Plus Therapeutics - Q1 2024

Executive Summary

• Q1 2024 showed improving operating leverage driven by higher CPRIT grant revenue and lower losses: grant revenue rose to $1.68M vs $0.51M YoY and net loss narrowed to $3.26M (EPS $(0.75)) from $4.81M (EPS $(2.07)) YoY; cash ended at $2.90M, down from $8.55M at 12/31/23 as the company awaited mid-year CPRIT draws.
• Funding visibility improved post-quarter via a $19.25M private placement ($7.25M upfront ≈ 12 months’ incremental runway) plus scheduled CPRIT advances of ~$6.9M in 2024 and ~$1M DoD pediatric funding starting late Q3/Q4; management guided 2024 grant revenue to $6–$7M.
• Clinical momentum: LM Phase 1 single-dose dose-escalation advanced through Cohort 5 (66.1 mCi), with 12 of 18 patients alive as of March; FDA Type C meeting scheduled (June 10) for a multi-dose expansion; GBM Phase 2 continues with encouraging OS signal (13 months reported Nov-2023 vs ~8 months SOC).
• Potential stock catalysts: FDA feedback (LM multi-dose, pediatric IND in 2H24), LM Phase 1 completion and pivotal trial design, GBM Phase 2 data update later in 2024, and CNSide diagnostic commercialization plan (as soon as Q4 2024).

What Went Well and What Went Wrong

• What Went Well

  • Accelerating LM program and clearer regulatory path: “we believe multiple doses of rhenium obisbemeda will be the optimal therapeutic approach” with a Type C FDA meeting scheduled and goal to complete LM Phase 1 enrollment in 2024; 12/18 patients remained alive as of March data cut.
  • Strengthened funding roadmap and runway: $7.25M gross from private placement closed May 9 (part of up to $19.25M), specific CPRIT cash advance timing (~$3.4M late Q2/early Q3 and ~$3.5M late Q4), and ~$1M DoD pediatric grant expected in 2024; CFO guided 2024 grant revenue to $6–$7M.
  • Strategic expansion via CNSide diagnostic assets and management hires; validation of CNSide CSF tumor cell assay implemented as an exploratory endpoint in ReSPECT-LM, with plans for commercial launch as soon as Q4 2024 and a >0.5M tests TAM discussed by management.

• What Went Wrong

  • Cash burn remained significant ahead of CPRIT advances: cash fell to $2.90M at 3/31/24 (from $8.55M at 12/31/23), driven by $(4.51)M operating cash outflows in Q1 despite higher grant revenue.
  • No commercial revenue and continuing losses: Q1 operating loss was $(3.30)M, net loss $(3.26)M (EPS $(0.75)); while improved YoY, sequential improvement is dependent on grant timing and continued cost control.
  • Estimates context unavailable: Wall Street consensus (S&P Global) could not be retrieved for Q1 2024; beat/miss vs expectations cannot be assessed this quarter (see Estimates Context).

Transcript

Operator (participant)

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics' first quarter 2024 results conference 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. Also, 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 quarter 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 H. Hedrick (President anf CFO)

Thank you, Victor. 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 first quarter 2024 financial results. Joining me for the call today are Mr. Andrew Sims, our Chief Financial Officer, and Dr. Norman LaFrance, our Chief Medical Officer. I'll begin the call by reviewing our recent corporate and clinical progress in the first quarter, and then turn the call over to Andrew to review our financials. Dr. LaFrance then will be joining us for Q&A. Let me begin by highlighting some recent corporate updates before discussing our specific therapeutic and diagnostic programs.

So first of all, on May 9th, 2024, we closed a private placement financing for an aggregate proceeds of up to $19.25 million, which consisted of an initial upfront funding of approximately $7.25 million and up to an additional approximately $12 million upon cash exercise of accompanying warrants at the election of the investors. The financing included participation from AIGH Capital Management LLC, with additional participation from healthcare-focused institutional investors and insiders. Second, we received a notice of award for a $3 million grant from the United States Department of Defense Congressionally Directed Medical Research Programs. The award will be used to fund a phase 1-2 trial for pediatric patients with high-grade glioma and ependymoma following IND approval from the FDA.

