differently.

I think that also for me as a scientist and clinician, I'm also interested in the genetics of those individuals as well, right? Because in some regions of the world, metabolics are different. And so I'm kind of considering those types of things. Liza can speak to the feasibility and clinical trial site selection. So I'll turn that over to her.

Liza Micioni (32:47.82)
Yeah, so I think as Joe mentioned, I have experience where in Europe, they were OK with an active comparator, but the US wanted a placebo and it was a pediatric population. We ended up doing this study only in Europe because no one was going to put their child in a study that was placebo controlled in a rare disease in the US. And so

I think once we figure out where we're going, we do feasibility. there are some, I used to do rare lung disease and there were some areas of the world that it just didn't exist. And so it all sort of depends on what the indication is that we're looking at.

I think feasibility wise for pain, I think we can find that anywhere globally. But I think a lot of times it depends on the actual indication and what you're looking for when you go to certain countries. As you mentioned, there are different timelines in different countries, but while parts of it might be shorter, other parts of it might be longer. Contracting might take longer even though the ethics might be shorter. so sometimes the timing

It all just sort of depends. Like as we know in the US, if it's an academic site that uses a local IRB and does their own contracting, it could take eight months to a year to get them up and running. So I think it all depends on picking particular sites and knowing what the limitations of those sites might be.

Jesus Moreno (34:31.13)
So understanding the context is key in deciding whether it aligns with the primary objectives of the project or if you're willing to invest more in either time or money at a a better aligned context to what you're trying to achieve. And I think that's true of every player in the space.

in particular in drug development and really in any startup space. There's this concept that we talk about fairly frequently in this show, which is the valley of death, or in other words, that brutal stretch where the money dries up before the product is proven to work. I understand that Trish has leveraged platform technology

technological platforms such as Liquid XR, correct me if I'm mispronouncing that, but you use that platform as an essential or foundational better way of building over what you already have proven to be successful. How does having that technological head start act as a bridge over that valley?

saving both capital and years of development time.

Joseph Grieco (36:03.869)
Yeah, I'll take that question. Yeah, Tris has been around for about 25 years and has over that 25 years been very successful at using these platforms, you said, LiquiXR, for instance, to take short acting drugs and make them not only accessible to people who maybe can't take a pill, but also make them longer acting. So using these technologies, what we typically do is follow what's called the 505b2 path.

which is where we can utilize this drug efficacy and safety data of drugs that have already been approved and shorten the timeline to approval by using those data that have already been produced. What we end up doing is we will conduct phase one or pivotal types of bioequivalence studies and show that in terms of bioequivalence PK, which is pharmacokinetics and pharmacodynamics,

that we have a matching bioequivalence profile. And using that profile, the FDA is comfortable using the safety data from other companies' products to allow us to gain a marketing approval on those drugs. An example of that recently is a Clonidine product that we produced, which is called Anita. And we are currently marketing that now in the ADHD space. But that Clonidine has been around a long time.

we applied our platform to clonidine and now have a non-stimulant medication to treat ADHD.

Jesus Moreno (37:43.525)
So leveraging what is available already in the market is, let's say, a strategic move for those entrepreneurs that are fighting that burn down rate and might be faced with difficult decisions ahead. Looking to how to leverage already proven therapies might be a strategic move. It's what I'm hearing you say, Joe. Is that correct?

Joseph Grieco (38:11.037)
Yeah. Yeah, it's also identifying a space or a gap or a need, right? For ADHD, know, stimulants have been the gold standard treatment. But what we found through our medical affairs and our connections with the physicians that treat people with ADHD, as well as the patients themselves, is that sometimes the stimulant isn't enough.

And so what we noticed was that stimulants were being provided, yes, but the physicians were using other medications off-label, one of those being clonidine. And so the idea was that if we could fill that space, we could fill that need and extend the efficacy of the clonidine product, then we could offer that as another option or combination option for patients with ADHD. So.

Again, our company has been very successful over last 25 years looking for those spaces, looking for those gaps in what the patients' needs are, and then finding a product, reformulating that product to then bring that product to the patient to fill that need.

Jesus Moreno (39:28.07)
It's very interesting. I heard recently that you are close to announcing or you recently announced better that you will be presenting the Butyl trial data for your investigation in pain medication. I believe it's called Severinopadol.

Joseph Grieco (39:54.761)
practice.

