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spk05: Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics fourth quarter and full year 2021 results call. At this time, all participants have been placed in a listen-only mode, and the floor will be open for your questions following the presentation. If you would like to ask a question at that time, please press the star and 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing the pound key. We ask that you please pick up your handset to allow for optimal sound quality. If you should require operator assistance, please press star and zero. Before we begin, we want to advise you that over the course of the call and the question and answer session, forward-looking statements will be made regarding events, trends, business prospects, and financial performance, which may affect Plus Therapeutics' future operating results and financial position. All such statements are subject to risk and uncertainties, including the risks and uncertainties described under the risk factors section included in PLUS Therapeutics annual report on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time. PLUS Therapeutics advises you to review these risk factors in considering such statements. Plus Therapeutics assumes no responsibility to update or revise any forward-looking statements to reflect events, trends, or circumstances after the date which they are made. It is now my pleasure to turn the floor over to Dr. Mark Hendrick, Plus Therapeutics President and Chief Executive Officer. Sir, you may begin.
spk06: Thank you very much, David. Good afternoon, everyone. Thank you once again for taking the time to join us today. as we provide an overview of recent business highlights and discuss our 2021 fourth quarter and full year financial results. Joining me on the call today is Andrew Sims, our Chief Financial Officer. In addition, joining Andrew and I on the call today for the first time is Dr. Norman LaFrance, our new Chief Medical Officer who joined PLUS at the end of 2021. We are very excited to have Dr. LaFrance on board. as he brings many years of highly relevant clinical, regulatory, and commercial expertise in radiotherapeutics and oncology to the PLUS Therapeutics Management Team. Welcome aboard, Norman. I'll begin the call by reviewing our recent corporate and clinical progress before turning the call to Norman, who will provide commentary on our clinical expectations for the remainder of 2022. Following Norman, Andrew will review our financials. 2021 and early 2022 has been marked by significant progress as we work toward our mission to become a global leader in developing precision targeted radiotherapeutics for cancer. In 2021, we continue to advance our lead investigational targeted radiotherapeutic drug, rinium nanoliposome, or RNL, in our U.S. respect GBM trial. As a reminder, the trial is a dual phase 1-2 multicenter sequential cohort open label volume and dose escalation study. The trial is currently funded to a significant degree by the US NCI or National Cancer Institute. Our initial indication for RNL is recurrent glioblastoma, which affects approximately 13,000 patients annually in the US and about the same number of patients in Europe. It's the most common and lethal form of brain cancer and the treatment of this devastating disease remains a significant unmet challenge. Recall also that RNL is proprietary liposomal encapsulated radionuclide that is delivered local regionally via targeted three-dimensional convection enhanced delivery. It is administered directly to the tumor bypassing the blood-brain barrier. The active agent is the rhenium-186 isotope, which is a dual-energy emitter releasing both cancer-killing beta particles, which are high-energy electrons, as well as gamma particles, which are useful for imaging, localization, and dosimetry. We provided positive interim data from the Phase I to respect GBM trial in patients with recurrent GBM at the Society for Neuro-Oncology Annual Meeting and Education Day last November 2021, and then we updated the data set at the BioCEO Conference in New York this month. Both of those presentations can be found now on our website. According to the most recently presented interim clinical data set, 186-RNL delivered via convection-enhanced delivery is feasible up to at least 31.2 milliliters of radiation and 12.3 milliliters of volume. No delivery failures were observed. An average absorbed dose of 276 gray of radiation was delivered to the tumors over the course of the trial thus far. Average absorbed radiation to the tumor increased and correlated with dose escalation. In fact, we've shown that we can successfully deliver up to 740 gray or 20 times the amount of radiation dose one can deliver with traditional external beam radiation in the recurrent setting. As an aside about radiation therapy, published studies indicate that EBRT external beam radiation provides the best incremental improvement in survival of all therapies currently available for glioblastoma, which is about five months in improved survival. And it remains, to this day, an essential component of multimodal therapy for GBM and many other cancers. So there's no question radiation works in GBM. Furthermore, in their SPECT trial, key drug delivery parameters, such as flow rate, catheter number, et cetera, were increased during the course of the trial. And that increase correlated with better drug delivery outcomes and improved overall survival. 