Bridgebio Pharma, Inc. · NASDAQ:BBIO
Bridgebio Pharma — Investor Presentation (March 2021)
28 slides from Bridgebio Pharma's investor presentation, Mar 22, 2021
Slide 1: Encaleret Proof-of-Concept in ADH1
Encaleret Proof-of- Concept in ADH1 March 2021
Slide 2: Forward-Looking Statements and Disclaimer
Forward-Looking Statements and Disclaimer Statements in this Presentation that are not statements of historical fact are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such fo
Slide 3: Encaleret in ADH1 is the first of four major clinical data readouts in 2021
Encaleret in ADH1 is the first of four major clinical data readouts for BridgeBio in 2021 Q4 / Q1 Value to patients and shareholders CAH: Ph1 data Goal: Endogenous cortisol of 5 ug/dL or above Q4 Achon: Ph2 data Q4 Goal: >1.3 cm/yr increase from baseline Q1 ATTR: Ph3 data in growth velocity Goal: >5
Slide 4: Encaleret for autosomal dominant hypocalcemia type 1 (ADH1) overview
Encaleret for autosomal dominant hypocalcemia type 1 (ADH1) overview ADH1 overview Prevalence Genetic driver Pathophysiology 12K individuals harboring Calcium-sensing receptor Decreased blood calcium, variants in US1 (CaSR) hyperactivation elevated urine calcium, and lower parathyroid hormone secret
Slide 5: ADH1 Overview
ADH1 Overview Phase 2 Clinical Study Update Program Next Steps Alexis and Jackson ADH1 patients 5
Slide 6: Encaleret is designed to treat ADH1 at its source by normalizing CaSR sensitivity
Encaleret is designed to treat ADH1 at its source by normalizing CaSR sensitivity CaSR senses and regulates Hyperactive CaSR causes Acute symptoms and blood Ca levels dysregulation of Ca homeostasis long-term complications Presenting symptoms Ca2+ Decreased blood Hypocalcemic seizures calcium ADH1 d
Slide 7: Current therapy for ADH1 raises blood Ca but does not address disease mechanism
Current therapy for ADH1 (oral calcium, activated Vitamin D) raises blood Ca but does not address disease mechanism; increases UCa, suppresses PTH Without supplementation Summary of key disease measures in ADH1 patients with and without supplementation With supplementation Blood calcium Urine calciu
Slide 8: CaSR antagonists increase PTH secretion and renal calcium reabsorption
CaSR antagonists increase PTH secretion and renal calcium reabsorption Parathyroid cell CaSR Renal tubule Antagonist PTH CaSR Urine Plasma PTH Gaq + Gai CaSR Antagonist CaSR PTH mRNA PTH Gene Mg2+ + - Ca2+ Na+ Nucleus Antagonizing CaSR increases PTH synthesis and Antagonizing CaSR increases renal ca
Slide 9: Encaleret proof of mechanism in a mouse model of ADH1 and in humans with wild-type CaSR
Encaleret proof of mechanism in a mouse model of ADH1 and in humans with wild-type CaSR Encaleret normalized blood and urine calcium in the Encaleret was well-tolerated except for increased blood ADH1 (CaSRv knock-in) mouse1 calcium in osteoporosis patients2,3 11.0 Baseline Month 6 Blood Calcium (mg
Slide 10: Phase 2b study will continue as we plan the Phase 3 study
Phase 2b study will continue as we plan the Phase 3 study Complete Ongoing Phase 2b Period 1 Phase 2b Period 2 Phase 2b Period 3 Individualized dose escalation Individualized dose adjustment Outpatient extension 5 days, inpatient 5 days, inpatient 6 months, outpatient (N=6) (N=11-16) (N=11-16) Progr
Slide 11: Phase 2 Clinical Study Update
ADH1 Overview Phase 2 Clinical Study Update Program Next Steps Alexis and Jackson ADH1 patients 11
Slide 12: Presenter's Disclosures
Presenter’s Disclosures The NIDCR receives/received research funding from two BridgeBio affiliates: • QED for research in Tumor-induced Osteomalacia • Calcilytix for research in ADH1 12
Slide 13: Case: 40-year-old man with ADH1
Case • 40-year-old man • Tetany as a newborn, seizures at age 4-5 years, muscle cramps, paresthesia – no evaluation or treatment • Diagnosed with idiopathic hypoparathyroidism at age 24 – started on calcium/calcitriol plus intermittent hydrochlorothiazide • Came to NIH in 2010 to participate in a PT
Slide 14: While on PTH 1-34 replacement, patient developed significant nephrocalcinosis
While on PTH 1-34 replacement, patient developed significant nephrocalcinosis Baseline One year of PTH 1-34 BID Normal kidney ultrasound Medullary nephrocalcinosis Both conventional therapy and PTH 1-34 BID were inadequate in managing his hypocalcemia and hypercalciuria or preventing renal morbidity
Slide 15: Case: now aged 50 years
