Plus Therapeutics, Inc. (PSTV) Q3 2022 Earnings Call Transcript

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Plus Therapeutics, Inc. (NASDAQ:PSTV) Q3 2022 Earnings Conference Call October 20, 2022 5:00 PM ET

Corporate Participants

Marc Hedrick – President and Chief Executive Officer

Norman LaFrance – Chief Medical Officer

Andrew Sims – Chief Financial Officer

Conference Call Participants

Justin Walsh – Jones Trading

Edward Woo – Ascendiant

Sean Lee – HC Wainwright

Brandon Carney – B. Riley

Operator

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics Third Quarter 2022 Results Call.

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. Sir, you may begin.

Marc Hedrick

Thank you, Josh. Good afternoon, everyone. And 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 third quarter financial results. Joining me for 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 clinical progress before turning the call over to Andrew to review our financials. And Dr. LaFrance will be joining us for Q&A.

The company made perhaps the most progress ever in a single quarter that I can remember. First in September 2022 results from the company’s Phase 1 ReSPECT trial for recurrent GBM was presented at the European Society for Medical Oncology Meeting in Paris by Dr. Andrew Brenner the trial pi. In summary, 21 patients across six dosing cohorts received 1 to 22 mCi radiation and 0.6 to 8.8 milliliters of volume. The mean tumors treated in those 21 patients was 8.3 milliliters and patients had a mean of 1.7 recurrences and very poor prognostic factors. All recurrent glioma patients had computerized treatment planning and up to four intracranial catheters placed in each patient.

Each patient received a single administration of 186RNL by convection enhanced delivery and whole-body planar SPECT/CT imaging on days one through eight following treatment, assess dosimetry and radiation distribution. Patients were followed for safe radiation delivery and overall survival. The mean absorbed radiation dose to the tumor was 271 Gy with negligible systemic exposure. There were no dose limiting toxicities, and the overall safety profile was favorable.

Patients were stratified by mean absorbed radiation dose to the tumor, those receiving greater than 100 Gy mean therapeutic dose and equals 12 in that group, had a median and mean overall survival of 129.7 and 106.4 weeks respectively with four patients still alive in that group. Patients receiving less than 100 Gy mean absorbed dose, essentially a sub therapeutic dose and was equal to nine in that group had a median and mean overall survival of 22.3 and 24.6 weeks respectively, none of those patients remain alive.

Kaplan-Meier analysis of patients receiving mean absorbed dose greater than 100 Gy or therapeutic dose versus those with less than 100 Gy a non therapeutic dose showed a statistically significant difference in overall survival, favoring those that received a therapeutic dose. The study concluded that a single administration of 186 RNL by convection enhanced delivery in recurrent glioma patients with poor prognosis is feasible, safe and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor.

A recommended Phase 2 dose of 22.3 mCi in 8.8 milliliters was selected for patients with tumors of up to 20 CCs or 20 milliliters in the Phase 2 trial plan for later this year. And I’ll discuss the Phase 2 plan further in a moment.

Also during Q3, we received guidance from two Type C meetings with the FDA on the next steps in our program for the development of our lead investigational drug Rhenium-186 Nanoliposome. The first Type C meeting focused on the company’s Current Good Manufacturing Practice, or cGMP clinical and commercial manufacturing process for 186RNL. The FDA indicated agreement with our proposed application of cGMP guidance for radio therapeutics, small molecule drug products, and liposomal drug products for 186RNL in support of our ongoing and future glioblastoma clinical trials, manufacturing scale up and commercialization.

We expect that this FDA feedback will apply to 186 RNL used in other clinical development programs including leptomeningeal metastases, and pediatric brain cancer.

I’m happy to report that we have now completed all key manufacturing objectives for cGMP 186 RNL production to support ongoing and planned clinical trials in 2022 and beyond. During a separate clinically focused Type C meeting, the FDA and Plus agreed the respect GBM clinical trials should proceed to the planned Phase 2. The key focus areas of ongoing clinical investigation in the recurrent GBM development program will be further dose exploration including both increased dosing i.e., advancing to cohort aid and study of multiple doses and also collecting additional safety and efficacy data to inform the design of the future registrational trial.