186 RNL is also thus far well tolerated without those limiting toxicities. It has an acceptable safety profile. There were no adverse events thus far in the trial with the outcome of death or discontinuations due to adverse events. And placement of up to four catheters in a patient has thus far been safe. As to efficacy, And it's interestingly similar, the efficacy results thus far, to our preclinical results. An absorbed radiation dose of greater than 100 gray in patients correlates with increased overall survival. Although the phase one trial has neither design nor power for efficacy, we are observing promising signals of both biological effect and increased overall survival. In the latter cohorts of the trial, specifically cohorts 5 through 8, receiving greater drug volumes and radiation doses and, frankly, more optimized delivery parameters, 9 of the 12 patients, or 82% of those patients in cohorts 5 through 8, received a therapeutic dose of 100 gray or better. And we believe it's entirely possible to achieve a 90% or greater coverage of 100 gray or better going forward. Thus far, in 23 total subjects treated in respect with recurrent GBM, the median, excuse me, the mean and median overall survival for the entire group is currently at 38 weeks and 50 weeks, respectively, with seven patients remaining alive. It's interesting to note that in this current trial, which was initiated by the academic physicians back in 2015, it's very unusual to have such long-term overall survival data, which we do in this trial. Therefore, when we take the logical step and take advantage of what's been done by the academics that started the trial and assess a subset of patients who received At least a minimum therapeutic dose of radiation, and as I mentioned, that's greater than 100 gray of radiation. They were treated in the initial five cohorts, which ranged from a start date of March 2015 through to July 2020, which is the longest survival data we have in the trial thus far. Immediate and mean overall survival stands at 82 and 88 weeks, respectively, with two patients still alive. That compares very favorably with the 32 weeks overall survival published in a recent meta-analysis covering nearly 700 patients with recurrent GBM treated with Bevucizumab monotherapy in the recurrent setting. And that reference can be found on our website in our corporate presentations. Furthermore, our team continues to make excellent progress in our drug scale-up and manufacturing activities. Specifically, during 2021 and thus far in 2022, the company entered into multiple collaboration agreements to support its process development in analytical chemistry activities, as well as to strengthen our supply chain in compliance with GMP practices for planned late-stage clinical trials. The company remains on track to deliver GMP-186-RNL by mid-2022. Before I turn the call over to Norman, and he will update you on the path forward for 186-RNL, I'd like to highlight the agreement that we announced right at the beginning of January and consummated at the end of December that substantially expands our oncology portfolio. As we stated before, We fundamentally believe in the future of cancer therapy is going to be in the precise targeting of tumors with the most potent cancer killing agents while minimizing damage to normal tissues. To that end, we entered into an agreement with the University of Texas for a worldwide exclusive license to develop and commercialize novel interventional therapeutics for cancer. The licensed patents include composition and matter patents for biodegradable alginate microspheres, which we call BAM, containing nanoliposomes loaded with imaging and or therapeutic payloads. Therapeutic payloads may include radiotherapeutics, chemotherapeutics, or thermotherapeutics. The BAM technology is delivered into the vascular system via standard interventional vascular technology that are placed precisely in the vessels feeding blood to the tumors. Once injected, BAM both blocks all blood flow to the tumors and simultaneously delivers very high doses of cytotoxic compounds for an extended period of time. Many days later, following full radiation decay, BAM resorbs, are physiologically metabolized and then excreted from the body. With this technology, we can target almost any solid organ tumor in the body using standard interventional radiologic methods to leverage the breadth of the human vascular system and deliver a resorbable biomaterial embolic technology coupled with a highly potent radioisotope. The company will initially focus on developing 188 RNL-BAM as a next-generation radial embolization therapy for liver cancer, in which BAM blocks the hepatic artery segments that supply blood to the malignant tumor, while also providing 188-RNL radiotherapy and directly irradiating the tumor. Next steps in this program are technology transfer from academia and completing key IAD-enabling CMC and preclinical work. And with that, I'll turn the call over to Norman.
