Cellectar Biosciences, Inc. (CLRB) Earnings Call Transcript & Summary

Good morning, everyone. This is Susan Chor, an associate with Kevin DeGeeter. I have here CEO of Cellectar, James Caruso. He will begin his presentation shortly. And if you have any questions, please e-mail them to [email protected] or submit them to the chat. Without further ado, please begin, James.

Terrific. Thank you, Susan, and good morning to all. I thank you for your interest in Cellectar Biosciences and participation in this presentation. Cellectar is traded on the NASDAQ Exchange under the ticket symbol CLRB. Here, you can see the obligatory safe harbor statement. I direct you to our reports filed with the SEC. On this slide, essentially, you can view the presentation topics. Today, I will provide a general overview with a focus on our lead asset, CLR 131, for adult heme and pediatric applications. Okay, for company background -- it's not working here. Excuse us for one moment, technical issue. I'm going to have to advance these. Terrific. All right. So we've satisfied our technical interest issues at this time. For background, as you may or may not know, Cellectar is focused on the development of orphan and ultra-orphan adult and pediatric oncology indications, indications that we believe the company can effectively compete and win in both the clinic as well our market. The foundation of this focus is our PLE cancer targeting platform. Our lead product is CLR 131. CLR 131 is a small molecule targeted radiotherapeutic, which combines the PLE with the radioisotope iodine-131. CLR 131 possesses a differentiated product profile, novel mechanism of action with demonstrated efficacy in B-cell malignancies such as multiple myeloma, Waldenstrom's as well as DLBCL. We have initiated a pivotal study recently in January of this year in Waldenstrom's, an indication with very limited treatment options and remains an area of high unmet need. In parallel, we are advancing multiple myeloma as part of our Phase IIb study and pediatrics as part of our Phase I study in malignant brain tumors, neuroblastoma as well as sarcomas. This slide really talks to how we think about the strategic construction of CLR 131 or the CLR 131 franchise. Our objective is to establish multiple pathways to value creation, mitigating risk and establishing what we believe are highly cost-effective, higher probability clinical development opportunities for CLR 131. One of these programs, top left-hand side in the box you can see, is Waldenstrom's. The Phase II data is impressive, and this is in an extremely challenging patient population that we'll talk through over the course of this presentation. This population has very limited treatment answers. The ongoing pivotal study is international and is targeting approximately 50 sites. Top right-hand box, you can see in terms of multiple myeloma. The data is also very strong, and this is in a highly refractory patient population. Response rates in very difficult-to-treat subsets, including high rate -- risk patients range essentially from 40% to 60%. So for our adult hematology program, we have a clear registration pathway in WM, and in parallel, we continue to enrich our multiple myeloma refractory dataset to strengthen 131's compendia profile to enhance registration pathways and maintain marketing opportunities as well. Bottom half of the slide, you can see, this talks to our pediatric program, which we believe represents potential for yet another accelerated regulatory pathway. We are evaluating a variety of pediatric CNS tumors, high-grade gliomas, neuroblastomas and multiple pediatric soft tissue sarcomas. 131 has been granted 4 rare pediatric drug designations, which under certain circumstances makes the company eligible for pediatric voucher. These voucher price points have ranged. Currently, they're sitting at around $100 million. CLR 131 also has 4 orphan drug designations, which provides, among other benefits, significant intellectual property protection. Additionally, when you think about the franchise strategic construction, certainly relative to WM pivotal study, we have received FDA alignment on clearly defined primary end points, including the study size of 50, clinical performance expectations in the tune of approximately 20% statistical hit or hurdle relative to major response rate. We believe this primary study objective is certainly achievable, especially based on the clinical data that we've secured to date. Our fast track designation for WM will further accelerate the registration pathway. The 131 product profile is particularly well suited for WM, and one unique benefit is the extended treatment-free remission/treatment-free survival. And you can see this defined in the footnotes as the time from the last treatment of CLR 131 to initiation of a new therapy progression or death. This TFS or TFR for 131 is currently reported at approximately 330 days and ongoing. Now for perspective, the only approved drug in Waldenstrom's is ibrutinib. Ibrutinib must be taken every day, and upon discontinuation, patients typically experience disease progression in 2 to 4 weeks. There's also the benefit of a shifting Waldenstrom's treatment dynamics relative