Plus Therapeutics, Inc. (PSTV) Q4 2021 Earnings Report, Transcript and Summary

Good afternoon, ladies and gentlemen, and 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. [Operator Instructions]. Before we begin, we want to advice you that over the course of the call and 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 and including the risks and uncertainties described under the Risk Factors section included in Plus Therapeutics' annual reports 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 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. LaFranceon board as he brings many years of highly relevant clinical regulatory and commercial expertise in radio therapeutics in 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 radio therapeutics for cancer. In 2021, we continue to advance our lead investigational targeted radiotherapeutic drug rhenium Rhenium 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 of the U.S. NCI or National Cancer Institute. Our initial indication for RNL is recurrent glioblastoma with defects approximately 30,000 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 saving disease remains a significant unmet challenge. We call also that RNL is proprietary liposomal encapsulated, radionuclide that is delivered locally regionally via targeted three dimensional convection enhanced delivery. It is administered directly to the tumor, bypassing the blood brain barrier. The activation 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 1/2 ReSPECT-GBM to the 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. 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 millicuries and 12.3 milliliters of volume. No delivery failures were observed. An average absorbed dose of 276 grade 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 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 improve survival. And it remains to this day and a central component of multimodal therapy for GBM and many other cancers. There's no question radiation works in GBM. Furthermore, in ReSPECT trial, key drug delivery parameters such as flow rate, catheter, 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 also thus far well tolerated without those limiting toxicities, has an acceptable safety profile. There were no adverse events, thus far in the trial with the outcome of death, or discontinuation due to adverse events, and placement of up to four catheters in a patient thus far have been safe. As to efficacy, and it's interestingly similar, the efficacy results thus far to our preclinical results and absorb radiation dose of greater than 100 gray in patients it's with increased overall survival. Well, the Phase 1 trial is neither designed or powered for efficacy, we are observing promising signals of both biological effect and increased overall survival. In the latter cohort of the trial specifically cohorts five through eight, receiving greater drug volumes in radiation doses, and frankly more optimized delivery parameters. Nine of the 12 patients are 82% of those patients in cohorts five to eight, received a therapeutic dose of 100 gray are better. And we believe it's entirely possible to achieve a 90% or greater coverage of 100 gray or better bone forward. This 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 have such long-term overall survival data which we do in this trial. Therefore, we take the logical step and take advantage of what's been done by the academics who 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 range from the start date of March 2015 through to July 2020, which is longer survival data we have in the trial thus far, immediate and mean overall survival stands at 82 and 88 weeks respectively, the two patients still alive. That compares very favorably with the 32 weeks overall survival published in a recent med analysis, every nearly 700 patients with recurrent GBM treated with Bevacizumab monotherapy in recurrent setting. And that reference can be found on our website in our corporate presentations. Furthermore, our team continues to make excellent progress in drug scale up and manufacturing activities. Specifically during pretty funny one in this by 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 in mid-2022. Before I turn the call over to Norman, 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, consummated the end of December. This substantially expands our policy 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 of matter patents for biodegradable alginate microspheres, which we call BAM, containing the nanoliposomes loaded with imaging and our therapeutic payloads. Therapeutic payloads may include radio therapeutics chemotherapeutics, or thermal therapeutics. 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 radio isotope. The company will initially focus on developing 188 RNL BAM as a next generation radioembolization for liver cancer, in which BAM blocks the hepatic artery segments is supplied 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 TID 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 to this call. Plus Therapeutics is focused on radio therapeutics positions is firmly for long-term growth. I'm excited to lead the development expansion of its promising pipeline. Following Marc’s comments on the ReSPECT-GBM trial in patients with recurrent glioblastoma. In 2022, we expect to materially advanced the investigational drug 186 RNL recurrent GBM and other indications. First we plan to meet with FDA midyear proposed taking our 8.8 milliliter and 22.3 millicurie as our recommended Phase 2 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 2 pivotal trial designs that may incorporate the use of real world data, also known as synthetic control arm to improve trial costs to facilitate enrollment. In addition, as we have yet to reach those limiting toxicity, the respect GBM trial, and we anticipate to be able to treat larger tumors with 186 RNL, our goal is to keep the Phase 1 dose escalation trial open and report data both on the previously treated patients and on future potential cohorts. We may also consider exploring improve 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 186 RNL as they benefit from an additional RNL dose. GBM is a notoriously difficult to eradicate for the brain. And we believe a subset of patients a 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 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 cranial spinal acts. We expect LM trial is a multicenter sequential cohort, open label single dose, dose escalation phase one study and will evaluate the maximum tolerated dose, maximum feasible dose, safety and efficacy of the single administration 186 RNL via intraventricular catheter for the Leptomeningeal metastases treatment, following standard surgical radiation or chemotherapy treatment of these patients. The primary endpoint of the study is the incidence and severity of adverse events and serious adverse events and dose limiting metastasis 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 the IND clearance from the FDA last year, in fourth quarter of last year, the company began screening and consenting patients and respect on Phase 1 trial in patients with leptomeningeal metastases. Regarding pediatric brain cancer, based on our pre-IND meeting feedback received in 2021. Company expects to submit an IND for Phase 1 trial with 186 RNL 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, 20 21. 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. The main changes between 2020 and 2021 as follows. In 2021 to 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 and our 2021 run-rate 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 continue to CMC development RNL to GMP standard. The 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 2025 minute pre-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. Interesting expense decreased by approximately $400,000 in 2021, from $1.3 million in 2020 to $907,000 in 2021. This decrease cost reflects the $5 million in principle paid off in 2020, with a further $300,000 in 2021. These payments reduce the remaining principles due to Oxford below $4 million at December 31, 2021. Net loss for 2021 is $13.4 million as compared to a net loss of $8.2 million in 2020. Excluding the gains on the warranty of $2.3 million that we’re reported in the first quarter of 2020, the change in net loss reflects the incremental R&D and G&A and 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. 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 we have GMP Phase 3 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 2 clinical plan and trial design using 8.8 ml and 22.3 millicurie recommended Phase 2 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 2 enrollment and potentially reduced power costs. In 2022, we plan to continue to report Phase 1 data and provide enrollment updates in an ongoing manner in the current Phase 1 trial. Regarding the ReSPECT-186 RNL LM trial. Our goal is to complete enrollment in the 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 radioembolization therapy technology we put in to complete the technology transfer in other key CMC, and FDA IND enabling studies for this asset in 22. So at this point, move to Q&A. And David, I'll turn it over to you.

