Hey, great. Thanks, everybody. It's 12:30 P.M. We have TriSalus Life Sciences, TLSI is the ticker. Mary and James are joining us once again, CEO and IR respectively. For those of you that don't know this company, we launched coverage of about a year ago.
Mm-hmm.
Came public via SPAC-
Yep
As I recall. I think it's a little bit unknown to the street, though, that traction is starting to build. I think it's actually very important. And another key aspect of the company is that it is revenue generating with its TriNav device, that it's used for in TACE and TARE procedures. And then it also has a clinical side,
Mm
...with a TLR9 agonist, which is pretty cool because we've seen activity around the TLR9s historically, seeing good data with intratumoral injection. They're able to take their device and leverage that to deliver it to the liver, which is basically impossible to do, so very cool things happening there. So, you know, I think what would be great, Mary, is if you can give us a high-level overview of the company, and then maybe we can break it up into the business side and the clinical side for updates.
Sure, sure. So, you know, we're a company where the mission really is to improve outcomes for patients with liver and pancreatic cancer, and we have a very innovative technology that can deliver more therapeutic to the tumor, and improve outcomes, and we do that today. It's a very high-margin technology, that we use in liver procedures, where they deliver radiation or chemotherapy beads deep into the tumor, and they're called either, you mentioned, Jason, TACE or TARE. It's transarterial chemoembolization or transarterial radioembolization. And this is an important treatment for patients who have HCC or liver metastases from other cancers, and really helps extend life and, you know, give patients a break from their typical systemic regimens.
And the data that we have on this is that we can deliver more drug to the tumor, we can reduce complications, patients have less post-procedure visits to the ER, and we got an exclusive reimbursement code from CMS for the compelling data that we produced, not only from our clinical data, but from a very large health, economic, and outcome research study over two years. So we're very excited about this technology. Sales are growing in excess at 50% a year, and we're guiding that for the foreseeable future. We have very low market share, and we're very excited about its growth. You know, we're coming up on our next quarter earnings. We're excited about that, very robust growth.
What I think is really unique to this company is that we have a very broad clearance, that we can use our technology, which modulates pressure and flow, to increase that delivery into the tumor throughout the body. We were approached by a physician group in Florida. They started using the technology to treat multinodular goiter, which is a very significant market. Conservatively, roughly, we're targeting another 50,000 procedures, and the beauty of this is that they can use our technology, avoid you know, risk of stroke or surgery.
Ablation is used for the very small nodules, but for multinodular goiter, which is a very challenging one to treat, we can, you know, do that minimally invasively, avoid a scar in the throat, these are typically women, avoid long-term thyroid replacement therapy, and avoid some of the complications of stroke and nerve injury. So there's enormous excitement in the interventional radiology community on that. And we've launched a program to collect data on that, really to become standard of care in that procedure as well, which expands our market significantly. We also have a pancreatic device that is FDA-cleared. We're very excited about that as well. This is where we can deliver drug directly to the pancreatic tumor. And we approach the pancreas in a very unique way vascularly.
We go through the venous arterial network, which allows us to get into bigger vessels. We can get and place our technology and deliver drug directly to the tumor, and we're exploring it in two ways. We're exploring it with radioembolization, so on-market therapies, and also with our TLR9 agonist that Jason had mentioned, that we think is really the right drug for that environment. Pancreatic tumor microenvironment is known to be devoid of immune cells, and what this drug is really stimulate the innate immune environment and eliminates a key cell type that suppresses the immune system, and we're gonna be releasing, you know, some data on our phase one trial on that, you know, hopefully in the first quarter of this year. We just enrolled a couple more patients.
We were planning to do it at SITC, but we got more interest in the clinical trial and just enrolled a few more patients. And then we're also gonna be releasing data at SITC on our liver trial in uveal melanoma liver metastases. So I'll just pause there. That's kind of a very broad, high-level overview, and see if there's questions.
So-
I don't know, Jim, if you wanted to add anything further to it?
At this point, you know, we can... Let's just take the questions, and we'll go from there.
