Perspective Therapeutics, Inc. · AMEX:CATX
Perspective Therapeutics — Investor Presentation (November 2024)
106 slides from Perspective Therapeutics's investor presentation, Nov 15, 2024
Slide 1: Corporate Presentation November 2024
Corporate Presentation November 2024 NYSE AMERICAN: CATX
Slide 2: Forward-looking statements
This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Statements in this presentation that are not statements of historical fact are forward-looking statements. Words such as “may,” “will,” “should,” “expect,”
Slide 3: Next generation targeted radiopharmaceutical therapies
Multiple expected near-term readouts and milestones through to 2025 Proprietary chelator-based peptide targeting platform provides engine for pipeline expansion Developing the Next Generation of Targeted Radiopharmaceutical Therapies (RPT) Key Differentiators Enable an Expanded Therapeutic Window an
Slide 4: Deeply Experienced Management Team in RPT & Oncology Drug Development
Deeply Experienced Management Team in RPT & Oncology Drug Development Michael Schultz, PHD Chief Science Officer Thijs Spoor Chief Executive Officer Jonathan Hunt Chief Financial Officer Markus Puhlmann, MD MBA Chief Medical Officer Frances Johnson, MD Chief Innovation Officer Amos Hedt Chief Busine
Slide 5: Radiopharmaceutical Therapy Poised to Revolutionize Oncology Treatment
Despite multiple treatment modalities, cancer remains the 2nd leading cause of death in the US1 Targeted therapies e.g., TKIs, mAbs Surgery Bone marrow transplantation External beam radiation Chemotherapy Immunotherapy Hormone therapy Antibody-drug conjugates Radiopharmaceuticals Physical removal or
Slide 6: Molecular imaging companion diagnostics and theranostics
Molecular imaging companion diagnostics enable visualization of the therapeutic target Enables the selection of patients who may best respond to therapy Perspective’s elementally matched isotopes are paired for imaging and therapy Radioligands can precisely deliver radiation directly to cancer cells
Slide 7: Unique Payload Delivery Technology Offers Pan-Cancer Opportunities
Targeting Peptide Engineered for cancer-specific receptors to ensure highly directed uptake Linker Selected to assist peptide binding and optimize clearance from blood and healthy tissues Isotope 203Pb for SPECT imaging Chelator Perspective’s proprietary platform technology enabling stable radiolabe
Slide 8: Broad Proprietary Pipeline
Construct Target Disease Discovery Human Clinical Imaging First in Human Therapy Phase 1/2 Phase 3 Key Milestones VMT-⍺-NET Neuroendocrine cancers For Neuroendocrine Tumors: Late 2024: Preliminary Cohort 1/2 Data Update Late 2025: Preliminary Expansion Cohort Update Other SSTR2 expressing tumors VMT
Slide 9: Key future milestones & expected timelines
1 Investigator led research in India in patients with neuroendocrine tumor and medullary thyroid carcinomas. 2 RP2D = recommended Phase 2 dose; ICI = immune check point inhibitor. Program Target Tumor Types Nominate Candidate IND Filing Initiate Cohort 1 Enrolled Cohort 2 Preliminary Update RP2D2 St
Slide 10: Lead-212: The Optimal Therapeutic Isotope
1Company estimates and assumptions based on current literature and known physical constants Lead (212Pb) Iodine (131I) Lutetium (177Lu) Actinium (225Ac) Implication1 Emission Profile Alpha Beta Beta Alpha Potent Half Life 0.46 days 8 days 6.7 days 10 days High dose-rate Off Target Toxicity Risk Low
Slide 11: Perspective's Proprietary Pb-Specific Chelator
1”Pb-Specific Chelator”; 2Mirzadeh et al., Radiochimica Acta, 1993 Generic chelators have not been optimized for Pb isotopes, potentially compromising safety, efficacy and manufacturing efficiency Commercially Available Perspective’s Chelator Perspective’s Proprietary Chelator: Designed specifically
Slide 12: Pb-based Theranostics Enable Diagnosis and Treatment
Pb-based Theranostics Enable Both Diagnosis and Targeted Treatment of Cancer Identical Distribution of 203Pb and 212Pb for Imaging and Treatment, Respectively Unpublished Company data
Slide 13: Neuroendocrine Tumors: VMT-α-NET
Neuroendocrine Tumors: VMT-⍺-NET Targeting the somatostatin receptor to treat rare neuroendocrine-type cancers