As a reminder, this grant illustrates our ongoing strategy to use external grant funding to support the initial preclinical and clinical development of new technology or indications, while minimizing the impact to the balance sheet and shareholder dilution. More specifically, our GBM program had just been acquired when we found out that we had a five-year grant funding from the NCI to fund that program through phase 1-2. Second, our LM program received nearly $18 million of funding over three years from CPRIT, and today that strategy continues with this DoD award for pediatric brain cancer therapeutic development. We're going to continue to leverage our novel technology, subject matter, and grant management expertise to drive this strategy forward for the foreseeable future. Finally, to strengthen our team for planning for forthcoming pivotal trials, we added neuro-oncologist, Dr. Andrew Brenner and Dr.

Barbara Blouw to our management team. Dr. Brenner is an MD, PhD, and has been instrumental in developing rhenium obisbemeda and the related clinical strategy. Dr. Blouw is a PhD with extensive experience in clinical operations, CNS tumor biology, biomarker development, and neoplasms of the cerebrospinal fluid. Now, in terms of our clinical programs, I'll begin with updates on our ReSPECT-LM phase 1 dose escalation basket trial for a single administration of rhenium obisbemeda for leptomeningeal metastases. This trial is substantially funded by a 3-year, nearly $18 million product development award from CPRIT. During Q1, we announced the enrollment of the 3 required patients for dosing in cohort 5 at a single radiation dose of 66.1 millicuries. As of the most recent data update in March 2024, 12 of 18 patients dosed remained alive.

Multiple compassionate use doses have now also been made available to clinicians for patient survivors that have exceeded the trial follow-up period and continue to do well. We expect to present updated enrollment and safety data at the SNO ASCO meeting in August 2024 in Denver. Furthermore, investigator and KOL enthusiasm for the trial and the investigational therapy remains high and continues to grow. Recently, we added an additional five sites to the trial that will participate in patient recruitment for both the phase 1 and subsequent follow-on trials. Our goal is to complete enrollment in the phase 1 basket trial for a single dose this year, and then to present the full dataset from all cohorts of the phase 1 trial as they exist at that time at the SNO Annual Meeting in November 2024 in Houston.

In parallel, we are presently in dialogue with the FDA regarding a multi-dose expansion arm of the phase I trial. Ultimately, we believe multiple doses of rhenium obisbemeda will be the optimal therapeutic approach to suppress and potentially cure LM. We will provide an update once the plan is finalized and FDA approval is obtained. Additionally, as we move forward towards a recommended phase II dose of rhenium obisbemeda for LM, we intend to expand our communications with the FDA regarding a pivotal phase 2,3 trial design, which is currently in development with our team and KOL advisors. The initial planned pivotal trial will be focused on LM and metastatic breast cancer, for which we have orphan designation from the FDA. Last week, we hosted an investor call focused on the acquisition of the synergistic LM diagnostic platform called CNSide.

Rather than fully revisiting the details of that call today, I would like to provide the highlights and encourage you to investigate the recording, which can be found on our website, to learn more about this tremendous new opportunity for the company. So here are the key highlights, and I'll begin with the four key points outlining the rationale for the acquisition. First of all, leptomeningeal cancer is a tough diagnosis to make, and the current state-of-the-art diagnostics, which include MRI and cytology, lack diagnostic sensitivity. Second, we developed experience with the CNSide assay in our ReSPECT-LM trial and saw firsthand its value. Additionally, we had the opportunity to engage with multiple KOL physicians who have come to see CNSide assay as a game changer in their practice. Third, autopsy studies indicate LM is likely significantly underdiagnosed.

As such, an enhanced diagnostic such as CNSide means more patients may be able to take advantage of our rhenium therapy for LM. Finally, we recognize that there is a substantial standalone commercial opportunity to develop, commercialize, and then monetize the CNSide technology in the near term. So, based on that rationale and our supporting analysis, we exclusively acquired all essential CNSide-related assets to provide CNSide testing commercially, and this includes three types of tests. First of all, the cancer cell enumeration or CTC, circulating tumor cell, testing, which we call CSF-01. This quantifies adenocarcinoma and melanoma tumor cells in the CSF. Second, we obtained the FISH or fluorescence in situ hybridization testing we call CSF-02, that determines cancer-specific gene expression for therapeutic guidance.