I think, could you help everybody understand a little bit more about just basic TACE, and then what Pressure-Enabled Drug Delivery actually is? Because it sounds like they're two different things, but it's in the same vein.
... right, so
Unintended with the arteries and veins and such, so-
Right. I mean, you know, probably the simplest way to describe it is, what an interventional radiologist does is when they're doing TACE or TARE, you know, where they put the beads of either radiation or chemotherapy into the tumor, it's an outpatient procedure. They go through the femoral vein. If you guys are familiar with how a stent is placed, you know, they actually advance the catheter, you know, up through the major vessels in the artery. They take a left turn at the liver, and what they do is they advance the catheter into an artery that is supplying the tumor. What's unique about our technology is often these tumors are very high pressure, and what that means is the pressure within the tumor is higher than what the heart can pump at.
So often you can see, and largely, many of these are hypovascular, so the heart cannot pump enough pressure to completely infuse that tumor, so they need a... They need help. And so what our technology is, and I think you'd wanna think about it, is we have a smart valve technology that opens and closes in synchrony with diastole and systole. So it almost acts like a little auxiliary pump in the vessel feeding the tumor, and we modulate pressure and flow. And you can actually see it when the physician's trying to target where he's gonna place the drug. He's got... You know, he's imaging these vessels under fluoroscopy, and with our technology, you can just see the complete vasculature of the tumor just illuminate.
We've actually measured this, both preclinically and clinically, that we can improve distribution of therapeutic anywhere from 30% to up to 500%, so it depends on the tumor. But we know that if you get more drug into the tumor, you get better outcomes. Better outcomes can lead to overall survival. So that's the therapies that are used. There's about 30,000 procedures that are used today. We have very low market share, you know, roughly 4%-5%. It's about a $400 million market. We sell our technology for, you know, $7,750. It's about a 90% margin, and so lots of opportunity to penetrate just that liver TACE and TARE market. But as I mentioned earlier.
You may wanna touch on-
... there's other applications. I'm sorry?
Yeah, you may wanna touch on the competition and exactly, you know, who we're competing with the microcatheters and maybe touch on that a little bit.
Yeah, and-
Maybe how many centers, too. Like, it's 30,000 procedures, but they're constant... They're relatively-
Only in about 400 hospitals.
Yeah.
They do about 95% of all the volume of these procedures, so it's a very targetable market opportunity. You know, there's 1,300 hospitals in the United States, but 400 do 95% of the volume, and there's really no other technology that can do what we can do, and that's why CMS actually gave us an exclusive code. It was written specifically for us, and our competition is just a standard microcatheter. Think of a standard microcatheter just as a tube with two holes. It really can't influence pressure in any way. It can't overcome pressure. Actually, you'll see it back up in the vessel on fluoroscopy, which could be very clinically challenging for the physician because if it's backing up and getting reflux, you're actually getting that drug into normal tissue.
And for many of these patients, they have very little compromised, you know. They have a very compromised liver and very little normal tissue left, so you don't wanna do that, and that's the beauty of this technology. It's exquisitely targeting, and it delivers substantially more drug to the tumor. And interventional radiologists have a term that they call T to N. So how much more do they get to the tumor versus how much more do they get to the normal tissue? And we substantially influence that.
These are unresectable patients, right? I mean, they-
Yep
... they can't-
They're late stage. You know, these are people who, you know, are not, you know, they can't be resected. They, you know, typically have failed multiple treatments. They're in the latter stage of their disease. But these treatments can be really meaningful. What they can do is, you know, delay, you know, progression of the disease for up to two years, and potentially for earlier patients, sometimes it's used to down stage them, you know, on a bridge to transplant if they feel like they could become a candidate for it. But typically, they're sicker patients.
The other population is the metastatic group of patients, and if you get, you know, liver metastases, that can be a driver of a mortality, so often a physician would like to treat the liver even though he's getting systemic treatment, for, you know, the other primary cancer.
You had started a program called DELIVER, right?
Yes.