Jesus Moreno (39:56.497)
That's going to be presented in the American Association of Psychiatrics in Medicine 2026 conference. And Joe, correct me if I'm wrong, but I believe you're the principal investigator for this program backed by a 17 million NIH NID grant. And well, please, please go ahead.

Joseph Grieco (40:16.561)
Yeah, yeah, let me talk to you a little bit. I'll talk to you a little bit about that. Yeah, so there are two different programs actually. The initial indication that we're going for for Sobernop et al. with the FDA is the acute pain indication. And you referenced the presentation of that data that was actually presented this past Friday in Salt Lake City by Dr. Todd Berta.

And so that was kind of the debut of what we call the alleviate one and alleviate two clinical trials. That was a abdominoplasty and bunionectomy pain model. FDA requires that when you go for an acute pain indication that you do it, you do your studies in at least two pain models, one skeletal pain and one visceral pain. So the abdominoplasty is that visceral pain model or that soft tissue model and the bunionectomy is that skeletal model.

In both of those studies, those phase three studies, we showed statistically significant efficacy over placebo, which is important. However, the most important feature of this medication is the safety profile. We have also conducted the safety studies, what are called human abuse potential trials. We've conducted a few of those trials.

And in both of those studies that we conducted, we showed that compared to opioid comparators like oxycodone, our drug was not what they call liked. This is an indicator of abuse potential. Most importantly from one of our studies, we compared it against the schedule for tramadol and the drug was not liked like even tramadol was, suggesting that while we are getting superior

efficacy with this medication, we do not have the same abuse potential that some of the opioid products out there have.

Joseph Grieco (42:18.835)
So that's the pain of patient. Now you mentioned the grant. And yes, it is true. We have a grant for about $17 million. This is with NIH NIDA, National Institutes on Drug Abuse. This particular grant is a grant in opioid use disorder. So early on in the development of this drug, what we found in some animal models was that

there was a potential for this drug, severinopital, to treat animals that were addicted to heroin. And there's a whole animal paradigm that I could talk to you about for hours. But the reality is, the short version of this is that these animals at one point liked heroin, they went on to the severinopital drug, and then they avoided the heroin when they were reintroduced to it. So this suggested to us that there could be a potential for

treating opioid use disorder. We have a tremendous amount of data in this drug in terms of safety. And so what we did was we found a grant, what's called RFP, request for proposal, and we applied our science. We wrote up everything we knew about this medication, as well as a five-year plan for developing this medication and opioid use disorder. And we applied for the grant to NIDA.

Jesus Moreno (43:28.068)
Thanks

Joseph Grieco (43:38.781)
They reviewed the science and they said, we agree with you. This looks like a fantastic idea. You should explore this. And so that's exactly what we're doing is trying to get some of that basic science information and early human experience to see if this is an opportunity to move forward with.

Jesus Moreno (43:59.961)
And for those founders in our audience that are used to that capital heavy venture model where they have to dilute their, they have to use dilutive strategies to partner with venture capitalists. This is an alternative. Finding evidence in the animal models and applying for grants that

might be a strategy worth exploring for some of our audience members. And yeah, it's a valid strategy.

Joseph Grieco (44:35.465)
Absolutely. I have a friend and colleague that, yeah, sorry to interrupt you, go ahead.

Jesus Moreno (44:42.434)
No, I was going to finish the idea by saying that's a less common but valid strategy to overcoming that valley of death or that extreme burn rate that sometimes leads entrepreneurs to get involved in dilutive partnerships that might affect their exit strategies later on.

Joseph Grieco (45:07.561)
Yeah, no, I agree with you 100 % on that. I was just going to make the comment that I actually have a colleague and friend that has started a whole company and only operates off of grant funding. And so, you know, that's not as common as having a mix or trying to get venture capital dollars or some other investment, but it is a possibility to do, yes.

Jesus Moreno (45:37.489)
Well, that's worth exploring, I'm sure. excuse me, Liza, Liza, I wanted to bring you back into the conversation and ask you about running a pivotal phase three pain studies with a novel mechanism of action requires intense orchestration. Whether it is investigators, CROs or

internal teams, how do you bring all these moving parts to deliver the precious data in time for a major debut like the AAPM 2026?

Liza Micioni (46:21.774)
So it's important that your CRO and your other vendors are partners. And yes, they are vendors. They do work for us. However, I think it's important that you build those relationships. I am a big believer in face-to-face interaction. So.