Third, we acquired the next-generation sequencing of cell-free DNA, called CSF-03, that analyzes DNA to identify genetic mutations related to LM. In Q1 2024, prior to the acquisition, we validated and clinically implemented the CSF-01 test into our ReSPECT-LM trial as an exploratory endpoint and is currently in use today. As part of the acquisition, we acquired the ForeSEE clinical trial data, which evaluates CNSide and its clinical utility in addressing therapeutic decision-making in LM. Last week, we disclosed that the trial met its primary endpoint, and a presentation of the full ForeSEE trial data is planned for the August 8-10 SNO ASCO meeting in Denver. Now looking forward in terms of next steps, we will be expanding the availability of the test in our ReSPECT trial to longer time points in conjunction with our planned multiple dosing regime.

We are also finalizing a complete business evaluation, including a reimbursement optimization strategy, with the intention of commercially launching the test as soon as Q4 2024. As discussed in last week's call, we anticipate a total addressable market of over 500,000 tests annually, with the potential for additional growth. We plan to further discuss the commercial opportunity and the plan at a later date. Finally, in parallel, we are talking to potential diagnostic business development partners that have expressed interest in CNSide. Then finally, just a reminder, you can learn more about the CNSide asset or acquisition of that by visiting our website and looking at the related press release and investor call details. Now shift gears and regarding our ReSPECT-GBM trial, evaluating rhenium obisbemeda in patients with recurrent glioblastoma.

We continue to enroll both phase II patients with GBM tumors less than or equal to 20 milliliters, and also phase I patients with GBM tumors that are greater than that. That's in our dose escalation phase I, that's still ongoing and now in cohort 8. As the NIH NCI funding for this trial that I mentioned earlier, which has been the primary financial supporter for the trial, is winding down in 2024, and as we work to finish enrollment in the phase II study, we are able to add new sites that will help speed trial completion and set us up for the phase III study. Besides our Texas sites in Dallas, Houston, and San Antonio, we are now adding 3 new sites to the trial focused on key population centers.

in the upper Midwest, The Ohio State University, in the New York area, North Shore and Lenox Hill Hospitals, which are part of the Northwell Network, and in Florida, AdventHealth. These three sites to enroll in the second half of 2024 and will substantially contribute to a pivotal trial. We have set the goal for ourselves to complete enrollment in 2024 or early 2025, and enrollment timing will be influenced to a significant degree by participation of these new sites. We plan to provide a complete update on the phase 2 data this fall at one of the key neurosurgery or neuro-oncology meetings, and that final meeting designation is to be determined.

As a reminder, the data seen and reviewed to date in the phase 2 trial has been highly, excuse me, highly promising in terms of both safety and efficacy, demonstrating thus far a 13-month overall survival as of November 2023, compared to approximately 8 months for the standard of care, or 63% improvement in OS over standard of care. As I mentioned last quarter, given the safety profile and the unprecedented amount of radiation we can deliver to the CNS using our technology, we believe there's a tremendous potential for improving upon the standard of care in GBM, and also there's a broader opportunity to leapfrog the primary means of radiation delivery for all CNS neoplasms, which is essentially external beam radiation therapy at this point.

We continue to work behind the scenes with existing and potential partners that share our view of this opportunity and want to collaborate to explore the potential in a focused manner. In parallel to our plans to finalize the phase 1 and phase 2 trials, we are also planning our pivotal trial strategy and plan to meet with the FDA later this year to discuss the phase 2 data and align on a pivotal trial design in GBM. Finally, I would like to briefly update you on our pediatric brain cancer program. As I also noted at the beginning of the call, with U.S. Department of Defense funding support, we will be finalizing our IND with the FDA and initiating a phase 1 trial for children with pediatric high-grade glioma and ependymoma.

