SEEING IS BELIEVING SARCOPHAGINE CHELATORS AND COPPER ISOTOPES FOR IMAGING AND THERAPY Sydney Vital and STEaM Neuroendocrine Tumour Preceptorship May 2018 Amos Hedt Head of Clinical Development 1
CLARITY HIGHLIGHTS 2 Clarity is a leading innovative radiopharmaceutical company Clinical stage radiopharmaceutical company Pipeline of copper-based radiopharmaceutical assets Leading patented technology Building a world class team Collaborations with world leading institutes
Positive movement MARKET OVERVIEW 3 The Global Nuclear Medicine Market is poised to grow at a CAGR of around 10.2% over the next decade to reach approximately $11.3 billion by 2025 PET Radio therapeutics By 2021, PET procedure volume is predicted to increase to 11 million per year with sales of $5.0 billion Radiotherapeutics represented 4% of the total nuclear medicine market in 2013. By 2030, it is forecast to represent over 50% of the $24 billion nuclear medicine market PET SPECT Market Drivers Lu-177, Cu-67, alpha Theranostics / CDx Peptides/Antibodies Centralised manufacturing I-131, Y-90, In-111 Diagnostics Small molecules Hospital radiopharmacy Negative movement
CLARITY S CANCER TECHNOLOGY Clarity uses Copper-64 (Cu-64) for PET imaging and dosimetry. This may enable a tailored dose of Copper-67 (Cu-67) for therapy. 4 Cu-64 Peptide IMAGING PRODUCT (PET) Diagnose Select patients Monitor therapy Cu-67 Delayed Imaging Prospective dosimetry Dose per tumour Rate limiting organs Tailored therapy Peptide THERAPY PRODUCT
COPPER ISOTOPES:PERFECT PAIRING 5 There are many advantages of using the Cu-64/Cu-67 pairing Cu-64 - Ideal diagnostic PET isotope - T½ 12.7 hours - Centralised supply - GMP suitable - Imaging over 48hrs - Cyclotron produced Cu-67 - Ideal therapy isotope - T½ 2.6 days - Centralised supply - GMP suitable - LINAC produced - IAC
VERSATILITY OF Cu-67 Cu-67 may have benefits in efficacy and versatility in timing of dose due to the shorter half-life Characteristic Shorter half life Higher decay rate Faster decay Less side effects off target Better radiation safety Opportunity Better efficacy in some tumours? Fractionated dosing closer together Paediatrics Patients released earlier Linear Quadratic equation: Cell survival as a function of dose for different dose rates
COPPER ISOTOPES 7 Why is Cu-64/Cu-67 coming of age now? Chelator Clarity s proprietary SAR chelators do not leak copper in vivo, which enables Cu-67 therapy and dosimetry calculations Supply Cu-64 is produced on cyclotrons, can be GMP, available weekly in the USA, EU, Australia Cu-67 is made on demand in the USA, can become GMP, and is commercially scalable Industry Dosimetry calculations for Cu-67 enabled by Cu-64 Theranostic imaging limit products toxicity and coming maximise on the efficacy market Dosimetry 2.5 days half-life increasing allows repeat dosing to improve efficacy
CENTRALISED RADIOPHARMACY Cu-64 and Cu-67 can be produced under GMP conditions and enable centralised manufacture benefits, making supply of a finished GMP product available to all hospitals and private centers 8 Cu-64 Cyclotrons Regional Radiopharmacy Cu-67 LINACS Shipping finished product (GMP) Hospital Hospital Private Practice Private Practice Radiology (PET) Therapy Centre Patient is injected by a nurse
CENTRALISED RADIOPHARMACY Cu-64 and Cu-67 enable regional radiopharmacy distribution. Clarity will ship finished product from a regional centre to all its clinical trial sites. 9 Adelaide St Louis
CLARITY S Cu-64/Cu-67 PLATFORM Clarity s platform derives its strength from the SAR-chelator technology and a strong IP position around the technology as well as composition patents 10 Cu-64/Cu-67 THERANOSTICS Cu-64 CDx SARTATE -NETs -Neuroblastoma -Meningioma SAR-PSMA -Prostate SAR-BBN -Breast -Prostate -Ovarian -Glioma -Lung SAR-Discovery -Pan-Cancer -Breast -Glioma -Melanoma -Pre-targeting SAR- PlateView -Unstable Plaque SAR-Fibrosis - Fibrosis World Leading Clinical Investigators and Advisers Regulatory Strategy Quality Management System Intellectual Property Strategy
CLARITY S CANCER THERANOSTICS Clarity s pipeline is aimed at tapping into achievable markets that can be better served with radiopharmaceutical technologies 11 THERANOSTICS Preclinical Phase1/2a Phase2b SARTATE NETs/Meningioma NETs PET Imaging NETs Therapy SARTATE KIDS Neuroblastoma PET Imaging Neuroblastoma Therapy SAR-PSMA Prostate Cancer PET Imaging Prostate Cancer Therapy SAR-BBN Prostate/Breast/Ovarian/Glioma/Lung PET Imaging Prostate/Breast/Ovarian/Glioma/Lung Therapy Complete Planned
