Plus Therapeutics Q2 2024 Earnings Report

Plus Therapeutics EPS Results

• Actual EPS: -$17.75
• Consensus EPS: N/A
• Beat/Miss: N/A
• One Year Ago EPS: N/A

Plus Therapeutics Revenue Results

• Actual Revenue: $1.28 million
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Plus Therapeutics Announcement Details

• Quarter: Q2 2024
• Date: 8/14/2024
• Time: N/A
• Conference Call Date: Wednesday, August 14, 2024
• Conference Call Time: 5:00PM ET

Plus Therapeutics (NASDAQ:PSTV) is a clinical‐stage biopharmaceutical company specializing in the development of targeted radiotherapeutics for oncology. Its platform technologies leverage nanoliposomes and microspheres to deliver therapeutic radioisotopes directly to tumor sites. The company’s lead candidate, 90Y-HP-DO3A, is in Phase 2 development for recurrent high-grade gliomas, while its rhenium-based nanoliposome program is under investigation for diffuse intrinsic pontine glioma and brain metastases.

The pipeline also includes investigational treatments for bone metastases, malignant pleural effusions and other hard-to-treat solid tumors. Plus Therapeutics has secured orphan drug and rare pediatric disease designations for select compounds, reflecting its focus on addressing unmet needs in both adult and pediatric oncology. Clinical studies are conducted in collaboration with academic medical centers and contract research organizations across North America.

Headquartered in Austin, Texas, Plus Therapeutics is led by an executive team with extensive experience in radiopharmaceuticals and oncology drug development. The company maintains research, manufacturing and administrative operations in the United States and continues to expand strategic partnerships to advance its targeted radiotherapeutic portfolio.

Plus Therapeutics Q2 2024 Earnings Call Transcript

Key Takeaways

• RESPECT LM trial through Cohort 4 (N=16) showed no dose-limiting toxicities, a high therapeutic window and a median overall survival of 12 months versus the 2–6 month standard of care.
• 4C diagnostic trial of CInsight met its primary endpoint by influencing treatment decisions in over 90% of cases, with an 80% tumor cell detection rate versus 29% for cytology and actionable mutations identified in 24% of decisions.
• Plus ended Q2 with $8.4 million in cash and investments, reported a $6.2 million net loss for H1 2024, and raised $7.25 million at closing of a $19.25 million private placement plus potential $12 million from warrant exercises and $10 million in upcoming grants.
• The company expects IND approval for a multi-dose LM trial, CLIA certification for CInsight and initiation of a pediatric brain cancer trial in late 2024, with detailed updates at SNO 2024 in November.
• RESPECT GBM study continues enrollment with three new convection-enhanced delivery sites, aiming to complete enrollment by early 2025 and present Phase 1/2 data at the Congress for Neurological Surgeons this fall.

Presentation

[Operator]

Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics' second quarter 2024 results conference call. Before we begin, we want to advise you that over the course of the call, including any 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.

[Operator]

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 and CEO at Plus Therapeutics]

Thank you, Cherie, and 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 second quarter 2024 financial results. Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and corporate progress in the second quarter, then turn the call over to Andrew to review our financials, and then we'll both come back on for Q&A. So let me begin with updates from the 2024 Society for Neuro-Oncology and American Society of Clinical Oncology CNS Metastases Conference, which met last week in Denver. At SNO/ASCO, Plus was quite busy.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

We had 4 presentations, sponsored a symposium on novel emerging diagnostics and therapeutics for leptomeningeal metastases, and participated in a panel discussion on the opportunity for emerging therapies for brain metastases alongside senior executives from Novartis and Pfizer. Two of our 4 presentations warrant highlighting on our call this afternoon, and the full data from those presentations and from the symposium will be available soon on our website. First of all, Dr. Andrew Brenner, the ReSPECT-LM trial principal investigator, presented an interim update on the trial through cohort 4, and that's N=16 patients. This is the most significant update that we provided since the SNO 2023 presentation. His presentation showed that through cohort 4, which is an administered dose of 44 millicuries, rhenium obisbemeda was safe and well-tolerated, with no dose-limiting toxicities, and the maximum tolerated dose had not been reached.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Furthermore, supporting the relative safety of the drug thus far, the PK data demonstrated a high therapeutic window. Specifically, the mean absorbed radiation dose to the ventricles and cranial subarachnoid space was approximately 160 gray, compared to only about one gray to the spleen. Also, a linear increase in absorbed dose to the regions of interest, specifically the cranial subarachnoid space and cerebrospinal fluid, was noted from cohort 1 to cohort 4 to increase, but there was no increase noted in the spleen, which was the critical organ. In terms of response data, circulating tumor cell data was not available through cohort. Temporarily unavailable at that time, but it's now available, and we are back up and using the test currently in cohort 5.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

