We're good.
Great. Thanks, everyone, for joining us. My name is Roanna Ruiz. I'm one of the senior biotech analysts here at Leerink Partners, and it's my pleasure to introduce Lantheus to the podium. With me today, I have the CEO, Brian Markison. I guess, without further ado, I'll just let it hand the mic to you, because I know you have a little bit of a presentation to go through.
Yeah, I appreciate that, and thank you. Thank you for having me this afternoon. Before I dive into the corporate presentation, please note the safe harbor. I won't bore you and read the whole thing, but maybe I'll start at the beginning. For those of you that are not that familiar with the story, Lantheus is a leading radiopharmaceutical-focused company. Our raison d'être, if you will, to find, fight, and follow disease, to deliver better patient outcomes, is kind of why we wake up every morning. I'll take you through a little bit of our journey, a little bit of our history, and then where we're going when we wrap up this presentation. We've said in our fourth quarter and full year 2024 earnings call that we're planning for or setting the stage, if you will, for double-digit growth in 2026 and beyond.
I think we have a number of near-term catalysts, but clearly our big driver is Pylarify, followed by Definity. When we're fortunate enough to close on Life Molecular Imaging, we certainly anticipate the addition of Neuraceq to our portfolio as another driver of the business. You could see in the column that's marked number two on the slide, MK6240, NAV4694, Octevi, and Point PNT2003, all in late-stage development and all planning for near-term launches in the 2026-2027 time period. Of course, I can't leave out Evergreen, which we're very excited about, that brings Octevi to the portfolio and a pipeline of very interesting early development compounds. We hope to close on both Life Molecular Imaging and Evergreen early in the second half of the year. We're very excited about that.
Here's a depiction of our historical sales performance, adjusted EPS, and free cash flow. What I'd like to do is bring your attention to that black box or rectangle in the middle of the slide where we projected free cash flow for 2025. Obviously, a very strong performance in the wind for us, strong tailwinds for the business, and we're quite motivated to get this done. Lantheus has essentially a fairly lengthy history in nuclear medicine and the radiopharmaceutical market. I'm not going to drag everybody through the beginning of old New England Nuclear. What I'm going to focus on are some of the more recent transactions and happenings in the company. You could see in 2002, we acquired Progenics. That was really the beginning of sort of this new renaissance in Lantheus. Shortly thereafter, Pylarify got approved.
In 2022, we did the deal with Point Biopharma, which now is Lilly. In 2023, we picked up MK6240 from Cerveau. We also looked at the approval of Pylarify in Europe, our work with Curium to be our partner there to distribute Pylarify in Europe. In 2024, it became really busy. We acquired a number of assets that I'll talk about. We were working on Life Molecular Imaging at Evergreen during that period of time as well. I do want to thank all the team members that worked at Lantheus to get these deals done and over the finish line. I know how hard it's been, but it's also been a lot of fun on this journey. I'll cover some of the more interesting things here on the slide as we go through the presentation, but I'm not going to drag everyone through it.
Pylarify is clearly our leading workhorse, if you will, and sustainable business driver. We anticipate a very strong cash flow from Pylarify over our planning period. We do anticipate it to grow with the market. We're quite excited about Pylarify. I think for people to really understand what's happening in the market, you almost have to go back and look at the data and the basis for approval, where you could see the two grayscale images are conventional imaging, and then the two images in color are Pylarify images. What we're finding versus conventional imaging is metastases that would normally have not been found. That has led to the change in therapy. That is a sea change in this market that everybody is now sort of taking for granted. This fuels the TAM. Now, what is Pylarify exactly?
Pylarify, we need to start with an F18 cyclotron. The cyclotron is then fed into the Trasis box. What you see in the second picture is the Pylarify kit. As the F18 line comes into the Trasis box, all of these different things get admixed and out comes a Pylarify vial. It is then put into patient-ready doses through pharmacy. You can see in the third box, there is the little pig that they are called, which is a lead-lined tube that the patient-ready dose goes in. Lo and behold, it makes its way to the patient. We have spent since launch bringing up the largest network of PET manufacturing facilities with strong partnerships with SOFIE, PharmaLogic, and PETNET and others.
