Good afternoon, everyone. Thank you for joining us today. I'm Jeff Jones. I'm one of the analysts here at Oppenheimer, taking us through our annual healthcare conference, and I'm delighted to be joined by Cellectar Biosciences and their CEO, Jim Caruso. Jim, I will hand it off to you and let you take us through the story.
Terrific. Thank you, Jeff. We certainly, as always, appreciate the opportunity to participate in the conference. As a reminder to the audience, Cellectar is traded on the NASDAQ, and our symbol is CLRB. Here you see our obligatory safe harbor statement. Of course, I also would direct your attention to our periodic reports filed with the SEC.
When you think about a concise overview for Cellectar, I think it's fair to say that we're focused on the research and development of oncology assets for rare pediatric and adult cancers. The foundation of this focus is our phospholipid drug conjugate, or PDC, platform. Our lead PDC is iopofosine I 131, a beta emitter, and our most advanced indication is Waldenstrom's macroglobulinemia, or WM. The company recently completed a successful phase two study in WM, and based on discussions with the FDA, prior to the study completion, the company believed that successful achievement of the primary study endpoint of major response rate and secondary endpoint of duration of response from the phase two CLOVER- WaM study were acceptable to support accelerated approval and regulatory submission for a conditional approval.
Despite excellent patient outcomes in the most relapsed refractory patient population ever studied to date in WM, including an overall response rate of approximately 84% and exceeding primary study endpoints with a major response rate of approximately 58% and an impressive median duration of approximately 11.4 months and ongoing, the company learned that it is likely that an additional study to include a major response rate endpoint was required for a conditional approval, and a progression-free survival endpoint from the same study was required for full approval. To fully understand the FDA's requirements for conditional approval under the accelerated approval pathway, the company has scheduled an end-of-phase two meeting with the agency that will occur in the first quarter of this year.
Based on what we currently know, we anticipate a randomized control trial, approximately 50 patients per arm, with a conditional approval endpoint of major response rate and the full approval based upon PFS. We believe that this design has limited clinical risk. We anticipate the total cost of the phase three study to be approximately $30 million-$35 million. Importantly, about $20 million of this cost is required to fully enroll the study, with the remaining $10 million-$15 million necessary for your more traditional and standard patient follow-up and study closure costs, et cetera. Based on the quality of our data, awareness of our data, and high unmet need in later lines of WM, we are currently estimating approximately 18 months to fully enroll the study from the time the first patient is enrolled.
As previously cited, we are also evaluating strategic options to support costs associated with the execution of our phase three study. Based upon the quality of iopofosine's WM data, limited perceived clinical risk to approval, and a robust market opportunity in both the US and ex-US, we continue to receive inbound inquiry regarding our interest in a range of collaborations, including licensing type deals, which is, quite frankly, our preferred non-dilutive funding approach. The net is we feel very good about our go-forward plan with iopofosine and WM. It is cost-efficient with limited execution and clinical risk. We are also excited about our phase one ready assets, which we will review over the course of this presentation, which include an alpha emitter and an Auger emitter, both of which highlight the novel utility of our delivery platform.
Our current cash position extends into the fourth quarter of 2025, which provides ample time to gain clarity on the regulatory pathway, craft a non-dilutive licensing deal, and for our stock to experience organic price increase based on the company's current undervaluation, anticipated milestones, and the rebound from the market overcorrection regarding the delay associated with our WM NDA submission. Let's start with a review of our PDC platform and pipeline. I think most of you are aware as we reviewed our mechanism of action in the past, lipid rafts play a significant role in cancer. In fact, lipid rafts represent a unique and previously unexploited universal target for cancer and are essential for cancer cell development, growth, cell survival, and the ability to overcome resistance and transformation to metastatic disease. Lipid rafts are also essential to cancer cells.
They are uniformly present and excessively abundant across cancer cells. In terms of the profile, our PLEs, or phospholipid ethers, have been specifically designed to provide targeting to lipid rafts and possess a unique chemical handle, which allows conjugation of diverse molecules. Our molecules bind to the cancer cell and then are internalized directly to the cytoplasm. This process occurs rapidly and allows targeting to almost any cancer in any environment. Cellectar has conjugated and validated both in vitro and in vivo each of the oncology therapeutic franchise payloads, or MOAs, listed on this slide: cytotoxic molecules, biologics, nucleic acids, and of course, radioconjugates. As it relates to radioconjugates, we have attached to our PLE a wide variety of isotopes, including beta, alpha, Auger, and other emitters. Essentially, we have tested and evaluated every significant therapeutic radioisotope across the emitter landscape, with each demonstrating excellent tumor uptake and activity.
