EX-99.1 2 d804804dex991.htm EX-99.1 EX-99.1

Exhibit 99.1 Corporate Presentation March 2024


Forward Looking Statement This presentation contains statements that may be deemed “forward-looking statements” within the meaning of U.S. securities laws, including statements regarding clinical trials, expected operations and upcoming developments. All statements in this presentation other than statements of historical fact are forward-looking statements. These forward-looking statements may be identified by future verbs, as well as terms such as “potential,” “anticipating,” “planning” and similar expressions or the negatives thereof. Such statements are based upon certain assumptions and assessments made by management in light of their experience and their perception of historical trends, current conditions, expected future developments and other factors they believe to be appropriate. These statements include, without limitation, 186 186 statements regarding the following: the potential promise of rhenium ( Re) obisbemeda including the ability of rhenium ( Re) obisbemeda to safely and effectively deliver radiation directly to the tumor at high doses; expectations as to the Company’s future performance including the next steps in developing the Company’s current assets; the Company’s clinical trials including statements regarding the timing and 186 186 characteristics of the ReSPECT-GBM, ReSPECT-LM and ReSPECT-PBC clinical trials; possible negative effects of rhenium ( Re) obisbemeda; the continued evaluation of rhenium ( Re) obisbemeda including through evaluations in additional patient cohorts; and the intended functions of the Company’s platform and expected benefits from such functions. The forward-looking statements included in this presentation could differ materially from those expressed or implied by these forward-looking statements because of risks, uncertainties, and other factors that include, but are not limited to, the following: the early stage of the Company’s product candidates and therapies, the results of the Company’s research and development activities, including uncertainties relating to the clinical trials of its product candidates and therapies; the Company’s liquidity and capital resources and its ability to raise additional cash, the outcome of the Company’s partnering/licensing efforts, risks associated with laws or regulatory requirements applicable to it, market conditions, product performance, litigation or potential litigation, and competition within the cancer diagnostics and therapeutics field, ability to develop and protect proprietary intellectual property or obtain licenses to intellectual property developed by others on commercially reasonable and competitive terms, and material security breach or cybersecurity attack affecting the Company’s operations or property. This list of risks, uncertainties, and other factors is not complete. Plus Therapeutics discusses some of these matters more fully, as well as certain risk factors that could affect Plus Therapeutics’ business, financial condition, results of operations, and prospects, in its reports filed with the SEC, including Plus Therapeutics’ annual report on Form 10-K for the fiscal year ended December 31, 2023, quarterly reports on Form 10-Q, and current reports on Form 8-K. These filings are available for review through the SEC’s website at www.sec.gov. Any or all forward-looking statements Plus Therapeutics makes may turn out to be wrong and can be affected by inaccurate assumptions Plus Therapeutics might make or by known or unknown risks, uncertainties, and other factors, including those identified in this presentation. Accordingly, you should not place undue reliance on the forward-looking statements made in this presentation, which speak only as of its date. The Company assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made unless the Company has an obligation under U.S. federal securities laws to do so. 2


Targeted Radiotherapeutics for CNS Cancers Corporate overview Compelling Platform Mid 2025 Significant CNS Cancer Survival Data Technology Cash Runway Milestones Focus + Nanoliposome and Rhenium + Aggregate market opportunity of + Completing rGBM Phase 2 + Interim rGBM Phase 2 data + Sufficient to fund isotope-based theragnostic $10B for current indications in in next 12 months and operations through mid- (n=15): 13 months median pipeline development interim data analysis at SNO 1 2 2025 OS vs. SOC ~8 months 2024 + Novel directly targeted CNS + Leptomeningeal metastases (LM) + 2 active grants totaling + LM Phase 1 dose escalation radiotherapy platform has 250-400k patients per year + Completing LM single dose $25M in support with (n=15): No DLTs and median with no approved treatments and Phase 1 in 2024 and + Highly scalable supply chain many others pending 1 OS of 10 months vs. poor diagnostics interim data analysis at SNO 3 expected SOC ~4 months 2024 + Recurrent glioblastoma (rGBM) has recurrence in nearly all + Presenting FORESEE LM patients with few approved diagnostic trial data in 2024 treatment options 1. Data analyzed as of 01Oct23, presented at SNO 2023. 2. Wen et. al. Neuro Oncol. 2020 Aug 17;22(8):1073-1113.doi: 10.1093/neuonc/noaa106. 3 3. Nguyen et. al. Curr Oncol. 2023 Jun 19;30(6):5906-5931. doi: 10.3390/curroncol30060442.