That was on the last earnings call in August, to deal with or build data around quote, unquote, "complex patients." Can you just discuss some more detail about, you know, what that is and how you can leverage that information to ultimately drive adoption or increase adoption?
Right. So, you know, we started DELIVER because we did a very large health economic and outcome research study, and what we found where physicians were using our technology. We did it over two years, and we compared the use of our technology in all of these embolization procedures just to standard, you know, procedures using the microcatheter. And what we found was that physicians were using our technology in very complex patients, but getting outcomes that were favorable to, you know, even favorable to much healthier patients. And so we could treat a complex patient with... and deliver results at a patient who was much earlier in the stage of his disease.
And we saw where they were using it, and we had seen that these are patients that have very large tumors, they have very diffuse disease, they failed embolizations previously, they have multi, you know, tumor, significant tumor burden. Our technology performed exquisitely well in that. So what we launched with DELIVER is just an overall program. It's a cadre of different studies that were embarked upon, and the vision is that we create data that we can actually get this in the NCCN guidelines. And we know that if we can get in the NCCN guidelines, that could significantly drive adoption, because hospitals will adhere to those very rigidly. And so that will be another significant expansion. And that's where we actually saw that our technology was being used to actually treat multinodular goiter. We actually saw that patients were...
It was even used for subdermal, you know, hematomas. So we saw all these new applications in that data. We'll be updating that HEOR data set, and we'll do that every year, and that data is so robust because it covers roughly 98% of all the payers. It was a data set of over 300 million people, and so when we present that data to the NCCN guidelines or payers or even CMS, it's quite compelling.
So to get into the hospitals, because there's 400 centers or so, right? Do you have to go through, I guess, like, a hospital review board?
Yep
... do they have to allow their institution to start using these things? And, is that an obstacle, or is it just part of the process, really, that you-
It's just-
Okay
... part of the process. I mean, I'd say most hospitals, it's about a six-month process. It's called the value analysis committee. It's really dependent on. The reason why it takes a lot, you know, six months, is just when they meet. I mean, they only meet maybe once a quarter. So you present, you know, in the first quarter, you give them all their information, then they meet again, and they can approve that. And, this past year, we got into an additional 100 new hospitals. So we have a very high rate of capturing new hospitals, and really, as we move forward, it's about penetrating those new hospitals, 'cause it does take a lot of time and effort to do that.
But we'll always be approaching hospitals and getting into that top 400, so it's available on formulary for patients to have access to it.
Just going back to DELIVER really quickly, I don't know if I got it right. To get into the NCCN guidelines, you're gonna leverage the complex-
Mm-hmm
... patients' data.
Yep.
The nodular-
Submit to-
Okay
... about four or five different guidelines. We looked at the criteria, the type of data we needed, what we needed to collect, and so DELIVER was really predicated on creating that data so we could submit to the various guidelines, so this technology would be used in a wide array of different settings.
Okay. And then what about the number of sales reps? I know you guys were expanding over the last-
Yep
... year. Is that expansion continuing?
Yep.
And then also the introduction of the large vessel-
Yep
... device.
We continue to expand. I'd say overall we're still kind of sorting through. We have a mixture of clinical specialists and reps. We have about 50 people in that commercial organization. Our clinical specialists often, you know, while they're clinical specialists, all really do a lot of sales support as well. And we believe that's, you know, kind of a good size. We'd like to get to about probably 60 or 70 people in total, but we've been very thoughtful about where to add them, making sure that we get a good return on the investment in those representatives. And we plan to launch TriNav Large, which is for larger vessels, and really round out the portfolio, which I think is gonna also help with adoption.
We miss about 15%-20% of the cases because we don't have that larger size, and we'll launch that on November 4th. We did a very extensive market valuation of that and got, you know, extremely favorable feedback, so we're pretty excited about it, and that's included in our reimbursement code.
Right.
So we'll be moving forward with that.
Large vessel means staying in the liver, though, or are there others?
It's still in the liver, just a larger vessel size. Our current one covers about one and a half to three and a half millimeter vessel size. This will go from about three and a half to about five and a half. So it will cover virtually all the vessel sizes that a physician encounters in the liver.
