Lisata Therapeutics, Inc. (LSTA) November 10, 2026 Conference Transcript

Welcome to Guggenheim's I guess this is our third annual Healthcare Innovations Conference here in Boston. Really pleased to be joined by Mireya Therapeutics. The, I guess, active ticker for the time being is under Lissata. But, you know, really pleased to have the team here. To my immediate left is Josh Lehrer. He's CEO of Mireya, President and COO of Lissata. And Ian Clements, immediately to his left, he's CFO. So, you know, we've asked Josh to kind of provide an overview of the company because as a reverse merger, I think there's an opportunity to learn more, but excitingly, there were data just presented at the American Heart Association for their NGPTL4 antibody, and I think that really is particularly exciting because there was a New England Journal of Medicine article associated with it as well. So I'll turn it over to Josh to kind of kick it off.

Great. Thanks, Seamus, and thanks for having us here. It's great to be here. So, we're not even completely through this reverse merger, and we're in the fortunate position of having two molecules that have initial clinical validation and look like drugs, both first in class. So, we're very excited. I'll give you a quick overview on our programs, and then we kind of touch on the reverse merger financing. So our lead program is a first-in-class antibody directed to ANG-PTL4. This is a target with very strong human genetic validation, well-understood biology. It's in the same family of targets as APOC3 and ANG-PTL3, other lipid-related targets. And we're developing this for a large group of patients who have severely elevated triglycerides, severe hypertriglyceridemia. And where we think that this could be really compelling and address an unmet need is because these patients are both at risk of pancreatitis, but also mostly have diabetes, and many have established coronary artery disease. So we have an opportunity, we think, to have a differentiated product that can be comparable to the type of really groundbreaking efficacy, Antroglyceride lowering seen with the APOC3 class, but really completely avoiding the dysglycemia and the worsening diabetes and cardiovascular risk factors, which can be, which have been seen as a class effect with the APOC3 drugs. And the data that we'll get to that was presented to AHA goes a long way towards establishing that profile that we think could, you know, address a large group of these patients and, you know, and ultimately have a significant share of what's It's projected to be over a $10 million market in the US. And then our second program is an endocrine program. This is a first-in-class antibody targeting the growth hormone receptor. Investors are probably aware of the chronetics palthusatine program that was also to address these patients. The main thing to know about this program is that the majority of patients with acromegaly require chronic, lifelong medical therapy with the goal of controlling the disease and normalizing IGF-1. And most patients never achieve a normal IGF-1 level, and that's because the drugs that are in the class of paltuzetine, the somatosanoreceptor ligands, it's only a minority of patients who respond, about a third of patients responds. We have an opportunity with a drug that's in a different class that's already really validated by a commercial product, the target is validated, but with a much better profile, potentially, we think we could be best in class and address a double the number of patients, actually, Especially that are treated by SRLs right now and that's a big amount of need and it's also a big opportunity. So about a billion dollars total in the U.S., projections for the U.S. somatosatin receptor ligand market for acromegaly, and we think that we could address twice the number of patients of the SRL class. Great. And then on the kind of what's coming next, 27 will be a big year for us. We'll be, I mean, we can kind of get into some more detail, but we'll have kind of an important additional clinical catalyst for both programs, and we're also working on a pipeline with next generation programs that follow our lead program.

Great. So, you know, Maybe we can just kind of go through yesterday at AHA, you know, you presented the title, Timmy78 data as a late breaker. Maybe just walk us through the key findings, you know, I think in particular the 40% triglyceride reduction overall, but the way triglyceride lowering actually scaled with baseline triglycerides I think was uniquely interesting.

Yeah, so I know this is a conversation, but sometimes it's easier to kind of see visually than to talk about lots of numbers. But, so really, that, that, I mean, the, the main thing we learned in this study that we didn't know before was this, you know, pretty dramatic scaling of efficacy or, or, of triglyceride lowering with baseline, the baseline triglyceride levels. So we published data from a phase 2A study in, last year in the Lancet in patients who had lower, you know, moderate elevations in triglycerides, mostly under 300. So, kind of what you see on the far left of this slide, and we saw about 40% lowering, and we see that again. But what's new is that we also had patients in this study that covered a wide range. We had some, and we had some patients who had severe elevations over 500. And when we break down the participants in this study by baseline level, What was, you know, really encouraging for us is to see this really scaled efficacy. So going from about 35 percent, near 40 percent at the high dose in patients who are under 300 milligrams per deciliter to about 45 percent in patients who are 300 to 500. And then in our target patients going forward with triglycerides over 500, we're seeing the efficacy go up to 70 percent, 72 percent at the high dose. And that is very much comparable to what's been seen in terms of change from baseline with the APOC3 class. And the reason that's important for these patients is that to really remove the risk of pancreatitis, you want to get patients below 500. And if you deliver this kind of mean reduction, you're going to be moving the vast majority of patients below 500, and that's translated into clinical pancreatitis benefit with the APOC3 inhibitors. The other important result is that we saw a very clean profile. So really, no safety and tolerability concerns, and very specifically, no evidence of an increase in glucose in the diabetic patients. We have a lot of diabetic patients in this study, and from prior studies, we see none of the liver fat signal that's been seen with members of the APOC3 class. Interesting.