Recent Press and Partnerships Highlight Accelerating Interest in Radiopharmaceuticals Innovator Acquirer Date 2/13/2023 4/24/2023 5/10/2023 10/3/2023 12/26/2023 1/9/2024 Deal Type Asset Acquisition License Deal Strategic Collaboration Company Acquisition Company Acquisition License Deal Aggregate Value $63M $425M $1.7B $1.4B $4.1B $61M • $750K option fee • $45M upfront • $1.5M option exercise • $40M upfront • Development and • $10.5M • Development, • $28M upfront commercial-based clinical/regulatory regulatory, and $12.50/share – 87% $62.50/share – 104% • $33M equity investment Key Deal Terms milestones ($1.7B) milestones commercial-based premium premium (19.9% of outstanding • Mid-single • $50M sales milestones milestones ($425M) shares) to double-digit tiered • Low-single digit • Tiered royalties royalties royalties 4


Unique Challenges with CNS Cancer Treatment Plus’ technology overcomes all key limitations Radiotherapy Limitations Locally Invasive Blood Brain Barrier Only 2% of drugs cross the EBRT dose limited by off target 90% of GBM recurs 2 cm from BBB safety concerns primary tumor Chemoresistance Complex Anatomy Surgical Therapy Inadequate MGMT status and acquired Getting ‘drug on tumor’ more Clean surgical margins unobtainable resistance difficult Wen et. al. Neuro Oncol. 2020 Aug 17;22(8):1073-1113.doi: 10.1093/neuonc/noaa106. Nguyen et. al. Curr Oncol. 2023 Jun 19;30(6):5906-5931. doi: 10.3390/curroncol30060442. 5 Friedman, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–4740.


186 Rhenium ( Re) Obisbemeda is a 3-Part Formulation Radiotherapy Prolongs persistence at tumor and optimizes convection while sparing healthy tissue Tumor Retention 186 Rhenium-186 ( Re) 60% 186Re-NanoLiposomes 186Re-BMEDA 50% Proprietary formulation 186Re-Perrenate demonstrates persistence in 40% the tumor throughout the 30% decay cycle of the isotope 20% 10% 0% 0 50 100 150 Time (hours) BMEDA Small Molecule 186 Chelates Re before loading into the nanoliposome where it Improved Drug Distribution is irreversibly trapped 100 nm Nanoliposome 99m 99m Tc-BMEDA only Tc+NanoLiposome 186 Carries BMEDA- Re to target tumor and improves Proprietary formulation retention improves convection and distribution throughout the brain 6 % Injected Activity


Direct RT Drug Delivery Strategies for CNS Cancers Overcomes barriers to CNS drug delivery Convection-Enhanced Delivery (CED) Intraventricular Catheter (Ommaya reservoir) + FDA-approved and utilized for 60+ years + FDA-approved and utilized for 20+ years + Bypasses BBB + Bypasses BBB + Small subcutaneous reservoir with direct ventricle access + ‘Biological fracking’: Controlled pressure and flow are optimal for drug delivery to region of interest + Allows multidosing and CSF sampling + Utilized for GBM and other brain tumors + Commonly placed in LM patients Brain Parenchyma Cerebrospinal Fluid 7


A New Paradigm for CNS Radiotherapy A direct targeted approach is a step function improvement in CNS radiation delivery Gold Standard New Paradigm External Beam Plus’ Directly Radiation Therapy Targeted RT Delivery + Direct delivery to the tumor site + Standard of care for decades + Key challenges eliminated + Requires fractionation + Monitor drug location with real-time imaging + Limited absorbed dose due to off-target toxicity + Quantify absorbed doses + Mature technology + Safe delivery of high activity Imaging & Pre-Treatment Biopsy & Convection Dosimetry & Planning Catheter Enhanced Imaging Placement Delivery 8


