* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download 150917 AV Basel Presentation
Survey
Document related concepts
Psychopharmacology wikipedia , lookup
Drug design wikipedia , lookup
Pharmacognosy wikipedia , lookup
Drug interaction wikipedia , lookup
Neuropharmacology wikipedia , lookup
Clinical trial wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Prescription costs wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Drug discovery wikipedia , lookup
Transcript
SACHS BIOTECH FORUM September, 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 for Precision Medicines ─ Therapies leveraging Novel Biomarkers for Patients with LifeThreatening Cancers APTO-253 Lead Agent at Phase Ib/II Stage of Development ─ Mechanism of action: “INDUCER OF KLF4 GENE” ─ Treatment of AML, MDS and other hematologic malignancies ─ Potential as a “Targeted Drug” for AML Experienced Management and Clinical Development Teams ─ Personnel Located in San Diego, San Francisco, Toronto Raised >$45 Million from Premier US Healthcare Investors New Corporate Vision & New Brand Listed on NASDAQ as “APTO” on October 23, 2014 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 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 6 AML MEDICAL NEED, MARKET AND CHALLENGES TO CREATE NEW DRUGS Approximately 19,000 Cases Per Year in the U.S. ─ Leading to ~10,000 deaths annually Majority of Patients >65 Years of Age ─ Dismal Survival Rate: 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 7 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 Silences KLF4 Transcription 8 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 9 (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 10 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 11 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 12 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 13 (1) Cercek et al, ECC ESMO 2013 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 15 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 (IC50 = 0.007-0.3 µM) ─ Safe Clinical Exposure Levels from Prior Trial (Cmax = 2-6 µM) ─ Suggest Entering Therapeutic Range for Heme Cancers 16 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 ̶ Collaborations will reveal additional data for APTO-253 (Beat AML, drug combination collaborations) ̶ Seek to Build a Staged Pipeline of Multiple, Targeted Cancer Drugs 17 Thank You! 18