Slide 1: Effects of EB613 Tablets on Trabecular and Cortical Bone Using 3D-DXA
Effects of EB613 Tablets [Oral PTH(1-34)] on Trabecular and Cortical Bone Using 3D-DXA: Post-Hoc Results from Phase 2 Study Gregory Burshtein, Constantin Itin, Hillel Galitzer, Michal Kushnir, Miranda Toledano, Ludovic Humbert, Rogely Boyce, Serge L Ferrari, Rachel B Wagman, Felicia Cosman 1
Slide 2: Disclosures
Disclosures ▪ Rachel B Wagman – Key clinical advisor and scientific advisory board member, Entera Bio Ltd. ▪ Felicia Cosman – Key clinical advisor and scientific advisory board member, Entera Bio Ltd. ▪ Serge L Ferrari – Consultant, Entera Bio Ltd. ▪ Rogely Boyce – Consultant, Entera Bio Ltd. ▪ Ludo
Slide 3: Background
Background Anabolic agents are currently used in a minority of 500 EB613 Oral PTH(1-34) Pharmacokinetics patients for whom these agents are appropriate PTH(1-34) plasma concentration (pg/ml) EB613 2.5 mg • This treatment gap is in part related to the need for 400 EB613 1.5 mg subcutaneous administra
Slide 4: EB613 Phase 2 Clinical Study Design
EB613 Phase 2 Clinical Study Design Primary Endpoint Key Inclusion Criteria Placebo QD • Serum PINP % change from • 50+ years old baseline (placebo-adjusted) • 3+ years post-menopause EB613 0.5 mg QD at Month 3 • Low bone mass EB613 1.0 mg QD Secondary Endpoints • High risk; no prior fracture Screen
Slide 5: EB613 Increased Bone Formation (PINP) and Decreased Bone Resorption (CTX)
EB613 Increased Bone Formation (PINP) and Decreased Bone Resorption (CTX) EB613 2.5 mg 50 40 p<0.001 Mean % Change from Baseline 30 20 p<0.005 p<0.05 PINP 10 0 Anabolic window -10 -20 CTX -30 p<0.01 0 1 2 3 4 5 6 Time (months) PINP, serum N-terminal propeptide of Type 1 collagen; CTX, serum crosslin
Slide 6: EB613 Increased BMD from Baseline to Month 6 at All Measured Skeletal Sites
EB613 Increased BMD from Baseline to Month 6 at All Measured Skeletal Sites BMD Change from Baseline to Month 6 3 * 2.57 Placebo EB613 2.5 mg Mean % Change from Baseline 2.5 * 1.98 2 † 1.5 1.34 1 0.5 0 -0.5 -0.16 -0.50 -1 -0.78 Lumbar Spine Femoral Neck Total Hip EB613 vs baseline: * p-value = 0.01;
Slide 7: Objective of Current Study
Objective of Current Study Characterize effects of EB613 on trabecular & cortical bone of the proximal femur using 3D-DXA modeling at 6 months 7
Slide 8: Methods
Methods ▪ All Phase 2 study subjects from the EB613 2.5 mg (n=21) and placebo (n=38) groups who had DXA scans of the proximal femur at baseline and 6 months were included ▪ 3D-DXA analyses were performed using 3D-Shaper® software to assess trabecular and cortical compartments ▪ For each parameter, %
Slide 9: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics EB613 2.5 mg Placebo Parameter (Mean, SD) (N = 21) (N= 38) Age 62.2 (4.5) 61.2 (5.4) Body mass index 26.6 (4.3) 25.3 (5.1) Baseline T-score Lumbar spine -2.2 (0.8) -2.3 (0.7) Total hip -1.9 (0.7) -2.0 (0.6) Femoral neck -2.2 (0.5) -2.1 (0.6) 9 Subgroup analy
Slide 10: Percentage Change from Baseline to Month 6 in aBMD by DXA and vBMD by 3D-Shaper
Percentage Change from Baseline to Month 6 in aBMD by DXA and vBMD by 3D-Shaper Placebo- Group EB613 Placebo Parameter adjusted Difference (N = 21) (N = 38) (Mean % Change, SD) % change p-value Areal BMD Total hip 1.4 (2.7) -0.5 (2.8) 1.8 <0.01 Femoral neck 1.9 (2.5) -0.7 (3.9) 2.6 <0.01 Integral vB
Slide 11: Percentage Change to Month 6 in Selected Cortical Parameters by 3D-Shaper
Percentage Change from Baseline to Month 6 in Selected Cortical Parameters by 3D-Shaper Placebo- Group EB613 Placebo Parameter adjusted Difference (N = 21) (N = 38) (Mean % Change, SD) % change p-value Cortical vBMD Total hip 0.4 (4.3) 0.0 (3.4) 0.4 0.36 Femoral neck 0.6 (3.7) -0.1 (3.2) 0.7 0.21 Co
Slide 12: Distribution of Average Cortical Surface BMD % Change from Baseline to Month 6
Distribution of Average Cortical Surface BMD % Change from Baseline to Month 6 Placebo (N = 38) EB613 (N = 21) Posterior View Anterior View Posterior View Anterior View 12 Cortical sBMD (mg/cm2) is calculated as the multiplication of the cortical thickness and the cortical volumetric BMD
Slide 13: Summary
Summary ▪ 6 months of treatment with EB613 showed evidence of an early effect on both trabecular and cortical bone of the proximal femur ▪ Findings are consistent with the dual mechanism of increased bone formation and decreased resorption ▪ Safety and efficacy of EB613 will be further evaluated in
Slide 14: We thank the investigators and study subjects for their participation
We thank the investigators and study subjects for their participation 14