Corporate Overview www.centurionbiopharma.com - Targeted Cancer Therapies
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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 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.
1
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
our companion diagnostic will allow us to enrich the population most likely to
respond to the therapy
2
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
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
Kratz, Journal of Controlled in the tumor
Release (2008) 132:171
of the hind leg
(72 h)
Sinn, H., et al. Int J Rad Appl
Instrum B (1990) 17:819
6
LADRTM: Enhanced Permeability and
Retention of Albumin
Normal
Tissue
100‒500 nm
EPR Effect
Tumor
Tissue
albumin
EPR = Enhanced Permeability and Retention
7
LADR™ Albumin Binding
Drug Conjugates
8
Linker Activated Drug Release
(LADRTM) 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
9LADR™ Mechanism of Action
Cytotoxic Albumin
Agent Linker
2
1
Rapid and specific
binding to circulating 3
Cytotoxic albumin as the target
Agent Linker
Drug-linker conjugate
is infused Tumor cells
4
Albumin transports drug
to the tumor and
surrounding
microenvironment
Linker breaks in the acidic (low pH)
environment and releases the drug payload
10Natural 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)
11Tubulin Forms Microtubules
https://www.cherrybiotech.com/scientific-note/microtubule-dynamics-and-maps
https://en.wikipedia.org/w/index.php?title=File:Kinetochore.jpg 12Toxins Inhibit Tubulin Polymerization
Molecular Docking to Tubulin
Auristatins Maytansinoids
Peptide Binding Site Vinca Binding Site
α1 tubulin chain – Tan surface α tubulin chain – White/tan surface
β2 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
13LADR™ Efficacious in Large Tumor Models
Auristatin LADR™ Maytansinoid LADR™
(LADR-7 and LADR-8) (LADR-9 and LADR-10)
LXFA 737 (NSCLC) A2780 (Ovarian)
Tumor volume ∼ 330 mm3 Tumor volume ~ 350 mm3
n=8 n=8
800
Median Absolute Tumor Volume (mm3)
700
600
500
400
300
200 Comparator ~ 1/8 LADRTM dose
Comparator ~ 1/10 LADRTM dose
100
0
0 10 20 30 40 50 60
Days after randomization Dose
administration
†
Pes et al., Journal of Controlled Premature death
Release (2019) 296:81 *
Tumor burden Poster LADR 9 and 10
Premature death
Euthanized due to
skin toxicology
14Auristatin 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
15LADRTM Proof of Concept
Aldoxorubicin
16First Generation
Aldoxorubicin Results
Doxorubicin: approved life-time dose 550 mg/m2 due to
cardiomyopathy
Aldoxorubicin cumulative doxorubicin equivalent dose at the time
of 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
17Aldoxorubicin: 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
18ACDx
Albumin Companion
Diagnostic
19Test Advantages
Increases The Likelihood For Efficacy
(Enriched Population)
Shortens The Timeline For Development
Combined With a Therapeutic –Targeted
Therapy (Precision Medicine)
20ACDx Agent 111In-C4-DTPA
• Fast binding to cysteine-34 of albumin
• High radiolabeling efficiency with 111indium as
the radionuclide
• High stability of the imaging diagnostic
111In-C4-DTPA
HO O
111Inis a
γ-emitting Albumin-binding
radionuclide maleimide group
O O
N O
O O
HO 111In
O N
O N N
O
H
N O
O
21Preclinical 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 ~2 min
min
22SPECT/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)
23ACDx and LADRTM
Summary
24ACDx & 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
25ACDx 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
26Centurion 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 Preclinical Phase 1 Phase 2
Conjugates
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
27Management
Gail L. Brown, M.D., M.B.A., Chief Medical Officer
In 2014, Dr. Brown founded The Brown Group, LLC providing services in clinical research, regulatory affairs,
DMC and financial services to biotechnology companies. She has advised the following companies: Tularik,
Abgenics, Cell Genesys, Onyx Pharmaceuticals, Versicor and Gilead Sciences.
