Transcript 150917 AV Basel Presentation

SACHS BIOTECH FORUM
September, 2015
NASDAQ: APTO
TSX: APS
Except for historical information, this presentation contains forward-looking statements, which reflect APTOSE Biosciences
Inc.’s (the “Company”) current expectations regarding future events. These forward-looking statements involve risks and
uncertainties, which may cause actual results to differ materially from those statements. Those risks and uncertainties
include, but are not limited to, our ability to raise the funds necessary to continue our operations, changing market conditions,
the successful and timely completion of clinical studies, the establishment and maintenance of corporate alliances, the
market potential of our product candidates, the impact of competitive products and pricing, new product development,
uncertainties related to the regulatory approval process and other risks detailed from time to time in the Company’s ongoing
quarterly filings and annual reports.
Forward-looking statements contained in this document represent views only as of the date hereof and are presented for the
purpose of assisting potential investors in understanding the Company’s business, and may not be appropriate for other
purposes. The Company does not undertake to update any forward-looking statements, whether written or oral, that may be
made from time to time by or on its behalf, except as required under applicable securities legislation. Investors should read
the Company’s continuous disclosure documents available at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml,
especially the risk factors detailed therein.
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RECENT CORPORATE HIGHLIGHTS
Built a Biotech Company for Precision Medicines
─
Therapies leveraging Novel Biomarkers for Patients with LifeThreatening Cancers
APTO-253 Lead Agent at Phase Ib/II Stage of Development
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Mechanism of action: “INDUCER OF KLF4 GENE”
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Treatment of AML, MDS and other hematologic malignancies
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Potential as a “Targeted Drug” for AML
Experienced Management and Clinical Development Teams
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Personnel Located in San Diego, San Francisco, Toronto
Raised >$45 Million from Premier US Healthcare Investors
New Corporate Vision & New Brand
Listed on NASDAQ as “APTO” on October 23, 2014
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VISION FOR APTOSE CRAFTED BY
EXPERIENCED LEADERSHIP TEAM
Gregory Chow
SVP, Chief Financial Officer
Avanish Vellanki
SVP, Chief Business Officer
Citigroup Global Markets: Biopharma Investment Banking
RBC Capital Markets: Director, Head Life Sciences Private Placements
Bear, Stearns & Co: Equity Research Publishing Analyst
Wells Fargo: Led Private Capital Group
Proteolix, Inc.: Sr. Director of Corporate Development
BDO Seidman, LLP: Senior Auditor, CPA (inactive), State of California
Dr. William G. Rice, PhD
Chairman, President & CEO
Achillion Pharmaceuticals: Founder, CEO, President, CSO, Director
National Cancer Institute-FCRDC: Sr. Scientist, Drug Mechanism Lab
Cylene Pharmaceuticals: Chairman, CEO, President, CSO
Elizabeth Williams
VP, Finance and Administration
Ernest Kitt
Sr. Director, Clinical Operations
Ernst and Young LLP: Audit Manager with International Co. Specialty
Amgen/Onyx: Molecule Lead Director for Kyprolis in Clinical Operations
Chartered Professional Accountant and Chartered Accountant
Oncosec Medical: Executive Director of Clinical Operations
Bachelor of Business Administration from Wilfrid Laurier University
Medicinova Inc: Associate Director of Clinical Operations
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CLINICAL DEVELOPMENT TEAM
WITH ONCOLOGY PEDIGREE
Dr. Stephen Howell, MD
Serves as Chief Medical Officer
