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

Ladies and gentlemen, thank you for standing by, and welcome. [Operator Instructions] Please be advised that today's conference may be recorded. I would now like to hand the conference call over to Anne Marie Fields, Managing Director at Precision AQ. Please go ahead.

Thank you. Thank you, operator. Good morning, and welcome to Cellectar Biosciences First Quarter 2025 Financial Results and Business Update Conference Call. Joining us today from Cellectar are Jim Caruso, President and CEO, who will provide an overview of the company's progress before turning the call over to Chad Kolean, CFO, for a financial review of the quarter and the year. Following this, Jarrod Longcor, Chief Operating Officer, will give an update on the company's progress and plans for its promising clinical development pipeline of radiopharmaceuticals. Cellectar issued a press release earlier this morning detailing the content of today's call. A copy can be found on the Investor page of Cellectar's corporate website. I want to remind callers that the information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and in the company's SEC filings. The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 13, 2025. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call and webcast. As a reminder, this conference call and webcast are being recorded and archived. We will begin the call with prepared remarks and then open the line for your questions. I will now turn the call over to Jim Caruso. Jim?

Thank you, Anne Marie, and thank you all for joining us this morning as we review the progress Cellectar has made throughout the first quarter of 2025. We entered 2025 with continued focus on our PDC platform, our radioconjugate pipeline and finalizing the requirements from the FDA and EMA, or European Medicines Agency, regarding iopofosine I 131 for the treatment of Waldenstrom's Macroglobulinemia, or WM. We rapidly scheduled and completed a productive meeting with the U.S. Food and Drug Administration regarding the accelerated approval, regulatory path for iopofosine I 131 in WM. The results from the Phase II CLOVER-WaM clinical trial of iopofosine I 131 as a treatment for relapsed/refractory WM demonstrated the drug's unique efficacy and safety product profile, which we believe represents a significant opportunity as a promising therapeutic candidate in a relapsed/refractory market where no approved drugs currently exist. In parallel, we are seeking guidance from the EMA on conditional approval for iopofosine I 131 as a treatment for WM based on the CLOVER-WaM Phase II study. We believe the compelling results from the study support the conditional marketing authorization strategy and will make available this critically needed new medicine to WM patients in Europe more rapidly. In addition to our iopofosine program in WM, we continue to progress our solid tumor-focused radioisotope programs, which include our alpha emitter for pancreatic cancer and the Auger emitter for evaluation in triple-negative breast cancer, both of which highlight the novel utility of our delivery platform. Jarrod will speak further to these programs later in the call. As we explore strategic alternatives for the company, we have engaged Oppenheimer as an exclusive financial adviser to assist us. These alternatives may include, but are not limited to, mergers, acquisitions, partnerships, joint ventures, licensing arrangements or other non-dilutive transactions. Now, let me turn the call over to Chad for a review of our financial results. Chad?

Thank you, Jim, and good morning, everyone. I will address our financial results for the period ended March 31, 2025. We ended the quarter with cash and cash equivalents of $13.9 million. This compared to $23.3 million as of December 31, 2024. We expect the cash on hand is adequate to fund budgeted operations into the fourth quarter of 2025. As Jim stated, we have engaged Oppenheimer & Co. to serve as our exclusive financial adviser as we seek to explore strategic alternatives available to Cellectar that will allow us to maximize shareholder value moving forward. Regarding our results from operations, research and development expenses for the 3 months ended March 31, 2025, were approximately $3.4 million compared to approximately $7.1 million for the 3 months ended March 31, 2024. The overall decrease in research and development was largely driven by the reduction in patient follow-up activities for our CLOVER-WaM Phase II clinical study in WM and a reduction in personnel costs. General and administrative expenses for the 3 months ended March 31, 2025, were $3.0 million compared to $4.9 million for the same period in 2024. The decrease in G&A was primarily driven by a reduction in pre-commercialization and personnel costs. Net loss for the 3 months ended March 31, 2025, was $6.6 million, or $0.14 per share, compared to $26.6 million, or $0.91 per share, during the 3 months ended March 31, 2024. Now, I will turn the call over to Jarrod for an operational update, including plans for our promising pipeline of radiopharmaceuticals.

