Q2 2024 Plus Therapeutics Inc Earnings Call

August 14, 2024

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Unknown Executive: Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics, 2nd quarter, 2024 Results Conference. 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 performance. All such statements are subject to risk and uncertainties, including the risk 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 advises you to review these risk factors, considering such a- 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 be...

Unknown Executive: Good afternoon, ladies and gentlemen.

Unknown Executive: Welcome to Plus Therapeutics, 2nd 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 positions. All such statements are subjects to risk and uncertainties, including the risk and uncertainties described under the risk factor 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.

Good afternoon, ladies and gentlemen.

Speaker Change: Welcome to Plus Therapeutics second quarter 2024 results conference call.

Speaker Change: 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.

Speaker Change: which may affect Plus Therapeutics' future operating results and financial position.

Speaker Change: All such statements are subject to risk and uncertainties, including the risk 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.

Unknown Executive: 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.

Speaker Change: advises you to review these risk factors in considering such statements.

Speaker Change: 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.

Unknown Executive: 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, Sheree, 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 2nd quarter 2024 financial results. Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer.

Marc Hedrick: 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 Andrew to review our financials, and then we'll both come back on for Q&A.

Marc Hedrick: I'll begin the call by reviewing our recent clinical and corporate progress in the 2nd 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 Combined American Society for Clinical Oncology, CNS Metastasis Conference, which met last week in Denver. At Snow Asco, plus was quite busy; we had four presentations, sponsored a symposium on novel, emerging diagnostics and therapeutics for leaptum and injule metastasis, and participated in a panel discussion on the opportunity for emerging therapies for brain metastasis alongside senior executives from Novartis and Pfizer.

Marc Hedrick: Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer.

Marc Hedrick: 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.

Marc Hedrick: Let me begin, with updates from the 2024 Society for Neuro-Oncology and Combined American Society for Clinical Oncology, CNS, at the TASCYS conference, which met last week in Denver, at Snow Asco, Plus was quite busy. We had four presentations, sponsored a symposium on novel, emerging diagnostics and therapeutics for leptom and 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 four presentations weren't 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 L.M.

Marc Hedrick: So let me begin with updates from the 2024 Society for Neuro-Oncology and Combined American Society for Clinical Oncology CNS Metastases Conference which met last week in Denver.

Speaker Change: At SNO ASCO, PLUS was quite busy. We had four presentations, sponsored a symposium on novel emerging diagnostics and therapeutics for leptomeningeal metastases.

Speaker Change: and participated in a panel discussion on the opportunity for emerging therapies for brain metastases alongside senior executives from Novartis and Pfizer.

Marc Hedrick: Two of our four presentations weren't 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 L.M. trial principal investigator, presented an interim update on the trial through cohort 4, and that's in equal 16 patients. This is the most significant update that we provided since the Snow 2023 presentation. His presentation showed that through cohort 4, which is an administered dose of 44 milicuries, Renium Obispermata was safe and well tolerated, with no dose limiting toxicities, and the maximum tolerated dose had not been reached.

Speaker Change: Two of our four presentations weren't highlighting on our call this afternoon and the full data from those presentations and from the symposium will be available soon on our website. Thank you.

Marc Hedrick: trial principal investigator presented an interim update on the trial through cohort 4, and that's n equals 16 patients. This is the most significant update that we provided since the snow 2023 presentation. His presentation showed that through Cohort 4, which is an administered dose of 44 millicuries, rhenium obispomate was safe and well tolerated with no dose limiting toxicities and the maximum tolerated dose dose had not been reached. 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.

Speaker Change: Dr. Andrew Brenner, the RESPECT-LM Trial Principal Investigator, presented an interim update on the trial through Cohort 4, and that's N equals 16 patients.

Speaker Change: This is the most significant update that we've provided since the SNOW 2023 presentation.

Speaker Change: His presentation showed that through cohort 4, which is an administered dose of 44 milicuries, Rynium Obispermaida was safe and well-tolerated with no dose limiting toxicities and the maximum tolerated dose had not been reached.

Marc Hedrick: For the more, 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 split. Also, a linear increase in absorbed dose to the regions of interest, specifically the cranial subarachnoid space and cerebral spinal 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 available at that time, but it's now available and we are back up and using the test currently in cohort 5.

Speaker Change: Furthermore, supporting the relative data demonstrated a high therapeutic window.

Speaker Change: 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.

Marc Hedrick: A linear increase in absorbed dose to the regions of interest, specifically the craniest subragnode space and cerebral spinal fluid was noted from cohort 1 to cohort 4, to increase, but there was no increase noted in his plane, which was the critical organ. In terms of response data, circulating tumor cell data was not available. Drew Cohort, Temporarily unavailable at that time, but it's now available, and we are back up and using the test currently in Cohort 5.

Speaker Change: Also...

Speaker Change: A linear increase in absorbed dose to the regions of interest, specifically the craniosubarachnoid 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.

Speaker Change: In terms of response data, circulating tumor cell data was not available through cohort

Speaker Change: Temporarily unavailable at that time, but it's now available, and we are back up and using the test currently in cohort five.

Marc Hedrick: But recall that we observed a mean 53 percent reduction in CTC circulating tumor cells in the CSF for the first three treated cohorts. It 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 5 is currently being reviewed and will be presented in detail at Snow in November, and I'll talk more about that in a moment. In terms of the median overall survival signal, again with 16 valuable patients through cohort 4, median overall survival was 12 months, with half the cohort, cohorts that's 8 out of the 16 treated patients remaining alive at the time of analysis.

Marc Hedrick: 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 the 28 days post-treatment, but the CTC number came back up by 56 days post-treatment. Additional, and Significant Response Data through Cohort 5 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.

Speaker Change: But recall that we observed a mean 53% reduction in CTCs, Circulating Tumor Cells, in the CSF for the first three treated cohorts.

Speaker Change: It was observed out to 28 days post-treatment, but the CTC number came back up by 56 days post-treatment.

Speaker Change: Additional and significant response data through Cohort 5 is currently being reviewed and will be presented in detail at SNO in November and I'll talk more about that in a moment.

Marc Hedrick: Again, with 16 valuable patients through cohort 4, median overall survival was 12 months, with half the cohorts, that's 8 out of the 16 treated patients remaining alive at the time of analysis. This is an increase from that that was reported after Cohort 3 last November, which showed a median overall survival of 10 months. 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 two to six months after diagnosis, depending on primary tumor type.

Speaker Change: In terms of the median overall survival signal,

Speaker Change: Again, with 16 evaluable patients through cohort 4, median overall survival was 12 months, with half the cohorts, that's 8 out of the 16 treated patients, remaining alive at the time of analysis.

Marc Hedrick: This is reported after cohort 3 last November, which showed a median overall survival of 10 months. To put that data in perspective, LM is a devastating disease, I think most of you know, from both the morbidity and mortality perspective, with typical survival rates ranging from two to six months after diagnosis, depending on primary tumor type. So this emerging efficacy signal, though early, is very encouraging vis-à-vis the standard of care.

Speaker Change: This is an increase from that that was reported after Cohort 3 last November, which showed a median overall survival of 10 months.

Speaker Change: 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 two to six months after diagnosis, depending on primary tumor type.

Marc Hedrick: 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 Kumtekar, who reported the top-line clinical results from our 4C trial. 4C evaluated the clinical utility of C-Inside, our newly acquired novel CNS diagnostic, for treatment decision-making by physicians in 40 patients.

Speaker Change: So this emerging efficacy signal, though early, is very encouraging vis-a-vis the standard of care.

Marc Hedrick: There was also a second presentation at Snow-ASC0, Dr. Priya Kumpekar, who reported the top-line clinical results from our 4C trial. 4C evaluated the clinical utility of C inside are newly acquired novel CNS diagnostic, unleptomininial metastases treatment decision-making by physicians and 40 patients. The trial used a well-described trial design that's used commonly in the diagnostic space. Specifically, she reported that 4C met its primary endpoint, with C inside influencing treatment decisions in over 90% of clinical decisions. That's 50% clinical decision-making points evaluated, and that substantially exceeded the 20% level, which was the target for the primary endpoint to show effect.

Speaker Change: There was also a second presentation at SNO ASCO.

Marc Hedrick: The trial used a well-described trial design that's used commonly in the diagnostic space. Specifically, she reported that 4C met its primary endpoint with C-Inside influencing treatment decisions in over 90% of clinical decisions. That's 50% of clinical decisions. Medical 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 C-Inside helped identify actionable mutations in the CSF, such as HER2 amplification, that influenced 24% of therapeutic selection decisions.