DIAGNOSTICS Clarity s pipeline is aimed at tapping into achievable markets that can be better served with radiopharmaceutical technologies 12 COMPANION DIAGNOSTICS Preclinical Phase 0 (FIH) Phase1/2a Partner/Fund PET Imaging Products Vulnerable Plaque PlateView Belgium grant funded Fibrosis Marker Pulmonary/Hepatic/Cardiac NHMRC grant funded Complete Planned
SARTATE SARTATE (Cu-64/Cu-67) is a first-in-class, highly targeted theranostic radiopharmaceutical, which can image, perform prospective dosimetry, and subsequently treat cancers that express somatostatin receptor 2 (SSTR2) 13 Clinical Demand Require a diagnostic tool for prospective dosimetry Industry demand Centralised manufacture of product GMP Products Decrease COGS
RATIONALE FOR APPROACH 64 Cu-SARTATE allows for multiple scans out to 24 hrs to calculate the therapeutic window to maximise therapeutic dose whilst minimising toxicity For PRRT most centres used fixed administered activity (7-8 GBq of 177 Lu-DOTAoctreotate (LuTate) and 2-4 GBq of 90 Y-DOTA-octreotate (Ytate) Sink effect means that dose to tumor and normal tissues vary markedly with disease burden and avidity Differential radiation doses impact efficacy and toxicity, especially to susceptible target organs such as the kidneys Current dosing plans mean every patient is either over or under-dosed We need better prospective dosimetry estimation, but single time point scanning such as 68 Ga-DOTA-octreotate does not assist with calculation of clearance kinetics from tumour and kidneys
STUDY DESIGN Completed Study 15 Clinical Study Clarity-01 Positron Emission Tomography (PET) Imaging of Patients with Low & Intermediate Grade Neuroendocrine Tumors using 64 Cu- SARTATE : A Single Centre, Open-Label, Non-Randomized, Phase-0 Microdosing Investigation
STUDY DESIGN 16 Study Parameters Recruitment 10 Patients with neuroendocrine tumors Primary Objectives safety, biodistribution, and dosimetry Secondary Objectives Dose Investigate the interaction of 64 Cu-SARTATE with malignant tissues 200MBq of activity in a maximum of 20µg of peptide Key Inclusion Criteria Low and Intermediate grade NETs (Ki-67 index <20%), prior positive 68 Ga-DOTATATE PET/CT scan, sufficient life expectancy and renal function Key Exclusion Criteria somatostatin sensitivity, current somatostatin treatment, other serious condition
Within 28 days STUDY DESIGN 17 Patient Flowchart 68 Ga-DOTATATE PET/CT Scan - Standard of Care Screening Informed Consent / Screening / Baseline Assessments Day 1 Treatment & Scans PET/CT scans performed at 30 minutes, 1hr (PET only) & 4hrs following SARTATE Day 2 Scan PET/CT scan performed 24hrs* following SARTATE * Note due to clinic schedules planned 24hr scans were performed at 20hrs Day 8 Exit Follow-up safety assessment
RESULTS: PATIENT DATA 18 Safety Detailed safety review after Pts 001, 002, 005 No SAEs or significant SARTATE-related adverse events observed in any patients All patients completed the study successfully and exited at Day 8
RESULTS: PATIENT DATA 19 Patient 001 Unresectable pancreatic primary being considered for neoadjuvant PRRT with Lutate to shrink the tumour to make it operable Borderline renal function (note retention of signal in the kidneys) High tumour retention and good liver clearance at late timepoint
RESULTS: PATIENT DATA 20 Patient 002 Extensive nodal and small volume cardiac metastases High tumour retention and good liver clearance at later time point Progressive renal clearance as the signal from the kidneys diminishes
RESULTS: PATIENT DATA 21 Patient 003 Patient had tumour surgically removed previously Suspected recurrence at resection margin in the tail of the pancreas Note high uptake in target lesion at 20 hrs compared to GaTate scan
RESULTS: PATIENT DATA 22 Patient 003 continued Suspected recurrence at resection margin in the tail of the pancreas Second lesion identified only on delayed imaging and not on standard of care GaTate scan
RESULTS: PATIENT DATA 23 Patient 006 Pancreatic NET Progressive liver clearance enhances visualisation of small hepatic metastases at late time points
RESULTS: PATIENT DATA 24 Patient 007 Pancreatic NET Comparison to clinical FDG and GaTate Note improved definition of hepatic metastases in late time point scan