Right now, we have about 62 PMFs around the country, a lot of duplicative PMFs or coverage in high service areas where there's a lot of prostate cancer, obviously. For example, in the state of Montana, we may have a little bit of trouble delivering doses, so we'll fly them in if we need to. This is a kind of look at the TAM as we're looking at it today, and then also what we're projecting out in the future. I think the segment that we're projecting the most growth for is the dark black box, which is radioligand therapy driven. The middle box, which is suspicion of recurrence, obviously continues to grow. That upper box, which is initial staging, I think that may grow even more than our TAM suggests. We're developing data now to basically substantiate it.
This is the slide of the MIRA study, which is looking at favorable intermediate risk prostate cancer. This is basically people who you're assuming, based on MRI, et cetera, biopsy, that the prostate cancer is confined to the prostate bed. What we're looking at with Pylarify is, do we find metastases when, according to conventional imaging, you would not? The answer to this study is going to be yes. They're already using it there. What's even more interesting, though, was a poster that we presented at ASCO GU, where we looked at a zero change in PSA, or undetectable, all the way down to less than 0.2 nanograms per mL. We were finding lesions in a large percentage of the population. I think as the future unfolds, you're going to see PSMA being far more interesting and predictable than PSA.
PSA is clearly the lead indicator that gets you to the urologist. That is pretty exciting. Definity, our second driver, has been a real steady growth engine for the company. We did project a slowdown in that growth because our competition was out of the market last year. They are back in the market. We were relatively comfortable with a very consistent 80+% market share. We plan on resuming that and not being much higher, unless our competition cannot really stay in the game. What does Definity do? On the left image, which is the unenhanced or without contrast, it is a very poor picture of the heart valve. I think when you look at the Definity image and that line in the middle, for those of you that are not that close to this, that is an excellent picture of the heart valve.
To see a dynamic image, you can see the heart valve in motion and really understand what's going on in an echo with Definity. Again, very interesting, excellent science. Our TAM here for Definity is really defined by the contrast market size, not so much the sort of non-contrast ultrasound market, which is enormous. Here we have the three agents that are in the market today, and that really defines our TAM. I'm going to switch now to our pipeline a little bit. This is a view of the pipeline with the potential closing of Evergreen in blue and Life Molecular Imaging in the brown. Ultimately, all of this is going to be in green. You could see how it layers in with the current Lantheus pipeline. I'll talk about some of the more exciting components of this right now.
I think when both these businesses close, you're going to see a company with a lot of very interesting shots on goal, both diagnostically and therapeutically. First up in the pipeline is PNT2003, our partnership with Lilly Point. That is the radio equivalent to Lutathera. Essentially, we will be competing in the Lutathera market for market share. We will be launching with our PNT2003, Octevi, which will be the diagnostic, or if you will, we'll be introducing a theranostic pair into the marketplace. I think we'll compete quite nicely for the full range of neuroendocrine tumors with Octevi and also for the Lutathera market with PNT2003.
I think it's sort of a soft entry for us, if you will, in being able to enter the radioligand therapy market with a known asset in a known place with a very interesting diagnostic agent as a precursor to the therapeutic. We made a pretty big bet on Alzheimer's disease. I think what I call this is a Gretzky move, which is we're skating to where the puck is going to be. You sort of have to believe that Alzheimer's is going to become a big market in order to get your head around this opportunity, which we think when you look at the portfolio that we're amassing in Alzheimer's, that is going to be of similar scale to what we're seeing now with Pylarify. I don't think one single agent, but I think the portfolio.
What we have on this slide is a very distinct amyloid plaque signature and also tau tangles and how they appear. Also on the right is basically the prevalence and the growing incidence of Alzheimer's disease. This is a population that is certainly far in excess of what we're seeing with prostate cancer, unfortunately. I think there's no doubt that all the associations that are behind the tau tracers, the beta amyloid tracers, they basically concur that you need both for a positive diagnosis of Alzheimer's disease. Here's a rough cut of the TAM that we see for 2030 in terms of market size on the left side of the slide, which is monitoring, staging, and screening. Clearly, all of this is driven by therapeutics. We've got two beta amyloid therapeutics in the market today.
