Earnings Call Transcript - CLRB Q1 2025

Operator, Operator

Ladies and gentlemen, thank you for standing by, and welcome. At this time all participants are in listen-only mode. Following the presentation, there will be a question-and-answer session. 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.

Anne Marie Fields, Managing Director

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's 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'll now turn the call over to Jim Caruso. Jim?

Jim Caruso, President and CEO

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 radio conjugate 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 US Food and Drug Administration regarding the accelerated approval regulatory path for iopofosine I 131 in WM. The results from the Phase 2 CLOVER WaM clinical trial of iopofosine I 131 as a treatment for relapsed refractory WM demonstrated the drug's unique efficacy and safety 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 2 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 advisor 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?

Chad Kolean, CFO

Thank you, Jim, and good morning, everyone. I'll address our financial results for the period ended March 31, 2025. We ended the quarter with cash and cash equivalents of $13.9 million as compared to $23.3 million as of December 31, 2024. We expect that cash on hand is adequate to fund budgeted operations into the fourth quarter of 2025. As Jim stated, we have engaged Oppenheimer & Company to serve as our exclusive financial advisor 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 three months ended March 31, 2025, were approximately $3.4 million, compared to approximately $7.1 million for the three months ended March 31, 2024. The overall decrease in research and development is largely driven by the reduction in patient follow-up activities for our CLOVER WaM Phase 2 clinical study in WM, and a reduction in personnel costs. General and administrative expenses for the three 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 three 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 three months ended March 31, 2024. Now, I'll turn the call with Jarrod for an operational update, including plans for our promising pipeline of radiopharmaceuticals.

Jarrod Longcor, Chief Operating Officer

Thank you, Chad, and good morning, everyone. I'll now review the regulatory and clinical status of iopofosine and two of our exciting earlier stage radio conjugates. 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 the major response rate for MRR and to obtain full approval based on progression-free survival or PFS. In a randomized controlled Phase 3 study evaluating the activity of iopofosine I 131 versus an investigator's choice comparator arm, which will provide the study investigators a choice between one of two 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 two NCCN guideline listed drugs for the comparator arm. As for our earlier stage pipeline, CLR 121225 is our lead alpha emitting radio conjugate 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 1 trial for CLR 121225 is designed to comprehensively evaluate compound 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 compound’s 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 PLE technology with alpha emitters, potentially showcasing this radioconjugate’s unique ability to safely treat large, bulky, solid tumors. Our Auger-emitting radioconjugate product candidate, CLR 121125, represents the peak of precision in targeted radiotherapy with its emissions traveling only a few nanometers. Without a 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 1b study in triple negative breast cancer. This trial will evaluate three distinct doses and dosing regimens, and the primary objective of identifying the optimal recommended Phase 2 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 are dependent on the company obtaining the necessary funds. With that, let me turn the call back to Jim for closing remarks. Jim?

Jim Caruso, President and CEO

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, Operator

Thank you. Your first question comes from Aydin Huseynov from Ladenburg. Please go ahead.

Aydin Huseynov, Analyst

Hi. Good morning, everyone. Thank you for taking the questions and appreciate the updates this morning regarding the application for conditional approval in Europe. So, I wanted to ask question regarding a hypothetical match of 131, iopofosine I 131 against rituximab in early lines. So, since you're going to run the Phase 3 trial anyways and going to take more than perhaps two years to read this out, would it make sense to run against rituximab in early lines of therapy just to get the bigger market? And what do you think about the hypothetical efficacy against rituximab in early lines? Thank you.

Jim Caruso, President and CEO

Yes, 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 US 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 believe we have very clear line of sight on what a pivotal study would look like, certainly in the US, based on the FDA's guidance. One of those comparator arms in the relapsed refractory setting will most likely be rituximab. Based on data in these later lines of therapy, rituximab certainly in the third line or greater is in this kind of 10% to 20% range based on the data that we have observed using data and claims in the US. In earlier lines of therapy, there are clinical studies available, and I'll have Jarrod speak to our thinking around that.

Jarrod Longcor, Chief Operating Officer

Yes. As Jim said, Aydin, we did look at going to an early line. The challenge with going to an early 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 major response rate that Jim just quoted for 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 significantly, making the cost of the study considerably more than what we're looking at right now. So, we've hesitated on that.

Aydin Huseynov, Analyst

Yes, makes sense. And regarding the Phase 3 trial design, the investigator choice out of 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 of trial? And are there any eligibility criteria where 131 would be the best suitable option versus other potential options that NCCN recommends?

Jim Caruso, President and CEO

Yes, it's a great question. And before I hand this off to Jarrod, as you think about this, there is 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 approach, keeping in mind this is a much older patient population that may already 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 is 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 is a high unmet medical need there based on the data claims utilizing information from third party community-based integrated oncology delivery networks you typically see in third line or greater, with a response rate kind of in the 10% to 20% range based on the data we are able to gather.