Distinguished Professor of Medicine, UCSD Moore’s Cancer Center
Physician scientist conducting research to address drug resistance
Expertise in pharmacology and design and conduct of clinical trials
Dr. Daniel Von Hoff, MD, FACP
Serves as SVP of Medical Affairs – Key Advisor
Winner of 2010 Karnofsky Memorial Award
Prior President of AACR and Board Member of ASCO
Appointed to President’s National Cancer Advisory Board
Dr. Brian J. Druker, MD
Collaborator & Chair of SAB
Key Role in Dev’t of Gleevec and Member, National Academy of Sciences
Winner of Karnofsky Award and Lasker “America’s Nobel” Award
Leader of Inter-institutional Beat AML Initiative
Dr. Michael Andreeff, MD, PhD
Collaborator & Member of SAB
Professor of Medicine, Chair in Genetics, MD Anderson Cancer Center
Physician Scientist, expert in AML / drug resistance / drug mechanisms,
Published over 450 peer-reviewed papers / books / chapters
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NEW TEAM REDIRECTED APTO-253 FOR
TREATMENT OF AML / MDS / HEME
Drug
Indication
Partners
APTO-253
(KLF4 Inducer)
Solid Tumors
--
Hematologic
Malignancies
(AML & MDS)
--
IL-17E
(IL-17E Receptor
Agonist)
Oncology
Genentech(1)
APTO-500
(MELK Inhibitor)
Oncology
--
Small Molecule
Program
Various
Eli Lilly /
(2)
Elanco
Early Discovery
Program
Various
--
(1)
(2)
APTOSE owns global rights in oncology
Exclusive rights to license for veterinary applications
Discovery
Pre-Clinical
Phase I
Phase II
New IND and
Phase Ib/II Trial
• Mechanistic Rationale
• Identify Most Sensitive
Cancers with Biomarkers
• Targeted AML Therapy
Completed
Ongoing
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AML MEDICAL NEED, MARKET AND
CHALLENGES TO CREATE NEW DRUGS
Approximately 19,000 Cases Per Year in the U.S.
─
Leading to ~10,000 deaths annually
Majority of Patients >65 Years of Age
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Dismal Survival Rate: Only ~5% will Survive 5 Years
Function of Standard of Care (“7+3”)
̶
Combination: cytarabine and daunorubicin
̶
Elderly exhibit poor response and significant toxicity
Need for Less Toxic “Targeted Therapies”
Challenge of Creating Targeted Drugs to Treat AML
̶
Extreme Heterogeneity of Disease
Conventional Wisdom
̶
There is No Unifying Mechanism that Drives AML
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UNDERLYING CAUSE OF AML LINKED TO
ALTERATIONS IN CDX2 AND KLF4 GENES
CDX2 Embryonic Gene
̶
Should Not be Expressed in Adult Hematopoietic Cells
CDX2 ON: 90% AML Patients (All Subtypes)
̶
NORMAL
40% MDS (Pre-AML) CDX2 Gene Turned ON
CDX2 Silences KLF4 Transcription
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CDX2 EPIGENETICALLY SILENCES
KLF4 – RESULTING IN AML
KLF4 Promoter
CDX2 ON
CDX2 Protein
CDX2
Protein
KDM5b
Demethylase
Genetic and Epigenetic
Alterations Turn On
Epigenetic Demethylation
of Histone H3K4-Me3
At KLF4 Gene
CDX2 Gene in 90% AML
KLF4 ON
CDX2 OFF
NORMAL
KLF4 
CDX2 ON
AML
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(1) Source: J. Clin. Invest. 2013; 123(1); 299-314
APTO-253 INDUCES KLF4 EXPRESSION
AND AML APOPTOTIC CELL DEATH
AML
CDX2 ON
(1)
KLF4 
APTO-253
Genetically Induced KLF4
o
o
o
o




o
o
o
o
p21
G1 Arrest
Caspase 3
Annexin V




p21
G1 Arrest
Caspase 3
Annexin V
KLF4 
APOPTOSIS
(1) Source: J. Clin. Invest. 2013; 123(1); 299-314
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APTO-253: ACTS THROUGH INTENDED
MECHANISM IN AML
Cell Cycle Arrest
(Pause)
+
APTO-253
7.00
KLF4
6.00
p21
CASPASE 3
5.00
Apoptosis
(Delete)
4.00
3.00
2.00
1.00
18.00
16.00
20.00
KLF4
18.00
14.00
16.00
12.00
14.00
DMSO
p21
G1 Arrest
0.5 uM APTO-253
Fold Increase
DMSO
0.5 uM APTO-253
12.00
10.00
DMSO
p21
1.00
6.00
Annexin V
10.00
8.00
8.00
6.00
6.00
4.00
2.00
PI
4.00
2.00
-
-
DMSO
Fold Increase
DMSO
0.5 uM APTO-253
0.5 uM APTO-253
KLF4
1.00
15.32
DMSO
Fold Increase
DMSO
0.5 uM APTO-253
0.5 uM APTO-253
p21
1.00
18.64
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APTO-253: AML CELLS
