Slides
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed January 2025 Corporate Presentation NASDAQ: CLRB
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Forward-Looking Statements and Disclaimers This presentation contains forward-looking statements. Such statements are valid only as of today, and we disclaim any obligation to update this information. These statements are only estimates and predictions and are subject to known and unknown risks and uncertainties that may cause actual future experiences and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Factors that might cause such a material difference include our ability to pursue strategic alternatives; our current views with respect to our business strategy, business plan and research and development activities; the progress of our product development programs, including clinical testing and the timing of commencement and results thereof; our projected operating results, including research and development expenses; our ability to continue development plans for CLR 121225, CLR 121125, CLR 1900 series, CLR 2000 series, and iopofosine I 131 (also known as CLR 131 or iopofosine); our ability to continue development plans for our Phospholipid Drug Conjugates (PDC); our ability to maintain orphan drug designation in the U.S. for iopofosine as a therapeutic for the treatment of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia multiple myeloma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and Ewing's sarcoma, and the expected benefits of orphan drug status; any disruptions at our suppliers; our ability to advance our technologies into product candidates; our enhancement and consumption of current resources along with ability to obtain additional funding; our current view regarding general economic and market conditions, including our competitive strengths; uncertainty and economic instability resulting from conflicts, military actions, terrorist attacks, natural disasters, public health crises, including the occurrence of a contagious disease or illness, cyber-attacks and general instability; the future impacts of legislative and regulatory developments in the United States on the pricing and reimbursement of our product candidates; our ability to meet the continued listing standards of Nasdaq; assumptions underlying any of the foregoing; any other statements that address events or developments that we intend or believe will or may occur in the future; our ability to receive NDA approval for our iopofosine I 131 program and our ability to commercially manufacture and launch our product candidate if we receive regulatory approval. A complete description of risks and uncertainties related to our business is contained in our current and periodic reports filed with the Securities and Exchange Commission, including our Form 10-K for the year ended December 31, 2024, and our subsequent reports on Form 10-Q. This presentation includes industry and market data that we obtained from industry publications and journals, third-party studies and surveys, internal company studies and surveys, and other publicly available information. Industry publications and surveys generally state that the information contained therein has been obtained from sources believed to be reliable. Although we believe the industry and market data to be reliable as of the date of this presentation, this information could prove to be inaccurate. Industry and market data could be wrong because of the method by which sources obtained their data and because information cannot always be verified with complete certainty due to the limits on the availability and reliability of raw data, the voluntary nature of the data-gathering process, and other limitations and uncertainties. In addition, we do not know all of the assumptions that were used in preparing the forecasts from the sources relied upon or cited therein. 2
