seeing is believing - sydney vital · by 2021, pet procedure volume is predicted to increase to pet...

SEEING IS BELIEVING

Amos HedtHead of Clinical Development

Sydney Vital and STEaM Neuroendocrine Tumour Preceptorship

May 2018

SARCOPHAGINE CHELATORS AND COPPER ISOTOPES FOR

IMAGING AND THERAPY

1

CLARITY HIGHLIGHTSClarity is a leading innovative radiopharmaceutical company

2

• Clinical stage radiopharmaceutical company

• Pipeline of copper-based radiopharmaceutical

assets

• Leading patented technology

• Building a world class team

• Collaborations with world leading institutes

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

MARKET OVERVIEW

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

By 2021, PET procedure volume is predicted to increase to

11 million per year with sales of $5.0 billionPET

Radio

therapeutics

Market Drivers

PET

Lu-177, Cu-67, alpha

Theranostics / CDx

Peptides/Antibodies

Centralisedmanufacturing

SPECT

I-131, Y-90, In-111

Diagnostics

Small molecules

Hospital radio-pharmacy

Po

sitive

mo

ve

me

nt

Ne

ga

tive

mo

ve

me

nt

3

CLARITY’S CANCER TECHNOLOGY4

IMAGING PRODUCT(PET)

Cu-64

THERAPY PRODUCT

Cu-67

• Diagnose

• Select patients

• Monitor therapy

Delayed

Imaging

• Prospective dosimetry

• Dose per tumour

• Rate limiting organs

• Tailored therapy

Peptide

Peptide

Clarity uses Copper-64 (Cu-64) for PET imaging and dosimetry. This may

enable a tailored dose of Copper-67 (Cu-67) for therapy.

There are many advantages of using the Cu-64/Cu-67 pairing

- Ideal diagnostic PET isotope

- T½ 12.7 hours

- Centralised supply- GMP suitable

- Imaging over 48hrs

- Cyclotron produced

Cu-64

- Ideal therapy isotope

- T½ 2.6 days

- Centralised supply

- GMP suitable

- LINAC produced - IAC

Cu-67

COPPER ISOTOPES:PERFECT PAIRING

5

VERSATILITY OF Cu-67

Linear Quadratic equation: Cell

survival as a function of dose for

different dose rates

Cu-67 may have benefits in efficacy and versatility in timing of dose due to

the shorter half-life

Characteristic

Shorter half life

Opportunity

Higher decay rate Better efficacy in

some tumours?

Faster decay Fractionated dosing

closer together

Less side effects –

off target

Paediatrics

Better radiation

safety

Patients released

earlier

Why is Cu-64/Cu-67 coming of age now?

― 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

― Clarity’s proprietary SAR chelators do not leak copper in vivo, which enables Cu-67 therapy and dosimetry calculations

Chelator

Supply

― Dosimetry calculations for Cu-67 enabled by Cu-64 imaging limit toxicity and maximise efficacy

― 2.5 days half-life allows repeat dosing to improve efficacy

― Theranostic products coming on the market― Dosimetry increasing

Industry

COPPER ISOTOPES

7

CENTRALISED RADIOPHARMACYCu-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

Shipping “finished product” (GMP)

Patient is injected by a nurse

Regional

Radiopharmacy

Cu-64

Cyclotrons

Cu-67

LINACS

Hospital Hospital Private Practice

Therapy Centre

Private Practice

Radiology (PET)

8

9

CENTRALISED RADIOPHARMACYCu-64 and Cu-67 enable regional radiopharmacy distribution. Clarity will ship

finished product from a regional centre to all its clinical trial sites.

St Louis

Adelaide

CLARITY’S Cu-64/Cu-67 PLATFORMClarity’s platform derives its strength from the SAR-chelator technology and

a strong IP position around the technology as well as composition patents

10

Quality Management System

Cu-64/Cu-67 THERANOSTICS

Regulatory Strategy

World Leading Clinical Investigators and Advisers

Cu-64 CDx

SAR-

PlateView™-Unstable Plaque

SAR-Fibrosis- Fibrosis

SAR-BBN-Breast

-Prostate

-Ovarian

-Glioma

-Lung

SAR-Discovery-Pan-Cancer

-Breast

-Glioma

-Melanoma

-Pre-targeting

SARTATE™-NETs

-Neuroblastoma

-Meningioma

SAR-PSMA-Prostate

Intellectual Property Strategy

CLARITY’S CANCER THERANOSTICSClarity’s pipeline is aimed at tapping into achievable markets that can

be better served with radiopharmaceutical technologies

Complete Planned

THERANOSTICS

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

Preclinical Phase1/2a Phase2b

11

COMPANION DIAGNOSTICS

PET Imaging Products

Vulnerable Plaque

PlateView™

Fibrosis Marker

Pulmonary/Hepatic/Cardiac

Preclinical Phase 0 (FIH) Phase1/2a Partner/Fund

DIAGNOSTICSClarity’s pipeline is aimed at tapping into achievable markets that can

be better served with radiopharmaceutical technologies

Belgium grant funded

Complete Planned

NHMRC grant funded

12

Clinical Demand

• Require a diagnostic tool for prospective

dosimetry

Industry demand

• Centralised manufacture of product

• GMP Products

• Decrease COGS

13

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)