Speaker Change: Dr. Priya Kuntekar who reported the

Marc Hedrick: 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, see inside demonstrated more than twice the sensitivity in detecting tumor cells in the 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, see inside, exhibit at a very high specificity in that no tumor cells were detected in patients without leftom and angelic metastasis.

Speaker Change: 4C evaluated the clinical utility of C-Inside, our newly acquired novel CNS diagnostic, on leptomeningeal metastases treatment decision-making by physicians and 40 patients.

Speaker Change: The trial used a well-described trial design that's used commonly in the diagnostic space.

Speaker Change: Specifically, she reported that 4C met its primary endpoint with C-Inside influencing treatment decisions in over 90% of clinical decisions.

Speaker Change: clinical decision points evaluated. And that substantially exceeded the 20% level, which was the target for the primary endpoint to show effectiveness.

Marc Hedrick: in this. Moreover, the study also showed that C inside helped identify actionable mutations in the CSF, such as her two 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, C inside demonstrated more than twice the sensitivity in detecting tumor cells in the 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, C inside exhibited a very high specificity in that no tumor cells were detected in patients without leptomeningeal metastases.

Speaker Change: Moreover, the study also showed that C-Inside helped identify actionable mutations in the CSF.

Speaker Change: such as HER2 amplification that influenced 24% of therapeutic selection decisions. That's 14 out of 55 clinical decision points evaluated.

Speaker Change: Importantly, and related to the current state-of-the-art diagnostically that's found in major hospitals around the country, CNSci demonstrated more than twice the sensitivity in detecting tumor cells in the CSF compared to what is now the gold standard, which is cytology.

Speaker Change: Specifically, it showed a detection rate of tumor cells of 80% versus 29% for cytology.

Speaker Change: Also important, C-Inside exhibited a very high specificity in that no tumor cells were detected in patients without leptomeningeal metastases.

Marc Hedrick: We were pleased to see this data and present it formally in these 4C results highlight and validate our previous high conviction that C inside as a diagnostic and therapeutic selection and diagnostic therapeutic monitoring tool fulfills a critical clinical need in brain metastases that now has been showed to improve patient management, and we believe will lead to better patient outcomes in the near future.

Marc Hedrick: We were pleased to see this data and present it formally. And these 4C results highlight and validate our previous high conviction that see inside 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 we'll 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 the SNMI Annual Meeting, in June 2024.

Speaker Change: We were pleased to see this data.

Speaker Change: and presented formally, and these 4C results highlight

Speaker Change: and validate our previous high conviction.

Speaker Change: that see inside.

Speaker Change: 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.

Marc Hedrick: Finally, in addition to our presentations at Snow ASCO, we also reported important data at the 2024 Society for Nuclear Medicine and Molecular Imaging known as SNMI Annual Meeting in June 2024. The reported study used asymmetry data from the respective 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 radio nuclides such as RINIUM 186 largely spare the spinal cord versus other beta radio nucleotides that we studied. These findings further support the thesis that RINIUM 186 is an ideal radio nuclide for CNS cancers, hitting the therapeutic window, delivering high therapeutic doses to the region of interest while minimizing toxicity.

Speaker Change: 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 the SNMI Annual Meeting in June 2024.

Marc Hedrick: 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 spared the spinal cord versus other beta radio nucleotides that we studied.

Speaker Change: 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

Speaker Change: largely spare the spinal cord versus other beta radionucleotides that we studied.

Marc Hedrick: These findings further support the thesis that Runion 186 is an ideal radion nuclei for CNS cancers, hitting the therapeutic window, delivering high therapeutic doses to the region of interest while minimizing tucks, that kind of moving on in terms, of our Leptomeningeal Program, broadly speaking. First of all, therapeutically, the current phase one 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. 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.

Speaker Change: 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.

Marc Hedrick: Now, kind of moving on in terms of our left-to-menendial program broadly speaking. First of all, therapeutically, the current phase 1 single administration respect LM dose escalation trial will continue dosing until the next DSNB meeting, and at that time we will determine if progressing to cohort 6 is advisable. But thus far, as mentioned, a maximum tolerated dose has not been reached despite delivering up to a maximum of 66 militaries 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.

Speaker Change: Now, kind of moving on, it in terms...

Speaker Change: of our Leptomeningeal program, broadly speaking. First of all, therapeutically, the current phase one 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.

Speaker Change: 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.

Marc Hedrick: 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 obispomede 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.

Speaker Change: 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.

Marc Hedrick: To date, we have dose the total of 25 patients and also treated a subset of patients with multiple doses of RINIUM abyspamada 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. 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.

Speaker Change: To date, we have dosed a total of 25 patients and also treated a subset of patients with multiple doses of rhenium obispomede under compassionate use, and those patients have done really well.

Speaker Change: 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.

Marc Hedrick: 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. That trial is anticipated to begin enrolling later in 2024 at the current seven trial sites with a number of news sites, to be added in the interim. The Leptomeningo Program continues to be significantly supported by an approximately $18 million product development award from CPRIT that covers approximately two-thirds of programmatic expenditure. Also, the company continues to be involved in active dialogue with CEPRIT regarding program advancement and are actively seeking expanded ways to work with CEPRIT that are mutually advantageous, in terms of our diagnostic L.M. program.

Speaker Change: Once formally approved with final agreement with the FDA, the company will share the details of that trial protocol.

Speaker Change: That trial is anticipated to begin enrolling later in 2024 at the current seven trial sites with a number of new sites.

Marc Hedrick: The Laptop Ninja program continues to be significantly supported by an approximately $18 million product development ward from Seapret that covers approximately two-thirds of programmatic expenditures. Also, the company continues to be involved in active dialogue with Seapret regarding program advancement and is actively seeking expanded ways to work with Seapret that are mutually advantageous.

Speaker Change: to be added in the interim.

Speaker Change: The Lepto-Meningeal Program continues to be significantly supported by an approximately 18 million dollar product development award from CPRIT that covers approximately two-thirds of programmatic expenditures.

Speaker Change: Also, the company continues to be involved in active dialogue with SEPRIT regarding program advancement and are actively seeking expanded ways to work with SEPRIT that are mutually advantageous.

Marc Hedrick: In terms of our diagnostic L.M. program, we are in the process of expanding our C inside diagnostic capabilities at our facility in Houston, Texas, in specific, targeted, but strategic ways. First of all, we hire Dr. Greg Fuller, former chief of neuropathology at MD Anderson Cancer Center in Houston, and an L.M. expert to be the full-time medical director of the C inside lab and oversee lab operations and also help support our L.M. therapeutic objectives. We have also improved the lab quality assurance systems in our capabilities to steadily increase testing capabilities as anticipated for growing research use, both from pluses growing trial number in L.M., but also other trials that have contacted us with similar interest.

Marc Hedrick: We are in the process of expanding our CSI diagnostic capabilities at our facility in Houston, Texas, in specific, targeted, but strategic ways. First of all, we hired Dr. 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 C-Inside Lab and oversee lab operations and also help support our LM therapeutic objectives. We have also improved the lab quality assurance systems in 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.

Speaker Change: In terms of our Diagnostic LM program, we are in the process of expanding our CSI diagnostic capabilities at our facility in Houston, Texas, in specific, targeted, but strategic ways.

Speaker Change: First of all, we hired Dr. Greg Fuller, former chief of neuropathology at MD Anderson Cancer Center in Houston, and an LM expert.

Speaker Change: to be the full-time medical director of the C-Inside Lab and oversee lab operations and also help support our LM therapeutic objectives.

Speaker Change: We have also improved the lab quality assurance systems in 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.

Marc Hedrick: In addition, we have applied for CLEA certification for C inside as a laboratory developed test, and approval under CLEA is anticipated later in 2024. We anticipate providing further business updates on the C inside diagnostic program later this year as developments warrant.

Marc Hedrick: In addition, we have applied for CLIA certification for a C-Inside as a laboratory developed test and approval under CLIA is anticipated later in 2024. We anticipate providing further business updates on the C&C Diagnostic Program later this year as developments. Now I'd like to shift gears to our RESPECT GBM trial.

Speaker Change: In addition, we have applied for CLIA certification for a C-Inside as a laboratory-developed test, and approval under CLIA is anticipated later in 2024.

Speaker Change: We anticipate providing further business updates on the C&C Diagnostic Program later this year as developments warrant.

Marc Hedrick: Now, I'd like to shift gears to our respect GBM trial. As most of you know, this trial evaluates a single dose of Rhenium Obispermata in patients with recurrent glioblastoma and is funded mostly through the NIH. We continue to enroll both phase two 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 one now at cohort eight for patients with larger tumors. We anticipate three 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.

Speaker Change: Now I'd like to shift gears to our RESPECT GBM trial.