spk04: Thank you, Mark. I'm delighted to have joined PLUS Therapeutics and to be joining you here today for this call. PLUS Therapeutics' focus on radiotherapeutics positions is firmly for long-term growth. I'm excited to lead the development expansion of its promising pipeline. Following on Mark's comments on the RESPECT GBM trial in patients with recurrent pleoblastoma, In 2022, we expect to materially advance the investigational drug, 186-RNL, recurring GBM, and other indications. First, we plan to meet with FDA mid-year to propose taking our 8.8 milliliter and 22.3 milliliter as our recommended Phase II dose. We believe this dose is appropriate for 50 to 75% of patients with recurrent glioblastoma based on tumor size and morphology. As publicly announced earlier this week, we are currently exploring potential Phase II pivotal trial designs that may incorporate the use of real-world data, also known as synthetic control arm, to improve trial costs and facilitate enrollment. In addition, as we have yet to reach dose-limiting toxicity in the respect GBM trial, and we anticipate to be able to treat larger tumors with 186-RNL, our goal is to keep the phase one dose escalation trial open and report data both on the previously treated patients and on future potential cohorts. We may also consider exploring improved drug dosing parameters. Recently, we have filed a new clinical protocol with the FDA to allow us to treat patients with recurrent glioblastoma previously treated once with RNL that may benefit from an additional RNL dose. GBM is notoriously difficult to eradicate from the brain, and we believe a subset of patients may benefit in terms of greater safety and efficacy following two or more administrations of 186-RNL. Furthermore, in 2022, the company will review other GBM disease subtypes to potentially expand the use of 186-RNL. Regarding additional indications, 186-RNL is also being developed for leptomeningeal metastases and pediatric brain cancer. Leptomeningeal metastases is an increasingly common secondary cancer affecting over 100,000 patients per year in the U.S., and patients can present with a broad range of signs and symptoms due to simultaneous involvement in multiple areas of the craniospinal axis. The RESPECT-LM trial is a multi-center, sequential cohort, open label, single dose, dose escalation phase one study. It will evaluate the maximum tolerated dose, maximum feasible dose, safety, and efficacy of a single administration of 186-RNL via intraventricular catheter for the leptomeningeal metastases treatment following standard surgical radiation or chemotherapy treatment in these patients. The primary endpoint of the study is the incidence and severity of adverse events and serious adverse events and dose-limiting toxicities, if any. Secondary endpoints include overall response rate, duration of response, progression-free survival, and overall survival. In addition, we have received FDA Fast-Track designation for 186-RNL for the treatment of leptomeningeal metastases. Following IND clearance from the FDA last year, in fourth quarter of last year, the company began screening and consenting patients in respect on phase one trial and patients with leptomeningeal metastases. Regarding pediatric brain cancer, based on our pre-IND meeting feedback received in 2021, the company expects to submit an IND for Phase 1 trial with 186 R&L this year for the treatment of pediatric brain cancer and to investigate the use of R&L on kids with brain cancer. At this point, I'll stop and turn the call over to Andrew for a brief review of the full-year financial results.
spk02: Andrew? Thank you, Norman, and good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the full year ended December 31, 2021. As of December 31, 2021, cash and cash equivalents were $18.4 million compared to $8.3 million as of December 31, 2020. Cash used in operations for the 12 months ended December 31, 2021, was $10.3 million compared to $8.4 million in 2020, with the main changes between 2020 and 2021 as follows. In 2021 through early 2022, the company strengthened its balance sheet by raising approximately $28.5 million of capital. As of January 31, 2022, the company's cash balance was approximately $23 million. at our 2021 run rate that represents over two years of operating cash. Research and development expenses were $5.3 million for the full year 2021 as compared to $2.7 million in 2020. This increase is primarily due to continued CMC development of RNL to GMP standard. This development remains on track to be completed by summer of this year, 2022. Please also note that the company continues to leverage the five-year NCI grant awarded in 2020 to fund P clinical activities. G&A expense was $6.9 million for 2021 as compared to $6.4 million in 2020. This increase is primarily due to expenses for new patent filings, professional fees related to the BAM transaction, together with other legal expenses and employee recruiting fees. interest expense decreased by approximately $400,000 in 2021 from $1.3 million in 2020 to $907,000 in 2021. This decreased cost reflects the $5 million of principal paid off in 2020 to the further $300,000 in 2021. These payments reduced the remaining principal due to Oxford below $4 million at December 31, 2021. Net loss for 2021 was $13.4 million as compared to a net loss of 8.2 million in 2020. Excluding the book gains on the warrants of 2.3 million that were reported in the first quarter of 2020, the change in net loss reflects the incremental R&D and G&A spend, as mentioned earlier. And now I'll turn it back to you, Mark.