We anticipate, based on several previous rounds of discussion with the FDA, that we can obtain IND approval in 2024 and perhaps be ready to begin enrollment early next year at our initial site, Lurie Children's Hospital in Chicago. Once the final trial details are agreed upon, we will provide an update on those. Now, with respect to our next generation radioembolic device, called Rhenium-188 or 186 nanoliposome, biodegradable, degradable alginate microsphere or RNL-BAM. As previously mentioned, feedback from the FDA has said BAM will be regulated as a device, not a drug. With that decision in hand, we are now working on the device-related quality system, finalizing the device design requirements and expanding the related IP portfolio, and I anticipate providing more updates when warranted in the near future.

Finally, although our current supply chain is both reliable and sufficient for our near-term needs, as we contemplate pivotal trials beginning in 2025, we are devoting significant energy to build out a supply chain that is ready for both pivotal trials and ultimately commercialization. Two key focus areas are as follows: First is to have a redundant and high-capacity GMP manufacturing capability. So to complement our two existing manufacturers of the final drug product, we are in the process of selecting a third partner that meets GMP standards. This addition, serving as an alternative and redundant source, will ensure that collectively, we can fulfill our demand projections for rhenium obisbemeda through 2028. Second focus area is for additional radiation services capability. So to support the commercial radioisotope supply, a key part of the overall manufacturing process, we will need to expand our network of providers.

We are currently well into that process today, and I'll report more as we are able to update. Moreover, we're enhancing both exclusive and non-exclusive supply agreements for key starting materials and intermediate drug products. We are also refining inventory-based strategies to guarantee reliable drug availability under any foreseeable demand scenario. With that, I'll now turn the call over to our Chief Financial Officer, Andrew Sims, who will review the financials. Andrew?

Andrew Sims (CFO)

Thank you, Marc. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the first quarter ended March 31, 2024. The cash balance was $3 million at March 31, 2024, compared to $8.6 million at December 31, 2023. The company recognized $1.7 million in grant revenue in the first quarter of 2024, compared to $0.5 million in the first quarter of 2023. This represents CPRIT's share of the cost incurred for our rhenium obisbemeda development for the treatment of patients with LM. We expect 2024 grant revenue to be in the range of $6 million-$7 million, i.e., tracking... Total operating loss for the first quarter of 2024 was $3.3 million, compared to $4.8 million in the same period of 2023.

The decrease was primarily due to increased grant revenue. Net loss for the first quarter of 2024 was $0.75 per share, compared to $2.07 per share for the same period the prior year. I would also like to provide a more detailed update on our runway and cash position based on the recently announced private placement, and provide guidance on our grant funding for the remainder of 2024. There are two additional sources of cash that Plus has access to beyond the balance disclosed in cash on hand and liquid investments on our Q1 2024 balance sheet. The first, as we announced last week on May 6, we closed a private placement financing of up to $18 million from new healthcare-focused institutional investors and company insiders.

In addition, it should be noted that, as reported after market on Form 8-K on May 9, this financing was subsequently upsized to $19.25 million, with a total of $7.25 million received at closing. This $7.25 million amount represents approximately 12 months of incremental runway at our current burn. The second source of cash remains our continued funding through now three announced grants. Firstly, the CPRIT grant to support the ReSPECT-LM trial. With respect to expected grant advances from CPRIT in 2024, and to be clear, cash advances from CPRIT, we are on track to receive advances totaling $6.9 million in 2024. $3.4 million will be received in late Q2 or early Q3, and an additional $3.5 million will be received in late Q4.

An additional $3.5 million is then due from CPRIT in 2025. Secondly, as reported on April 22, Plus has received an award recommendation from the United States Department of Defense for $3 million to support the upcoming ReSPECT pediatric brain cancer trial. This funding is expected to commence in late Q3 or early Q4 of 2024, and materially cover the costs of the planned phase 1 trial. Funding is generally received annually in advance and covers a 3-year period, i.e., approximately $1 million will be received under this grant in 2024. Plus also continues to benefit from the NIH grant to support the ReSPECT-GBM phase 1/2 trial. Although expected to be complete in 2024, it currently covers approximately 90% of the overall trial costs.