Okay, so maybe we could jump over, with the remaining time, to the clinical side-
Sure, sure
... of the company and the TLR9, and every time I go to pronounce it, nelatolimod.
Nelatolimod, yeah. I know.
Yeah, getting it better. I have to pronounce so many different drugs every day.
Right. You do.
But it was SD-101. You picked it up from Dynavax.
Right.
You've had some good data so far.
Yeah.
They had good intratumoral data.
Yep.
You've taken it to the liver and you recently, well, relatively recently, had an update on the PERIO studies, and you are narrowing your focus on certain indications. Can you just walk us through a little bit more detail on what you've seen there, and where you're going?
Right. So we acquired this drug from Dynavax, and we did this very intentionally. We looked at over 350 assets, and we liked this asset for what I mentioned previously. It can stimulate the tumor microenvironment. You know, it's essentially just 31 snippets of synthetic bacterial DNA, so the tumor thinks it's being invaded by bacteria, so the whole immune system is turned on. But it had another dual feature that we really felt was critical, and that is that it could eliminate a certain cell type, myeloid-derived suppressor cells, that is really immunosuppressive. And by eliminating that cell type, you know, you now allow the immune system to recognize the cancer, and we've seen some really profound immune-modulating effects of this drug.
The intention was to take it into a few phase one trials in the liver and in the pancreas, and with the goal of really moving forward in one indication. We only wanted to get into an indication that met very clear criteria, that it had, you know, a very significant treatment effect, had a regulatory path that we could move forward with rapidly, and that we could fund ourselves. So where we are is, at the end of the year, I think what we'll be able to do is announce where we wanna move forward. The data so far across all three trials have been... you know, exceeded our expectations. I think really the challenge for us right now is picking it, what is really the best commercial opportunity for us to pursue, and what's the fastest timeline and clearest regulatory path?
We're still sorting that through, and we'll be announcing that shortly.
Okay. Whatever that path is going to be, does that include combination with immune therapy, possibly checkpoint inhibitors?
It could be a range of different things. We've looked at... You know, I think the next phase is we'd probably combine it with a number of different things, standard of care therapy, checkpoint, and look at what is the best arm to it to pursue. That's kind of the big debate right now, that we're consulting with. We have a big collaboration with MD Anderson, and we're sorting through all of that right now.
But also despite MDSCs and that angle to TLR9 agonism, those other immune therapies have not had success in the liver.
No
... and pancreas and such, right? So maybe you could provide a little bit more color on that, and-
Yeah. I mean, you know, I think in the liver and pancreas, you know, checkpoint has largely not been effective. And we know that one of the big reasons why it hasn't been effective is just the severe immunosuppression in these tumors. There's just not a lot of T cells in them, and, you know, in the pancreatic tumor, they call it the immune desert. And what nelatolimod does is activates the immune system in the tumor. You know, it pulls into those T cells, so really enables those other immunomodulatory drugs to work effectively. And that's what we, you know, what we saw in some of these phase one trials, just the combination of these drugs and how effective they could be, and that's what's guiding us to the next indication.
Okay. And your CMO, Steven Katz-
Yes
... actually did this with P, the pressure enabled with CAR T.
Right, and so the diff-
So it's actually, it's interesting just from an aspect for investors who everybody knows CAR T, and liver's been impossible, but it gives you a sense of what the pressure-enabled drug delivery can do. It's delicate enough, I guess might be the right word-
Yep
... for T cells to be put in there.
Right. I mean, the reason why we were really attracted to Steven and asked him to come to the company, he released some really fundamental research. He was using the technology and doing research on CAR T therapy. And, you know, he was seeing with a standard microcatheter, he was infusing the T cells, putting them right there in the tumor, yet when we went to measure it, there was nothing there. And so when he used our technology, the pressure-enabled drug delivery, he could actually improve T-cell delivery by fivefold, 500%. And that's what really compelled him to come to the company, because delivery really matters, particularly in these organs that have severe, you know, elevated pressure.