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 3 Overview • Validated PDC platform possessing the capacity to deliver a broad array of oncology therapeutic modalities; capable of conjugating any radioisotope to target solid and hematologic tumors – Streamlines and overcomes typical drug conjugate development challenges – Initiated CLR 125 Phase 1b Triple Negative Breast Cancer (TNBC) Study - Auger emitting therapeutic – Completed IND package for CLR 225 (actinium) program - Phase 1 targeting pancreatic cancer – Preclinical data with targeted radiotherapies including Lu177, Pb212, and At211 • Phospholipid Radioconjugate (PRC), iopofosine I 131 in Waldenstrom’s macroglobulinemia (WM) – Achieved statistically significant response rate (primary endpoint) in Phase 2b CLOVER WaM study – Granted U.S. FDA Breakthrough Therapy and EU EMA PRIME designations – Submitting EU conditional marketing authorization (CMA) application 3Q26 following formal guidance from Scientific Advice Working Party confirming eligibility – Preparing U.S. FDA accelerated approval application utilizing Phase 2b CLOVER WaM study data Discovering and Developing the Next Generation of Phospholipid Drug Conjugates (PDC’s)
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Formula for Value Creation 4 • Leverage novel PDC platform - Advance into Phase 1 solid tumor studies – Execute CLR 125 TNBC study ~ r/r global market potential ~$11B – Initiate CLR 225 targeting pancreatic cancer, ~ r/r global market potential ~$10B – Thoughtful investment in preclinical program development • Optimize WM regulatory approval pathway for iopofosine I 131 – CMA application submission 3Q26 to European Medicines Agency; potential 2027 EU commercialization – Phase 3 confirmatory study supports accelerated approval in US (pre-filing) potential approval in 2027 • Complete US and EU iopofosine I 131 development and commercialization partnerships • Secure additional platform collaborations for accelerated asset development and non-dilutive funding • Competitive advantage created by unique radiotherapeutic manufacturing and supply chain infrastructure • Extensive IP portfolio; radio-conjugates, small molecules, oligonucleotide payloads and linker technology Strategic Growth and Expansion
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Pipeline 5 Compound Disease State Preclinical Phase 1 Phase 2 Phase 3 Iopofosine I 131 Iodine-131 β-emitting radioconjugate Waldenström macroglobulinemia b-cell Malignancies Pediatric High-grade Glioma CLR 121125 Iodine-125 Auger-emitting radioconjugate Solid Tumor - TNBC CLR 121225 Actinium-225 α-emitting radioconjugate Solid Tumor - Pancreatic Early Pipeline Alpha Emitters (211At, 212Pb, 223Ra) Beta Emitters (177Lu, 90Y, 67Cu) Phase 1 Ready Phase 1b Phase 1b DLBCL, MM & NHL Clover WaM Phase 2 Study r/r WM CONDITIONAL MARKET AUTHORIZATION APPROVAL ACCELERATED APPROVAL Phase 1a/b Ready IND Enabling
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 6 Milestones Defined Global Regulatory Pathway for Iopofosine in WM FDA Approval Rate for Oncology Drugs with BTD is 79%, EMA Approval Rate 80% with Confirmation of CMA Eligibility 2 3
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Phospholipid Drug Conjugate (PDC) Platform Mechanism of Action (MOA)
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Universal, Intracellular Targeting with Diverse Payloads Enhanced Targeting, Limited Resistance, No Need for Bystander Effect, Improved Toxicity PDC CONTAININGDESIREDPAYLOADWITH TUMOR-TARGETINGPHOSPHOLIPIDETHER 8 SPECIFIC TARGETING OF LIPID RAFT ON CANCER CELL MEMBRANE INTERCELLULAR DELIVERY AND RELEASE OF PAYLOAD BY TRANSMEMBRANE FLIPPING OF LIPID RAFT PROFILE DIVERSE PAYLOAD PAN-CANCER TARGETING CANCER SPECIFIC TARGET RAPID UPTAKE CNS PENETRATION CYTOPLASMIC ENTRY Phospholipid Drug Conjugate1 (PDC) PDCs Overcome Drug Conjugate Challenges