What about remnant cholesterol, you know, other potential results from the study itself?

So remnant cholesterol, also, we saw reductions that were very consistent in line with the triglyceride lowering. That remnant cholesterol is kind of thought to inform on cardiovascular risk and residual risk. For SHCG specifically, it's really, really the triglycerides that we're focusing on. The remnant cholesterol endpoint was there because we had also been considering kind of the larger ASCVD and CV risk reduction indication for this molecule. The genetics are very strong there. And that, I think, is still a potential, you know, sort of life cycle management or future option to expand into for this molecule and for this target.

Yeah. And just in terms of that sort of scaled efficacy, can you just help us understand, you know, what is it about this mechanism that is resulting in what looks like kind of scaled efficacy? Typically, when we look at, you know, LDL-lowering therapies, you see, you know, it's... You know, PCSK9 will do somewhere between 50 and 60 percent, almost regardless of baseline.

Yeah, so that's right. I mean, typically what you see is the absolute change goes up and the relative change is pretty similar. And that is actually what you see with the ApoC3 class. And if you treat normal, healthy volunteers with the ApoC3 inhibitor, you'll cut the normal triglycerides in half. So that's not true here, and there are some unique aspects of the target, of this target, and actually of the genetics. So what's different about NGPTL4 compared to the other targets is that its action is really in the adipose tissue, and it's very specific for one particular lipase that hydrolyzes triglycerides, and it's heavily induced. So it's a gene that's regulated by P bar gamma, so as free fatty acids are induced and go up, the levels of NHP2O4 can go up by 10 or 20-fold, compared to other targets that are pretty constantly expressed, really across the range. So the least hypothesis is that this is kind of causing the most problem in the sickest patients. The levels of NHP204 go up along with triglycerides, and then we have an opportunity, you know, more targets to knock down, and then that's why we see the greater efficacy.

Got it. Okay, great. And then, you know, key differentiation here, it really seems like is a very, very clean metabolic profile. You mentioned, you know, sort of most patients in the SHTG population already have diabetes or are pre-diabetic, but, you know, maybe you can put some numbers around that to help us understand it a little bit better.

Yeah. Yeah, so I think, I mean, I think just to begin with, we think that the data on the ApoC3 drugs is really compelling, and, you know, Ionis is now doing the hard work of building the market and addressing those patients. And the efficacy that's seen in the clinical benefit is really transformative for these patients. Where we see the opportunity and really what we have heard back from physicians in market research is that while the glucose increases that have been seen with the ApoC3 class and the liver fat signal that has been seen is not a showstopper. High-risk patients are going to get these drugs because they need them to prevent these really bad pancreatitis events. That if there's an alternative available that doesn't worsen glycemic control, doesn't cause pre-diabetics to become diabetic, doesn't cause diabetic patients to deal with insulin and become more difficult to manage, that especially in patients who already have diabetes, that's going to be preferable. And because the fraction of SHTG patients with The diabetes, if we look back to the Phase III, Core I, Core II study, it was 60% to 70%. So it's the majority of these patients have diabetes. We think that this is a compelling differentiated profile for kind of a large chunk of the patients who need these therapies. When we've, you know, kind of thought forward to how this could kind of play in the landscape, we think that largely it will be in new starts. And what we've heard is that all things being equal in diabetic patients for new starts, this would be the number one choice for a diabetic patient.

Got it. And, you know, if I look at the, I mean, what's encouraging is with the dose response, you see this confidence interval kind of tightening up across the board, but in particular in the over 500 group, despite a small number of patients in there. Can you talk a little bit about, you know, your confidence as you advance into, you know, your phase two programs to kind of prove out the, you know, the data next year, just how you're conducting the phase two, your confidence in that, you know, sort of 70% reduction in that patient population?

Yeah, so, I mean, the caveat, of course, is that this is, these are small numbers. This was not designed as a pure SHCG study. Part B of this study will be a pure SHCG study, so that'll be the data that's coming next year. But I think what's really encouraging to us is really two things. One is this trend across the data set, and we see this clear correlation between baseline triglycerides and then effect size. And we see this really across the board, and that's in all, you know, across the 230 plus patients in the study. And then, and then specifically in the, in the, in the dozen patients here who had triglycerides over 500, while it is small numbers, it's, it's precisely those error bars. And if kind of, if we kind of drill down into that further, we saw that actually every single patient that was in the middle or high dose group had a reduction in the range of 60 to 80%. So I think we can, you know, we can be. You know, as confident as we can be until we've done bigger studies, that with more numbers, we'll be somewhere in that range of 60 to 80, and I think that's really the target to be comparable to the APOC3 class.

