Thank you for your patience, everyone. Just resolving a few technical issues. Jeff Jones, one of the analysts here at Oppenheimer on the biotech team. I'd like to introduce now Cellectar Biosciences, and Jim Caruso, their President and CEO. Jim, over to you.
All right. Thanks, Jeff. Appreciate the introduction. Certainly a pleasure for me to be presenting here at your conference. Very much appreciated. Cellectar Biosciences is, in fact, traded on the Nasdaq Exchange under the ticker symbol CLRB. Here you have our obligatory safe harbor statement. Of course, I would direct your attention to our periodic reports filed with the SEC. As many of you are aware, Cellectar Biosciences is focused on the research and development of rare adult and pediatric cancers, and the foundation of our focus remains our phospholipid ether, or PDC, delivery platform. Regardless of the oncology therapeutic payload that we have added to our delivery vehicle, it demonstrates preferential treatment or targeting to cancer cells, stem cells, and metastases, sparing healthy tissue.
Or said another way, modifies the payload, the oncology payload's therapeutic index by enhancing activity and improving the adverse event profile. Our lead asset is a radioisotope, a beta emitter, iopofosine I-131 . And as most of you know, we recently announced successful top-line data from our pivotal study, CLOVER WaM, for the treatment of Waldenström's macroglobulinemia, or what we refer to as WM, as we advance throughout the presentation. We have, in addition to WM, significant and substantial data in a variety of hematologic malignancies, including multiple myeloma, DLBCL, as examples, as well as other heme malignancies, B-cell lymphomas. I will say this, we have paid a significant amount of attention and applied a significant amount of resources to our manufacturing system or process, if you will. It's highly efficient, both from a manufacturing perspective as well as a logistical perspective.
I-131 is off the shelf. It is ready to use. We can deliver around the globe within 72 hours. And importantly, another area of differentiation is the 17+ day shelf life, which provides both the healthcare provider, the caregiver, as well as the patient, optionality in terms of the scheduling of the doses. We recently received an additional $44 million in milestone-based funding, post the delivery of our successful top-line data for the CLOVER WaM study. As most of you are aware, the radiopharmaceutical space is white hot. What you may or may not be aware of is that Cellectar Biosciences is the leader in radiopharmaceutical patents and applications. And as you can see here, we are followed by Novartis, Lantheus, Bayer, and Biogen. Many of these companies, over the last handful of years or recently, have advanced into the radiopharmaceutical space.
We've been engaged in radiopharmaceuticals for a number of years and have been very methodical in terms of expanding our intellectual property portfolio. We'll briefly talk to our development strategy, and I'll direct your attention to the left side of this slide under payloads, specifically small molecules, biologics, and nucleic acids. You could scan across the page, you can see the conjugates that we typically use for those three areas of payloads, as well as the mechanism of action. We believe these areas will be value creative for the organization, for our stockholders over time. For the sake of today's presentation, we'll focus on our radiotherapeutic programming, in particular, iopofosine I-131 . I do want to point out our alpha emitter program. We have done significant work here, not only with actinium, but with astatine and lead-212, a variety of alpha emitters.
We have seen preclinical data, very positive preclinical data across the board with all of those isotopes, and that's what makes our delivery platform unique, and we'll talk a little bit more about this as we advance through this presentation. Then, as I mentioned earlier, our lead asset, iopofosine I-131 , a beta emitter, recently achieved successful top-line data out of a pivotal study for Waldenström's macroglobulinemia. On this slide, you can see some R&D-related milestones over predominantly 2024 and 2025. With iopofosine I-131 , we recently announced that top-line data. In January, we are going to provide an update to this data in the Q2 of the year. Second half of the year, we anticipate the submission of our NDA, and in parallel to the submission, our priority review package as well, which would allow for a six-month review by the FDA.
Our planned launch for iopofosine in WM is in the first half of the year. In our ongoing Phase IIa program, you can see we will announce some data around the completion of enrollment in our multiple myeloma and primary CNS lymphoma arms, and then for pediatric high-grade gliomas, we recently announced the initiation of our first patient, and we'll have updated data there over the course of the second half of 2024. Our TAT program, or alpha-emitter program, we have initiated IND-enabling studies, and this is with actinium as the payload. I'll direct your attention to the bottom of the slide. As you scan across from manufacturing, in the second half of this year, we will establish EU manufacturing, which will reduce that 72-hour around-the-globe delivery time for certain regions of the world.
In summary, on our iopofosine lead asset, from a designation perspective, top part of this slide, you can see 8 designations, one from orphan drug, 6 U.S., 2 ex-U.S. We have 4 rare pediatric drug designations, 3 Fast Track designations, in addition to WM, multiple myeloma, DLBCL, and then that PRIME designation is for WM. And that really is important for us as we engage the European authorities from a regulatory perspective, and there's meaningful benefits from a commercial perspective as well. I'll direct your attention to the bottom of this slide, and you can just see from a market expansion strategy at this point in time, the 3 aforementioned studies that we have ongoing. Now, the WM market itself is very substantial, and, as you can see from a market sizing perspective, the prevalence is significant, 26,000 across the U.S.