Thank you. The floor is now open for questions. [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 saying.

Thanks, David. First question is from Justin, can you reminds 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?

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. 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 -- there surgically getting the catheters in the tumor leverages existing, tried and true brain biopsy technology. It's common place in hospitals that have neurosurgical services. The technology itself allows very precise delivery within about a millimeter or so. And actually, there are many navigation systems that allow -- that sort of geospatial delivery technology to be the place we'd prefer the brain labs technology, that's one that we've used. In fact, I've gone through the full training on my neurosurgeon and [technical difficulty] I feel after a day of trading I’m 100% capable of doing that. So part [technical difficulty] of that I don’t think is the barrier. What initially 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 it kind of I think the story is adequately told in 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 wider cohorts, I think I referred to this in the script, like cohorts five to seven, where we've got more volume. We've gotten higher radiation doses, just more catheters, higher flow rate, et cetera. We're able to cover the tumors with therapeutic radiation, about 80% plus of the time in those cohorts. And I'm increasingly comfortable, where we're going to able to get that to 90% or greater think that's achieved. So 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, 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 or have been solved.

Justin’s second question is, can you provide some additional color on a regulatory precedent for using a synthetic control arm? What are some of the potential advantages and disadvantage of that trial design approach?

Normally, would you mind answering that?

Yes, I'll be happy to. Thanks. It's a great credit 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 Celsion's OVATION 1 study, in ovarian cancer, with their Gen 1 asset, and also the Athena in glioblastoma. So this approach has been used successfully with recurrent glioblastoma with [Indiscernible] and seizure drug review groups within FDA. Now 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 their significant data with the with the group world expert group, who are dealing with this for understanding of our early phase single arm trial data that Marc mentioned. And Marc mentioned that this doesn't have as Phase 1, are designed not to have the 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 1. So with this phase one we believe to have will begin -- 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 advancements to Phase 2 with FDA. As you heard from both Marc and I, we plan on approaching FDA by midyear for this Phase 2 pivotal advancement. The availability of a control arm means that the randomization for control active treatment will not be one-to-one. That will encourage these unfortunate patients to enroll their studies. It's always a personal decision. Patients understandably would like active treatment. This in turn accelerates development faster to market and commercialization and save development costs. So Marc, I don't know if you have anything else on it, but I think that 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.

That's great. Thank you. Maybe it's a follow up question. So David, turn it back to you for the questions.

Of course, we'll take our first live phone question from Jianing Li with Maxim Group. Please go ahead. Your line is open.

Hi, this is Jianing, thanks for taking the question and congratulations on the progress this quarter, especially on the positive data presented at the SNL. Given that greater overall survival rate 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 goalposts keep moving?