We also continue to source other non-dilutive sources of grant capital, with a target of applying for at least $10 million per year. We will continue to only report on individual grants when they are awarded. Taken in total, this cash on hand placement financing, warrants are fully exercised, and committed and contractual grant revenue is in excess of $35 million. I'll now turn it back to you, Marc.

Marc H. Hedrick (President anf CFO)

Thank you, Andrew. Before we move on to Q&A, I'll take a moment to provide guidance on anticipated key events and milestones, taking us through the remainder of 2024. First, in terms of presentations, the company will be making. We will attend the Society for Nuclear Medicine and Molecular Imaging annual meeting in June. That's the 8th through the 11th in 2024. We have two accepted abstracts. The first will be the RESPECT-LM trial and an update of initial safety and feasibility through cohorts 1 through 4. We also have a dosimetry presentation on the radiation absorbed dose to the spinal cord using beta emission radiopharmaceuticals and leptomeningeal metastases.

We also intend to attend the SNO, ASCO, or Society for Neuro-Oncology and American Society of Clinical Oncology combined CNS Metastases Conference on August eighth through tenth in 2024. We have 3 anticipated abstracts. The first is the ReSPECT-LM trial and an update of enrollment and safety, as mentioned earlier in the presentation. Also, we will be presenting the full ForeSEE clinical trial dataset on CSF tumor cell detection and data on its ability to help in clinical management of breast cancer and non-small cell lung cancer with patients with leptomeningeal disease. We'll also have a third presentation, which is based on the feasibility and relevance of CNSide, as a scalable platform for disease management for patients with leptomeningeal disease.

Later in the year, we anticipate a comprehensive update on safety and efficacy data from the phase 1 ReSPECT-LM trial at the SNO Annual Meeting in November 2024. Also, later in 2024, we anticipate a meaningful update on the ReSPECT-GBM trial at either a neurosurgical or neurooncology meeting, and that exact meeting is to be determined. In terms of FDA updates, we plan to provide feedback when available on two specific work streams. The first is the ReSPECT-LM Type C meeting for a multi-dose phase 1 dose escalation trial that was granted by the FDA and scheduled for meeting on June 10, 2024. We also anticipate FDA feedback in the second half of 2024 for the ReSPECT-PBC investigational new drug application for pediatric ependymoma and high-grade glioma, with the aim of securing regulatory approval for the trial.

Additionally, we anticipate completing the ReSPECT-LM phase 1 dose escalation trial enrollment this year and determining the maximum tolerated and recommended phase 2 doses. Also, we will report results of the preclinical combination studies of Rhenium-186 obisbemeda with PD-1 and PD-L1 checkpoint inhibitors when that data is completed. We also will contract with a second GMP manufacturing supplier to better support the Rhenium-186 obisbemeda supply for pivotal trials and commercial readiness. And then finally, as Andrew mentioned, we are on track to file at least $10 million in new grant applications in 2024, and we'll announce those upon receipt of the notification of award. So with that, Victor, I'll turn it back over to you, and let's have our Q&A session.

Operator (participant)

Thank you. To ask a question, you need to press star one, one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. Once again, to ask a question, it's star one, one. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question comes from the line of Justin Walsh from JonesTrading. Your line is open.

Justin Walsh (Director of Healthcare Equity Research)

Hi, congrats on the progress. Thanks for taking the questions. I know there's a lot of potential variability here, but I was wondering what your current thoughts are on the overall development timelines for rhenium obisbemeda in GBM versus LM?

Marc H. Hedrick (President anf CFO)

Hey, Justin, it's Marc. So, you know, I think that, actually, the LM development timeline on the whole could actually mean an approved product prior to GBM. And if you'd asked me that, you know, a year or two ago, I might have said something different because we were more advanced in GBM. GBM, as you know, there are multiple competitive trials. It's a much smaller number of patients, and the work required to enroll patients, do the case planning and so forth, is materially different than with LM. Furthermore, if you look at LM, there's no approved products.