to the space. These also favor CLR 131. Ibrutinib, currently the standard of care for second-line Waldenstrom's treatment, is transitioning into a first line as part of a combination with rituximab, which means it's vacating the second line leaving only salvage therapies as remaining treatment options. As mentioned earlier, we continue to focus and enrich our multiple myeloma refractory datasets through evaluation of additional patient subsets, highly refractory patient subsets to maintain optionality for compendia listing and/or future registration and/or authorization studies. The phospholipid ether, as we refer to it as our PLE, is our proprietary platform that preferentially delivers oncology warheads to tumor cells. I think it's fair to say that the delivery vehicle can be represented as a fatty acid mimetic. Now cancer or tumor cells utilize lipids as an energy source for cell membrane production, and cancer cells, as you may know, use much greater quantities than normal cells. Now as mentioned earlier, the PLE does provide targeted delivery of drug payload. This is the primary tumor stem cells as well as metastases. This exploits this inherent tumor cell need for lipids or fatty acids. Now unlike ADCs, which may deliver very low digit percentages, 1%, 2%, 3% of its warhead or payload to the tumor, the PLE consistently delivers 20% to 40% of infused drug, getting more payload to the cancer cells. And then, of course, for clarity, as briefly touched upon on the introductory slide, 131 is a phospholipid radio conjugate. And this is a combination or a conjugation of the PLE, our delivery vehicle, with the radioisotope iodine-131 creating our targeted radiotherapeutic CLR 131. This slide reviews some interesting science as it relates to B-cell lineage. It is important to note that Waldenstrom's has disease characteristics similar to multiple myeloma as well as DLBCL. And one could view Waldenstrom's as this bridge between NHL and multiple myeloma. And as you can see by this schematic, Waldenstrom's maintains a unique position in the spectrum of B-cell malignancies. It really represents the point on what the bridge between NHL subtypes and multiple myeloma. You can see TKRs, as you may know, or cholest in lipid rafts, one TKR that is highly overexpressed across these cells as FGFR3. Now in multiple myeloma, FGFR3 is overexpressed in approximately 50% of all patients. In Waldenstrom's, this overexpression is 100%. As you think back to the overall response rate shared earlier, multiple myeloma is sitting in that kind of 40% to 60% range, very much aligned with this 50% overexpression, and our overall response rate for Waldenstrom's is 100%, also aligned with this overexpression. So the net is the biology is aligned with the CLR 131 clinical data that we've observed to date. Here, we'll advance into WM and briefly discuss the disease and the market. It is a rare disease, annual incidence approximately 6,500 globally. And one of the benefits of this approximate 8-year survival post diagnosis is an annual prevalence of approximately 60,000 globally. WM, like multiple myeloma, is an incurable disease, and you can see the laundry list of associated pathological conditions. Unfortunately, WM, as cited earlier, maintains high unmet medical need, both for patients as well as treatment tools for clinicians. Clinicians really require or approve therapies here that can provide some real benefits, as you can see listed there, rapid, durable responses; extended treatment-free survival or remission; efficacy across a broad range of genotypes. And as a result of the product profile for CLR 131, we really believe this is a great fit in this space, and it will provide clear patient benefits and as you can also see on the far right, potential for significant top line revenue with very meaningful NPVs. And as you would expect and assume with other cancers, risk profile and genotypes really impacts disease progression here. WM, there's clear extensive need. And in particular, relative to patient responses with a variety of stratifications, in this case, you can view gene mutations and risk levels as having a significant and meaningful impact on patient outcomes. If you direct your attention to the box top right-hand side of the slide, you can see the difference between mid-88 wild type, and we're talking time to median progression of approximately 1.3 years versus the 5.1 for mutated. And then directly below, and you can see again yet another box, risk group, median time to progression, and you can view the difference between high risk of 1.9 years and low risk of 9.3 years. This slide has a number of key efficacy takeaways. Clearly, the 100% overall response rate, the very deep and durable responses, all major responses achieving with 70% or greater reduction in IgM. And just for some -- as way of background, 50% reduction in IgM equates to a major response in this patient population. And as you can view the graph on the far right-hand side, you can see all 5 patients were considerably north of the red line, which represents 50% reduction in IgM, and you can see all patients at a minimum of a 70% response or greater. Now I think what makes this data even