Plus Therapeutics Inc (PSTV) 2022 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics' First Quarter 2022 Results Call. (Operator Instructions)

Before we begin, we want to advise 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, 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 they are made.

It is now my pleasure to turn the floor over to Dr. Marc Hedrick, Plus Therapeutics' President and Chief Executive Officer.

Thank you very much, Christian. 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 2022 first quarter financial results. Joining me on the call today is Dr. Norman LaFrance, our Chief Medical Officer; and Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent corporate and clinical progress before turning the call over to Norman, who will provide commentary on our clinical progress for 2022. And then following Norman, Andrew will review our financials.

Despite the short interval since we last reported quarterly results, I continue to be very pleased with our overall progress as we work towards several meaningful catalysts and milestones throughout 2022. During the first quarter, we began enrolling patients in our ReSPECT-LM trial of 186RNL in patients with leptomeningeal metastases or LM. The trial is a multi-center Phase 1/2a dose-escalation study to determine the MTD, maximum tolerated dose, in MFD and safety and efficacy of RNL186 in LM.

LM is a typically fatal complication associated with advanced cancers that affect the fluid line structures of the central nervous system or leptomeninges. Median survival with current aggressive treatment is about 3 to 8.5, depending on which primary tumor caused the LM. And the 1 and 2 year survival rate is 7% and 3% respectively. Survival without treatment is only a few weeks.

LM is diagnosed in approximately 5% of cancers with 20% of patients at autopsy. U.S. annual incidence is about 110,000 patients and growing, and the prevalence of neurologic impairment in these patients is about 50%. Most common tumors giving rise to LM are breast cancer, lung cancer, melanoma and gastrointestinal malignancies. There are no FDA-approved therapies. And standard treatment that is employed includes external beam radiation therapy to the affected sites, followed by chemotherapy given either orally or intravenously or even directly into the cerebral spinal fluid.

Although we can only draw limited conclusions from our initial experience, we're very pleased with the outcome in the first patient receiving a single administration of 186RNL. Specifically, we found that the drug circulated rapidly throughout the cerebral spinal fluid space. We found that radiation was released through leptomeninges and CSF for at least one week after treatment. The patient exhibited no adverse events. And 186RNL reduced the circulating tumor cell counts by over 90% at 2 weeks after treatment. This is really about as good as it gets in a first-in-man -- first patient in a Phase 1 trial. So we're very excited about this very [preliminary] result. We now have 2 active sites screening LM patients with another 6 sites being onboarded as we speak. We're on track to have at least the first 2 cohorts completed by the end of 2022, and hopefully a bit more than that.

As to our ongoing clinical development program for 186RNL in recurrent glioblastoma, we have a number of updates. First, as a reminder, that trial is a dual Phase 1/2a multi-center sequential cohort, open label, volume and dose escalation study for recurrent glioblastoma or GBM. The trial is currently funded through significantly, as many of you may know, by the U.S. National Institutes of Health and the NCI. Glioblastoma affects about 13,000 patients annually in the U.S. and about the same number of patients in the EU. It's the most common and lethal form of brain cancer and treatment of this devastating disease remains a very significant unmet medical challenge.

Now in terms of the clinical data, 23 patients have been treated and 186RNL appears to be safe and well tolerated. And this data presented most recently back in March can be found in detail on our website, and that's accessible to anyone. In summary, no dose limiting toxicities have been observed. Generally, mild-to-moderate AEs have been seen and 7 SAEs, all grade 3 or lower and most are not deem to be RNL-related.

In terms of drug delivery, we are now reliably able to deliver over 100 gray of absorbed radiation dose to tumors, which is our empirically-determined minimal dose threshold of adequate absorbed radiation. And we can get well over 80%, but we think 90% is achievable in terms of reliable dose delivery of 100 gray. Finally, we have observed both the median and mean overall survival signal that exceeds the best published rate for monotherapy bevacizumab.