And you mentioned, you know, some of the distribution is to adipose tissue. You know... What is interesting is, you know, if we see some hepatic fat forming with the APOC3 drugs, is that kind of, you know, it seems like that's one of the differentiating characteristics here, but mechanistically, is it really that the adipose tissue that's, you know, accepting triglycerides, I guess, to some degree, is predominantly subcutaneous? Is that the right way to think about it?

Yeah, I mean, I guess the first thing I would say on the differentiation, I think the strongest thing we've heard is really about the dysglycemia. Yeah, okay. And then, you know, sort of why is that seen with the APOC3 class, and why are we not seeing it here? The hypothesis, and this has actually been talked about in the discussion of the, you know, the New England Journal publication for the APOC3 drugs, as well as in the recent publication for ours, is thought to be kind of where the fat goes, Where the triglyceride goes, so, you know, both types, both drugs, you know, both inhibition of both targets clears triglycerides from the blood. With ApoC3, those triglycerides are largely flowing to the liver or liver and muscle. And with NHPTL4 inhibition, those triglycerides are really flowing to the adipose tissues. You can kind of think of this as, we think of this as kind of putting fat where it belongs. If there's one place to put fat, it's probably in healthy adipose depots. And by offloading triglyceride delivery to the liver, at least the biological hypothesis that makes a lot of sense, is that you're avoiding the potential for ectopic fat being deposited in the liver, and you're avoiding kind of flooding the hepatocytes with fatty acids that would make them, you know, metabolize less glucose as a consequence.

Understood. In terms of just the estimate of the market opportunity, you know, I think one of the dynamics of being a potential third entrant with a differentiated profile is you get the benefits of somebody else helping to build the market. So how are you thinking about that? And what are you watching for in terms of like the key market, you know, sort of building characteristics over time? I guess our view is that with a good commercial team, an effective commercial team, you still are probably going to have a look and feel of Lectvia. To some degree, is that a reasonable way to think about it?

Yeah, I mean, I think another way of saying it is it's going to take time, and, you know, I think we'd – And incidentally, Lectio is tracking to be a $5 billion drug. Right, right. And I think – I mean, we feel that we're – it's a nice position to be in to have IONIS, and then, you know, we expect Arrowhead next year. We deserve a lot of credit for really developing these effective drugs and also doing a lot of work to establish the market. I think that what we're looking for, I think the positive part of the story is that there's a lot of interest from physicians. There seems to be a lot of demand from physicians, and there's also broad coverage to the label.

Great. Um, and then just beyond SHTG, other opportunities, hypertriglyceridemia, remnant cholesterol, other targets. Obviously, ASCVD, a very costly future potential development opportunity once you're generating lots.

Yeah, I mean, we're, you know, we can talk about sort of the resources and capital we have now, but we're, you know, we're well-financed, but we're also, you know, we're also a small company, and we're really laser-focused on this initial indication of SHTG. The genetics and biology with NHPTL4 are, continue to be very exciting around coronary disease. It's one of the most well-validated genetic targets that hasn't been pursued yet. But that's something I think we would not do on our own. It's also something we could consider with some of the pipeline programs. So we do have SIRNA adipose-directed programs, where we're planning on developing a next-generation version of this ANGPTL4 monoclonal with an SIRNA. And that could be a molecule that we could think with a partner about expanding to bigger indications.

Let's talk about acromegaly. Absolutely. You know, just, you know, remind us, I mean, we talked a little bit about the unmet need, but, you know, how are you thinking about, I think there's roughly 30,000 U.S. patients affected, more than half, at least in our research, with, you know, experts we've talked to, it's just that half are still uncontrolled. You know, maybe just kind of give us the lay of the land on the sort of treatment opportunity that you see ahead.