You're essentially seeing amyloid scans double in a very short period of time with the advent of Lilly's new therapeutic into the market. We are really excited about MK6240. I'm going to describe in the next few slides why it's so interesting to us. MK is a second-generation tau agent. It is perhaps more specific, more sensitive than the other tau tracers, and also has much less off-target binding. We've got a fair amount of data from the HEAD study, which is being conducted by Dr. Pascoal at Pittsburgh. I'll explain that in a second. Right now, MK6240 is in over 103 academic studies and 15 major pharmaceutical trials looking at tau therapeutics. This is, I think, a significant recognition of how valuable this tracer is. We sell MK6240 in this setting. We don't give it away for free.
People are buying our tracer to use in these studies. We do make it affordable. We try to make it easy. Of course, we want the data. I mean, that's part of the price. This is data from the HEAD study where Dr. Pascoal, under an NIH grant, is the first person to really look at comparing all the tau tracers that are currently in development. I think what you could see here head to head in the same patients is the four different tracers. MK6240, if you look at the nice images of the brains, clearly picks up early tau the earliest and also the most pronounced imaging. A lot of that is driven by the sensitivity of the tracer. Again, here's just a much better view of the four different tracers in the same patient, relatively same time frame.
You can see the performance of MK6240 versus the other tau tracers. Once again, highly specific with less off-target binding. This slide is a correlation between p-tau or plasma tau and MK6240. What we're seeing here is that MK6240 has the highest correlation for p-tau. If you're looking for a blood test to determine whether a patient should get a scan, here we have the highest correlation. Also on sensitivity, this graph, again, taken from Dr. Pascoal in the HEAD study. I want to thank him for his permission to let us use these slides. Directly comparable, MK6240 is clearly the most sensitive. It also is more sensitive than p-tau. It picks up centiloids much, much earlier in the game than the other tau tracers. A true second generation.
We will disclose our plans for filing a little bit later this year. We are very interested to see how our phase three trials develop. Switching gears to beta amyloid, NAV is a second-generation beta amyloid agent. Again, similar hallmarks to MK6240 in improvements in chemistry, in less off-target binding, more specific binding to the target itself. Ultimately, what we are looking at with NAV is the ability to pick up centiloids much earlier. Again, beta amyloid, early AD has the best response to therapy. You want to begin to pick up these patients as early as possible. The standard, if you will, for Dr. Pascoal was carbon 11, which is on the bottom of the slide, the bottom of the top half of the slide.
You could see that NAV is right in there with carbon 11 in the ability to pick up early centiloids. Also, NAV has superior gray matter to white matter sort of disposition, if you will, which really leads to essentially the ability to read these images much better with more clarity. You really do not need NAV for the advanced population on the far right, which is the positives that you could see they light up like a Christmas tree. If you are looking at the subjects in the middle that test negative or positive, you could see patient number two. On conventional imaging, it is not that straightforward. When you are using NAV4694, you get a startling image here. With NAV, it is the ability to pick up very low centiloid counts or early centiloids. Here is some of the comparison of the tracers.
I guess what we're looking at with NAV is gray matter to white matter ratio and making visual reads much better. Again, a second-generation agent. It's going to have to sort itself out. It's further back in development than MK. The first agent in for us is basically going to be Neuraceq. Because once we close on Life Molecular Imaging, we're in the market right now with a beta amyloid. The next up in the pipeline is our GRPR targeting agent, both the gallium and the therapeutic pair with lutetium. GRPR is very interesting to us because we wanted to stay in prostate cancer, but we didn't want to beat our brains on the wall with another PSMA-targeted agent. What you find in early prostate cancer, GRPR expresses practically to the same extent as PSMA.
As you progress in the prostate cancer paradigm, if you will, where one overexpresses, the other does not. For example, while PSMA is high, GRPR is down. When GRPR is high, PSMA is down. There is a very interesting role for combination therapy, but also for 15%-25% of the patients that do not express at all for PSMA, but do express for GRPR. Our imaging agent is already in phase one. The therapeutic, we're preparing to have a very healthy conversation on a pre-IND meeting with the FDA in the very near future. Here is again some of the scans from Dr. Iagaru out in California looking at RM2 gallium scans, conventional imaging, then with GRPR.