But recall that we observed a mean 53% reduction in CTCs, circulating tumor cells, in the CSF for the first three treated cohorts. That was observed out to 28 days post-treatment, but the CTC number came back up by 56 days post-treatment. Additional and significant response data through cohort five is currently being reviewed and will be presented in detail at SNO in November, and I'll talk more about that in a moment. In terms of the median overall survival signal, again, with 16 evaluable patients through cohort four, median overall survival was 12 months, with half the cohort, cohorts, that's eight out of the 16 treated patients, remaining alive at the time of analysis. This is an increase from that, that was reported after cohort three last November, which showed a median overall survival of 10 months.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

To put that data in perspective, LM is a devastating disease, I think, as most of you know, from both the morbidity and mortality perspective, with typical survival rates ranging from 2-6 months after diagnosis, depending on primary tumor type. So this emerging efficacy signal, though early, is very encouraging vis-a-vis the standard of care. There was also a second presentation at SNO/ASCO by Dr. Priya Kumthekar, who reported the top-line clinical results from our FORESEE trial. FORESEE evaluated the clinical utility of CNSide, our newly acquired novel CNS diagnostic, on leptomeningeal metastases treatment decision-making by physicians in 40 patients. The trial used a well-described trial design that's used commonly in the diagnostic space. Specifically, she reported that FORESEE met its primary endpoint, with CNSide influencing treatment decisions in over 90% of clinical decisions.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

That's 50 clinical decision points evaluated, and that substantially exceeded the 20% level, which was the target for the primary endpoint to show effectiveness. Moreover, the study also showed that CNSide helped identify actionable mutations in the CSF, such as HER2 amplification, that influenced 24% of therapeutic selection decisions. That's 14 out of 55 clinical decision points evaluated. Importantly, and related to the current state-of-the-art diagnostically that's found in major hospitals around the country, CNSide demonstrated more than twice the sensitivity in detecting tumor cells in a CSF compared to what is now the gold standard, which is cytology. Specifically, it showed a detection rate of tumor cells of 80% versus 29% for cytology. Also important, CNSide exhibited a very high specificity in that no tumor cells were detected in patients without leptomeningeal metastases.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

We were pleased to see this data and present it formally, and these FORESEE results highlight and validate our previous high conviction that CNSide, as a diagnostic and therapeutic selection and diagnostic, therapeutic monitoring tool, fulfills a critical clinical need in brain metastases that now has been shown to improve patient management and we believe will lead to better patient outcomes in the near future. Finally, in addition to our presentations at SNO/ASCO, we also reported important data at the 2024 Society for Nuclear Medicine and Molecular Imaging, known as SNMMI Annual Meeting in June 2024.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

The reported study used dosimetry data from the ReSPECT-LM clinical trial to evaluate the safety and potential for spinal cord toxicity of beta emitters or beta emission radioisotopes in the related physics, and found that lower beta energy radionuclides, such as rhenium-186, largely spare the spinal cord versus other beta radionuclides that we studied. These findings further support the thesis that rhenium-186 is an ideal radionuclide for CNS cancers, hitting the therapeutic window, delivering high therapeutic doses to the region of interest while minimizing toxicity. Now, kind of moving on, in terms of our leptomeningeal program, broadly speaking, first of all, therapeutically, the current Phase 1 single administration ReSPECT-LM dose escalation trial will continue dosing until the next DSMB meeting, and at that time, we will determine if progressing to cohort six is advisable.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

