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

Hello to all. I'm Jim Caruso, the President and CEO of Cellectar Biosciences, and I thank you for accessing our virtual corporate presentation. Cellectar is traded on the NASDAQ Exchange under the symbol CLRB. Here, you can see the obligatory safe harbor statement. Please review reports filed with the SEC as needed. On Slide 3, you can review today's presentation topics. Based on the limited time to present, I'll review the upfront slides a little bit more thoroughly, and we'll then quickly touch on the remaining slides. Let's begin with a company overview. Cellectar is focused on the development of orphan and ultra-orphan adult and pediatric oncology indications. The foundation of this focus is our PLE cancer-targeting platform, which has demonstrated the capacity to preferentially deliver oncology payloads, the cancer cells versus healthy cells. It spares healthy tissue, it modifies the payload's therapeutic index. We plan to optimize this platform to further expand our development pipeline beyond CLR 131. Today, we'll focus on CLR 131, our lead product. It's a small molecule, targeted radio therapeutic with a differentiated product profile and demonstrated high response rates in later line for highly refractory B cell patients, including multiple myeloma and Waldenstrom's. Importantly, we have initiated a pivotal study involved in Waldenstrom's with WM for BTKi failed or suboptimal response patients. This is a population which has limited, effective treatment options and remains an area of both clear and high unmet need. In parallel, we continue to advance our Phase I pediatric study in malignant brain tumors neuroblastoma and soft tissue sarcomas. From a cash position perspective, our balance sheet supports the company through our projected NDA approval for Waldenstrom's. This slide talks to how we think about the strategic construction of CLR 131 and the CLR 131 franchise. Our objective is to establish multiple pathways to value creation, to mitigate risk by establishing as many cost-effective, higher probability, clinical development opportunities for CLR 131. One of these higher probability programs is WM. The Phase IIa cohort data, as you can see, is impressive, and this is in an extremely challenging patient population, which currently has no treatment answers. In terms of multiple myeloma, as you can also see, the data is strong in highly refractory patients. ORRs in these difficult-to-treat subsets, including high-risk patients, range from approximately 40% to 62%. Our adult hematology program clearly provides a registration pathway in WM. And in parallel, we continue to enrich our multiple myeloma refractory dataset to strengthen CLR-131's compendia profile and to enhance registration pathway options. Bottom half of the slide here, we have our pediatric program, which also likely represents another accelerated regulatory pathway. We are evaluating a variety of pediatric CNS tumors, high-grade gliomas, neuroblastomas. And as I mentioned earlier, multiple pediatric soft tissue sarcomas. CLR 131 has been granted 4 pediatric designations, which under certain circumstances, makes the company eligible for a pediatric voucher with market values in and around this approximately $100 million range. 131 also has 4 drug designations, which provide competitive immunity from an intellectual property perspective. Relative to the WM study, we have received FDA alignment on a clearly defined primary endpoint, study size and clinical significance performance expectations. We believe the primary study objective is certainly achievable and our WM Fast Track designation should help accelerate the registration pathway. The 131 product profile is particularly well suited for WM. One unique benefit provided is extended treatment-free survival and this is defined as the time from the last treatment of CLR 131 to initiation of a new therapy, progression or death. You can see this definition on the bottom of Slide 6 in the footnote. The average treatment-free survival for CLR 131 is 330 days. This is ongoing, and this is as of November 2020. For perspective, the only approved drug in WM, which is ibrutinib, must be taken every day and upon discontinuation, patients typically experience disease progression within 4 weeks. The shift in treatment dynamics in this space also favors CLR 131. Ibrutinib, the standard of care for second-line WM treatment is transitioning into first line as part of a combination with rituximab, which means it is vacating the second line in leaving salvage therapies as the remaining treatment options. Let's briefly review WM, the disease in the market. WM, as we know, is an ultrarare disease. You can see the annual incidence of approximately 6,500 patients globally. And as a result of a robust 8-year plus survival rate, the annual prevalence is 60,000 patients globally. WM, like multiple myeloma, is an incurable disease, and you can view the list of associated pathological conditions. Unfortunately, high unmet medical need remains, and this is for both patients and clinicians, which -- and we clearly require additional approved therapies and therapies that provide rapid and durable responses, extended treatment-free survival efficacy for all genotypes, the infrequent dosing and obviously, safety and tolerability. Said another way, a drug with the product profile of CLR 131. We view this space as 1 where 131 can provide clear patient benefits and is certainly representative of, as you can see, significant top line revenue and a very favorable NPV. A lot of key takeaways on this slide as well. You can see the 100% overall response rate, they're very deep, they're very durable responses, all major responses achieving a 70% or greater reduction in IgM protein and of course, the 83% major response rate. Now what makes the data even more impressive is the challenging nature of the patients. And you can do these in the chart on the left under the WM patient demographics. All patients were BTKi failed or suboptimal response patients, and 4 of the 6 were high-risk patients who typically have immediate time to progression of 1.3 years post their first line treatment. All 4 risk patients achieved major response, I should say, high-risk patients achieved a major response. One was a complete response. And this is the only complete response reported by a monotherapy in these later-line refractory patient populations. And these results were achieved, as I cited earlier, with a very simplified administration of 4 15- to 20-minute infusions of CLR 131. This slide also talks to the unique efficacy