Importantly, 10,000 are relapsed/refractory patients, and there's plus 4,000 in the third-line treatment arena. What's important and interesting to know about this market in general is the scalability of it. It's highly concentrated, and here you can see 80% of the patients are located within 15 states. 60% of the patient population is within 10 states, and these are typically your Sun Belt states. This is a disease of older patients, and so those retirement states, the Florida, as an example, California, you typically see an increase in the number of WM patients there. At this point in time, about 55% of these patients are located in the community and 45% academically. The scalable nature of this is significant, and there's a number of reasons for that.
Limited marketing, medical, commercial investment can really drive top-line utilization because of the nature of this marketplace. It's also important to know there's no large multinational pharmaceutical, commercial, or marketing, or medical machinery in this space as well. Thought leadership and access to those accounts that are driving the business is pretty open. From a patient treatment journey perspective, 80% of the patients are receiving treatment, 80% of the patients will receive third-line treatment. This is a significant area. If you take a look at that third bullet under patient treatment journey, there's approximately 1,000 patients that are currently not treatment seekers.
The reason why is that there's no available treatments or no new treatments for these patients, which tells us they've been through some of the standard treatments, the salvage chemotherapeutics, et cetera, in addition to those agents that are typically used, for these patients. So that 1000 is patients, about 50% based on market research, would seriously consider a new agent for treatment if, in fact, it was available. According to multiple data sets, you're gonna see this major response rate, this third, fourth, fifth line in this 4%-12% range, and we continue to build out our data set there that we will share, not only with the medical community, but with the FDA as we advance our additional work in that area.
Obviously, in this third line or later population is very limited available treatment agents there. And the fixed therapy that we have, that we'll talk to in a moment, is a significant benefit, both from a clinical perspective, from those healthcare professionals, as well as from a patient perspective. This slide talks through the design of our recently completed study. You can see enrollment criteria on the left-hand side. WM patients had to receive 2 prior lines of therapy, including those that have failed or suboptimal response to BTKi therapy. You can see the major endpoint, major response rate, and then the key secondary duration of response, obviously ORR, and then treatment-free remission. Toward the bottom of this slide, you can see the dosing paradigm, and this is what makes iopofosine I-131 unique and very desirable in this patient population.
Day 1, day 15, and then a 6-week drug holiday, day 57 and 71. It's important to note that the infusion time on average is only 15-20 minutes. So typically, soup to nuts in the academic center or in the community-based infusion center, patients are spending approximately 2 hours in total, which is also a departure from what you typically see with those agents that are infused. Before I leave this slide, it's important to note that in alignment with the FDA, the major response rate, primary endpoint, was 20%. And now I'm gonna share with you, over the next handful of slides, some of the data that came out of, out of this study.
Prior to doing that, I wanna talk about what we believe is not only the largest study for WM, this relapsed/refractory patient population, but according to key thought leadership, community-based clinicians as well, this is the most refractory or most challenging WM patient population that has ever been studied in clinical trials, and that's unanimous across the board. You can see in this patient population, the age range as high as 88. That's significant because these patients in their 70s and 80s are very frail, yet we've demonstrated the capacity to treat these patients comfortably. I'll direct your attention to the IPSS-WM score and to the medium and high percentages in particular. These are negative prognostic factors for overall response rate and progression-free survival.
To date, approximately 40% of the patients in this study are identified as medium or high. If you flash to the right side of this, I think one of the most significant elements here from a patient characteristic perspective is the median prior lines of therapy. 4 doublets, triplets, combination chemotherapeutic soups, as well as the standard agents that were used here, BTKIs and rituximab. So, on average, iopofosine was the fifth treatment used for these patients. Importantly, there was a high degree of refractoriness to BTKIs. As you can see, 50% of these patients were refractory to BTKIs. If you look at rituximab, 40% of the patient population was refractory to rituximab. So between BTKI and rituximab, I'll do the math, that's 90% of these patients, right? Or an overlap. Let's talk about dual refractory.
That's just under 30%. So an extremely challenging patient population. We'll include the chemoimmunotherapy refractory level as we continue to dig through the data. So you have this triple class refractory number, that would be substantially beyond the 26.7%. Now, I will say this, for MYD88 wild type, what you'll notice is that's a very challenging subtype to treat, and BTKIs have a high resistance to MYD88 wild type. And high resistance to MYD88 wild type is a nice way of saying they don't work. In this patient population, approximately 30% of the overall patients treated with iopofosine were MYD88 wild type patients that do not respond to BTKI treatment. p53 mutated, regardless of the indication, is an extremely challenging patient type. Here's the data. Remember, the hurdle was 20% from a statistical perspective.