In addition, during the meeting, there was agreement than in the planned future registrational trial overall survival should be used as a primary endpoint. The company and the FDA also agreed to hold future meetings to consider the use of external data to augment the control arm in the registrational trial facilitated by our orphan and fast track designations.

Earlier this month, an IND amendment was submitted regarding this plan that sits with the FDA as of today.

The plan Phase 2 trial design will incorporate the following features. The cohort six dose will be used which is also the recommended Phase 2 dose from cohort six as mentioned, which will be 22.3 mCi in 8.8 milliliters of volume. The study will roll up to an additional 31 patients at five planned sites including the current three sites plus an additional two sites which are currently in process of coming online. Subjects will remain on study until disease progression by [Reno] [ph] criteria recognizing of course the potential for pseudo progression that complicates the use of [Reno] [ph] criteria and we’re working on the imaging analysis today to be able to resolve that issue, or potentially a pi decision that’s in the best interest of the patient.

The primary endpoint, as mentioned will be overall survival following single administration. Secondary endpoints will assess the safety, tolerability, objective response rate, partial response, serious treatment emergent adverse events up to three [Technical Difficulty] free survival and progression free survival at six months. We’ll make known the final details pending further feedback from our IND amendment, which is with FDA as mentioned.

I’ll now pivot to discuss our leptomeningeal metastases program. Our team was very honored to learn in the third quarter that we had been awarded a $17.6 million product development research funding award from the Cancer Prevention & Research Institute of Texas, also called CPRIT. This award will cover the majority of the development cost, including funding for up to 150 enrolled patients for our leptomeningeal metastases program over three years.

For those that you aren’t familiar with CPRIT. CPRIT is the second largest global public funder of cancer research in the world after the NIH with $6 billion allocated by the state. And also of note plus a $17.6 million grant award is the largest in the most recent CPRIT review cycle in one of the top 10 largest all time awarded by CPRIT in its history. Besides the asset, the award is a material source of non-dilutive funding that significantly strengthens the company’s balance sheet and extends our expected cash runway. Andrew will provide some greater perspective on that momentarily.

While this is all exciting news, let me just back up a bit and recap our current development plan starting with our Rhenium 186 Nanoliposome development. As I mentioned, the company recently completed key manufacturing objectives for cGMP 186RNL to support ongoing and planned clinical trials in 2022 and beyond, [NP] [ph] drug of sufficient quality and scale to enable the completion of all further clinical investigation, including for ongoing and planned Phase 2 and Phase 3 clinical trials in patients with glioblastoma, leptomeningeal metastases, pediatric brain cancer, and really any conceivable future disease targets.

Having access to cGMP drug is an important milestone as we prepare to transition from early to late stage clinical investigation and commercialization. Relatedly, I’m pleased to announce that the World Health Organization has approved rhenium 186 [bis-BMEDA] [ph] as a generic name for 186RNL. As required this generic name will be used in all future IND and NDA submissions in branding development and related go-to-market planning is currently in process and here to forward we will now use the 186 rhenium, 186 bis-BMEDA name in lieu of the 186RNL research name.

Regarding the GBM program based on the positive safety profile and promising efficacy signals observed thus far it with clear feedback from the FDA. Most importantly, we intend to move into Phase 2 in the U.S. by the end of 2022. And that effort will be funded by us to a significant degree as it has in the past by the U.S. NIH National Cancer Institute’s. Second, pursuant to FDA guidance, we intend to continue the dose escalation to cohort eight and that’s a 16.6 milliliter volume and 41.5 mCi infused dose that’s an approximate 33% increase above volume infused in radiation dosage.

Notably, we recently received the SMB approval to advance to cohort eight from cohort seven. Any further escalations and volume or dosage will be based on observations from cohort eight. But again, the overarching goal here is to dose escalate until we reach dose limiting toxicity, or the maximum practical dose. The ongoing Phase 1 is intended to explore further dose escalation on large tumors as we have yet to observe any dose limiting toxicities. And we also continue to work to further optimize the delivery and dosing approach.