But thus far, as mentioned, a maximum tolerated dose has not been reached, despite delivering up to a maximum of 66 millicuries to the CSF. In terms of upcoming data releases, a definitive trial update is planned for Society for Neuro-Oncology 2024, that will be held in Houston this November. To date, we have dosed a total of 25 patients and also treated a subset of patients with multiple doses of rhenium obisbemeda under compassionate use, and those patients have done really well. Also, the company has filed a new protocol under its open FDA IND to treat individual patients with a multiple dosing regime. This submission follows a positive FDA Type C meeting in Q2. Once formally approved with final agreement with the FDA, the company will share the details of that trial protocol.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

That trial is anticipated to begin enrolling later in 2024 at the current seven trial sites, with a number of new sites to be added in the interim. The leptomeningeal program continues to be significantly supported by an approximately $18 million product development award from CPRIT, that covers approximately two-thirds of programmatic expenditures. Also, the company continues to be involved in active dialogue with CPRIT regarding program advancement and are actively seeking expanded ways to work with CPRIT that are mutually advantageous. In terms of our diagnostic LM program, we are in the process of expanding our CNSide diagnostic capabilities at our facility in Houston, Texas, in specific, targeted, but strategic ways. First of all, we hired Dr.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Greg Fuller, former chief of neuropathology at MD Anderson Cancer Center in Houston and an LM expert, to be the full-time medical director of the CNSide lab and oversee lab operations and also help support our LM therapeutic objectives. We have also improved the lab quality assurance systems and our capabilities to steadily increase testing capabilities as anticipated for growing research use, both from Plus's growing trial number in LM, but also other trials that have contacted us with similar interest. In addition, we have applied for CLIA certification for CNSide as a laboratory developed test, and approval under CLIA is anticipated later in 2024. We anticipate providing further business updates on the CNSide diagnostic program later this year as developments warrant. Now I'd like to shift gears to our ReSPECT-GBM trial.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

As most of you know, this trial evaluates a single dose of rhenium obisbemeda in patients with recurrent glioblastoma and is funded mostly through the NIH. We continue to enroll both Phase 2 patients with recurrent GBM, and that's for tumors that are less than or equal to 20 cc's, and also enrolling patients in our Phase 1, now at cohort 8, for patients with larger tumors. We anticipate 3 new active GBM convection enhanced delivery sites will be enrolling soon, and these should be able to transition to pivotal trial sites when the time warrants. Those are The Ohio State University, providing us a site in the upper Midwest and North Shore University Hospital, part of the Northwell Lenox Hill network in the Greater New York region. We are also evaluating other additional sites with the intention of adding at least one site in the greater Southern California region.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

These sites, specifically OSU and North Shore University Hospital, Lenox Hill Hospital, are on track to enroll patients in 2024. Additional sites beyond those mentioned are also being investigated for activation to support a potential pivotal trial. We are working to complete enrollment by the end of 2024, but more likely to wind up completing enrollment in the first half of 2025. A faster timeline will be influenced to a significant degree by participation of these new sites. Our plan is to provide a substantial update on the Phase 1 and Phase 2 data this fall at the CNS, or Congress of Neurological Surgeons annual meeting, which is in late September, early October, in Houston, Texas. This will be our first time to be on the podium presenting this data to the neurosurgical community.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

In addition, I'd like to briefly update you on our pediatric brain cancer program. We've previously announced that we received a U.S. Department of Defense award for $3 million to substantially support the Phase 1 trial for children with pediatric brain cancer, specifically pediatric high-grade glioma and ependymoma. That award is in an administrative phase and is anticipated to begin funding this September 2024. We are also on track to obtain IND approval for this trial, and Lurie Children's Hospital will be the initial clinical trial site. Finally, we are making good progress behind the scenes on a number of important business items, specifically building in redundancy and commercial readiness in our supply chain and enhancing our drug delivery capabilities, and we plan to make material public updates on those in the near future.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

With that, I'll now turn the call over to our Chief Financial Officer, Mr. Andrew Sims, who will review the financials. Andrew?