Dr. Brown served as chief medical officer at Telik, Inc., and ARMO BioSciences. She served as Senior Medical
Director at AbbVie and worked on the Venetoclax hematological malignancies programs. She has 25 years
experience in early stage clinical drug development and launched international registrational trials in solid
tumors and hematologic malignancies.
Dr. Brown served on the faculty at Harvard Medical School Department of Medicine, Division of Hematology
and Oncology. She holds an M.D. degree from the University of Rochester School of Medicine and an M.B.A.
degree from St. Mary's College of California.
John Y. Caloz, Chief Financial Officer
Mr. Caloz served as Chief Financial Officer of Occulogix, Inc, a NASDAQ listed medical therapy company and
Chief Financial Officer of IRIS International Inc., a Chatsworth, CA based medical device manufacturer. He also
served as Chief Financial Officer of San Francisco-based Synarc, Inc., a medical imaging company, and SVP,
Finance and Chief Financial Officer of Phoenix International Life Sciences Inc., a CRO. Mr. Caloz, a Canadian
citizen, is a licensed Chartered Accountant in Canada and a graduate of York University, in Toronto, Canada.
28Development and Regulatory
Outsourcing
Hurley Consulting Associates Ltd.
Since 1987 Hurley Consulting Associates Ltd. has been providing drug development consulting and services including CMC,
nonclinical and clinical program support, technical writing, QA/QC functions, and submission preparation for FDA and other
regulatory authorities. The company acts as the U.S. agent and authorized representative for regulated products for the entire
IND through NDA process and post-approval regulatory matters including regulatory strategy, Health Authority negotiations,
and application approvals. Hurley Consulting has prepared or contributed to over 60 applications and prepared over 50 FDA
Meeting Requests, Briefing Books, and participated in the meetings.
Hurley Consulting has worked with the company in oncology since 2015. The Hurley Consulting pharmacology, toxicology, CMC, and
regulatory staff performed a detailed assessment of the work performed at Centurion BioPharma in 2017 – 2020 for the LADRTM
Program.
Margaret E. Hurley, M.D., FRAPS, President and CEO
Margaret E. Hurley, M.D., a recognized expert in drug development, founded Hurley Consulting in 1987. As President and
Chief Executive Officer, she is responsible for the general management of the company known for its analytical thinking.
Dr. Hurley was Director, Cardiovascular Drug Development at Ciba-Geigy (now Novartis) from 1983 to 1987. Before entering the
pharmaceutical industry, Dr. Hurley was the Medical Director of the Hemodialysis Unit at Bellevue Hospital Center, New York and a
member of the faculty at New York University Medical Center. She was a National Kidney Foundation Fellow and did her internal
medicine and nephrology training at NYU.
Dr. Hurley holds a medical degree from The Medical College of Pennsylvania in Philadelphia, Pennsylvania, and a bachelor’s degree in
chemistry from Fordham University. In 2010 Dr. Hurley became a Fellow of the Regulatory Affairs Professional Society in recognition
of her professional achievements.
Charles G. Garlisi, Ph.D.
Charles Garlisi, Ph.D., joined Hurley Consulting in 2016 as Vice President, Scientific Affairs. He has over twenty-five years’
pharmaceutical industry experience in multiple therapeutic areas (immunology, allergy, inflammation, and infectious diseases). His
project experience includes target identification to clinical development and through marketing application. At Hurley Consulting Dr.
Garlisi has been responsible for nonclinical programs in several therapeutic areas including oncology and diagnostics.
Dr. Garlisi was a Director of In Vitro Pharmacology at Merck Research Laboratories. He holds a doctoral degree in biochemistry from
The Pennsylvania State University and a bachelor’s degree in biology from St. Francis College, Brooklyn, NY. He has authored or co-
authored over 50 journal articles, and has presented at many professional conferences.
29Board 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.
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