Thank you, Chad, and good morning, everyone. I will now review the regulatory and clinical status of iopofosine and 2 of our exciting earlier-stage radioconjugates. The first is our alpha-emitting actinium-based compound CLR 121225. And the second is CLR 121125, our lead Auger-emitting radiotherapeutic. The path to achieve conditional approval of iopofosine I 131 is based on major response rate, or MRR, and to obtain full approval based on progression-free survival, or PFS. In a randomized controlled Phase III study evaluating the activity of iopofosine I 131 versus an investigator's choice comparator arm, which will provide the study investigators a choice between 1 of 2 NCCN approved treatment options. The primary endpoint for accelerated conditional approval is superiority based upon the MRR, progression-free survival from the same patients will be used to receive full approval. This trial is expected to enroll approximately 100 patients per arm. Since there is no data available for efficacy of any comparator in this patient population, Cellectar is working with the FDA to utilize claims data demonstrating the current utilization patterns by physicians to select the 2 NCCN guideline listed drugs for the comparator arm. As our earlier-stage pipeline -- as for our earlier stage pipeline, CLR 121225 is our lead alpha-emitting radioconjugate product candidate. To date, it has shown excellent biodistribution and uptake into solid tumors with demonstrated activity across multiple solid tumor animal models, including challenging to treat pancreatic and refractory colorectal cancers. CLR 121225 has been observed to be well tolerated in these experiments. The Phase I trial for CLR 121225 is designed to comprehensively evaluate the compound's biodistribution, safety and tolerability in patients with pancreatic adenocarcinoma. The study will commence with the dosimetry phase aimed at determining the absorbed dose in both normal and tumor tissues. This initial assessment will provide valuable insights into the compounds biodistribution and potential therapeutic window, laying the foundation for subsequent phases of the trial and future development. Following dosimetry, the study will progress to a dose escalation phase, systematically evaluating increasing doses of CLR 121225 to establish the maximum tolerated dose. This approach offers an opportunity to demonstrate proof of concept for our innovative combination of phospholipid ether, or POE, technology with alpha emitters, potentially showcasing this radioconjugates unique ability to safely treat large bulky solid tumors. Our Auger-emitting radioconjugates product candidate, CLR 121125, represents the peak of precision in targeted radiotherapy with its emissions traveling only a few nanometers. With our delivery mechanism providing the necessary targeting to the tumor, entry into the cell and transport to the nucleus as validated through preclinical studies, we have seen CLR 121125 demonstrate significant tumor uptake and activity with enhanced tolerability across multiple challenging animal models, including triple-negative breast cancer and metastatic breast cancer. We are preparing CLR 121125 for a Phase Ib study in triple-negative breast cancer. This trial will evaluate 3 distinct doses and dosing regimens and the primary objective of identifying the optimal recommended Phase II dose. The study will include an imaging component to further elucidate the biodistribution of CLR 121125, providing crucial insights into its targeting and potential efficacy. It is important to note that the initiation and timing of these trials is dependent on the company obtaining the necessary funding. With that, let me turn the call back to Jim for closing remarks. Jim?

Thank you, Chad and Jarrod. Before opening the call to questions, I would like to thank our dedicated and talented Cellectar team who continue to work with tremendous determination to move these important programs and our company forward. We remain committed to the WM community and sincerely appreciate the abundance of support and continued encouragement to advance iopofosine I 131 to market. Operator, we are ready to open the call for questions.

[Operator Instructions] Your first question comes from Aydin Huseynov from Ladenburg.

I appreciate the updates this morning regarding the application for conditional approval in Europe. So I want to ask a question regarding a hypothetical match of 131, iopofosine 131 against rituximab in earlier lines. So since you're going to run the Phase III trial anyways and going to take more than perhaps 2 years to read this out, would it make sense to run against rituximab in earlier lines of therapy just to get the bigger market? And what do you think about the hypothetical efficacy against rituximab in earlier lines?

Thank you, Aydin. I appreciate your participation today and certainly the question. As you would imagine, we've evaluated a number of different study designs and opportunities for iopofosine, not only in the relapsed/refractory setting, which would be our initial to market play. But, obviously, in earlier lines of therapy, there could be a real benefit for patients that either do not tolerate BTKis. BTKis are not effective. And in your particular case, rituximab or rituximab combinations as well. I will say that for the U.S. FDA, the team has done a really nice job based on our November discussion to very rapidly secure an additional meeting with the FDA that occurred in March. And as part of that, we have, we believe, very clear line of sight on what a pivotal study would look like, certainly in the U.S. with -- based on the FDA's guidance. And one of those comparator arms in the relapsed/refractory setting will most likely be rituximab. Based on data there in these later lines of therapy, rituximab, certainly in third line or greater is in this kind of 10% to 20% range based on the data that we can -- we have observed using data and claims in the U.S. In earlier lines of therapy, there are clinical studies available, and I'll have Jarrod speak to our thinking around that.

