Slide 1: Six-month Phase 2 Study of Oral PTH in Postmenopausal Women With Low Bone Mass
\ ~ A Six-month Phase 2 Study of Ordl, PTH in Postmenopausal Wome With Low npone Mass - a) Hee ne Mineral, ‘Ne ASBMR 2021 Annual Meeting o # > C ~ ——- Entera
Slide 2: Co-Authors and Affiliations
Co-Authors and Affiliations Liana Tripto-Shkolnik - Chaim Sheba Medical Center, Israel Auryan Szalat - Hadassah Medical Center, Israel Gloria Tsvetov - Rabin Medical Center, Israel Vanessa Rouach - Tel Aviv Sourasky Medical Center, Israel Chana Sternberg - Chana Sternberg Consultancy Ltd., Israel Ph
Slide 3: Background
Background ▪ Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue that leads to decreased bone strength and increased risk of fracture ▪ Teriparatide [hPTH(1-34)] for injection (Forteo®) is an osteoanabolic treatment that reduces the risk of vertebral fr
Slide 4: Background: EBP05 oral formulation pharmacokinetics
Background ▪ EBP05 is an oral formulation of hPTH(1-34), based on the proprietary drug delivery technology which promotes enteric absorption and stabilizes the teriparatide in the gastrointestinal tract Pharmacokinetics of 1.5mg oral PTH(1-34) formulation (EBP05) and of Forteo® 20ug in healthy volun
Slide 5: Study Design
Study Design ▪ A Phase 2, 6-month, randomized, dose-ranging, placebo-controlled study ▪ Conducted at 4 sites in Israel between June 2019 and May 2021 Screening Endpoints Key inclusion criteria ▪ >50 yr old and >3+ yr Primary – at 3 months post menopause ▪ Serum P1NP change from baseline at 3 ▪ BMD T
Slide 6: Study Design: Randomization and Treatment Arms
Study Design ▪ A Phase 2, 6-month, randomized, dose-ranging, placebo-controlled study ▪ Conducted at 4 sites in Israel between June 2019 and May 2021 Treatment – Oral PTH Arm 1: Placebo tablets QD Randomization N=161 Arm 2: 0.5 mg * Arm 3: 1.0 mg * Arm 4: 1.5 mg QD Arm 5: 2.5 mg QD * ** Arm 6: 2.5mg
Slide 7: Demographics & Baseline T-Scores
Demographics & Baseline T-Scores EBP05 EBP05 EBP05 EBP05 EBP05 Placebo 0.5 mg QD 1.0 mg QD 1.5 mg QD 2.5 mg QD 2.5 mg titrated (N=43) (N=25) (N=29) (N=28) (N=19) QD (N=17) Age Mean 59.9 61.2 62.4 61.4 62.4 61.9 (years) (SD) (5.1) (6.0) (4.7) (6.5) (4.1) (5.3) Weight Mean 65.6 68.7 65.9 65.2 70.0 65.
Slide 8: 6 Months BMD Results: Lumbar Spine
6 Months BMD Results ▪ Oral PTH produced a statistically significant dose response in lumbar spine BMD (p<0.0001) LS BMD 4 Difference versus Placebo ** * p <0.008 ** p <0.002 3 * % change from Day 1 2 1 0 -1 -2 Placebo PTH 0.5 mg PTH 1 mg PTH 1.5 mg PTH 2.5 mg 8
Slide 9: 6 Months BMD Results: Femoral Neck and Total Hip
6 Months BMD Results ▪ Oral PTH produced a statistically significant dose response in femoral neck (FN) (p<0.002) and total hip (TH)(p<0.008) BMD ▪ Oral PTH 2.5 mg produced a placebo-adjusted 2.76% increase in FN (p<0.002), and a 1.84% increase in TH BMD (p<0.02) at 6 months Femoral Neck BMD Total H
Slide 10: 6 Months BMD Results: 2.5 mg Dose
6 Months BMD Results ▪ There were placebo adjusted increases in BMD at the lumbar spine (3.78%), total hip (1.38%), and femoral neck (2.42%) at 6 months, in subjects treated for 6 months with 2.5 mg PTH. BMD Percent Change from Baseline at Month 6 with Daily Oral hPTH(1-34) 2.5 mg (Mean and SE) 6 6
Slide 11: 6 Months BMD - 2.5 Titrated vs Non-Titrated
6 Months BMD - 2.5 Titrated vs Non-Titrated Placebo adjusted LS BMD 6 Historical data (Leder BZ et.al. JCEM 2015) % change from Day 1 5 4 1.6% Placebo vs 5.5% Teriparatide 3 2 Difference = 3.9% 1 0 PTH 2.5mg Titrated PTH 2.5mg Non-Titrated Placebo adjusted FN BMD 4 % change from Day 1 3 2 1 0 0.8% P
Slide 12: 6 Months Bone Markers Results
6 Months Bone Markers Results ▪ In the 2.5 mg PTH group, Serum CTX decreased 21% from baseline at 6 months (p <0.01) while P1NP was unchanged Change in Bone Markers - 2.5mg PTH 50 40 P1NP sCTX 30 % change from baseline 20 10 0 0 1 2 3 4 5 6 -10 -20 -30 Time (months) * Biomarker data for Months 1-3 p
Slide 13: Safety Results
Safety Results ▪ The safety profile of oral PTH was consistent with the known profile of subcutaneous PTH ▪ AEs commonly attributed to vasodilatation with subcutaneous PTH were observed - headache, nausea, presyncope and dizziness*. ▪ There were no serious drug-related AEs ▪ Mean serum calcium and c
Slide 14: Conclusions
Conclusions In this study of postmenopausal women with osteoporosis or low BMD, Six months of treatment with oral PTH 2.5 mg: • Increased lumbar spine, femoral neck and total hip BMD compared to placebo, and compared to start of treatment • The increase in spine BMD was similar in magnitude to that
Slide 15: Plans for Future Studies of Oral PTH
Plans for Future Studies of Oral PTH ▪ Based on the results of this phase 2 dose ranging study Entera is preparing for a 1-year phase 3, head-to-head comparison study of Oral PTH versus Forteo in 2022 ▪ The six-month increases in BMD with the 2.5 mg dose position EBP05, Entera’s oral hPTH(1-34), as