OBI Pharma, Inc. Global Innovator in Immuno-Oncology and Targeted Cancer Therapies. Amy Huang General Manager

Transcription

1 OBI Pharma, Inc. Global Innovator in Immuno-Oncology and Targeted Cancer Therapies Amy Huang General Manager 37th Annual J.P. Morgan Healthcare Conference January 9, 2019

2 This presentation contains certain forward-looking statements. Safe Harbor Statement These forward-looking statements may be identified by words such as believes, expects, anticipates, projects, intends, should, seeks, estimates, future, or similar expressions or by discussion of, among other things, strategy, goals, plans, or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1. Pricing and product initiatives of competitors 2. Legislative and regulatory developments and economic conditions 3. Delay or inability in obtaining regulatory approvals or bringing products to market 4. Fluctuations in currency exchange rates and general financial market conditions 5. Uncertainties in the discovery, development, or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side effects of pipeline or marketed products 6. Increased government pricing pressures 7. Interruptions in production 8. Loss of or inability to obtain adequate protection for intellectual property rights 9. Litigation 10. Loss of key executives or other employees 11. Adverse publicity and news coverage OBI Pharma cautions that this foregoing list of factors is not exhaustive. There may also be other risks that management is unable to predict at this time that may cause actual results to differ materially from those in forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date on which they are made. OBI undertakes no obligation to update publicly or revise any forward-looking statements. Any statements regarding earnings growth is not a profit forecast and should not be interpreted to mean that OBI s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed published earnings or earnings per share forecasts of OBI Pharma, Inc. 2

3 Agenda Company Introduction Globo Series Science Leadership Novel Cancer Pipeline Key Milestones and Inflection Points 3

4 Agenda Company Introduction Globo Series Science Leadership Novel Cancer Pipeline Key Milestones and Inflection Points 4

5 OBI Pharma, Inc. (TPEx: 4174.TWO) Founded: April 29, 2002 Shanghai CHINA IPO on TPEx: March 23, 2015 Market Cap. (Jan. 4, 19): Fund Raised at IPO: Net Cash on Hand: ~US$920M (~NT$28.5B) ~US$200M (~NT$6.2B) ~US$115M Hong Kong CHINA Global HQ Taipei TAIWAN San Diego USA Employees: 117 Melbourne AUSTRALIA 5

6 Experienced Global Management Team Michael Chang, PhD Founder and Chairman Amy Huang General Manager Tony Yu, PhD Chief Science Officer and Executive VP Kevin Poulos Chief Commercial Officer Max Chan Chief Financial Officer Victoria Lin General Counsel Mitch Che Chief Operating Officer OBI USA Chen-En Tsai, MD, PhD VP Medical and Clinical Development David Hallinan, PhD VP Regulatory Affairs Jiann-Shiun Lai, PhD VP Research Sophie Lee, PhD VP Statistics and Biometrics 6

7 Scientific and Medical Advisors Chi Huey Wong, PhD Yun Yen, MD, PhD Stephan Landisch, MD Pan Chyr Yang, MD, PhD Alice Yu, MD, PhD Russell Greig, PhD Shaw T. Chen, MD, PhD Tillman Pearce, MD Chuan Shih, PhD Yu Wang, MD 7

8 OBI Pharma Is at the Forefront of Innovation in Cancer Therapy INNOVATION DRIVERS Explosion in Immunotherapy Driven by PD1/PD-L1 and Novel Antigens/MOAs Continued Growth of Targeted Therapy Driven by CAR T Improved Chemotherapies Tumor-Specific Improved Formulations INNOVATION TRENDS Synergistic Combinations Anchored by PD-1/PD-L1 Antibody-Drug Conjugates (ADCs) Bispecific Antibodies Targeted Prodrugs IV Oral Therapy OBI INNOVATION OBI Pharma is Focused on: Novel Antibodies Innovative Technologies Synergistic Combinations Tumor-Specific Chemotherapy CAR T, chimeric antigen receptor T-cell therapy; IV, intravenous; MOA, mechanism of action; PD-1, programmed death 1; PD-L1, programmed death ligand 1. 8

