27th Annual Healthcare Conference
Piper Jaffray Palace Hotel, NYC, New York
December 2nd, 2015
NASDAQ: APTO TSX: APS
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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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Biotech Company Creating Precision Medicines
─ Leveraging Recent Scientific Advancements and Predictive Biomarkers
to Develop Targeted Agents for Patients with Life-Threatening Cancers
APTO-253 Lead Agent at Phase Ib/II Stage of Development
─ “Targeted Drug for AML”, MDS and Other Hematologic Malignancies
─ Epigenetic Silencing of KLF4 Gene is Key Event in Majority of AML
─ APTO-253 Only Clinical Stage “Inducer of KLF4 Gene”
Dual-Targeting Epigenetic Inhibitor Program
─ Preclinical Program Developing Single Molecules that Simultaneously
Inhibits Bromodomain (BRD) Proteins and Synergistic Kinase Enzyme(s)
Listed on NASDAQ as “APTO” on October 23, 2014
Experienced Management and Clinical Development Teams
─ Personnel Located in San Diego, San Francisco, Toronto
RECENT CORPORATE HIGHLIGHTS
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CLINICAL DEVELOPMENT TEAM WITH ONCOLOGY PEDIGREE
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. 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. 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
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
APTO-253 TARGETED THERAPY FOR
ACUTE MYELOID LEUKEMIA (AML)
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Most Common Form of Acute Leukemia in Adults
─ Highly Aggressive Cancer of Blood and Bone Marrow
─ Among Adults >Age 65 with AML Only ~5% Survive 5 Years
Current Standard of Care (“7+3”)
─ Combination Regimen of Cytarabine and Daunorubicin
Elderly Exhibit Poor Response and Significant Toxicity
No Major Therapeutic Advances Since 1970’s
Need for New and Less Toxic “Targeted Therapies”
Challenge of Creating Targeted Drugs to Treat AML
Extreme Heterogeneity of Disease
Belief : No Single Underlying Mechanism that Causes AML
AML MEDICAL NEED, MARKET AND
CHALLENGES TO CREATE NEW DRUGS
CDX2 Protein
CDX2 ON
Genetic and Epigenetic
Alterations Turn On
CDX2 Gene in 90% AML
KLF4 ON Master TF
CDX2 OFF Embryonic Gene
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UNDERLYING CAUSE OF AML LINKED TO
ALTERATIONS IN CDX2 AND KLF4 GENES
NORMAL AML
CDX2 ON KLF4
KDM5b
Demethylase
Epigenetic Demethylation
of Histone H3K4-Me3
At KLF4 Gene
KLF4 Promoter
CDX2
Protein
(1) Source: J. Clin. Invest. 2013; 123(1); 299-314
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APTO-253 INDUCES KLF4 EXPRESSION AND AML APOPTOTIC CELL DEATH
AML
CDX2 ON
KLF4
KLF4
Genetically Induced KLF4
o KLF4
o p21
o Caspase 3
o Annexin V
o KLF4
o p21
o Caspase 3
o Annexin V
APOPTOSIS
APTO-253
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APTO-253: AML CELLS HIGHLY SENSITIVE IN VITRO
Source: APTOSE Biosciences, Inc . 2014 AACR Poster
Small Molecule Pharmaceutical Agent
─ Patent Through 2028 / Plus Extensions Developing CDX2 & KLF4 Companion Diagnostics
AML Cell Lines Highly Sensitive (IC50 = 0.007-0.3 µM)
─ 10-1,000 Times More Sensitive than Many Solid Tumor Cell Lines
APTO-253 Antitumor Activity In Murine Xenograft Model of Human AML
─ Well tolerated, with dose and schedule dependent antitumor activity
75
125
175
225
275
325
375
425
475
1 5 11 15 18 22 28 31 35 38 42 45
TU
MO
R S
IZE
(M
M3
)
OBSERVATION PERIOD (DAY)
Grp-1-Control
Grp-2-LOR-253 HCl : 2T-12B-2T p=0.99
Grp-3-LOR-253 HCl : 2T-5B-2T p=0.09
Grp-4-LOR-253 HCl : 3T-5B-3T p=0.058
20
22
24
26
28
30
1 5 11 15 18 22 28 31 35 38 42 45
We
igh
t (g
)
Observation Period (Day)
Mean Body Weight Profile
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Potently Kills AML Cells in Patient Samples
─ Kills Majority of Isolates (ηM)
─ Synergistic with JQ-1 BRD Inhibitor
─ Synergistic with Quizartinib FLT3 Inhibitor
Anticipate Highly Differentiated Efficacy / Safety Profile
─ AML Cells from Patients Highly Sensitive (ηM)
─ Data Suggest µM Levels Safely Achieved & Impact AML in Patients
─ Does NOT Suppress Normal Bone Marrow (1)
Could Serve as Foundation of Combination Therapy
─ Synergistic with Approved and Investigational Agents
APTO-253: PRECLINICAL FINDINGS SUPPORT DEVELOPMENT IN AML & MDS
(1) Cercek et al, ECC ESMO 2013
Poster by OHSU at ASH
Arm A
AML and High Risk MDS 1o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule
2o Endpts: PK, Biomarkers, Efficacy, Transfusions