spk06: Thanks, gentlemen. Before we move on to Q&A, let me just summarize some key milestones anticipated for 2022. I think we've touched on most of these already. First of all, with respect to the 186 respect clinical trial in recurrent GBM. Regarding the 186 R and L drug availability, the CMC activities for R and L remain on track to complete this plan and to have GMP phase three drug supply available by mid 2022. We currently plan a CMC-focused FDA meeting in the second quarter of 2022 to clarify and resolve any open CMC issues that may exist as of that time. We also plan a clinically-focused FDA meeting mid-year to propose a Phase II clinical plan and trial design using the 8.8 mL and 22.3 mL Curie recommended Phase II dose, as Dr. LaFrance noted. We also plan to explore the use of real-world data, which is ongoing, in the clinical and regulatory plan to accelerate Phase II enrollment and potentially reduce trial costs. In 2022, we plan to continue to report Phase I data and provide enrollment updates in an ongoing manner in the current Phase I trial. Regarding the RESPECT-186-RNL-LM trial, Our goal is to complete enrollment in at least the initial cohort of three patients this year. Regarding the pediatric brain cancer trial, we plan to submit an IND in 2022 and initiate this trial soon thereafter. Regarding our recently acquired rights to the 188 RNL-BAM radial embolization therapy technology, we plan to complete the technology transfer and other key CMC and FDA IND enabling studies for this asset in 2022. So, at this point, I'll move to Q&A, and David, I'll turn it over to you.
spk05: Thank you. The floor is now open for questions. At this time, if you have a question or comment, please press the star and 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing the pound key. Again, we do ask that while you pose your question, you please pick up your handset to provide optimal sound quality. While live questions queue, we have previously received a question by email from Justin Walsh with B. Reilly. This will be asked by Andrew Singh.
spk02: Thanks, David. The first question is, from Justin, can you remind us how much of a barrier to potential adoption would you expect physician training to be? And are surgeons well equipped to make use of the asset?
spk06: Yeah, so there is a barrier, but it's 100% soluble. We've got two years of experience under our belt working with this novel technology. And we think about it in a couple of ways. First of all, there's the neurosurgical aspect. And the second part is the case planning aspect, which is really about getting radiation on the tumor. So in terms of the neurosurgical aspect, so essentially getting the neurosurgically getting the catheters in the tumor leverages existing tried and true brain biopsy technology. It's commonplace in hospitals that have neurosurgical services. The technology itself allows very precise delivery within about a millimeter or so. And actually, there are many neuro-navigation systems that allow that sort of geospatial delivery technology to be placed. We prefer the Brain Labs technology. That's the one that we've used. And frankly, I've gone through the full training. And although I'm a neurosurgeon, I'm a cranial facial surgeon, I feel after a day of training, I'd be 100% capable of doing that. So part of that I don't believe is a barrier. What initially I was worried about maybe two years ago when we acquired the asset is How about case planning? How do we ensure that we can reliably cover the tumor with the appropriate amount of radiation? And I think the story is adequately told in the respect clinical trial data. If you look back at cohorts one through four, Justin, we were only able to cover the tumor with adequate radiation, greater than 100 gray, adequate radiation, about 40% of the time. But if you look at the latter cohorts, I think I referred to this in the script, like cohorts five through seven, where we've got more volume, we've gotten higher radiation doses, especially more catheters, higher flow rate, et cetera. We're able to cover the tumors with therapeutic radiation about 80-plus percent of the time in those cohorts, and I'm increasingly comfortable we're going to be able to get that to 90 percent or greater. I think that's achievable. In terms of implementation of the case planning, currently and through the clinical trials, we'll do that centrally. We think it's really important from a quality control perspective we do that, and we do that corporately in consultation with the treating neurosurgeon. And that may be the model going forward commercially. We just don't know, but basically we're very confident now that those barriers are well on the way to be solved or have been solved.