9 OBI Has Transformed Into a Multi-Asset Company With a Diversified Portfolio of Novel Therapies GSL mab Antibody-Drug Conjugate Bispecific mab Targets: Globo H (+), SSEA-4 (+), AKR1C3 (+) Tumors Assays: Globo H, AKR1C3 GSL Vaccine Targeted Prodrug mab, monoclonal antibodies; GSL, glycosphingolipid. 9

10 Agenda Company Introduction Globo Series Science Leadership Novel Cancer Pipeline Key Milestones and Inflection Points 10

11 OBI Pharma is the only company with a mid-to-late-stage Immuno-Oncology pipeline targeting the Globo Series of Glycosphingolipids: Globo H, SSEA-3, SSEA-4 11

12 Globo Series: A Unique Class of Glycosphingolipids (GSLs) Involved in Tumor Development and Survival GSLs Globo Series GSLs β3 α2 α3 SSEA-3 Globo H SSEA-4 Ceramide Ceramide Ceramide Glc GalNAc Gal Sialic Acid Fuc Functional Roles of Lipids and Membranes William Dowhan, Mikhail Bogdanov, Eugenia Mileykovskaya Department of Biochemistry and Molecular Biology, The University of Texas at Houston Medical School, Houston, Texas. 12

13 Globo Series Antigens are Expressed on Multiple Epithelial Cancer Cells Cancers Globo H* SSEA-3 SSEA-4* Esophagus 100% 0% 50% Stomach 100% 50% 67% Pancreas 75% 38% 100% Prostate 25% 25% 100% Liver 90% 40% 60% Ovary 56% 22% 89% Colon 86% 0% 71% Kidney 86% 0% 83% Mouth 85% 15% 62% Cervix 25% 50% 75% Breast 61% 26% 74% Brain 35% 53% 71% Lung 65% 25% 65% Bile duct 60% 20% 40% * >50% expression highlighted. Note: Expression of Globo Series was determined by flow cytometry; More than 15% is regarded as positive. Lou YW, et al. Proc Natl Acad Sci U S A. 2014;111(7):

14 Globo H Plays an Essential Role in Tumor Survival Promotes Immunosuppression Promotes Tumor Survival Signaling Lymphocytes Ub Ub Degradation Notch1 Promotes Angiogenesis Endothelial Cells TRAX Ca 2+ Tumor Shedding of Globo H Ceramide Kinase Kinase Kinase Tumor Cells Tumor Survival Cancer Res AACR Special Conference Abstract A20. Cheng JY, et al. Cancer Res. 2014;74(23): J Cancer Sci Ther. 2013;5(7): OBI Data on File. 14

15 Agenda Company Introduction Globo Series Science Leadership Novel Cancer Pipeline Key Milestones and Inflection Points 15

16 The OBI Pharma Diverse Cancer Pipeline PRODUCT TYPE TARGET CANCER DISCOVERY PRE-CLINICAL P1 P2 P3 Adagloxad Simolenin Vaccine Globo H Breast (TNBC) Ovarian OBI-833 Vaccine Globo H Multiple Cancers OBI-888 mab Globo H Multiple Cancers OBI-999 ADC Globo H Multiple Cancers OBI-898 mab SSEA-4 Multiple Cancers OBI-866 Vaccine SSEA-4 Breast Liver (HCC) OBI-3424 Prodrug AKR1C3 Prostate (CRPC) T-ALL ALL, acute lymphoblastic leukemia; CRPC, castration-resistant prostate cancer; HCC, hepatocellular carcinoma; TNBC, triple-negative breast cancer. 16