Slide 14: Targeting the Somatostatin Receptor to Treat Neuroendocrine and Other Cancers
Image Panel: Whole body SPECT scan of NETs patient imaged with [203Pb]VMT-𝛼-NET Initiated therapy (2022) investigator led study in India – data on 13 patients presented at SNMMI in June 2024 Fast Track Designation for first line therapy received October 2022 Therapeutic trial in PRRT naïve setting…
Slide 15: Preclinical superiority of VMT-α-NET
SSTR2 tumor model demonstrates superiority of VMT-𝛼-NET to generic compounds 8-fold improved tumor uptake with decreased kidney retention Key Takeaways vs Generic Compounds Generic 203Pb-DOTATOC Proprietary 203Pb-VMT-α-NET Tumor Kidneys Drug Administered [212Pb]VMT-α-NET (1 x 120 µCi) Vehicle…
Slide 16: 203Pb SPECT Imaging Reveals Favorable VMT-α-NET Properties
Tumors visible within 1 hour indicates rapid binding to SSTR2 target High intensity above background implies excellent therapeutic window Unbound drug in bladder within 1 hour for excretion Low renal retention due to neutral charge on proprietary Pb-specific chelator 21 hours Rapid Tumor Targeting a
Slide 17: 212Pb SPECT/CT Imaging Confirms VMT-α-NET Tumor Uptake
Both 203Pb and 212Pb can be imaged directly using SPECT SPECT/CT shows very rapid tumor uptake and retention of [212Pb]VMT-α-NET After 24 hours more than 80% of alpha particles will be generated This high alpha dose rate is ideally matched to the biological clearance of the VMT-α-NET peptide 203Pb S
Slide 18: Significant Response After Single Dose of [212Pb]VMT-α-NET
Tumor Before Treatment Tumor After 1 Dose Significant Response After Single Dose of [212Pb]VMT-⍺-NET Metastatic NET Pancreas with Adrenal Crisis – Maximum Intensity Projection (MIP) 68Ga-DOTA-NOC PET images at base line and post 1st dose of [212Pb]VMT-α-NET MIP suggesting strong reduction of intensi
Slide 19: Almost Complete Response After 3 Doses
1 Serum Adrenocorticotropic Hormone Fortis Memorial research institute (FMRI), Gurugram, India (S.ACTH)1– 790 pg/ml S.ACTH – 96 pg/ml Tumor Before Treatment Tumor After 1 Dose Tumor After 3 Doses Significant Response After Single Dose, Almost Complete Response After 3 Doses Metastatic NET Pancreas w
Slide 20: Interim Clinical Data from India Investigator-Led Study
Status as of Data-Cut Off Date Patients with prior lines of therapy, late-stage, anatomically different NETs (mean age: 51 years; 6 females) 13 patients administered [212Pb]VMT-⍺-NET 6/13 patients continuing on therapy 2 patients completed all 6 treatments 45 total [212Pb] VMT-α-NET doses administer
Slide 21: Presented at SNMMI 2024
Dr Ishita Sen, Fortis Memorial research institute (FMRI), Gurugram, India. Presented at SNMMI 2024
Slide 22: Trial Design: [212Pb]VMT-α-NET Phase 1/2a
Trial Design: [212Pb]VMT-α-NET mTPI-2 Phase 1/2a For Neuroendocrine Tumors PRRT = peptide receptor radionuclide therapy | mTPI-2: Modified toxicity probability index For additional details regarding trial parameters, including criteria for patient selection, please refer to slide 68 or https://clini
Slide 23: Melanoma Program: VMT01/02
Melanoma Program: VMT01/02 Using the melanocortin receptor MC1R to target melanoma for imaging and therapy
Slide 24: Melanoma Program: VMT01/02
Image: Whole body PET scan of a metastatic melanoma patient using VMT02; 1SEER*Explorer: Surveillance Research Program, National Cancer Institute; 2024 Apr 17. cited 2024 Sep 25; 2Su DG, et al. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precis Oncol. 2024;8:e23007
Slide 25: Radiopharmaceutical therapy and immune activation
Abbreviations: APC, antigen-presenting cell; DAMPs, damage-associated molecular patterns; dsDNA, double-stranded DNA; RPT, radiopharmaceutical therapy. Adapted from Pouget JP, Chan TA, Galluzzi L, Constanzo J. Radiopharmaceuticals as combinatorial partners for immune checkpoint inhibitors. Trends Ca
Slide 26: [212Pb]VMT01 with Immune Checkpoint Inhibitors
1. Rodman et al., International Symposium on Radiopharmaceutical Sciences iSRS 2023, 22-26 May 2023, Honolulu, Hawaii. In C57Bl6 albino mice inoculated with B16.F10 allograft tumors, treatment with [212Pb]VMT01 monotherapy shows increasing efficacy with higher doses (left). When combined with immune