Based on this data, I'd like to just explain our big picture plan. We plan to bifurcate the current GBM clinical development plan based on tumor size. So for tumors of approximately 15 to 20 CCs in volume, which represents about 1/2 to about 2/3 of all recurrent glioblastomas. We plan to use the Cohort 6 dose of 22.3 and 8.8 CCs of volume as a recommended first Phase 2 registrational dose. For tumors of larger size, potentially requiring greater radiation dosages and treatment volumes, we intend to continue our Phase 1/2 dose escalation trial to establish the upper limits of dose and potential for DLTs or dose-limiting toxicities.

In 2022, for GBM, we have 2 key regulatory milestones. We have already in 2022 submitted and asked for the first of 2 FDA meetings, specifically a Type C CMC meeting to determine the sufficiency of our CMC package for GMP 186RNL to support a registrational trial, and then relatedly to the CMC development. Our team continues to make excellent progress in our drug scale-up and manufacturing activities. Specifically, the company has finalized key RNL drug development and characterization activities for GMP manufacturing to support our planned Phase 2 registrational trial and commercialization activities thereafter. The company remains on track to deliver GMP RNL by mid-2022. The second FDA meeting is a clinically-focused meeting planned for Q2, Q3 to solicit FDA feedback on our planned Phase 2 registrational trial using our recommended Phase 2 dose, as mentioned, 22.3 millicuries in a little less than 9 CCs of volume.

Also during Q1, we completed another key milestone. Specifically, we successfully completed the preliminary evaluation phase and entered into a broad partnership with Medidata to use its Synthetic Control Arm platform and Real World Data as the comparators for our glioblastoma trials. The primary goal of this partnership is to develop an FDA-compliant controlled group of patients identical to the patients thus far treated in our Phase 1/2a trial and in the planned Phase 2 registrational trial. That data will be used to support our planned end-of-phase meeting with the FDA and proposed Phase 2 registrational trial.

More generally, Synthetic Control Arm or SCA platform facilitates the use of historical clinical trial data in a manner that has been favorably received by the FDA. These SCAs reduce the time and costs associated with complex clinical trials in rare diseases such as glioblastoma, allowing for fewer patients to be exposed to placebos or existing standard of care treatments that might not be effective for them. It offers them greater access to potentially life-extending therapies. And although, a recent advancement, the FDA has already agreed to recognize a Phase 3 clinical design incorporating an SCA in a registrational randomized control arm for recurrent glioblastoma. Besides initiating our Phase 2 registrational trial with RNL in recurrent GBM, as I mentioned above, we also continued enrollment in our Phase 1/2a dose escalation GBM trial, and that will continue.

Finally, this quarter, we intend to open a Phase 2 multi-dosing extension trial of RNL in recurrent glioblastoma. As you know, if you follow the company, glioblastoma is notoriously difficult to cure and recurrent disease is the norm. This extension trial will give us important information about the utility of multiple potential doses of 186RNL in the overall treatment paradigm for these patients.

The goal of the trial is to determine the safety, feasibility and potential efficacy of using additional doses of RNL in patients following the initial single administration of RNL as we have done previously in the Phase 1/2a trial. This is really important to our big dream. One day, if not curing GBM, returning it into a chronic disease in which we help patients live with brain cancer.

Finally, in Q1, we announced our license of a novel radioembolic microparticle technology from the University of Texas. As we've said many times, we believe the future of cancer therapy is precise targeting of tumors with the most potent cancer-killing agents while minimizing damage to normal tissues. This transaction builds upon our existing Rhenium Nanoliposome technology. And with this new technology, we can with a resorbable biomaterial embolic technology coupled with a highly potent radiotherapeutic isotope, target almost any solid organ tumor in the body using the standard interventional radiologic means and leverage the breadth of the human vascular system.

Rhenium-188, not 186, but Rhenium-188 Nanoliposome Biodegradable Alginate Microspheres, we call 188RNL-BAM or just BAM for short, is a next-generation fully resorbable technology that solves many of the existing problems with current radioembolic technology that's been out there for many decades. The BAM technology incorporates Rhenium-188 isotope for use as the radiotherapeutic source with a different emission criteria and characteristics than 186. It emits a high-energy beta particle, but with a half-life of only about 17 hours for a longer path length of over 3 millimeters. It also produces gamma energy that we can use for high-quality real-time imaging of the BAM construct in the organ. The company will initially focus on developing the BAM technologies and next-generation radioembolization therapy for liver cancer in which it can blocks hepatic artery segments that supply blood to (inaudible) tumor while also providing radiotherapy by directly irradiating the tumor.

