Preliminary Dosimetry Results from a First-in-Human Phase 1 Study Evaluating the Efficacy and Safety of [225Ac]-FPI-1434 in Patients with IGF-1R Expressing Solid Tumors

SNMMI 2021 Publication # 74 Preliminary Dosimetry Results from a First-in-Human Phase 1 Study Evaluating the Efficacy and Safety of [225Ac]-FPI-1434 in Patients with IGF-1R Expressing Solid Tumors Daniel Juneau1, Fred Saad1, Alejandro Berlin2, Ur Metser2, Igor Puzanov3, Dominick Lamonica3, Richard Sparks4, Eric S. Burak5, Ryan Simms5, John Rhoden5, James O’Leary5, Julia Kazakin5, Courtney Watson5, Lauren Creeden5, Thomas Armor5, Jean-Mathieu Beauregard6, Maxime Chénard-Poirier6 1Centre Hospitalier de l’Université de Montréal, Montreal, QC; 2Princess Margaret Hospital, Toronto, ON; 3Roswell Park Comprehensive Cancer Center, Buffalo, NY; 4CDE Dosimetry Services, Inc. Knoxville, TN; 5Fusion Pharmaceuticals, Hamilton, ON; 6CHU de Québec - Université Laval, Quebec City, QC [225Ac]-FPI-1434 Background Copyright © 2021 Fusion Pharma Inc. All Rights Reserved 2 OO O H N O O O O N N N N O O OO O N H O 111In 4-Arm DOTA Chelator PEG3 Linker FPI-1175 Imaging 4-Arm DOTA Chelator PEG3 Linker FPI-1175 Therapy OO O H N O O O O N N N N O O OO O N H O 225Ac [111In]-FPI-1547 [225Ac]-FPI-1434 IGF-1R Implicated in: • Increased cellular proliferation • Metastatic potential • Cell survival • Chemotherapy and radiotherapy resistance Type I insulin-like growth factor receptor (IGF-1R) is a transmembrane protein which is overexpressed in solid tumors SNMMI 2021 Publication # 74 "File:Protein IGF1R PDB 1igr.png" by Emw is licensed with CC BY-SA 3.0. [225Ac]-FPI-1434 Key Study Objectives / Design Copyright © 2021 Fusion Pharma Inc. All Rights Reserved 3 First-in-Human Phase 1 Study FPX-01-01 (NCT03746431)  Primary Objective: Evaluate the safety and tolerability of [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection in patients with advanced refractory solid tumors  Patient selection and individualized patient dosimetry based on imaging with [111In]-FPI-1547  3+3 dose-escalation  Identify maximum tolerated dose / recommend Phase 2 dose of [225Ac]-FPI-1434  Single dose escalation completed, enrollment into multi-dosing cohorts and cold antibody sub-study ongoing SNMMI 2021 Publication # 74 [225Ac]-FPI-1434 Imaging Procedure and Dosimetric Methodology 4 SNMMI 2021 Publication # 74 Subject 204-007 65 y.o. female with Ovarian Cancer SNMMI 2021 Publication # 74 [225Ac]-FPI-1434 Subject 202-008 69 y.o. male with Castrate-resistant Prostate Cancer SNMMI 2021 Publication # 74 [225Ac]-FPI-1434 [225Ac]-FPI-1434 Radiation Absorbed Dose Estimates 7 Administered therapeutic activity was not to exceed protocol-defined thresholds of 18 Gy (kidneys), 31 Gy (liver), and 16.5 Gy (lungs) using an RBE value of 3.4 for all calculations SNMMI 2021 Publication # 74 N=13 Patients with evaluable [111In]-FPI-1547 Image Data for Dosimetry N=12 Patients received therapy with [225Ac]-FPI-1434 N=1 patient eligible per imaging but not treated due to rapid disease progression [225Ac]-FPI-1434 Study Population / Therapeutic Administrations Key eligibility criteria  IGF1R-expressing advanced solid tumors  TBR >2:1 relative uptake to compared to skeletal muscle  ECOG 1-2 and adequate end-organ function  Prior therapeutic radiopharmaceuticals >6 mos of enrollment  Prior radiation to large areas of bone marrow <20 Gy  Safety Review Committee review following each cohort 8 Mean Min Max Cohort 1 (10kBq/kg) N=4 884 797 984 Cohort 2 (20kBq/kg) N=4 1840 1290 2290 Cohort 3 (40kBq/kg) N=4 3394 2400 4179 [225Ac]-FPI-1434 Administration (kBq) SNMMI 2021 Publication # 74 Median Age (range) 61.0 (36-78) years Gender, n (%) Male 9 (75%) Female 3 (25%) Race, n (%) White 10 (83%) Asian 1 (8%) Not reported 1 (8%) Tumor type, n (%) Prostate cancer 6 (50%) Colorectal cancer 3 (25%) Adrenocortical carcinoma 1 (8%) Fibromyxoid sarcoma 1 (8%) Ovarian cancer 1 (8%) Baseline ECOG, n (%) 0 7 (58%) 1 5 (42%) Patient Characteristics Safety Population Treated with [225Ac]-FPI-1434 (N=12) [225Ac]-FPI-1434 Safety Assessments 56-day DLT evaluation period following therapeutic administration for dose-limiting toxicity assessment through single-administration dose-escalation. 9 All Grades (≥2pts) , n (%) Thrombocytopenia 5 (42%) Neutropenia 4 (33%) Fatigue 4 (33%) Lymphocyte count decrease 3 (25%) White blood cell count decrease 3 (25%) Nausea 2 (17%) Grade 3, n (%) *Neutropenia 1 (8%) *Lymphocyte count decrease 1 (8%) *White blood cell count decrease 1 (8%) No Grade 4 AEs observed Most Common FPI-1434-related AEs Cohorts 1-3 Patients, n (%) Any Adverse Events (AEs) 12 (100%) Serious Adverse Events (SAEs) 1 (8%) FPI-1434-related AEs 8 (67%) FPI-1547-related AEs 1 (8%) FPI-1434-related SAEs 0 (0%) FPI-1547-related SAEs 0 (0%) Post-Treatment Safety Events Safety Population – Cohorts 1-3 (N=12) No DLTs, treatment-related SAEs, or dose interruption/modification were reported in Cohorts 1-3 SNMMI 2021 Publication # 74 * Gr 3 WBC decrease , neutropenia, lymphopenia were attributed to the same patient Dosimetry for the first 3 cohorts of [225Ac]-FPI-1434 administered as a single dose at 10, 20, 40 kBq/kg [225Ac]-FPI-1434 – Dose Escalation Cohorts SNMMI 2021 Publication # 74 Radiation Dose Estimates per Unit of Administered Activity (mGy-Eq/MBq) N=13 Target Organ Mean ±SD Kidneys 988 305 Liver 934 319 Lungs 626 175 Red Marrow 807 303 Spleen 3,668 1881 Total Body 140 16 [225Ac]-FPI-1434 Conclusions 100% of patients imaged were eligible based on imaging to receive [225Ac]-FPI-1434. Prospective and personalized treatment planning for targeted alpha therapy of IGF-1R expressing tumors is an important safety checkpoint to estimate risks to critical organs. Dosimetric results well within pre-specified limits in a single-dose regimen up to 40 kBq/kg. [225Ac]-FPI-1434 demonstrated a manageable safety profile with no drug-related serious adverse events and/or dose limiting toxicity in administered activity up to 40 kBq/kg body-weight. Recruitment to multi-dose and cold antibody cohorts ongoing. 11 SNMMI 2021 Publication # 74

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