Slide 27: [68Ga]VMT02 PET Imaging in Metastatic Melanoma
[68Ga]VMT02 PET Imaging in Patient with MC1R Positive Metastatic Melanoma Diagnostic Peptide Demonstrates Similar Uptake to FDG in Tumors 18F-FDG (Standard of Care) [68Ga]VMT02 Xiaowei Ma, M.D., Ph.D. Assoc. Prof. & Director Department of Nuclear Med. The Second Xiangya Hospital Central South Univer
Slide 28: Key Takeaways: Combination with checkpoint inhibitors
Key Takeaways High response rates in multiple tested models >70% complete and durable response when combined with PD1 immunotherapy in a model highly resistant to checkpoint inhibitors3 Combination with immune checkpoint inhibitors induced synergistic anti-tumor effect 1Li et al., Mol. Pharm., 2019;
Slide 29: Trial Design: [212Pb]VMT01-T101 Phase 1/2a
De-escalation for Cohort 3 onwards, possibility for intermediate doses 1mTPI-2: Modified toxicity probability index For additional details regarding trial parameters, including criteria for patient selection, please refer to slide 76 or https://clinicaltrials.gov/study/NCT05655312 Monotherapy Dose-f
Slide 30: Pan Cancer Target: PSV359
Pan Cancer Target: PSV359 Preclinical Efficacy and First in Human Images of Novel Peptide Targeting Fibroblast Activation Protein alpha (FAPɑ)
Slide 31: Pan Cancer Program: PSV359
Image: Whole body SPECT image of osteosarcoma patient using [203Pb]PSV359 1Modified from EvaluatePharma® July 2020, Evaluate Ltd.; Surveillance, Epidemiology, and End Results (SEER) Program IND-enabling preclinical studies complete IND for US Therapeutic Dose Escalation Trial under preparation Precl
Slide 32: FAP is a Pan Cancer Target
Kratochwil et al., JNM, 2019 FAP is primarily expressed on tumor stroma cells, but also on some cancer cells Tumor stroma cells do not typically express cancer-specific markers like SSTR2 or MC1R Pan Cancer Program: PSV359 Fibroblast Activation Protein alpha (“FAP”) is a Pan Cancer Target
Slide 33: FAP-targeted Novel Compound Development
Compound 3-30 Compound 3-42 Compound 3-59 Fibroblast Activation Protein-targeted Novel Compound Development In-house peptide synthesis and in vivo capability allows rapid iteration and optimization of novel compounds Phage display screening Phage display followed by affinity maturation Bioconjugate
Slide 34: Preclinical [212Pb]PSV359 Targeted Alpha Therapy
1Perspective unpublished data; 2Zboralski et al., EJNMMI, 2022 Preclinical [212Pb]PSV359 Targeted Alpha Therapy1 [212Pb]PSV359 Demonstrates Preclinical Efficacy in Human Fibrosarcoma Model Compares favorably against other therapeutic products in development2 40-day results hFAP-HT1080 Fibrosarcoma M
Slide 35: FIH Imaging of [203Pb]PSV359: Patient 1
[203Pb]PSV359 SPECT/CT Source: Cagle et al. European Association of Nuclear Medicine 2024, Presentation Number: OP-473 [203Pb]PSV359 Lesion in head of left humerus 1 hr 4 hr 18 hr 4 hr 18 hr FIH Imaging of [203Pb]PSV359 in Different Types of Cancers Patient 1 Chondroblastic Osteosarcoma
Slide 36: FIH Imaging of [203Pb]PSV359: Patient 2
[203Pb]PSV359 [203Pb]PSV359 SPECT/CT 4 hr 18 hr 1 hr 4 hr 18 hr FIH Imaging of [203Pb]PSV359 in Different Types of Cancers Patient 2 Neuroendocrine Tumor Source: Cagle et al. European Association of Nuclear Medicine 2024, Presentation Number: OP-473
Slide 37: FIH Imaging of [203Pb]PSV359: Patient 3
Lytic lesion in sacrum Lytic lesion in thoracic vertebra [203Pb]PSV359 [203Pb]PSV359 SPECT/CT 1 hr 4 hr 18 hr FIH Imaging of [203Pb]PSV359 in Different Types of Cancers Patient 3 Lung Adenocarcinoma Source: Cagle et al. European Association of Nuclear Medicine 2024, Presentation Number: OP-473
Slide 38: Prostate Cancer Program: PSV401
Prostate Cancer Program: PSV401 A differentiated PSMA-targeted radiohybrid molecule for dual PET imaging and targeted alpha therapy
Slide 39: Prostate Cancer Program: PSV40X
1Johnson et al., RPT Interest Group June 7 2023 https://rrp.cancer.gov/working_groups/AlphaPET-RPT_Int_group_lecture.pdf Technology licensed from Mayo Clinic January 2024 IND-enabling studies underway First in human data to follow Has shown promise in reduction of salivary gland uptake in preclinica
Slide 40: PSV40X: Improved Preclinical Metrics