We think the likely that the FDA will accept a phase 2, 3 pivotal versus the requirement for a pivotal trial in GBM with overall survival as, as the endpoint. So, so, like, to your question, as it relates to LM, if we sort of say that, is likely, if first to market, if you will, with the rhenium obisbemeda product. As we think about a, a potential phase 2, 3 pivotal single dose trial for breast cancer, beginning in early next year, we're thinking about 100-150 patients, perhaps a year or less to enroll and about a half a year in terms of follow-up. Then you're kind of looking at an approval timeline that's pretty potentially aggressive.

So that's kind of where we are on the whole, and I'll just stop there, and Dr. LaFrance wants to weigh in as well.

Norman D. LaFrance (CMO)

It's a great question, Justin. This is Norman LaFrance. Everything that Mark says, I think, is spot on in terms of explaining how LM is going. I think a key point I want to emphasize is LM has pleasantly surprised us in the phase 1 dose escalation by showing, similar to GBM, an efficacy signal. We really didn't expect to get that kind of data until the phase 2, which Mark had mentioned during his remarks, is fully funded through phase 2. Given our success in the phase 1 dose escalation, the leptomeningeal development is accelerating much more quickly than we anticipated. Of course, we have to go to the FDA in some of the aspects that Mark mentioned in terms of the study design.

But instead of a standalone phase 2, there's a reasonable likelihood that we could discuss with FDA a phase 2/3 pivotal trial, perhaps a phase 2 with a lead into phase 3. I won't go into the details now. But the key point is, in the last year, the LM data results have been so positive that it's really allowed us to really gain on the GBM trial, in addition to the points Mark made. Thanks.

Justin Walsh (Director of Healthcare Equity Research)

Thank you, Doc. Got it. Thanks. Yeah, so my next question, you laid out the, I think pretty well, the different data catalysts and conferences we can expect things. I think you mentioned different cohorts. I'm wondering if there's any color you can provide on kind of expectations on how many additional patients worth of data we can expect at some of these? I know, I'm sure it'll change, but by the time I actually get to the presentation.

Marc H. Hedrick (President anf CFO)

Yeah. So, the way I would guide you, Justin, is, you know, I think, as we've said in the past, with respect to GBM, we're looking for another couple of patients in cohort eight, and we think cohort eight is likely the last cohort, just as a maximum feasible dose.

Justin Walsh (Director of Healthcare Equity Research)

It's phase 1.

Marc H. Hedrick (President anf CFO)

In phase 1, exactly. Then in terms of the phase 2, we said that's a total of 34 patients. You know, we think that, depending on what meeting we're at, we think we'll have a meaningful update. Our goal, as I said, to get all of those patients enrolled this year. I think that'll be a halfway to do that, and adding three additional sites should help us. That should give you an idea of kind of what we're looking at from GBM. From LM, so kind of reverting back to previous guidance. The FDA, we originally did cohorts 1-3, and then we had to go back and do a Part B, which they approved, which was cohorts 4-7.

We think, cohort 7 is probably at the upper end of what is likely to be a safe dose with a single administration. So, as I mentioned today, we've dosed the first 3 patients and or the 3 patients required in cohort 5. So we have a couple of stopping points that are required as part of the trial with the FDA, but I think, I think there's a good chance we'll get through all of those, cohorts, whether we get a DLT in, one of those cohorts or multiple DLTs that, cause us to take that as the recommended phase 2 dose. That sort of still remains to be seen.

I will say that we are at some of the previous cohorts where we've dose escalated. We've done our three patients, not had a safety issue, move forward. We've now gone back and backfilled some of those cohorts to maintain momentum in the trial and because the demand for the product for these patients is so enormous. So we have an obligation, I think, to try to treat as many patients as we can, the FDA will allow. And as I mentioned also, the demand for additional compassionate use doses, as it continues to escalate, and it's actually stretching our resources a bit across the board.

But by going back and enrolling additional cohorts and finishing them out to 6 patients each, it allows to collect additional safety data that we think will be overall beneficial for the overall program. So that's a lot. I'll stop there and see if you have any follow-up.

