J.P. MORGAN 34TH ANNUAL HEALTHCARE CONFERENCE San Francisco, CA, USA January 11-14, 2016 NASDAQ: APTO TSX: APS

Transcription

1 J.P. MORGAN 34TH ANNUAL HEALTHCARE CONFERENCE San Francisco, CA, USA January 11-14, 2016 NASDAQ: APTO TSX: APS

2 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 and EDGAR at especially the risk factors detailed therein. 2

3 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 3

4 VISION FOR APTOSE CRAFTED BY EXPERIENCED LEADERSHIP TEAM Avanish Vellanki SVP, Chief Business Officer Citigroup Global Markets: Biopharma Investment Banking Bear, Stearns & Co: Equity Research Publishing Analyst Proteolix, Inc.: Sr. Director of Corporate Development Gregory Chow SVP, Chief Financial Officer RBC Capital Markets: Director, Head Life Sciences Private Placements Wells Fargo: Led Private Capital Group 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 Ernst and Young LLP: Audit Manager with International Co. Specialty Chartered Professional Accountant and Chartered Accountant Bachelor of Business Administration from Wilfrid Laurier University Ernest Kitt Sr. Director, Clinical Operations Amgen/Onyx: Molecule Lead Director for Kyprolis in Clinical Operations Oncosec Medical: Executive Director of Clinical Operations Medicinova Inc: Associate Director of Clinical Operations 4

5 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

6 APTOSE PROGRAM PIPELINE Drug Indication Partners Discovery Pre-Clinical Phase I Phase II APTO-253 (KLF4 Inducer) Solid Tumors -- Hematologic Malignancies (AML & MDS) -- Dual-Targeting Bromodomain Program Oncology Moffitt Dual-Targeting Epigenetic Program Oncology LALS Oral KLF4 Program Various -- (1) Aptose in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology 6

7 APTOSE PROGRAM PIPELINE Drug Indication Partners Discovery Pre-Clinical Phase I Phase II APTO-253 (KLF4 Inducer) Solid Tumors -- Hematologic Malignancies (AML & MDS) -- Dual-Targeting Bromodomain Program Oncology Moffitt Dual-Targeting Epigenetic Program Oncology LALS Oral KLF4 Program Various -- (1) Aptose in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology 7

8 APTO-253 : PRIOR ALL-COMER SOLID TUMOR PHASE I TRIAL Mean Cmax ± SD (um) Safe, Well-Tolerated, Dose-Dependent Pharmacokinetics Observed Modest Antitumor Activity in a Few Patients At that Time No Means to Identify Sensitive Patients 2-6 µm Levels Safely Achieved Cmax as a Function of Dose Solid Tumor Phase I Trial Data Day 1 Cmax (um) Day 2 Cmax (um) Not Toxic to Normal Bone Marrow Cells APTO-253 Dose (mg/m2) 8

9 APTOSE PROGRAM PIPELINE Drug Indication Partners Discovery Pre-Clinical Phase I Phase II APTO-253 (KLF4 Inducer) Solid Tumors -- APTO-253 (KLF4 Inducer) Hematologic Malignancies (AML & MDS) -- Dual-Targeting Bromodomain Program Oncology Dual-Targeting Epigenetic Program Oncology Moffitt LALS Oral KLF4 Program Various -- Mechanistic Rationale Identify Most Sensitive Patient Population with Genetic Biomarkers Targeted AML Therapy (1) Aptose in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology 9

10 DEVELOPMENT OF APTO-253 FOR ACUTE MYELOID LEUKEMIA (AML): MOST COMMON FORM OF ACUTE LEUKEMIA IN ADULTS HIGHLY AGGRESSIVE CANCER 0F BONE MARROW

11 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 11

12 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 Across All Subtypes 40% MDS (Pre-AML) CDX2 Gene Turned ON CDX2 Inappropriately Expressed in AML Healthy 12

13 UNDERLYING CAUSE OF AML LINKED TO ALTERATIONS IN CDX2 AND KLF4 GENES CDX2 ON KLF4 Promoter CDX2 Protein CDX2 Protein Genetic and Epigenetic Alterations Turn On CDX2 Gene in 90% AML KDM5b Demethylase Epigenetic Demethylation of Histone H3-K4(Me3) at KLF4 Gene Altered Chromatin Structure CDX2 OFF Embryonic Gene KLF4 ON Master TF KLF4 CDX2 ON NORMAL AML 13