Jarrod Longcor, Chief Operating Officer

Yes. And Aydin, if I may follow up a little bit. 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'll make a lot more sense, but at the end of the day, no matter what drug you pick or pair of drugs you select as the investigator choice, you obviously have the FDA to approve those choices. The FDA wants to stick to what is the most common treatment paradigm that is ongoing right now. Obviously, physicians aren't likely to prescribe 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 already coming into 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 symptoms associated with the disease, like peripheral neuropathy and reduction in their fatigue. What's interesting is what does that mean? That means, as Jim mentioned, most of these other drugs, at least from what we're seeing, have very low major response rates and very short progression-free survival. As we said, rituximab or even some of the rituximab combinations range in that 10% to 30% maximum major response rate in under six months of progression-free survival. And so, we feel very confident that with our nearly 60% major response rate, which I think was 58.2% in the overall patient population, that we will easily be able to demonstrate with the major response rate the potential of iopofosine here. And when you look at the PFS, again, if you're looking at under six 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. 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 essentially looking at rituximab and rituximab combinations only as your alternative. On the other piece, when you think about eligibility, you asked the question about whether there’s a way to enhance eligibility to ensure better patient population for iopofosine? 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 it important? What we've seen both anecdotally and through claims data, is that patients who have had a BTKI tend to fail almost every subsequent treatment after that. However, as noted in our study and in our press release, we look at the post-BTKI population with iopofosine: you are looking at an approximately 59% major response rate in that specific patient population. So, again, we don't see a change, and we think that just selecting that patient population enhances a true separation and really identifies the need for iopofosine.

Jim Caruso, President and CEO

Yes, 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 typically what you see is rituximab or some rituximab combination being used in multiple lines of therapy. Hypothetically, if it was used first, you may see it in third and fourth lines, and it's in the 30% to 40% range for treatments used and in the second, third, and fourth lines of therapy. Each time it's used, it typically becomes less and less effective by line of therapy as you administer it to rechallenge patients. And as a result, it truly speaks to the high unmet medical need that exists here in this patient population.

Aydin Huseynov, Analyst

Yes, makes a lot of sense. One additional question I have regarding the conditional marketing application in Europe, so there's a 10-year report from EMA that says six out of 10 drugs that were submitted got approved conditionally at first, and some of them actually got full approval after that. How do you assess the commercial opportunity in Europe after you 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 to hear your thoughts on this.

Jim Caruso, President and CEO

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

Jarrod Longcor, Chief Operating Officer

Yes. So, Aydin, to your point, six out of 10 drugs seeking conditional approval in Europe receive 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, scientific advice meeting with the EMA previously. During that meeting, it was commented by them about the study design on - sort of separate from the US; they were much more focused on a single trial design approach for the drug. They were very impressed with the data they were looking at from the CLOVER WaM study. They did not have all of the data, so they are looking forward to receiving that. We expect, as you mentioned, that we will have the meeting with them to discuss that pathway and to ensure that we are eligible and that we should seek the approval on that study. We also think that because of the new Phase 3 study design that we've come up with in collaboration with the FDA, we'll be sharing that with the EMA as essentially the confirmatory study for full approval in Europe. We believe that study design will ensure that they are more amenable to the conditional approval, as it does address several of their traditionally desired aspects: 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 components will help them to be in a position to grant the conditional approval. Regarding the commercial side, yes, pricing is different in Europe, and yes, it is significantly lower than here in the US. However, a new regulation, new approach there requires a comparative controlled trial to get appropriate pricing justification. In a rare disease like this, you get some benefit, as this disease is predominantly one of older northern European descendants. It is more common or equally as common in Europe, even though the population size is lower. Importantly, rituximab will be one of the comparator arms, as it is much more highly utilized in Europe than it is in the US. As Jim mentioned earlier, rituximab generally in the US, irrespective of the line of therapy, is being given around 30% to 40% of the time, and it's almost double that in Europe. So, you are looking at one of the leading utilized drugs across Europe, and if you demonstrate that you can outperform it with a superiority study, you should be placed at the forefront of utilization in Europe. While price might be different, we predict an increase in total volume still while establishing that price differential.

Jim Caruso, President and CEO

And Jarrod, for clarity, regarding the conditional approval timeline, we will know from the EMA in the third quarter regarding whether a regulatory pathway for conditional approval would be acceptable.

Jarrod Longcor, Chief Operating Officer

Correct. Essentially, from there it would take about 12 months from the filing for the EMA.

Aydin Huseynov, Analyst

Right. Okay, thank you. Thanks so much for taking the questions and appreciate the discussion.

Operator, Operator

Thank you. 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.

Jim Caruso, President and CEO

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.

Operator, Operator

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