Yeah, so that's about, you know, 30,000 patients, and it tends to be underdiagnosed. I think Krenetics and now Vertex is doing work to really expand identification of these patients. And generally after surgery, really these patients are managed by measuring IGF-1 levels, which reflect how much excess growth hormone signaling is going on. Tracks very well its symptoms. If IGF-1 is elevated, they have early mortality, actually from cardiovascular events. You're going to have bad diabetes, joint pain. So it's a very symptomatic, morbid disease if you don't control IGF-1. So there's a strong drive to treat to IGF-1 goals. And the reason that, as you said, that the majority of patients never get to control is because of limitations of medical therapy. So the somatostatin receptor ligands, there are many good options, injectables, depot, monthly injections, and now an oral, paltuzetine, that can get patients to control. But the problem is that the response rates are only about a third of patients. And that's a biological issue. So that's because many patients, their tumors express low levels of the somatosent receptor. So many patients, those drugs just won't get them to, you know, to normalization. And then in contrast, there is an available drug commercially from a different class. It's a drug from Pfizer called Pegvizamont that directly blocks the receptor downstream. And that achieves effective control in over 80% of patients in clinical trials. So it's actually a very effective drug. But in the real world, it doesn't deliver on that promise, because patients just can't stick with it. We kind of mentioned some of the limitations, safety, tolerability, dosing, daily dosing, reconstitution from a vial. So what we think an optimal direct growth hormone antagonist can do is to address Yes, those two-thirds of patients who don't get to IGF-1 control on the somatosan receptor ligand class. And to do that, the goal is pretty simple. It's to deliver efficacy, and I can put this slide up here, deliver efficacy on IGF-1 lowering that is comparable to what's been seen with this effective Pfizer product, this competitive antagonist called pegvisomont, but to do that with much better dosing, much better durability, and without the LFT elevations and injection site. reactions that have been seen with that, with that drug. And we're, we actually just started dosing in a phase two study, so of course we'll be getting more data, but the nice thing here is that even in healthy volunteers, this is data from phase one, we can look at IGF-1 suppression and benchmark that to what was seen with, with Pegvizumont and, and, and understand that we're right where we need to be. So this is showing kind of different dose groups, it's showing IGF-1 levels over time. That red dotted line shows kind of the, the, the highest We're actually exceeding that with multiple doses, so that gives us a lot of confidence, and then based on this very long duration of effect that you can see on this slide, we're anticipating that in patients, we should be at, you know, a biweekly injection, sub-Q, the goal will be an auto-injector, so really, I mean, transformative from what patients, from the options they have today. Patients who don't get control on SRLs.

And you dose the first patient, I guess, in the phase two in October. You know, just to maybe quickly walk us through the design, you know, versus placebo. You know, you've got a loading dose, you know, but maybe just the timing of what's, you know, when we see the data and what success looks like.

Yeah, so I mean, largely we'll be looking to reproduce these effects. We know that with these other drug classes that what you see in healthy volunteers predicts what you see in patients, and that's what we'll be looking to confirm. IGF-1 lowering happens fast, so we don't need a lot of time. So we'll have a 10-week endpoint. We're doing a loading dose just to make sure that we've gotten to steady state by 10 weeks. We don't anticipate that the loading dose is necessarily going to be required, you know, in phase three or commercially. And then we're looking at three, we're dosing biweekly, and we're looking at three dose levels, bracketing what we expect to be the clinical dose, at least for most patients, of 300. And then looking at IGF-1 at 10 weeks, we'll be including, actually, patients who are on background therapies like paltuzetine, other SRLs that have gotten partial responses but not a goal yet. So we'll be looking at this both in a monotherapy setting in washout patients or naive patients, as well as added on to SRLs. And that's how we also expect to design the phase three to support a broad label.

Yeah, interesting. And just the market opportunity, you know, how are you looking at it? You said a billion dollars. Is there an opportunity for, you know, potentially a bigger market opportunity than that from your perspective to unlock more patients?

Yeah, I mean, I think that a, you know, kind of a relevant number is the projections for the SRL class, which are really just talking about the one-third of patients who respond, and that's projected to be a billion dollars in aggregate with increase in diagnosis, increase awareness. Vertex, at least, believes that could grow significantly. And then just based on the addressable patients, whatever the SRL is going to address in aggregate, we think this class and this mechanism is going to address double that just based on the response rate. So whatever the SRL market grows to, we think this potentially could be double that.

Got it. And Ian, you've got the $225 million private placement. Maybe just remind us what that funds in terms of operations. And then, you know, beyond that, you know, the opportunities for some of these catalysts to really drive incremental optionality.

Yeah, sure. I mean, I think that a great result in terms of bringing some fantastic investors into the pipe to support us through the next, into the middle of 2028, basically. So, as you can see on the slide here, I think, and as Josh has kind of alluded to as well, a number of catalysts during this time period across Mars 001. We're looking at the selection of the dose for a half-life extended version that we would ultimately take into Phase 3 and actually getting the data from that cohort of patients with SHTG as well by the end of next year. And then turning to Acromegaly, having interim data from the Phase 2 study that Josh outlined the design of, as well as by the end of the year, having the full proof of concept data set in that Phase 2. And then within that timeframe as well, with the capital that we raised, actually also being able to start both of the Phase 3s with NSHTG and in Acromegaly as well.

A lot to do in a relatively short period of time, but some huge catalysts in 2027, exciting times. Thanks for spending the time with us today, and, you know, obviously, we're looking forward to the future of Mireya.

Excellent. Great. Thanks, Seamus. Thanks, Seamus. Appreciate it.