Corporate Overview www.centurionbiopharma.com 2020 - PowerPoint PPT Presentation

Targeted Cancer Therapies Corporate Overview www.centurionbiopharma.com 2020 Non-Confidential

Centurion Biopharma Highlights  Centurion is a private, preclinical-stage oncology-focused biotechnology company pioneering the development of ultra-high potency cytotoxins with a diagnostic for patients with advanced solid malignancies.  Centurion’s LADR TM technology was developed by our preclinical laboratory personnel who were early innovators in developing acid sensitive linkers attached to cytotoxins.  Our 4 preclinical product candidates LADR-7, LADR-8, LADR-9, and LADR-10 were developed by us exclusively, as well as our diagnostic ACDx (Albumin Companion Diagnostic).  Centurion retains worldwide development and commercialization rights to all of its preclinical product candidates.  Our plans are to initiate IND enabling studies and the clinical Phase 1-2 trial(s) with our diagnostic ACDx. 1

Centurion’s Technology Platform LADR TM (linker activated drug release) maximizes full potential to target and kill cancer cells while minimizing toxicity Concentrates ultra high potency drugs inside the tumor, maximizing cancer cell  kill and minimizing toxicity Cancers are identified by the transport of our companion diagnostic (ACDx)  bound to circulating albumin which accumulates in the tumor LADR TM has demonstrated preclinical anti-tumor activity across solid tumor  types (e.g. breast, NSCLC, ovarian, melanoma, head & neck, and others) ACDx and LADR TM drugs will reduce the time to complete clinical trials because  our companion diagnostic will allow us to enrich the population most likely to respond to the therapy 2

LADR TM Target Product Profile  Highly Toxic Agents That Can Be Safely Administered  Each Toxic Agent Formulated With a Linker That Will Result in Selective Binding to Albumin In vivo  Demonstrated Coupling to Albumin After Intravenous Administration  Stable in Circulation (pH 7.4 at Normal Body Temperature or Febrile State)  Decouple and Release Toxic Agent at Acidic pH and Normal Body Temperature or Febrile State  Companion Diagnostic (ACDx) Developed With the Therapeutic 3

Role of Albumin in Targeting Solid Tumors 4

Albumin: Targeting Delivery Vehicle Human Serum Albumin (HSA)  Major source of essential amino acids (“fuel ″ ) for cancer cells  Localizes at tumor through the Enhanced Permeability and Retention Effect (EPR) effect and macropinocytosis  Serves as a transport molecule for metabolites, hormones, and nutrients  Long half-life (20 days) 5

Albumin Accumulates in Tumors Accumulation in tumor tissue due to the EPR effect (enhanced permeability and retention) i.v. injection of radiolabeled albumin • Tumor mass: ca. 6 % of body weight • ~23 % of the injected dose W-256 accumulated Sarcoma in the tumor Kratz, Journal of Controlled Release (2008) 132: 171 of the hind leg (72 h) Sinn, H., et al. Int J Rad Appl Instrum B (1990) 17: 819 6

LADR TM : Enhanced Permeability and Retention of Albumin lymphatic capillary Normal normal tissue Tissue 100‒500 nm blood stream EPR Effect Tumor Tissue tumor tissue albumin macromolecules EPR = Enhanced Permeability and Retention 7

LADR™ Albumin Binding Drug Conjugates 8

Linker Activated Drug Release (LADR TM ) Platform Target albumin with ultra high potency drug to the tumor, minimize systemic toxicology 1 2 3 1. Ultra High Potency 2. Cleavable Linker 3. Targeting Drug Payload • Novel linker keeps the • Ensures rapid and • Payloads are 10-1,000 highly potent drug selective binding to times more potent than payload inactive until the circulating serum albumin standard anti-cancer conjugate reaches the • Serum albumin transports agents tumor the LADR™ drug to the • Similar to those used for • The linker is then cleaved tumor ADCs (auristatins, which releases the maytansinoids) payload 9

LADR™ Mechanism of Action Cytotoxic Albumin Agent Linker 2 1 Rapid and specific binding to circulating 3 albumin as the target Cytotoxic Linker Agent Drug-linker conjugate Tumor cells is infused 4 Albumin transports drug to the tumor and surrounding microenvironment Linker breaks in the acidic (low pH) environment and releases the drug payload 10

Natural Toxin Tubulin Binders • ADCETRIS is an antibody-drug conjugate with anti-CD30 linked to an auristatin analogue (monomethyl auristatin E) • KADCYLA is is an antibody-drug conjugate with anti-HER2 linked to a maytansinoid analogue (DM1) 11

Tubulin Forms Microtubules https: / / www.cherrybiotech.com/ scientific-note/ microtubule-dynamics-and-maps https: / / en.wikipedia.org/ w/ index.php?title= File: Kinetochore.jpg 12

