Bridgebio Pharma, Inc. · NASDAQ:BBIO
Bridgebio Pharma — Technical Presentation (June 2023)
16 slides from Bridgebio Pharma's technical presentation, Jun 17, 2023
Slide 1: Sustained Normalization of Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1
Sustained Normalization of Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1: Results from a Phase 2 Study Over 18 Months of Encaleret (CLTX-305) Treatment (NCT04581629) R I G a f n i , I R H a r t l e y, K L R o s z k o , E F N e m e t h , K A P o z o , A S M a t h e w, M S R o b e r t
Slide 2: Disclosures
Disclosures • This study was supported by a public/private partnership between the NIDCR Intramural Research Program and BridgeBio affiliate Calcilytix Therapeutics, Inc. • Encaleret is currently under clinical development, and its safety and efficacy have not been evaluated by any regulatory author
Slide 3: Blood calcium is maintained by four organs regulated by the CaSR and PTH
Blood calcium is maintained by four organs regulated by the CaSR and PTH Ca2+ = ionized calcium; PTH = parathyroid hormone; CaSR = calcium-sensing receptor 3
Slide 4: Activating variants in the CASR cause Autosomal Dominant Hypocalcemia (ADH1)
Activating variants in the CASR cause Autosomal Dominant Hypocalcemia (ADH1) Activating variants in the CASR Hyperactive CaSR causes Clinical Manifestations increase tissue sensitivity to Ca2+ dysregulation of Ca homeostasis Acute symptoms Parathyroid Hypocalcemic seizures Wild Decreased parathyroid
Slide 5: Encaleret, an investigational oral calcilytic, may be a potential treatment for ADH1
Encaleret, an investigational oral calcilytic, may be a potential treatment for ADH1 • Calcilytics are negative allosteric modulators of the CaSR that decrease CaSR sensitivity to extracellular calcium • Normalizing CaSR sensitivity could correct hypocalcemia, hypercalciuria, and low PTH in individu
Slide 6: Encaleret Phase 2B Study Design – CLTX-305-201
Encaleret Phase 2B Study Design – CLTX-305-201 Period 1 1 Period 2 1 Period 3 LTE Individualized dose Individualized dose Outpatient Long-term extension escalation titration extension (LTE) 5 days, inpatient (N=6) cv 5 days, inpatient (N=13) 24 weeks, outpatient cv (N=13) cv (N=12) Outpatient Month
Slide 7: Baseline Characteristics
Baseline Characteristics Characteristic Study Population (N = 13) Normal Range Age, mean, yr (range) 39 (22-60) Female, n (%) 8 (62%) Corrected Calcium1,2 (mg/dL) 7.1 ± 0.4 8.4 –10.2 Intact PTH (pg/mL) 6.3 ± 7.8 15 – 65 Phosphate (mg/dL) 4.5 ± 1.1 2.3 – 4.7 Magnesium (mg/dL) 1.7 ± 0.2 1.6 – 2.6 24h
Slide 8: Phase 2B Oral Encaleret Dosing Summary
Phase 2B Oral Encaleret Dosing Summary Period 3 (n=13) LTE (n=12) Optimized dose adjustments Maintenance dose Week 24 Mean: 172.0±140 mg/day Month 12 Mean: 150.8±132.6 mg/day Individual Patient Dosing 360 Encaleret sulfate dose (mg/day) 270 180 90 0 1 2 3 4 6 8 12 16 20 24 12 3 6 9 5 k k k k k k o o
Slide 9: Encaleret was well-tolerated with no serious adverse events reported
Encaleret was well-tolerated with no serious adverse events reported Periods 2 and 3 LTE N=13 N=13 Number of subjects experiencing any Serious Adverse 0 (0%) 0 (0%) Event Number of subjects experiencing any Adverse Event 13 (100%) 12 (92%) Mild 13 (100%) 12 (100%) Moderate 3 (23%) 4 (33%) Severe 0 0
Slide 10: Encaleret normalized mean iPTH and blood calcium over an 18-month period
Encaleret normalized mean iPTH and blood calcium over an 18-month period 100 75 ** (pg/mL) 50 iPTH 25 0 0 8 16 24 36 3 48 6 60 9 72 12 11 ** 10 Blood cCa (mg/dL) 9 8 7 6 0 8 16 24 36 3 48 6 60 9 72 12 Period 3 LTE Weeks Months Data reported as mean+SD. Values below limit of assay quantitation record
Slide 11: Encaleret decreased mean urine calcium into the normal range
Encaleret decreased mean urine calcium into the normal range 800 600 (mg/24 h) Urine Ca 400 ** 200 0 0 8 16 24 36 3 48 6 60 9 72 12 Period 3 LTE Weeks Months No progression of renal calcifications on ultrasound observed at Period 3 Week 24 or LTE Month 12 Data reported as mean+SD. Values below limit
Slide 12: Encaleret decreased mean blood phosphate and increased mean blood magnesium
Encaleret decreased mean blood phosphate and increased mean blood magnesium 6 5 ** Phosphate (mg/dL) 4 3 2 1 0 0 8 16 24 36 3 48 6 60 9 72 12 3 ** Magnesium 2 (mg/dL) 1 0 0 8 16 24 36 3 48 6 60 9 72 12 Period 3 LTE Weeks Months Data reported as mean+SD. Gray shading reflects normal range. The measur
Slide 13: Encaleret increased bone turnover markers
Encaleret increased bone turnover markers 5 CTX Relative to ULN 4 (CTX/ULN) 3 5/12 participants >1 2 at LTE Month 12 1 0 0 8 16 24 36 3 48 6 60 9 72 12 6 P1NP Relative to ULN 5 4 (P1NP/ULN) 3 4/12 participants >1 2 at LTE Month 12 1 0 0 8 16 24 3 36 6 48 9 60 12 72 Period 3 LTE Weeks Months CTX and
Slide 14: Encaleret had minimal short-term effects on bone density
Encaleret had minimal short-term effects on bone density Screening Period 3, Week 24 LTE, Month 12 DXA Anatomical Z-score Z-score Z-score Site Mean ± SD Mean ± SD Mean ± SD n = 11 (n = 11) (n = 11) (n = 10) Total Body 2.1 ± 1.4 2.0 ± 1.3 N/A AP Lumbar Spine 2.6 ± 1.5 2.3 ± 1.7 2.5 ± 1.7 Total Hip 2.
Slide 15: Summary
Summary • In patients with ADH1, encaleret administered twice daily for 18 months restored mineral homeostasis as demonstrated by: • Increase in PTH • Correction of hypocalcemia • Normalization of mean 24-hr urine calcium • Reduction in mean blood phosphate • Increase in mean blood magnesium • Bone
Slide 16: Acknowledgements
Acknowledgements Thanks to the patients, referring physicians, and the support staff at the National Institutes of Health 16
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