Case • Now aged 50 years • Treated with PTH 1-34 for almost 5 years, resumed conventional therapy in 2015 • Returned to NIH in 2020 to participate in the encaleret trial 1 year of PTH1-34 Pre-encaleret Pre-PTH 1-34 BID (Oct 2020) Corrected Ca (mg/dL) (8.4-10.2) 7.5 8 7.9 Intact PTH (pg/mL) (15-65) <
Slide 16: Period 1 Schema
Period 1 Schema Admission Day Dose Escalation Screening Visit Day -1 Day1 Day2 Day3 Day4 Day5 Day 6 Period 1 | Up to | Up to | j i i 30 Pto upto | x x Cohort 1 Locallab _. Discontinue mg 90 mg 480 mg! mg : Xmg Discharge assessments Calcitriol QD \ ; BID , BID (n=6) : QD: QD: Objectives: Safety and t
Slide 17: Baseline characteristics
Baseline characteristics Encaleret Characteristic Normal Range N=6 Age, mean (range) 40 (22-60) Female, n (%) 3 (50%) Nephrocalcinosis, n (%) 4 (67%) ECG QTcB (msec) 452 ± 9 < 440 Corrected Calcium (mg/dL)* 7.6 ± 0.6 8.4 –10.2 Intact PTH (pg/mL)* 3.4 ± 4.5 15 – 65 Phosphate (mg/dL)* 4.5 ± 0.7 2.5 –
Slide 18: Encaleret was generally well-tolerated with no serious adverse events reported after 5 days
Encaleret was generally well-tolerated with no serious adverse events reported after 5 days N=6 Number of subjects experiencing any Serious Adverse Event 0 (0%) Number of subjects experiencing any Adverse Event 5 (83%) Mild 5 (83%) Moderate 0 (0%) Severe 0 (0%) Number of Adverse Events Reported 9 Mi
Slide 19: Dose dependent increases in PTH mirrored encaleret levels
Dose dependent-increases in PTH mirrored encaleret levels Plasma Encaleret (μm) 8 30 90 180 180 180 180 180 * mg mg mg mg mg mg mg 6 4 2 0 250 iPTH (pg/mL) 200 150 100 ULN 50 LLN 0 Day 1 Day 2 Day 3 Day 4 Day 5 19 Data shown as mean ± SD. *One subject reduced second dose on Day 5 to 120 mg. Dashed l
Slide 20: Encaleret normalized blood and urine calcium
Encaleret normalized blood and urine calcium 30 90 180 180 180 180 180 * Blood cCa (mg/dL) 11 mg mg mg mg mg mg mg ULN 10 9 LLN 8 7 6 Urine Ca (mg/24 h) 1200 800 400 ULN 0 Day 1 Day 2 Day 3 Day 4 Day 5 Data shown as mean ± SD. Values below limit of assay quantitation were marked as “0”. *One subject
Slide 21: Encaleret reduced blood phosphate
Encaleret reduced blood phosphate 30 90 180 180 180 180 180 * mg mg mg mg mg mg mg 6 Phosphate (mg/dL) 5 4 3 2 1 0 Day 1 Day 2 Day 3 Day 4 Day 5 Additional findings: • Blood magnesium normalized • Baseline prolonged QTcB normalized on Day 5 21 Data shown as mean ± SD. *One subject reduced second dos
Slide 22: Individual and mean responses on Day 1 and 5 of Period 1
Individual and mean responses on Day 1 and 5 of Period 1 Baseline Value (Day 1) Mean Value (Day 5) Blood calcium Urine calcium Blood parathyroid hormone mg/dL mg/day pg/mL 11 1000 120 10 800 90 9 600 60 8 400 30 7 200 6 0 † 0 All Subjects Average All Subjects * Average All Subjects * Average *Values
Slide 23: Back to our case's individual response
Back to our case’s individual response 10.5 400 10.0 Urine Calcium 9.5 (mg/24 hour) Blood cCa 300 9.0 (mg/dL) 8.5 200 8.0 7.5 7.0 100 6.5 6.0 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 1 Day 2 Day 3 Day 4 Day 5 5.5 75 Phosphate 4.5 (mg/dL) Blood (pg/mL) 50 iPTH 3.5 25 2.5 0 1.5 Day 1 Day 2 Day 3 Day 4 Day
Slide 24: Conclusions
Conclusions • Encaleret was well-tolerated when administered in escalating oral doses once or twice daily over 5 days, with no serious adverse events reported and no adverse events of moderate or severe intensity • Blood calcium, PTH, and phosphate were normalized and maintained within the normal ra
Slide 25: Acknowledgements
Acknowledgements Sincere thanks to the patients, investigators, referring physicians, clinical research staff, Calcilytix employees, and collaborating research partners participating in the study. This study was supported by a public/private partnership between the NIDCR Intramural Research Program
Slide 26: Program Next Steps
ADH1 Overview Phase 2 Clinical Study Update Program Next Steps Alexis and Jackson ADH1 patients 26
Slide 27: Next steps for encaleret include generating further evidence in ongoing Phase 2b study
Next steps for encaleret include generating further evidence in ongoing Phase 2b study Planned activities ✓ Initiate Phase 2b study in ADH1 2020 ▪ Phase 3 registrational study in ADH1 ✓ Receive ODD from FDA for ADH ▪ Pediatric development program in ADH1 ▪ Evaluation of encaleret in non-genetic ✓ Re
Slide 28: Questions and Answers
brdaal . briagebio Questions and Answers
BridgeBio Pharma — Investor Presentation (March 2021) on 6ix