more impressive is the challenging nature of these patients. So on the last slide, we saw some of the challenges associated with high-risk patients and mid-88 patients. Here, you can see all of these patients were failed or suboptimal BTKi patients. Four were high-risk patients. And as mentioned, these high-risk patients have a median time to progression of approximately 1.3 years. With 131, all 4 high-risk patients achieved a major response and 1 achieved a complete response, which we believe is the only monotherapy CR reported in a refractory population. This slide also talks to or addresses the unique efficacy benefits of CLR 131 in Waldenstrom's. As you can see, there's a very rapid response, typically within 3 weeks. And a major response is typically observed at approximately 45 days or so. Additionally, there is that extended or prolonged disease response, which really makes CLR 131 very unique in this patient population. In fact, this treatment-free survival or treatment-free remission occurred with just 2 to 4 15- to 20-minute infusions. As cited earlier in the presentation, the average treatment-free survival is approximately 330 days to date, and importantly, no patients have required initiation of new therapy. I think it's important to note, in contrast, ibrutinib, which is the only approved drug for WM, provides no treatment-free survival with disease progression typically occurring within 2 to 4 weeks after patients discontinue treatment. So let's close the WM discussion with a brief summary of our global pivotal study design. Importantly, as cited earlier, we secured FDA alignment on key study parameters, such as endpoint, patient size and response rate. It is a single-arm registration study. Single arm, which means we have access via the open-label portion of this, a line of sight on how these patients are doing and enrollment is for 50 patients. These are patients who had failed or had a suboptimal response to BTKi. Enrollment is projected to be approximately 15 to 18 months. And as the call-out suggests, a major response rate of 20% achieved statistical significance. But please recall that the major response rate to date in the refractory setting for CLR 131 is north of 83%. And so we're excited about this study, and we look forward to sharing top line data. So now let's shift into multiple myeloma. And on this side, you can see similar to Waldenstrom's, this multiple myeloma patient population studied with CLR 131 to date is also extremely difficult to treat, very challenging, and mirrors real world late-line patients. The median age is approximately 70 years. As you can see, 90% of patients, 90% of patients were refractory to prior therapy. 63% were quad, penta patients. And as you can see, bottom, the very bottom of this chart, we see triple class refractory, 96% of patients dosed at this greater than 60 millicurie total body dose of CLR 131 were triple class. Response rates here, also very good. And you can see particularly these highly refractory multiple myeloma patient populations, and if you direct your attention to the graphs, you can see on the top left-hand side, for those patients with greater than 60 millicurie total body dose, a response rate of 47% was achieved. And then on the top right-hand side, you can see the 2 bar graphs there as well and the 62% response rate in high-risk patients. You can also see a clear dose response, once patients achieve a total body dose of greater than 60 millicuries of CLR 131. And this is typically achieved for most patients using our new 2-cycle dosing regimen or the dosing -- said another way, the dosing regimen that we introduced in the Phase II portion -- [ phased away ] portion of our study. The bullet points below these graphs really address other efficacy data. You could read those. I would say that the one that's most impressive to me is the 88%, 88% of all patients achieved a clinical benefit along with at least or minimum 2 months of progression-free survival. Now when we view 131's triple-class refractory and penta-drug patient response rates, you see similar positive results. As of this time, there is limited competitive data for these important subsets. There was a recent approval, but drugs of real interest include selinexor, which was approved with its approximate 26% response rate for quad penta patients; and belantamab, approved in triple class also with this approximate 31% response rate. And really to summarize this slide, available datasets with at least 10 patients evaluated, this is across the literature, CLR 131 has demonstrated the best response rates for both triple-class refractory at this approximate 40% range and penta drug at approximately 54%. And so we really look forward to leveraging the Phase IIb portion of our study to further enrich this dataset, enrolling triple and quad class patients as well as highly refractory patients and other unit subsets. This slide summarizes really adverse events for all of the B-cell malignancies for CLR 131. And this about approximately 88 highly refractory patients, many of them being very late-line multiple myeloma. You can see the drug has established a very well-tolerated safety profile. You can see the most