The utility to attach any radioisotope, as demonstrated by our PLE delivery platform, provides obviously unique targeted delivery benefits for a more elegant and effective development approach, allowing for the selection of the right isotope or the right tumor when considering how to attack different cancers. Each type of isotope, whether it be a beta, alpha, or Auger emitter, provides unique and different physical properties, including energy length, as depicted by the arrows in the pictures, and this allows for the selection of the optimal isotope, which enhances the likelihood of a positive drug development outcome. In terms of our product pipeline, we have built a diverse pipeline of products with our lead program, iopofosine I 131, entering a phase three confirmatory study in Waldenstrom's macroglobulinemia.
Additionally, we have impressive data in other hematologic diseases such as DLBCL in a relapsed refractory environment, a 30% response rate with CRs demonstrated, multiple myeloma with ranges, response rates in later lines of therapy ranging from 40-60%, pediatric high-grade gliomas demonstrating extended progression-free survival, as well as head and neck cancers in combination, achieving a 60% complete response rate. Very impressive across a wide range of both hematologic malignancies as well as solid tumors associated with head and neck cancers. As cited earlier, our two additional clinical stage assets are CLR 121225 as part of our actinium program and CLR 121125, the Auger emitter. As we look at both of these assets, we will be prepared to initiate phase one studies in the first half of 2025. Slide 10 talks to our unique PLE delivery platform and the landscape in which it's competing.
Cellectar is the only company developing three different radioisotopes in unique tumor types and in large, more difficult-to-treat tumors such as pancreatic and triple-negative breast cancer. These are currently indications not in active development with other radiotherapeutics. Let's talk a little bit about our phase two CLOVER- WaM study for the treatment of WM. As you can see, this slide provides an overview of patient characteristics. While there is a lot of interesting data, we can summarize by saying that this was a highly challenging population, and based upon just age and other factors, these patients are frail and high risk. Patients presented with a median of four prior lines of treatment, with over three quarters of the patients refractory to the two most common WM treatments, BTKIs and rituximab, and nearly 60% of patients were refractory to both the BTKIs and rituximab.
The efficacy in this challenging patient population is quite impressive. As you can see, nearly 84% of patients experienced an overall response, which represents a significant drop in disease burden and typically the target metric for both doctors and patients. From an FDA or regulatory perspective, the 58% major response rate was almost triple the required study major response rate target outcome of 20%, along with achieving extended PFS and DOR. It is noteworthy that these patients achieved these results receiving only four approximately 15-20 minute infusions of iopofosine I 131 over a 70-day period. I mean, importantly, strong efficacy data was achieved across the spectrum of WM patient subpopulations, including high-risk cytogenetics and prior treatment-exposed or refractory patients. As you can see, the overall response rate and major response rates were consistent across all challenging WM subpopulations. This slide truly represents the classic pictures, say, a thousand words.
The waterfall plot demonstrates the effectiveness of iopofosine with every patient but one benefiting from the treatment with iopofosine. The data clearly demonstrates that iopofosine is highly efficacious. You know, but the question is, how about its safety? Iopofosine was shown to be extremely well tolerated in an elderly and fragile patient population, and the AE profile is consistent with other heme malignancies previously studied. All, and that's all grade three or greater adverse events were hematologic in nature and were mostly cytopenias, thrombocytopenia, and neutropenia. Importantly, these patients experiencing thrombocytopenia did not have any clinically meaningful bleeding or severe bruising. Despite the neutropenia, the rates of infection were low, which is also consistent with our previous data. The AEs remained predictable and manageable, and all patients recovered from hematologic-related counts.
I believe it's appropriate to remind the audience that WM is a disease of the bone marrow, and the patient population was elderly, heavily pretreated, and thereby susceptible to hematologic adverse events. Also appropriate to share that outside of the mentioned heme events, there were zero grade three or greater non-hematologic adverse events. Zero. To summarize the CLOVER- WaM study, patients tested were extremely challenging and achieved impressive safety as well as efficacy results. The company is now focused on our discussion with the FDA to finalize a confirmatory study design supporting the accelerated approval pathway and anticipate greater clarity by the end of Q1. With this slide, we can briefly discuss the WM market opportunity. It is substantial.