14 APTO-253 INDUCES KLF4 EXPRESSION AND AML APOPTOTIC CELL DEATH AML CDX2 ON KLF4 Genetically Induced KLF4 o KLF4 o p21 o Caspase 3 o Annexin V APTO-253 o KLF4 o p21 o Caspase 3 o Annexin V Reversed Epigenetic Silencing of KLF4 (1) Source: J. Clin. Invest. 2013; 123(1); KLF4 APOPTOSIS 14

15 APTO-253: ACTS THROUGH INTENDED MECHANISM IN AML PI + APTO-253 KLF4 p21 Apoptosis CDX CASPASE MV4-11 Cells DMSO DMSO 0.5 um APTO-253 Fold Increase p21 DMSO um APTO APTO-253 Induces Expression of KLF4 Master Tspn Factor KG-1 Cells Annexin V 15

16 APTO-253: AML CELLS HIGHLY SENSITIVE IN VITRO TUMOR SIZE (MM3) Weight (g) Small Molecule Pharmaceutical Agent Patent Through 2028 / Plus Extensions Developing CDX2 & KLF4 Companion Diagnostics AML Cell Lines Highly Sensitive (IC 50 = 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 OBSERVATION PERIOD (DAY) Mean Body Weight Profile 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= Source: APTOSE Biosciences, Inc AACR Poster

17 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 (1) Cercek et al, ECC ESMO 2013 Synergistic with Approved and Investigational Agents 17

18 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. 18

19 CLINICAL DEVELOPMENT PLAN Phase 1b Dose Escalation Trial Underway At Elite Clinical Sites Arm A AML and High Risk MDS 1 o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule 2 o Endpts: PK, Biomarkers, Efficacy, Transfusions Arm B Lymphomas and Multiple Myeloma 1 o Endpt: MTD, DLT & RP2D - Twice Weekly Schedule 2 o Endpts: PK, Biomarkers, Efficacy 2016 Patient Selection: CDX2 Single Agent Expansions AML (15) and MDS (15) ORR, Efficacy, Biomarkers, Safety KLF4 Phase 2 Drug Combination Phase 2 AML Drug Combination Trial Approved Drug + APTO o : Biomarkers (p21, CDX2, KLF4) 2 o : Efficacy Phase 2 MDS Drug Combination Trial Approved Drug + APTO o : Biomarkers (p21, CDX2, KLF4) 2 o : Efficacy/Transfusions Note: Phase 1b expansion cohorts and Phase 2 trials contingent on Phase 1b outcomes 19

20 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

21 APTOSE PROGRAM PIPELINE Drug Indication Partners Discovery Pre-Clinical Phase I Phase II APTO-253 (KLF4 Inducer) Solid Tumors -- Hematologic Malignancies (AML & MDS) -- Dual-Targeting Bromodomain Program Oncology Moffitt Dual-Targeting Epigenetic Program Oncology LALS Oral KLF4 Program Various -- (1) Aptose in-licensed intellectual property for composition; Aptose owns IP for Use in Oncology 21

22 DUAL-TARGETING SINGLE AGENT INHIBITORS OF BROMODOMAINS / KINASES RATIONAL TARGETING OF EPIGENETIC PROCESSES

23 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 c-myc CDK6 Aurora B BCL2 Acts Through Disruption of Crucial Epigenetic Processes Act Synergistically & Avoids Rapid Emergence of Drug Resistance 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

24 RATIONALE: DUAL-TARGETING SINGLE AGENT APPROACH 24

25 FIRST-IN-CLASS DUAL TARGETING EPIGENETIC INHIBITORS 25

26 DUAL-TARGETING EPIGENETIC INHIBITOR PROGRAM Clinical Candidate Expected: Late 2016 Laxai Avanti Life Sciences Potent, dual-targeting, single-agent inhibitors Exhibit single-digit ηm potency against BRD and specific oncogenic kinases (including JAK2, FLT3) CONFIDENTIAL Marquis medicinal chemistry organization Drug discovery collaboration for dualtargeting epigenetic therapeutics Developing multiple clinical candidates, including optimization of Moffitt molecules 26

27 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

28 SUMMARY FINANCIAL DATA: END OF Q $ in CAD At September 30, 2015 Exchanges: NASDAQ: APTO TSX: APS Cash, Cash Equivalents and Investments: $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

29 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 Seek to Resume Dosing of APTO-253 Seek to Demonstrate Clinical Efficacy with APTO-253 in Patients with AML 29 Seek to Continue Building a Staged Pipeline of Targeted Cancer Drugs

30 Thank You! 30