We have the CEO here. I'm not attempting to pronounce the name, so go ahead, please. Welcome.
Sure. My name's Jarrod Longcor. I'm the Chief Operating Officer at Cellectar Biosciences. I'm going to go pretty quickly, so I will apologize. I'm going to be moving fast because I do have a very full deck today. That is our forward-looking statement. We are a publicly traded NASDAQ-listed company. I'll leave the rest of that. Just as a way of background, so the company was founded really to take advantage of a metabolic change that goes on in tumor cells that allows us to specifically target them in a novel and unique way.
That metabolic change is similar to what most people have looked at before with the Warburg effect, with the overutilization of glucose. However, in this case, what we've done is we've taken advantage of the other system that's going, is upregulated, which is the overutilization of lipids and long-chain fatty acids to produce energy.
Because of that change, the tumor cells actually undergo a modification to the cell membrane and they modify and create these little, these, what we call microdomains known as lipid rafts. Our targeting moiety, our, our targeting ligand, actually specifically targets those lipid rafts and thereby gains entry into the tumor cell. Because of that, we've developed our lead asset, which is iopofosine I-131, which we announced earlier this year.
We, positive data in a pivotal trial in Waldenstrom's macroglobulinemia, which is a, subset of non-Hodgkin's lymphoma. In addition to that, we have an ongoing phase I study in pediatric high-grade glioma because these molecules do cross the blood-brain barrier and allow us to penetrate into that protected area. In addition to that, we have a number of other indications in development with other molecules, with other small molecules, as well as with other radioisotopes.
With that, I will go forward. Just by way, further little explanation on the platform itself. I'm going to avoid the first image there and focus on the second one. The dark area is what are essentially lipid rafts. These regions are made up of cholesterol and sphingomyelin. Our molecule actually binds in between those two molecules and then is actually, as you bind more and more of them, it depolarizes that region and then they pass directly into the cytoplasm.
In the last image there, that's sort of showing that we're right into the cytoplasm, transit along the Golgi apparatus network, and get delivered perinuclear, which really helps us from the standpoint of putting the radioisotope exactly where you want it, right next to the DNA. Importantly, it also allows us sort of some unique benefits over other targeting ligands. One, pan cancer targeting.
So we tested this in over 110 different tumor types and show that we can get access to all of them. In addition to that, we get rapid uptake. So when we infuse these in the animal models, within about 5-10 minutes of the infusion, you start to see uptake into the tumor. In humans, you see it takes about a half hour to an hour to start getting that uptake. So you get rapid uptake.
As I mentioned, penetration of the CNS is a competitive advantage as well. Now, what have we done with this molecule? As I led, was referring to before, we're going to spend most of today talking about the top bucket there, the radiotherapeutic space.
As you can see, if you look all the way to the far right, the mechanism of action, we've actually done this with almost every radioisotope out there. So we've used lutetium, we've used actinium, astatine, lead-212, I-131, which is our lead program, as well as several others.
Beyond that, we've also demonstrated that we can attach to this cytotoxic small molecules of various types, biologic molecules such as peptides and antibodies, in addition to that, oligonucleotides, so our ability to attach siRNA or mRNA to these molecules and knock in and knock out genes. And we've validated every single one of these treatment modalities and shown in vivo that we can actually affect the outcome of the tumor. Over the next 18-20 months, here's sort of what we expect as key milestones for the organization.
Most importantly, as I mentioned already, we had the Waldenstrom's macroglobulinemia study that we had to read out earlier this year. We plan to submit the NDA the back half of this year with the proposed launch and the first half of next year. In addition to that, we're going to be announcing data from our other B-cell malignancy programs that includes multiple myeloma and primary CNS lymphoma.
In addition to that was the pediatric high-grade glioma study where we expect to announce phase 1B interim assessment data where right now we're seeing really interesting outcomes in these patients. In addition, we've launched an actinium-based program in solid tumors. We expect to file an IND back half of this year and potentially even initiate the phase 1 study yet this year.
And then, as you can see, we got additional radiotherapeutic molecules in development and then, our other pipelines will continue to move forward as well. With that, I think this was discussed earlier today a bit, which is, you know, if you look at the late-stage assets out there, basically everybody's in two buckets, either NETs or pancreatic cancer.
Only two, only two late-stage assets right now are in anything else, and that's Actinium and us, both using I-131, both looking at hematologic malignancies. Theirs is more of an inpatient, total ablation of the bone marrow where ours is an outpatient targeted therapy driven to basically allow the patients to stay at home and get well.
Just to give you a sense, again, as we look at this, our molecule has some unique benefits, as I talked through already, the chance and opportunity to use almost any type, any radioisotope with it. And importantly, as you can see, we can target both the primary tumor as well as the metastatic tumor, looking at that middle image. And then in the latter image, again, crossing the blood-brain barrier.