[Andrew Sims, CFO at Plus Therapeutics]

Thank you, Marc. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter ended June 30, 2024. The cash and investments balance was $8.4 million at June 30, 2024, compared to $8.6 million at December 31, 2023. The company recognized $2.9 million in grant revenue in the first half of 2024, compared to $2.3 million in the same period of 2023. This represents CPRIT's share of the costs 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. Total operating loss for the first half of 2024 was $7 million, compared to $6.2 million in the same period of 2023.

[Andrew Sims, CFO at Plus Therapeutics]

The increase is primarily due to increased spend related to the ReSPECT-LM trial. Net loss for the first half of 2024 was $6.2 million, or $1.15 per share, to $6.3 million, or $2.06 per share, for the same period the prior year. An update on our runway and cash position and provide guidance on our grant funding for the remainder of 2024. There are two additional sources of cash to which Plus has access beyond the balance disclosed in cash on hand and liquid investments on our Q2 2024 balance sheet. First, and as a reminder, we announced in May that we closed a private placement financing of up to $19.25 million from new healthcare-focused institutional investors and company insiders, with a total of $7.25 million received at closing.

[Andrew Sims, CFO at Plus Therapeutics]

In addition, there are up to $12 million of cash on exercise of the 1- and 5-year warrants. As a side note, at June 30, 2024, the warrants issued as part of this private placement were recorded as a liability on the balance sheet. As outlined in the subsequent events, footnote 14, the warrant form was amended, eliminating the liability, and henceforth, these warrants will be accounted for under the equity accounting method. The second source of cash remains our anticipated ongoing funding through now three awarded grants. First, the CPRIT grant to support the ReSPECT-LM trial. As reported, we received the first of two expected amounts from CPRIT in 2024, the first in Q2 of $3.3 million. We remain on track to receive the next advance from CPRIT of $3.7 million in mid- to late Q4 2024.

[Andrew Sims, CFO at Plus Therapeutics]

An additional $3.7 million is expected from CPRIT in 2025. Second, as reported on April 22, Plus has received an award recommendation from U.S. Department of Defense for $3 million to support the upcoming ReSPECT pediatric brain cancer trial. This funding is expected to commence in September 2024 and materially cover the cost of the planned Phase 1 trial. Funding is received annually in advance and covers a 3-year period, i.e., approximately $1 million will be received under this grant in 2024. Third, 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.

[Andrew Sims, CFO at Plus Therapeutics]

We also continue to source other non-dilutive sources of grant capital and have applied for approximately $13 million in additional grant funding year to date. We will continue to only report on individual grants when they are awarded. In summary, this provides incremental access to cash of $22 million, $10 million from CPRIT and DoD, and $12 million from the exercise of A and B warrants from the May private placement. Now I'll turn it back to you, Marc.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Great. Thanks a lot, Andrew. Before we move to Q&A, just let me take a moment to provide some specific guidance for key events and milestones that we're looking towards through the remainder of 2024. As mentioned during the Congress of Neurological Surgeons, CNS, and that's in late September, early October, Dr. John Floyd, who's the chief of neurosurgery at UT Health Science Center in San Antonio, will be presenting an update on the current GBM Phase 1 and Phase 2 trial and most recent results. At the Society for Neuro-Oncology Annual Conference, which will be held in Houston, November 22 through 26 of this year, we'll have three presentations. The first is a substantial update, as I mentioned earlier, on the ReSPECT-LM trial. In addition, we have two CNSide diagnostic abstracts.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

The first is entitled CSF Tumor Cell Detection, Quantification and Biomarker Assessment, and how it helps in the clinical management of breast cancer and non-small cell lung cancer in patients with leptomeningeal disease. The second, which actually deals with a very important emerging issue of genetic drift in LM patients. That is where patients have a certain genetic component to their cancer that flips from their primary tumor to a metastases, for example, in the CSF. And the title of that is The Oncogenic Flip in Patients with Leptomeningeal Metastases, specifically the longitudinal detection in cerebrospinal fluid tumor cell counts, and what it reveals in terms of implications for the differential treatment of the LMD tumor. And so all three of those will be on again for SNO at the main in the November timeframe this year.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

We also anticipate FDA approval on the ReSPECT-LM Phase 1 multiple dose trial. So the IND for the Phase 1/2 study of rhenium obisbemeda for pediatric ependymoma and high-grade glioma patients is anticipated also, later this year. So with, with those, Cherie, I'll turn it back over to you, and we can have our Q&A session.

