Strengthening the Foundation of Cancer Care

Transcription

1 NASDAQ HNAB Strengthening the Foundation of Cancer Care

2 Forward Looking Statements This material contains forward looking statements as defined by the Private Securities Litigation Reform Act of These include statements concerning plans, objectives, goals, strategies, future events or performance and all other statements which are other than statements of historical fact, including without limitation, statements containing words such as believes, anticipates, expects, estimates, projects, will, may, might and words of a similar nature. Such statements involve risks and uncertainties that could cause actual results to differ materially from those projected. Some important factors that could cause actual results to differ include dependence on the efforts of third parties; dependence on new and uncertain technology and its uncertain application to new business ventures; regulatory actions or delays, or uncertainties related to product development, testing or manufacturing; ability to form and maintain strategic alliances; ability to complete certain transactions and realize anticipated benefits from acquisitions; dependence on certain intellectual property rights of both Hana and third parties; the competitive nature of Hana's industry; risks of obsolescence of certain technology; and ability to develop viable products for the health care market including the achievement of successful pre clinical and clinical results. The forward looking statements contained herein represent the judgment of Hana as of the date this material was drafted. Hana disclaims, however, any intent or obligation to update any forwardlooking statements. 2

3 Key achievements in last 6 months Focused development on Marqibo and menadione Initiated Marqibo registration enabling rally trial in adult ALL Initiated Marqibo pilot Phase 2 uveal melanoma trial Submitted and opened Menadione IND in U.S. and Canada Demonstrated single agent activity in Alocrest Phase 1 trial Submitted and opened Brakiva IND Reduced cash burn rate to $5 7M per quarter Ended with approximately $21M in cash/cash equivalents Closed a $30M structured debt financing 3

4 Current widely used anti cancer drugs have limitations 4

5 Hana s pipeline is addressing these limitations = 2007 accomplishment 5

6 Addressing a treatment limiting toxicity THE RASH Hidalgo et al. J ClinOncol. 2001;19:3267. Courtesy of E.S. Kim, MD. 6

7 Menadione will target a large unmet supportive cancer care need Rash occurs in up to 90% of patients treated with EGFR inhibitors Dose reduction or treatment cessation in up to 30% of affected patients Rash believed to be due to EGFR inhibition in normal skin Topical menadione restores normal EGFR signaling in murine skin cells Normal skin pegfr Absence of pegfr after erlotinib dosing pegfr after 5 days of BID topical menadione Normalized pegfr after erlotinib plus topical menadione Perez Soler, R et al., ASCO 2006, abstract #3036 7

8 Optisomes deliver chemotherapy like a Smart Bomb Sphingomyelin and cholesterol bilayer 100 nm mean diameter Acidic (ph 4) aqueous core Core features enable high concentration loading and prevent payload hydrolysis Capacity to hold 10,000 drug molecules per Optisome Able to retain payload long enough to reach areas of tumor involvement Predictable drug release rates Webb MS, et al. Br J Cancer 1995;72:

9 Optisomes enhance penetration and retention of cell cycle specific chemotherapies Improved PK Targeted delivery Increased concentration Prolonged exposure Prolonged (100 fold) plasma circulating half life ( 19 h) and increased ( fold) AUC Preferentially exit the circulation from cancer blood vessels Accumulate in cancerous tissues with 3 to 10 fold greater drug concentrations Extended and continuous drug exposure due to gradual drug release over several days with 5 to 15 fold greater intra tumor AUC Johnston MJ et al. BiochimBiophys Acta.2006;1758: Semple SC et al. J PharmSci 2005;94: TardiP et al. Cancer Res. 2000;60:

10 Optisomes are distinct from other technologies Technology & Purpose Source Extends circulation time Targets tumors Drug freely disassociates from carrier OPTISOME Nanoparticle Technology Nanoparticle albumin-bound nab technology to improve drug solubility Biodegradable polyglutamate polymer link to transport drug through porous vessels Nano-emulsion to transport lipophilic and insoluble drugs Hana Abraxis CTI AdventRx Vitamin E oil emulsion to solubilize and stabilize drugs Sonus 10

11 Optisomes accumulate in tumors 1 minute post injection 60 minutes post injection Healthy tissue with normal vasculature Optisomes remain intravascular Tumor tissue with leaky vasculature Optisomes leave the vasculature and accumulate in the tumor tissue Intravital microscopy following administration of fluorescein-labeled vincristine Optisomes Shan S et al. Cancer ChemotherPharmacol 2006;58:

12 Marqibo (VincristineOptisome ) is our most advanced compound Potential indications Acute lymphoblastic leukemia (ALL) Hodgkin s disease and non Hodgkin s lymphoma Multiple myeloma Solid tumors (e.g., malignant melanoma) Preclinical comparison data demonstrate Increased circulation time and plasma AUC 5.7 to 7.4 fold greater drug tissue (bone marrow, lymph node, implanted tumor, spleen and liver) exposure (tissue AUC) Increased therapeutic index Facilitates 2.25 mg/m 2 weekly dosing without dose capping compared to 1.4 mg/m 2 with a 2 mg cap for conventional vincristine U.S. FDA Orphan Drug designation and Fast track Status in adult ALL Wong M et al. AACR NCI EORTC Inter Conf 2007, Abstract C

13 Marqibo delivers more vincristine to lymphoid cancers Vincristine concentration (mcg/g tissue) Marqibo Vincristine 4 hours 16 hours 48 hours Marqibo Vincristine 4 hours 16 hours 48 hours Implanted Tumor Bone Marrow Cullis, P et al., ASH 2007, abstract #

