Plus Therapeutics Inc (PSTV) 2021 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics Fourth Quarter and Full Year 2021 Results Call. (Operator Instructions)

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 risks 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. Marc Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin.

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. 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 continued to advance our lead investigational targeted radiotherapeutic drug, Rhenium NanoLiposome or RNL, in our U.S. ReSPECT-GBM trial. As a reminder, the trial is a dual Phase I/II multicenter, sequential cohort, open-label, volume and dose escalation study. The trial is currently funded to a significant degree by the U.S. NCI, or National Cancer Institute. Our initial indication for RNL is recurrent glioblastoma, which affects approximately 13,000 patients annually in the U.S. 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 debilitating disease remains a significant unmet challenge.

Recall also that RNL is a proprietary liposomal encapsulated radionuclide that is delivered loco-regional 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/II 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 BIO CEO Conference in New York this month, and both of those presentations can be found now on our website.

According to the most recently presented interim clinical data set, 186RNL delivered via convection-enhanced delivery is feasible up to at least 31.2 millicurie radiation and 12.3 milliliters of volume. No delivery failures were observed, and the 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 20x 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 5 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 the ReSPECT 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. 186RNL is also, thus far, well tolerated without dose-limiting toxicities and 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 4 catheters in a patient has thus far been safe.

As to efficacy, and it's interestingly similar to 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. While the Phase I trial is neither designed or powered 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 7 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 for cohorts 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 5 cohorts, which ranged from the start date of March 2015 through to July 2020, which is the longest survival data we have in the trial thus far. The median and mean overall survival stands at 82 and 88 weeks, respectively, with 2 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 bevacizumab 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 and 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 186RNL by mid-2022.

Before I turn the call over to Norman, and he will update you on the path forward for 186RNL, 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 that 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 of 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 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, the 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 188RNL-BAM as a next-generation radioembolization therapy for liver cancer in which BAM blocks the hepatic artery segments that supply blood to the malignant tumor while also providing 188RNL radiotherapy and directly erasing the tumor. Next steps in this program are technology transfer from academia and completing key IND-enabling CMC and preclinical work.

And with that, I'll turn the call over to Norman.

Thank you, Marc. I'm delighted to have joined Plus Therapeutics and to be joining you here today on this call. Plus Therapeutics' focus on radiotherapeutics position is firmly for long-term growth, and I'm excited to lead the development expansion of its promising pipeline.

Following on Marc's comments on the ReSPECT-GBM trial in patients with recurrent glioblastoma, in 2022, we expect to materially advance the investigational drug 186RNL in recurrent GBM and other indications. First, we plan to meet with FDA midyear, propose taking our 8.8-milliliter and 22.3 millicurie 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 cost 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 186RNL, our goal is to keep the Phase I 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 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 2 or more administration of 186RNL. Furthermore, in 2022, the company will review other GBM disease subtypes to potentially expand the use of 186RNL.

Regarding additional indications, 186RNL is also being developed for leptomeningeal metastases in 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 of multiple areas of the craniospinal axis.

The ReSPECT-LM trial is a multicenter, sequential cohort, open-label, single-dose, dose escalation Phase I study that will evaluate the maximum tolerated dose, maximum feasible dose, safety and efficacy of the single administration of 186RNL 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 186RNL 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 to ReSPECT-LM Phase I trial in 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 I trial with 186RNL this year for the treatment of pediatric brain cancer and to investigate the use of RNL 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. 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 2 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 5-year NCI grant awarded in 2020 for funding 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 with a 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, Marc.

Thanks, gentlemen. Before we move on to Q&A, let me just summarize some key milestones anticipated for 2022, and 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 RNL drug availability, the CMC activities for RNL remain on track to complete as planned and to have GMP Phase III 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 midyear to propose a Phase II clinical plan and trial design using the 8.8 mL and 22.3 millicurie recommended Phase II dose, as Dr. LaFrance noted. We also plan to explore the use of real-world data, which is ongoing, and 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 186RNL LM trial, our goal is to complete enrollment in the -- at least the initial cohort of 3 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 188RNL-BAM radioembolization 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.