Justin Walsh (Director of Healthcare Equity Research)

Great. Yeah, no, that's perfect. One more for me. It's pretty obvious that you guys are, I think, quite confident in Rhenium Obisbemeda's potential in GBM and LM. I'm kind of wondering what you believe the key clinical questions are for the asset at this point, of course, beyond having to meet the endpoints in any of your current and upcoming trials?

Marc H. Hedrick (President anf CFO)

You know, that's a great question, and it's probably different for each of those two indications, and you could probably expand that to whether you're treating a solid tumor in the brain or spinal cord. That could be, you know, primary GBM, secondary GBM, or brain mets, or whether you're treating something in the CSF. So as it relates to a solid mass in the brain or spinal cord, ultimately, the key issue is delivery and absorbed dose. And I alluded to this in my remarks, but there is interest amongst partners and potential partners to expand that to other indications in the CNS and compete where EBRT has sort of established anchor. And the key to that is case planning and delivery.

And I think the drug is there developmentally, and we've shown it to be safe, even in large volumes and high radiation doses. The question is: how do we optimize delivery? I think we know how to do that. So now, the question of building out case planning and software tools that can make that happen. So that's how I would characterize that answer as it relates to those indications. The other is CSF, and I think that's a different issue. Delivery is easy. It's a 30-second procedure in the clinic. The question is: what's the dose and what's the dosing profile? How many times can these patients tolerate that? And I don't think that's a mystery. Just like with GBM, I think we've solved the mystery as it relates to case planning.

We just need to implement it. I think we've solved the mystery as to whether the drug stays in the CSF and works. The question is: how do you, to use kind of archaic language that Dr. LaFrance loves, fractionate that? How do we take that, that dose and fractionate it over time, so we can either suppress or cure LM patients? I think that's the key clinical question there. Long answer, sorry.

Justin Walsh (Director of Healthcare Equity Research)

Got it. Yeah. No, no, no problem. Very, very enlightening. Thanks for taking the question.

Marc H. Hedrick (President anf CFO)

Thank you.

Operator (participant)

Thank you. One moment for our next question. Our next question comes from the line of Edward Wu from Ascendiant Capital. Your line is open.

Edward Woo (Equity Research Analyst)

Yeah, congratulations on all the progress. My question specifically is on the, you know, $3 million grant from the U.S. Department of Defense. You said that it's only to cover a phase one in pediatric brain cancer. Is there any opportunities to expand that beyond the phase one funding?

Norman D. LaFrance (CMO)

Hi, this is Norman LaFrance. Good question. And yeah, the short answer is yes. And, we're not at liberty to comment about that, but we are cautiously optimistic there'll be other funding capabilities to either accelerate the phase one beyond a single site, and to get additional funding for our own financing once those preliminary data are known. Given the adult data, and given what we're hearing from the pediatric neuro-oncologists and pediatric neurosurgeons, they're pretty optimistic that we'll get the same platform of benefit that we're seeing in adults and be able to move forward in children. So your point of what's after the phase one in terms of our interest and our potential resource and funding capability, we already have some funding options in play.

I don't mean to be coy, but we're not at liberty to go over those now. But again, we're cautiously, cautiously optimistic, as Marc has mentioned, that those are developing. And we already have a very good platform for the phase one and one of the premier sites in this area. And I would see expanding the number of sites to accelerate completion of phase one and going into a phase two as quickly as possible.

Shawn Li (Equity Research Analyst)

Thanks.

Edward Woo (Equity Research Analyst)

Great. Thanks for taking my questions, and I wish you guys good luck. Thank you.

Norman D. LaFrance (CMO)

Thank you.

Marc H. Hedrick (President anf CFO)

Thanks, Edward.

Operator (participant)

Thank you. One moment for our next question. Our next question will come from the line of Sean Lee from H.C. Wainwright. Your line is open.

Shawn Li (Equity Research Analyst)

Hi, good afternoon, guys, and thanks for taking my questions. My first one is on the upcoming ReSPECT-LM updates. So in the prepared remarks, you mentioned that you are expected to present those updates at quite a few conferences this year. So I was wondering whether there are any qualitative differences to the type of data that you're looking to present. For example, what can we expect to see at a Society for Nuclear Medicine meeting in June versus what we can expect to see at the SNO ASCO meeting in August?