17 Adagloxad Simolenin First-in-Class Active Immunotherapy Inducing Globo H Antibodies 17

18 Adagloxad Simolenin Induces ADCC- and CDC-Mediated Tumor Apoptosis Globo H KLH IgG Adagloxad Simolenin MHC TCR T Cell IgM Complement Antigen-Presenting Cell B CTL Anti-Globo H IgG Anti-Globo H IgM ADCC Antibody-Dependent Cellular Cytotoxicity Tumor cell CDC Complement-Dependent Cytotoxicity APC, antigen-presenting cell; CTL, cytotoxic T-lymphocyte; KLH, keyhole limpet hemocyanin; MHC, major histocompatibility complex; TCR, T-cell receptor.. 18

19 Lessons Learned From Adagloxad Simolenin Phase II Trial in Patients With Metastatic Breast Cancer (MBC) Higher Globo H tumor expression correlates with improved PFS Higher Anti-Globo H IgG levels following vaccination correlates with improved PFS Patients receiving 9 injections had improved PFS PFS, progression-free survival. Clinicaltrials.gov. Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Metastatic Breast Cancer Subjects. NCT

20 Adagloxad Simolenin Global Phase III Trial in High-Risk Early-Stage Triple-Negative Breast Cancer High-Risk Early-Stage TRIPLE-NEGATIVE BREAST CANCER n = 668 patients Neoadjuvant patients with residual disease, or Adjuvant patients with 4 axillary nodes Globo H positive ECOG PS 0-1 R 1:1 EXPERIMENTAL ARM Adagloxad Simolenin (Adagloxad Simolenin 30 μg + OBI μg) n = 334 Study treatment approximately 2 years (21 doses) PLACEBO ARM Placebo (phosphate-buffered saline) n = 334 Primary Endpoint: IDFS (Invasive Disease-Free Survival) Secondary Endpoints: Overall Survival (OS), Quality of Life, Safety, Tolerability Interim Analysis: Evaluate primary endpoint at 70% information time Study Duration: 2-year enrollment, 3-year IDFS evaluation, + 2 years for OS follow-up Phase III Clearance: United States, Australia, Taiwan, Hong Kong ECOG PS, Eastern Cooperative Oncology Group Performance Status. Clinicaltrials.gov. Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy. NCT

21 OBI-888 First-in-Class Monoclonal Antibody Targeting Tumors Expressing Globo H 21

22 OBI-888 Inhibits Tumor Growth in 5 Cancer Xenograft Models CANCER TYPE TUMOR MODEL DOSE(mg/kg) TREATMENT REGIMEN TGI AT TOP DOSE TESTED, % Breast MCF7 1, 3, 10 Q2W x 6 85 Breast HCC , 10, 30 Q2W x 6 55 Pancreatic HPAC 5, 20, 80 Q2W x 5 47 Colorectal SW Q2W x 4 49 Lung NCI-H526 10, 30, 100 Q2W x 5 43 Q2W, every 2 weeks; TGI, tumor growth inhibition. OBI Data on File. 22

23 OBI-888 is Highly Tumor Specific NORMAL MICE MCF7-TUMOR BEARING MICE Distribution of labeled Globo H mab (OBI-888) in the tumor of the MCF7 mouse Eppendorf tubes for reference purposes OBI Data on File. 23

24 OBI-888 Protects T Cells From Inactivation by Globo H Ceramide Intensity of T-cell's "Glo" (RLU) Globo H Ceramide OBI 888 aapc/cho K1 aapc/cho-k1 Cells T-cell activity with Globo H Ceramide OBI-888 aapc, artificial antigen-presenting cells; CHO-K1, Chinese hamster ovary K1 cells. PD-1 effector cells were pretreated with 40 µm Globo H Ceramide for 20 hours in the presence or not of 10 µm OBI-888, and then incubated with aapc/cho-k1 cells for 6 hours. The RLU signal was determined after 10 minutes developing with Bio-Glo Luciferase Assay Reagent. Each treatment was performed in quintuplicate. RLU shown as mean ± standard deviation (SD). OBI Data on File fold increase 24