(Operator Instructions) While live questions queue, we have previously received a question by email from Justin Walsh with B. Riley. This will be asked by Andrew Sims.

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?

Yes. So there is a barrier, but it's 100% soluble, and we've got 2 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 1 millimeter or so. And actually, there are many neuronavigation systems that allow that sort of geospatial delivery technology that to be placed. We prefer the Brainlab's 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 preclinical surgeon, I feel after a day of training, I'd be 100% capable of doing that. So (inaudible) apart of that, I don't believe it's a barrier.

What initially I was worried about maybe 2 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 kind of -- I think the story is adequately told in the ReSPECT clinical trial data. If you look back at cohorts 1 through 4, 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 5 through 7 where we've got more volume, we've gotten higher radiation doses, 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% or greater. I think that's achievable.

So in terms of implementation and 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.

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 disadvantage of that trial design approach?

Norman, will you mind answering that?

Yes. No, I'll be happy to. Thanks. It's a very (inaudible) question by Justin. I'll jump right to the bottom line that this real-world data and this synthetic control arm data already has established precedent successfully for interaction with the FDA. Folks on the call may be aware of Celsion's OVATION I study in ovarian cancer with their Gen-1 asset and also the Medicenna in glioblastoma. So 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 over, in general, why an SCA real-world approach will be valuable, 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 Marc mentioned.

This -- and Marc mentioned that this doesn't have Phase I's -- our design not to have the -- an efficacy control arm. We'll be able to rectify that with the synthetic control arm resecting the enrollment criteria that we had in that Phase I. So with this Phase I, we believe that we will have -- we'll be generating additional data beyond the very impressive overall survival data that's been reported at the SNO Annual Meeting last year, demonstrating 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 Marc and I, we plan on approaching FDA by midyear for this Phase II pivotal advancement. The availability of a control arm means that the randomization for control of active treatment will not be 1:1. That will encourage these unfortunate patients to enroll in the studies. It's always a personal decision, but patients understandably would like active treatment. This, in turn, accelerates development, asset marketing and commercialization and save development costs. So Marc, I don't know if you have anything else to add 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.

No, that's great. Thank you. Maybe there's a follow-up question. So Dave, I'll turn it back to you for further questions.

We'll take our first live phone question from Joanne Lee with Maxim Group.

This is Joanne. And congratulations on the progress this quarter, especially on the positive data presented at the SNO. Given the greater overall survival rate that's 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 GMB setting, particularly as the survival goalposts keep moving.

Yes, I'll take that. Thank you, Joanne. So on the first part of the question, so the dosing plan, we sort of -- let me back up. So we've bifurcated the trial, continued the Phase I and continued 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 in dosing cohort 8 right now, which is about 12 ccs of volume, I think 31 millicuries of radiation.

The -- kind of moving into the Phase II, kind of the other half of the bifurcation, the plan is to take the prior dose at which we have 6 patients, which is where the trial's design is sufficient to move into a Phase II recommended dose, which is at 8.8 ccs and I think about 21 millicuries. So we've got no DLTs. 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 (sic) [22.3 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 the small- to medium-sized tumors based on the data we have thus far. And then we'll 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, and only 23 patients at this point. But it looks like there's a pretty clear biologic signal as we dose escalate it. 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.

Great. And just regarding the trial size in recurrent GBM, can you do a registration study with a single arm, say, 100 patients and get approval? Because we've seen drugs gain approval in other indications in a severe unmet need setting through that pathway.

And just as a follow-up, you mentioned the use of a synthetic control in the next trial. Could you give us some details around that decision? And -- as it's an approach we've observed the FDA being more open to in recent years, particularly in GBM.

