May 28 – 30, 2015, Montréal, Québec The future supply of reactor- produced medical isotopes François Couillard May 28 th, 2015

Disclosure Statement May 28 – 30, 2015, Montréal, Québec I have a financial affiliation with a pharmaceutical company and/or medical device: I own common shares of GE and J&J. I have no conflicts of interest to disclose. I have no other financial relationship or advisory role with pharmaceutical or device- making companies, or CME provider. I will not discuss or describe in my presentation at the meeting the investigational or unlabeled ("off-label") use of a medical device, product, or pharmaceutical that is classified by Health Canada as investigational for the intended use.

3 1954

4 Petten reactor, Nl 1958 BR2 reactor, Bel 1959 Osiris reactor, Fr 1957

MAPLE reactors 5

Overview 6 About Tc-99m Supply chain What’s the problem? Mitigation strategies Cyclotron produced Tc-99m- a game changer? National and international collaboration

Tc-99m Most widely used nuclear isotope in Nuclear Medicine % of all procedures million exams per year worldwide Uses: – Cardiac function – Blood flow – Bone metastases Distributed via generators to separate: – Mo-99m half-life: 66 hours – Tc-99m half-life: 6 hours 7

Current Tc-99m supply chain 8

9 NRU, Canada BR2 Bl HFR, Nl SAFARI, SA OPAL, Australia OSIRIS, Fr Major Mo-99 producing reactors Maria, Po LVR-15 CR

A complex world- partial logistics map 10 Reactors Mo-99 extraction & purification Tc-99m Generator manufacturing HRF Mallinckrodt, NL Maria IRE, Belgium IRE, Belgium Lantheus Mallinckrodt ANSTO, Australia NTP, S.A. NTP, S.A. AECL & Nordion BR2 LVR-15 OSIRIS NRU OPAL SAFARI

What’s the problem? Supply: NRU to stop regular production in 2016* OSIRIS to stop production end 2015 Other reactors except for OPAL (SA) are old and expected to stop production by HEU to LEU conversion Processing capacity insufficient Economic viability? Pricing Future pricing unknown- concept of « full-cost recovery » * NRU will be in remain in “hot-standy” mode from Oct to March 31,

OECD forecast April 2014 report : « clearly, insufficient processing capacity will be a major risk for secure supply in the next 5 years » Major economic & technical challenges to convert from HEU to LEU Likely delay of new projects Competing agendas in the supply chain Economic fundamentals sustainable? Expecting a new forecast by summer

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Potential solutions Increase Production Capacity Increase reactor base/capacity + processing capacity New Mo-99 producers (LINACS, reactors) Produce Tc-99m directly with Cyclotrons Optimize distribution and utilization Substitute tests with other tracers or modalities 14

Major new projects Major new Irradiators or increased capacity ( ) – NortStar Medical Radioisotopes/MURR +Linac (USA) – Nortwest Medical Isotopes (USA) – SHINE (USA) – Coqui Pharma (USA) – Nordion/MURR (USA/Canada) – OPAL (Australia) – Korea – RIAR (Russia) – FRM-II (Germany) – China Advanced RR – Brazil MR – Ra-10 (Argentina) – Jule Horowitz RR (France) 15

Major New Projects Major new processing facilities ( ): – NortStar/Murr (USA) – NortStar (LINAC) (USA) – SHINE (USA) – Northwest – ANSTO – RIAR (Russia) – Maria – Korea – Brazil – Ra-10 16

Canadian projects 17

Mo-99 production: a new game 18 Few major suppliers Many smaller players One technology Many technologies Global supply chain Global & local Artificially low prices Full Cost Recovery prices

A more diverse supply 19 Cyclotron Clinic

Canada: Great innovation- lots of work remaining Reliable production Reliable sourcing of target material (Mo-100) Manufacturing and recycling of targets Chemistry Clinical trials Regulatory approvals Distribution model uncertain Commercial model and infrastructure (incl. costs) Back-up mechanism 20

Current assessment 21 We need to be in a state a alertness between apathy and panic…

Conditions for success Investors with deep pockets and an appetite for risk Proven/reliable technology Secure source of target material Reliable distribution Commitment to system-wide funding increase

What will ensure success? Information sharing and collaboration 23

National & international collaboration International: ISRRT, SNMMI, OECD, EANM Industry (AIPES, CORAR) Canadian Multi-stakeholder Working Group on Medical Isotopes (Federal & Provincial Governments, associations, industry) CAMRT Tc99m supply Expert Group CAMRT website resource centre Canadian Medical Imaging Team (CAMRT, CANM, CAR…) 24

Questions? 25