A US prevalence of approximately 26,000, approximately 11,500 relapsed refractory patients, 4,700 third-line or greater patients, and approximately 1,000 patients that are no longer treatment seekers, which is likely the result of limited to no effective therapies for this later line patient population. The graph also tells an interesting story. As you can see, approximately 50% of all patients are rechallenged with the same drug at some point in their treatment, and 60% of all WM treatments are not FDA approved. The high unmet need in WM is further demonstrated by the substantial rechallenging and reuse of the BTKIs and rituximab, as you can see across all lines of therapies. As you can also see, real-world data from sophisticated oncology community-based delivery networks report response rates of approximately 4-12% in third-line plus WM patient populations.
These and other factors make the WM market highly attractive and present a real opportunity to benefit patients and the communities that we serve. Let's now advance to our alpha emitter program, actinium-based CLR 121225. It has demonstrated activity in multiple solid tumors, including pancreatic cancer. Here you can see that both high doses of CLR 121225 resulted in tumor volume reduction, with the highest dose achieving near complete resolution of the tumor. We also evaluated or tested the compound in prostate cancer and showed increased drug uptake into the tumor model, and both distribution and uptake were like other isotopes in other models that we have previously tested. In the prostate model presented here, we observed excellent activity as well as an interesting survival benefit. This slide reviews the safety and dose escalation phase one trial design for testing CLR 121225 in pancreatic cancer.
We expect to complete dosimetry data on patients and evaluate both single and multiple dose regimens, and we will be prepared to initiate the study in the first half of 2025. Let's now advance into the Auger emitter. Like our other radiotherapies, the Auger emitter, in this case, CLR 121125, has demonstrated strong tumor uptake, activity, and also extended survival, in this case, in triple-negative breast cancer animal models. From a safety perspective, there were no signs of end-organ toxicity and no hematologic toxicities. Like the actinium program, we will be prepared to initiate the study in the first half of 2025. From an abbreviated cap table perspective, common stock outstanding approximately 46 million shares. Unfortunately, the warrants listed here are currently out of the money. Our cash position as of September 30, 2024, was approximately $34 million, and our cash runway extends into the fourth quarter of 2025.
You know, in summary, iopofosine I 131 achieved excellent patient outcomes in the most relapsed refractory patient population ever studied in WM, including an overall response rate of approximately 84%, exceeding primary study endpoints with a major response rate of approximately 58% and a very impressive median duration of response of approximately 11.4 months, which is ongoing. We plan to gain clarity on the FDA's requirements for conditional approval under the accelerated approval pathway, and we have an end-of-phase two meeting with the agency in the first quarter of this year. We estimate the cost of our phase three WM study to be approximately $30 million-$35 million. It's important to note that the cost of full patient enrollment is approximately $20 million, and we project approximately 18 months to fully enroll the study from first patient in.
We remain engaged in advanced discussions, including licensing deals, which is our preferred non-dilutive funding approach. As cited earlier, we will be prepared to initiate phase one studies for both the alpha in pancreatic cancer and the Auger for triple-negative breast cancer in the first half of 2025. As cited, our current cash runway extends into the fourth quarter of 2025. With that, Jeff, I'll close on this slide. Obviously, on behalf of the company, I thank you and the audience for your interest in Cellectar and look forward to addressing any questions you and/or the audience may have.
Thank you very much, Jim, and really appreciate the clarity and thoughts as you guys look forward. Obviously, you know, it was a surprise to you and everyone else in terms of the feedback you got from the agency in December regarding the path to an approval.
It obviously makes sense for you to go back for a formal end-of-phase two to get formal feedback. As you said, that's scheduled for the first quarter. In terms of when you can share feedback from that meeting, is that following receipt of meeting minutes? How should we be thinking about expectations around timing there?
Yeah, that's a great question. You know, we submitted our proposal for the end-of-phase two meeting, which incorporates, you know, our thinking as well as incorporating feedback that we received from the FDA prior to that. I think we have a pretty good line of sight, you know, as to what the study would be required. Randomized control, approximately 50 patients in each arm.
As I cited, they'll allow us to submit a conditional approval based on the MRR data and then subsequently file for the full approval based on progression-free survival. We expect this meeting to go well. We believe we're aligned with the FDA on next steps, and we would clearly be able to provide feedback to the street no later than the close of the first quarter of this year.