Seamless drug supply into patient workflow Highly scalable workflow to meet commercial demand Centralized GMP Standard RAM Shipping and Drug Order and Scheduling Overnight Delivery Manufacturing Receiving Drug order scheduled and timed to The patient’s dose is batch Drug is delivered to hospital via In-hospital transfer to nuclear imaging patient surgery date manufactured on demand prior to standard overnight delivery for drug infusion administration 9


Therapeutic Product Pipeline Status and 2024 milestones IND/ Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones 2024 IDE 186 Rhenium ( Re) Obisbemeda 186 Rhenium ( Re) Obisbemeda • Data presentation at SNO Nov 2024 Single dose administration trial ReSPECT-LM Single Dose Trial • Begin P2 in breast cancer in 2024 Leptomeningeal Metastases ReSPECT-LM Multidose Trial Multidose trial • Initiate P1 trial (all comers) in 2024 • Complete enrollment in 2024 (n=34) Recurrent glioblastoma for small-to- ReSPECT-GBM • Interim data at SNO Nov 2024 medium sized tumors • Present pivotal trial design in 2024 Malignant Gliomas Pediatric high-grade glioma and ReSPECT-PBC • IND approval & initiate enrollment in 2024 ependymoma Rhenium NanoLiposome Biodegradable Alginate Microsphere (RNL-BAM) Various Solid Tumors • Formulation optimization Primary and Secondary Liver Cancer CNS tumors Glioblastoma • Proof-of-concept studies 10


Leptomeningeal Metastases Power and precision in cancer radiotherapeutics


Leptomeningeal Metastases from Solid Tumors Poor prognosis and no FDA-approved treatments LM Treatment LM Diagnosis + Poor survival of 4-6 weeks without + Late-stage cancer complication in which Melanoma treatment cancer cells metastasize from any primary Breast tumor to the CSF space and leptomeninges + No approved therapies + Increasing incidence with ~155,000 U.S. patients per year + No standard of care; treatments (systemic (5-8% of those with solid tumors) Solid and therapy for primary cancer and Hematologic craniospinal-directed chemo and + Likely 2-4x underdiagnosed based on Tumors radiation) may relieve symptoms, but do autopsy findings not halt disease progression nor impact survival Opportunities: Other + First-in-class radiotherapeutic with a targeted dose delivered in a single outpatient Lung administration + First-in-class highly sensitive and specific diagnostic to monitor disease and therapy 12


Leptomeningeal Metastasis Incidence About 250,000 new cases of LM are diagnosed each year in the US U.S. Incidence Standard of Care: Primary Tumor Type (% solid tumors) Median Overall Survival Patients Breast 12-34%* 3.5-4.4 months ~210,000 Lung 10-26%* 3-6 months ~130,000 Melanoma 17-25%* 1.7 to 2.5 months ~45,000 Other Cancer 5%* 2-4 months ~200,000 + *Le Rhun, E., et. al. (2013). Surgical neurology international. https://doi.org/10.4103/2152-7806.111304 + ~300,000 new breast cancer cases estimated to be diagnosed in US in 2024 (https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html) + ~240,000 new lung cancer cases estimated to be diagnosed in US in 2024 (https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html) + ~100,000 new melanoma cases estimated to be diagnosed in US in 2024 (https://www.cancer.org/cancer/types/melanoma-skin-cancer/about/key-statistics.html) + ~1.3M other cancers diagnosed in US in 2023 (https://seer.cancer.gov/statfacts/html/common.html) 13 + 2-4X underdiagnosed


ReSPECT-LM Phase 1 Single Administration Dose Escalation Trial 186 Targeted delivery of Rhenium ( Re) Obisbemeda by Ommaya reservoir + Dose escalation: 3+3 modified Fibonacci + Primary objective: Safety and tolerability Single Administration Phase 1 Dose Escalation Plan + Maximum Tolerated Dose / Maximum Feasible Dose Administered Administered Administered + Secondary objectives: Efficacy Cohort Activity Concentration Volume + Overall Response Rate (ORR) (mCi) (mCi/mL) (mL) + Duration of Response (DoR) + Progression Free Survival (PFS) 1 5 6.6 1.32 + Overall survival (OS) 2 5 13.2 2.64 + Exploratory objectives: Analysis on cerebral spinal fluid 3 5 26.4 5.28 (CSF) pre- and post-administration + CSF tumor cell enumeration 4 5 44.10 8.82 + Pharmacodynamic (PD) markers 5 5 66.14 13.23 + QoL assessments CURRENT 6 5 87.97 17.59 + Funding: $17.6M grant from largest state funding agency (CPRIT) 7 5 109.96 21.99 14