Liver cancer is a rare disease with an increasing annual incidence and a 5 year overall survival rate of only about 20%. The global opportunity for localized embolization, [hemalization], radioembolization are for primary and secondary cancer in the liver is about 1.3 billion opportunity globally. We have 3 objectives in 2022 for our BAM program. The technology [cancer] phase, which has been completed. And we are on track to complete key CMC feasibility studies, IND-enabling preclinical studies in an FDA pre-IND meeting this year.

So with that, I'll turn the call over to Dr. LaFrance. Norman?

Thank you, Marc. Following on Marc's comments, in 2022, in our GBM clinical development plan to extend the existing ReSPECT GBM trial and program into a strong development plan, first and most importantly, is the ReSPECT GBM Phase 2 registrational trial using the Cohort 6 recommended Phase 2 dose, that Marc mentioned earlier. The company and its key advisers believe the safety profile and the clinical efficacy signal of a potential doubling of overall survival of patients with the absorbed radiation doses greater than 100 gray has the potential to be an approvable NDA for recurrent GBM. Pending the outcome of our planned FDA meetings, our 2 planned FDA meetings, we will initiate the first cites for that registrational trial by year end. In the interim, we'll be executing our clinical operations plan to be ready to achieve this milestone.

Second is the continuation of the Phase 2 dose escalation trial supported by NCI for larger tumors. And third is a Phase 2 multi-dose extension trial for patients previously treated and patients that will be treated in the 2 trials just mentioned.

In terms of GBM data presentations for 2022, we plan to provide key GBM clinical updates at the following medical meetings; the Society of Nuclear Medicine Meeting this June in Vancouver; the SNOW ASCO-sponsored Clinical Trials & Brain Mets Meeting in Toronto in August; EANO and ESMO in Vienna and Paris respectively, both in September; and potentially EANM in Barcelona in October; and the SNOW Annual Meeting in Tampa in November. Additionally, I'll be participating at the Medidata Synthetic Control Arm Focused Industry Roundtable next week on April 26.

As Marc mentioned, our clinical team and investigators were very pleased with the first patient outcome in ReSPECT LM trial. Treating the first patient of any new condition with an investigational drug is always an exciting, but with many unknowns. A few comments. The feedback from one of the very experienced investigators in the trial was that they had never seen such a clinical response in the first patient in the Phase 1 first-in-man trial. The delivery of RNL in this trial was very simple and straightforward with 5 minute outpatient procedure to an existing Ommaya reservoir. There are substantial existing biomarkers such as tumor cell count which we are measuring in CSF, which is simple to obtain in these patients. There are also a number of additional exploratory biomarkers we are looking at as well.

Additionally, Plus will perform several preclinical studies to evaluate additional LM treatment paradigms with 186RNL, specifically multi-dose administrations and combination treatment with immunotherapies such as PARP and checkpoint inhibitors, both known to be synergistic with radiation. Despite impressive initial results at the first dose with a single RNL monotherapy, Plus believes optimal patient benefit can be amplified with multiple RNL doses and/or combination therapies. For our current trial, I'm optimistic enrollment will proceed rapidly based on the significant unmet medical need, very well tolerated and easy dose administration and the enthusiastic responses received from investigative clinical sites along with other oncologists once they hear of our trial.

Developing preliminary clinical data and medical meeting presentations planned for LM in 2022 were presented a few minutes ago. And finally, RNL is being developed for pediatric brain cancer. The key goal here is to obtain FDA IND approval to investigate the use of 186RNL for children with brain cancer. And we are working with our lead site, Lurie Children’s Hospital in Chicago and are on track to hit this milestone later this year.

Next, I'll turn the floor to our CFO, Andrew Sims, who will review financials. Over to you, 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 2022 first quarter ended March 31, 2022. As of March 31, 2022, cash and cash equivalents were $21.2 million compared to $18.4 million as of December 31, 2021. This represents 18 to 24 months of cash on hand.