We've actually, with our clinicians in these clinical trials, have measured the pressure in these tumors, and they can be in excess of 150 millimeters of mercury. I mean, if you're a healthy and, you know, adult person, your mean arterial pressure is gonna be, probably be between 70 and 90. So you don't need to be a PhD in physics to figure out that nothing's getting in that tumor.
Right.
That's what we saw. The beauty of this technology is really it overcomes that pressure, offers a very physiologic way to infuse into the tumor without damaging these very immature vessels, and provides substantially better drug delivery.
There's a question coming in, a couple on just talking about competitive landscape on both the catheter side and the development side, meaning the TLR9.
... Sure. You know, I think in terms of competitors, we don't see anybody doing exactly what we're doing, you know, to date on the catheter side. Our biggest competitor is just the standard microcatheter, which is, you know, clearly just a commodity-type item. And we don't think TriNav should be used in every case. I mean, if it's a hypervascular tumor, a standard microcatheter is fine. Where we really provide value is in that complex patient or, you know, in the challenging patients with, you know, very extensive disease where it's likely hypovascular or diffuse. This is where our technology really provides value. And then in terms of competition, you know, TLR9 has, you know, as a class, you know, they largely haven't been successful because it's only been delivered via needle injection.
The beauty of what we can do is we can deliver it intravascularly, and we've actually shown that we don't have a lot of systemic, you know, therapeutic, you know, concentration in the blood, so it's very well-tolerated. However, we can deliver very large concentrations to the site of disease.
I think even to the audience members asking that question, I would say anything that's looking at MDSCs and knocking down... There's so many people trying to do this. It doesn't have to be TLR9 specifically.
Yeah.
But I would think about it-
There's a lot... myeloid is a big area of focus for everyone.
It's huge.
Yeah.
Huge.
Huge.
But I would think about it from an indication perspective. Liver, it's not that crowded in terms of trying to do this there.
No, we don't. You know, 'cause delivery is still a challenge. I mean, that's the big issue. Getting it into a liver tumor, very different. I mean, the liver's a very tolerogenic organ. It's very hard to get into these tumors and actually get the concentrations that you need.
Before we wrap up, when do you think we'd hear more about the multinodular goiter indication?
We're just starting.
That could really-
Yeah, so they're actually gonna publish some data in the first quarter about all the initial, you know, 40 cases that were done, you know, in Florida, and then we're embarking on our study. We hope to have kind of a six-month update, and then a 12-month update, so middle of the year next year, and then at the end of the year next year, and that will include five sites, several hundred patients.
Okay, and, maybe just to close, can you guys, run us through the next six months of what to expect? You had mentioned SITC and a couple of other things.
Yeah, so we-
Right, that's an option.
Yeah. I mean, you know, we have SITC coming first quarter. We have a number of data releases on our device clinical trials. You know, I think we're just mapping that right out, exactly when they're published for the first half of the year. There's gonna be three or four different, you know, data releases on that, and expansion of the DELIVER study. So, you know, significant more clinical data coming across the board.
What's the timeline, just quickly, on EBITDA positive?
Yeah, you wanna comment on that, Jim? That's the intention, in 2025. Yep, we're-
Yeah, you know, at this point, we've always kind of said EBITDA positive. We're hoping to kind of turn that corner mid to late next year, and of course, it depends on many things. It depends on sales, it depends on margin, and spending, and everything else. But that's kind of our goal, is to get to a point next year where we turn that corner, probably mid to late 2025.
Yeah. Yep.
So it's-
And then it will depend, of course, heavily on clinical spending, you know. And then to the extent the clinical spending ramps up, you know, then it. But we believe that in 2025 will be kind of a lighter year for clinical spending, and really improve the cash flow perspective of the company.
And TLSI $140-$150 million in market cap, somewhere thereabout, but I think largely unknown coming out from last year and starting to build some traction. I think it's absolutely a name for investors worth paying attention to. So Mary, James, thank you as always-
Yep, thank you so much.
... for coming on. We'll catch up with you soon.
Okay, great.
Thanks, Jason.
Bye-bye.
Take care.