[Operator]

Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, press star one one again. One moment while we compile the Q&A roster. Our first question will come from the line of Justin Walsh with JonesTrading. Your line is open.

[Justin Walsh, Director at JonesTrading]

Hi, thanks for taking the question. I was wondering if you could provide some more context around the types of treatment decisions that are likely to be informed by CNSide. Obviously, therapy selection is one, but the 24% that informs therapy selection is lower than the 90% total decisions that were impacted.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Yeah, that's a good question, Justin. So, one of the key decisions is, a, does the patient have the disease or not? And having a highly sensitive test, like the circulating tumor cells, and we showed the comparative data with cytology from the FORESEE trial, informs whether or not the patient requires treatment for LMD. And there have been a number of reports that we've received where patients have indeterminate clinical signs, indeterminate imaging, or maybe even supportive imaging consistent with LM disease, but their spinal fluid is negative. So that's a really, that's probably the most important decision, quite frankly. Do they have the disease or not? And even with the combination of clinical evaluation, MRI and CTCs and cytology, that can often be a difficult decision to make.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Generally, what physicians are using now is they look to get two repeat CTC cell determinations and then make the decision if the patient does not have LM and doesn't require treatment. So that's kind of number one. Number two is an assessment of the genetic drift issue. And we think that goes beyond just the HER2 issue, but into other actionable biomarkers that will dictate whether certain type of drug checkpoint inhibitor might be utilized in one kind of tumor versus the other. And that genetic drift goes both ways, from positive to negative in the leptomeningeal space or the opposite. The other issue is whether it's potentially advantageous to stop treatment.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

For example, there are some case reports, certainly not significant series, but case reports, where therapy can drive the number of circulating tumor cells down to zero. And then one can theoretically stop treatment, monitor the patients that are doing well, and then reevaluate based on the ongoing CTC count going forward. So, we're just beginning to open the envelope on what the data means, but there are at least, I think, three solid ways where decision impact, decision-making can be impacted by the clinician.

[Justin Walsh, Director at JonesTrading]

Got it. Thanks. Quick follow-up. It might be a little early, but I'm curious if you have any expectations with respect to timing once you get into the multi-dose LM portion of the trial?

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Timing in terms of, when it gets started or?

[Justin Walsh, Director at JonesTrading]

Yeah. Yeah, and if you think there'll be relatively rapid enrollment or if it'll maybe be along the same pace as the single-dose version. Just curious about your-

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Oh, I hear you.

[Justin Walsh, Director at JonesTrading]

On that front.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Yeah, yeah, yeah. So thank you, Justin. So yeah, a couple of things. So, the IND is open. I think we're optimistic that what we've currently negotiated with FDA will ultimately go through. So we'll hear back, you know, less than 30 days. And assuming that's the case, and in fact, we're already talking to sites and doing the activities you would do for site startup, there'll be a different protocol that's got to go through IRB review and budget and so forth. But because we have an open IND, that's very similar, I think it ought to go pretty quickly. Our plan is to go back to the current 7 sites that we're working with, where this should also go more quickly.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

But we've also got a number of leading sites that want to participate. So we'll be. That'll be an important part of the plan. So I think, as mentioned, we'll get the trial up and running later this year. You know, some sites will be before other sites, obviously. So that's number one. In terms of how long it would take to enroll, the Phase 1 single administration was plagued by a couple of things. Number one, it had a Part A and a Part B.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

The FDA was very, very the amounts in terms of the administered dose of radiation that we were giving and wanted a formal stopping point, and we had to go back, as you'll recall, to move forward to the second half of that trial, which we're now in. Plus, we had intra-cohort DSMB decisions that we could roll very quickly, but then we had to wait for 90 days from the first patient and 30 days from the last patient before we go back to the DSMB. So bottom line is, I think we'll be getting data a lot more quickly from this. What's currently contemplated is we're dialing in multiple doses for these patients without going back to the FDA.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

So I think the data will accumulate quickly, both in terms of number of patients and longitudinal data on a variety of endpoints within four individuals. My preference is to wait till once we have the final feedback from the FDA, which we anticipate shortly, and then we'll make all that public and then put out some guidance about timing.