benefits of 131 in WM. As you can see, there is a rapid response typically within 3 weeks and a major response typically within 45 days. Additionally, there is extended or prolonged disease response. In fact, again, with just 2 to 4 20-minute infusions. The 131 average treatment-free survival is 330 days. It's ongoing, and it's as of November data, and that's November 2020. And to this point, no patients have required initiation of new therapy. In contrast, you can think about ibrutinib, which provides no treatment-free survival with disease progression typically occurring within 4 weeks after treatment continuation. And we'll close the WM discussion with a brief summary of our pivotal study design. It is a global design, is a global study. We had FDA alignment on key study parameters. It is a single-arm registration study with planned enrollment for 50 patients, again, who have failed or had a suboptimal response to BTKi. If you go to the middle of the slide, 2 boxes in on the left, you can see that this is up to 4 doses. It's 2 cycles. It's day 1, day 15. We provide a 40-day drug holiday, then day 57 and 71. We built in a futility assessment, primary endpoint is MRR. Secondary endpoints, treatment-free survival, duration of response and the total evaluation number is 50. We project patient enrollment to be between 15 to 18 months. And as you can see in the call out, a major response rate of 20% achieved statistical significance. Now please recall that the major response rate for CLR 131 to date is 83.3%. Okay. Now we're transitioning to multiple myeloma and as observed with WM, CLR-131's response rates here for the treatment of highly refractory multiple myeloma are also pretty good. If you direct your attention to the graphs, both on the left and right-hand side of the pages, what you'll see is a 47% response rate for CLR 131 as well -- and that's in a median of sixth line of treatment. And then on the right-hand side, a 62% response rate in high-risk multiple myeloma patients. And you can also see or observe the clear dose response between those patients with approximately 50 millicuries total body dose and those that receive greater than 60 millicuries total body dose of CLR 131. And that amount is typically achieved for most patients with our current dosing regimen. The bullet points below the graphs really address other efficacy data. I would say that the 1 that impresses me the most that I believe is the most impressive result is that 88% of all patients achieved a clinical benefit along with at least 2 months of progression-free survival. When we review CLR-131's triple class refractory and penta drug patient response rates, we see similar positive results. I mean, as of this time, there's limited competitive data in the space for these important subsets. However, on the left-hand graph, you can see selinexor, which was recently approved with a 25.6% response rate for quad/penta patients and belantamab which was approved for triple-class refractory with a 31% response rate. To date, an available data sets with at least 10 patients evaluated, CLR 131 has demonstrated the best response rates, and this is for both triple-class refractory at 40% and penta-drug at 54%. This slide really is a summary of CLR 131, the adverse events for all B-cell malignancy patients in 88 highly refractory patients, many being late line multiple myeloma. The drug has established a very well-tolerated safety profile. As you can see, the most frequent treatment-emergent adverse events or cytopenias, which is what you would expect based on the nature of the disease of i.e., the presence in the bone marrow, certainly for multiple myeloma and WM. Most importantly, there were no GI toxicities, cardiotoxicities, liver, renal toxicities, keratopathy, et cetera and these are the types of adverse events typically observed with cancer drugs used to treat this patient population. All right, now let's quickly shift gears to pediatrics. We'll find ourselves on Slide 17. And the graphic on the top of this page depicts the pediatric study design. As you can see, there's 2 cohorts by age group. One is less than 10 years of age and the second is greater than 10. The dosing levels highlighted in green display the current dose currently being explored. We do this study in 2 parts, Part A to determine the safety, tolerability and the early efficacy of CLR 131 and then part B, to confirm efficacy with the potential to act as a Phase Ib pivotal study. You can read the eligibility criteria. And as you can see, every indication represents a cancer for which there are no standard treatments with curative potential. On this slide, we share some initial data prompting the evaluation of 131 for the CNS tumors, the soft tissue sarcomas and metastases, et cetera. Far left, you can see the in-vitro pediatric glioma experiments demonstrating efficacy. In the middle, in-vivo testing, which showed clear tumor targeting in all cancer models tested. And then, of course, on the far right, you see 2 pictures, human data with both PET and SPECT scans, showing CLR 131, crossing the blood-brain barrier to broadly target brain tumors. To summarize this program, I believe it's fair to say that the company remains cautiously optimistic regarding the potential clinical utility of CLR 131 in these pediatric patient populations. Okay. Our cap sheet reports 80 million shares fully diluted, which includes 17.5 million warrants. Our cash position as of 12/31/20 is $57 million, which provides a cash runway supporting the company's strategic plan into the third quarter of 2023, which coincides with our expected WM NDA approval. And in summary, there's high unmet medical need in WM and multiple myeloma. We maintained an impressive product profile in both malignancies. This is how we're thinking about our near-term clinical development plan, high operational focus and urgency in all the areas, in particular, the execution of our WM study in MM. As you can see, enrich later line refractory data sets. This strengthens our compendia profile, helping from a reimbursement perspective when on the market in WM, maintain optionality for registrational approval pathways where the pediatric Phase I continue, this exciting evaluation in solid tumors and soft tissue. And finally, we expect to further lever our cancer targeting platform to selectively expand our oncology clinical development pipeline with the additional value creation as well as risk mitigation. So I thank you for listening to this abbreviated virtual presentation. Your interest is appreciated. The entire corporate deck can be found on our Cellectar website.