RATIONALE FOR APPROACH

• For PRRT most centres used fixed administered activity (7-8 GBq of 177Lu-DOTA-

octreotate (LuTate) and 2-4 GBq of 90Y-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 68Ga-DOTA-octreotate does not assist with calculation of clearance kinetics

from tumour and kidneys

64Cu-SARTATE allows for multiple scans out to 24 hrs to calculate the

therapeutic window to maximise therapeutic dose whilst minimising toxicity

STUDY DESIGN – Completed Study15

Clinical Study Clarity-01

• Positron Emission Tomography (PET) Imaging

of Patients with Low & Intermediate Grade

Neuroendocrine Tumors using 64Cu-

SARTATE™: A Single Centre, Open-Label,

Non-Randomized, Phase-0 Microdosing

Investigation

• Recruitment

• 10 Patients with neuroendocrine tumors

• Primary Objectives

• safety, biodistribution, and dosimetry

• Secondary Objectives

• Investigate the interaction of 64Cu-SARTATE with malignant tissues

• Dose

• 200MBq of activity in a maximum of 20µg of peptide

• Key Inclusion Criteria

• Low and Intermediate grade NETs (Ki-67 index <20%), prior positive 68Ga-DOTATATE PET/CT scan,

sufficient life expectancy and renal function

• Key Exclusion Criteria

• somatostatin sensitivity, current somatostatin treatment, other serious condition

STUDY DESIGN16

Study Parameters

STUDY DESIGN17

Patient Flowchart

Day 8 ExitFollow-up safety assessment

Day 2 ScanPET/CT scan performed 24hrs* following SARTATE

Day 1 Treatment & ScansPET/CT scans performed at 30 minutes,

1hr (PET only) & 4hrs following SARTATE

ScreeningInformed Consent / Screening / Baseline

Assessments

68Ga-DOTATATE PET/CT Scan - Standard of Care

With

in 2

8 d

ays

* Note due to clinic schedules planned 24hr

scans were performed at 20hrs

• 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 DATA18

Safety

• 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


Patient 001

• 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


Patient 002

• 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


Patient 003

• 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


Patient 003 continued…

• Pancreatic NET

• Progressive liver clearance enhances visualisation of small hepatic metastases at late time

points


Patient 006

• Pancreatic NET – Comparison to clinical FDG and GaTate

• Note improved definition of hepatic metastases in late time point scan


Patient 007

• Pancreatic NET

• Major impact on

definition of small intra-

hepatic metastases at

delayed time point


Patient 009

• 64Cu-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 64Cu-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)

RESULTS: TISSUE CLEARANCE26

Overall, 64Cu-SARTATE shows clearance from key organs and high retention in

tumours, indicating the promise of a personalised therapeutic 67Cu-SARTATE

PRRT approach

• Whole body Effective Dose (ED) was estimated to be 7-8 mSv for a 200 MBqinjection of 64Cu-SARTATE.

• This compares favourably with 18F-FDG where 5-6 mSv whole body ED for an injected amount of 250-300 MBq.

• Estimate radiation dosimetry for 64Cu-SARTATE in children and for therapeutic administration of 67Cu-SARTATE in adults.

• Lesion based dosimetry to estimate Gy

Delayed imaging enables dosimetry calculations over 24 hours

DOSIMETRY RESULTS

• Sarcophagine chelator leads to stable 64Cu binding in vivo, allowing for accurate

clearance kinetics to be calculated

• There was high retention of 64Cu-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

• 64Cu-SARTATE offers prospective dosimetry and theranostic pair with 67Cu-SARTATE

CONCLUSIONS28

• 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

SARTATE™ KIDSSARTATE™ Kids is being developed for the treatment of neuroblastoma,

one of the most aggressive childhood cancers

Source: Kong et al 201568Ga-DOTATATE AND PRRT WITH 177Lu-DOTATATE

29

SSTRs are expressed in high

densities in the following

childhood cancers:

• Medulloblastomas

• NETs

• Neuroblastomas

• Ganglioneuromas

• Ganglioneuroblastomas

• Hepatocellular carcinoma

• Astrocytoma

• Brain stem glioma

30

SARTATE™ KIDSSSTRs are expressed in a number of childhood cancers, building potential for

successful treatment with SARTATE™

THERAPY

PRODUCT

Cu-67

Delayed

Imaging

• Prospective dosimetry

• Dose per tumour

• Rate limiting organs

• Tailored therapy

Peptide

2017 2018 2019

Nov 2017 – Q3 2018

Phase 1/2a

imaging study

Q3 2018 – Q4 2019

Phase 2b

imaging study

Q4 2018 – Q3 2018

Phase 1/2a

therapeutic study

31

Phase 1 Adults Therapy

Clinical Study Clarity-02:

Peptide Receptor Radionuclide Therapy of

Patients with Meningioma with 67Cu-

SARTATE™: A single-centre, open-label,

non-randomised, personalised-dose,

Phase I-IIa Theranostic Clinical Trial

32

Phase 1 Kids Diagnostic

Clinical Study Clarity-03:

First-In-Human Phase I Clinical Trial of 64Cu-

SARTATE for Imaging and Dosimetry

Estimation in Paediatric Patients with High-

Risk Neuroblastoma

Clarity has established close relationships with industry thought leaders

and gained access to world-class facilities, thus facilitating innovation

and constantly honing its capabilities

CLARITY’S PARTNERS33

CLARITY

IN USACLARITY

IN AU

http://iac.isu.edu/index.html

• 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 SUMMARY34

DR ALAN TAYLORExecutive Chairman

Ph: +61 (0)413 871 165

E: [email protected]

DR MATT HARRISCEO

Ph: +61 (0)439 620 125


www.claritypharm.com

CLARITY’S CONTACTS35

AMOS HEDTHead of Clinical Development

Ph: +61 (0)400 034 495


seeing is believing - sydney vital · by 2021, pet procedure volume is predicted to increase to pet...

Documents