HIGHLY SENSITIVE IN VITRO
AML Cells Highly Sensitive (IC50 = 0.007-0.3 µM)
─
10-1000 Times More Sensitive than Many Solid Tumor Cell Lines
PK Exposures of 2-6 µM Should Impact AML Cells
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Source: APTOSE Biosciences, Inc . 2014 AACR Poster
APTO-253: PRECLINICAL FINDINGS
SUPPORT DEVELOPMENT IN AML & MDS
APTO-253 Small Molecule, Targeted Agent
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COM/Use Patent Coverage Through 2028; Plus Typical Extensions
Expect Single Agent Efficacy Against AML in the Clinic
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AML Cells and AML Xenograft Tumors Highly Sensitive
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PK Exposure Levels Should Impact AML in Humans
Could Serve as Foundation of Combination Therapy
•
•
•
•
•
cytarabine
daunorubicin
azacitidine
decitabine
others
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Preclinical Synergy with Approved and Investigational Drugs
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APTO-253 Does NOT Suppress Normal Bone Marrow (1)
Developing Companion CDX2 & KLF4 Diagnostics: IP Filed
̶
Planned for Patient Selection and Therapeutic Signals
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(1) Cercek et al, ECC ESMO 2013
APTO-253
Clinical Development
CLINICAL DEVELOPMENT PLAN
Phase 1b Dose Escalation Trial Underway:
Patients Being Dosed on Both Arms
Arm A
AML and High Risk MDS
2016
Patient Selection: CDX2
1o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule
2o Endpts: PK, Biomarkers, Efficacy, Transfusions
KLF4
Single Agent Expansions
AML (15) and MDS (15)
Arm B
Lymphomas and Multiple Myeloma
ORR, Efficacy, Biomarkers, Safety
1o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule
2o Endpts: PK, Biomarkers, Efficacy
Phase 2
Phase 2 AML Drug Combination Trial
“Approved Drug” + APTO-253
1o: Biomarkers (p21, CDX2, KLF4)
2o: Efficacy
Drug Combination
Phase 2 MDS Drug Combination Trial
“Approved Drug” + APTO-253
1o: Biomarkers (p21, CDX2, KLF4)
2o: Efficacy/Transfusions
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Note: Phase 1b expansion cohorts and Phase 2 trials contingent on Phase 1b outcomes
STATUS OF PHASE IB TRIAL
Elite Clinical Sites
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MD Anderson Cancer Center
̶ OHSU
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University of Michigan
̶ Baylor Cancer Center
Biomarker Analysis
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Bone Marrow and Peripheral Blood Collected and Processed
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Effort to Identify Most Sensitive Patient Population (Aptose & Beat AML)
Dosing Schedule: Day 1, 2 of Each Week on a 28d Cycle
Patients Dosed at 20, 40, and 66 mg/m2
Next Dose Level Cohort is 100 mg/m2
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AML Cell Sensitivity (IC50 = 0.007-0.3 µM)
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Safe Clinical Exposure Levels from Prior Trial (Cmax = 2-6 µM)
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Suggest Entering Therapeutic Range for Heme Cancers
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EXECUTIVE SUMMARY:
BUILDING FOR SUCCESS
Built Experienced Executive and Clinical Teams
Redirected APTO-253 as Targeted Agent for AML
̶
AML, HR-MDS and Hematologic Malignancies
̶
Personalized Drug Opportunity with Companion Diagnostics
Built Strong Financial and Operational Foundation
̶
Raised >$45 Million from Premier Fundamental Healthcare Investors
Listed on NASDAQ (APTO)
Looking Forward
̶
Seek Clinical Efficacy with APTO-253 in Patients with AML/MDS
̶
Collaborations will reveal additional data for APTO-253 (Beat AML, drug
combination collaborations)
̶
Seek to Build a Staged Pipeline of Multiple, Targeted Cancer Drugs
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Thank You!
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