This Week at the 35th annual Congress for the European Association Nuclear Medicine, the company presented data, which indicated that the direct administration of rhenium bis-BMEDA is safe in patients with recurrent GBM, with no dose limiting toxicities in 24 total patients. That’s the total patient set treated thus far. And I refer you to that press release for further information.

So now on to our leptomeningeal metastases or LM development program. That trial is a multicenter Phase 1/2 dose escalation study to determine the maximum tolerated dose, safety and efficacy of 186 rhenium bis-BMEDA. LM is an in stage fatal complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system or leptomeninges. The incidence of LM is growing with better local cancer care, and there are no FDA approved therapies. Standard treatment includes external beam radiation therapy to the affected sites, followed by chemotherapy given either orally, intravenously, or often administered twice weekly directly into the CSF space. In the third quarter of 2022, the company initiated enrollment of cohort 2, that’s a doubling of the dose over cohort 1 and the ReSPECT LM dose escalation trial. We anticipate completing enrollment of cohort 2 by the end of 2022 and the cohort 3 by the end of Q1 2023.

In cohort 1, 186 rhenium bis-BMEDA was successfully delivered without dose limiting toxicities and the independent respect LM DSMB approved the plan to move forward with cohort 2. By the way also at the annual Congress of the European Association of Nuclear Medicine this week, the company presented from the podium data demonstrating that 186 rhenium bis-BMEDA administered through an intraventricular catheter at 6.6 mCi in 5 CCs achieved absorbed dosages of 18.7 to 29 Gy to the ventricles and cranial subarachnoid space, which was well tolerated with no treatment related adverse events greater than grade one.

Additionally, all three patients in the cohort were observed to have prompt and complete 186 rhenium bis-BMEDA made a distribution throughout the CSF that was durable past one week and very well tolerated. All patients showed a decrease in CSF cell count by microfluidic chamber assay after treatment, ranging from a decrease to 45% up to 92%, which was also durable.

Now regarding our development program and pediatric brain cancer, the company is on track to meet its objectives to submit an investigational new drug application in the fourth quarter of 2022, for what will be called the respect PBC Phase 1 dose finding an efficacy study of 186 rhenium bis-BMEDA for pediatric brain tumors, and that will be submitted in conjunction with our lead academic institution hospital of Northwestern University in Chicago.

Finally, regarding our novel in-licensed radio embolic microparticle technology called 188RNL-BAM, we have completed the Technology Transfer phase and key CMC feasibility studies. And we are on track to submit a pre-IND meeting and have that meeting by year-end. With this reservable biomaterial embolic technology coupled with a highly potent radiotherapeutic in this case, 188 rhenium, we can target almost any solid organ tumor in the body using standard interventional radiologic means and leverage the breadth of the human vascular system to selectively reach almost any tumor.

Rhenium 188 Nanoliposome biodegradable alginate microsphere is a next generation fully resorbable technology that solves many of the existing problems with current radio embolic technology that have been in the market for many decades and represents an existing total addressable market of about $1.3 billion. The company will initially focus on developing the BAM technology as a next generation radio embolic therapy for liver cancer.

Liver cancer is a rare disease with an increasing annual incidence globally and a five-year overall survival rate of only about 20%.

So with that summary, I’ll turn the floor over to our Chief Financial Officer, Andrew Sims who will review the financials. Andrew?

Andrew Sims

Thank you, Marc. Good afternoon, everyone.

Please refer to our press release issued earlier today for a summary of our financial results for the 2022 third quarter ended September 30, 2022.

As of September 30, 2022, cash and cash equivalents were 20.3 million compared to 18.4 million as of December 31, 2021. The company believes the combination of current cash committed grant funding, in conjunction with existing discretionary capital sources secures our cash runway through 2025.

Cash used in operations for the nine months ended September 30, 2022 was 10.7 million compared to 7.7 million in the same period for the previous year. The main year-over-year changes between the third quarters of 2022 and 2021 are as follows.