Higher tumor accumulation/retention Significantly lower salivary gland uptake and retention Significantly lower kidney accumulation and retention Higher therapeutic window and reducing the potential for xerostomia that limits current PSMA-targeted prostate cancer radiopharmaceutical therapies PSV40X
Slide 41: Pre-Targeting Platform
Pre-Targeting Platform The Next Generation of Targeted Alpha Particle Radiopharmaceuticals
Slide 42: Pre-Targeting Platform
1 Administer cold modified monoclonal antibody or targeting protein 2 After several days, mAb will have accumulated on tumor and cleared from blood 3 Administer radiolabeled ligand 4 Ligand binds specifically to mAb and clears rapidly from circulation Radioligand on tumor Radioligand clears circulat
Slide 43: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics The Path to Commercial Supply
Slide 44: 212Pb is Plentiful, Storable, Scalable & Suitable for Distributed Logistics
Naturally occurring in mining waste Also produced in industrial nuclear processes Can be made on demand if needed Isotope Source Other therapeutic isotopes require capital-intensive infrastructure and manufacturing processes (e.g. irradiation) Isotope Purification VMT-𝛼-GEN enables shipping of…
Slide 45: Isotope Decay Chain Dictates Supply, Purification, Manufacturing & Logistics
Plentiful Supply: Naturally occurring, or produced as a waste product Chemical Separation: Allows for Ra-based generators of 212Pb 228Th Thorium 1.9 y 224Ra Radium 3.6 d 212Pb Lead 10.6 h 212Bi Bismuth 61 m Chemical Separation from 224Ra: Isotope used for manufacturing finished product High dose-rat
Slide 46: 212Pb Isotope Purification Without Just-in-time Irradiation
212Pb Isotope Purification Without Just-in-time Irradiation Simple chemical separation technology of natural decay products de-risks supply chain
Slide 47: 212Pb Supply via Reusable Desktop Isotope Generator
5.7” 11” VMT-𝛼-GEN Extensive feedstock from nuclear and mining waste material Long-term supply contract secured with US DOE On demand daily doses Auto-regenerates overnight ~1 week shelf life Small, Elegant 212Pb Isotope Generator Integrated lead shielded containment Simple inlet and outlet ports…
Slide 48: Scalable Manufacturing and Distribution Logistics
Commercial supply will require the use of an isotope production system of larger scale than the current 224Ra/212Pb generators The current isotope separation process remains highly scalable with larger activity levels Regional CDMOs will have capabilities to expand capacity as needed as more 212Pb p
Slide 49: Infrastructure Modeling: Commercial History of PET Pharmacy Network
2014: 78 2024: 101 Infrastructure Modeling: Commercial History of PET Pharmacy Network Development Nuclear medicine capability filled in to meet demand as clinical adoption of ultra short half-life PET agents widened PET Pharmacies1 1 Company estimates There were 40+ million diagnostic nuclear medic
Slide 50: Isotope Decay Chain Dictates Supply, Purification, Manufacturing & Logistics
228Th Thorium 1.9 y 224Ra Radium 3.6 d 212Pb Lead 10.6 h 228Th 224Ra 224Ra 224Ra 224Ra 224Ra 224Ra 212Pb 212Pb 212Pb 212Pb 212Pb Central continental supply Eluted weekly for 224Ra Distributed continentally Eluted daily for 212Pb Daily manufacture of finished doses Leverages existing networks for log
Slide 51: Regional Manufacturing Allows Commercialization of 212Pb-labeled Products
Planned/Existing Locations Population Radius 11 hr – 400 miles Somerset, NJ 75 m Chicago, IL 66 m Los Angeles, CA 48 m Houston, TX 37 m Potential Locations Atlanta, GA 57 m Orlando, FL 31 m Top 6 sites cover 300 million people + within a one half-life (11 hr) delivery radius1 Products can also be dr
Slide 52: Intellectual Property Portfolio
5 Issued Patents (Expiry in 2037 and 2040, with potential PTE) Composition of matter for melanoma targeted radiopharmaceutical compounds; methods of combination therapies; methods of creating radiopharmaceutical compounds using Pb-specific chelators 1 Allowed AU Patent Application (Expiry in 2039) m
Slide 53: Strong Financial Position
Funding into mid-2026 Strong Financial Position Cash, cash equivalents and short-term investments as of September 30, 2024 $267.8 million Share count as of September 30, 2024 67.6 million Outstanding common stock warrants & options as of September 30, 2024 7.7 million Outstanding pre-funded warrants