Marc Hedrick: As most of you know, this trial evaluates a single dose of rhenium obispimate in patients with recurrent glioblastoma and is funded mostly through the NIH. We continue to enroll both Phase II patients with recurrent GBM, and that's for tumors that are less than or equal to 20 cc's, and also enroll in patients in our Phase I now at Cohort VIII for patients with larger tumors. We anticipate three new active GBM convection enhanced delivery sites will be enrolling soon.

Speaker Change: As most of you know, this trial evaluates a single dose of Rhenium Obispermaida in patients with her current glioblastoma and is funded mostly through the NIH.

Speaker Change: We continue to enroll both Phase II patients with recurrent GBM, and that's for tumors that are less than or equal to 20 cc's, and also enroll in patients in our Phase I now at Cohort VIII for patients with larger tumors.

Speaker Change: We anticipate three new active GBM convection-enhanced delivery sites will be enrolling soon.

Marc Hedrick: And these should be able to transition to pivotal trial sites when the time warrants. Those are Ohio State University, providing us a site in the Upper Midwest, and North Shore Hospital, part of the Northwell-Lenox Hill Network in the greater New York region.

Speaker Change: And these should be able to transition to pivotal trial sites when the time warrants.

Marc Hedrick: Those are Ohio State University providing us a site in the upper Midwest and North Shore Hospital, part of the Northwell Linux 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. Foundation. These sites, specifically OSU and North Shore Hospital, Linux Hill, are contracted in role 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.

Speaker Change: Those are Ohio State University, providing us a site in the Upper Midwest.

Speaker Change: and North Shore 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 Hedrick: We are also evaluating other additional sites with the intention of adding at least one site in the greater Southern California region. These sites, specifically OSU, and North Shore Hospital, Lenox Hill 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.

Unknown Executive: Good afternoon ladies and gentlemen.

Speaker Change: These sites, specifically OSU

Unknown Executive: Welcome to Plus Therapeutics, 2nd 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 positions. All such statements are subjects to risk and uncertainties, including the risk and uncertainties described under the risk factor section, included in Plus Therapeutics Annual Report on Form 10K and Quarterly Reports on Form 10Q, 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.

Speaker Change: and North Shore Hospital, Lenox Hill, 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.

Speaker Change: 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.

Marc Hedrick: A faster timeline will be influenced to a significant degree by participation of these new sites.

Marc Hedrick: Our plan is to provide a substantial update on the Phase 1 and Phase 2 data this fall at the CNS or Congress for Neurologic Surgeons Annual Meeting, which is in late September early October in Houston, Texas. And this will be our first time to be on the podium presenting this data to the neurosurgical community.

Marc Hedrick: Our plan is to provide a substantial update on the phase one and phase two data this fall at the CNS, or Congress for Neurologic Surgeons annual meeting, which is in, of late September, early October in Houston, Texas. And this will be our first time to be on the podium presenting this data to the neurosurgical community. 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 I trial for children with pediatric brain cancer, specifically pediatric high-grade glioma and ependymoma.

Speaker Change: Our plan is to provide a substantial update on the Phase I and Phase II data this fall at the CNS, or Congress for Neurologic Surgeons, annual meeting, which is in September .

Speaker Change: late September, early October in Houston, Texas. And this will be our first time to be on the podium presenting this data to the neurosurgical community.

Marc Hedrick: 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 cancers, specifically pediatric high-grade glioma and epinoma. That award is an administrative phase, and it's anticipated to begin funding this September 2024. We are also on track to obtain IND approval for this trial, and Lori Children's Hospital will be the initial clinical trial site.

Marc Hedrick: 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 and 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. And with that, I'll now turn the call over to our Chief Financial Officer, Mr. Andrew Sims, who will review the financials. Andrew?

Marc Hedrick: It is now my pleasure to turn the floor over to Dr. Marc Hedrick, plus Therapeutics President and Chief Executive Officer. Sir, you may begin. Thank you, Sheree, 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 2nd quarter 2024 financial results.

Speaker Change: In addition, I'd like to briefly update you on our Pediatric Brain Cancer Program.

Speaker Change: We've previously announced that we received the 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.

Speaker Change: 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.

Marc Hedrick: 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 2nd quarter, then turn the call over 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 Neuroncology and Combined American Society for Clinical Oncology, CNS Metastasis Conference, which met last week in Denver.

Marc Hedrick: 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.

Speaker Change: 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.

Speaker Change: and enhancing our drug delivery capabilities and we plan to make material public updates on those in the near future.

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

Marc Hedrick: At Snow Asco, plus was quite busy, we had four presentations, sponsored a symposium on novel, emerging diagnostics and therapeutics for leaptum and injule metastasis, and participated in a panel discussion on the opportunity for emerging therapies for brain metastasis alongside senior executives from Novartis and Pfizer. Two of our four presentations weren't highlighting on our call this afternoon and the full data from those presentations and from the symposium will be available soon on our website.

Speaker Change: And 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: Thank you, Mark.

Andrew Sims: 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 23. This represents a separate share of the cost incurred for our premium abyspometer development for the treatment of patients with LM. We expect 2024 grant revenue to be in the range of $6.7 million.

Andrew Sims: Thank you, Marc. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter ending 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 SIPRIT's share of the costs incurred for Irenium Abispermida development for the treatment of patients with LM. We expect 2024 grant revenue to be in the range of six to seven 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: Thank you, Mark. 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.

Andrew Sims: The cash and investments balance was $8.4 million at June 30, 2024, compared to $8.6 million at December 31, 2023.

Andrew Sims: 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.

Marc Hedrick: First of all, Dr. Andrew Brenner, the Respect L.M, trial principal investigator, presented an interim update on the trial through cohort 4, and that's in equal 16 patients.

Speaker Change: This represents Siprit's share of the costs incurred for Irenium Abyss Bermuda development for the treatment of patients with LM.

Speaker Change: We expect 2024 grant revenue to be in the range of $6 to $7 million.

Andrew Sims: Total operating loss for the first half of 2024 was $7 million compared to $6.2 million in the same period of 2023. 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 of $6.3 million or $2.6 per share for the same period of the price. here.

Marc Hedrick: This is the most significant update that we provided since the snow 2023 presentation. His presentation showed that through cohort 4, which is an administered dose of 44 milicuries, Renium Obispermata was safe and well tolerated with no dose limiting toxicities, and the maximum tolerated dose had not been reached. For the more, 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 split.

Speaker Change: 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: 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, of $6.3 million or $2.6 per share for the same period of the price, update on our runaway in 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.

Speaker Change: The increase is primarily due to increased spend related to the RESPECT-LM trial.

Speaker Change: Net loss for the first half of 2024 was $6.2 million, or $1.15 per share.

Speaker Change: of 6.3 million or two dollars and six cents per share for the same period the prior year.

Andrew Sims: Update on a runway in 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 balances 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. In addition, there are up to 12 million of cash on exercise of the one and five year warrants.

Speaker Change: www.microsoft.com.

Marc Hedrick: Also, a linear increase in absorbed dose to the regions of interest, specifically the cranial subarachnoid space and cerebral spinal 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.

Speaker Change: ...update on our runaway in cash position and provide guidance on our grant funding for the remainder of 2024.

Speaker Change: 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.

Andrew Sims: First, and as a reminder, we announced the May that we closed a private placement financing of up to 19.25 minutes, from New Healthcare Focused, Institutional Investment, and Company Insiders, with a total of 7.25 million received a closing. In addition, there are up to $12 million of cash on exercise of the 1 and 5 year warranty. As a side note, at June 30, 2024, the warrants issued as part of this private placement where recorded the liability on the balance. 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 Act.

Speaker Change: 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.

Marc Hedrick: In terms of response data, circulating tumor cell data was not available through cohort temporarily available at that time, but it's now available and we are back up and using the test currently in cohort 5. But recall that we observed a mean 53 percent reduction in CTC circulating tumor cells in the CSF for the first three treated cohorts. It was observed out to 28 days post treatment, but the CTC number came back up by 56 days post treatment.

Speaker Change: with a total of 7.25 million received a closing.

Speaker Change: In addition, there are up to 12 million of cash on exercise of the one and five-year warrants.

Andrew Sims: 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 event's footnote 14, the warrant form was amended, eliminating the liability; and henceforth, these warrants will be accounted for under the equity accounting method.

Speaker Change: 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.

Speaker Change: And 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.

Andrew Sims: The second source of cash remains our anticipated ongoing funding through now three awarded grants. First, the Cypriot grant to support the respect to LM trial. As reported, we received the first of two expected amounts from Cypriot in 2024, the first in Q2 of 3.3 million. We remain on track to receive the next advance of Cypriot of 3.7 million in mid to late Q4 2024. An additional 3.7 million is expected from Cypriot in 2025.