Yes. As Jim said, Aydin, we did look at going to an early line. The challenge with going to an earlier line is the size of the study becomes much larger. As you might imagine, looking at differentials in major response rate or progression-free survival in earlier lines with going against rituximab, where there is a relatively higher rate of responses as opposed to the 20% -- approximate 20% that Jim just quoted for major response rate in later lines, it jumps up to 60%, 70% or 80% depending on exactly what line you're looking at. That then alters your patient population sizing, so the number of patients required to execute that study goes up pretty quickly and pretty significantly, making the cost of the study considerably more than what we're looking at right now. So we've hesitated on that.

Yes. Makes sense. Makes sense. And regarding the Phase III trial design, the investigator choice out of the all possible sort of NCCN recommended choices, what is the weakest essentially comparator -- hypothetical comparator arm you would choose or sort of compel physicians to choose in order to improve the chances of 131 in this Phase III trial? And are there any eligibility criteria where 131 would be the best suitable option versus other potential options that NCCN recommends?

Yes. That's a great question. And before I hand this off to Jarrod, as you think about this, there's little to no data available relative to most of those treatments that are identified in NCCN guidelines. They're there because they're treating other hematologic malignancies. And oftentimes in WM, in second line, you can already be in a salvage therapy mode in some form of a combination, chemotherapeutic soup, et cetera. Keeping in mind, this is a much older patient population that may already be -- have been treated with multiple lines of therapy prior from an adverse event perspective, it could be a challenge for these patients. And so, there's clearly, to your point, a dearth of information relative to the performance of these drugs, certainly in second line and beyond and clearly in a relapsed/refractory setting. So there's high unmet medical need there based on the data claims and utilizing information from third-party community-based integrated oncology delivery networks, you typically see in third line or greater this kind of 10% to 15% response rate based on the data that we're able to garner.

Yes. And Aydin, if I may follow up a little bit. So the interesting piece, and I'll put it back into the hypothetical. The interesting piece of your question is the hypothetical piece is, can you identify essentially the weakest drug to go against to ensure success. And I'll come to why we don't really care in a moment. I think it will make a lot more sense. But at the end of the day, what -- no matter what drug you pick or pair of drugs you pick, whatever you pick as the investigator choice, you obviously have the FDA to approve those choices. And the FDA wants to stick to what is the most common treatment paradigm that is ongoing right now. Obviously, physicians aren't likely to be prescribing drugs that they know are failing rapidly. That said, one of the things that I think leads to this is, when you get into the second line and the third line, like Jim said, and you're in this sort of already coming into a salvage therapy, frequently, what you actually see is, physicians are just satisfied with patients not having a major response, but achieving stable disease or suppression of the sequelae associated with the disease, so peripheral neuropathy, maybe reduction in their fatigue, what have. And that's what they're really trying to do. They're not actually trying to alter the disease course. They're just trying to ameliorate symptoms and signs of the disease essentially. What's interesting is, what does that mean? That means, as Jim said, most of these other drugs, at least from what we're seeing, have a very -- have very low major response rates and very short progression-free survival. So as we said, rituximab or even some of the rituximab combinations range in and around this 10% to 30% maximum major response rate and sub-6 months of progression-free survival. And so, we feel very confident that with our near 60% major response rate, which I think was at the 58.2% in the overall patient population that we will easily be able to demonstrate with major response rate, the potential of iopofosine here. And then when you look at the PFS, again, if you're looking at sub-6 months and you look at what our ongoing PFS was in the study, the last time we reported, which was north of 11 months. Again, we think we have a very strong compelling position as it relates to any comparator that we will select. And we do think with the discussions with the agency, the selection here is really about a fixed course therapy that compares with our fixed course therapy. And so, that means you're basically rituximab and rituximab combinations only as your alternative. I think on the other piece, when you think about eligibility, you asked the question about, is there a way to enhance the eligibility to ensure, again, better patient population for iopofosine. And we think we've done that. Fundamentally, this post-BTKi patient population that we're pursuing, keeping in mind that now with ibrutinib approved in the first line, you're seeing a lot more utilization of BTKi in combination with rituximab in that first line setting. What does that mean? And why is that important? What we've seen through, both anecdotally and then also through the claims data that Jim referred to, what you see is that, patients who've had a BTKi tend to fail almost every subsequent treatment after that. However, as you will note from our study and in our press release, I think, this morning, when we look at the post-BTKi population with iopofosine, you're looking at a 15.9% or essentially a 60% or 59% -- sorry, a 59% major response rate in that patient population. So, again, we don't see a change. And we think that just select that patient population enriches a true separation and really identifies the need for iopofosine.