Again, we can see that GRPR really lights it up quite favorably when expressing for when the avidity is there for GRPR versus the subject A, which is conventional imaging. Very clear signal that we light up GRPR when it's expressed, and we know we can deliver the therapeutic to the tumor. The next one up is LLRC15, potential first-in-class targeted antibody, fully humanized, again, linked to lutetium in this instance. The expression profile here is very interesting. Our first shot on goal, if you will, will be for osteosarcoma. The target here has an extremely healthy profile in overexpression in a number of malignancies and no expression to very low expression in basically non-cancerous the rest of the human body.
If you look at breast cancer, for example, on the bottom right, you could see the tumor overexpression versus normal tissue, head and neck, lung, et cetera, pancreatic. We are being very careful here. We hope to be in the clinic at the end of the year, if not at the very beginning of the year. We already had a very successful pre-IND meeting with the agency. We are looking forward to just finishing off some of the CMC and getting into the clinic. Again, if this product can show a glimmer of activity in osteosarcoma, it will be sort of the first time in a while that an improvement has been delivered to this population, which really is an unfortunately tough malignancy to treat. Here is our FAP agent, our diagnostic for right now being worked up in sarcoma.
We are also very interested in looking at FAP and its potential outside of oncology. We have experimental studies up and running in COPD and cardiac applications in NASH or fatty liver NASH. People often call them different things, but we're going to go with NASH and also fibrosis. Lung fibrosis could be a major indication here. We are very interested to see where we can take this agent because it's believed that if FAP was available before FDG, it might have been a better pan-tumor agent than FDG. I think our search here is we feel very comfortable that we'll be able to get an indication in sarcoma. That is a small patient population. How can we really expand it into some of the really exciting areas?
We believe right now that for helping with the assistance of diagnosis and management of lung cancer, the FAP agents could deliver much more information, if you will, than FDG, which is not all that great for lung cancer. While FDG is widely used today, we think we have a very good chance of taking some of that market with FAP. Kind of wrapping up, looking at 2025, some of our milestones and what we've got to get accomplished this year, we have to close on two really important acquisitions. We have to close Life Molecular Imaging. We have to close on Evergreen. We have to advance our GRPR theranostic pair. We've got to advance LLRC15. PNT2003 is with the FDA. We're waiting for a tentative approval. We also have to wade through the Hatch-Waxman exclusivity period of potential litigation with Novartis.
We have to get our tracers over the finish line and filed. A lot is going on, a lot of catalysts first coming up. I think we're kind of busy. That's a good thing. We're powering our future here. We are an industry leader. We're relying on our expertise to avoid the pitfalls that others have made and also improve our probability of success. We are actively diversifying the portfolio and trying to get out of the concentration risk that we're seeing with Pylarify. I think anyone with common sense would say that's a good move. We're sharpening our strategic focus. We want to be preeminent in molecular imaging. We want to be highly selective with radioligand therapy where we're looking at best or first in class.
Our theranostic pair approach really will help guide us in making sure that we pick the winners in therapeutics. That's really it. That's the end of the prepared remarks. We have how much time for questions?
We have about six minutes. Maybe I'll open it up if anybody in the audience has any questions. If not, I can jump in as everybody gets warmed up. I know you're focusing a lot on the pipeline. There's a lot going on in a good way, which I agree with. Maybe starting with Alzheimer's diagnostics and thinking about the space there, some questions that I've gotten from investors is, what wins in that space among tracers? Is it specificity? Is it selectivity? There's room for multiple products as well.
There's clearly room for multiple products. There's three of them right now.
I think when you look at beta amyloid and the future of beta amyloid, I think the game is going to be mostly about the ability to pick up very early Alzheimer's. That means a low centiloid count. That's where we're playing with NAV. Right now, Neuraceq is an excellent product. It's a workhorse. The three beta amyloid tracers that are available today are basically doubling year over year because of the therapeutic march from Lilly and Eisai Biogen. That's a market that's growing because the therapeutics are available. I think the earlier you can pick up the disease with the tracer, the better. You really do not need a tracer if somebody is loaded with amyloid or tau and they have severe symptoms. What is it going to tell you? That you have advanced disease. Good luck.