ReSPECT-LM Safety MTD/MFD not reached over 5 cohorts Average Absorbed Doses 180 160 140 120 + Generally safe and well tolerated 100 + Complete CSF circulation of drug within hours 80 and duration at least 7 days 60 + No evidence of systemic radiation toxicity 40 20 + Absorbed doses to key therapeutic areas increase 0 with administered dose Cohort 1 Cohort 2 Cohort 3 Cohort 4 + Absorbed doses to critical organs remains low Spleen Ventricles and Cranial Subarachnoid Space Spinal Fluid + All but one SAE unrelated to study drug Trial Safety Summary Grade % n >5% AEs SAEs Grade 1 64.10% (68) Grade 2 27.35% (31) Grade 3 7.27% (8) Headache (5.45%) 5 Grade 4 0.91% (1) Grade 5 0.91% (1) 15 Gy


ReSPECT-LM Phase 1 Treatment Response Data Median overall survival and percent CSF tumor cell change show effect of treatment Median Overall Survival Average Percent CSF Tumor Cell Change Over Time 150% 100% 50% 0% -50% -100% -150% 0 10 20 30 40 50 Time (Days) + N = 13 evaluable patients + N = 10 patients, cohorts 1-3 + Max percent reduction in CSF tumor cells at D28 was 90% + mOS was 10 months* + Average of 53% CSF tumor cell reduction at D28 + 5 of these patients remain alive** *August 1, 2023 16 **As of 12Mar2024 % Change


ReSPECT-LM Individual Patient Analysis Analysis by survival time following single administration Overall Survival By Cohort D28 CSF TC mOS -53% 684 1-02 + N = 18 evaluable patients -6% 558 2-01 0% 411 + 12 of 18 patients alive 2-02 -90% 334 3-02 + Tumors by primary disease -81% 333 3-04 -53% + Lung: 6 311 1-03 -100% 200 4-01 + Breast: 9 -94%* 172 4-02 + Other: 3 NA 94 3-03 -90% + 2 patients received compassionate use 94 1-01 6% nd 82 2-03 2 dose NA 60 4-04 NA 41 4-03 NA 33 5-01 -2%* 3-01 20 LEGEND NA 5-03 5 • Black: breast primary cancer • Orange: lung primary cancer NA 5 5-02 • Blue: other primary cancer NA • Hatched fill: Alive 4-05 4 • Solid fill: Deceased • Star: Retreatment date 0 100 200 300 400 500 600 700 800 Overall Survival Time (Days) Breast cancer OS *24 hours 17 Lung cancer *Analysis 11Mar24 OS Cohort-Patient


CNSide Tumor Cell Enumeration Assay Highly sensitive and specific test of metastatic carcinomas in the CSF Proprietary Technologies Proprietary Testing Process Individual Cell Data CSF collection & transport system Sample Collection 1 • Stabile at ambient temperature (4 days) Shipping & Receiving CEE-Sure collection 2 system • Preserves membrane antigens Primary Antibody 3 Cocktail Cell enumeration testing The CNSide test is designed to quantitate CSF tumor cells 4 Secondary Antibody originating from breast, GI, cervix, kidney, lung, pancreas, prostate and stomach or melanomas originating from skin. Microfluidic Cell Capture 5 CNSide assay available for Monoclonal Antibody Cocktail Automated Cell ReSPECT-LM trial EpCAM, MET, SUSD2, Trop2, MUC1, CD318, 6 Visualization & Analysis HER2, FOLR1, MCAD, EGFR as of Q1 2024 7 Report 18


