Download J.P. MORGAN 34TH ANNUAL HEALTHCARE CONFERENCE

J.P. MORGAN 34TH ANNUAL
HEALTHCARE CONFERENCE
San Francisco, CA, USA
January 11-14, 2016
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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CORPORATE HIGHLIGHTS
Oncology Biotech Company Creating Precision Medicines
─
Scientific Breakthroughs and Predictive Biomarkers to Develop Targeted Agents
─
Pipeline of Highly Differentiated Inhibitors of Epigenetic Abnormalities
APTO-253 Lead Agent “KLF4 Inducer” at Phase Ib/II Stage
─
Reverses Epigenetic Silencing of KLF4 Gene Seen in Majority of AML
─
“Epigenetic Targeted Drug for AML” and Other Hematologic Disorders
─
Delayed Dosing / Enrollment due to CMC-Related Matter
Initiated New Dual-Targeting Epigenetic Inhibitor Program
─
Preclinical Program Creating Single Molecules that Simultaneously Inhibit
Epigenetic Bromodomain (BRD) Proteins and Synergistic Kinase Enzyme(s)
Listed on NASDAQ as “APTO” on October 23, 2014
Built Experienced Management and Clinical Development Teams
─
Personnel Located in San Diego, San Francisco, Toronto
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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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APTOSE PROGRAM PIPELINE
Drug
Indication
APTO-253
(KLF4 Inducer)
Solid Tumors
--
Hematologic
Malignancies
(AML & MDS)
--
Dual-Targeting
Bromodomain
Program
Oncology
Dual-Targeting
Oncology
Epigenetic Program
Oral KLF4 Program Various
(1) Aptose
Partners
Discovery
Pre-Clinical
Phase I
Phase II
Moffitt
LALS
--
in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology
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APTOSE PROGRAM PIPELINE
Drug
Indication
APTO-253
(KLF4 Inducer)
Solid Tumors
--
Hematologic
Malignancies
(AML & MDS)
--
Dual-Targeting
Bromodomain
Program
Oncology
Dual-Targeting
Oncology
Epigenetic Program
Oral KLF4 Program Various
(1) Aptose
Partners
Discovery
Pre-Clinical
Phase I
Phase II
Moffitt
LALS
--
in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology
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APTO-253 : PRIOR ALL-COMER
SOLID TUMOR PHASE I TRIAL
Safe, Well-Tolerated, Dose-Dependent Pharmacokinetics
Observed Modest Antitumor Activity in a Few Patients
At that Time No Means to Identify Sensitive Patients
Cmax as a Function of Dose
Solid Tumor Phase I Trial Data
Not Toxic to
Normal Bone
Marrow Cells
Day 1 Cmax (uM)
Mean Cmax ± SD (uM)
2-6 µM Levels
Safely Achieved
12
10
Day 2 Cmax (uM)
8
6
4
2
0
0
100
200
300
400
APTO-253 Dose (mg/m2)
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APTOSE PROGRAM PIPELINE
Drug
Indication
Partners
APTO-253
(KLF4 Inducer)
Solid Tumors
--
APTO-253
(KLF4 Inducer)
Hematologic
Malignancies
(AML & MDS)
--
Dual-Targeting
Bromodomain
Program
Oncology
Discovery
Moffitt
Pre-Clinical
Phase I
Phase II
• Mechanistic Rationale
• Identify Most Sensitive
Dual-Targeting
Oncology
Epigenetic Program
LALS
Patient Population with
Genetic Biomarkers
Oral KLF4 Program Various
(1) Aptose
--
• Targeted AML Therapy
in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology
9
DEVELOPMENT OF APTO-253 FOR
ACUTE MYELOID LEUKEMIA (AML):
MOST COMMON FORM OF ACUTE LEUKEMIA IN ADULTS
HIGHLY AGGRESSIVE CANCER 0F BONE MARROW
AML MEDICAL NEED, MARKET AND
CHALLENGES TO CREATE NEW DRUGS
Most Common Form of Acute Leukemia in Adults
─
Highly Aggressive Cancer of Blood and Bone Marrow
─
Among Adults >Age 65 Diagnosed with AML, Only ~5% Survive 5 Years
Current Standard of Care (“7+3”)
─
Combination of Cytotoxins: 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”
Challenges to Creating Targeted Drugs to Treat AML
1.
Extreme Heterogeneity of Disease
2.
Heterogeneity Driven Primarily by Epigenetic Plasticity
3.