Slide 54: Appendix
Appendix
Slide 55: α-Particles Have Superior Tumor Killing Properties vs. β-Particles
1Li et al., Cancers, Jul 22;13(15), 2021 α-particles are >7,000-fold greater in atomic mass More Powerful Effects Than Approved β Therapy Higher atomic mass Lethal double-stranded DNA breaks DNA repair mechanisms overwhelmed Precision Delivery Provides Targeted Cell Destruction Deposit energy over 3
Slide 56: Lead-212: The Optimal Therapeutic Isotope
Beta range (up to 200 cell diameters) Alpha particle range (up to 3 cell diameters) The destructive energy of an alpha particle is deposited within several cell diameters. A beta particle spreads its lower energy over a longer range Tumor Cells 10mm 𝛼 β ✚ - - - ✚ - - ✚ ✚ - ✚ - - ✚ 1mm - - - ✚ ✚ ✚ -
Slide 57: Lead (Pb): The Ideal Theranostic Isotope
Ideal agreement between imaging and therapeutic compounds 203Pb and 212Pb matched pair Readily available isotope Generator produced Ideal chelator Proprietary chelator carries 0 net charge Rapid clearance from blood Conjugation to small peptides High tumor retention @24 hours High and sustained bind
Slide 58: Peptides are Ideal Ligands for Radiopharmaceutical Therapy
Blood clearance: rapid Tumor accumulation: rapid Time Injected Dose Ensures efficacy Peptide Kinetics mAb Kinetics Blood clearance: extended Tumor accumulation: extended Time Injected Dose Potential for toxicity mAb Size: 150 kDa 10 nanometers Peptide Size: 1.5 kDa 10 nanometers Monoclonal antibodie
Slide 59: VMT-α-NET is Developed to Address the Unmet Need in NETs
1cancer.net; ; 2www.futuremarketinsights.com/reports/neuroendocrine-carcinoma-market; 3LUTATHERA PI; 4Strosberg et al (2021); 5Navalkissoor et al (2019) Projected to be $2.9 billion+ in 20292 Existing radiopharmaceutical treatment LUTATHERA® (Novartis) has an overall response rate (ORR) of only 13–
Slide 60: 225Ac Isotope Decay Chain and Potential for Off-Target Toxicity
α α ꞵ α OH Potential for Off-Target Toxicity 221Fr Francium 5 Min 217Rn Radon 0.5 ms 213Bi Bismuth 46 m 209Pb Lead 3.3 h 213Po Polonium 4.3 µs 209TI Thallium 2 m α α α α α β β Isotope Supply Production 221Ra Radium 28 s 217At Astatine 32 ms 205Tl Thallium stable 209Bi Bismuth 2×1019 y β β α α α β Th
Slide 61: Daughter ingrowth post radiolabeling of 225Ac
T0 Post Final Purification Dose Vial 225Ac 225Ac 221Fr 217At 213Po 213Bi ß “Free” Radiometals: Labeled 4 hours. T4 4 h post Radiolabeling 221Fr+ 217At- 213Bi3+ 213Po2+ 225Ac Ac-225 Decay and Daughter Ingrowth 1 kBq 225Ac starting dose size. Hours Post Purification 0 2 3 4 5 6 1 4x more unl
Slide 62: 212Pb Isotope Decay Chain and Importance of the Pb-Specific Chelator
Therapy 228Th Thorium 1.9 y 224Ra Radium 3.6 d 220Rn Radon 1 m 216Po Polonium 0.1 s 212Bi Bismuth 61 m 208Tl Thallium 3 m 212Po Polonium 0.1 µs 208Pb Lead Stable 212Pb Lead 10.6 h α α α α α α β β β Isotope Supply Production α β 212Pb 212Bi Perspective’s proprietary chelator retains 98% of 212Bi afte
Slide 63: 212Pb Hits Tumors Hard and Fast and Disappears
212Pb Hits Tumors Hard and Fast and Disappears 212Pb is a “high dose rate” alpha emitter with a short half life – energy is deposited rapidly to tumor and then gone Comparative alpha Particle Decay Over Time1 Comparative alpha decays 0 ~80% of total 212Pb/212Bi alphas delivered to tumor within 24 hr
Slide 64: Isotope: Decay chain – Biological Implications
Isotope: Decay chain – Biological Implications Isotope selection drives potential for off target toxicities 225Ac has potential for off target toxicity Decay products circulate and continue to emit radition 212Pb decay is limited to tumor Toxicity to liver and kidneys Recoil breaks chemical bonds
Slide 65: Clinical Trial Principal Investigators
Clinical Trial Principal Investigators Renowned Experts in Radiotherapy Development Geoffrey B. Johnson MD, PhD Chair, Division of Nuclear Medicine Chair, PET/MR R&D Associate Professor Departments of Radiology and Immunology Mayo Clinic – Rochester, MN Vikas Prasad MD Professor of Radiology Associa
Slide 66: Appendix: VMT-α-NET Additional Material from Fortis Memorial Research Institute
