Solid Tumor-Agnostic Platform: Ground-Breaking Companion Diagnostic + LADR Candidates - Centurion BioPharma ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
Solid Tumor-Agnostic Platform:
Ground-Breaking Companion Diagnostic
+ LADR™ Candidates
August 2018
www.centurionbiopharma.com NON-CONFIDENTIAL
Centurion BioPharma
Highlights
Our albumin companion diagnostic (ACDx) is a ground breaking
companion diagnostic in the preclinical stage that is being
developed to work in conjunction with our albumin binding drug
conjugates called LADRTM (linker activated drug release)
ACDx enhances the value of our pipeline because it enables a
personalized medicine approach in development
Personalized medicine: by utilizing ACDx to select the optimal
solid tumor patients for treatment, consistent impressive
response rates and outcomes can be attained with treatment by
LADRTM across solid tumor types (tumor agnostic development)
Centurion BioPharma filed US provisional patent application for
ACDx in July 2018
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
1
Centurion BioPharma Contents
OUR VISION:
Personalized Medicine with Solid Tumor-Agnostic Treatment
Targeting solid tumors utilizing albumin
ACDx (albumin companion diagnostics) introduction
ACDx proof of concept
LADRTM (linker-activated drug release) mechanism
Pre-clinical LADRTM data
Pipeline
Milestones
Management team
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
2
Vision and Development
Strategies for ACDx + LADRTM
OUR VISION:
Personalized Medicine with Solid Tumor-Agnostic Treatment
Study ACDx and LADRTM to work in conjunction in solid tumors
LADRTM has demonstrated broad utility across solid tumor types (lung,
breast, ovarian, skin, head & neck)
ACDx identifies tumors eligible for treatment with LADRTM
By identifying optimal patients with ACDx, LADRTM treatment will
consistently deliver impressive response rates and outcomes to a broad
group of solid tumor patients
Build tumor- Easily train
Establish Attain
agnostic oncologists
treatment blockbuster
development on the
globally revenue
plan technology
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
3
LADRTM Targeting Tumors
with Albumin as a Drug Carrier
1. Accumulation in tumor tissue
due to the EPR effect
(enhanced permeability and retention)
2. Prolonged circulatory retention
3. Improved tolerability allows for higher doses
Effective tumor targeting using
albumin as a drug carrier
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
4
EPR Effect of Albumin
100‒500 nm
albumin
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
5
Companion Diagnostic:
ACDx (albumin companion dx)
When positively screened with ACDx, patients will have an very
Goal
high response rate when treated with LADRTM.
ACDx is an imaging test that identifies albumin uptake in
tumors. By determining if albumin is in the tumor and how it is
What is
distributed in the tumor, we can determine if treating with
ACDx?
LADRTM (an albumin binding drug conjugate) is appropriate. This
is personalized medicine that is highly valued by oncologists.
Uses Single Photon Emission Computed Tomography (SPECT),
commonly used by oncology practices throughout the world.
How is ACDx
ACDx will be a new product sold in a vial to oncology and
used?
radiology practices. It can be a reimbursed drug and procedure
that will be very attractive to oncology practices.
6
ACDx has potential to transform
solid tumor treatment
OUR VISION:
Personalized Medicine with Solid Tumor-Agnostic Treatment
ACDx creates value when working as a companion diagnostic with LADRTM
Improve
Identify eligible Improve probability of Rationale for Justification for
patients for outcome of breakthrough payer premium
treatment clinical trials status and reimbursement pricing
approval
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
7Molecular Imaging – how ACDx
will be developed and utilized
Companion Imaging
Diagnostic SPECT:
Single Photon
Emission
Computed
Tomography
Advantages:
• Clinically widely used
• Straightforward clinical translation
• Unlimited penetration depth
8Preclinical SPECT/CT Imaging
with 111In-C4-DTPA
Establish methodology in two
human tumor xenograft models
Tumor type:
LXFL 529 (NSCLC)
OVXF 899 (ovarian cancer)
Study outline:
Bilateral implantation
TV ~100‒300 mm3 (left and right flank)
4 mice
~40 min ~2 min
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
9ACDx results in tumor-bearing
nude mice (LXFL 529)
Representative 2D SPECT/CT images of a tumor-bearing nude mouse
Visualization and
quantification of
albumin uptake by
tumors
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
10ACDx results in tumor-bearing
nude mice (LXFL 529)
Representative 3D SPECT/CT image after 72 h
Distinct accumulation of albumin
in the tumors
Kidneys are visible as the organs of
elimination
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
11ACDx results in tumor-bearing
nude mice (OVFX 899)
Representative 2D SPECT/CT images of a tumor-bearing nude mouse
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
12ACDx results in tumor-bearing
nude mice (OVFX 899)
Representative 3D SPECT/CT image after 72 h
Distinct accumulation of albumin
in the tumors
Kidneys are visible as the organs of
elimination
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
13ACDx for Personalized Medicine
• Continue development to a first clinical trial so that cancer
patients can be identified as prime candidates for
albumin-based drug therapy
High responding
cancer
patients to
LADRTM
treatment
Clinical SPECT/CT Imaging
14LADRTM Platform Overview
Goal: accumulate drug in the tumor and minimize systemic toxicity
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 activates the
maytansinoids) payload
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
15LADR™ Mechanism of Action
Cytotoxic Albumin
Agent Linker
2
1
Rapid and specific
binding to circulating 3
Cytotoxic albumin
Agent Linker
Drug-linker conjugate
is infused Tumor cells
4
Albumin transports drug
to the tumor and
surrounding
microenvironment
Linker dissolves in the acidic (low pH)
environment and releases the drug payload
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
16Albumin as a Drug Delivery Vehicle
Albumin
Most abundant protein in human blood plasma
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)
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
17AACR Poster: LADR-7, LADR-8
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
18AACR Poster: LADR-7, LADR-8
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
19LADR-7, 8 efficacy and toxicity
LADR-7
• NSCLC: CR 100%
• Melanoma: CR 79%, PR 14%
• Ovarian: CR 36%, PR 50%
LADR-8
• NSCLC: CR 30%, PR 0%
• Ovarian: CR 53%, PR 13%
• Durable responses averaged 60-90 days
• Demonstrated statistically significant superiority over the control
group and parent compound
• Highly effective, even in large tumors starting at 270-380 mm3
• No toxicity findings to prevent from moving forward in IND
enabling studies
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
20AACR Poster: LADR-9, LADR-10
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
21AACR Poster: LADR-9, LADR-10
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
22LADR-9, 10 efficacy and toxicity
• Statistically significant anti-tumor activity of in:
• Lung, breast, ovarian, renal cell, head & neck
• Durable responses averaged 60-90 days
• Demonstrated statistically significant superiority over the
control group and parent compound
• Highly effective, even in large tumors starting at 350 mm3
• No toxicity findings to prevent from moving forward in IND
enabling studies
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
23LADR™ vs. ADCs: targeting,
manufacturing and cost of goods
LADRTM ADC’s
Broad solid tumor targeting Target selection is limited to
Very high revenue potential the gene expression
Manufacturing simplicity vs.