Our major response rate to date, 61%, 75.6% overall response rate, which is also exceptionally impressive. Then, to me, 100% disease control, which means every patient dosed with our drug received a treatment benefit. So as a result of that, you take a step back, and you think about the fifth, you know, the positioning here, the severity of disease with these patients, the age of these patients. This is clearly a paradigm shifter, a game changer in the care and relapsed refractory WM patients. I will mention the complete response rate here, 7.3%. I'm gonna flash to a slide in a moment, which will give you better line of sight as to how that plays out. But I want you to think about this in combination with a BTKi and rituximab in first line.
Naive patients have not received any other treatment. Complete response rate was approximately 5%. In this fifth-line setting, monotherapy iopofosine, at this point, 7.3. We're highly encouraged that this number will go higher. Obviously, when you think about those numbers, and let's say it's about 1 in 10 in this third, fourth, fifth line, that respond to treatment, so for those 10% of the patients, so that 1 out of 10 patients, it's approximately 6-month duration of response. For the 61% major response patients that have, to date, responded, we're at 8 months and growing. And as I mentioned earlier, there's a broad utility here, which is significant.
So regardless of the patient type, you can dose with iopofosine I-131 and be confident you're gonna get a positive outcome, which makes this unique in terms of the treatment of WM. This, I think, speaks for itself. When you take a look at the best response by patients, and this is reduction in IgM, if you look at the Y-axis, you'll see reduction in IgM. You know, the X-axis essentially is those number of patients, across the top here, and the percentage and maximum change. I will bring to your attention that 0-24.99% is considered stable disease. When you go beyond that, and you're at 25-49.99%, now, now it's a minor response, and beyond 50% is a major response. That 75% line and, and beyond is a very good partial response.
Now, I'll direct your attention to the far right portion of this slide, in which you'll see our three complete responses, and then three others that have achieved a complete response via IgM, and we're now waiting to confirm this with bone marrow. Again, I go back to combination therapy, first line, BTKi, rituximab, 5% complete response rate, monotherapy iopofosine, potentially six patients here, or approximately 15% in five lines, four lines of prior treatment and as a fifth-line therapy. This, I think, is also significant. This gives us some degree of confidence that we have the opportunity to improve on a major response rate. I'll. If you take a look at the left-hand side of this slide, or the Y-axis, that is, percentage of major response or percentage of overall response in general.
And then as you take a look at the X-axis, that's in months. And at approximately 2 months, in the first 25 patients in this study, because this is time related, a function of time, 28% had a major response, 72% had an overall response. As they continue with therapy over time, you can see a significant increase where your overall response rate is just under 90%, and you see this enhancement in major response to 72%. And that's a function, really, of the mechanism of this drug, and how it continues to impact the disease over time. Again, making this atypical relative to BTKI therapy, where once you discontinue, within a handful of weeks, your IgM levels spike, and symptoms would return.
The only other element here that I wanna bring your attention to is the rapid nature of the responses, and you can see you have that within the first 30 days or so. The Kaplan-Meier curve, N of 30 patients, also very impressive, despite the fact that this is early on, as noted by the Kaplan-Meier curve itself. But you can take a look at the middle, far right in the box. The middle bullet point says it all: our confidence interval supports, at this point, a minimum duration of response of 11.4. We believe, as the data matures, this number goes significantly north. And again, think about those one in 10 patients that are achieving approximately 6 months.
Not only is the major response rate threefold that of the statistical hurdle, you can also see we're already twice that of the response or the durability of those responses. This talks to the adverse events associated with iopofosine I-131 in this patient population. As you can see, very consistent with what has been historically presented with I-131 . I will bring up the fact that there's 3 elements associated with this. One, the age of this patient population. Two, it is a disease of the bone marrow. And again, this is 5 lines. You know, we're a 5th line therapy here, 4 prior lines of therapy. So these patients are pretty beaten up, and so you would expect cytopenias.
I'll direct your attention to the left side of this slide, and you can see the 0% treatment-related discontinuation, 0% treatment-related deaths, and as importantly, 0% clinically significant bleeding, which means there's no sequelae, there's no ramifications for the patient based on the cytopenias. I will say all patients recover from their cytopenias, and the onset and recovery are very standard. They're very predictable and manageable. Now, what don't you see? You don't see cardiovascular events. You don't see neuropathies. You don't see GI, CNS, renal, hepatic adverse events, which you typically see with other agents. So, in summary, this is the largest study to date in relapsed refractory patient population. It is the first to study dual refractory patients, just under 30%.
