Perspective Therapeutics, Inc. · AMEX:CATX
Perspective Therapeutics — Investor Presentation (August 2024)
111 slides from Perspective Therapeutics's investor presentation, Aug 13, 2024
Slide 1: Corporate Presentation August 2024
Corporate Presentation August 2024 NYSE: CATX
Slide 2: Legal Disclaimers
Legal Disclaimers 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,” “s
Slide 3: Investment Highlights
Platform radiopharmaceutical company targeting pan-cancer opportunities utilizing 2nd generation ⍺-emitter Robust clinical pipeline with three clinical-stage programs. VMT-⍺-NET for neuroendocrine tumors; VMT01 for melanoma; PSV359 for multiple solid tumors Multiple expected near-term readouts and m
Slide 4: Strong Financial Position
Funding into mid-2026 Strong Financial Position Cash, cash equivalents and short-term investments as of June 30, 2024 $292.9 million Share count as of June 30, 2024 67.4 million Outstanding common stock warrants & options as of June 30, 2024 7.4 million Outstanding pre-funded warrants as of June 30,
Slide 5: Platform Expansion Engine: Three Lead Programs in Clinic and Broad Pipeline
Platform Expansion Engine Three Lead Programs in Clinic and Broad Proprietary Pipeline Program Tumor Type Discovery Human Clinical Imaging First in Human Therapy Phase 1/2 Phase 3 VMT-⍺-NET Neuroendocrine cancers Pheochromocytomas, paragangliomas Small cell lung cancer VMT01/02 Melanoma (MC1R imagin
Slide 6: 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 7: Management Team
Michael Schultz, PHD Chief Science Officer 20+ years industry and research experience in radiopharmaceuticals; co-founder Viewpoint MT & inventor of Perspective products Thijs Spoor Chief Executive Officer 20+ years of expertise in biotechnology companies; public and private companies; oncology and
Slide 8: Radiopharmaceutical theranostics platform advantages
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 9: Perspective's Radiopharmaceutical Optimization Process
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 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 Enabling Technology for Pb-based Radiopharmaceuticals
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 Targeted Treatment
Pb-based Theranostics Enable Both Diagnosis and Targeted Treatment of Cancer Identical Distribution of 203Pb and 212Pb for Imaging and Treatment, Respectively Unpublished data
Slide 13: Neuroendocrine Tumors: VMT-⍺-NET
Neuroendocrine Tumors: VMT-⍺-NET Targeting the somatostatin receptor to treat rare neuroendocrine-type cancers
Slide 14: VMT-⍺-NET Development Status
Image Panel: 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 currently…
Slide 15: SSTR2 is an Attractive Target Expressed Across Several Tumor Types
Neuroendocrine tumors (NETs) Neuroendocrine cells are specialized cells that secrete hormones and other bioactive substances Neuroendocrine cells are found throughout the body Often grow in the pancreas or other areas of the gut, such as the stomach, small intestine, rectum, colon or appendix SSTR2
Slide 16: Potential Superiority of Platform Technology vs Generic Compounds
SSTR2 tumor model demonstrates superiority of VMT-𝛼-NET to generic compounds 8-fold improved tumor uptake with decreased kidney retention Key Takeaways Generic 203Pb-DOTATOC Proprietary 203Pb-VMT-α-NET Tumor Kidneys Potential Superiority of Perspective’s Platform Technology vs Generic Compounds…
Slide 17: VMT-α-NET Shows Significant Improvement vs Standard of Care in Preclinical Models
Drug Administered [212Pb]VMT-α-NET (1 x 120 µCi) Vehicle [212Pb]VMT-α-NET (4 x 30 µCi) [177Lu]DOTATATE (3 x 500 µCi) Standard of Care VMT-α-NET Shows Significant Improvement vs Standard of Care in Preclinical Models Superior Clinical Activity with Single Dose or Multiple Administrations in AR42J SST
Slide 18: 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 19: 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 20: Significant Response After Single Dose of [212Pb]VMT-⍺-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 21: Significant Response After Single Dose, Almost Complete Response After 3 Doses
1 Serum Adrenocorticotropic Hormone (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 with Adrenal Crisis
Slide 22: Investigator-led study in India: current status, response and safety
Current Status 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 administered to date Respo
Slide 23: Presented at SNMMI 2024
Dr Ishita Sen, Fortis Memorial research institute (FMRI), Gurugram, India. Presented at SNMMI 2024
Slide 24: VMT-⍺-NET US Phase 1/2a trial design
1mTPI-2: Modified toxicity probability index https://clinicaltrials.gov/study/NCT05636618 Note: average administered activity from Indian investigator led research was 2.9 mCi per cycle Primary Objective: To determine the MTD/MFD of [212Pb]VMT-α-NET (RP2D) Imaging: FDA approved SSTR2 PET/CT Populati
Slide 25: Melanoma Program: VMT01/02
Melanoma Program: VMT01/02 Using the melanocortin receptor MC1R to target melanoma for imaging and therapy
Slide 26: VMT01 Development Status
Image: Top panel - PET/CT cross section of a metastatic melanoma patient using FDG; middle panel - PET/CT of the same patient with VMT02; lower panel - SPECT/CT of same patient with VMT01 Targeting melanocortin 1 receptor (MC1R) which is over-expressed in melanoma Preclinical data shows synergistic
