BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES

Transcription

1 BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES Clinical Development Program Prof. Moshe Phillip, MD VP Clinical & Medical Affairs 1

2 Rationale for BL-8040 Development in AML CXCR4 is an important prognostic factor in AML Mozobil phase 1/2 clinical study in combination with chemotherapy (MEC) in patients with r/r AML, observed modest leukemic cells mobilization Resulting in CR+CRi 46% (CR 39%) higher than expected in patients with advanced AML Preclinical studies with BL-8040 demonstrated: Accelerated mobilization of leukemic blasts from the BM to the PB Stimulated apoptosis of cells from AML patient Synergistic cytotoxic effect with Cytarabine in AML cells 2

3 CXCR4 Expression Level Correlates with Overall Survival Rate of AML Patients Impact of CXCR4 expression on OS in AML patients Expression of CXCR4 High: MIFRs, >10 Intermediate: MIFRs, 5 10 Low MIFRs, <5 Low: mean OS 24.3 month n=32 MEC: mitoxantrone, etoposide, cytarabine (PIII, CR 21%) High: mean OS 12.8 month n=32 Intermediate: mean OS 17.4 month n=26 Expression of CXCR4 defined by mean fluorescence intensity ratios (MFIRs) Blood 2007;109:,

4 Outline of BL-8040 on-going Phase 2 Clinical Study in AML patients A Phase 2, Multicenter, Open-label Study Designed to Evaluate Safety and Efficacy Profile of Repeated Escalating Doses of BL-8040 in Adult Subjects with Relapsed or Refractory Acute Myeloid Leukemia Patient population: r/r AML aged 18-75, (n=up to 50) Treatment: 2 consecutive days of BL-8040 mono-therapy 5 days of BL Chemotherapy (high dose Ara-C) Dose escalation phase: 3+3 design, up to 5 doses (0.5, 0.75, 1, 1.25, 1.5 mg/kg) Effective dose expansion phase: up to 50 subjects will be enrolled. 4

5 Study Objectives Primary To assess the safety and tolerability of escalating repeated doses of BL-8040 administered as monotherapy for two days, followed by five days of combined administration with standard chemotherapy in AML adult subjects with relapsed or refractory disease Secondary To assess the clinical efficacy (response rates) of escalating repeated doses of BL-8040 To assess the apoptotic effect of BL-8040 on leukemic blasts To assess the effect of BL-8040 on mobilization of AML blasts to peripheral blood Pharmacokinetic and additional pharmacodynamic effects 5

6 Current status Partial results of phase 2 clinical study expected at end of 2013 Participating sites: MD Anderson Cancer Center, Houston, US Dr. Gautam Borthakur Northwestern University, Chicago, US Dr. Jessica Altman Sheba Medical Center, Ramat Gan, Israel Dr. Arnon Nagler Sharei-Tzedek Medical center, Jerusalem, Israel Dr. Jacob Rowe Rambam Medical Center, Haifa, Israel Dr. Yishai Ofran Haddasah Medical center, Jerusalem, Israel Dr. Dina Ben-Yehuda Memorial Sloan-Kettering Cancer Center, NYC, US Dr. Martin Tallman Ichilov Medical Center, Tel-Aviv, Israel Dr. Nadav Sarid 6

7 Current status (cont.) BL-8040 raised significant interest among KOLs and will be further explored via investigator-initiated studies BioLineRx plans to initiate additional clinical studies with BL during 2014 for hemato-oncological indications 7

8 BL-8040 Phase 1/2a Clinical Study in MM patients Objective: Primary Endpoints: Safety and tolerability Secondary Endpoints: Pharmacokinetics, Pharmacodynamics (CD34+ cell number in blood) Patient population: MM patients who underwent stem cell mobilization and collection for autologous stem cell transplantation (n=18) Treatment: Single s.c. injection after G-CSF treatment for 5-days. Dose: 0.006, 0.03, 0.1, 0.3, 0.9 mg/kg 8

9 Results of Phase 1/2a Study in MM Patients Safety - none of the patients developed grade 3-4 toxicity PK - dose dependent increase of exposure, rapid absorption, short T1/2 Pharmacodynamics BL-8040 significantly increased stem cell mobilization in dose-dependent manner BL-8040 reduced the number of apheresis sessions required for transplantation from at low dose to 1 at the high dose BL-8040 Mozobil Dose 0.9 mg/kg 0.24 mg/kg Patients required a single apheresis to collect 6 x 10 6 CD34+ cells 100% 54.2% Number of cell by a single apheresis 20.9 x 10 6 cells/kg 7.01 x 10 6 cells/kg 9

10 Stem Cell Mobilization - Summary BL-8040 can be safely administrated with minimal toxicity and side effects BL-8040 significantly increases HSC mobilization BL-8040 at the high doses ( mg/kg) reduces number of apheresis sessions required for transplantation BioLineRx will initiate additional clinical study with BL-8040 during 2014 for stem cells mobilization Design and patient population yet to be determined 10