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

Corporate Overview

www.centurionbiopharma.com 2020 Non-Confidential

Targeted Cancer Therapies

1

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 LADRTM 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.

2

Centurion’s Technology Platform

LADRTM (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

• LADRTM has demonstrated preclinical anti-tumor activity across solid tumor

types (e.g. breast, NSCLC, ovarian, melanoma, head & neck, and others)

• ACDx and LADRTM drugs will reduce the time to complete clinical trials because
• ur companion diagnostic will allow us to enrich the population most likely to

respond to the therapy

3

LADRTM 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

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Role of Albumin in Targeting Solid Tumors

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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)

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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 accumulated in the tumor

• f the hind leg

(72 h)

W-256 Sarcoma

Sinn, H., et al. Int J Rad Appl Instrum B (1990) 17: 819 Kratz, Journal of Controlled Release (2008) 132: 171

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LADRTM: Enhanced Permeability and Retention of Albumin

100‒500 nm EPR = Enhanced Permeability and Retention EPR Effect

lymphatic capillary blood stream normal tissue tumor tissue macromolecules

albumin

Normal Tissue Tumor Tissue

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LADR™ Albumin Binding Drug Conjugates

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Linker Activated Drug Release (LADRTM) Platform

• 2. Cleavable Linker
• Novel linker keeps the

highly potent drug payload inactive until the conjugate reaches the tumor

• The linker is then cleaved

which releases the payload

• 3. Targeting
• Ensures rapid and

selective binding to circulating serum albumin

• Serum albumin transports

the LADR™ drug to the tumor

• 1. Ultra High Potency

Drug Payload

• Payloads are 10-1,000

times more potent than standard anti-cancer agents

• Similar to those used for

ADCs (auristatins, maytansinoids)

Target albumin with ultra high potency drug to the tumor, minimize systemic toxicology 1 2 3

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LADR™ Mechanism of Action

Drug-linker conjugate is infused

Tumor cells

Albumin transports drug to the tumor and surrounding microenvironment Linker breaks in the acidic (low pH) environment and releases the drug payload Rapid and specific binding to circulating albumin as the target

1 2 3 4

Cytotoxic Agent Linker Cytotoxic Agent Linker Albumin

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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)

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Tubulin Forms Microtubules

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

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Toxins Inhibit Tubulin Polymerization

Pes et al., Journal of Controlled Release 296 (2019) 296: 81

Auristatin E – White sticks Auristatin E-Keto – Salmon sticks α1 tubulin chain – Tan surface β2 tubulin chain – Blue surface

Venghateri et al., PLoS ONE (2013) 8: e75182

Vinblastine – Pink sticks Ansamitocin – Brown sticks Maytansine – Blue sticks

Auristatins

Peptide Binding Site

Maytansinoids

Vinca Binding Site α tubulin chain – White/tan surface β tubulin chain – Cyan surface

Molecular Docking to Tubulin

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LADR™ Efficacious in Large Tumor Models

100 200 300 400 500 600 700 800 10 20 30 40 50 60

Median Absolute Tumor Volume (mm3) Days after randomization

LXFA 737 (NSCLC)

Tumor volume  330 mm3 n = 8

Poster LADR 9 and 10

Auristatin LADR™ (LADR-7 and LADR-8) Maytansinoid LADR™ (LADR-9 and LADR-10)

Pes et al., Journal of Controlled Release (2019) 296: 81

A2780 (Ovarian)

Tumor volume ~ 350 mm3 n = 8

Comparator ~ 1/8 LADRTM dose Comparator ~ 1/10 LADRTM dose † *

Dose administration Premature death Tumor burden Premature death Euthanized due to skin toxicology

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Auristatin and Maytansinoid LADR™s Are Efficacious in Different Xenograft Tumor Models

Pes et al., Journal of Controlled Release (2019) 296: 81 and Supplemental Material; Poster LADR 9 and 10

• Breast
• Head and Neck
• Melanoma
• NSCLC (lung)
• Ovarian
• Renal

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LADRTM Proof of Concept Aldoxorubicin

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First Generation Aldoxorubicin Results

• Doxorubicin: approved life-time dose 550 mg/m2 due to

cardiomyopathy

• Aldoxorubicin cumulative doxorubicin equivalent dose at the time
• f the primary efficacy analysis was up to 7,800 mg/m2 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

18

Aldoxorubicin: LADRTM Prototype

Safety

• Aldoxorubicin can be administrated at 10-fold or higher dosage

compared with doxorubicin

• LADRTM 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.