Andrew Sims: The Second Source of Cash, remains our anticipated ongoing funding through now three awarded grants. Specific grants to support the RespectLM trial. As reported, we received the first of two expected amounts from SIPRID in 2024, the first in Q2 of $3.3 million. We remain on track to receive the next advance from SIPRID of $3.7 million in mid-to-late Q4 2024. An additional $3.7 million is expected from CPRID in 2025.

Speaker Change: The Second Source of Cash

Speaker Change: remains our anticipated ongoing funding through now three awarded grants.

Marc Hedrick: Additional and significant response data through cohort 5 is currently being reviewed and will be presented in detail at snow in November, and I'll talk more about that in a moment. In terms of the median overall survival signal, again with 16 valuable patients through cohort 4, median overall survival was 12 months, with half the cohort, cohorts that's 8 out of the 16 treated patients remaining alive at the time of analysis. This is reported after cohort 3 last November, which showed a median overall survival of 10 months.

Speaker Change: First,

Speaker Change: The CIPRI grant to support the RespectLM trial

Speaker Change: As reported, we received the first of two expected amounts from SIPCRA in 2024, the first in Q2 of $3.3 million.

Speaker Change: We remain on track to receive the next advance from SIPRID of $3.7 million in mid-to-late Q4 2024.

Speaker Change: An additional $3.7 million is expected from CPRID in 2025.

Andrew Sims: Second, 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 Respects pediatric brain cancer trial. This funding is expected to commence in September 2024 and maturity cover the costs that the plan phase one trial. Funding has received annually in advance in covers a three year period, by approximately one million. What we received under this grant in 2024.

Andrew Sims: Second, as reported on April 22nd. Plus has received an award recommendation from the United States Department of Defense. 3 million to support the upcoming RESPECT pediatric brain cancer trial. This funding is expected to commence in September 2024 and maturely cover the cost of the planned phase one trial. Funding is received annually in advance and covers a three year period, i.e. approximately one 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 Trials, Although expected to be complete in 2024, it currently covers approximately 90% of the overall trial cost.

Speaker Change: Second, as reported on April 22nd, 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.

Marc Hedrick: To put that data in perspective, LM is a devastating disease, I think is most of you know, from both the morbidity and mortality perspective, with typical survival rates ranging from two to six 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.

Speaker Change: This funding is expected to commence in September 2024 and maturely cover the cost of the planned Phase 1 trial.

Speaker Change: Funding is received annually in advance and covers a three-year period, i.e. approximately 1 million will be received under this grant in 2024.

Andrew Sims: Third, plus also continues to benefit from the NIH grant to support the respect GBM phase one trial. Although expected to be complete in 2024, it currently covers approximately 90 percent of the overall trial costs. 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're awarded.

Speaker Change: Third, PLUS also continues to benefit from the NIH grant to support the RESPECT-GBM Phase 1-2 trial.

Marc Hedrick: There was also a second presentation at snow-asco, Dr. Priya Kumpekar, who reported the top-line clinical results from our 4C trial. 4C evaluated the clinical utility of C inside are newly acquired novel CNS diagnostic, unleptomininial metastases treatment decision-making by physicians and 40 patients. The trial used a well-described trial design that's used commonly in the diagnostic space. Specifically, she reported that 4C met its primary endpoint with C inside influencing treatment decisions in over 90% of clinical decisions.

Speaker Change: Although expected to be complete in 2024, it currently covers approximately 90% of the overall trial costs.

Andrew Sims: We also continue to source other non-dilutive sources of grant capital and have applied for approximately $13 million in additional grant funding yet to date. We will continue to only report on individual grants when they are awarded.

Marc Hedrick: That's 50% clinical decision-making points evaluated, and that substantially exceeded the 20% level, which was the target for the primary endpoint to show effect, in this. Moreover, the study also showed that C inside helped identify actionable mutations in the CSF, such as her two 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, C inside demonstrated more than twice the sensitivity in detecting tumor cells in the 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, C inside exhibited a very high specificity in that no tumor cells were detected in patients without leptomanagial metastases.

Speaker Change: 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.

Speaker Change: We will continue to only report on individual grants when they are awarded.

Andrew Sims: In summary, this provides incremental access to cash of 22 million, 10 million from Cypriot and DOD, and 12 million from the exercise of NB warrants from the May private placement.

Andrew Sims: In summary. This provides incremental access to cash of $22 million. 10 million from CPRIT and DoD. 12 million from the exercise of NB warrants from the May private place.

Speaker Change: In summary,

Speaker Change: This provides incremental access to cash of $22 million.

Speaker Change: $10 million from CPRID and DoD, and $12 million from the exercise of NB warrants from the May private placement.

Marc Hedrick: And now I'll turn it back to you, Mark. Great, thanks a lot, Andrew.

Marc Hedrick: And now I'll turn it back to you. 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 the remainder of 2024. As mentioned during the Congress from Neurological Surgeons, CNS, and that's in late September, early October, Dr. John Floyd, who's the chief of neurosurgery at UTesca, University of Texas Health Science Center, and 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 22nd through 26th of this year.

Marc Hedrick: 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 from neurological surgeons, CNS, and that's in late September early October. Dr. John Floyd, who's the chief neurosurgery at Utesca, University of Texas Health Science Center. and Antonio will be presenting an update on the current GBM phase one and phase two trial and most recent results.

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

Marc Hedrick: Great. Thanks a lot, Andrew.

Marc Hedrick: Before we move to Q&A, just let me take a moment to provide some specific guidance for key events and milestones.

Marc Hedrick: that we're looking towards through the remainder of 2024.

Speaker Change: As mentioned during the Congress from Neurological Surgeons, CNS, and that's in late September, early October, Dr. John Floyd, who's the Chief of Neurosurgery at UTESCA, University of Texas Health Science Center.

Speaker Change: and Santonio will be presenting an update on the current GBM phase 1 and phase 2 trial and most recent results.

Marc Hedrick: At the Society for Neuro-oncology Annual Conference, which will be held in Houston, November 22nd through 26th of this year. We'll have three presentations. The first is a substantial update, as I mentioned earlier, on the respect L.M. trial. In addition, we have two C's inside diagnostic abstracts. 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 L.M. patients. That is where patients have a certain genetic component to their cancer that flips from their primary tumor to a metastasis, for example, in the CSF.

Speaker Change: at the Society for Neuro-Oncology Annual Conference, which will be held in Houston, November 22nd through 26th of this year.

Marc Hedrick: 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 CSI diagnostic abstracts. 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.

Speaker Change: 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 CSI Diagnostic Abstracts.

Speaker Change: The first is entitled CSF Tumor Cell Detection

Speaker Change: 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.

Marc Hedrick: We were pleased to see this data and present it formally in these 4C results highlight and validate our previous high conviction that C inside as a diagnostic and therapeutic selection and diagnostic therapeutic monitoring tool fulfills a critical clinical need in brain metastases that now has been showed to improve patient management and we believe will lead to better patient outcomes in the near future.

Marc Hedrick: 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 metastasis, for example, in the in the CSF. And the title of that is the oncogenic flip in patients with leptomeningeal metastasis. Specifically, the longitudinal detection in cerebral spinal fluid tumor cell counts, and what it reveals in terms of implications for the differential treatment of the LND tumor.

Speaker Change: The second

Speaker Change: with 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

Speaker Change: that flips from their primary tumor to a metastasis, for example, in the CSF, in the title that is the oncogenic flip in patients with leptomininial metastases.

Marc Hedrick: Finally, in addition to our presentations at Snow Asco, we also reported important data at the 2024 Society for Nuclear Medicine and Molecular Imaging known as SNMI Annual Meeting in June 2024. The reported study used asymmetry data from the respective 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 radio nuclides such as RINIUM 186 largely spare the spinal cord versus other beta radio nucleotides that we studied. These findings further support the thesis that RINIUM 186 is an ideal radio nuclide for CNS cancers hitting the therapeutic window delivering high therapeutic doses to the region of interest while minimizing toxicity.

Marc Hedrick: In the title, that is the oncogenic flip in patients with leptomeningeal metastases, specifically the longitudinal detection and cerebral spinal fluid tumor cell counts and what it reveals in terms of implications for the differential treatment of the L.M.D. tumor. All three of those will be on again for snow in the November of time frame this year. We also anticipate FDA approval on the respect L.M. Phase I multiple dose trial. So the I.N.D.

Speaker Change: specifically the longitudinal detection in cerebral spinal fluid tumor cell counts.

Speaker Change: and what it reveals in terms of implications for the differential treatment of the LND tumor. And so all three of those will be on again for for Snow at the main in the November of time frame this year. We also anticipate FDA approval on the RESPECT-LM phase one multiple dose trial.