Now this is using our iopofosine I 131 SPECT/CT imaging to show and demonstrate our uptake and ability to cross into different tissues. So as it comes to the Waldenstrom's study and the data we announced earlier this year, the study, CLOVER WaM as it was called, was designed to really look at Waldenstrom's, but confirmed Waldenstrom's patients who had received at least two prior lines of therapy, preferentially prior BTKi exposure as well.
We were looking to enroll at least 50 patients. The patients were going to get 2 cycles broken into 2 fractions. So each, each cycle is composed of 2 doses for a total of 4 doses broken out over essentially 2 months sort of, 2.5 months sort of timeframe. So day 1, day 15, followed by day 57, day 71, and then done.
The important piece was the outcome for the FDA was a major response rate, which is partial response or better in this patient population. And that they were to achieve a minimum of a 20% response in that patient population would be considered statistically significant. I think what we'll show you is that we far exceeded that, that expectation.
I'm not going to worry about the left side of the characteristics of the patients, but rather focus you on the right side, which is if you look at this patient population, it is clearly the most refractory and the most treated patient population in Waldenstrom's ever to be reported in a clinical study. These patients had four prior lines of therapy. Importantly, 80% of them had prior BTKi exposure, 90% had had rituximab prior exposure.
In each of those subsets, the BTKi, 50% of them were refractory to BTKi, 40% refractory to rituximab. You can see the chemotherapeutics, rituximab and chemotherapy is often used together, and you can see that there's a 80% of the patients had prior chemotherapeutic, utilization. If you look at dual refractory, nearly 27% of the patients were dual refractory. This is the first, first dataset to ever report dual refractory patients in Waldenstrom's.
The latter piece down there is the genotypic data. So if you look at MYD88 wild type, that is the most resistant, most refractory patient population. Importantly, that confers resistance to BTKis. And as you can see, we're enriched in that by about three times what you would normally see in the general population. So our responses, 61% of the patients had a major response, keeping in mind that 20% was the hurdle.
In addition to that, 75%, 76% had an overall response rate, and 100% of the patients had disease control. If you look importantly in frontline therapy, first line therapy in these patients, they get a complete response rate of less than 5% with frontline patients. Fourth line patients were at 7% complete response rate in this patient population.
And with that, when you look at duration of response or progression-free survival at the time we announced the data in January, we had a median follow-up of eight months, and had not reached the median for either PFS or DOR in these patients and continued. The waterfall plot sort of speaks for itself. It is, it is heavily weighted to the left, which is really what you want to see. And importantly, every single patient had a benefit.
That's that 100% disease control rate. Every patient saw reduction in their tumor volume, which is important. And as you can see, once you get to the green, those are all major responses. The six on the far left are the complete responses and VGPRs. Three of those patients are VGPRs only because we're still waiting for their bone marrow results to come in.
If they come in as expected, because the criteria for this is complete bone marrow resolution of the disease, those patients will also be complete responders. As they always say, picture's worth 1,000 words. In this case, you're looking at a patient who had extramedullary disease. They had a very large 660 square millimeter tumor lesion.
As you look across at day 28, you can see that has significantly reduced down. And by day 57, they had 100% resolution of that large bulky tumor, which is often a problem for most radiotherapies. So duration of response, as we looked at that, just to give a little sense on this, the green line is actually what we're measuring. And as you can see, there's a bunch of ticks to the far left.
What we did was we sort of set the upper and lower bound for it with the two red lines, just to give a sense of where we might come out since this was taken very early on in the patient analysis. What we see is that even in our worst case scenario, inside of that confidence interval, so the bottom red line, at about 12 months, approximately 12 months, we would still have DOR if in their worst case scenario.
Now, because these patients were isolated out early on, you know, basically what we're saying is that what we believe is that this line, the green line, will go up and out to the left, improving over the course of time. That's what we expect to actually publish in the coming weeks.
Safety profile, we think it's a very good safety profile for this group of patients. Importantly, you know, I sort of skipped over it, but in the characteristics, you know, our median age was 71 years of age, with our oldest patient being 88 years old. So you have the extreme of age in that patient population. Those patients are going to have limited stem cell. These patients are getting high treatment with prior therapies that are bone marrow depleting.
And no shock when you give them a drug to treat a disease of the bone marrow, especially a beta emitter, you're going to see some uptake and cytopenia is present. And that's exactly what we saw: thrombocytopenia, some neutropenia, and anemia. After that, we really don't see anything else. We're not seeing any GI upset. We're not seeing any end organ toxicities.
So no liver changes, no renal changes, nothing else going on, no peripheral neuropathies associated with it. In fact, this disease actually causes peripheral neuropathies, and we see a reduction in those in some of the patients. So importantly, you know, it's a very clean profile other than the cytopenias, which are expected. The important piece about the cytopenias is that they are manageable.