The only other thing -- that was very comprehensive, Jarrod. Thank you. The only other thought that I would provide to Aydin is, this concept of rechallenging, where what you typically see is rituximab or some rituximab combination being used in multiple lines of therapy. Hypothetically, if it was used in first, you may see it in third and fourth. And it's in this kind of, I think, 30% to 40% range for treatments used in the second, third, fourth, fifth lines of therapy. And that's really -- and each time it's used, typically, it becomes less and less effective by line of therapy as you use it to rechallenge patients. And as a result of that, it just really talks to the high unmet medical need that exist here in this patient population.

Yes, makes a lot of sense. One additional question I have regarding the conditional marketing application in Europe. So this is -- I think there's a 10-year report from EMA that says 6 out of 10 drugs that were submitted, got approved conditional first and some of them actually got full approval after that. But how do you assess the commercial opportunity in Europe after you will hear back from EMA, I think you mentioned third quarter 2026? So how do you assess the commercial opportunity given the pricing environment there, given the market size environment there? Just curious your thoughts on -- to hear your thoughts on this.

Sure. I think first, perhaps an update in terms of where we sit with the EU in terms of potential for conditional approval there and how we're thinking about the regulatory pathway. And we also aid and view that market as a very rich one as well.

Yes. So, Aydin, to your point, 6 out of 10 drugs that seek conditional approval in Europe received it, which is a nice percentage. 60% of the time, you're going to get it. We think that our possibilities there may be enhanced because we have the PRIME designation and the data set that we have is so strong. We did have a meeting -- a scientific advice meeting with the EMA previously. During that meeting, it was commented by them about the study design sort of separate from the U.S., they were much more focused on a single trial design approach for the drug, and they were very impressed with the data they were looking at, at that point from the CLOVER-WaM study. They did not have all of the data. So they are looking forward to receiving that. So we expect, as you sort of said, that we will have the meeting with them to discuss the pathway and to basically ensure that we are eligible and that we should seek the approval on that study. We also think because -- where we sit right now is with the new Phase III study design that we come with the FDA, we'll be sharing that with EMA as essentially the confirmatory study for full approval in Europe. And we think that, that study, as it is designed, will ensure that they are more amenable to the conditional approval because, obviously, it does then address several of their traditionally desired things, a comparator-controlled trial, a comparator that is widely used throughout Europe, one that you can then use from a pricing perspective as well. So all of these things will help them to be in a position to grant a conditional approval. And then I think as you asked the question on the commercial side, yes, pricing is different in Europe. And yes, it is significantly lower than here in the U.S. However, one of the new regulations and new approaches there is, you have to do a comparator-controlled trial so that you can get appropriate pricing and justify. In a rare disease like this, you get some benefit. Keeping in mind that this disease is predominantly a disease of older Northern European descendants. It is more common or equally as common in Europe, even though the population size is a bit lower, it is relatively common. And I would say that the other key component there is, we do believe that rituximab will be one of the comparator arms as that is much more highly utilized in Europe than it is here in the U.S. I think as Jim quoted a little bit ago, rituximab generally in the U.S., irrespective line of therapy is being given at 30-ish, 40-ish percent of the time. And Europe is almost double that. So now you're taking out one of the leading utilized drugs across Europe. And if you're demonstrating that you can beat it with a superiority study, you should be instantly placed in front of it as utilization across Europe. While the pricing might be different, you actually will likely see an increase in total volume offsetting that price differential.

And Jarrod, for clarity relative to the conditional approval time line, we will know from our friends at the EMA in the third quarter of this year as to whether or not a conditional regulatory pathway with conditional approval would be acceptable.

Correct. And then it would -- essentially from there, it's approximately -- the filing would go in and then it's 12 months from the filing generally for EMA.

[Operator Instructions] There are no further questions at this time. I will now turn the call over to the Cellectar team for closing remarks. Please go ahead.

Well, operator, thank you for facilitating the call, and also thank you to everyone participating today. This does conclude our call, and you may disconnect. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.