Appendix: VMT-⍺-NET Additional Material and Data from Clinical Investigation at Fortis Memorial Research Institute, Gurgaon, India
Slide 67: NET Trials
NET Trials 177Lu-DOTATATE Study NETTER-1 (1) (2) RCT; randomized 2:1 N = 229 Dose Level (administered) 4 x Q8W 200 mCi Patient Population SSTR2+, GEP-NETs Prior PRRT 0% Median time from dx 3.8 years Performance Status Karnofsky Performance Scale Median was 90 Histology Well differentiated G1 (66%),
Slide 68: Entry Criteria: [212Pb]VMT-α-NET Phase 1/2a
Entry Criteria: [212Pb]VMT-α-NET mTPI-2 Phase 1/2a https://clinicaltrials.gov/study/NCT05636618 Adult (ages ≥18) subjects with NETs by local pathology. Locally advanced/unresectable or metastatic NETs. Radiological evidence of measurable disease by RECIST v1.1 criteria on CT with contrast or MRI of
Slide 69: Patient 3: Metastatic NET Pancreas with Liver Metastases
MIP image Before Treatment MIP image After 2nd Treatment Liver Metastases after treatment with two doses Liver Metastases before treatment Significant Tumor Response After Two Doses Patient 3: Metastatic NET Pancreas with Liver Metastases
Slide 70: Patient 5: Pancreatic NET
Tumor Before Treatment Tumor After Treatment Reduction in Size of Necrotic Masses After 2 Doses Patient 5: Pancreatic NET
Slide 71: Favorable Safety and Tolerability Profile
Hemoglobin Levels Platelet Counts Serum Creatinine Total Leukocyte Count Favorable Safety and Tolerability Profile Four Months Post-Treatment (5 Patients)
Slide 72: Serious Adverse Event in Patient 2
Pre-Therapy Post-Therapy 79 year-male Metastatic Medullary Carcinoma thyroid Disease progression of TKI’s Received total 3 doses of [212Pb]VMT-α-NET therapy at an interval of 8 weeks (Cumulative dose 9.6 mCi) Shows Partial response for disease till date. Developed MDS on routine blood investigations
Slide 73: Serious Adverse Event in Patient 6
25 year-male Metastatic NET-pancreas Long-standing disease (>6 years duration) Heavily pre-treated with Inj. Sandostatin and 4 cycles of 177Lu-DOTATATE along with CAPTEM regimen Received 1 dose of [212Pb]VMT-α-NET therapy (3.5 mCi) Acute Cardiac Event (Possible Carcinoid Heart Syndrome) Significant
Slide 74: Appendix: VMT01
Appendix: VMT01
Slide 75: Refractory Metastatic Melanoma Trials
Refractory Metastatic Melanoma Trials (1) US prescribing information; (2) doi:10.1136/jitc-2022-005755; (3) doi:10.1200/JCO.22.02072; (4) doi:10.1200/JCO.21.00079; (5) doi:10.1038/s41591-023-02498-y; (6) https://www.onclive.com/view/second-line-nivolumab-plus-ipilimumab-improves-pfs-in-advanced-mela
Slide 76: Entry Criteria: [212Pb]VMT01-T101 Phase 1/2a
Entry Criteria: [212Pb]VMT01-T101 Phase 1/2a https://clinicaltrials.gov/study/NCT05655312 Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study Aged ≥ 18 years Diagnosed with unresectable Stage III or Stage IV
Slide 77: Appendix: Preclinical Programs: Pre-targeting Platform
Appendix: Preclinical Programs: Pre-targeting Platform
Slide 78: Pre-targeting Rationale: Current Radiopharmaceutical State of the Art
Peptide and peptide-like small molecules Rely on fast clearance from the body to reduce radiation dose to non-target tissues Typically clear through the kidneys Sometimes tumor retention is an issue Less suitable for long-lived isotopes Examples: LUTATHERA®, PLUVICTO®, VMT01, VMT-α-NET etc Blood cle
Slide 79: Pre-targeting Rationale: mAbs Have Significant Role in Cancer Therapy
FDA has approved over 100 mAbs: 9 of the top 20 therapeutic products worldwide with more than $75 billion in sales (2021)1 ADCs are commercially successful (current market size approx $10 billion2) but some safety issues with Blackbox warnings3 Success of mAbs as vectors to target radiation has been
Slide 80: Specificity of mAbs: [203Pb]mAb SPECT Imaging
Unpublished data, undisclosed target 48 hours post- injection 120 hours post- injection Observations Question? Specificity of mAbs: [203Pb]mAb SPECT Imaging Preclinical Example Is it possible to exploit the tumor targeting and uptake of mAbs, but retain the rapid clearance properties of peptides and
Slide 81: Biokinetic Properties of mAbs are Ideal for Accumulation on Target