They're very predictable. What do I mean by that? When we treat the patient about 30 days after the treatment, you're going to start to see the cytopenia. 14-21 days after that, they're going to recover, and all patients recover. Importantly, and it's not on these slides anymore, we had no patients discontinue treatment in this study. So as a summary of this study, as I said, you know, first and most difficult patient population we think ever treated in Waldenstrom's.
We still got a 61% major response rate, 72% overall response rate. And, you know, this is on a fixed course of therapy. I think it's important to remind people, BTKi is the only approved therapy in these patients, and that is continuous therapy. So once they go on a BTKi, they can never come off of it.
They got to get treated over and over and over again, every day for the rest of their lives or until progression. So where do we go from here? So as we think about our, well, this actually gets into the commercial side of things, why we, why we chose this marketplace.
So one of the things we did, you know, recognizing that radiotherapeutics have had a challenge when it comes to manufacturing and supply chain, we went about a process of really making a redundant and robust system, which we believe is pretty essentially uninterruptible. And so we've secured radioisotope from multiple sources. I-131 coming from three separate sources around the globe.
We've contracted with, or are contracting with, multiple finished product manufacturers. We're not doing it internally. We're outsourcing that completely. We have partnered with a number of radio pharmacies, and then our logistics and our supply chain. That latter part of that, the logistics is really important here. We did something very different and that we developed a formulation that gives us a 17-day shelf life from the day of manufacturing. That gives this drug the potential to essentially operate like it's off the shelf.
So when a patient, you know, when a site wants the drug, it's there, it's ready, it's able to be shipped. I think somebody in the morning session said, "Oh, we can't get that in 20, you know, you can't get I-131 in a conjugated form in 24 hours or 40 hours." This product does allow that.
And that's a major change in sort of the marketplace. It also allows the flexibility at the patient end because you know what, life actually happens. And they get in a car accident or their grandkids are coming over or what have you, and they need to postpone their dosing. This allows the flexibility to give them another week or two to come back in and get their dose done.
The last piece is we also designed it to be very patient-centric, you know, keep them down to a very fast infusion, about 12-15 minutes, and then a couple of saline flushes and out the door they go. We think that this is a 100% outpatient setup. So these patients aren't hospitalized.
They're in the, they're in the infusion suite for about 30 minutes, maybe an hour max, and then they go home. With that, as we look at the market, there's 26,000 patients with Waldenstrom's in the, in the U.S. right now, about 1,900 newly diagnosed annually. So that's your incidence rate. Importantly, 80% of these patients will progress and will go on to third line therapy. This is an incurable disease. So eventually all patients progress. It's just a matter of how and when.
Importantly, when you look at that third line, traditional numbers that have been reported in the third line setting, only 4%-12% of patients will get a major response in the community setting, according to the EHR data that's out there. If you take a deeper look at this, that means there's about 12,000 patients who are relapsed or refractory Waldenstrom's patients currently on an annual basis.
That leads to about 4,700 patients today that are seeking therapy. Importantly, there's about 1,000 patients that today do not seek therapy. They don't seek therapy because the only therapies that remain for them is to be rechallenged on stuff they've gotten before, which didn't work before. Why would they want to get retreated and go through feeling sick again? Because of that, we think the population we're targeting, it's about 5,700 patients at the start.
Like everybody else talked about earlier again this morning, you know, indications to come in in the late line setting and then move forward up into earlier lines of that setting as things go. This sort of explains that marketplace, right? So as you look by line of therapy and utilization of current therapies that are out there, you essentially have patients getting rechallenged over and over and over again.
No real standard of care. BTKIs, again, are the only approved therapy, whether first line or second line. There is nothing approved in the third line setting. In our other indications, as I mentioned, we are looking at a number of other places, refractory Primary CNS lymphoma, which we've already shown and demonstrated a Complete Response in.
Additionally, relapsed pediatric high-grade glioma that I mentioned before, where we've demonstrated in a dose escalating study that we can get progression, increased or enhanced progression-free survival. On the right there, you know, there are DLBCL patients where we saw about a 30% major response or overall response rate and a 10% complete response.
And then most recently, in an IST, we looked at head and neck cancer, recurrent head and neck cancer, where we had a 64% complete response rate in these patients, and a 70% overall response rate. In multiple myeloma, as I mentioned, we do have a study going on in that. We've seen everything from a 30% to a 50% response rate, again, depending on the patient population, depending on the refractoriness of the patients and the treatments that they've gotten before.
In fact, as they become more refractory, we tend to have a more efficacious response. So now onto the alpha emitter programs. It was interesting, as we always tell the story internally and now externally, we're doing something a little different here. We're trying to find the right isotope for the right disease setting. So because we have this pan-targeting capability and we don't have to swap out the ligand to go after new tumor types, we're able then to swap the isotope and see which isotope works better in which tumor type.