Cash used in operations for the 3 months ended March 31, 2022 was $3.9 million compared to (inaudible) million in the first quarter of 2021, with the main changes between 2021 and 2022 as follows. Total operating expenses for the first quarter 2022 were $3.9 million compared to total operating expenses of $2.5 million for the first quarter 2021. Approximately $0.7 million of this increase is due to research and development expenses and $0.6 million is due to legal, intellectual property and professional fees in 2022.

Interest expense decreased from $247,000 in the first quarter of 2021 to $198,000 in the first quarter of 2022. This decreased cost reflects the principal paydown that commenced in November 2021 on the Oxford debt. Net loss for the first quarter of 2022 was $4.1 million or $0.19 per share compared to a net loss of $2.7 million or $0.33 per share for the first quarter of 2021.

And now I'll turn it back to you, Marc.

Thank you, Andrew. Before we move on to Q&A, let me just summarize key milestones anticipated for 2022. First, with respect to the 186RNL GBM trial, we're planning for a clinically-focused FDA meeting mid-year 2022 to propose a Phase 2 registrational clinical trial and trial design using the Cohort 6, 8.8/22.3 millicurie dose, as detailed earlier. We expect to initiate the Phase 2 towards the end of the year.

We anticipate the CMC-focused FDA meeting in the second quarter of 2022 or perhaps the beginning of the third quarter. And to clarify, that's to resolve any open CMC issues that may exist at that time. Regarding drug availability, very important that we have GMP drug availability to proceed with the trial. We're on track with CMC activities for RNL. We plan to complete those and have that GMP Phase 3-ready drug supply available by mid-2022. Also in 2022, we will report Phase 1/2 data and enrollment updates in an ongoing manner, as Norman mentioned, for the ReSPECT LM trial and our goal is to complete enrollment in at least the initial 2 cohorts this year.

Regarding the pediatric brain tumor trial, we plan to get our IND submitted relatively soon this year and be able to initiate that trial towards the end of the year. Regarding our recently acquired rights to the 188RNL-BAM radioembolization therapy technology, we plan to complete key CMC and FDA IND-enabling studies in a pre-IND meeting also this year.

So at that point, I think we'll move to Q&A, and I'll turn the call over to Gretchen. Gretchen, back to you.

(Operator Instructions) Our first question is coming from Ed Woo from Ascendiant.

I was wondering, you have a couple of meetings planned with the FDA this year. Do you know if the timing has reverted back to normal post-COVID or do you see that there's still possible delays that this possibly running a little bit longer than you expect?

Norman, would you answer that?

Ed, that's a great question. We won't know until FDA gets back to us. But I'm anticipating they'll probably follow their published guidances for these meetings, meaning they'll provide an answer usually within 3 or 4 weeks and the meeting date by 75 days. As you know, they have the right to actually move those meeting dates up sooner than the PDUFA guidances require them. But I'm not anticipating those to be pushed out further than usual as they were occurring earlier in the pandemic.

And then my last question is, your current GBM trial is funded by the NIH. Do you anticipate trying to get additional funding for some of these other indications that you guys are working on?

So one of the reasons we're based in Texas is because there are opportunities to Texas-specific oncology-related grants, as I know you're aware, that's called CPRIT. And we've been very interested in obtaining CPRIT funding for our various programs. Unfortunately, for the GBM program, they typically don't fund Phase 3 trials, but they will fund Phase 1 to Phase 2. So that's definitely something that's of interest. We're up at the plate with CPRIT and continue -- we'll continue to be. They have 2 funding cycles a year. And so we spend a lot of time trying to find non-dilutive ways to gain funding like CPRIT. So we'll continue to do that. But as per our previous plan, we won't talk about specific grants we commend. But once we -- and if we get something approved and funded, we'll certainly talk about that once we're notified.

(Operator Instructions). We'll take our next question from Sean Lee at H.C. Wainwright.

This is Sean Lee from H.C. Wainwright. My first one is on the LM study. It's good to hear that first patient is doing well. And -- but traditionally, with chemotherapy -- intrathecal chemotherapy to treat LM, one of the issues that they face is that there is insufficient penetration of the drug into larger solid tumors. So I was wondering, is that something that you guys could potentially face with RNL as well?