Grant revenue of 73,000 was reported related entirely to CPRIT. Total operating expenses for the third quarter of 2022 were 5.2 million, compared to 3.5 million for the third quarter of 2021. The increase is due primarily to the following. CMC-related activities to develop and produce cGMP quality drug material, as well as expenses associated with the development of the synthetic control arm platform for future clinical trials. These projects and related spend have now been substantially completed, to a lesser extent an increase in legal IP and other general corporate expenses.

Interest expense decreased from 232,000 in the third quarter of 2021 to 173,000 in the third quarter of 2022. This decrease reflects the continued principal pay down that commence in November 2021 on the company’s Oxford debt.

Net loss for the third quarter of 2022 was 5.2 million or $0.19 per share, compared to a net loss of 3.7 million or $0.28 per share for the third quarter of 2021.

I’d also like to take this opportunity to provide an overview of the positive impact on cash and the financial statements of the 17.6 million CPRIT grant to develop the ReSPECT LM indication. As disclosed in the September 22, 2022 press release, this grant covers the three-year period ending August 31, 2025, with the funding tracking the company proposed clinical development plan. The total plan grant for year one is 3.7 million increasing to 6.7 million in year two, and 7.2 million in year three.

Let me walk you through the cash impact of CPRIT and the process to access the 17.6 million. CPRIT initially funds 50% of the first-year budget, which for Plus is just under 1.9 million. The request for this 1.9 million has been submitted, and we expect to receive this funding within the next one to two weeks. Once greater than 90% of this initial 1.9 million is utilized, the next request will be submitted. CPRIT typically takes less than two weeks to advance the requested funds.

The design of the funding is to ensure the company is not out of pocket for grant-related expenses, which will obviously be substantial. Quarterly reports are submitted summarizing payments and development progress during the previous quarter. And CPRIT has the right to conduct an annual audit of expenses. These are typical requirements especially for such substantial levels of funding.

As Plus incurs costs, the costs will be reported in our income statement under the Research and Development line item and the matching CPRIT grant will be reported as revenue in the grant revenue line on the income statement. Note seven on Page 11 of Form 10-Q outlines the accounting of finance for the grant and associated project specific costs.

Now I will turn it back to Marc.

Marc Hedrick

Thanks, Andrew. Before we move to Q&A, let me just summarize key milestones anticipated for the remainder of 2022. We plan to [Technical Difficulty] of 186 rhenium bis-BMEDA for recurrent GBM as mentioned, we plan to present updated data from the ReSPECT GBM trial, the LM trial and forthcoming pediatric brain cancer trials at the Society for Neuro Oncology Annual Meeting and Education Day that will be held in Tampa on November [Technical Difficulty] and one poster presentation there.

We’ll complete Cohort 2 of ReSPECT LM Phase 1/2 dose escalation trial in Q4. We’ll submit an IND for the study of 186 rhenium bis-BMEDA in patients with pediatric brain cancer as mentioned, and we plan to complete key CMC and IND enabling studies for the BAM program and complete a related pre-IND meeting as planned all on track.

At this point, now let me turn it back to Josh for a Q&A session. Josh, let’s have questions if there are any.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question comes from Justin Walsh with Jones Trading. You may proceed.

Justin Walsh

Hi, thanks for taking the questions and congrats on all the progress. My first one, it’s great that we’re seeing decreases in the CSF tumor cell count in the LM patients. But it looks like the cell counts have rebounded and at least some of these patients treated so far. I know that we’re in the early phases of dose escalation here and repeat dosing might be key. But how do you think we should think about interpreting these readouts? Is there a reason to expect some potential benefit from a temporary reduction in the CSF tumor cell count? Or do you think the major takeaway is that were just potentially seeing some anti-tumor effects and we need to wait a little longer for clinically meaningful readouts?