Toxins Inhibit Tubulin Polymerization Molecular Docking to Tubulin Auristatins Maytansinoids Peptide Binding Site Vinca Binding Site α 1 tubulin chain – Tan surface α tubulin chain – White/tan surface β 2 tubulin chain – Blue surface β tubulin chain – Cyan surface Auristatin E – White sticks Vinblastine – Pink sticks Auristatin E-Keto – Salmon sticks Ansamitocin – Brown sticks Maytansine – Blue sticks Pes et al., Journal of Controlled Venghateri et al., PLoS Release 296 (2019) 296: 81 ONE (2013) 8: e75182 13

LADR™ Efficacious in Large Tumor Models Auristatin LADR™ Maytansinoid LADR™ (LADR-7 and LADR-8) (LADR-9 and LADR-10) A2780 (Ovarian) LXFA 737 (NSCLC) Tumor volume  330 mm 3 Tumor volume ~ 350 mm 3 n = 8 n = 8 800 Median Absolute Tumor Volume (mm 3 ) 700 600 500 400 300 Comparator ~ 1/8 LADR TM dose 200 Comparator ~ 1/10 LADR TM dose 100 0 0 10 20 30 40 50 60 Days after randomization Dose administration † Premature death Tumor burden Pes et al., Journal of Controlled Poster LADR 9 and 10 * Premature death Release (2019) 296: 81 Euthanized due to skin toxicology 14

Auristatin and Maytansinoid LADR™s Are Efficacious in Different Xenograft Tumor Models  Breast  Head and Neck  Melanoma  NSCLC (lung)  Ovarian  Renal Pes et al., Journal of Controlled Release (2019) 296: 81 and Supplemental Material; Poster LADR 9 and 10 15

LADR TM Proof of Concept Aldoxorubicin 16

First Generation Aldoxorubicin Results  Doxorubicin: approved life-time dose 550 mg/m 2 due to cardiomyopathy  Aldoxorubicin cumulative doxorubicin equivalent dose at the time of the primary efficacy analysis was up to 7,800 mg/m 2 with no dose limiting cardiac adverse events  Aldoxorubicin in Global Phase 3 – Investigator Choice relapsed or refractory to >1 regimen of prior non-adjuvant chemotherapy, metastatic, locally advanced, or unresectable soft tissue sarcomas did not meet primary endpoint (PFS).  US, Canada, & Australia (72% of the patients with soft tissue sarcoma) statistically significant [p=0.0276, Hazard ratio (95% Confidence Interval) = 0.71 (0.53, 0.97)]  Europe and Latin America: Not significant  Aldoxorubicin was licensed to ImmunityBio 17

Aldoxorubicin: LADR TM Prototype Safety  Aldoxorubicin can be administrated at 10-fold or higher dosage compared with doxorubicin  LADR TM can be administrated at ~6- to 10-fold higher dosage compared with auristatin E or maytansine (xenograft data) Efficacy  Aldoxorubicin is efficacious in clinical trials. If aldoxorubicin was only carried to the tumor by albumin and never released, then no efficacy would have been observed in clinical trials.  LADR TM is efficacious in animal models and superior to the payload given alone 18

ACDx Albumin Companion Diagnostic 19

Test Advantages  Increases The Likelihood For Efficacy (Enriched Population)  Shortens The Timeline For Development  Combined With a Therapeutic –Targeted Therapy (Precision Medicine) 20

ACDx Agent 111 In-C4-DTPA • Fast binding to cysteine-34 of albumin • High radiolabeling efficiency with 111 indium as the radionuclide • High stability of the imaging diagnostic 111 In-C4-DTPA O HO 111 In is a Albumin-binding γ -emitting maleimide group radionuclide O O O N O O HO 111 In O N O N N O H N O O 21

Preclinical SPECT/CT Imaging With 111 In-C4-DTPA Establish methodology in human tumor xenograft models Study outline:  Bilateral implantation  TV ~100 ‒ 300 mm 3 (left and right flank)  4 mice ~40 ~2 min min 22

SPECT/CT Identifies ACDx-Labeled Albumin in Tumor-Bearing Nude Mice Representative 3D SPECT/CT image after 72 h 3D Spect/CT image Distinct accumulation of albumin in the s.c. tumors Kidneys are visible as the organs of elimination Model: LXFL529 (NSCLC) 23

ACDx and LADR TM Summary 24

ACDx & LADR TM Target Solid Tumors  ACDx (diagnostic) Identifies Tumor Candidates That Accumulate Albumin  Targeted Solid Tumor Characteristics (EPR Effect)  Increased vascularity  Abnormal local lymphatic system  High albumin concentration  Acidic local tissue and intracellular environment  LADR TM Exploits These Solid Tumor Characteristics  Injected LADR TM drug links itself to albumin to form a Trojan horse that hides the drug toxicity while in circulation  Albumin- LADR TM drug complex is brought to the cancer through the vascular system and the abnormal local lymphatic system traps it in the tumor  The acidic tumor environment releases the drug from the LADR TM linker 25