CNSide Clinical Impact and Next Steps FORESEE clinical feasibility trial enrolled and data readout pending + CNSide test available commercially and reimbursed prior to Q3 2023 + FORESEE Clinical Trial (NCT0541123) CNSide CSF-TC results & treatment status now enrolled + Prospective multicenter trial + N = 40 patients + Primary endpoint: Determine the impact of CNSide in combination with MRI, cytology, and clinical evaluation on clinical decision making + Secondary: Correlate TCs with LM clinical response and cytology + Data anticipated mid 2024 + Next steps: Clinical Impact- single patient longitudinal follow up + Publication FORESEE data + Reinstate CLIA certification + Seek inclusion in NCCN guidelines + Re-launch commercial testing in 2025 19


ReSPECT-LM and CNSide Pipeline Clinical development timelines Therapeutic Pre 2024 2025 2026 2027 2028+ 2024 Phase 2/3: Single dose pivotal trial, Phase 1: Single dose escalation breast cancer basket trial Phase 1: Multidose escalation Phase 2/3: Multidose pivotal trial, basket trial breast cancer Phase 2/3: Multidose pivotal trial, additional indications Diagnostic Pre 2024 2025 2026 2027 2028+ 2024 FORESEE Feasibility Trial FORESEE Validation Trial 20


Recurrent Glioblastoma Power and precision in cancer radiotherapeutics


Malignant Gliomas The brain’s most frequent and deadly tumors despite decades of research GBM Treatment GBM Diagnosis Ependymoma Oligodendroglioma + 14,500 patients newly diagnosed GBM + No standard of care following patients in US each year recurrence + Poor survival rate, 7% at 5 years + Only 5 FDA-approved therapies in the last 50 years + Almost all reoccur several months from surgery + Clinical trial recommended by NCCN guidelines for CNS cancers upon + Poor survival after recurrence, ~8 months recurrence mOS Astrocytoma GBM Opportunities: Treat adult & pediatric malignant gliomas with a first-in-class targeted Pediatric High-Grade Glioma radiotherapeutic that directly delivers high-dose radiation to the tumor while sparing healthy Pediatric DIPG tissue 22


Multiple Therapeutic Opportuntities for Rhenium (186Re) Obisbemeda Significant clinical & commercial upside for this therapeutic platform Addressable Standard of Care: Proposed Indication U.S. Incidence Patients Median Overall Survival Recurrent Glioblastoma 14,250 8 months 9,500 Primary Glioblastoma 15,000 ~14 months 5,000 Pediatric Ependymoma 250 Chronic 250 Pediatric High-Grade Glioma 800 14 months 200 70,000-400,000 Brain metastases 12 months or less 10-50% (10-40% of patients with solid tumors) 23


186 Rhenium ( Re) Obisbemeda for Glioblastoma PLUS’ novel approach overcomes limitations of all 3 current treatment modalities GBM Tumor Pathophysiology Surgery PLUS Extremely Difficult to Treat Obtaining adequate surgical margins nearly impossible 186 Rhenium ( Re) Obisbemeda Systemic Drugs Only 2% of drugs pass the BBB External Beam Radiation Therapy Inadequate tumoricidal doses because of toxicity to heathy Infiltrative Margin Goal- treat both tumor and infiltrative brain tissue 90% recurrences: 2 cm margin with at least 100 Gy radiation 24


186 Rhenium ( Re) Obisbemeda Advantage Over EBRT More targeted radiation delivery with 10x increase in max absorbed dose 186 EBRT Rhenium ( Re) Obisbemeda EBRT vs. 186 Rhenium ( Re) Obisbemeda 28.5 Gy 250 Gy Max dose Max dose 5 Gy 5 Gy 25


ReSPECT-GBM Treatment Workflow Inpatient single administration SoC Biopsy and Catheter Personalized Drug Infusion Patient Monitoring Treatment Planning Placement Day 1 Day 2-3 Day 0 Prior to Treatment MRI imaging to assess Confirmatory biopsy followed by Single ~4-hour infusion Catheter removal, patient and plan catheter number, neuro navigation & precision with real-time SPECT/CT imaging in discharge and follow dosimetry & trajectory, and location catheter placement Nuclear Medicine imaging 26