Marc Hedrick

So I’m going to appreciate the question. Let me divide that up. I’m going to take a little bit of it, I’m going to refer to Dr. LaFrance to talk about a recent patient experience. So first of all, one of the great aspects of the LM indication is the ability to check tumor markers, the first of which is the tumor cell count, which we do over time in all these patients. And it’s heartening to see it even the lowest possible dose of what I would consider almost maybe just north of a homeopathic dose we’re seeing decreases a pretty significant magnitude in all patients, every patient had a reduction. So that’s important.

Number two, is that there is a duration of that effect. So it looks like it’s lasting for a month. We know from the dosimetry data that radiation is there for at least a week probably longer, it seems to mirror what we’ve sort of seen in GBM patients. So there’s a duration of effect, there’s a meaningful effect even at a very low dose. Now, the question is that the right tumor marker to look at? And the answer is maybe but we’ve actually working with a principal investigator we have filed — the grants been filed to look at additional tumor markers in evidence of radiation damage and our plan is to look at that with or without the grant. There’s a lot of opportunity here to look at tumor markers in this clinical model.

And then finally, I would just say, we don’t know, at this point what these tumor cell markers actually mean, Dr. LaFrance, I think mentioned in Barcelona in his recent meeting, one of the patients had a pretty significant improvement in clinical symptoms. And that was the one that had the lowest decrease in tumor cell. Maybe you want to comment on that Norman?

Norman LaFrance

Well, I’ll start with then. Thanks, Marc. And I think it’s a great question, by the way. And I’ll start with the last patient, Marc just alluded to. One caveat that Marc didn’t mentioned is, this patient was [indiscernible] chemotherapy. So in fact, his cell counts were much higher, and our continued therapy and he didn’t tolerate that chemotherapy, he came off of it. But we maintained that benefit, but more importantly, this unfortunate patient was wheelchair bound. Quite had lots of pain other LM neurological manifestations, unfortunate manifestations. And after the therapy within a few days, his doctor who is PI at the particular site, reported the patient was out of the wheelchair, walking, albeit with some assistance, but minimal assistance, and his pain was significantly decreased.

And your point about well, the duration of the benefit, I want to really emphasize Marc’s point that were at the absolute lowest dose. We will continue the other cohorts, already in cohort 2, and doubling it, we will double again in cohort 3. So it’s really crucial to see these next cohorts and we’ll have a fourfold range of doses, that will give us a pretty good idea. The ultimate registrational trial, which we don’t know how that will look, we need obviously, this dose escalation trial may be an overall survival, there may be another surrogate endpoint depends on FDA discussions. And you raise a point that we’ve already talked about internally. The best way for this LM is — as devastating complication, and it may make more sense to have multiple doses to make it a controllable, devastating complication because these really impact these patients’ quality of life. They get this leptomeningeal complication. And even though there’s some chemotherapy that works, they will discontinue it just because of the tolerability. So multiple doses make sense. And that will be one of our analyses.

Justin Walsh

Thank you. You got it. Thanks. Couple more questions, if that’s all right, so sticking on the trial design. I believe that the ReSPECT LM trial is enrolling LM patients with any primary tumor type. I’m wondering if you think that it’s possible that 186 RNL could receive a broad LM label upon potential approval, or do you think primary tumor type will play an important role and maybe limit the breadth of the label down the line?

Marc Hedrick

Good question. As you probably know, FDA almost always wants a disease specific indication. And by the way, although all solid tumors have the potential for leptomeningeal complications, breast and lung, by far are the most common etiologies. Based on that and what we know now we will certainly drive those which will represent probably the most significant commercial application.

We will discuss with FDA, depending on the findings and these first patients will be all comers and we can show with other tumor types, that there potentially is a benefit. We’ll have that conversation with FDA, but it may make regulatory sense, may be regulatorily required that we be disease specific. And we’ve already selected those that are the highest incidence contributors. But there’s other grant capabilities we have for further funding. I like your idea of a broad indication, but we’re the most highly regulated industry on the planet and FDA has their criteria and I repeat myself it’s usually disease specific.