[Justin Walsh, Director at JonesTrading]

Great. Thanks for taking the question.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Thanks, Justin.

[Operator]

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

[Sean Lee, VP of Equity Research at H.C. Wainwright]

Good afternoon, guys, and congrats on the clinical progress this quarter. My first question is on the CNSide assay. So my understanding is that, correct me if I'm wrong, but all the tech transfer has been completed, and you're now just setting up the tests to be manufactured and marketed. So I was wondering, what are the next steps that you have to do before that, before you can start selling the tests to the market, or at least to the clinical sites?

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Hey, Sean. Thanks, thanks for the question. Yeah, let me, let me kind of review where we are and the plan, the plan going forward. So what we've done is we've, we've acquired all the IP, hard assets, know-how, SOPs, and, technology-related information, plus customer information. Remember, this test was commercial for a couple of years and was growing at about a 30% year-over-year rate, with about 200 individual customers at the time the test became unavailable, prior to our acquiring it. So we, we transferred the technology, I think, back in, Q1 of this year, got the test up and running, re-implemented it in, our Cohort Five, as mentioned, and we're now, we're now, performing the test within our trial. In the background, what we've done is we have, we've hired a medical director.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

We are actually manufacturing ourselves some of the chips that the test is done on, the microfluidic chips. We're now manufacturing those. Those were a gating item in terms of expanding the testing. We're now manufacturing those, so those are no longer a critical supply element. And so now it's really scaling the test. Now we can scale the test effectively for our multiple dose trial. We're gonna be testing, doing many more tests on patients longitudinally, because they're getting multiple doses, and that's gonna require pretty significant ramp up in testing throughput. And so now we're kind of positioned well to accommodate that from a QA perspective. And as I mentioned, Dr. Fuller's on board, will be the medical director.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

So in the background, we are doing a significant amount of commercial evaluation to determine what the magnitude of the commercial opportunity for this test, and then what's the required investment. That analysis is going well. Thus far, it looks very positive, but I think before we kind of commit, we wanna have a full and well-thought-through plan, and be ready to execute on that before we say too much more. But I will say that's going well, and those we'll be talking about that relatively soon as we finalize that plan.

[Sean Lee, VP of Equity Research at H.C. Wainwright]

Great. Thanks for that. My second question is on the LM studies. Now that you have a multi-dose study in the works, does it still make much sense to continue the single-dose study, especially into higher dose cohort? Or would you maybe be switching your focus mainly to the multi-dose study going forward?

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

It's a really good question, and here's how I would respond to that. The FDA, both in our GBM trial and related to this LM trial, they're very interested to getting to a maximum tolerated dose. They've made that very clear. So, I think we're committed to understand where the level of toxicity lies. And I think we're close, quite honestly. I think what we see from the safety signals in Cohort 5 kind of lead us to believe that we're probably pretty close, if not there. But as I mentioned, we don't. We have not officially reached an MTD at this point.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

But we'll continue that until we get to the formal stopping point, or we get to a maximal feasible dose, so we're not there yet. Secondly, I think we wanna, we wanted... We think long term, based on what we see in the single administration trial, and specifically that small group of patients that have had multiple doses, they're doing quite well. We believe we can get with this disease, but it likely will require multiple doses. So we wanted to get that multiple dose trial going quickly at our Cohort Two dose, and that data, thus far from a single administration perspective, has looked very promising. And you've seen that data, and we've now presented that multiple times. So that's up and running.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

So I think the next step, really, I know it's a long answer, but look at the Phase 1 data, understand it, look at the response data, discuss with FDA, get the multiple dose study up and running, and then we'll make a decision about whether or not we wanna take a single administration dose into a Phase 2, 3 pivotal, as envisioned in our CPRIT grant, for example. That was the initial clinical plan. That may still be the right thing to do. That may accelerate things, but provide a bit more risk, or we might wait for the data related to multiple doses. But if we look like it's potentially safe and effective with a single administration, then we have to really seriously consider whether or not we wanna take that to a pivotal or not.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

It'll be an interesting discussion, but that'll be a good problem to have.