Yeah, I'll take that. Thank you, Jianing. So the first part of the question, so the dosing plan, we back up so we bifurcated the trial, continue to Phase 1 and continue the current dose escalation scheme. And that's -- I can walk you through that to degree you're interested in what that is. But right now, we're dosing cohort eight right now, it's about 12 CC's of volume, I think 31 millicuries of radiation. And moving into the Phase 2, the other half of the bifurcation, the plan is to take the prior dose at which we have six patients, which is what the trials designed sufficient the move into a Phase 2 recommended dose, which is at 8.8 CC's. And I think about 21 millicuries. So we've got the DLTs, we've got a very accessible safety profile. The dosimetry data from the clinical trial shows that we can cover not only the tumor, but also a rim of the 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 8.8 21, 23 [ph] millicurie dose will treat about 15 is perhaps up to 75% of its typical recurrent GBM, we think that's a totally appropriate dose to take into Phase 2 for the small to medium sized tumors, based on the data we have as far. And 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 been directly derived the fact that 100 gray or greater seems to be therapeutic. And only 23 patients at this point. But there's a pretty clear biologic signal as we dose escalated in. 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 grays to the tumor. And the interesting thing is, we're now delivering 740 grades. 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 and the current GBM. Can you do a registration study with the single arm 100 patients and get approval? Because, we've seen drug screening approvals and other indications in a severe unmet need setting through that pathway. And just as a follow up, you mentioned the use of the recent data control in the next trial, could you give us some details for that around a decision? And as an approach we've observed. Ahat da be more open to in recent years, particularly in GBM?

Yeah, this is a little too early to tell what the trial size looks like, from budget so forth. But we've said previously, I think we still believe this, we have no reason to believe differently that approximately 100 patients, it's about the size of that trial. As we've mentioned previously, we have a 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 breakeven designation pathway, that that may be an alternative here as well. So that's 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 your follow up question on the synthetic control arm, Norman alluded to this that Medicina as received approval from the FDA to go into a Phase 3 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, inclusion criteria to the trial. So we -- there's an increase in the well worn path of 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.

Great. Sounds very helpful. Thanks again.

Thank you.

We'll take our next question from Sean Lee with H.C. Wainwright. Please go ahead, your line is open.

Good afternoon, guys. And thanks for taking my questions. So I just have a couple of your clinical development plans. So the first question is, you guys mentioned you wanted to try reducing your patients. Now, sometimes that means that within the same Phase 1 study, we do expect in cohort for that?

Hey, Sean, it’s Marc, It would be a separate protocols, it would be to be outside the Phase 1 design in the sense that the covers it and so forth. And so I don't -- we don't end up back 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 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 studying them on?

So, yeah. It's a great question. So 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't eradicate it. And so there kind of two patients, they're the patients where maybe the morphology of the tumors is not ideal. Difficult to cover the tumor, that anatomic location is challenging, and so forth. And we know right off the back that there might be a little bit of area that's going to be at risk for recurrence based on the dosimetry data sets [Indiscernible] type patient where we know right off the bat that there may be -- may be a problem, we want to be hyper vigilant on 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 requesting here to take the cohort six does, that's the one we're taking the recommended Phase 2 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.

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 so to incorporate these or are you happy with, I think 8.8 mil that you guys are set off?

Yeah, we're happy with that. I think it's tumor size dependent. I mean, I think we've mentioned this before, and again, I've talked about this. But the concept is you want to cover the tumor and have what appears to be normal brain because that 90% of patients that -- 90% of the recurrences will occur in a 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 so that's the rationale and those escalation arm is continued to escalate and be able to treat those higher tumors. But in the retreatment context, these patients get imaged every 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 a dose -- the radiation dose requirement would be perhaps a bit less than what we would treat in the first recurrence.

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 issues that you guys go after with this product. And while it's very rare cancer here in the U.S., it's a very common one out in Asia, especially China and Japan, they will move quickly. So something like international collaboration to test it in those countries be something that you guys would consider?

I completely agree. That's 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 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.

I see. Thanks. That’s all I have.

Thanks, Sean.

[Operator Instructions] We'll take our next question from Ed Woo with Ascendiant Capital. Please go ahead. Your line is open.

Yeah. Congratulations on the progress so far. Also touching back on the BAM product. So what was your rationale in terms of what you guys really liked about this? And should we see this in terms of how does it I guess, balanced out with RNL 186 in terms of priorities for the company?

Thanks for the question. Yeah, we're very excited about the BAM opportunity. The delivery technology is very mature, individual radiographic technologies used all the time. As opposed to the RNL 186, which although we're very confident is going to work. It is sort of new novel technology. The angiographic individual technology, it’s 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 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 CMC perspective, from a drug development clinical perspective, so this is right up our alley as an add on technology. As to the liver cancer issue, absolutely right. It's a rare disease. There are products that have been used for approximately 25 years commercially, pretty broadly in liver cancer area, but they have some significant shortcomings. And so like 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 I think the next steps for us though, before we get too far down the road is as I mentioned previously, at the tech transfer complete and then do some proof of concept CMC ex-vivo work on the scalability and consistency of the of the drug product before we get into clinic, which we think is scheduled late, 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 micro scale drug as opposed to a nanoscale, completely different mechanism of targeting that we have for the 186 and it allows us to gain related experience in the 188 isotope which is different than 186. 188 actually made not in a nuclear reactor, but is much easier to make 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.

Great, thank you for the explanation. And I wish you guys good luck. Thank you.

Thanks, Ed.

[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 that is that listening to the recorded version. And on behalf of the board I 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 trial. 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.