Justin Walsh

Got it. Thanks. And one more for me. I’m just wondering if you can provide any color on what we might expect to see at the SNOA conference. Obviously, there isn’t a lot of time between SNOA and the EAMM conference. So just wondering if you think that maybe we’ll see one or two more patients or just what we can kind of look forward to you there.

Marc Hedrick

Yes. I mean, I wouldn’t expect transformational news. I think the goal here will be to provide incremental news. And I think, to see kind of you can understand the rationale behind it is, we’re very much in the marketing phase, we’re going from a sleepy academic study, to try to going into Phase 2 in GBM, and trying to accelerate enrollment in LM. So part of what we’re trying to do here is get the word out to the neuro oncology community, where we’ll have an investigator dinner. We will bring in new sites into these trials very soon, both the GBM trial and the LM trial, as well as a pediatric brain cancer trial. We will have an opportunity to talk with them one on one, and to go into detail on the data.

So there are multiple reasons to present at a meeting like this. And I think this is less about presenting, significant changes in the data, will be incremental data, but to be able to really get the word out to the community. And I think, thus far, the community’s been very accepting, but we’ve got to go through the work to get that news out. And Dr. LaFrance, would you like to add anything?

Norman LaFrance

You’re right. The timing between the meeting is close. Of course, the likelihood of a few more patients is there. And we’ll share that. Importantly, the data we’ve had is remarkably consistent both and the GBM as we get to these higher efficacious dose levels. And what’s remarkable for these earliest doses in LM, every patient has behaved the same way. They’ve had decreases in CSF tumor counts, and their distribution and the durability of distribution and their tolerability have all been right on target and exactly the same. So usually, you’ll see a little more variability, but one of the strengths of radiopharmaceuticals. Once you have some of this proof, and preliminary data there’s — and particularly the way we’re giving it, we don’t expect, we expect more of the same of course we got to develop that data but few more patients but we already have a very good signal.

Justin Walsh

Got it. Looking forward to it regardless. Thanks for taking all the questions.

Marc Hedrick

Thanks, Justin.

Norman LaFrance

Thank you.

Operator

Thank you. One moment for questions. Our next question comes from Edward Woo with Ascendiant. You may proceed.

Edward Woo

Yes. Thank you for taking my question. I just want a clarifying question, you mentioned that with the grant and your current source of cash, you have enough cash to last through to 2025. Does that include all three clinical trials costs?

Andrew Sims

Ed thanks. Thanks, Ed, appreciate the question. So the short answer is, yes, it does. I’m still pinching myself from the kind of recovering from the announcement of the CPRIT grant, which is obviously kind of transformational for the company. So we’re in a position today where the lead indication GBM by the NIH. Our second indication for leptomeningeal metastases Phase 2 for up to [Technical Difficulty]. Then, the third indication pediatric brain cancer, we expect a fairly slow enrollment for that typically, kind of six to ten patients per year at most.

And I think what I would add is on that, we do not yet have funding or grant funding for that indication. But I think as Marc and I have said in previous earnings calls, that the management team is focused on looking for non-dilutive funding sources and given the success that we’ve had, we will continue that approach and we take that very seriously so.

Edward Woo

Great. Well, definitely congratulations for all the guys that grant is definitely a game changer, to prevent investor from getting too excited or whatnot. But what are the opportunities and other grants that are out there? Are there other stuff? Or is this pretty much the main thing that you guys are focused on? Are there other grants and opportunities or stuff like that?

Marc Hedrick

Yes, there are Ed. Its Marc. So kind of look at it and we have got two axis, one axis is to work with our academic collaborators, to develop grants to study, maybe not specifically to fund clinical research, but also potentially to fund side projects. And we’re working on one specifically as it relates to looking at novel biomarkers in the LM trial, so that would be kind of one area of pursuit. Another area of pursuit is frankly CPRIT and one of the reasons, we decided to move the company to Texas is, we felt like there was a real opportunity there to leverage an awful lot of state support for cancer funding and fortunately we were able to land a nice amount of support early on. We know one company that has three CPRIT grants. So now that I think we’ve cracked the code on that I think we have ability to go back and get more.