Slide 27: Metastatic Melanoma: significant unmet need
Advanced stages of disease occurs throughout the body requiring aggressive systemic treatment 1https://www.marketdataforecast.com/market-reports/melanoma-therapeutics-market, 2cancer.org, 3curemelanoma.org [212Pb]VMT01 target indication: MC1R-positive melanoma Projected market opportunity for melan
Slide 28: [68Ga]VMT02 PET Imaging in Patient with MC1R Positive Metastatic Melanoma
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 University China Clinical Collaborator: Patient information: Male, Asian, 33 years old [68Ga]VMT02: 7 mCi injection, 45 min post-injection imagi
Slide 29: Combination with immune checkpoint inhibitors induced synergistic anti-tumor effect
Key Takeaways High response rates in multiple tested models >70% complete and durable response if 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; 2
Slide 30: VMT01 Phase 1/2a trial design
De-escalation possible for Cohort 2 – 4 including for intermediate doses 1mTPI-2: Modified toxicity probability index https://clinicaltrials.gov/study/NCT05655312 Monotherapy Escalation phase n ≈ 32 Recruitment Complete Cohort 1 [212Pb]VMT01 n = 3 / 3 mCi x 3 Recruited Cohort 2 [212Pb]VMT01 n = 7 /
Slide 31: Pan Cancer Target: PSV359
Pan Cancer Target: PSV359 Preclinical Efficacy and First in Human Images of Novel Peptide Targeting Fibroblast Activation Protein alpha (FAPa)
Slide 32: Fibroblast Activation Protein α is a Pan Cancer Target
Fibroblast Activation Protein 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
Slide 33: Fibroblast Activation Protein α is a Pan Cancer Target
1Kratochwil et al., JNM, 2019 Sarcoma Expression of FAP- on Tumor Cells Expression of FAP- on Tumor Stroma Cells Lung Cancer NETs Average SUVmax of 68Ga-FAPI PET/CT Across 28 Different Cancer Types Fibroblast Activation Protein is a Pan Cancer Target1 Multiple imaging products in development suc
Slide 34: 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 Bioconjugat
Slide 35: [212Pb]PSV359 Demonstrates Preclinical Efficacy
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 36: First in Human Imaging of [203Pb]PSV359 in Different Cancers
[203Pb]PSV359 SPECT/CT FIH Imaging of [203Pb]PSV359 in Different Types of Cancers Source: Unpublished data Patient 1 Chondroblastic Osteosarcoma [203Pb]PSV359 Lesion in head of left humerus 1 hr 4 hr 18 hr 4 hr 18 hr
Slide 37: [203Pb]PSV359 Imaging: Neuroendocrine Tumor Patient
Patient 2 Neuroendocrine Tumor Source: Unpublished data [203Pb]PSV359 [203Pb]PSV359 SPECT/CT Lesion in head of left humerus 4 hr 18 hr 1 hr 4 hr 18 hr
Slide 38: [203Pb]PSV359 Imaging: Lung Adenocarcinoma Patient
Patient 3 Lung Adenocarcinoma Source: Unpublished data Lytic lesion in sacrum Lytic lesion in thoracic vertebra [203Pb]PSV359 [203Pb]PSV359 SPECT/CT 1 hr 4 hr 18 hr
Slide 39: FAP: Potential Indications
FAP: Potential Indications 1Unmet need defined as one- minus five-year survival rate (overall for heme, metastatic for solid). 2 Patient size calculated as annual incidence for heme, and larger of mortality and metastatic incidence for solid. 3Modified from EvaluatePharma® July 2020, Evaluate Ltd.;
Slide 40: Summary – PSV359 FAP-α Program
FAP- is a pan-cancer target that is highly expressed in many cancers Perspective’s in-house discovery team has developed an optimized peptide with potential best-in-class characteristics as demonstrated in preclinical models First in human clinical SPECT/CT imaging suggests the tumor targeting and
Slide 41: Prostate Cancer Program: PSV401
Prostate Cancer Program: PSV401 A differentiated PSMA-targeted radiohybrid molecule for dual PET imaging and targeted alpha therapy
Slide 42: Prostate Cancer Program: PSV40X
Prostate Cancer Program: PSV40X A differentiated PSMA-targeted radiohybrid molecule for dual PET imaging and targeted alpha therapy 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 20
Slide 43: PSV40X: Improved Preclinical Metrics for a Superior Therapeutic Window
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 44: Pre-Targeting Platform
Pre-Targeting Platform The Next Generation of Targeted Alpha Particle Radiopharmaceuticals
Slide 45: Pre-Targeting Platform Background
Pre-Targeting Platform Background Relies on the different kinetics of large proteins and small molecules and a multi-step process 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 radiolabe
Slide 46: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics The Path to Commercial Supply
Slide 47: 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 All other therapeutic isotopes require capital-intensive infrastructure manufacturing processes (irradiation) Isotope Purification VMT-𝛼-GEN enables shipping of isotope…
Slide 48: 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 49: 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 50: 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 51: 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 52: Isotope Decay Chain Dictates Supply, Purification, Manufacturing & Logistics
228Th Thorium 1.9 y 224Ra Radium 3.6 d 212Pb Lead 10.6 h 212Bi Bismuth 61 m 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 existi