25 Synergistic Protection of T-Cell Activity by OBI-888 and an Anti-PD-L1 mab aapc/cho K1 Cells PD-L1 aapc/cho-k1 Cell T-cell activity in PD-L1(+) cells with Globo H Ceramide OBI-888 and a-pd-l1 mab 8-fold increase a-pd-l1 mab 2-fold increase OBI Data on File. Globo H Ceramide a-pd-l1 mab OBI

26 OBI-888 Potential Combination With PD-L1 mab and Other Therapies Globo H expression was correlated with PD-L1 expression in ADC Stage I NSCLC patients (P=0.021) and also associated with EGFR (ADC, P=0.026) and PI3K expression (SqCC, P<0.001), Globo H overexpressed in 38.6% of patients with Stage I NSCLC 21% Dual Expression PD-L1 overexpressed in 46% of patients with Stage 1 NSCLC N = 228 patients with Stage 1 NSCLC, including both ADC and SqCC ADC, adenocarcinoma; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; SqCC, squamous cell carcinoma. Yang CY, et al. Cancer Biomark. 2017;21(1):

27 OBI-888 Ongoing Phase I Study Multiple Solid Tumors Pancreatic, Breast, Gastric, Esophageal, Colorectal, Lung Part 1 DOSE ESCALATION OBI-888 Part 2 COHORT EXPANSION OBI-888 Measuring Globo H Expression Levels With IDE-Approved Assay Apostolia M Tsimberidou, MD, PhD Department of Investigational Cancer Therapeutics Division of Cancer Medicine IDE, Investigational Device Exemption. Clinicaltrials.gov. Study to Evaluate the Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. NCT

28 OBI-999 Antibody-Drug Conjugate (ADC) Targeting Tumors Expressing Globo H 28

29 OBI-999 Targeting Tumor-Specific Globo H ADC Utilizing Novel Site-Specific Linker Technology ThioBridge Cancer cell specific cytotoxic payload released to the targeted cancer cells with high Globo H expression Unique linker technology maintains the stability of the antibody and a consistent drug-to-antibody ratio (DAR) Worldwide exclusive license to use the ThioBridge technology for ADCs targeting the Globo series ThioBridge is the registered trademark of Abzena 29

30 OBI-999 Inhibits Tumor Growth in 4 Cancer Models CANCER TYPE TUMOR MODEL DOSE (mg/kg) TREATMENT REGIMEN RESPONSE OR TGI AT HIGHEST DOSE, % Breast MCF7 1, 3 QW x 6 or Q3W x 2 Complete Response Gastric NCI-N87 1, 3,10 QW x 4 Complete Response (CR achieved at both 3 and 10 mg/kg) Complete Response = Tumor Free Pancreatic HPAC 10 QW x 4 Complete Response Lung PDX LU , 3, 10 QW x 4 Complete Response PDX, patient-derived xenograft; TGI, tumor growth inhibition; QW, every week; Q3W, every 3 weeks. OBI Data on File. 30

31 OBI-898 Monoclonal Antibody Targeting Tumors Expressing SSEA-4 Antigen

32 SSEA-4 Antigen Expression is Highly Specific to Cancer Cells Cancers Globo H* SSEA-3 SSEA-4* Esophagus 100% 0% 50% Stomach 100% 50% 67% Pancreas 75% 38% 100% Prostate 25% 25% 100% Liver 90% 40% 60% Ovary 56% 22% 89% Colon 86% 0% 71% Kidney 86% 0% 83% Mouth 85% 15% 62% Cervix 25% 50% 75% Breast 61% 26% 74% Brain 35% 53% 71% Lung 65% 25% 65% Bile duct 60% 20% 40% Note. Expression of Globo Series Antigens was determined by flow cytometry; >15% expression was regarded as positive. Lou YW, et al. Proc Natl Acad Sci U S A. 2014;111(7):