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform: Therapeutic Modalities 9 Near Term Focus on Radiotherapeutics THERAPUTIC MODALITIES CONJUGATES ONCOLOGY PAYLOADS Radioconjugate (PRC) Radioconjugate • Targeted delivery of any radioisotope • Auger, alpha and beta emitters • Iopofosine I 131 - confirmatory study • Beta emitter (131I, 177Lu, 90Y, 67Cu, etc.) • Alpha emitter (211At, 225Ac, 223Ra, 213Bi, etc.) • Auger emitter (125I, 123I, 201Tl, etc.) • Additional isotopes (153Gd, 67Ga, etc.) Cytotoxic Molecule (PCC) Small-molecule Conjugates • Observed in vivo tolerability and activity in multiple animal models • Pico and nanomolar activity • PLK-1 • Seco-duba • MMAF • Collaboration - undisclosed target Biologics (PPC) Peptide and Nanobody Conjugates • Targeting intracellular pathways that cannot be targeted with small molecules • Ribosomal peptide • Protein inhibitors • Collaboration - undisclosed target Nucleic Acid (POC) Oligo Conjugates • Intracellular delivery of nucleic acids providing knockdown or knock-in gene control in cancer cells • RNAi-/siRNA • mRNA • cDNA • Collaboration - undisclosed target Extensive Intellectual Property Portfolio; Radio-Conjugates, Small Molecules, Oligonucleotide Payloads and Linker Technology
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Lipid Rafts The Role of Lipid Rafts as a Universal Target in Cancer 10 Lipid Rafts: Specialized microdomains within the plasma membrane play a significant role in cancers by facilitating processes like cell signaling, proliferation, survival, invasion, metastasis, and drug resistance. The enriched presence of cholesterol, sphingolipids, and specific proteins in these microdomains enhances the ability of tumor cells to thrive in challenging environments Enhanced oncogenic signaling • Concentrate and stabilize growth factor receptors Survival and resistance to apoptosis • Help cancer cells survive and escape programmed cell death Cancer invasion and metastasis • Facilitate cancer cell migration, invasion, and metastasis Targeting cancer • High prevalence on tumor cells vs. healthy tissue • Stabilize for approximately 10 days in tumor cells compared to milliseconds for healthy tissue • Uniformly present across tumor cells and tumor types Lipid rafts and play an essential role in cancer Lipid Rafts Play an Influential Role in Cancer
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Lipid Rafts Mediate Entry into Tumor Cells 11 Overabundance of Lipid Rafts on Tumor Cells Targeting and Uptake by Lipid Rafts Proof of Concept MBCD pretreatment Disrupted lipid rafts Uptake decreased by ~60% A549 NSCLC A549 labeling vs Fibroblast Co-cultured Prostate Pancreatic Kidney Lung No MBCD pretreatment Intact lipid rafts Lipid Rafts Fluorescent-labeled with Cholera Toxin Subunit Methyl-β-cyclodextrin (MBCD) Selectively Disrupts Lipid Rafts Green = fluorescent tagged PDCRed = labeled lipid rafts
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Utility Provides Competitive Advantage Ability to Use a Broad Range of Radiotherapeutic Emitters 12 Beta Emitting Alpha Emitting Auger Emitting A Radiation Provides Therapeutic Bystander Effect • Enhanced anti-tumor immune response Our Isotopes • I-131, Lu-177, Y-90 Targets • WM, MF, iNHL, pHGG, MM, Prostate, etc Radiation Confined to Tumor Environment • Enhanced adjacent tumor cell death Our Isotopes • Ac-225, At-221, Ra-223, Pb-212 Targets • Pancreatic, Ovarian, etc Radiation Confined to Tumor Cell • Enhanced precision improves therapeutic index Our Isotopes • I-125, I-123 Targets • Triple negative Breast, Lung, etc PDC Platform Provides Rapid Isotope Comparison and Selection
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Allows for Rapid Determination of Right Isotope Flexibility Provides Ideal Results 13 CLR-225Ac CLR-177Lu CLR-125I • Activity with all three emitters (alpha, beta, & auger) in different tumors (pancreatic, breast, triple negative breast) • Provides the ability to optimize the type of radiotherapy to the tumor and microenvironment • Different isotopes have better outcomes in different tumors Selection of the Right Isotope for the Right Job Optimizes Outcomes