[Sean Lee, VP of Equity Research at H.C. Wainwright]

Thanks for that. That's very helpful. My last question is on the GBM study. I think in the prepared remarks, you mentioned that the grant for the GBM studies will be coming to an end towards the end of this year. So I was wondering whether we can expect any more data updates from that later this year as well? Thanks.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Yeah. So, with respect to the GBM trial, so, as mentioned, we'll do a meaningful update on the Phase 1 progress and the Phase 2 progress at the CNS, the Congress of Neurological Surgeons, which will be in late September and into early October in Houston this year. So that'll be the next update. And the goal is to get enrollment completed this year. As mentioned, I think that's gonna be difficult. We've got 2 new sites that are in the final stages of onboarding right now. If those can contribute substantially, we've got a chance at getting that trial enrolled by the end of the year. If not, we think it'll be in the first half of next year. And then at that point, we'll evaluate the data.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

We've had continued to have good safety signals, and very interesting efficacy signals related to standard of care. If we continue to see that, then I think based on our previous discussions with the FDA, we have a pretty good idea what a pivotal trial design would look like, and we'll be ready to pull the trigger on that.

[Sean Lee, VP of Equity Research at H.C. Wainwright]

Great. That's all I have. Thanks again for taking my questions.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Thank you, Sean.

[Operator]

Thank you. One moment for our next question. That will come from the line of Edward Woo with Ascendiant Capital Markets. Your line is open.

[Edward Woo, Director at Ascendiant Capital Markets]

Yeah. Congratulations on all the progress, and congratulations on, you know, lining up additional potential grant funding. I was wondering, is there any seasonality to the grant funding? Are they issued all in certain times of the year? And have you noticed any change in the funding that's out there? Has it been more or less, or has it been about the same? Thank you.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Hey, Ed. Yeah, no, thanks for the question. It's definitely seasonal in this regard. And I'll take CPRIT, for example. CPRIT has historically had two times of the year where they accept grants. And so it takes about six months to go through that funding cycle. So if you submit a proposal in, let's say, July or August, in that timeframe, it takes about six months to go through the review process to get a decision for funding, and then get the administrative award mechanics finalized so you can receive funding. So it's seasonal in that we're responding to their granting calendar. And our experience with the NIH is similar, but oftentimes it's more sporadic, where they have requests for proposals, specifically our DoD proposal that we responded to, an RFP, as I recall.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

That's more of a one-off situation. So there, there's some peculiarities that can be seasonal, but also can be sporadic, in affecting the timing. As mentioned, I think we've developed a really good relationship, working with CPRIT. We know of companies that have up to at least three grants per company. And we also know that CPRIT will fund up to $20 million through Phase 2. So I think there's... you know, that's been a nice relationship, and that capital has been very important to us.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

And so I think that's what we'll continue to try to work with them closely, as well as look at some of these more sporadic alternatives to continue to leverage that non-dilutive capital and minimize the dilution to shareholders.

[Edward Woo, Director at Ascendiant Capital Markets]

Great. Well, thanks for answering my questions, and I wish you guys good luck.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Thank you.

[Andrew Sims, CFO at Plus Therapeutics]

Thanks, Ed.

[Operator]

Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Dr. Marc Hedrick for any closing remarks.

[Marc H. Hedrick, President and CEO at Plus Therapeutics]

Thank you, Cherie. We thank everyone, our analysts and shareholders and investors for listening to this call. I also wanna thank our patients. I'll be talking to two of them next week in Texas, who trust us to give them this investigational treatment. Thank you to all our employees who work so hard to make it happen. We wish everyone a nice evening. Thank you.

Participants

Executives

• Andrew Sims, CFO
• Marc H. Hedrick, President and CEO

Analysts

• Edward Woo, Director at Ascendiant Capital Markets
• Justin Walsh, Director at JonesTrading
• Sean Lee, VP of Equity Research at H.C. Wainwright