Marc Hedrick: And so all three of those will be on again for for Snow at the main in the November of time frame this year. 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 obispomata for pediatric ependymoma and high-grade glioma patients is anticipated also later this year. So with those, Cherie, I'll turn it back over to you, and we can have our Q&A session. Thank you. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, press star 1-1 again.

Marc Hedrick: for the Phase I II study of Renium Obispermata for pediatric epinomoma and high grade glioma patients is anticipated also later this year.

Cherie: So the IND for the Phase 1-2 study of rhenium obispomata 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.

Unknown Executive: So, with those, Sheree, I'll turn it back over to you, and we can have our Q&A session.

Unknown Executive: Thank you to ask a question. Please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, press star 11 again. One moment while we can tell the Q&A roster.

Speaker Change: Thank you to ask a question. Please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, press star 11 again. One moment while we can call the Q&A roster.

Marc Hedrick: Now, kind of moving on in terms of our left-to-menendial program broadly speaking. First of all, therapeutically, the current phase 1 single administration respect LM dose escalation trial will continue dosing until the next DSNB meeting and at that time we will determine if progressing to cohort 6 is advisable but thus far as mentioned a maximum tolerated dose has not been reached despite delivering up to a maximum of 66 militaries to the CSF.

Unknown Executive: One moment while we compile the Q&A roster. And our first question will come from the line of Justin Walsh with Jones Trading. Your line is open. I was wondering if you could provide a, on Textrum.

Justin Walsh: And our first question will come from the line of Justin Walsh with Jones Trading. Your line is open.

Speaker Change: And our first question will come from the line of Justin Walsh with Jones Trading. Your line is open.

Justin Walsh: 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 sea inside. Obviously, therapy selection is one, but the 24 percent that informed therapy selection is lower than the 90 percent total decisions that were impacted.

Justin Walsh: Hi, thanks for taking the question.

Justin Walsh: I was wondering if you could provide some more context around the types of treatment decisions that are likely to be informed by CN-SIDE. Obviously, therapy selection is one, but the 24% that informed therapy selection is lower than the 90% total decisions that were impacted.

Marc Hedrick: In terms of upcoming data releases, a definitive trial update is planned for Society for Neuroncology 2024 that will be held in Houston this November. To date, we have dose the total of 25 patients and also treated a subset of patients with multiple doses of RINIUM abyspamada 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.

Marc Hedrick: 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 4-C 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 LN 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?

Marc Hedrick: Obviously, therapy selection is one, but the 24% that informed, 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 show the comparative data with cytology from the 4C 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 their spinal fluid is negative. So that's that's a really that's probably the most important decision, quite frankly. Do they have the disease or not?

Justin Walsh: Yeah, that's a good question, Justin.

Speaker Change: One of the key decisions is, A, does the patient have the disease or not? And having a highly sensitive test.

Speaker Change: like the circulating tumor cells, and we showed the comparative data with cytology from the 4C trial, informs whether or not

Speaker Change: The patient requires treatment for LMD and there have been

Marc Hedrick: 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. 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.

Speaker Change: a number of reports that we've received where patients have indeterminate

Speaker Change: clinical signs, indeterminate imaging or maybe even supportive imaging

Speaker Change: consistent with LM disease but their their spinal fluid is negative so that's that's a really that's probably the most important decision quite frankly do they have the disease or not

Marc Hedrick: And even with the combination of clinical evaluation, MRI, and CTCs in cytology, that can often be a difficult decision to make. 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 left dimensional space, or the opposite.

Marc Hedrick: And even with the combination clinical evaluation, MRI, and CTCs in psychology, that can often be a difficult decision to make. And generally what physicians are using now is they look to get to repeat CTC cell determinations and then make the decision if patient does not have LM and doesn't require treatment.

Marc Hedrick: The Laptop Ninja program continues to be significantly supported by an approximately $18 million product development ward from Seapret that covers approximately two-thirds of programmatic expenditures. Also, the company continues to be involved in active dialogue with Seapret regarding program advancement and are actively seeking expanded ways to work with Seapret that are mutually advantageous.

Speaker Change: And even with the combination of clinical evaluation, MRI, and CTCs in cytology, that can often be a difficult decision to make.

Speaker Change: Generally what physicians are using now is they they look to get to repeat

Speaker Change: CTC

Speaker Change: Cell determinations and then make the decision the patient does not have

Marc Hedrick: 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 a 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 left of menial space or the opposite.

Speaker Change: 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

Marc Hedrick: In terms of our diagnostic L.M, program, we are in the process of expanding our C inside diagnostic capabilities at our facility in Houston, Texas in specific, targeted, but strategic ways. First of all, we hire Dr. Greg Fuller, former chief of neuro pathology at MD Anderson Cancer Center in Houston, and an L.M, expert to be the full-time medical director of the C inside lab and oversee lab operations and also help support our L.M, therapeutic objectives.

Marc Hedrick: We have also improved the lab quality assurance systems in our capabilities to steadily increase testing capabilities as anticipated for growing research use, both from pluses growing trial number in L.M., but also other trials that have contacted us with similar interest. In addition, we have applied for CLEA certification for C inside as a laboratory developed test and approval under CLEA is anticipated later in 2024.

Speaker Change: 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.

Marc Hedrick: The other issue is whether it's potentially advantageous to stop treatment. 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 patients that are doing well and then re-evaluate based on the ongoing CTC count going forward. So we're just beginning to open the envelope on what the data means.

Marc Hedrick: The other issue is whether it's potentially advantageous to stop treatment. For example, there's 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 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-making can be impacted by the clinician.

Speaker Change: The other issue is whether it's potentially advantageous to stop treatment. For example, there are some case reports, certainly not.

Speaker Change: 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.

Speaker Change: monitor the patients that are doing well and then re-evaluate based on the ongoing CTC count going forward. So we're just beginning to

Marc Hedrick: But there are at least, I think, three solid ways where decision making can be impacted by the clinic. 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. Timing in terms of when it gets started?

Marc Hedrick: We anticipate providing further business updates on the C inside diagnostic program later this year as developments warrant.

Speaker Change: Open the envelope on what the data means, but there are at least, I think, three solid ways where decision-making can be impacted by the clinician.

Justin Walsh: Got it. Thanks.

Marc Hedrick: Now, I'd like to shift gears to our respect GBM trial. As most of you know, this trial evaluates a single dose of Rhenium Obispermata in patients with recurrent glioblastoma and is funded mostly through the NIH. We continue to enroll both phase two patients with recurrent GBM and that's for tumors that are less than or equal to 20 CCs and also enrolling patients in our phase one now at cohort eight for patients with larger tumors.

Justin Walsh: 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. Timing in terms of when it gets started. 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 health.

Speaker Change: 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 portion of the trial.

Speaker Change: Timing in terms of when it gets started? Yeah. Yeah. And if you think they'll be relatively

Marc Hedrick: Yeah. Yeah. And if you think they'll be relative. Rapid Enrollment, or if it'll maybe be a long. Deluxe Version.

Marc Hedrick: We anticipate three 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 Ohio State University providing us a site in the upper Midwest and North Shore Hospital, part of the Northwell Linux 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.

Speaker Change: rapid enrollment or if it'll maybe be along the same pace as the single dose version.

Marc Hedrick: Oh, I hear you. Yeah, so thank you, Justin. So a couple of things. So the IED is open. I think we're optimistic that the, that what we've currently negotiated with FDA will ultimately go through. So we'll hear back in 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.

Marc Hedrick: Yeah, so thank you, Justice. So a couple of things. So the IEDs is open. I think we're optimistic that what we've currently negotiated with FDA will ultimately go through. So we'll hear back 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 IED that's very similar, I think it ought to go pretty quickly. Our plan is to go back to the current seven sites that we're working with, where that should also go more quickly, but we've also got a number of leading sites that want to participate.

Speaker Change: just.

Speaker Change: I'm curious about your thoughts on that.

Speaker Change: Yeah, yeah, yeah. So, thank you, Justin. So, yeah, a couple things. So, the INDs is open. I think we're optimistic that the

Speaker Change: that what we've currently negotiated with FDA will ultimately go through. So we'll hear back, you know, less than 30 days.

Speaker Change: and assuming that's the case...

Speaker Change: 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.

Marc Hedrick: Foundation. These sites, specifically OSU and North Shore Hospital, Linux Hill, are contracted in role 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.

Marc Hedrick: 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, seven sites, that that we're working with, where that should also go more quickly. But we've also got a number of of leading sites that want to participate.

Speaker Change: Our plan is to go back to the current...

Speaker Change: seven sites.