antibodies
Small molecule manufacturing
Lower costs, less risk
Low cost of goods vs.
antibodies
Better profit margin
>30 different targets being
Pricing flexibility
pursued for solid tumors
Br J Cancer. 2016 Feb 16; 114(4): 362–367.
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
24Centurion BioPharma Pipeline
Four albumin binding ultra high potency LADR™ candidates
ready for IND enabling studies
Companion diagnostic – identifies patients to treat
LADR™ Albumin Binding Drug Preclinical Phase 1 Phase 2
Conjugates
Auristatin Program
LADR-7: AE-Keto-Sulf07
LADR-8: AE-Ester-Sulf07
Maytansinoid Program
LADR-9: PP072
LADR-10: FN296
Companion Diagnostic –
ACDx (albumin companion dx) identifies
patients across solid tumor types
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
25Centurion BioPharma Milestones
Event Completion Date
File one or more LADRTM patent applications Q4 2017
Initiate activities for GMP manufacturing of LADRTM linkers Q4 2017
Nominate one or more candidates for advancement into
Q1 2018
IND enabling studies
Present preclinical data on LADRTM candidates at AACR ‘18 1H 2018
Begin LADRTM pharma partnering discussions 1H 2018
File patent application for companion diagnostic 3Q 2018
Deal completion date in 2H and close By Dec 31, 2018
Partnership will determine next steps on pre-IND mtg,
studies and filing
FIGHTING CANCER WITH
CUTTING EDGE SCIENCE
Represents a completed milestone 26Experienced Management Team
Eric Curtis, CEO and President Felix Kratz, Ph.D., Vice President Drug Discovery
Mr. Curtis brings 25 years of life science leadership Dr. Kratz is a medicinal chemist with more than 25 years
experience, specializing in oncology and orphan of pertinent experience in the preclinical development of
diseases. He was instrumental in the US and global anticancer drugs, prodrugs and protein conjugation
development and commercialization of Votrient®, chemistry and profound knowledge of translational
Doxil®, Velcade®, Benlysta®, Tykerb® and research from the laboratory to the clinic. He has
Adempas®. Prior to joining Centurion, Mr. Curtis successfully transferred aldoxorubicin from bench to
served in senior leadership roles as President and COO bedside Dr. Kratz graduated in Chemistry from the
of CytRx Corporation, President, U.S. Commercial at University of Heidelberg with Magna Cum Laude. He
Aegerion Pharmaceuticals, VP and GM – Rare Disease established the Division of Macromolecular Prodrugs at
Business Unit at Bayer Healthcare, VP and global the Tumor Biology Center Freiburg. He has authored
commercial leader at GlaxoSmithKline, and roles of approximately 260 scientific publications, book articles
increasing responsibility at Centocor/J&J. and proceedings and is the inventor of over 20 patents
and patent applications.
Anna Warnecke, Ph.D., Sr Director Drug Discovery John Caloz, Interim Chief Financial Officer
Dr. Warnecke is a medicinal chemist with more than Mr. Caloz served as Chief Financial Officer of
15 years of relevant experience in the preclinical Occulogix, Inc, a NASDAQ listed, a medical therapy
development of oncology prodrugs. Prior to joining company, Chief Financial Officer of IRIS International
Centurion, Dr. Warnecke served as the Head of Inc., a Chatsworth, CA based medical device
Chemistry in the Division of Macromolecular manufacturer. He served as Chief Financial Officer of
Prodrugs, Tumor Biology Center. Dr. Warnecke San Francisco-based Synarc, Inc., a medical imaging
completed her Ph.D. at the Department of company, and SVP, Finance and Chief Financial
Macromolecular Chemistry, University of Freiburg, Officer of Phoenix International Life Sciences Inc.
with a thesis entitled “Maleimide-functionalized
Water-Soluble Derivatives of Clinically Established
Anticancer Drugs.”
27Summary
Centurion BioPharma is a private oncology company focused on
transformational oncology treatment
Our vision for ACDx and LADRTM is a personalized medicine, solid
tumor agnostic development plan
LADRTM and the ACDx companion diagnostic represent significant
pipeline value
Highly experienced leadership team
Novel LADRTM technology platform has applicability in oncology
and potentially other disease states
Goal – a Centurion BioPharma major strategic alliance to be
closed by end of 2018
FIGHTING CANCER WITH
28
CUTTING EDGE SCIENCEYou can also read