Furthermore, I think there are some opportunities corporately beyond CPRIT in terms of NIH, Department of Energy, these are radiopharmaceuticals and nuclear energy. So there are some opportunities there. So that becomes an area of significant interest. And we’ve actually just brought on a real superstar, Dr. Melissa Moore, who is director of Clinical Operations, but she has a PhD from UCLA Molecular Imaging and knows the space very well. So that brings an added dimension to the team.

Edward Woo

Great. Well, congratulations and wish you guys good luck. Thank you.

Andrew Sims

Thanks, Ed.

Operator

Thank you. One moment for questions. Our next question comes from Sean Lee with HC Wainwright. You may proceed.

Sean Lee

Good afternoon, guys and congrats on all the progress. My first question is on the repeat dosing like that’s something that you’ve been mentioning for the last quarter. So I was wondering whether that’s something that you look to try in the upcoming Phase 2 study or is it going to be a separate cohort in the current Phase 1 study? Or is it, do you plan to start another — a new study just for the repeat dosing?

Marc Hedrick

Hi, Sean thanks. It’ll be a separate study, the protocol has been approved by the FDA. As you can imagine for repeat dosing, it’s based on recurrence and so with a relatively small number of patients that have received the treatment so far and this being relatively recent development that’ll, it’ll be sporadic. But part of the rationale here is to explore safety of multiple doses and get the FDA comfortable with that.

The other way to look at that is, are there instances where maybe there are some areas of the tumor that we don’t cover for whatever reason, for example if the tumor has a very unique or difficult morphology it may be difficult to address it with three or even four catheters or as we get to bigger tumors the morphology and the size of the tumor such driving delivery efficiency. So having a protocol in place that allows us to potentially go back and treat a patient that we that are dosimetry evaluation postoperatively clearly shows that there’s [anitaus] [ph] for potential recurrence that we want to treat that.

So I think I’ve mentioned in previous call this idea though of getting really long-term survivors here as possible but it’s likely because of the peskiness of eradication of all the malignant cells is so difficult that we might have to provide some sort of re-treatment strategy either two or three years later, when the a well-treated tumor actually recurs or maybe early in the post-operative phase after single administration where maybe the tumor was so difficult we just couldn’t cover the whole thing reliably. So that’s the approach but that’ll be separate to the Phase 2. The Phase 2 data is strong enough to support [Technical Difficulty] moving that forward as a single administration trial for small to medium sized tumors, and can — we think can succeed on its own as a single administration.

Sean Lee

I see. Thanks for the clarification. With regards to the LM study, in the summation [indiscernible] it’s likely going to favor a more — primary to a specific indication, is there any one that you are leaning towards at this point?

Norman LaFrance

Just to be clear, is that in the LM indication you’re speaking about?

Sean Lee

Yes.

Norman LaFrance

Great question. And yes, and for LM, the most prominent demographic contributors are breast and lung right behind them are GI some head and neck and another area that would be potentially of great interest would be melanoma and we all know those melanomas increased all the way. But for focus and the way we have separate funding, so we already have funding in place for the two biggest contributors to leptomeningeal metastases.

MarcHedrick

I think maybe if I could just add the way the current ideas is written and we plan to continue this, it would be that we’ll have all comers to the first nine patients and then after nine patients will be restricting down to breast and lung.

Norman LaFrance

Correct.

Sean Lee

Great. That’s all I have. Thanks for answering my questions.

Marc Hedrick

Thank you, Sean.

Operator

Thank you. [Operator Instructions]. Our next question comes from Yuan Zhi with B. Riley. You may proceed.

Brandon Carney

Hi. This is Brandon on for Yuan. So you mentioned earlier about the GBM study with the large or complex morphology. We were wondering what percentage of patients you see to have those like very large tumors or the morphology that might be too complex to dress with a single dose?

NormanLaFrance

Thanks for the question. Our current Phase 2 will proceed at the doses Marc mentioned we’re putting a conservative volume limit at 20 cubic centimeters. You’d probably get a little bit more tumor volume with that of our data showing, that’s about two-thirds or three quarters of all the glioblastoma presentations and that’s a conservative number.