Belief : No Single Underlying Mechanism that Causes AML
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UNDERLYING CAUSE LINKED TO EPIGENETIC
ALTERATIONS IN CDX2 AND KLF4 GENES
CDX2 Embryonic Gene
̶
Should Not be Expressed in Adult Hematopoietic Cells
CDX2 Expressed: 90% AML Patients
─
̶
Healthy
Across All Subtypes
40% MDS (Pre-AML) CDX2 Gene Turned ON
CDX2 Inappropriately Expressed in AML
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UNDERLYING CAUSE OF AML LINKED TO
ALTERATIONS IN CDX2 AND KLF4 GENES
KLF4 Promoter
CDX2 ON
CDX2 Protein
CDX2
Protein
KDM5b
Demethylase
Genetic and Epigenetic
Alterations Turn On
Epigenetic Demethylation of Histone
H3-K4(Me3) at KLF4 Gene
Altered Chromatin Structure
CDX2 Gene in 90% AML
CDX2 OFF
KLF4 ON
Embryonic Gene
Master TF
NORMAL
KLF4 
CDX2 ON
AML
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APTO-253 INDUCES KLF4 EXPRESSION
AND AML APOPTOTIC CELL DEATH
AML
CDX2 ON
KLF4 
APTO-253
Genetically Induced KLF4
o
o
o
o




o
o
o
o
KLF4
p21
Caspase 3
Annexin V
Reversed Epigenetic
Silencing of KLF4
(1) Source: J. Clin. Invest. 2013; 123(1); 299-314




KLF4
p21
Caspase 3
Annexin V
KLF4 
APOPTOSIS
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APTO-253: ACTS THROUGH INTENDED
MECHANISM IN AML
+ APTO-253
KLF4
CDX2
p21
Apoptosis
7.00
6.00
CASPASE 3
5.00
4.00
3.00
2.00
MV4-11 Cells
1.00
DMSO
0.5 uM APTO-253
DMSO
Fold Increase
DMSO
0.5 uM APTO-253
p21
1.00
6.00
APTO-253 Induces Expression
of KLF4 Master Tspn Factor
Annexin V
PI
KG-1 Cells
15
APTO-253: AML CELLS
HIGHLY SENSITIVE IN VITRO
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
Mean Body Weight Profile
425
30
28
375
Weight (g)
TUMOR SIZE (MM3)
475
325
26
24
22
20
275
1 5 11 15 18 22 28 31 35 38 42 45
Observation Period (Day)
225
175
Grp-1-Control
125
Grp-2-LOR-253 HCl :
2T-12B-2T p=0.99
75
1 5 11 15 18 22 28 31 35 38 42 45
Grp-3-LOR-253 HCl :
2T-5B-2T p=0.09
OBSERVATION PERIOD (DAY)
Grp-4-LOR-253 HCl :
3T-5B-3T p=0.058
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Source: APTOSE Biosciences, Inc . 2014 AACR Poster
APTO-253: PRECLINICAL FINDINGS
SUPPORT DEVELOPMENT IN AML & MDS
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 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
(1) Cercek et al, ECC ESMO 2013
17
Aptose Biosciences Granted Orphan Drug Designation by the U.S.
FDA for APTO-253 in Acute Myeloid Leukemia
June 2, 2015
SAN DIEGO and TORONTO, June 2, 2015 /CNW/ - Aptose Biosciences Inc. (NASDAQ:
APTO; TSX: APS), a clinical-stage company developing new therapeutics that target the
underlying mechanisms of cancer, today announced that the U.S. Food and Drug
Administration (FDA) has granted the company orphan drug designation for APTO-253 for the
treatment of acute myeloid leukemia (AML). APTO-253, a first-in-class inducer of the KLF4
gene, is the company's lead product candidate in a Phase Ib clinical trial in patients with AML,
high-risk myelodysplastic syndrome (MDS) and other hematologic malignancies in which
KLF4 silencing is reported as operative.