Okay. In terms of what you were saying about the conditional approval on the MRR endpoint, is that the MRR endpoint from the second study, the comparative study?
Yes. You know, we would expect and anticipate, obviously, to use our phase two CLOVER- WaM data as well. You know, of this N of 50, we will also obviously monitor the major response rates achieved.
The comparator arm is, you know, we have thoughts on what that would look like. We believe the FDA is aligned on that, but we perceive limited, very limited clinical risk in terms of in this relapsed refractory patient population or third-line or greater. There's really no other agents out there that are remotely close to the level of activity that we've observed and has demonstrated in a broad range of WM, all challenging patient subpopulations here. So we're highly encouraged and see limited risk from a major response rate perspective. And quite frankly, the same is true from a progression-free survival perspective. But to your point, you know, we would enroll the 50, we would provide major response rate data immediately following that, and then over the next handful of years, secure the necessary PFS data, and then at that point in time, submit for the full approval.
Got it. That actually, my next question was going to be on that comparator arm. Given this patient population and the relapsed refractory nature, curious what that could, I guess, what do you think that could look like?
When you factor in that this third-line or greater is post-BTKI, yeah, and that BTKIs are, you know, predominantly used in first and second line for the most part, although you'll see rechallenged use in third line, fourth line, and beyond just based on, you know, the dearth or limited number of available treatments for patients. They'll be rechallenged with BTKIs. Rituximab is also an agent, obviously, that gets significant use, approximately 30-40% across all lines of therapy, and is also used in, you know, third or fourth line and beyond.
You know, rituximab may be a consideration in terms of, you know, the additional arm under evaluation as part of our, you know, accelerated approval study.
Okay. You know, you noted that if you guys, you know, as you look at strategic options here, you're thinking about licensing as your preferred approach for some non-dilutive funding and partnering. What does, when you're thinking about licensing, are you thinking about ex-US territories or sort of what's your preferred structure?
Sure. Great question. As I, you know, as I mentioned earlier, the data is outstanding. The market opportunity is significant. There's little to no real competition in the space overall in this third line or beyond setting. It's a very attractive market, both in the US, and you could look ex-US with the patient population being about the same as the US.
Let's just say 26,000 prevalence in the US, you know, top five, top seven EU, in and around the same range. A pretty substantial patient population. What's interesting is ex-US rituximab, which may be the comparator agent, you know, in our phase three study, if you will, controls about 60-70% of the ex-US market. Where in the US, it's about 30-40%. Clearly, there's an opportunity for, you know, trial use, adoption, and significant market share acquisition, you know, for iopofosine I 131 in this third-line or greater patient population. There's a lot of inbound interest, both for US rights as well as ex-US rights. We are sorting through, you know, we are in advanced stages of discussion.
We're sorting through, you know, what's in the best interest of our shareholders in terms of, you know, what deal structure, upfront payments, potential milestones, and other types of, you know, revenue-producing or value-creating opportunities for our shareholders. You know, we have, as you mentioned, we believe a licensing deal with a significant upfront, which allows us to cover off the cost associated with the WM study, would be ideal, a non-dilutive approach. You know, that's something that would be toward the top of the list. Obviously, we have to listen to all potential opportunities that may present itself.
Got it. Just last minute, minute and a half or so, with respect to the alpha and the Auger-based programs, in which you said you could be in a position to start sort of towards the, I think, end of the first half of this year or first half of the year, is the regulatory feedback licensing deal gating to start that work, or are there other sort of pieces to that puzzle?
Yeah, we'll be prepared. We believe that those are significant value-creating assets. You know, we didn't really have a lot of time to talk about it today, Jeff, but clearly, triple-negative breast cancer and pancreatic cancer are atypical tumor types that are targeted by radiotherapeutics in general.
That's really a function of the unique nature of our delivery vehicle, able to target the tumor and get enough drug uptake into the tumor, and then dropping the payload within the cytoplasm, you know, really creates a unique and different method of targeting that other companies, quite frankly, have not demonstrated the capacity to do, which is why they're playing around in, you know, smaller tumor types like GEP-NETs, et cetera. We see that as a real value. We will be in a position to launch into both of those in the very near term. To your point, we'll be thoughtful and strategic about, you know, the best way to optimize value for our shareholders.
Okay. I think that is all we have time for today, Jim.
Thank you very much for the update and wish you the best of luck and continued progress with your discussions with the agency. Operator, I think you can take us clear.
Terrific. Thank you, Jeff.