33 OBI-898 Blocks SSEA-4 Binding to Immune Checkpoint Siglec-9 Releasing Immune Inactivation ITIM, immunoreceptor tyrosine-based inhibitory motif; P, phosphate; Siglec-9, sialic acid-binding Ig-like lectin 9 OBI Data on File. 33

34 SSEA-4 Upregulates Multidrug Resistance Protein 1 SSEA-4 upregulates multidrug resistance protein 1 (MDR1) expression through csrc and β-catenin signaling MDR1 overexpression is most commonly detected in drugresistant cancers MDR1 encodes for P-glycoprotein that extrudes anticancer drugs Liu YY, et al. Molecular Cancer. 2010;9:145. High expression of SSEA-4 was found in residual tumor cells surviving chemotherapy and in samples from patients with metastatic cancer who relapsed after neoadjuvant chemotherapy Aloia A, et al. Breast Cancer Research. 2015;17:146. GCS, glucosylceramide synthase; GEM, glycosphingolipids-enriched microdomains; GlcCer, glucosylceramide; Tcf4, T-cell factor 4; FAK, focal adhesion kinase; csrc, proto-oncogene (Schmidt-Ruppin A-2); Gb3, globotriaosylceramide; Gb5, globopentaosylceramide; MSGb5, monosyl-gb5. 34

35 OBI-898 Reduces EGFR Protein Expression Similar to the Tyrosine Kinase Inhibitor (TKI) Osimertinib (Targrisso ) 3 mpk 30 mpk OBI mpk 5 mpk Osimertinib ** EGFR L858R Western Blot was highly correlated to hematoxylin and eosin stain; P<0.01. Targrisso is the registered trademark of AstraZeneca. OBI Data on File 35

36 The Acquired Resistance Soon After TKI Treatment Warrants Novel Strategies in Combating Cancers With EGFR Mutations Major TKI Products and Companies PRODUCT GENERIC NAME COMPANY FIRST APPROVAL First Generation Second Generation Third Generation Iressa Gefitinib AstraZeneca 2003 Tarceva Erlotinib Genetech (Roche)/ Astellas 2004 Gilotrif Afatinib Boehringer Ingelheim 2013 Vizimpro Dacomitinib Pfizer Sept 2018 Tagrisso Osimertinib AstraZeneca 2015 Table summarized by OBI. 36

37 OBI-3424 Small Molecule Prodrug Targeting Tumors Expressing the AKR1C3 Enzyme 37

38 OBI-3424 Tumor-Specific Small Molecule Prodrug Activation by AKR1C3 Enzyme Releases Cytotoxic Agent in the Tumor Cell Tumor Cell OBI-3424 AKR1C3 Enzyme Present Prodrug AKR1C3 Active drug Tumor Cells Killed Healthy Cell No AKR1C3 Minimal Impact on Healthy Cells NADPH, nicotinamide adenine dinucleotide phosphate. 38

39 Targeting Cancers With High Unmet Need and Tumor Expression of AKR1C3 >50% CANCER CLINICAL DEVELOPMENT STATUS AKR1C3 EXPRESSION,* % Liver Ongoing 89 CRPC Ongoing 58 T-ALL P1 IND planned in Q2/2019 (NCI funded PPTC) 86 Kidney n/a 64 Bladder n/a 66 Stomach n/a 59 ** AKR1C3 Expression: Guise CP, et al. Cancer Res. 2010;70(4): CRPC, castration-resistant prostate cancer; IND, Investigational New Drug Application; n/a, not applicable; NCI, National Cancer Institute; PPTC, Pediatric Preclinical Testing Consortium; T-ALL, T-cell acute lymphoblastic leukemia. 39