Yes. So it's a little too early to tell what the trial size looks like, the 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 open 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 Medicenna has received approval from the FDA to go into a Phase III design using a real-world synthetic control arm to have a control group that is an amalgam of patients that have been randomized to the control group, but to supplement that with real-world data that are identically matched to the enrollment and the exclusion 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.

We'll take our next question from Sean Lee with H.C. Wainwright.

So I just had a couple on your clinical development plans. The first question is, you guys mentioned that you wanted to try redosing of patients. Now is that within the same Phase I study where you do expansion cohort for that?

Sean, it's Marc. It would be a separate protocol. It would be outside the Phase I design in the sense that the NCI covers it and so forth. And so I don't plan -- we don't plan to back it into that -- the NCI framework. So it would be a separate protocol but under the IND. And that's been submitted, and we just -- we haven't heard back from the FDA about our ability to move forward with that.

I see. In terms of that, what kind of patients are you particularly looking to redose? And what sort of -- what kind of doses will you be starting them on?

So yes, it's a great question. So it's almost impossible to eradicate GBM, and that's kind of why we're -- we've seen in the dose escalation trial that even though we've had a number of long-term survivors or one survivor that's 160 weeks out, almost 3 years, that we still can't eradicate it.

And so -- and there are kind of 2 patients. There are 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 recurrence so we could re-treat those patients.

The other type of patient is where we've got good coverage. Patient does well. We're seeing a safety and potential efficacy signal in that particular patient. But if that -- if the disease comes back, as it typically does, we want to be ready to re-treat them.

So the plan is to take the -- or the request from the FDA is to take the cohort 6 dose. That's the one we're taking in the recommended Phase II where we have 6 patients treated. That would be the maximum dose. We can potentially go down based on the size of the image of the recurrent tumor, but that would be the planned maximum dose going into that re-treatment protocol.

I see. In terms of testing these re-treatments and also testing higher doses in the Phase I study, if you do see some improved outcomes from these treatments, would you delay your Phase II to incorporate these? Or are you happy with the, I think, 8.8 mL that you guys are settled on?

Yes, we're happy with that. I think it's tumor size-dependent. I think we've mentioned this before. I think you and I have talked about this, that the concept is you want to cover the tumor and a rim of what appears to be normal brain because the 90% of patients that -- 90% of the recurrences will occur in the 2-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 re-treatment context, these patients get imaged every 60 days. So we think that we can be vigilant and aggressive in jumping on anything that we think might be recurrent disease and be able to knock that down, and the volume requirement would be the dose -- and the radiation dose requirement would be perhaps a bit less than what we would treat in the first recurrence.

I see. 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 will 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 in China and Japan, if I remember correctly. So something like an international collaboration to test it in those countries would be something that you guys would consider.

Yes. 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. The -- 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.

(Operator Instructions) We'll take our next question from Ed Woo with Ascendiant Capital.

Yes. 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 RNL 186 in terms of priorities for the company?

Ed, thanks for the question. We're very excited about the BAM opportunity. The delivery technology is very mature. Interventional radiographic technologies use it all the time as opposed to the RNL 186, which, although we're very confident it's going to work, it is sort of new novel technology. But the angiographic interventional technology is very mature, very effective for solid organ targeting. So I think that's sort of the key thing that excited us about this.

I guess the other thing that is worth noting is this is very -- this technology is very much aligned with our current 186RNL 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 2 products that have been used for approximately 25 years commercially pretty broadly in liver cancer area, but they have some significant shortcomings. And so I think the market is really ripe for a second-generation 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, as I mentioned previously, is the tech transfer complete and then do some proof-of-concept CMC and ex vivo work on the scalability and consistency of the drug product before we get in the 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 of 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 and 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.

(Operator Instructions) And there are no further questions on the line at this time. I'll turn the floor back to Dr. Hedrick for any additional or closing remarks.

Thank you, David. Let me just close by thanking everybody for joining us on the call today, and thank you to you that's listening 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.

This does conclude today's program. Thank you for your participation, and you may now disconnect.