spk02: Justin's second question is, can you provide some additional color on the regulatory precedent for using a synthetic control arm? What are some of the potential advantages and disadvantages of that trial design approach?
spk06: Norman, will you mind answering that?
spk04: Yeah, no, I'll be happy to. Thanks. It's a great question by Justin. I'll jump right to the bottom line that this real-world data and synthetic control arm data already has established precedent successfully for interaction with the FDA. Folks on the call may be aware of CELCION's Ovation 1 study in ovarian cancer with their Gen 1 asset and also the Medicina and glioblastoma. This approach has been used successfully with recurrent glioblastoma with both CBER and CDER drug review groups within FDA. And I'll spend one second if you allow me to go over in general why an SCA real-world approach will be valuable and particularly focusing on our application. So the first thing we will do is take advantage of this existing data, and there's significant data with the group, World Expert Group we're dealing with on this, for understanding of our early phase single-arm trial data that Mark mentioned. This, you know, and Mark mentioned that this doesn't have, as phase ones are designed not to have, an efficacy control arm. we'll be able to rectify that with a synthetic control arm, respecting the enrollment criteria that we had in that phase one. So with this phase one, we believe that we'll be generating additional data beyond the very impressive overall survival data that's been reported at the snow annual meeting last year, demonstrating you know, a strong overall survival benefit with the synthetic control arm validation. This all leads to the capability to analyze and justify advancement to Phase II with FDA. As you heard from both Mark and I, we plan on approaching FDA by mid-year for this Phase II pivotal advancement. Availability of a control arm means that the randomization for control and active treatment will not be one-to-one. That will encourage these unfortunate patients to enroll in studies. It's always a personal decision, but patients understandably would like active treatment. This, in turn, accelerates development, faster to market and commercialization, and saves development costs. So, Mark, I don't know if you have anything else on this, but I think that's a lot of the reasons why this approach, I think, is valuable, and we have great expectations for helping move development even faster than anticipated.
spk06: No, that's great. Thank you. Maybe just a follow-up question. So, David, I'll turn it back to you for further questions.
spk05: Of course, we'll take our first live phone question from Joanne Lee with Maxim Group. Please go ahead. Your line is open.
spk00: Hi, this is Joanne. Thanks for taking the question and congratulations on the progress this quarter, especially on the positive data presented at the SNL. Given that, you know, greater overall survival rate was seen in the higher dose cohorts, could you briefly, I know you touched on this, but could you repeat the dosing strategy for the next trial? Will it be at or above 100 gray and at what volume? And if you could shed some color on what extension of overall survival will be considered meaningful in the recurrent GBM setting? particularly as the survival goal posts keep moving?
spk06: Yeah, I'll take that. Thank you, Joanne. So the first part of the question, so the dosing plan, we sort of went back up. So we've bifurcated the trial, continue the phase one, and continue the current dose escalation scheme. And that's, I can walk you through that to the degree you're interested in what that is. But right now we're We're in dosing cohort eight right now, which is about 12 cc's of volume, and I think 31 milliliters of radiation. Moving into the phase two, kind of the other half of the bifurcation, the plan is to take the prior dose, at which we have six patients, which is sufficient to move into a phase two recommended dose, which is at 8.8 cc, and I think about 21 millicuries. So we've got no BLTs. We've got a very acceptable safety profile. The dosimetry data from the clinical trial shows that we can cover not only the tumor, but also a rim of brain tissue that appears normal by imaging, but we know is very likely to harbor microscopic disease, and we need to treat that as well to get long-term survival benefit. So we think that that 8.8, 21.3 millicurie dose will treat about 50 to perhaps up to 75% of sort of the typical recurrent GBM. So we think that's a totally appropriate dose to take into Phase II for these small to medium-sized tumors based on the data we have thus far. And it will continue to dose escalate in the effort to potentially treat tumors that are larger or have more complex morphologies that are difficult to get with the current volume and dosage. So as to the target in terms of the amount of radiation, so we've empirically derived the fact that 100 gray or greater seems to – be therapeutic in only 23 patients at this point. But it looks like there's a pretty clear biologic signal as we dose escalated. And it's interesting, as I mentioned on the script, that the preclinical data showed exactly the same thing, that you start seeing a statistically significant improvement in survival when you deliver over 100 gray to the tumor. And the interesting thing is we're now delivering 740 gray And we're able to do that with seemingly a pretty good safety profile. So that's the plan going forward. If you have any further follow-up questions, happy to try to address those.