RESULTS: PATIENT DATA 25 Patient 009 Pancreatic NET Major impact on definition of small intrahepatic metastases at delayed time point
RESULTS: TISSUE CLEARANCE Overall, 64 Cu-SARTATE shows clearance from key organs and high retention in tumours, indicating the promise of a personalised therapeutic 67 Cu-SARTATE PRRT approach 26 64 Cu-SARTATE cleared significantly from the liver and the kidneys between 60 minutes and 24 hours There was not significant clearance from the spleen between 60 minutes and 24 hours Average 64 Cu-SARTATE retention in each patient s hottest tumour remained very high and did not diminish significantly Hottest lesion to liver ratio increased from 8:1 to 21:1 and this was significant (p < 0.001)
DOSIMETRY RESULTS Delayed imaging enables dosimetry calculations over 24 hours Whole body Effective Dose (ED) was estimated to be 7-8 msv for a 200 MBq injection of 64 Cu-SARTATE. This compares favourably with 18 F-FDG where 5-6 msv whole body ED for an injected amount of 250-300 MBq. Estimate radiation dosimetry for 64 Cu- SARTATE in children and for therapeutic administration of 67 Cu-SARTATE in adults. Lesion based dosimetry to estimate Gy
CONCLUSIONS 28 Sarcophagine chelator leads to stable 64 Cu binding in vivo, allowing for accurate clearance kinetics to be calculated There was high retention of 64 Cu-SARTATE in tumour sites, with the signal increasing in intensity in the hottest lesions over 24 hrs The clearance of liver activity enhances lesion definition in this organ with the hottest lesion to liver ratio more than doubling Acceptable radiation dosimetry for diagnostic use (similar to existing clinical modalities) Distribution from centralised GMP radiopharmacy is feasible 64 Cu-SARTATE offers prospective dosimetry and theranostic pair with 67 Cu-SARTATE
SARTATE KIDS SARTATE Kids is being developed for the treatment of neuroblastoma, one of the most aggressive childhood cancers 29 Neuroblastoma (NB) is the most common cancer to be diagnosed in the first year of life and accounts for around 13% of paediatric cancer mortality (Maris 2010) 84% of neuroblastomas express SSTR2 (Watanabe et al. 2014) SARTATE Kids could help to minimise side effects of current treatments 68 Ga-DOTATATE AND PRRT WITH 177 Lu-DOTATATE Source: Kong et al 2015
SARTATE KIDS SSTRs are expressed in a number of childhood cancers, building potential for successful treatment with SARTATE 30 SSTRs are expressed in high densities in the following childhood cancers: Medulloblastomas NETs Neuroblastomas Ganglioneuromas Ganglioneuroblastomas Hepatocellular carcinoma Astrocytoma Brain stem glioma Delayed Imaging Prospective dosimetry Dose per tumour Rate limiting organs Tailored therapy Nov 2017 Q3 2018 Phase 1/2a imaging study Peptide THERAPY PRODUCT Q3 2018 Q4 2019 Phase 2b imaging study Cu-67 2017 2018 2019 Q4 2018 Q3 2018 Phase 1/2a therapeutic study
Phase 1 Adults Therapy 31 Clinical Study Clarity-02: Peptide Receptor Radionuclide Therapy of Patients with Meningioma with 67 Cu- SARTATE : A single-centre, open-label, non-randomised, personalised-dose, Phase I-IIa Theranostic Clinical Trial
Phase 1 Kids Diagnostic 32 Clinical Study Clarity-03: First-In-Human Phase I Clinical Trial of 64 Cu- SARTATE for Imaging and Dosimetry Estimation in Paediatric Patients with High- Risk Neuroblastoma
CLARITY S PARTNERS Clarity has established close relationships with industry thought leaders and gained access to world-class facilities, thus facilitating innovation and constantly honing its capabilities 33 CLARITY IN AU CLARITY IN USA
CLARITY SUMMARY 34 Clinical stage company with first product SARTATE in clinical trial development Ideal technology suited to biopharma assets for the theranostic treatment of serious diseases Strong patent position Several patent families with all major markets protected Attractive markets Achievable niche markets or large markets in partnership with pharma companies Effective team managing world class partners and researchers here and around the world Utilises Australia s competitive advantages Regulatory framework, clinical trials, radiopharmaceuticals, R&D tax rebate, foreign exchange
CLARITY S CONTACTS 35 DR ALAN TAYLOR Executive Chairman Ph: +61 (0)413 871 165 E: ataylor@claritypharm.com AMOS HEDT Head of Clinical Development Ph: +61 (0)400 034 495 E: ahedt@claritypharm.com DR MATT HARRIS CEO www.claritypharm.com Ph: +61 (0)439 620 125 E: mharris@claritypharm.com