ReSPECT-GBM Phase 1, Single Dose Trial Design 186 Single administration of Rhenium ( Re) Obisbemeda by Convection Enhanced Delivery (CED) Single Administration Phase 1 Dose Escalation Plan + Dose escalation: 3+3 modified Fibonacci, currently enrolling in cohort 8 Administered Administered Administered + Primary objective: Safety and tolerability Cohort Volume Activity Concentration + Maximum Tolerated Dose / Maximum (mL) (mCi) (mCi/mL) Feasible Dose 1 0.66 1.0 1.5 + Secondary objectives: Efficacy + Dose distribution 2 1.32 2.0 1.5 + Overall Response Rate (ORR) 3 2.64 4.0 1.5 + Progression Free Survival (PFS) 4 5.28 8.0 1.5 + Overall survival (OS) + Imaging 5 5.28 13.4 2.5 + Funding: NIH/NCI grant through Phase 2 RP2D 6 8.80 22.3 2.5 7 12.3 31.2 2.5 Current 8 16.34 41.5 2.5 27


ReSPECT-GBM Safety MTD/MFD not reached in dose escalation phase Average Absorbed Dose to Tumor by Cohort Tumors >20 mL Tumors <20 mL 450 + Generally safe and well tolerated over 28 patients in 8 dosing 400 cohorts, enrollment ongoing 350 + No evidence of systemic radiation toxicity 300 250 + The average absorbed dose to the tumor for all Phase 1 patients was 264 Gy (range: 8.9-739.5 Gy) 200 150 + Most Phase 1 adverse events (AEs) were mild or moderate and resolved with treatment 100 50 + Average absorbed dose to the tumor (n=15) of 309 Gy 0 1 2 3 4 5 6 7 8 + Increasing tumor size lowers absorbed dose (cohorts 7 & 8) Cohort + Phase 2 safety profile tracks with Phase 1 Trial Safety Summary Grade >5% AEs SAEs Grade 1 66.67% Headache (6.67%) Grade 2 25.71% Fatigue (5.24%) 17 Grade 3 7.62% 28 Gy


ReSPECT-GBM Phase 1 Efficacy Dichotomous patient stratification of patients based on 100Gy absorbed dose threshold Median Progression Free Survival Median Overall Survival Progression free survival or PFS Median overall survival or mOS + All patients: mPFS 4.0 m (95% CI 2.0-6.0 m, PFS6=0.21±0.11) + All patients: mOS was 11.0 m (95% CI 5.0-17.0 m, OS9=0.55±0.11) + Patients with <100 Gy: mPFS of 2.0 m (95% CI 1.0-4.0 m, PFS6=0.0) (blue) + Patients with <100 Gy: mOS of 6.0 m (95% CI 1.0-11.0 m, OS9=0.19±0.18) + Patients with ≥100 Gy: mPFS of 6.0 m (95% CI 3.0-8.0 m, PFS6=0.32±0.16) (blue) (red) + Patients with ≥100 Gy: mOS of 17.0 m (95% CI 8.0-35.0 m, OS9=0.84±0.11) (red) *At time of analysis, November 2023 29


ReSPECT-GBM Phase 2 Efficacy Phase 2 data similar to Phase 1 data Median Progression Free Survival Median Overall Survival + PFS: 11 months (95% CI 6-11 months) + OS: 13 months (95% CI 5 months-NA) *At time of analysis, November 2023 30


Comparative Survival Data Overall Survival Comparison ReSPECT-GBM vs. Real World Experience 20 18 + Meta analysis of >700 rGBM patients 16 + Plus and Medidata conducted 2 RWE control 14 arms with propensity match rGBM patients to 12 Plus Phase 1 data 10 + Propensity matching- baseline characteristics were well-aligned 8 + 38% improvement over RWE control for Phase 6 1 (to RP2D) 4 + Respect GBM phase 1 N = 21, phase 2 N = 15 2 (6 alive**) 0 Meta-analysis- + 113% improvement over RWE control in ReSPECT-GBM Phase 1 ReSPECT-GBM Phase 2 MEDS-Bevacizumab MEDS-CED Bevacizumab (>100 Gy) patients receiving therapeutic dose radiation (n=~700) (n=636) (n=163) (n=21) (n=15) (>100Gy) 186 Rhenium ( Re) Obisbemeda RWE Propensity Matched Meta Analysis data Controls Neuro-Oncology + 63% improvement in Phase 2 patients (n=15 of 34 planned patients) *Data sourced from from the Medidata Enterprise Data Store (MEDS) of deidentified patient-level historical clinical trial data, study and patient-level data from historical rGBM CED studies [D’Amico, J Neurooncol 2021], and from on- 31 going ReSPECT-GBM study. ** At time of analysis, 12Mar24