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Despite Significant R&D Investment Limited Indications under Development 14 Marketed Radiotherapeutic Indications: • 2 Prostate Cancer (mPC) • 1 Neuroendocrine Tumors (GEP-NET) Late-Stage Radiotherapeutic Indications (Population): • 3 mPC (142,290) • 3 GEP-NET (29,664) • 1 r/r WM (11,500) CLRB Radiotherapeutic Indications (Population): • Pancreatic Cancer (43,824) • Triple Negative Breast Cancer (~40,540) • r/r WM (11,500) • DLBCL • Multiple Myeloma • Non-Hodgkin Lymphoma • Pediatric High-Grade Glioma 3 7 7 PDC Platform: Evolving Radiotherapeutic Landscape
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PDC Platform MOA: Validated Clinically and Preclinically Enabling Treatment of Tumors through Enhanced Targeting and Novel Payloads 15 Clinical Proof of Concept Iopofosine I 131 Phase 2 data in WM (~84% ORR) and other hematologic indications Broad Radio-conjugate Proof of Concept In vivo activity in multiple tumor types with radioisotopes; Lutetium, Actinium, Lead, Astatine, Iodine and others Novel Payload Proof of Concept Demonstrated preclinical in vivo activity with small molecules, oligonucleotides, and peptides Targeting and Uptake Proof of Principle Clinical and in vivo imaging and dosimetry data demonstrates targeting and uptake
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Phospholipid Radioconjugate (PRC) Program Manufacturing and Distribution
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 17 Manufacturing & Supply Chain Multi-sourced Network Enables Uninterrupted Supply • Redundancy provides seamless & secure supply • GMP API sourced in kilogram scale providing >5 years of supply • CMOs provide overlapping regional supply centers • Every isotope is multi- sourced to guarantee sufficient supply • Optimized formulations provide potential “off-the- shelf” convenience Global Distribution Network Provides Drug to Patients Within 48 hours
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Phospholipid Radioconjugate (PRC) Program Auger Emitter
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC CLR 12125 (CLR 125): Auger Emitter (125I) Microenvironment, Tumor Biology & Isotope Properties Drive Safety and Efficacy 19 Composition Primary Mechanism of Cell Death Penetrating Power (Emission Distance) Relative Biologic Effect Alpha Particles 2 protons 2 neutrons Double strand DNA breaks 50 – 100um (80-100 keV/μm) ~5 Beta Particles 1 electron Single strand DNA breaks 12mm (∼0.2 keV/mm) 1 Auger Electrons Multiple electrons Double strand DNA breaks 2 – 500nm (4-26 keV/μm) 1 – 5 • Short penetrating power, requires intracellular delivery to be effective • Similar cell damage as alpha emitters – double strand and multi-base pair DNA breaks • Additional activity from reactive oxygen species, designed to provide enhanced immune stimulation • Short emission distance limits off target effects and adverse events Properties of Different Emitters Provide Enhanced Outcomes
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 110% 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Absorbed Dose per MBq of Injected CLR 124 Activity (mGy/MBq) Brain Breasts Stomach Heart Kidneys Liver Lungs Red Marrow Spleen Testes Thyroid Tumor PRC CLR 121125 (CLR 125): Auger Emitter (125I) Enhanced Tumor Absorbed Dose Results in Increased Cell Killing 20 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 Volume (%) Absorbed Dose per MBq of Injected CLR 125 Activity (mGy/MBq) Brain Breasts Stomach Heart Kidneys Liver Lungs Red Marrow Spleen Testes Thyroid Tumor CLR 124 CLR 125 CLR 131 CLR 121125 Demonstrated Greatest Tumor and Lowest Normal Tissue Absorbed Dose • Isotope half-life can drive absorbed dose (targeting ligand PK, uptake and retention key) • Tumor absorbed dose versus normal tissue = therapeutic window Absorbed Dose per MBq of injected 1-131 Activity [Gy/MBq]
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• Heatmap visualization of CLR 125 biodistribution at six timepoints in non-tumor bearing animals • Early uptake associated with residual blood in blood-rich organs (not real uptake) • Demonstrating predictable clearance kinetics • Thyroid uptake due to no SSTI (thyroid protection) use • Biodistribution implies potential for favorable safety profile PRC CLR 121125 (CLR 125): Auger Emitter (125I) Biodistribution Heatmap Limited to No Off-Target Uptake 21