spk00: Great. And just regarding the trial size and recurrent GBM, can you do a registration study with a single arm, say 100 patients, and get approval? Because, you know, we've seen drugs gain approval and other indications in a severe unmet need setting through that pathway. And just as a follow-up, you mentioned the use of resynthetic control in the next trial. Could you give us some details for that around that decision? And as it's an approach we've observed that VA being more open to in recent years, particularly in GBMs?
spk06: Yeah, so a little too early to tell what the trial size looks like, trial budget and so forth. But we've said previously, and I think we still believe this, we have no reason to believe differently, that approximately 100 patients is about the size of that trial. As we've mentioned previously, we have orphan designation for that indication. And we have fast-track status for the program with FDA. We believe, based on the data and what we know about the breakthrough designation pathway, that that may be an alternative here as well. So that's kind of what we're thinking right now. The synthetic control arm, as Norman mentioned, might be able to offset the total number of patients we randomize. And kind of to your follow-up question on the synthetic control arm, Norman alluded to this, that Medicina has received approval from the FDA to go into a phase three design using a real-world synthetic control arm to have a control group that is an amalgam of both patients that have been randomized to to the control group, but to supplement that with real-world data that are identically matched to the enrollment and the exclusion criteria, inclusion criteria to the trial. So we, there's an increasingly well-worn path to the FDA where they've accepted it, particularly in diseases like GBM. And I think we're increasingly more confident that we think that that's going to be useful here as well.
spk00: Great, that was very helpful. Thanks again.
spk06: Thank you.
spk05: We'll take our next question from Sean Lee with HC Wainwright. Please go ahead. Your line is open.
spk03: Good afternoon, guys, and thanks for taking my questions. So I just have a couple on your clinical development plans. So the first question is, you guys mentioned that you wanted to try redosing a patient. Now, is that within the same phase one study or do you expect a cohort for that?
spk06: Hey, Sean, it's Mark. It would be a separate protocol. It would be outside the phase one design in the sense that the NCI covers it and so forth. And so we don't plan to back it into the NCI framework. So it would be a separate protocol, but under the IND. And that's been submitted. and we haven't heard back from the FDA about our ability to move forward with that.
spk03: I see. In terms of that, what kind of patients are you particularly looking to redose, and what kind of doses would you be starting them on?
spk06: So, yeah, it's a great question. So, you know, it's almost impossible to eradicate GBM. And that's kind of why we've seen in a dose escalation trial that even though we've had a number of long-term survivors, one survivor that's 160 weeks out, almost three years, that we still can eradicate it. And they're kind of two patients. They're the patients where Maybe the morphology of the tumor is not ideal, difficult to cover the tumor, the anatomic location is challenging, and so forth. And we know right off the bat that there might be a little bit of area that's going to be at risk for recurrence based on the dosimetry data. So that's one type of patient where we know right off the bat that there may be a problem. We want to be hypervigilant on a recurrence so we could retreat those patients. The other type of patient is where we've got good coverage. patient does well, we're seeing a safety and potentially efficacy signal in that particular patient. But if the disease comes back as it typically does, we want to be ready to retreat them. So the plan is to take the request from the FDA to take the cohort six dose. That's the one we're taking in the recommended phase two where we have six patients treated that would be the maximum dose. We could potentially go down based on the size of the image recurrent tumor, but that would be the planned maximum dose going into that retreatment protocol.
spk03: I see. Thanks for that. In terms of testing these retreatments and also testing higher doses in the phase 1 study, if you do see some improved outcomes from these treatments, would you delay your phase 2 to incorporate these, or are you happy with the, I think, 8.8 mil that you guys are set along?