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CLINICAL DEVELOPMENT PLAN
Phase 1b Dose Escalation Trial Underway
At Elite Clinical Sites
Arm A
AML and High Risk MDS
1o
2o
2016
Patient Selection: CDX2
Endpt: MTD, DLT & RP2D - Twice Weekly Schedule
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
DOSING IN PHASE IB TRIAL
TEMPORARILY SUSPENDED
Patients Dosed at 20, 40, 66 and 100 mg/m2
─
Favorable Safety Profile to Date (All Patients Monitored and NO Drug-Related SAE)
─
PK Exposures Safely Achieved Levels of 1-2 µM (Suggest Entering Therapeutic Range)
Internal Review of Policies, Procedures and Documentation
─
Records of Drug Product Manufactured Prior to Current Team’s Arrival at Company
─
Manufacturing Documentation Irregularities when API Formulated into Drug Product
Voluntarily Suspended Dosing & Contacted FDA – Temporary Hold
─
API was Safe (No SAE)
─
Patients Received Expected PK Exposures
─
CMC (Manufacturing) Issue – NOT Safety Issue
Measures Underway to Return to Clinic
─
To Manufacture New Batches of Drug Product
Expect Delay in Enrollment, But Resolute Confidence in APTO-253
─
Potential as Targeted Single Agent and In Drug Combination for Treatment of AML
20
APTOSE PROGRAM PIPELINE
Drug
Indication
APTO-253
(KLF4 Inducer)
Solid Tumors
--
Hematologic
Malignancies
(AML & MDS)
--
Dual-Targeting
Bromodomain
Program
Oncology
Dual-Targeting
Oncology
Epigenetic Program
Oral KLF4 Program Various
(1) Aptose
Partners
Discovery
Pre-Clinical
Phase I
Phase II
Moffitt
LALS
--
in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology
21
DUAL-TARGETING SINGLE AGENT
INHIBITORS OF BROMODOMAINS / KINASES
RATIONAL TARGETING OF EPIGENETIC PROCESSES
RATIONALE:
DUAL-TARGETING SINGLE AGENT APPROACH
Desired Product Profile of New Agent
─
Inhibits Expression of Oncogenes (i.e., c-Myc)
─
Inhibits Key Cancer-Promoting Signaling Pathways
─
Acts Through Disruption of Crucial Epigenetic Processes
─
Act Synergistically & Avoids Rapid Emergence of Drug Resistance
c-Myc
CDK6
Aurora B
BCL2
Desired Product Profile – Tall Order
─
Requires Hitting Multiple Targets
─
Single Molecule Simultaneously Inhibits Two Classes of Drug Targets
Rational Selection of Targets for Dual-Targeting Approach
─
Target Epigenetic Bromodomain (BRD) Proteins and Kinase Enzymes
−
─
BRD Inhibitors and Kinase Inhibitors Clinically Validated Classes of Drugs
BRD4 has Kinase Activity and is Characterized as an “Atypical Kinase”
−
Might Expect BRD and Kinase Inhibitors to Share Structural Similarities
23
RATIONALE:
DUAL-TARGETING SINGLE AGENT APPROACH
24
FIRST-IN-CLASS DUAL TARGETING
EPIGENETIC INHIBITORS
25
DUAL-TARGETING
EPIGENETIC INHIBITOR PROGRAM
Clinical Candidate
Expected:
Late 2016
Laxai Avanti Life Sciences
Marquis medicinal chemistry organization
Potent, dual-targeting, single-agent
inhibitors
Exhibit single-digit ηM potency against
BRD and specific oncogenic kinases
(including JAK2, FLT3)
Drug discovery collaboration for dualtargeting epigenetic therapeutics
Developing multiple clinical candidates,
including optimization of Moffitt molecules
26
CONFIDENTIAL
ANTICIPATED CORPORATE TIMELINES
ASSOCIATED WITH DRUG PROGRAMS
Event
Timeline
Preclinical: APTO-253 Effect on Cells from Heme Cancer Patient Samples (Beat AML)
Late-2015 (ASH)
Preclinical: Dual-Targeting BRD/JAK2 Inhibitor Licensing and In Vitro Study Results
Late-2015 (ASH)
Clinical: APTO-253 Potential Lifting of Clinical Hold Phase 1b Dose Escalation Study (1) 1H 2016
Clinical: APTO-253 Complete Enrollment in Phase 1b Dose Escalation
2H 2016
Clinical: APTO-253 Phase 1b Dose Escalation Study Results
2H 2016
Clinical: APTO-253 Commence Phase 1b Single Agent Expansion Studies
2H 2016
Clinical: APTO-253 Commence Phase 2 Drug Combination Studies
Late-2016 / 2017
Preclinical: Select Lead Dual-Targeting BRD-Kinase Inhibitor Clinical Candidate
Late-2016
(1) Pending official discussion with FDA
27
SUMMARY FINANCIAL DATA:
END OF Q3 2015
$ in CAD
At September 30, 2015
Exchanges:
Cash, Cash Equivalents and Investments:
NASDAQ: APTO
TSX: APS
$23.4M
Basic Shares Outstanding :
12.0M
Fully Diluted Shares Outstanding 1 :
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
28
EXECUTIVE SUMMARY:
BUILDING FOR SUCCESS
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 (Current Hold)
̶
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
29
̶
Seek to Resume Dosing of APTO-253
̶
Seek to Demonstrate Clinical Efficacy with APTO-253 in Patients with AML
̶
Seek to Continue Building a Staged Pipeline of Targeted Cancer Drugs
Thank You!
30