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 22 PRC CLR 121125 (CLR 125): Auger Emitter (125I) Offers Benefits Vs Other Auger Emitters High Electron Delivery With Cleaner Emissions, Optimized Safety and Ease of Use AE = Auger electron IC = internal conversion β = beta electron emission X = X-ray γ = gamma emission Why I-125? • One of the highest Auger electron emitters • 57-day half-life enhanced outcomes • No Beta or Gamma emissions observed Existing data set supports entry into Phase 1b/2 clinical study • Initial indication Triple negative breast cancer • 3 dosing groups exploring multiple cycles with an expansion arm • Primary endpoint: Phase 2b dose selection γ
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 23 PRC CLR 121125 (CLR 125): Auger Emitter (125I) Observed Statistically Significant Activity and Well Tolerated In Vivo Validated Intracellular Delivery with CLR 121125 CLR 125 tested in MDA-MB-231 triple negative breast cancer • Observed significant tumor uptake (images A & B) • Single infusion resulted in growth inhibition at both tested doses (1.2mCi and 2mCi) – Image C • Observed statistically significant activity at 2mCi dose - data not shown No signs of end-organ toxicity, including hematologic toxicity A B C CLR 125 structurally identical to iopofosine I 131; potentially reduced development risk
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC CLR 121125 (CLR 125): Auger Emitter (125I) Phase 1b Dose Finding Study in relapsed Triple Negative Breast Cancer 24 Phase 1 Study Overview • Imaging and therapy study • Population: TNBC patients with progressive disease and no treatment option • Primary Endpoint: Recommended Phase 2 dose • Secondary Endpoints: Safety & tolerability; initial response assessment (RECIST v1.1 and PFS); distribution • Dose determination based upon preclinical data and imaging results Study Schematic 2 doses per cycle: 15 patients per arm 3 months 6 months 12 months Key Inclusion/Exclusion Criteria • Confirmed TNBC • Relapsed from at least 1 prior treatment • At least 1 measurable lesion of >10mm • No ongoing Grade 2 or greater adverse events • At least 2 weeks since prior antitumor treatment 32.75 mCi/m2/dose; Up to 4 cycles 62.5 mCi/m2/dose; Up to 3 cycles 95 mCi/m2/dose; Up to 2 cycles Expansion Cohort Dose TBD Mayo Clinic Network to Perform the Study
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Phospholipid Radioconjugate (PRC) Program Alpha Emitters
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 26 PRC CLR 121225 (CLR 225): Alpha Emitter (225Ac) Tumor Volume Reduction and Survival Benefit in Pancreatic Cancer Observed Tumor Volume Reduction and Survival Benefit at All Doses and All Doses Tolerated • 3 xenograft models of pancreatic cancer • Dose response exhibited in all models (Cold, 100nCi, 250nCi and 500nCi) • Tumor volume reduction and survival benefit observed in every model 0 7 14 21 28 35 42 49 56 0 10 20 30 40 50 60 70 80 90 100 BxPC-3 Time to Progression Time Since Dosing (days) Progression Free (%) Control 250 nCi 500 nCi 2 X 500 nCi 0 7 14 21 28 35 42 49 0 10 20 30 40 50 60 70 80 90 100 MIA PaCa-2 Time to Progression Time Since Dosing (days) Progression Free (%) Control 100 nCi 250 nCi 500 nCi 0 7 14 21 28 35 42 49 56 0 10 20 30 40 50 60 70 80 90 100 PANC-1 Time to Progression Time Since Dosing (days) Progression Free (%) Control 100 nCi 250 nCi 500 nCi
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC CLR 121225 (CLR 225): Alpha Emitter (225Ac) Biodistribution in Pancreatic Model 27 0 10 20 30 40 Brain Bone Muscle Small Intestines Large Intestines Stomach Pancreas Liver Spleen Kidney Heart Blood Tumor %ID/g 4 hours 24 hours 72 hours 144 hours High and Prolonged Tumor Uptake; Low Normal Tissue Uptake