Speaker Change: that we're working with, where that should also go more quickly. But we've also got a number of

Marc Hedrick: So that'll be an important part of the plan.

Speaker Change: of leading sites that want to participate. So that'll be an important part of the plan. So I think as mentioned, we'll get the trial up and running.

Marc Hedrick: So I think, as mentioned, we'll get the trial up and running later this year. Some sites will be before other sites, obviously. So that's number one, in terms of how long we'll take to enroll.

Marc Hedrick: So 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. Some sites will be before other sites, obviously. So that's number one, in terms of how long we'll take to enroll. The phase one single administration was plagued by a couple of things. Number one, it had a part A and a part B.

Speaker Change: 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,

Marc Hedrick: The Phase I single administration was plagued by a couple of things. Number one, it had a part A and a part B. The FDA was very worried about 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 intro 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 DSMB.

Speaker Change: The Phase 1 single administration was plagued by a couple of things. Number one, it had a Part A and a Part B. The FDA was very...

Marc Hedrick: The FDA was very, very loud. The, The amount 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 intro 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 DSMB.

Marc Hedrick: And this will be our first time to be on the podium presenting this data to the neurosurgical community.

Speaker Change: The

Marc Hedrick: 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 cancers, specifically pediatric high-grade glioma and epinomoma.

Speaker Change: the amounts in terms of the administered dose of radiation that we were giving and wanted a formal stopping point.

Speaker Change: And we had to go back, as you'll recall, to

Speaker Change: to move forward to the second half of that trial, which we're now in.

Speaker Change: Plus, we had

Speaker Change: inter-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 DSMB.

Marc Hedrick: That award is an administrative phase and it's anticipate to begin funding this September 2024. We are also on track to obtain IND approval for this trial, and Lori 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.

Marc Hedrick: So, 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. 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. Once we, My preference is to wait until 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. Thanks, Justin.

Marc Hedrick: 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. So I think the data will accumulate quickly, both in terms of number of patients and longitudinal data on a variety of end points within four individuals.

Speaker Change: So bottom line is, I think we'll be getting data a lot more quickly from this, what's currently contemplated as we're dialing in.

Speaker Change: multiple doses for these patients without going back to the FDA.

Speaker Change: So I think the data will accumulate quickly, both in terms of number of patients and longitudinal data on a variety of endpoints.

Marc Hedrick: And we plan to make material public updates on those in the near future.

Marc Hedrick: Once we, 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.

Speaker Change: within four individuals.

Andrew Sims: And with that, I'll now turn the call over to our Chief Financial Officer, Mr. Andrew Sims, who will review the financials. Andrew. Thank you, Mark. Good afternoon, everyone.

Speaker Change: What we.

Speaker Change: My preference is to wait until 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.

Unknown Executive: Great, thanks for taking the questions. Thanks, Justin. Thank you. One moment for our next question.

Andrew Sims: 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 23. This represents a separate share of the cost incurred for our premium abyspometer development for the treatment of patients with LM.

Speaker Change: Great, thanks for taking the questions.

Speaker Change: Thanks, Justin. Thank you. One moment for our next question.

Sean Lee: And that will come from the line of Sean Lee with HC Wainwright. Your line is open.

Unknown Executive: Thank you. One moment for our next question. And that will come from the line of Sean Lee with H.C. Wainwright, your line is open.

Speaker Change: And that will come from the line of Sean Lee with H.C. Wainwright. Your line is open.

Sean Lee: Good afternoon, guys, and congrats on the clinical promises quarter. My first question is on the, 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.., to be manufactured and, I was wondering, what are the next steps that you have to do before you can start selling the tests to the market or at least to the clinical side? Hey, Sean.

Sean Lee: Good afternoon, guys, and congrats on the clinical progress this quarter. My first question is on the CIS side, I'd say. 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...

Andrew Sims: We expect 2024 grant revenue to be in the range of $6.7 million. Total operating loss for the first half of 2024 was $7 million compared to $6.2 million in the same period of 2023. 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 of $6.3 million or $2.6 per share for the same period of the price, here.

Sean Lee: and Andrew Sims . . . . . . . . . . . .

Sean Lee: 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?

Speaker Change: I was wondering, what are the next steps that you have to do before you can start selling the tests to the market or at least to the clinical sites?

Marc Hedrick: Hey, Sean. Thanks for the question. Yeah, let me kind of review where we are and the plan, the plan going forward. So what we've done is 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. It 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 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 performing the test within our trial.

Marc Hedrick: 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.

Speaker Change: Hey, Sean. Thanks for the question. Yeah, let me kind of review where we are and the plan going forward. So what we've done is we've acquired all the IP, hard assets, know-how, SOPs,

Speaker Change: and technology-related information plus customer information.

Andrew Sims: Update on a runway in 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 balances 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.

Marc Hedrick: Remember, this test was commercial for, 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 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.

Speaker Change: Remember, this test was commercial for...

Speaker Change: a couple years and was growing at about a 30% year-over-year rate.

Speaker Change: with about 200 individual customers at the time the test became unavailable.

Speaker Change: prior to our acquiring it.

Speaker Change: So we transferred the technology, I think, back in Q1.

Speaker Change: of this year, got the test up and running, re-implemented it in our cohort five, as mentioned, and we're now

Marc Hedrick: In the background, what we've done is we've hired a medical director. 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 going to be testing many more tests on patients longitudinally because they're getting multiple doses, and that's going to require pretty significant ramp up in testing throughput.

Speaker Change: We're now performing the test within our trial.

Andrew Sims: In addition, there are up to 12 million of cash on exercise of the one and five 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 event's footnote 14, the warrant form was amended eliminating the liability and henceforth, these warrants will be accounted for under the equity accounting method.

Speaker Change: In the background, what we've done is we have

Marc Hedrick: We are actually manufacturing, ourselves, some of the 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.

Speaker Change: We've hired a medical director, we are actually manufacturing

Speaker Change: ourselves some of the

Speaker Change: The chips that the test is done on, the microfluidic chips, we're now manufacturing those.

Marc Hedrick: And so now, it's really, Scaling the test. Now we can scale the test effectively for our multiple dose trial. We're going to be testing many more tests on patients longitudinally because they're getting multiple doses. And that's going to 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, 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 that analysis is going well.

Speaker Change: 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 a pretty significant ramp up.

Marc Hedrick: 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. 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 is and then what's the required investment. That analysis is going well; thus far, it looks very positive. But I think I, before we kind of commit, want to have a full and well thought through plan and be ready to execute on that before we save too much more. But I will say that's going well, and those will be talking about that relatively soon as we finalize that plan.

Speaker Change: 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 is on board, will be the medical director.

Speaker Change: 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.

Andrew Sims: Second, 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 respects pediatric brain cancer trial. This funding is expected to commence in September 2024 and maturity cover the costs that the plan phase one trial. Funding has received annually in advance in covers a three year period, by approximately one million what we received under this grant in 2024.

Marc Hedrick: Thus far, it looks very positive, but I think I before we we kind of commit, we want to have a, 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 we'll be talking about that relatively soon as we finalize that plan. 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 to a higher dose cohort, or would you be switching your focus mainly to the multi-dose study going forward? It's a really good question, and here's how I would respond to that.

Speaker Change: Thus far, it looks very positive, but I think before we commit, we want to have a full and well-thought-through

Speaker Change: plan and be ready to execute on that before we say too much more. But I will say that's going well and we'll be talking about that relatively soon as we finalize that plan.

Andrew Sims: Third, plus also continues to benefit from the NIH grant to support the respect GBM phase one to trial. Although expected to be complete in 2024, it currently covers approximately 90 percent of the overall trial costs. 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're awarded.

Sean Lee: Great, thanks for that.

Sean Lee: My second question is on the IM 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 to hire those cohorts, or would you be switching your focus mainly to the multi-dose study going forward? 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 in 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.

Speaker Change: Great.

Speaker Change: Thanks for that. My second question is on the LM studies. Now that you have a multi-dose study in the works,

Speaker Change: Does it still make much sense to continue the single dose study, especially to hire a dose cohort, or would you be switching your focus mainly to the multi-dose study going forward?

Speaker Change: It's a really good question and here's how I would respond to that.

Andrew Sims: In summary, this provides incremental access to cash of 22 million, 10 million from Cypriot and DOD, and 12 million from the exercise of NB warrants from the May Private Placement.

Marc Hedrick: 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 have not officially reached an MTD at this point. But we'll continue that until we get to the formal stopping point, or we get to a maximal feasible dose. We're not there yet.

Speaker Change: The FDA, both in our GBM trial and related to this LM trial, they're very interested to getting to a maximum tolerated dose.

Marc Hedrick: And now I'll turn it back to you Mark. Great, thanks a lot Andrew.