ReSPECT-PBC 186 Rhenium ( Re) Obisbemeda for supratentorial recurrent, refractory, or progressive pediatric high-grade glioma and ependymoma + Dose escalation: 3+3 modified Fibonacci, varying Single Administration Phase 1 Dose Escalation Plan administered volume with tumor volume to maximize therapeutic effect Administered Administered Administered Tumor Volume + Primary objective: Safety and tolerability Cohort Volume Activity Concentration (mL) (mL) (mCi) (mCi/ml) + Maximum Tolerated Dose / Maximum Feasible Dose 0.5 1.4 0.7 0.5 + Secondary objectives: Efficacy A 1.8 2.7 1.35 0.5 + Dose distribution 4.2 4.7 2.35 0.5 + Neuropsychologic outcomes + Overall Response Rate (ORR) 8.2 7.5 7.5 1 + Progression Free Survival (PFS) B 14.1 11.2 11.2 1 + Overall survival (OS) 22.4 15.9 15.9 1 32


ReSPECT-GBM and ReSPECT-PBC Pipeline Clinical development timelines Recurrent Glioblastoma Pre 2024 2025 2026 2027 2028+ 2024 Phase 1: Single administration dose escalation MFD/MTD Phase 3: Single administration Phase 2: Single administration tumors < 20 mL vs. Control tumors < 20 mL vs. RWE Phase 2: Brain Mets Phase 2: Primary GBM Pediatric Brain Cancer Pre 2024 2025 2026 2027 2028+ 2024 Phase 1 Phase 2 33


Selective Internal Radiotherapy (SIRT) for Solid Tumors Power and precision in cancer radiotherapeutics


SIRT (Selective Internal Radiotherapy) Rhenium NanoLiposome Biodegradable Alginate Microsphere (RNL-BAM) is a next generation SIRT technology Current Market Liposomes & Re-BMEDA (BMEDA = chelator) + Inoperable liver tumors: primary & metastatic disease + Regulated as devices + TheraSpheres and SIR-Spheres + Permanent implants + Poor visibility of drug location + > $1B market opportunity for liver only 60-80 Biodegradable Alginate micrometers Microsphere RNL-BAM PLUS Product Differentiation + Bioresorbable- allows retreatment + Regulated as a device + Theragnostic (beta and gamma energy) + Visible on angiography Embolization of + Substantial upside potential for liver & other Tumor organs, including brain 35


Financials and Milestones Power and precision in cancer radiotherapeutics


Capitalization Summary As of December 31, 2023 Expected Runway Grant Funding Share Count Balance Sheet $17.6M Cash, Grants, and 4.5M CPRIT, with $6.9M Access to Capital $8.6M Basic Common forecast in 2024 to Financing Cash, Cash Shares Sources to Fund Equivalents, and Operations Investments 0.14M NIH into 2025 Series U Warrants Funding rGBM (Sept 2024) through Phase 1/2 trial 37


Upcoming 2024 Key Milestones LM Cancer Program & ReSPECT-LM Trial + Complete Phase 1 single dose trial and present data at SNO Nov 2024 + Determine RP2D for Phase 2 single dose trial + Initiate Phase 1 multidose trial 186 + Evaluate combination of Rhenium Re Obisbemeda with PDL1 and PD1 therapies for LM in preclinical models Brain Parenchymal Cancer Program & ReSPECT-GBM Trial + Complete Phase 2 single dose trial and provide interim data at SNO Nov 2024 + Present pivotal trial design Pediatric Brain Cancer Program & ReSPECT-PBC Trial + IND approval and initiate enrollment CSF Diagnostic Program & FORESEE Trial + Report FORSEE LM CSF clinical trial data in mid 2024 38


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