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 28 PRC CLR 121225 (CLR 225): Alpha Emitter (225Ac) Tumor Volume Reduction and Survival Benefit in Prostate Cancer • MyC-CaP and TRAMP-C1 prostate cancer xenograph models dosed after tumors reached 200mm3 • Doses of 200nCi or 500nCi • Dosimetry data showed increased uptake in TRAMP-C1 (0.58Gy/kBq) versus MyC-CaP (0.25Gy/kBq) model • Distribution and percent uptake into tumors consistent with other models and isotopes • Observed statistically significant tumor volume reduction and survival benefit in both models at both doses MyC-CaP TRAMP-C1 **p<0.001; ***p<0.0001; ****p<0.00001 CLR-225Ac (7.4kBq) CLR-225Ac (18.5kBq)
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC CLR 121225 (CLR 225): Alpha Emitter (225Ac) Phase 1 Clinical Study – Pancreatic Cancer 29 Excellent labeling efficiency with 225Ac Phase 1 study design Simplified reaction process Preferred formulation for toxicity studies (no polysorbate needed) Imaging and therapy study Dose escalation utilizing an accelerated titration design (allows intrapatientdose escalation for more rapid dose escalation); dose limiting toxicities to be assessed post-cycle 1 day 57 Dose escalations = 40% increases until first moderate toxicity; then standard 3+3 escalation Patient 1 Dose 1 Patient 1 Dose 2 Patient 1 Dose 3 Cohort 4 (n=3) Cohort 5 (n=3) Cohort 6 (n=3) Single Ascending Doses Multiple Ascending Doses
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Phospholipid Radioconjugate (PRC) Program Other Emitters: Astatine (211At) Lead(212Pb) Lutetium (177Lu)
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 31 PRC CLR 121211: Astatine (211At) Efficacious and Well Tolerated in Triple Negative Breast Cancer Model (HCC70) • A variety of doses and dosing regimens tested • Tumor volume at dosing ~150mm3 • All treatment doses show some tumor volume reduction and growth delay • Optimum response achieved with 2 doses given 3 weeks apart (20uCi total) or high specific activity at 10uCi given 2 weeks apart • Dosing optimization continues CLR 211 Expected to Provide Tumor Eradication at Doses of ~40 uCi Control Cold PLE 1 uCi 5 uCi 10 uCi 10 uCi 2xQ2W 10uCi 2xQ3W
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 32 PRC CLR 121212 (CLR 212): Lead (212Pb) Efficacious and Well Tolerated 10uCi PLE at 10uCi/10ng 10uCi PLE at 10uCi/100ng Cold PLE Buffer only Median Survival (weeks) Not reached Not reached 13,8571 11,5 0 20 40 60 80 100 120 140 160 180 200 0 500 1000 1500 2000 2500 Days since cell injection Tumor Volume (mm3) 10uCi PLE at 10uCi/10ng 10uCi PLE at 10uCi/100ng Cold PLE Buffer onlyPLE PLE PLE • Growth inhibitionwith both doses tested • Observedsurvivalbenefitwith high specificactivitydose • All doses well tolerated CLR 121212 tested in HCC70 triple negative breast cancer Days since cell injection Survival CurveEfficacy
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 33 PRC CLR 121177 (CLR 177): Lutetium (177Lu) Activity in Breast Cancer • Lutetium and Yttrium –PLEs tested in 4T07 (uptake) & 4T1 (efficacy) breast cancer xenograft model • Tumors achieved 200 mm3 prior to dosing CLR-177Lu CLR-177Lu 1. control: 2. 9.25MBq: 3. 18.5MBq: 4. fractionated 18.5MBq (2 x 9.25): 5. 3 x 9.25MBq
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC CLR 121177 (CLR 177): Lutetium (177Lu) Tissue Uptake and Distribution 34 CLR-177Lu CLR-86Y • Uptake and distribution is similar for CLR-177Lu and CLR-86Y: tumor uptake ~18% infused activity/g tissue • Approximately 2Gy/MBq delivered to the tumor with CLR-177Lu • Tumor volume reduction observed in dose response with complete tumor regression achieved with high dose fractionated CLR-177Lu 1. control: 2. 9.25MBq: 3. 18.5MBq: 4. fractionated 18.5MBq (2 x 9.25): 5. 3 x 9.25MBq
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Phospholipid Radioconjugate (PRC) program Beta Emitter Iopofosine I 131 Waldenstrom Macroglobulinemia
