Canaccord Genuity Annual Growth Conference

CANACCORD GENUITY
ANNUAL GROWTH CONFERENCE
August 13th, 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.
2
RECENT CORPORATE HIGHLIGHTS
Built a Biotech Company Creating Targeted Agents and
Validated Biomarkers for Patients with Life-Threatening Cancers
APTO-253 Lead Agent at Phase Ib/II Stage of Development
─
Treatment of AML, MDS and other hematologic malignancies
─
Targeted small molecule “INDUCER OF KLF4 GENE”
−
─
Silencing KLF4 gene key leukemogenic event in majority of AML
Potential as a “Targeted Drug” for AML
Strong Financial Foundation … Raised >$45 Million
─
Including Premier US Fundamental Healthcare Investors
Listed on NASDAQ as “APTO” on October 23, 2014
Experienced Management and Clinical Development Teams
─
Personnel Located in San Diego, San Francisco, Toronto
3
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
4
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
5
APTO-253 : EVALUATED PREVIOUSLY IN PHASE I
TRIAL IN PATIENTS WITH SOLID TUMORS
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
ONGOING
Phase Ib/II
Completed
Ongoing
6
APTO-253 : PRIOR ALL-COMER
SOLID TUMOR PHASE I TRIAL
Observed Modest Antitumor Activity in a Few Patients
But, No Genetic Means to Select Sensitive Solid Tumors
Safe, Well-Tolerated, Dose-Dependent Pharmacokinetics
Not Toxic to
Normal Bone
Marrow Cells
20000
Day 1 AUC ng*hr/ml)
Mean AUC (0-24) ± SD (ng*hr/ml)
Safely Achieved
Cmax Exposure
Levels of 2-6 µM
AUC as a Function of Dose
Solid Tumor Phase I Trial Data
Day2 AUC ng*hr/ml)
15000
10000
5000
0
0
-5000
50
100
150
200
250
300
350
400
450
APTO-253 Dose (mg/m2)
7
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
8
ACUTE MYELOID LEUKEMIA (AML):
MOST COMMON FORM OF ACUTE LEUKEMIA IN ADULTS
HIGHLY AGGRESSIVE CANCER 0F BONE MARROW
AML INCIDENCE INCREASES WITH AGE
AND PROGNOSIS WORSENS
US Population Statistics
Therapy Strategies
Prevalence
35,726
Clinical Trial
51%
Incidence
18,860
Chemotherapy
28%
Annual Deaths
10,460
Supportive Care
21%
Incidence (per 100,000)
AML Incidence by Age
AML most prevalent
in elderly patients
>65 years of age
Source: Datamonitor
Age (in years)
Source: American Cancer Society, Leukemia & Lymphoma Society
Source: SEER (Surveillance, Epidemiology and End Results) Cancer Statistics Review, 1975-2010. National Cancer Institute; 2013.
Source: Cancer Research UK 2013, Datamonitor
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AML MEDICAL NEED, MARKET AND
CHALLENGES TO CREATE NEW DRUGS
Dismal Survival Rate Among Adults >65 Years of Age
─
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 Inappropriately Expressed in AML
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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
13
(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
16
Source: APTOSE Biosciences, Inc . 2014 AACR Poster
APTO-253: PRECLINICAL FINDINGS
SUPPORT DEVELOPMENT IN AML & MDS
APTO-253 Small Molecule, Targeted Agent
─
COM/Use Patent Coverage Through 2028 ; Plus Typical Extensions
Expect Single Agent Efficacy Against AML in the Clinic
─
AML Cells and AML Xenograft Tumors Highly Sensitive
─
PK Exposure Levels Should Impact AML in Humans
Could Serve as Foundation of Combination Therapy
•
•
•
•
•
cytarabine
daunorubicin
azacitidine
decitabine
others
─
Preclinical Synergy with Approved and Investigational Drugs
─
APTO-253 Does NOT Suppress Normal Bone Marrow (1)
Developing Companion CDX2 & KLF4 Diagnostics: IP Filed
̶
Planned for Patient Selection and Therapeutic Signals
17
(1) Cercek et al, ECC ESMO 2013
BEAT AML RESEARCH INITIATIVE
Collaboration Using Primary Patient Isolates:
─
─
─
─
Testing APTO-253 as single agent and in combination
Identify optimal genetic profile for sensitivity / resistance
Identity optimal drug combinations strategies
Guide clinical development path
OHSU Submitted Abstract to 2015 ASH Meeting
18
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
20
Note: Phase 1b expansion cohorts and Phase 2 trials contingent on Phase 1b outcomes
STATUS OF PHASE IB TRIAL
Elite Clinical Sites
─
MD Anderson Cancer Center
̶ OHSU
─
University of Michigan
̶ Baylor Cancer Center
Biomarker Analysis
─
Bone Marrow and Peripheral Blood Collected and Processed
─
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
─
AML Cell Sensitivity (IC 50 = 0.007-0.3 µM)
─
Safe Clinical Exposure Levels from Prior Trial (Cmax = 2-6 µM)
─
Suggest Entering Therapeutic Range for Heme Cancers
21
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.
22
ANTICIPATED CORPORATE TIMELINES
ASSOCIATED WITH APTO-253
Event
Timeline
Preclinical: Single Agent & Combo Efficacy in AML Xenografts
Achieved
ASH Dec 2014
Clinical: Redirect / Commence Phase 1b Dose Escalation Trial
Achieved
Clinical: Obtain FDA Orphan Drug Designation for AML
Achieved
Preclinical: Response of Primary Isolates from Heme Cancer Patients (OHSU/Aptose)
Late-2015 (ASH)
Clinical: Potential Phase 1b Dose Escalation Interim Data (ASH)
Late-2015 (ASH)
Clinical: Complete Enrollment in Phase 1b Dose Escalation
Late-2015 / 1H 2016
Clinical: Phase 1b Dose Escalation Study Results
2H 2016
Clinical: Commence Phase 1b Single Agent Expansion Studies
2016
Clinical: Commence Phase 2 Drug Combination Studies
2016
23
SUMMARY FINANCIAL DATA:
EFFECTIVE END OF 2ND QUARTER 2015
$ in CAD
At June 30, 2015
Exchanges:
NASDAQ: APTO
TSX: APS
Cash, Cash Equivalents and Investments:
$25.2M
Debt - Promissory and Convertible Notes:
$0.28M
Basic Shares Outstanding (August 4, 2015):
11.9M
Fully Diluted Shares Outstanding 1 (August 4, 2015):
13.5M
Notes: 1) Comprised of A) 11,932,214 shares outstanding B) Warrants to purchase 138,835 shares,
C) options to purchase 1,731,096 shares at a weighted average price of $6.28 per share
and D) convertible notes that convert into 79,862 shares
24
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
̶
Seek to Build a Staged Pipeline of Targeted Cancer Drugs
25
Thank You!
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