We will add the chemo immunotherapy patients to this as well. 61% MRR in the first 41 evaluable patients, and as you can see, over time, as demonstrated by that response curve slide, 18 of the first 25 patients had a 72% major response rate. Based on that, the benefit of the additional follow-up time, we're very pleased with the safety profile, no treatment-related discontinuations. And again, the fixed course of therapy here is very important to patients from a quality of life perspective. And also, it's what clinicians prefer and want as well. The data on the right, we've chatted through that. Look at rituximab refractory population, just as an example. The response rates there are less than 10%, you know, regardless of whether it's, you know, second, third line and beyond.
One of the areas that we've invested significant amount of resources and dollars to ensure that we get this right, that's in our manufacturing and logistics. We do have a multi-source network. We have built-in redundancy here. As we talked about earlier, we do have the capacity to deliver around the globe within 72 hours. Simplicity, simplicity, simplicity. No cold chain logistics. You could move and transport this and store it at room temperature. It is off the shelf, right? Very simple, easy to use, ready to use for the patients, and most significantly, it's a 17-day-plus storage life. And when you look at other radiotherapeutics, it's all the... You know, they need to be infused almost upon receipt.
Here, you provide flexibility for the healthcare provider, for the patient, in order to create an optimal schedule for that patient, and it ensures dosing and no wastage of drug product. This is a slide. Obviously, we've seen this with astatine, we've seen this with lead-212. We're demonstrating an example here with actinium. Standard kind of preclinical work. You're demonstrating the activity based on tumor volume reduction. You're demonstrating safety based on weight percentage and body change there. It looks good, yes. What's the big takeaway here? The big takeaway here is, with our delivery vehicle, we can add or conjugate any radioisotope, which means any of the more commonly used alpha emitters beyond actinium, and see the same sort of performance and result.
And that's significant because now we can attack tumor biology and make decisions in terms of, with actinium, clearly triple-negative breast cancer, ovarian, are great examples of-- or pancreatic cancer, great examples of areas that we can attack with actinium. Where you see current, agents really kind of in this NETs arena and in prostate for a second-line, fragmenting those markets significantly. We can use the right payload for the right tumor. From a capitalization perspective, 30.5 million shares outstanding. I'll direct your attention under the reserved for issuance with the Series D, E, and Series E-3s. We have approximately 10 million shares that could be converted to common, plain vanilla, like any other common share.
I will also point out there is an option of approximately 7 million shares post our NDA approval for WM at $4.77. The $44 million, I think, is important to... You know, that funding is obviously critical for the company. And $44 million was in full received based on the announcement of our successful top-line data. In summary, we remain laser-focused. We understand the importance of WM and getting our regulatory house operating at a high level there. We have both internal and external teams of experts surrounding this submission. I have a high degree of confidence in providing a world-class document to the FDA. I will also say, our commercialization efforts, we have a lot of experience in-house with successful commercialization of oncology drugs. This is a scalable space.
It's important to note that our OpEx for 2025, you can build in around $25 million for our operations here, which you would typically see is more like $50-$70 million. This is a function, really, of the space itself and our capacity and understanding of smart data and how to lever that, and also our philosophy in terms of top-down system versus bottom-up, which you traditionally see in this space. We continue to work and enhance, not only in sister indications for WM, but in B-cell malignancies and plasma cell neoplasms as well. Then we're gonna run fast and hard with the alpha emitter program because we realize the value that that will create for our stockholders and the additional opportunities we have to advance a series of agents into phase I's.
With that, I thank you for your time today, and I'll turn it back over to Jeff or the group for any questions. Thank you.
Just one question, if you will, and since I know we're short on time. Are you anticipating the label for the product in WM to be third-line plus, or just something, say, post-BTKi refractory?
It's a great question, right? Because you are-- You know, our initial discussions with the FDA and the study was designed for third-line plus. And now you're saying, "Jim, based on those patient characteristics, you know, this is clearly a label that has potential in the relapsed refractory patient population," or potentially, to your point, post-BTKI, which would also be second line and beyond, because now you have the combination use of rituximab and BTKI in the first line. So it's a very fair question. I'll take a step back and say our original discussions with the FDA were third-line plus, and that's how the study was designed. But based on the population that we enrolled, it's clearly a relapsed refractory population. It's clearly, to your point, post-BTKI. So we're pretty excited about future discussions with the FDA.
I think the other important element here is, when we think about, you know, a relapsed refractory population, [it] is the performance of the drug, right? And so at the end of the day, the major response rates, the overall response rates, the duration of response responses, all which are getting better, and we anticipate to improve, will be a significant benefit to patients. And so you know, we view this as a meaningful discussion with the FDA.
Great. Well, thank you very much, Jim. I know we've all got additional investor meetings and things to go to, so I will turn you loose so you can take advantage of that opportunity. And thank everybody for attending this afternoon. With that, operator, can you take us clear?