14 Optisomal encapsulation increases vincristine delivery and activity 500 A431 Solid Tumor Xenograft Tumor size (% of baseline) Control Vincristine Marqibo (optimized release rate) TIME (days) DSPC/Chol Liposomal vincristine (fast release rate) Webb MS, et al. Br J Cancer.1995;72:

15 Marqibo has demonstrated promising activity Indication Regimen N Results Adult ALL (relapsed/refractory) Marqibo and pulse steroids 36 24% CR/CRp (19% ITT) 1 29% CR in 2 nd relapse 71% CRs able to undergo transplantation Metastatic melanoma Marqibo 26 31% Disease Control Rate (1 CR, 2 PR, 5 SD) 2 25% CR in the setting of uveal melanoma Hodgkin s disease (relapsed/refractory) Marqibo 28 36% ORR (18% CR, 18% PR) 3 Aggressive Lymphoma (relapsed/refractory) Marqibo % ORR (5% CR, 22% PR) 4 Aggressive Lymphoma (front line) R CHMP (M= Marqibo) 68 93% CR, (88% 17 months) 5 1 Thomas D et al. Blood 2006;108 abstract 4539; 2 Bedikian A et al. JCO; 3 Hana Biosciences, Inc., VSLI 05HD; 4 Winter JN et al. Blood 2007 (submitted); 5 Rodriquez A et al. JCO 2004;22 abstract 8080

16 rally & ALLy are designed for accelerated success Study Disease Study Population Study Design Study Treatment rally (registration enabling trial) Philadelphia chromosome ( ) acute lymphoblastic leukemia or lymphoblastic lymphoma Adults in second relapse or those who failed 2 prior lines of therapy Multi center, multi national, single arm, open label trial Single agent weekly intravenous Marqibo 2.25 mg/m 2 (no dose cap) ALLy (confirmatory trial) Philadelphia chromosome ( ) acute lymphoblastic leukemia or lymphoblastic lymphoma Elderly subjects ( 70 years of age) with newly diagnosed disease Randomized, double blinded, activecontrolled trial Multi agent treatment including either Marqibo 2.25 mg/m 2 (no dose cap) or vincristine 1.4 mg/m 2 (2.0 mg cap) Primary Outcome Measure Confirmed complete remission (CR) or complete remission without full platelet recovery (CRp) Sample Size 56 evaluable subjects 300 Target Response 16% CR/CRp rate 40% EFS at 1 year Event free survival (EFS) with death, failure to achieve CR/CRp, and relapse after CR/CRp as events 16

17 Alocrest (Vinorelbine Optisome ) targets NSCLC in elderly and breast cancer Potential indications Solid tumors (e.g., non small cell lung cancer and breast cancer) Hematologic malignancies (e.g., lymphoma) Preclinical comparison data demonstrate Prolonged plasma circulation time and 100 fold increased plasma AUC 9.5 fold increased vinorelbine exposure (tissue AUC) at tumor sites fold increased therapeutic index Potential for less neutropenia Interim Phase 1 dose escalation trial data revealed no dose limiting toxicity and stable disease in 3 of 11 subjects 17

18 Alocrest is more active than vinorelbine in xenograft models Median Tumor Volume (mm 3 ) MX 1 Breast Cancer * Comparable Alocrest activity At half the vinorelbine dose Saline VRL, 20 mg/kg VRL, 10 mg/kg Alocrest, 20 mg/kg Alocrest, 10 mg/kg Optisomes Cured animals with Alocrest Time (Days, Post Tumor Implantation) Eisenhardt ML et al., AACR 2004, abstract #633 18

19 Brakiva (Topotecan Optisome ) addresses solid tumor and hematologic cancers Potential indications Solid tumors (e.g., small cell lung cancer and ovarian cancer) Hematologic malignancies (e.g., relapsed AML and MDS) Preclinical comparison data demonstrate Prolonged plasma circulation time and increased plasma AUC 10 fold increased topotecan delivery to tumor sites fold increased anti cancer activity in nonclinical models Phase 1 dose escalation trial in solid tumors planned 19

20 Optisomal encapsulation protects topotecan from hydrolysis (inactivation) in plasma HO + N H N O O ph 7 N O OH O N Lactone OH O ph < 7 N Carboxylate O H O Topotecan (% of total) Lactone (active) Carboxylate (inactive) Conventional Topotecan 5 minutes minutes hour 95 5 Optisomal Topotecan 4 hours hours hours

21 Brakiva is more active than topotecan in xenograft models LX 1 Small Cell Lung Cancer MX 1 Breast Cancer Median Tumor Volume (mm 3 ) q7dx3 Untreated Topo, 30 mg/kg Topo, 10 mg/kg Brakiva, 5 mg/kg Brakiva, 2.5 mg/kg Brakiva, 1.25 mg/kg q3dx4 Untreated Topo, 10 mg/kg Topo, 2.5 mg/kg Topo, 1.25 mg/kg Brakiva, 5 mg/kg Brakiva, 2.5 mg/kg Brakiva, 1.25 mg/kg Brakiva, 0.5 mg/kg Time (Days, Post Tumor Implantation) Time (Days, Post Tumor Implantation) 21

22 Poised for a productive 2008 Compound Goal Target Status Menadione Activate IND Q1 Initiate Phase 1 trial in EGFRi treated patients Q2 rally trial (relapsed ALL) interim analysis 2H Marqibo Uveal melanoma trial interim analysis Initiate Phase 3 ALLy trial (front line ALL) Q4 Q4 Alocrest Complete and present Phase 1 trial Q2 Brakiva Initiate Phase 1 trial in solid tumors Q3 22

23 NASDAQ HNAB Strengthening the Foundation of Cancer Care