Marc H. Hedrick (President anf CFO)

Hey, Shawn, it's Mark. Yeah, no, good. Thanks for prompting us to clarify that. So, the SNMMI presentation will largely be a representation of data already presented, and the rationale for doing that there is that. Norman reminded me it's one additional cohort. The rationale for that is we've really got three audiences here. We've got the nuclear medicine doctors, we've got the neuro-oncologists, and we've got the neurosurgeons who put the Ommaya reservoirs in. So it's just- it's really important, we think, long term, for getting that data in front of those key constituencies. So it'll allow us to go back and present that data to the Nuc Med physicians.

The SNO ASCO presentation on LM will be an update of enrollment and also on safety, and that'll be as of that time. But we won't get into points of efficacy, cell count, and so forth. SNO will really be, I think, a more definitive presentation. That'll be in November. By that time, you know, I think there's a chance that the phase one will be completely enrolled, and we'll have some more meaningful data to discuss at that point. So that's the data plan. And then I think just as I think I mentioned this in my remarks, also at SNMMI, we'll be talking about the dosimetry data, and that's a group that really appreciates that data, and we'll be able to provide that and get academic feedback at that meeting.

Shawn Li (Equity Research Analyst)

Well, great. That makes it a lot more clear. Thanks. And my second question is on the pediatric study. So, have you decided on the dosing regimen for use for that? Because I know FDA tend to be pretty strict on these in trials.

Norman D. LaFrance (CMO)

Yeah, this is Norman. I'll take that one, Sean. Very appropriate question. We've, and I think Marc made this clear, that we've already had a couple of iterations with FDA, and I think it's fair to say we basically have the protocol approved in principle right down to the dosing. We have it basically broken down, and it's comparable to how we did LM, that we had the initial cohorts with lower. In the pediatric situation, where because ependymomas can be large, we're starting off with small, small tumors, and they'll be both a volume similar to GBM, a volume and administered dose definition that the FDA has accepted. I very clearly state the FDA very much like the idea of our breaking up the pediatric phase one into two segments, the small and medium-sized tumors, reviewing those.

That we did with LM, with the first initial cohorts, to give FDA comfort on what we're seeing, the safety profile, how well it's tolerated. And once they saw that in LM, they were, you know, gangbusters for us, proceeding for cohorts 4 through 7. We took that success and applied it to the pediatric interactions with FDA and got a similar unanimous acceptance of the pediatric trial. And we essentially are waiting, you know, we're waiting for this DoD grant submission and now funding, which we're very appreciative, you know, now send in the formal IND. We didn't wanna get that in and then have it languish, waiting for funding and having to work around that. And FDA knew that, and, and there's some final, I'll call it, housekeeping questions we'll take care of with that.

But I wanna emphasize the dosing, which will be a function, and it's beyond the scope of this call, and we can deal with it offline if you really wanna get into the study design. But it'll be a volume and administered dose escalation, you know, and with very strong collaboration with the Lurie neuro-oncologist and neurosurgical folks. We're very excited about it. Thank you.

Marc H. Hedrick (President anf CFO)

Sean, just, I agree, and I think it'll be scaled to cranial volume and to the uniqueness of those particular kinds of tumors, high-grade glioma, which tends to be very infiltrative, and ependymoma, which needs to be highly recurrent.

Shawn Li (Equity Research Analyst)

I see. Thanks for the clarity on that. That's all the questions I have.

Marc H. Hedrick (President anf CFO)

Great. Thank you.

Operator (participant)

Thank you. I'm not showing any further questions in the queue. I'd like to turn the call back over to Dr. Hedrick for any closing remarks.

Marc H. Hedrick (President anf CFO)

Thank you, everybody, for joining the call. We really appreciate the questions and appreciate your interest in the company. We're thankful to also to our doctors who work with us, to the patients that trust us, and our employees that help make it happen. Look forward to talking to you again soon. Thank you.

Operator (participant)

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.