Biokinetic Properties of mAbs are Ideal for Accumulation on Target Representative imaging across longer time frame demonstrates clearance and uptake kinetics 1O'Donoghue et al. J Nucl Med 2018 Long circulation time with little tumor uptake for the first 24 h High accumulation of mAb onto tumor with
Slide 82: Promise of Pre-Targeted Approach – Clinical Data
1Bodet-Milin et al., JNM 2021 Immuno-PET/CT with anti-CEA BsmAb and 68Ga-IMP288 peptide showing pathological lesions with heterogeneous SUVmax ranging from 3.0 to 20.1 Maximum-intensity-projection (MIP) image (A) showed several pathological lesions On the fusion axial images, arrows located mediasti
Slide 83: State of the Art in Pre-Targeting for Radiopharmaceuticals
Jallinoja et al. J Nucl Med. 2021. Clinically Evaluated (Phase I / II) Preclinically Evaluated only Not Modular Immunogenic Four platforms reported prior to 2021 3 of 4 have been promising preclinically All face specific hurdles for widespread clinical use: Lack of "modularity“ Immunogenicity Poor t
Slide 84: Perspective Pre-Targeting Platform: Host - Guest Chemistry
Jallnoya et al., JNM 2021 First synthesized 1905 (Behrend, Germany) Structure described analytically 1981 Named after the pumpkin family Cucurbitacea Cucurbit[7]uril (CB7) modified antibody (mAb) OR HOST An ideal pretargeting agent: High in vivo stability Modular Non-toxic Non-immunogenic No need fo
Slide 85: Host - Guest Chemistry and in vivo Experiment
Unpublished data Perspective Pre-Targeting Platform: Host - Guest Chemistry and in vivo Experiment Synthesized the Guest as an adamantane-PEG3-PSC (Perspective’s proprietary chelator) 6-day lag time demonstrates stability of the CB7 Terrific Tumor:Normal ratios Very low kidney/liver retention High t
Slide 86: Host - Guest Chemistry in vivo Imaging Experiment
Unpublished data Perspective Pre-Targeting Platform: Host - Guest Chemistry in vivo Imaging Experiment Representative images of ligand during optimization process 4 hours post guest 8 hours post guest 24 hours post guest MIP coronal MIP coronal MIP coronal Host is a mAb targeting Carcinoembryonic An
Slide 87: Opportunity to Expand into ADC space
Bosi et al., EJ Cancer 2023 54 distinct cell surface targets Li et al., Cancers, 2022 371 target membrane protein-coding genes Subbiah, Curr. Probl. Cancer, 2021 13 ADC targets – compared to radiopharmaceuticals Vast number of mAbs that are humanized and have been in human clinical trials Many have
Slide 88: Appendix: Prostate Cancer Program – PSV40X
Appendix: Prostate Cancer Program – PSV40X
Slide 89: Typical Theranostic Approach: One Molecule, One Chelator, One Isotope
Typical Theranostic Approach : One Molecule, One Chelator, One Isotope Separate But Chemically Identical Molecules Labeled with Either 203Pb or 212Pb for Imaging and Treatment, Respectively Note: One chelator One isotope Unpublished data
Slide 90: PSV401 DoubLET: One Molecule, Two Chelators, Four Possible Isotopes
Enables the same molecular entity to treat with lead-212 (212Pb) and image by PET with Copper-64 (64Cu) Co-labeled with non-radioactive Pb provides identical biodistribution, allowing reliable dosimetry using 64Cu Technology Licensed from Mayo Clinic January 20241 IND-enabling studies underway First
Slide 91: Prostate cancer market opportunity and unmet need
1www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html; 2www.precedenceresearch.com/prostate-cancer-market; 3PLUVICTO PI; 4Novartis AG Q3 2023 Earnings Call Transcript 5Sartor et al (2021); 6www.urotoday.com/clinical-trials/from-the-editor/142064-targeted-alpha-therapy-for-prostate-
Slide 92: PSV401: Preclinical 64Cu PET Imaging Data Showing Tumor Uptake
PSMA+ LNCaP tumor model suggests [64Cu]PSV401 targets tumor rapidly – suitable for diagnostic or treatment monitoring Imaging product also indicates effective renal clearance and no other dose-limiting organs, essential for targeted alpha particle therapy Key Takeaways PSV401: Preclinical 64Cu PET I
Slide 93: PSV401: Preclinical Comparison to Industry Standard
PSV401: Preclinical Comparison to Industry Standard1 [64Cu]PSV401 Compares Favorably to FDA-Approved Imaging Agent [68Ga]PSMA-11 (ILLUCCIX®, Telix)2 [64Cu]PSV401 [68Ga]PSMA-11 1LNCaP tumor athymic nude mice 2Johnson et al., RPT Interest Group June 7 2023 https://rrp.cancer.gov/working_groups/AlphaPE
