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27 th Annual Healthcare Conference Piper Jaffray Palace Hotel, NYC, New York December 2 nd , 2015 NASDAQ: APTO TSX: APS

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Page 1: 27th Annual Healthcare Conference - Aptoseaptose.com/wp-content/uploads/2014/08/Piper-Jaffray-27th-Healthcare... · 27th Annual Healthcare Conference Piper Jaffray Palace Hotel, NYC,

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

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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

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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

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(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

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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

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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!