40 OBI-3424 Ongoing Phase I Study in Hepatocellular Carcinoma and Castrate-Resistant Prostate Cancer Locally Advanced or Metastatic Tumors HCC, CPRC Part 1 DOSE ESCALATION OBI-3424 Part 2 COHORT EXPANSION OBI-3424 Measuring AKR1C3 Enzyme Expression With IDE-Approved Assay Apostolia M Tsimberidou, MD, PhD Department of Investigational Cancer Therapeutics Division of Cancer Medicine Clinicaltrials.gov. This Study is to Evaluate OBI-3424 Safe and Effective Treatment Dose in Subjects With Hepatocellular Carcinoma or Castrate Resistant Prostate Cancer. NCT

41 %hucd45+ in the PB Significant Reduction in Leukemia Bone Marrow Infiltration With OBI-3424 in PDX Model (T-ALL 31) Control Group Significant Difference in Event-Free Survival (EFS) OBI-3424 Group Days post-treatment initiation OBI-3424 is one of the most effective drugs we have ever tested against T-ALL in over 12 years of evaluating drugs at the Children s Cancer Institute using preclinical models of childhood ALL Prof Richard B. Lock Head of the Leukemia Biology Program Children s Cancer Institute in Australia PB, peripheral blood; PDX, patient-derived xenograft. OBI Press Release 30 Oct 2017: OBI Pharma announces OBI-3424 results from the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. 41

42 Potential for the Development of Globo Series Bispecific Antibody Therapies OTHER TARGETS GLOBO SERIES ANTIGENS PD-L1 Globo H SSEA4 + OX-40 CD-137 CD-40 Novel Bispecific Antibody VEGF VEGF, vascular endothelial growth factor. 42

43 Agenda Company Introduction Globo Series Science Leadership Novel Cancer Pipeline Key Milestones and Inflection Points 43

44 OBI Pharma Portfolio Strong Worldwide IP Protection Approved Patents Patents in Review Includes Patents Held By Licensors. 44

45 2018 Milestone Achievements Received FDA Clearance of an IND Application for a Phase I Study of a Monoclonal Antibody Cancer Immunotherapy Received FDA Clearance of an IND Application for a Phase I/II Study Targeting AKR1C3-Expressing Solid Tumors FDA Granted Orphan Drug Designation for the Treatment of Pancreatic Cancer FDA Granted Orphan Drug Designation for the Treatment of Acute Lymphoblastic Leukemia (ALL) and Hepatocellular Carcinoma (HCC) Initiated a Global Phase 3 Clinical Trial in Patients With Triple-Negative Breast Cancer Clinicaltrials.gov. This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. NCT Clinicaltrials.gov. This Study is to Evaluate OBI-3424 Safe and Effective Treatment Dose in Subjects With Hepatocellular Carcinoma or Castrate Resistant Prostate Cancer. NCT Clinicaltrials.gov. Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy. NCT

46 Key Milestones and Inflection Points Adagloxad Simolenin Initiated Global Phase III Triple- Negative Breast Cancer Trial Enrollment Ends Interim Analysis Unblinding IDFS OBI-888 Initiated Part 1 Dose Escalation Part 1 Data Part 2 Cohort Expansion Part 2 Data OBI-999 Submit IND P1 P1 Data P2 P2 Data OBI-3424 Phase IND 1 Submitted Part 1 Dose Escalation Part 1 Data Part 2 Cohort Expansion Part 2 Data 46 IDFS, invasive disease-free survival.

47 1 OBI Pharma Is a Global Innovator in Cancer Therapeutics With a Diverse and Novel Pipeline Global leader in Globo Series science with First-in-class therapeutic vaccines, mabs, and ADCs targeted to both Globo H and SSEA-4 Great synergistic potential to combine these products with other antibodies to build a wide range of Bispecific Antibodies First-in-class, tumor-specific AKR1C3 enzyme-activated small molecule prodrug Diagnostic assays to quantify antigen expression Strong global IP Protection Multiple inflection points driving value

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