spk06: Yeah, we're happy with that. I think it's tumor size dependent. I mean, I think we mentioned this before, and you and I have talked about this, that the concept is you want to cover the tumor in a rim of what appears to be normal brain because you know that 90% of patients that 90% of the recurrences will occur in a two centimeter rim around the primary tumor. So we want to cover that. That's very much a tumor size issue. So at higher volumes and higher doses, we can treat bigger tumors. So that's the rationale in the dose escalation arm is to continue to escalate and be able to treat those higher tumors. But in the retreatment context, these patients get imaged every day. 60 days, so we think that we can be vigilant and aggressive and jumping on anything that we think might be recurrent disease and be able to knock that down. And the volume requirement would be, and the radiation dose requirement would be perhaps a bit less than what we would treat in the first recurrence.
spk03: I see. Thanks for the clarification. My last question is on the BAM product. So from the sounds of it, liver cancer may be one of the first indications that you guys go after with this product. And while it's a fairly rare cancer here in the U.S., it's a very common one in Asia, especially China and Japan, if I remember correctly. So would something like an international collaboration to test it in those countries be something that you guys would consider?
spk06: Yeah, I completely agree and that is consistent with our thinking as well. In fact, we've already had partnering interest on that even as early as it is. But I think the cautionary note is that we're still early in the tech transfer and then the other IND-enabling studies. So, I think we still have a year of work before we're kind of ready to, I think, discuss publicly the clinical trial plan. But I don't see a scenario where we wouldn't include a trial plan that would not include sites in Asia Pacific region.
spk03: I see. Thanks. That's all I have.
spk06: Thanks, Sean.
spk05: As a reminder, if you'd like to ask a question today, please press the star and one keys on your telephone keypad. We'll take our next question from Ed Wu with Ascendant Capital. Please go ahead. Your line is open.
spk01: Congratulations on the progress so far. Also, touching back on the BAM product, what was your rationale in terms of what you guys really like about this? And should we see this in terms of how does it, I guess, balance out with, you know, our now 186 in terms of priorities for the company?
spk06: Hey, Ed. No, thanks for the question. We're very excited about the BAM opportunity. The delivery technology is very mature. uh, interventional, uh, radiographic technologies used all the, all the time, as opposed to the, the, um, RNL 186, which although we're very confident it's going to work, it is, it is sort of new novel technology, but the, the angiographic interventional technology is very mature, very effective for solid organ targeting. So I think that's, that's sort of the key thing that excited us about this. Um, I guess the other thing that is, worth noting is this technology is very much aligned with our current 186 RNL technology. It's really an extension or a bolt-on. So it really does beef up our IP portfolio. And we already have the expertise internally from a CMC perspective, from a drug development and clinical perspective. So this is right up our alley. as an add-on technology. As to the liver cancer issue, you're absolutely right. It's a rare disease. There are two products that have been used for approximately 25 years commercially, pretty broadly in the liver cancer area, but they have some significant shortcomings. And so I think the market is really right for a second generation a technology that carries a number of potential points of differentiation improvement over those. So I think the next steps for us, though, before we get too far down the road is, as I mentioned previously, get the tech transfer complete, and then do some proof of concept CMC and Exvivo work on the scalability and consistency of the drug product before we get into clinic, which we think is going to be late this year, early next year target, hopefully. In terms of balancing with the 186 technology, It does a couple things for us. It gives us a microscale drug as opposed to a nanoscale drug, a completely different mechanism of targeting that we have for the 186. And it allows us to gain a related experience in the 188 isotope, which is different than 186. 188 is actually made not in a nuclear reactor. but it's much easier to make in a generator. It has different isotopic physical properties that provide different features and benefits than the 186 technology. So it's a very logical expansion of our current 186 technology.
spk01: Great. Thank you for the explanation, and I wish you guys good luck. Thank you.
spk06: Thanks, Ed.
spk05: And once again, as a reminder, if you'd like to ask a question, please press the star and one keys on your telephone keypad. And we can pause for a moment to allow further questions to queue. And there are no further questions on the line at this time. I'll turn the floor back to Dr. Hendrick for any additional or closing remarks.
spk06: Thank you, David. Let me just close by thanking everybody for joining us on the call today, and thank you to you that have listened in to the recorded version. And on behalf of the board, I'd like to thank our employees specifically, our team members. Welcome, Dr. LaFrance, the physicians we work with, and, of course, we're always grateful for the patients that trust us and enter into our clinical trials. So thanks again for your participation, and have a good evening. Bye-bye.
spk05: This does conclude today's program. Thank you for your participation and you may now disconnect.
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