So I would then break down the answer for complex morphology you’d think of nice spherical tumors how they present many of them do or ellipsoid or whatever once in a while you get funnier shapes those are the ones, that’s a small percentage almost single-digit percentages that look funky and different. But even the regular tumors might benefit from additional administrations and Marc went over the basic example of there’s two options, one is our re-treatment on recurrence which is already approved for those patients who might qualify. And the second would be a more forward-looking study where we’ll have a multiple dose paradigm based on tumor coverage. So we have most of the tumors already covered and that’s why we’re continuing dose escalation to get those last 25% or 30%.

Brandon Carney

Thanks. That’s helpful. And then, regarding the LM study, I think you mentioned the potential for repeat dosing that earlier. Were just wondering if you would continue the single dose escalation beyond the cohort 3 before attempting multi dosing? Or if you would be able to do those simultaneously?

Norman LaFrance

Hey, Brandon, good question. The agreement with the FDA was that we would do nine patients with dose escalate twice through three cohorts doubling each time, single administration, as you mentioned, and then go back to the agency. So the plan is to do that, once that cohort 3 is completed. My view, and that’s subject to agency approval would be that we would continue single dose escalation until we get to dose limiting toxicity. I think there’s a good chance. We’re going to see something similar to what we’re seeing in GBM that we can get to super normal dosages without significant toxicity. So that’s based on the nature of the rhenium, how it works, its dose rate and density and the anatomy of the CSF space so that you don’t have the dose length of rhenium is only about two millimeters. So your penetration is going to be pretty small. So you’re really going to coat the CSF space and minimize damage to the white matter.

So I think the plan would be continued dose escalate to DLTs and then add a multiple dose treatment. As you may know, some products that are in investigation that are sort of similar nature, include multi dosing paradigms up to four doses in those patients. One can envision perhaps maybe titrating dosing to cell counts. That’s one of the benefits of having biomarkers that we hopefully will show that there’s something we could use to titrate dosing. That’s kind of how I’m looking at it, but that will be subject to the data and feedback from the FDA.

Brandon Carney

Thanks. That’s helpful. So the cell count thing that you just mentioned. Does that mean you think that it’s possible that the cadence of the multiple dosing would be on a per patient basis rather than as a set cadence for all patients?

Marc Hedrick

Yes. Norman mentioned the patient prior to have pretty significant symptomatic improvement and not much of a cell count but they’d had a much higher cell count I think part of that would have received some other therapy but didn’t tolerate it. So I think you’re ultimately as a doctor, speaking as a doctor, you’re ultimately going to go on clinical symptomatology. But if you’ve got a patient that is asymptomatic and has zero, a cell count of zero, maybe from a previous treatment or two, I think you’d be willing to retreat them. But if you have a patient, whose symptoms have worsened, and their cell counts going up, that might be a trigger to retreat them.

So I don’t think it’ll be a simplistic model just using cell count alone. It’ll take clinical factors in that but it’s great to have more data than right now imaging is a poor measure of this extent of disease. These patients have debilitating neurologic symptoms, they survive four to six weeks and treat it. So I think we’ll use, well adding additional diagnostic to determine dosing cadence is going to be important going forward and making a big impact in these patients.

Brandon Carney

Okay. Well, thanks for taking our questions. And congratulations on a very productive quarter.

Marc Hedrick

Thanks a lot, Brandon. Appreciate it.

Thank you. And I’m not showing any further questions at this time. I would now like to turn the call back over to Marc Hedrick, for any further remarks.

Marc Hedrick

Thank you, Josh. Just to close, I want to as usual, thank everybody that joined us on the call today, we’re appreciative of your interest in the company and what we’re doing. I also want to make sure to remember our employees, the physicians and scientists we work with on a daily basis. And of course, the patients who enter into these trials and trust us to deliver to look forward to updating everyone as we move forward and thank all of our stockholders also for their continued support and confidence. Back to you, Josh.

Operator

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



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