frequent treatment-emergent adverse events or cytopenias, which is really what you would expect to see based on the nature of this disease, i.e., the presence of disease in the bone marrow. And most importantly, there are -- it's a very clean AE profile. There are no GI toxicities, cardio toxicities, liver, renal toxicities, keratopathy, et cetera. These are the types of adverse events that you would typically observe with other prescribed drugs in this patient population. And so the net is or in summary, 131 is really a highly effective drug for multiple myeloma with a very predictable and very manageable adverse event profile. So at this point, let's shift gears for a pediatric update. As a company, we remain very excited about the potential of CLR 131 in this patient population. This graphic here on Slide 21, at the top of this slide, really depicts the study design. There are 2 cohorts by age group. One is less than 10 years of age, and the second is greater than 10 years of age. The dosing levels highlighted in green display the current dose of where CLR 131 is currently being explored. You can see in the greater than 10 and see the 75 millicurie per meter square range; and in under 10, more than 30 millicurie per liter square. And so we really view this study in 2 parts or, a, is really to determine the safety, tolerability, early efficacy of CLR 131, which you would typically expect in a Phase I; and then the part B, to really confirm efficacy and the opportunity or potential to expand into a Phase Ib pivotal study. You can see or read the eligibility criteria. These indications really represent cancers for which there are no standard treatment options, certainly none with curative potential. On this slide, we share some initial data, which -- with some of the early prompting for the evaluation of CLR 131 of CNS tumors, soft tissue sarcomas and metastases. You can see the in vitro pediatric glioma experiments really demonstrating efficacy; in vivo testing, which showed clear tumor targeting in all cancer models tested; and of course, the in-human data that you could observe on the far right-hand side of the slide, and this is both PET and SPECT scans showing very importantly CLR 131 crossing the blood-brain barrier and broadly targeting brain tumors. And so the net is we're 2 slides in, but to summarize this program, I believe it's fair to say that the company remains cautiously optimistic regarding the potential upside or, said another way, potential clinical utility of CLR 131 in these patient populations. So here's our tax structure. As you can see, the sheet reports approximately 83 million shares fully diluted. This includes 9.5 million preferred shares, which really possess no unique rights versus common shares and approximately 16.5 million in warrants. Our cash position as of year-end 2020 is $57 million, which is reflected on the slide. And this provides us with a cash runway into the third quarter of 2023, which is really supportive of the company's strategic plan and coincides with our expected NDA approval in WM in the third quarter -- second, third quarter of 2023. So in summary, as we think about this presentation, 131 maintains and has established an impressive product profile in WM as well as multiple myeloma. There clearly remains high unmet medical need in the market for both of these indications, certainly in later-line multiple myeloma, especially with combination therapies of doublets and triplets being used now in lines 1 through 3. And the fact that 4 out of 10 patients elect no further treatment after 3 lines of therapy with 1 approved product in WM and typically salvage therapies being used throughout further courses of treatment beyond first line, there's a clear market opportunity and clinical opportunity there as well. And so we're executing our near-term clinical plan. We're highly focused, high operational focus and urgency in all areas, in particular, the execution of our WM pivotal study. In terms of multiple myeloma, as we stated, we will continue to enrich later-line and refractory datasets to strengthen our compendia profile. And this is predominantly the third-party reimbursement and pending approval, third-party reimbursement and certainly maintain optionality for additional or marketing approval pathways. As for the pediatric Phase I, we'll continue the evaluation in solid tumors and the site of soft tissue sarcomas. And really finally, to further explore, over the course of these last handful of years, we continue to work in the background with preclinical work to further understand and explore the utility of our cancer targeting platform. And we will continue to do this in order to selectively expand our oncology clinical development pipeline for additional value creation as well as risk mitigation. And so I thank you for participation in this presentation, for taking the time to certainly listen. Your interest in Cellectar is appreciated. And now I will turn the floor back to Susan.

Thank you so much for that presentation, James. Unfortunately, we don't have time for questions, but you can always send them in, again, to [email protected]. That's all. Have a good day.

Thank you, Susan. Bye-Bye.