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed PRC Iopofosine I 131: Confirmatory Study for Full Approval Waldenstrom’s macroglobulinemia 36 Second Line or Later, Immediately Post-BTKi Randomized 1:1 Iopofosine I 131 Comparator: rituximab cyclophosphamide dexamethasone (RCD) Primary Endpoint: PFS (full approval) Secondary Endpoints: MRR, safety • Enrollment:200 patients (100/arm) • Dosing: Iopofosine I 131 (4 doses of 15 mCi/m2); package insert for RCD • Primary Endpoints: Superiority for PFS • Secondary Endpoint: MRR & Safety; Overall survival assessed for harm and futility • Phase 3 Top line data: Full enrollment 18 – 24 months; PFS expected 24 – 30 months post first patient enrolled • Estimated Total Study Cost $42M: ~ $15M to accelerated approval and $30M to full approval (PFS data) Phase 3 Confirmatory Study Required for U.S and EU Full Approval
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 37 PRC Iopofosine I 131: CLOVER-WaM Demographics Patient Characteristics Data Cut-off September 30, 2024 Most Refractory WM Patient Population Studied in Clinical Trials; 73% of Patients Met the EU CMA Requirement of Post-BTKi Patient Characteristics Patient Characteristics Safety population, n 65 Median Prior Lines of Therapy, n (range) 4 (2-15) Median age, years (range) 70 (50-88) Prior Treatment/Refractory n (%) Sex, n (%) BTKi 48 (73.8) / 37 (77.1)Male 48 (73.8) Female 17 (26.2) Rituximab 60 (92.3) / 45 (75.0) IPSSWM score n (%) Chemotherapy 55 (84.6) / 33 (60.0) Low 28 (43.1) BTKi & Rituximab (Dual Refractory) 43 (66.2) / 25 (58.1)Medium 20 (30.8) High 17 (26.2) BTKi, Rituximab & Chemo (Triple Refractory) 37 (56.9) / 18 (46.4) Median IgM, mdl (range) 2115 (252 – 7400) Genotype (%)Extramedullary Volume, mm3 (range) 2303 (210 – 17185) Bone Marrow Burden at Baseline, n (%) 52 MYD88 WT/Mut (n=65) 18 (27.7) / 47 (72.3) < 20% 21 (40.4) CXCR4 WT/Mut (n=53) 45 (84.9) / 8 (15.1)20 – 50% 17 (32.7) > 50% 14 (26.9) P53 WT/Mut (n=52) 42 (80.8) / 10 (19.2)
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 38 PRC Iopofosine I 131: CLOVER-WaM Efficacy Data Best Serum IgM Response by Patient (100%) (75%) (50%) (25%) 0% 25% 50% 75% 100% IgMReduction(%) CR/ VGPRPRMR SDPD * * * * * * * * * * * * * * * ORR = 83.6% MRR = 58.2% DCR = 98.2% Evaluable Efficacy Population (n=55) DOR and PFS Ongoing with Median of 11.4 Months of Follow-Up *
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 39 PRC Iopofosine I 131: CLOVER-WaM Safety Data Observed Cytopenias Consistent with Treatment of Hematologic Malignancies Most common TEAE* (>10% patients), n (%) Any grade n=65 Hematologic Toxicities Thrombocytopenia 56 (86.2) Neutropenia 52 (80.0) Anemia 42 (64.6) White blood cell count decreased 21 (32.3) Lymphocyte count decreased 9 (13.8) Febrile neutropenia 7 (10.8) Non-hematologic Toxicities Fatigue 22 (33.8) Nausea 19 (29.2) Diarrhea 13 (20.0) Dyspnea 11 (16.9) Headache 11 (16.9) Dizziness 10 (15.4) Epistaxis 9 (13.8) Decreased appetite 9 (13.8) Constipation 8 (12.3) Most common TEAE* (>10% patients), n (%) Grade ≥3 n=65 Thrombocytopenia 53 (81.5) Neutropenia 43 (66.2) Anemia 31 (47.7) White blood cell count decreased 18 (27.7) Lymphocyte count decreased 8 (12.3) Febrile neutropenia 7 (10.8) • No significant bleeding • Limited rate of infection (<10%) • All hematologic AEs were manageable • All patients recovered from cytopenias • All non-hematologic AEs < Grade 2 TEAE, treatment-emergent adverse event.*
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 40 European WM Prevalence Population ~30% Larger than United States PRC Iopofosine I 131: U.S. WM Market Opportunity Prevalent Patient Population Based Upon Claims = 26,000 5 No Established Standard of Care Across All Lines of Therapy 8 ~11,500 2nd line ~4,700 3rd line or greater ~1,000 Exhausted treatment options – currently not seeking Rx Patients are concentratedgeographically in large community and academic accounts6 ~80% of patientswill receive3rd line treatment ~50% of patients are retreatedwith the same or similar treatmentfrom prior lines of therapy >60% of therapiesutilized are not FDA-approvedand cannot be promoted ~80% of WM patients located in 15 states7 4-12% Major ResponseRates RWD beyond 2nd line 9 1st Line 2nd Line 3rd Line 4th Line Addressable Patients in a Concentrated Market with High Unmet Need