As you can see here, somebody said, "Oh, Lead-212 might work similar to Actinium." Well, in pancreatic cancer, it doesn't. Doesn't even come close. Actinium is much better in that setting than the Lead-212. It's not to say Lead-212 is not a good drug or a good isotope. It's just not in that setting.
When you look down below, when you look at triple-negative breast cancer, again, looking now at Lead-212 and Astatine, you can see that that in that environment, Astatine may edge out Lead-212 a bit, but they're pretty, they're not too dissimilar to one another. That may be something to do with the half-life, might be due to the timing of the dosing or the microenvironment, all of which are things that we're, we're looking at when we look at these.
Lastly, just sort of validation of our other programs. Interesting, you know, you can see in the middle there where we get our uptake into, that's breast cancer cell line versus normal tissue where you see really no uptake on the far right.
Again, you've got our small molecule program showing complete knockdown of the tumor, complete regression, and no regrowth after just, in one case, 2 doses and the other 4 doses. Again, validating the capability of our compounds to get in, whether they're small molecules, peptides, or what have you. With that, I thank you.
All right. Awesome. Any questions from the room? Whitney? No? All right. I had one. So, Iodine-131, there is sort of a natural, you know, affinity to the thyroid gland. So, you know, do you have, have you seen that and to what degree could that be a risk?
Yeah, so we have not seen thyroid uptake of it, of our Iodine-131. Now, when we, one of the key differences for our molecule is it's covalently bound. We're not using a chelator in this case. This is covalently bound to the molecule.
So unless you go through autoradiolysis, you're not getting the isotope falling off. And so that reduces your chance for a thyroid uptake because these molecules aren't going to go there otherwise. That said, the one piece that is always true with this, with the FDA, is everybody's got to go on thyroid protection medication no matter what because the agency won't let you do it otherwise. But when we do different models and we've done different testing, we don't see any uptake.
Okay. I may have missed it, but to the lipid targeting moiety, obviously the ones from data is very, very nice, very, very powerful, right? But you know, how tumor selective is this and do you worry about off-tumor effects in other indications perhaps?
Yeah. No, great question. So and because I was moving fast, I skipped over some of that. So what we tend to see, there are three fundamental differences between, how do I want to say that? Every target that is on a tumor cell is basically on normal tissue anyway, right? Irrespective of what we're targeting, I don't think anybody's gotten 100% clear on one and nothing on the other.
We're no different than that. But we have three fundamental differences that make this targetable on the tumor different from being on normal tissue, right? So on normal tissue, the number of lipid rafts are very, they're very limited. On a tumor cell, there are thousands of them. Then when you shift to the next piece, which is the size of the lipid raft. So in normal tissue, again, they're very, very small, only a few nanometers in size versus micrometers in size once they're on a cancer cell.
And that's because they start to fuse together and they get larger and larger over the course of time. The last piece, which is actually probably the more fundamental and most important piece, which is in normal tissue, they form and dissipate very rapidly, which makes them near impossible to target. In tumor tissue, they're stabilized on the order of 7-10 days. Now they become targetable. And it's that shift.
And the reason they become stabilized is because they act as signaling hubs. They actually coalesce the tyrosine kinase receptors, the GPCRs that we're targeting with antibodies and everything else everywhere else. The difference here is we gain, well, those systems will gain entry and track to the late endosome because of that mechanism. Our binding to it actually depolarizes it and allows us to enter just like what would happen in a micellar sort of environment. You penetrate and you depolarize that cell membrane and you slip right through.
And then, and I may have missed it, but sort of in iopofosine, what are sort of next steps, sort of FDA submission, et cetera?
Repeat that. Sorry.
The next steps in the iopofosine program. Oh, in the Waldenstrom's program.
Yeah. So right now we are, we're basically cleaning the data set, and we've written most of the NDA filing. We have a handful of, I'll call them handful of remaining meetings with the FDA, including a pre-NDA meeting to come. And then the submission goes in. And that's the back half of this year, we expect to be in front of the FDA with the full NDA package and then, middle of next year-ish, with the approval, hopefully with the approval.
Gotcha. And then what? What are your plans to, obviously with good monotherapy activity, to perhaps advance into early or maybe in first line therapy?
Yeah. No, I think, in this indication, because of the nature of it, as we think about early lines of therapy, we're thinking about combination treatments, because that's what's often done right now. First line is most often rituximab plus some chemotherapy, so immunochemotherapy. So one opportunity is to replace rituximab in that combination and demonstrate that we're much better than rituximab.
All right. Well, thank you so much. And, yeah, we'll look forward to updated information here. So appreciate the presentation. Thank you.
Thank you.