Marc Hedrick: 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 from neurological surgeons, CNS, and that's in late September early October. Dr. John Floyd, who's the chief neurosurgery at Utesca, University of Texas Health Science Center, and Antonio will be presenting an update on the current GBM phase one and phase two trial and most recent results.

Speaker Change: They've made that very clear. So, I think we're committed to understand where the level of toxicity lies.

Marc Hedrick: So, and I think we're close, quite honestly. I think what we see from the safety signals in cohort 5 leads us to believe that we're probably pretty close, if not there. But, as I mentioned, we have not officially reached an MTD at this point, but we'll continue that until we get to the formal stopping point, or we get to a maximum feasible dose. We're not there yet. Secondly, I think we want to 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.

Speaker Change: So, and I think we're close, quite honestly. I think what, kind of 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.

Speaker Change: an MTD at this point, but we'll continue that until we get to the the formal stopping point, or we get to a maximal feasible dose. We're not there yet.

Marc Hedrick: Secondly, I think we want to we want to we think long term. Based on what we see in the single administration trial, and specifically a 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.

Marc Hedrick: At the Society for Neuroncology Annual Conference, which will be held in Houston, November 22nd through 26th of this year. We'll have three presentations. The first is a substantial update, as I mentioned earlier, on the respect L.M, trial. In addition, we have two C inside diagnostic abstracts. 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 leptoman angel disease.

Speaker Change: Secondly, I think we want to, we wanted, we think long term.

Speaker Change: based on what we see in the single small group of patients that have had multiple doses. They're doing quite well. We believe we can get

Marc Hedrick: 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 the 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.

Speaker Change: with this disease, but it likely will require multiple doses.

Speaker Change: So we wanted to get that multiple dose trial going.

Speaker Change: quickly at our cohort two dose and that data thus far from the single administration perspective has looked very promising and you've seen that data and we've now presented that multiple times.

Marc Hedrick: We've now presented that multiple times. So that's up and running. So I think that so the next step, really, I know it's a long answer, but look at the phase one 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 want to 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.

Marc Hedrick: So I think the so the next step really I know is a long answer, but look at the phase one 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 want to take a single administration dose into a phase two, three pivotal as envisioned in our secret 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 want to take that to a pillow or not.

Speaker Change: So that's up and running. So I think that so the next step really I know it's a long answer, but look at the phase one data

Marc Hedrick: The second, which actually deals with a very important emerging issue of genetic drift in L.M, patients. That is where patients have a certain genetic component to their cancer that flips from their primary tumor to a metastasis, for example, in the CSF. In the title, that is the oncogenic flip in patients with leptoman angel metastases, specifically the longitudinal detection and cerebral spinal fluid tumor cell counts and what it reveals in terms of implications for the differential treatment of the L.M.D, tumor.

Speaker Change: Understand it, look at the response data, discuss with FDA, get the multiple those study up and running, and then we'll make a decision about whether or not we want to take a single administration dose into a phase two, three pivotal, as envisioned in our secret grant, for example.

Marc Hedrick: 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 want to take that to a pivotal or not. It'll be an interesting discussion, but that'll be a good problem to have.

Speaker Change: 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.

Speaker Change: 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,

Marc Hedrick: All three of those will be on again for snow in the November of time frame this year. We also anticipate FDA approval on the respect L.M. Phase I multiple dose trial. So the I.N.D, for the Phase I II study of Renium Obispermata for pediatric epinomoma and high grade glioma patients is anticipated also later this year.

Speaker Change: then we have to really seriously consider whether or not we want to take that to a

Sean Lee: It'll be an interesting discussion, but that'll be a good problem to have. Thanks for that. That's very helpful.

Speaker Change: a pillow or not. It'll be an interesting discussion, but that'll be a good problem to have.

Marc Hedrick: Thanks for that. That's very helpful. My last question is on the GBM study. I think in the preparatory remarks, you mentioned that the grant for the GBM studies will be coming to an end towards the end of this year. I was wondering whether we can expect any more data updates from that later this year as well. Yeah, so with respect to the the GBM trial, so, As mentioned, we'll do a meaningful update on the phase one progress and the phase two progress at the CNS, the Congress for Neurosurgeons, 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 going to be difficult.

Marc Hedrick: 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. Yeah, so with respect to the GBM trial. So, as mentioned, we'll do a meaningful update on the phase one progress and the phase two progress at the CNF, the Congress for Neurosurgeons, which will be in late September and into early October in Houston this year.

Speaker Change: Thanks for that. That's very helpful. My last question is on the GBM study. I think you need to prepare remarks.

Speaker Change: You mentioned that the grant for the GDM studies will be coming to an end towards the end of this year. I was wondering whether we can expect any more data updates from that later this year as well. Thanks.

Unknown Executive: So with those, Sheree, I'll turn it back over to you and we can have our Q&A session.

Speaker Change: Yeah, so with respect to the the GBM trial, so as mentioned, we'll we'll do a meaningful update on the Phase 1 progress and the Phase 2 progress at the CNS, the Congress for...

Justin Walsh: And our first question will come from the line of Justin Walsh with Jones Trading. Your line is open. 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 sea inside. Obviously, therapy selection is one, but the 24 percent that informed therapy selection is lower than the 90 percent total decisions that were impacted. Yeah, that's a good question, Justin.

Speaker Change: Neurosurgeons, 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 going to be difficult. We've got two new sites that are

Marc Hedrick: So that'll be the next update, and the goal is to get enrollment completed this year. As mentioned, I think that's going to be difficult. We've got two new sites that are in the final stages of onboarding right now. If those can contribute substantially, we've got a chance at getting trial and roll 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. We've had continue to have good safety signals and very interesting efficacy signals related to standard of care.

Marc Hedrick: We've got two 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.

Speaker Change: 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. We've had

Marc Hedrick: And then at that point, we'll evaluate the data. 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 it. Great. That's all I have.

Sean Lee: Thanks again for taking my question. Thank you, Sean. One moment for our next question. And that will come from the line of Edward Woo with Ascendant Capital.

Justin Walsh: 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 4-C 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 LN disease, but their spinal fluid is negative.

Speaker Change: continue 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 will be ready to pull the trigger on that.

Edward Wu: 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. Great. That's all I have. Thanks again for taking my questions. Thank you, Sean. Thank you. One moment for our next question.

Speaker Change: Great, that's all I have. Thanks again for taking my questions.

Speaker Change: Thank you, Sean. Thank you. One moment for our next question.

Edward Wu: And that will come from the line of Edward Wu with Ascendient Capital. Your line is open.

Unknown Executive: Your line is open. 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? 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. Hey, Ed.

Speaker Change: And that will come from the line of Edward Woo with Ascendant Capital. Your line is open.

Edward Wu: 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? Have you noticed any change in the funding that's out there? Has it been more or less, or it's been about the same?

Edward Wu: Yeah, congratulations on all the progress and congratulations on

Justin Walsh: 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 clinical evaluation, MRI and CTCs in psychology, that can often be a difficult decision to make. And generally what physicians are using now is they look to get to repeat CTC cell determinations and then make the decision if patient does not have LM and doesn't require treatment. So that's kind of number one.

Edward Wu: 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?

Speaker Change: 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.

Andrew Sims: Thank you. Hey, yeah, thanks for the question. It's definitely seasonal in this regard, and I'll take the secret for example. Secret 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 July or August in that time frame, it takes about six months to go through the review process and 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 in RFP, as I recall, and that's more of a one-off situation. So there's some peculiarities that can be seasonal, but also can be sporadic and in affecting the timing.

Edward Woo: Yeah, no, thanks for the question. It's definitely seasonal in this regard. And I'll take SIPRIT for example.

Marc Hedrick: SIPRIT 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 and 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.

Speaker Change: Hey Ed, yeah, thanks for the question.

Speaker Change: It's it's definitely seasonal in this regard and I'll take the secret for example secret has historically had to

Marc Hedrick: 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 in RFP, as I recall. And that's more of a one-off situation. So there's some peculiarities that can be seasonal, but also can be sporadic in affecting the timing.

Justin Walsh: 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 left of menial space or the opposite. The other issue is whether it's potentially advantageous to stop treatment.

Speaker Change: at 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, and let's say...

Speaker Change: July or August in that that time frame takes about six months to go through the review process to get a decision for funding and then get the administrative

Speaker Change: Award Mechanics finalized so you can receive funding. So it's seasonal in that we're responding to their granting calendar.

Justin Walsh: For example, there's 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, monitored 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-making can be impacted by the clinician.

Speaker Change: Our experience with the NIH is similar, but oftentimes it's more sporadic where they have requests for proposals.