Sometimes we have done face-to-face bid defenses or kickoff meetings. We did have face-to-face investigator meetings. And I think having everybody together, not just the CRO team and the sponsor team and the vendors, but we also get to meet the sites and the coordinators and the investigators. And we actually get to sit down and chat and have dinner together and have conversations that aren't entirely work-related.

a lot about work, but you sort of get to know the people that you're now going to work with for the next, you know, six, nine, however many months it is. So I'm a big believer that that is sort of how you start a study on the right foot.

If nothing else, you at least know your CRO and your vendor partners and build those relationships. I have known some investigators for so many years that I moved companies and I was in the rare respiratory disease space and one of my team members said, the investigator will not sign our CRFs for us. And I said, give me 10 minutes. And I texted him and I said, hey, I'm at this new company. I heard you're not signing your CRF.

And his response was, will be done by the end of the day, promise. So even though I didn't even know we were working with him, but those relationships have been so instrumental in my career because I know who I can count on. I know who I can call when I'm in, you know, need something urgently. But I think, you know, having those relationships built from the start is really important.

Jesus Moreno (48:05.275)
Wow.

Liza Micioni (48:29.006)
And I think that's why our phase three acute studies were so successful because we had those relationships up front and we had an amazing team with the CRO and the vendors. And we actually enjoyed meeting together every week. Sometimes those team meetings get a little tiresome, but I actually really enjoyed talking to them on a weekly basis because we just had such a great rapport.

Jesus Moreno (48:57.924)
That's wonderful.

Joseph Grieco (48:58.311)
Yeah, as the leader of the group, I encourage my team to get on the ground. I think that Eliza is on the road quite often because of her role, as well as some of our other individuals. But I completely support her and her team being in front of people. But I take it a step further. I'm in front of them too. I think that it's important for our science people to be in front of them too.

These are the investigators that do this on the daily. And so if you are breaking bread with somebody, if you're talking about what are some of their challenges, then when we are kind of conceptualizing our protocols, we can automatically build those things into the protocol so that you can cut down your review timelines, for instance, or you can make something much easier. so again, this just goes back to cross-functional team building and making sure that

you are including them as your team, but also getting the insights that they have because they do this every single day, day in and day out.

Jesus Moreno (50:07.268)
That's wonderful. And on that note, I want to give you guys an opportunity to comment on Trish's celebrating its 25th anniversary last year. And the momentum is palpable. As you look ahead to the commercialization of these innovative therapies, what is the core mission that keeps your team moving forward every day?

Joseph Grieco (50:33.939)
Liza, you wanna go first?

Liza Micioni (50:35.438)
It's all about the patience. You knew I was gonna say that.

Jesus Moreno (50:37.594)
Hmm.

Joseph Grieco (50:37.819)
I knew you were going to say that. didn't want to take it from you. It really is. It really is all about patients. think that Tris's core mission from the beginning, even before I arrived, which was only about three years ago, has always been about meeting the need of a particular patient. They focused a lot on the ADHD patient and having four branded products and now five.

But now we're able to transition or maybe not even transitions, probably not the right word, I guess, add to the pipeline, add to our abilities that new chemical entity experience, right? So CyberNAPIDAL will be our first new chemical entity. We, instead of following the 505b2 pathway, we'll be following the 505b1 pathway. And so we are in the process of preparing our...

our filings and all the data and getting all of our docs in a row to submit that first NCE, which is really exciting for our company, right? And I think that that's one of the reasons why I joined Tris was to, I saw that as an opportunity to lead a whole new era for Tris. And I think that that's also why at least Liza joined us as well. I know that that was a discussion that we had, but.

Jesus Moreno (51:41.478)
you

Joseph Grieco (52:01.929)
You know, we're able to cover a broad spectrum of individuals. Our pipeline is growing. As you mentioned, have ADHD products, have pain, we have opioid use disorder and substance use disorder, and in narcolepsy. We're working in the narcolepsy space as well. And that doesn't even touch the areas that our formulation scientists are working in. And so we have a very exciting pipeline coming up and a big future. 25 years is just the beginning.

Jesus Moreno (52:32.762)
Well, congratulations for that. Joe, Liza, this has been an absolute pleasure. You've shared with us how to accelerate clinical trials by having brilliant scientific design and the operational agility work in tandem. To our audience, thank you for joining us on this dual perspective deep dive. Remember, a great clinical protocol is only as successful as the team operating it.

Until next time, keep accelerating.