Sean, great question. So with leptomeningeal disease, there's 2 types. One is linear and the other is nodular. The nodular tumors can be a few millimeters in focal, whereas you have sort of more linear disease, which can be very thin, but it's just on the lining of the leptomeninges. So with that sort of as a background, one of the things we're excited about with RNL is it does have some penetration characteristics. It's delivered within the CSF. It has a path linked -- an average path length of about 2 millimeters, but it can have path links up to closer to 4 millimeters.

So you can actually get some penetration in nodular disease as well as hitting the linear disease. So we think that this could have a better effect in chemotherapy because of some of the limitations of chemotherapy and some of the benefits of a radiotherapeutic. And I just -- maybe solicit Dr. LaFrance. He is an expert in the CST, see if he has anything to add.

I think it's a great question. And one of the unique characteristics of the LM study design and unfortunately, these tragic disease complication of these patients is the leptomeningeal metastases really spread along the leptomeningeal membrane throughout the subarachnoid space. And you're absolutely right, whether you (inaudible) chemotherapy and even CSF administered chemotherapy systemically administered has the challenge of getting there. So you have your spot on in that observation.

And when administered intrathecally, it usually doesn't -- it escapes the CSF very rapidly. As you may know, the turnover volume of the CSF, which has a volume of about 125 ml is 5x a day. So you have something in there, but very quickly gets exits out with that kind of circulation. Think of it as the CSF physiology, circulation physiology. The RNL nanoliposome design, it's administered very easily through the Ommaya one, patient is not even aware of it. We use a 27-gauge pediatric butterfly needle. It goes in a 5-minute administration time period.

They get a little band-aid over which they don't really even need but a band-aid over the administration side on the skin over the Ommaya. And that's an outpatient procedure. And we have seen and as we predicted, not only is there excellent distribution that you heard Marc described, the duration of time that Marc also alluded to in his comments at the beginning of the call, we have objective evidence, imaging evidence because the simultaneous gamma ray this integration with the Rhenium-186 of RNL product staying in the subarachnoid space for over a week.

So given our half-life, basically, the product stays there during its effective energy particle decay period and you get full benefit by 3 or 4 half life though the whole time and you get kind of the full benefit of that product administration. In hindsight, that's probably why we saw this result and our -- at this very early -- at this first dose, which is a very small dose, 6 mil it carries and they get this kind of response. I think as I mentioned, one of our experienced investigators, he has never seen this before, and that's where we were pleasantly surprised.

Thanks, Marc, and thanks, Dr. LaFrance. It's very helpful. My second question is that because with LM, you're using a slightly different method of delivery. Would that place a limit on what kind of radiation dose you're able to deliver compared to the GBM study?

I appreciate that question because that's actually the benefit of the delivery in LM makes it so easy. So instead of having -- the amount that we will deliver is going to be part of our dose escalation trial, and we'll find that out. But I guess to really answer the quicker your question, we will go -- our next cohort doubles the dose we're doing the administered dose and the next cohort asset doubles it again.

So by -- we hope by year-end, we'll have experienced at 4x the dose we're using now. Given the response we saw in the first patient and given the preclinical work, we're going to start on nation therapies or multiple dosing therapies, I don't think the amount of administered dose delivery will be an issue. So you're absolutely correct that we're delivering it differently. That actually turns this into an outpatient therapeutic process as opposed to the required inpatient, albeit only a few days for the CED delivery.

That's great to hear and certainly looking forward to the results later this year. And my final question is on the upcoming Phase 2 GBM study. So other than the CMC part, and you're waiting for the FDA meeting as well. So what else does the company need to prepare before you are able to initiate that study?

[I will] give an overview. I know what you're saying actually. So a big part of what we need to do, Sean, is the -- is our work with Medidata in terms of developing the synthetic control arm. That's going to be an important part of the trial, not only in maximizing enrollment and the randomization scheme making it more patient friendly, but also decreasing the cost. So that's -- we've already done a feasibility assessment with them. We have a strong sense that it's feasible. That will be developed here relatively soon and then a lot of that will go into the trial. I think that's what you mean. Other than that, it's really just preparing the meeting package and the protocol synopsis and the statistical analysis plan and so forth. And all of those are in progress.