• LADRTM is efficacious in animal models and superior to the

payload given alone

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ACDx Albumin Companion Diagnostic

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Test Advantages

• Increases The Likelihood For Efficacy

(Enriched Population)

• Shortens The Timeline For Development
• Combined With a Therapeutic –Targeted

Therapy (Precision Medicine)

21

111In

N N O O N HO O O O O HO O O N H O N O O

ACDx Agent 111In-C4-DTPA

111In-C4-DTPA

111In is a

γ-emitting radionuclide

• Fast binding to cysteine-34 of albumin
• High radiolabeling efficiency with 111indium as

the radionuclide

• High stability of the imaging diagnostic

Albumin-binding maleimide group

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Preclinical SPECT/CT Imaging With 111In-C4-DTPA

Establish methodology in human tumor xenograft models

Study outline:

• Bilateral implantation
• TV ~100‒300 mm3 (left and

right flank)

• 4 mice

~40 min ~2 min

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SPECT/CT Identifies ACDx-Labeled Albumin in Tumor-Bearing Nude Mice

Representative 3D SPECT/CT image after 72 h

Distinct accumulation of albumin in the s.c. tumors Kidneys are visible as the

• rgans of elimination

Model: LXFL529 (NSCLC) 3D Spect/CT image

24

ACDx and LADRTM Summary

25

ACDx & LADRTM 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
• LADRTM Exploits These Solid Tumor Characteristics
• Injected LADRTM drug links itself to albumin to form a Trojan horse

that hides the drug toxicity while in circulation

• Albumin-LADRTM 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 LADRTM

linker

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ACDx and LADRTM Advantages

• Applicable to treat a broad array of solid tumors
• Targets cancer cells based on tumor pathophysiology
• Does not target a specific cell receptor or antigen
• Higher doses of toxic drugs can be administered

safely using LADRTM platform to achieve efficacy

• Therapeutic Target: Cancer cells
• Benefit: Protects normal cells from the toxic payload
• Compared to ADCs, a larger number of patients are

candidates for this therapy because the presence of a specific antigen is not required

27

Centurion BioPharma Pipeline

• ACDx and four ultra high potency LADR™ drugs were selected for development
• Non-GMP batches made and next step is technology transfer to make GMP material
• IND enabling studies can be initiated for 4 lead candidates. An IND submission is

targeted for 2021 and starting of our Phase 1-2 clinical trial in the first half of 2022.

• Long term patent protection (2035-2038) for LADR™ technology, drug candidates,

and diagnostic

LADR™ Albumin Binding Drug Conjugates Preclinical Phase 1 Phase 2 Auristatin Program LADR-7 LADR-8 Maytansinoid Program LADR-9 LADR-10 Companion Diagnostic – ACDx identifies patients across solid tumors which have the potential to respond

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Board of Directors

• Louis J. Ignarro, Ph.D, Chairman of the Board
• Dr. Ignarro received the Nobel Prize for Medicine in 1998 and is the co-founder of Centurion BioPharma
• Corporation. He served as the Jerome J. Belzer, M.D. Professor Emeritus in the Department of Molecular and

Medical Pharmacology at the UCLA School of Medicine. Dr. Ignarro had been at the UCLA School of Medicine since 1985 as a professor, acting chairman and assistant dean.

• Steven A. Kriegsman, Executive Chairman
• Mr. Kriegsman has been Centurion BioPharma Corporation's Executive Chairman and a director since its
• formation. He is the co-founder of Centurion. Mr. Kriegsman was formerly a Certified Public Accountant with

KPMG in New York City. In February 2006, Mr. Kriegsman received the Corporate Philanthropist of the Year Award from the Greater Los Angeles Chapter of the ALS Association and in October 2006, he received the Lou Gehrig Memorial Corporate Award from the Muscular Dystrophy Association.

• Joel K. Caldwell, Chairman Audit Committee
• Mr. Caldwell is an expert in Corporate Finance, Internal Audits, Executive Compensation, Long Term Finance,

Employee Benefits and Sarbanes-Oxley Internal Controls Compliance. He previously worked for the international CPA firm Arthur Andersen & Co. Mr. Caldwell is a Certified Public Accountant.

• Richard J. Kogan, Senior Advisor to the Board
• Mr. Kogan was formerly Chairman and CEO of Schering-Plough Corporation and Chairman of the International

Pharmaceutical Manufacturers Association. He also served as a Board Member of Colgate-Palmolive Company, The Bank of New York, and as Chairman of the Board of Saint Barnabas Medical Center.