Speaker Change: specifically our DoD proposal that we responded to in RFP, as I recall. And that's more of a one-off situation. So there's some peculiarities that can be seasonal, but also can be

Justin Walsh: Got it. Thanks.

Marc Hedrick: As mentioned, I think we, We've developed a really good relationship working with SEPRIT. We know of companies that have up to at least three grants per company. We also know that SEPRIT will fund up to $20 million through phase two. So I think there's, you know, that's been a nice relationship and that capital has been very important to us. 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 of the shareholding.

Speaker Change: and affecting the timing. As mentioned, I think we

Andrew Sims: As mentioned, I think we've developed a really good relationship working with Secret. We know of companies that have up to at least three grants per company, and we also know that Secret will fund up to $20 million through phase two. So I think that's been a nice relationship, and that capital has been very important to us. 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-delutive capital and minimize the dilution of the shareholders.

Speaker Change: We've developed a really good relationship working with SEPRIT. We know of companies that have up to at least three grants per company. We also know that SEPRIT will fund up to $20 million through Phase 2.

Speaker Change: So I think there's, you know, that's been a nice relationship and that capital has been very important to us. And so I think that's what we'll continue to try to...

Speaker Change: work with them closely as well as look at some of these more

Speaker Change: Spiratic Alternatives to continue to leverage that non-delutive capital and minimize the dilution to the shareholders.

Edward Wu: Great, well thanks for answering our questions, and I wish you guys good luck. Thank you.

Edward Woo: Great. Well, thanks for answering my questions, and I wish you guys good luck. Thank you. Thank you. I'm showing no further questions in the queue at this time.

Speaker Change: Great, well, thanks for answering my questions and I wish you guys good luck.

Marc Hedrick: I would now like to turn the call back over to Dr. Marc Hedrick for any closing room. Thank you, Cherie. And we thank everyone, our analysts and shareholders and investors for, for listening to this call, and I also want to thank our patients. We'll be talking to two of them next week in Texas, who trust us, to give them this investigational treatment.

Unknown Executive: I'm showing no further questions in the queue at this time.

Speaker Change: Thank you.

Marc Hedrick: I would now like to turn the call back over to Dr. Mark Hedrick for any closing remarks. Thank you, Sherry, and we think everyone are the analysts and shareholders and investors for listening to this call and also want to thank our patients. We're talking to two of them next week in Texas, who trust us to give them this investigational treatment. Thank you to all employees who work so hard to make it happen.

Speaker Change: 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.

Justin Walsh: So the IEDs is open. I think we're optimistic that what we've currently negotiated with FDA will ultimately go through. So we'll hear back 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 IED that's very similar, I think it ought to go pretty quickly.

Marc Hedrick: Thank you, Cherie. And we thank everyone, our analysts and shareholders and investors for

Speaker Change: for listening to this call, and I also want to thank our patients.

Speaker Change: We'll be talking to two of them next week in Texas.

Speaker Change: who trust us.

Unknown Executive: And thank you to all our employees who worked so hard to make it happen. We wish everyone a nice evening. Thank you. This concludes today's program. Thank you all for participating. You may now disconnect.

Speaker Change: to give them this investigational treatment and thank you to all our employees who worked so hard to make it happen. We wish everyone a nice evening. Thank you.

Justin Walsh: Our plan is to go back to the current seven sites that we're working with, where that should also go more quickly, but we've also got a number of of leading sites that want to participate. So 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. Some sites will be before other sites, obviously. So that's number one, in terms of how long we'll take to enroll.

Unknown Executive: We wish everyone a nice evening. Thank you.

Unknown Executive: This concludes today's program. Thank you all for participating. You may have a nice evening. Thank you all for joining us today. Thank you for joining us today. Thank you all for joining us today.

Speaker Change: This concludes today's program. Thank you all for participating. You may now disconnect.

Justin Walsh: The Phase I single administration was plagued by a couple of things. Number one, it had a part A and a part B. The FDA was very worried about 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 intro 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 DSMB.

Justin Walsh: 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. So I think the data will accumulate quickly, both in terms of number of patients and longitudinal data on a variety of end points within four individuals. Once we, 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. Great, thanks for taking the questions. Thanks, Justin. Thank you. One moment for our next question.

Sean Lee: And that will come from the line of Sean Lee with HC Wainwright. Your line is open.

Sean Lee: Good afternoon, guys, and congrats on the clinical problem versus quarter. My first question is on the CNS side SH. So my understanding is that correcting in general, but all the tech transfer has been completed, and you're not just setting up as to the manufacturer and market. 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?

Sean Lee: Hey, Sean. Thanks for the question. Yeah, let me kind of review where we are and the plan, the plan going forward. So what we've done is 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. It 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.

Sean Lee: So 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 performing the test within our trial. In the background, what we've done is we've hired a medical director, 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.

Sean Lee: And so now it's really scaling the test, now we can scale the test effectively for our multiple dose trial, we're going to be testing, many more tests on patients, longitudinally, because they're getting multiple doses and that's going to 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. Fullers on board will be the medical director 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 that analysis is going well thus far it looks very positive.

Sean Lee: But I think I before we kind of commit, we want to have a full and well thought through plan and be ready to execute on that before we save too much more, but I will say that's going well and those will be talking about that relatively soon as we finalize that plan. Great, thanks for that.

Sean Lee: My second question is on the IM 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 to hire those cohort, or would you be switching your focus mainly to the multi-dose study going forward? 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.

Sean Lee: They've made that very clear. So I think we're committed to understand where the level of toxicity lies. So, and I think we're close quite honestly. I think what we see from the safety signals in cohort 5 lead us to believe that we're probably pretty close, if not there. But as I mentioned, we have not officially reached an MTD at this point, but we'll continue that until we get to the formal stopping point, or we get to a maximum feasible dose.

Sean Lee: We're not there yet. Secondly, I think we want to 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 the single administration perspective has looked very promising and you've seen that data and we've now presented that multiple times.

Sean Lee: So that's up and running. So I think the so the next step really I know is a long answer, but look at the phase one 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 want to take a single administration dose into a phase two, three pivotal as envisioned in our secret grant, for example.

Sean Lee: 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 want to take that to a pillow or not. It'll be an interesting discussion, but that'll be a good problem to have. Thanks for that. That's very helpful.

Sean Lee: 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. Yeah, so with respect to the GBM trial. So as mentioned, we'll do a meaningful update on the phase one progress and the phase two progress at the CNF, the Congress for neurosurgeons, which will be in late September and into early October in Houston this year.

Sean Lee: So that'll be the next update and the goal is to get enrollment completed this year. As mentioned, I think that's going to be difficult. We've got two new sites that are in the final stages of onboarding right now. If those can contribute substantially, we've got a chance at getting get trial and roll 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.

Sean Lee: We've had continue 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. Great. That's all I have. Thanks again for taking my questions. Thank you, Sean. Thank you.

Unknown Executive: One moment for our next question.

Edward Wu: And that will come from the line of Edward Wu with Ascendient Capital. Your line is open. Congratulations on all the progress and congratulations on, you know, lining up additional potential grant funding.

Edward Wu: I was wondering, is there any seasonality to the grant funding? Are they issued all in certain times of the year? Have you noticed any change in the funding that's out there? Has it been more or less or it's been about the same? Thank you. Hey, yeah, thanks for the question. It's definitely seasonal in this regard and I'll take the secret for example. Secret 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 and let's say July or August in that time frame takes about six months to go through the review process and get a decision for funding and then get the administrative award mechanics finalized so you can receive funding.

Edward Wu: 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 in RFP as I recall and that's more of a one-off situation so there's some peculiarities that can be seasonal but also can be sporadic and in affecting the timing. As mentioned I think we've developed a really good relationship working with secret.

Edward Wu: We know of companies that have up to at least three grants per company and we also know that secret will fund up to $20 million through phase two so I think that's been a nice relationship and that capital has been very important to us and so I think that's what we'll continue to try to work with them closely as well as looks at some of these more sporadic alternatives to continue to leverage that non-delutive capital and minimize the dilution of the shareholders.

Unknown Executive: Great well thanks for answering our questions and I wish you guys good luck. Thank you. I'm showing no further questions in the queue at this time.

Marc Hedrick: I would now like to turn the call back over to Dr. Mark Hedrick for any closing remarks. Thank you Sherry and we think everyone are the analysts and shareholders and investors for listening to this call and also want to thank our patients. We're talking to two of them next week in Texas who trust us to give them this investigational treatment and thank you to all employees who work so hard to make it happen.

Unknown Executive: We wish everyone a nice evening. Thank you.

Unknown Executive: This concludes today's program. Thank you all for participating.

Unknown Executive: You may[inaudible]

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