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Phospholipid Radioconjugate (PRC) program Beta Emitter Iopofosine I 131 Additional Indications
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 42 -100 -80 -60 -40 -20 0 20 40 60 80 Best Response by Patient (n=64) Partial Response (PR) Very Good Partial Response (VGPR) Minor Response (MR) Patients receiving at least 60mCi 32% ORR 96% DCR 3.3 months mPFS in post-BCMA <60 mCi TAD >60 mCi TAD Quad-class refractory CLR 1501 Lipid Rafts Combined Multiple myeloma cell lines PRC Iopofosine I 131: r/r Multiple Myeloma Best Response Waterfall Plot of All Multiple Myeloma Patients Percent Reduction
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Complete Response 30% ORR with 10% CRR – CR PFS 6.8 years PRC Iopofosine I 131: Broad Clinical Activity Beyond WM Refractory Primary CNS Lymphoma Refractory Diffuse Large B-cell Lymphoma Relapsed Pediatric High-Grade Glioma Extended PFS (~12 months) 44 73% ORR with 64% CRR Recurrent Head & Neck Cancer
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Financials Capitalization
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 45 Financial Summary Cash Position as of September 30,2025 (millions) $12.6M Capitalizationas of October 20, 2025 Common Stock Outstanding 4,240,134 October 2025 Common Warrant I (Exercise Price $6.00) 1,048,094 October 2025 Common Warrant II (Exercise Price $6.00) 1,048,094 Convertible Series D Preferred Stock (111.11 shares) 3,704 Convertible Series E-2 Preferred Stock (35.60 shares) 13,040 July 2025 Warrants (Exercise Price $5.25) 436,000 July 2025 Representative Warrants (Exercise Price $7.75) 82,800 Warrants (Weighted Avg Exercise Price $105.33) 417,904 Options 211,816 Fully Diluted 7,501,586 Cash Position Does Not Include ~$5.2 Million Net Raised in October
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Formula for Value Creation 46 • Leverage novel PDC platform - Advance into Phase 1 solid tumor studies – Execute CLR 125 TNBC study ~ r/r global market potential ~$11B – Initiate CLR 225 targeting pancreatic cancer, ~ r/r global market potential ~$10B – Thoughtful investment in preclinical program development • Optimize WM regulatory approval pathway for iopofosine I 131 – CMA application submission 3Q26 to European Medicines Agency; potential 2027 EU commercialization – Phase 3 confirmatory study supports accelerated approval in US (pre-filing) potential approval in 2027 • Complete US and EU iopofosine I 131 development and commercialization partnerships • Secure additional platform collaborations for accelerated asset development and non-dilutive funding • Competitive advantage created by unique radiotherapeutic manufacturing and supply chain infrastructure • Extensive IP portfolio; radio-conjugates, small molecules, oligonucleotide payloads and linker technology Strategic Growth and Expansion
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Thank You
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed 48 Executive Management Team Greater than 95 years combined leadership experience James Caruso President, CEO and Director Jarrod Longcor Chief Operating Officer Chad Kolean Chief Financial Officer
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Confidential. For Internal Use Only |. For fonts to display correctly, make sure Roboto is downloaded & installed Footnotes 1. Dependent Upon Funding and Resource Deployment 2. Jefferies Biotechnology Report Oct 5, 2025 3. European Medicines Agency Report on 10 Years of Experience 4. Data on file 5. Internal claims analysis for Waldenstrom’s macroglobulinemia (January 2019-October 2023) 6. Putnam Market Sizing 2023 7. Putnam Quantitative Research 1Q 2023 (n=102 MDs); Putnam Analysis and WM Advisory Boards 8. Komodo Claims Data 9. Real-world data - large community oncology network 10. Puregmaa Khongorzul,Cai Jia Ling, Farhan Ullah Khan, Awais Ullah Ihsan, Juan Zhang; Antibody–Drug Conjugates:A Comprehensive Review. Mol Cancer Res 1 January 2020; 18 (1): 3-19. https://doi.org/10.1158/1541-7786.MCR-19-0582