You have the benefit of the ongoing trial. Sorry, go ahead.

No, that's good to hear. I'm just wondering, just a quick follow-up. Would the company seek to get a special protocol assessment with the FDA for this study?

It's possible. I don't know that we need one, honestly. Norman, do you have any thoughts about that?

That's a great question. And people always look to the FDA. Given our synthetic control arm approach, this being a rare orphan disease, we already have fast track the potential for breakthrough therapy certainly is there. Getting a special protocol assessment, you usually have to go to the FDA. And that actually would probably add time. So we're in very good shape to proceed about as rapidly as possible in drug development, given what we have, given the preliminary efficacy signal, given a very solid control arm that already has precedent at FDA for being accepted in GBM in particular.

So an SPA, I think, would be kind of redundant and would require additional FDA meetings and some interactions and negotiations. We believe by summer, we'll have an agreement third quarter and be able to have sites initiated by the year-end. You're very correct that we have to interact with FDA first, but we're doing it the fastest way possible.

(Operator Instructions) It appears we have no further questions at this time. I will now turn the floor back over to Andrew Sims.

Thanks, Christian. We have a question that was emailed in on the GBM trial. So the question is, it sounds like you're working towards a Phase 2 or registrational trial on GBM towards the end of 2022. What details can you provide about the trial design, including patient numbers?

So the answer is, I can't tell you anything definitively because we haven't talked to the FDA, but I can give you some guidance as to how we're thinking about it. And I think we've got a pretty reasonable level of confidence at this point that we're pretty close. Everything is dependent, of course, on what the FDA says. So in terms of number of patients, as we've said before, we think it's possible to have a successful registrational trial with 100 patients. I think we're going to be between 100 and 200 patients.

We'll know more after we talk to the FDA. Primary endpoint will be overall survival. I think that's clear, and that is above an GBM trials. On a randomization scheme, typically for rare disease, you might see a 2:1 randomization scheme or more typically a one-to-one randomization. One of the benefits of the synthetic control arm is that a randomization scheme where it's like a 3 to -- 2 to 1 perhaps, which has been done before where 3 patients get treated. And 2 patients in the control group come from your synthetic control arm. And then you actually randomize one patient to, you're likely your control arm.

So you get 3 out of 4 patients end up getting treated, which is very good for enrollment and good ethically for these patients. So that would certainly help costs and timing and so forth. So we're kind of hoping it's something more like that, which is something that a synthetic control arm can provide. On a control perspective, I think very likely we'll go to comparison against MD preference, which is essentially a kitchen sink approach. That's what these patients get because there's really no clear standard of care. These patients are in an extreme situation and they aren't good options.

So from a, I guess, a budget perspective, with the synthetic control arm in a lower trial size, we think this trial could be closer to $10 million. We've kind of been previously guiding to maybe closer to $20 million. I would say $15 million is probably a pretty good number and what else. I think in terms of sites, I think probably 10 sites makes most sense, particularly if we're on the lower end of that 100 or so patients that are in the trial. And those really correspond with what we know are world-class sites in terms of convection-enhanced delivery, which is a key part of the therapeutic design.

And then finally, in terms of timing, close to 100 patients, I think this trial could enroll with 10 sites maybe in 12 months if we get a good running start. Just it could take 18 months, but 12 to 18 is reasonable. Depending on the outcome and what the clinical benefit is, I think we're looking at kind of a 12 to 18-month follow-up period. So we're looking at a trial that last 24 to 36 months, hopefully closer to 24 months. So all that to say, this is what we're thinking and kind of giving you ranges, it's going to be dependent on what the FDA says.

Christian, are there any other questions?

No further questions over the phone.

Yes. Let me finish up. Thank you, Christian and Andrew. So just to close, I want to say thank you to everybody that joined us on the call and for those that are listening on the recorded version. Thank you. And on behalf of the Board, I'd just like to thank once again our employees and the broader members of our team, our consultants and so forth, the physicians that we work with and of course, the patients that trust us. Thank you very much for your participation, and have a good evening.

Thank you. This does conclude today's conference call. Please disconnect your line at this time, and have a wonderful day.