Phase 2 MDS Drug Combination Trial
“Approved Drug” + APTO-253 1o: Biomarkers (p21, CDX2, KLF4)
2o: Efficacy/Transfusions
2016
Single Agent Expansions
AML (15) and MDS (15) ORR, Efficacy, Biomarkers, Safety
Patient Selection: CDX2 KLF4
Note: Phase 1b expansion cohorts and Phase 2 trials contingent on Phase 1b outcomes
Phase 2 AML Drug Combination Trial
“Approved Drug” + APTO-253 1o: Biomarkers (p21, CDX2, KLF4)
2o: Efficacy
Arm B
Lymphomas and Multiple Myeloma 1o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule
2o Endpts: PK, Biomarkers, Efficacy
Phase 1b Dose Escalation Trial Underway
At Elite Clinical Sites
Phase 2
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CLINICAL DEVELOPMENT PLAN
Drug Combination
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Patients Dosed at 20, 40, 66 and 100 mg/m2
─ Highly Favorable Safety Profile to Date (NO Drug-Related SAE)
─ PK Exposures Safely Achieved Levels of 1-2 µM (Suggest Entering Therapeutic Range)
Internal Review of Policies, Procedures and Documentation
─ Drug Product Manufactured Prior to Current Team’s Arrival at Company
─ Identified Manufacturing Documentation Deficiencies when API Formulated into Liquid Drug Product
Voluntarily Suspended Dosing and Contacted FDA – Temporary Hold
─ API was cGMP Quality and Safe (No SAE)
─ Patients Received Expected PK Exposures
─ CMC Documentation Issue – NOT Safety Issue
Measures Underway to Return to Clinic
─ To Manufacture New Batches of Drug Product
Expect Delay in Enrollment, But Unwavering Belief in APTO-253
─ Potential as Targeted Single Agent and In Drug Combination for Treatment of AML
DOSING IN PHASE IB TRIAL TEMPORARILY SUSPENDED
DUAL-TARGETING, SINGLE AGENT
BROMODOMAIN-KINASE INHIBITOR RATIONAL TARGETING OF EPIGENETIC PROCESSES
Entirely New
Program
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Desired Profile of New Agent
─ Avoids Rapid Emergence of Drug Resistance
─ Inhibits Expression of Oncogenes (i.e., c-Myc)
─ Inhibits Key Cancer-Promoting Signaling Pathways
─ Acts Through Disruption of Crucial Epigenetic Processes
Rational Selection of Targets for Dual-Targeting Approach
─ Target Epigenetic Bromodomain (BRD) Proteins and Kinase Enzymes
─ BRD4 has Demonstrated Kinase Activity and is Characterized as an “Atypical Kinase”
─ Might Expect BRD and Kinase Inhibitors Share High Degree of Pharmacophore Similarity
RATIONALE:
DUAL-TARGETING SINGLE AGENT APPROACH
Desired Product Profile
Requires Hitting Multiple Targets
Single, small molecule simultaneously
inhibits two classes of drug targets
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DUAL-TARGETING
EPIGENETIC INHIBITOR PROGRAM
CONFIDENTIAL
Marquis medicinal chemistry organization
Drug discovery collaboration for dual-
targeting epigenetic therapeutics
Developing multiple clinical candidates,
including optimization of Moffitt molecules
Potent, dual-targeting, single-agent
inhibitors
Exhibit single-digit ηM potency against
BRD and specific oncogenic kinases
(including JAK2, FLT3)
Laxai Avanti Life Sciences
Clinical Candidate
Expected:
Late 2016
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SUMMARY FINANCIAL DATA: END OF Q3 2015
$ in CAD At September 30, 2015
Exchanges:
Cash, Cash Equivalents and Investments: $23.4M
Basic Shares Outstanding : 12.0M
Fully Diluted Shares Outstanding1 : 13.9M
Notes: 1) Comprised of A) 12,021,080 shares outstanding B) Warrants to purchase 131,335 shares,
and C) options to purchase 1,727,196 shares at a weighted average price of $6.28 per
share
NASDAQ: APTO
TSX: APS
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Built Experienced Executive and Clinical Teams
Built Strong Financial and Operational Foundations
Built Epigenetic-Focused Pipeline of Highly Differentiated Agents
Developing APTO-253 as Targeted Agent for AML
AML, HR-MDS and Other Hematologic Malignancies
Personalized Drug Opportunity with Companion Diagnostics
Only Clinical Stage Inducer of KLF4 Master-TF : Realm of Epigenetics
Introduced New Program for Dual-Targeting Single Agent Inhibitors
─ Single Molecule that Simultaneously Inhibits BRD Proteins and Kinase Enzymes
Looking Forward
Seek Clinical Efficacy with APTO-253 in Patients with AML/MDS
Seek to Continue Building a Staged Pipeline of Targeted Cancer Drugs
EXECUTIVE SUMMARY: BUILDING FOR SUCCESS
NASDAQ: APTO
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Thank You!
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