Slide 94: PSV401: Preclinical Comparison to Industry Standard
PSV401: Preclinical Comparison to Industry Standard [64Cu]PSV401 Significantly1 Improved Uptake/Clearance Compared to [68Ga]PSMA-112 Tumor Retention 1* indicates p < 0.05 [64Cu]PSV401 vs [68Ga]PSMA-11 (all data sets as indicated) 2Johnson et al., RPT Interest Group June 7 2023 https://rrp.cancer.gov
Slide 95: Preclinical [212Pb]PSV401 Therapy
All imaging performed with [64Cu]PSV401 microPET Treatment of PSMA+ prostate cancer xenograft with [212Pb]PSV401 reduced tumor size 38% in 3 days and complete response after 9 days Additional preclinical work underway Preclinical [212Pb]PSV401 Therapy Preliminary [212Pb]PSV401 Data Shows Potential t
Slide 96: Appendix: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Appendix: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Slide 97: Key Isotopes for Supply: 228Th and 224Ra
228Th Thorium 1.9 y 224Ra Radium 3.6 d 212Pb Lead 10.6 h 212Bi Bismuth 61 m Perspective currently has a 10 year supply agreement with US Department of Energy Produced as a waste by-product from isotope 223Ra (Xofigo) manufacture Irradiation to produce very large quantities (100s of Ci) in a high-flu
Slide 98: Flexible and Scalable Isotope Supply
Flexible and Scalable Isotope Supply 224Ra Enables Regional Manufacturing Hubs 228Th Thorium 1.9 y 224Ra Radium 3.6 d 212Pb Lead 10.6 h 212Bi Bismuth 61 m 212Pb grows in naturally (without irradiation) from 224Ra decay 224Ra half-life of 3.6 days allows weekly shipments to regional manufacturing sit
Slide 99: Key Isotopes for Supply: Th-228 and Ra-224
Parent Isotope Source Storage of Th-228 (half-life of 1.9 years) allows for “on-demand” purification of Ra-224 and Pb-212 There are multiple purification/production methods for Th-228 with different starting materials and processes including Ra-228 generators (half-life 5.7 years) Ra-224 (half-life
Slide 100: 212Pb Dose Modeling from Parent Isotope
228Th Replenishment 4 Ci per year 100,0001 Finished Doses per year 212Pb Dose Modeling from Parent Isotope Replenishable 228Th stockpile ensures supply of commercial quantities of 212Pb for finished dose manufacture1 Perspective Stockpile1 10 Ci 228Th Thorium 1.9 year 212Pb Lead 10.6 h Purification
Slide 101: Large quantities of precursor Th-228 available
Thorium-228 is available as a natural isotope but is also produced as a waste product from the nuclear fuel cycle, and as a result of production of therapeutic isotope Ra-223 (marketed as Xofigo, Bayer) Both Ac-227 (the parent isotope of Ra-223) and Th-228 are created when DOE’s ORNL irradiates radi
Slide 102: Pb-212 Isotope Purification
Pb-212 Isotope Purification Multiple purification paths to Pb-212 available Similar in size to Ga-68 generators Useful for preclinical R&D and clinical trials Nimble, portable supply available for either local or regional production Typically chromatography column based Using Ra-224 as parent Shelf
Slide 103: Centralized vs Distributed Network Production
Single centralized manufacturing facility Suitable for longer half-life isotopes (eg 177Lu, 131I, 225Ac, 67Cu) Allows for national/international production Shipping of finished product typically requires air and road transport Single point of failure (eg Novartis’ PLUVICTO® production issues) Nation
Slide 104: Isotope: Availability and Scalability at Clinical Development Stages
Isotope: Availability and Scalability at Clinical Development Stages Isotope Production methods Large, centralized capital-intensive infrastructure such as reactors, cyclotrons, LINACs etc. Suitable for longer half-life isotopes (eg. Lu-177, I-131, Ac-225, Cu-64/67, Pb-203 etc.) Allows for national/
Slide 105: Isotope and Finished Product Landscape: Commercial Supply
Isotope and Finished Product Landscape: Commercial Supply Centralized Isotope and Manufacturing - Competitors Pb-212-labeled Commercial Perspective Products Parent Isotope Source Isotope Production Method Purification of Isotope Isotope Shipping Finished Product Manufacturing Logistics Summary Funct
Slide 106: Slide 106
Perspective Therapeutics — Investor Presentation (November 2024) on 6ix