What you want to do is you want to pick it up early. Again, here's like MK6240 versus p-tau and the other tracers. If you can pick it up early, that's the name of the game. Then you want to track it longitudinally. You want to know how you're doing. That's where I think MK6240 comes in. Because with tau, what you can look at is the region of the brain that's affected. You can look at the relationship between that region and basically symptoms. So correlate region to vision, speech, memory, balance. You can track the patients longitudinally. There are huge benefits, and the field is exploding around us. It's all driven by this tremendous prevalence.
Yep. That makes sense. Talking about tracking patients, I was curious.
There's been a little bit of a debate thinking about blood-based biomarkers versus PET tracers, et cetera. Some of the first Alzheimer's therapeutics have had a slower launch than expected. What's your take on those moving pieces? Does patient monitoring, following progression, sort of help disconnect the PET tracer growth a little bit more in terms of boost it over time?
That's a bunch of questions. Yes. We want the blood test to be fairly sensitive because we want to be able to rule in and rule out the need for a PET scan. The best analogy I have, quite frankly, is the PSMA market. You have a rising PSA, you go to urology, and then you get a workup depending upon how that clinician views your case. I think here we have a positive blood test.
You go to neurology, and the neurologist will begin to work you up and decide whether or not you need a molecular imaging scan. The unfortunate thing is I think the blood test, the biomarkers right now are not that sensitive. As a general screening tool, we really want them out there. It is not practical to image everyone with a molecular imaging scan if they think you have got Alzheimer's. I think that is where it is going. What a blood biomarker cannot do is give you a region. It cannot give you how much of your brain is affected. If you look at, for example, these Neuraceq scans on the bottom left, a biomarker, a blood marker is not going to tell you that. You really need to see. If you are monitoring therapy, you really need to understand if your therapy is working.
A lot of it, the current therapies are sort of, if you will, the resolution of amyloid plaques. As that plaque goes away, where is it happening? How is it going away? How much is going away? The current therapeutics come with some side effects that need to be managed. The burden with a number of MRIs is not trivial. I think they're going to grow. I think the market's poised for tremendous growth. I think we have very good targets to shoot for on the therapeutic side to make modest improvements to get more widespread usage, which will blow open the tracer market.
Got it. Interesting. I noticed, I think it's where 2403, you just got pre-IND feedback. I was curious if you could give us a little more color of what was the feedback like?
How does that inform some of your next steps? What are you excited about?
2403 is the LLRC15 agent that we have that really has a very unique profile in terms of expression in malignant tumors versus non-malignant. The one thing that we're working with Dr. Noah Federman on the West Coast is one of the preeminent thought leaders in pediatric oncology. The meeting we had with the FDA was really nothing but collaborative. They're very much interested in seeing this program progress. Our big quest in the phase one study coming up is to not underdose the patients because these patients are going to be fairly far along. They will have been administered a number of rounds of chemotherapy. Some of the drugs are as old as I am. They're not very easy to tolerate. These patients are quite resilient.
I think we're going to be going in with a reasonable dose. We'll be very quickly able to see if this product can have an effect one way or the other in its anti-tumor properties. We're very, very excited to get this in the clinic.
Sounds good. I did want to squeeze in a question in the last minute. Positioning of Octevi in PNT2003, how are you thinking about that as a possible theranostic pair in the marketplace? How could the sort of paradigm evolve at that point?
We're thinking about it exactly as you described as a theranostic pair. Octevi can compete across the board for all the neuroendocrine tumors, regardless of what the therapeutic approach is. Clearly, when it's paired with PNT2003 or Lutathera, it makes perfect sense.
I think we're going to have a couple of touch points for nuclear medicine to want to work with us. Again, radio equivalent to Lutathera in 2003 is an AB-rated generic at the end of the day. I think it will look like the biosimilar market in terms of uptake and market share over time because these are not easy drugs to make, as everybody knows. You need expertise. You need outstanding supply chain and customer service. Those are all the things we're really good at.
Sounds good. I think with that, we are at time. Thanks again, Brian, for coming out and joining us for the discussion.
Yep. Glad to be here. Thank you.