Slide 53: 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 54: Regional Manufacturing Allows Commercialization of 212Pb-labeled Products
Location Radius 11 hr – 400 miles Coralville, IA 51 m Somerset, NJ 75 m Los Angeles, CA 46 m Austin, TX 32 m Atlanta, GA 57 m Orlando, FL 25 m Top 6 sites cover nearly 300 million people within a one half-life (11 hr) delivery radius1 Products can also be driven further or flown as necessary Propose
Slide 55: Strong Intellectual Property Portfolio
2 Issued Patents (Expiry in 2037, with potential PTE) Composition of matter and method of use on melanoma targeting peptides with Pb-specific chelator 1 Allowed AU Patent Application (Expiry in 2037) Composition of matter and method of use on melanoma targeting peptides with Pb-specific chelator 28
Slide 56: Appendix
Appendix
Slide 57: Our Mission
Targeting cancer from the inside out We are developing game-changing Precision Medicine Therapeutics which harness the power of targeted Alpha-Particle Radiotherapies that make an impactful difference for cancer patients and the clinicians who treat them. Our Mission
Slide 58: Who We Are
Who We Are Perspective Therapeutics (NYSE:CATX) is a clinical stage precision medicine company, debuting as a public company in 2023. With a broad pipeline and two prioritized lead programs in clinic, we are disrupting traditional radiation therapy treatment for cancer though developing a new class
Slide 59: 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 60: 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 61: 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 62: 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 63: 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 64: Ac-225 Decay and Daughter Ingrowth
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 65: 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 66: 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 67: 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 68: 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 69: 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 70: Appendix: VMT-⍺-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 71: 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 72: 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 73: Patient 5: Pancreatic NET
Tumor Before Treatment Tumor After Treatment Reduction in Size of Necrotic Masses After 2 Doses Patient 5: Pancreatic NET
Slide 74: 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 75: Serious Adverse Event in Patient 2: Myelodysplastic syndrome
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 76: Serious Adverse Event in Patient 6: Acute Cardiac Event
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 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: Pre-Targeting Platform Background
Pre-Targeting Platform Background Relies on the different kinetics of large proteins and small molecules and a multi-step process 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 radiolabe
Slide 83: 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 84: 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 85: 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 86: 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 87: 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 88: 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 89: Appendix: Prostate Cancer Program – PSV40X
Appendix: Prostate Cancer Program – PSV40X
Slide 90: 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 91: 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 92: 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 93: 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 94: 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 95: 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 96: 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 97: Appendix: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Appendix: Manufacturing, Production and Logistics of 212Pb-labeled Therapeutics
Slide 98: 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 99: 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 100: 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 101: 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 All other therapeutic isotopes require capital-intensive infrastructure manufacturing processes (irradiation) Isotope Purification VMT-𝛼-GEN enables shipping of isotope…
Slide 102: Key Isotopes for Supply: Th-228 and Ra-224
Parent Isotope Source Storage of thorium-228 (half-life of 1.9 years) allows for “on-demand” purification of Ra-224 and Pb-212 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 3.6
Slide 103: 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 Stockpile 10 Ci 228Th Thorium 1.9 year 212Pb Lead 10.6 h Purification M
Slide 104: 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 105: 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 106: 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 107: 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 108: 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 109: 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 110: 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 111: Slide 111
Perspective Therapeutics — Investor Presentation (August 2024) on 6ix