BridgeBio Pharma, Inc. · NASDAQ:BBIO

BridgeBio Pharma — Technical Presentation (July 2025)

16 slides from BridgeBio Pharma's technical presentation, Jul 14, 2025

  1. Slide 1: Sustained Normalization of Mineral Homeostasis in ADH1: Phase 2 Over 42 Months of Encaleret

    Sustained Normalization of Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1: Results from a Phase 2 Study Over 42 Months of Encaleret (CLTX-305) Treatment (NCT04581629) RI Gafni1, IR Hartley1, KL Roszko1, EF Nemeth2, KA Pozo1, REJ Meadows1, EA Ferguson1, AS Mathew3, MS Roberts3, SH Adle

  2. 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 authority.

  3. 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

  4. Slide 4: Activating variants in the CASR cause Autosomal Dominant Hypocalcemia Type 1 (ADH1)

    Activating variants in the CASR cause Autosomal Dominant Hypocalcemia Type 1 (ADH1) Activating variants in the CASR Hypersensitive CaSR causes Clinical Manifestations increase tissue sensitivity to Ca2+ dysregulation of Ca homeostasis Parathyroid Acute symptoms Wild PTH Secretion PTH Decreased PTH s

  5. 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 Parathyroid Kidney ▪ Encaleret is an investigational negative allosteric modulator of the ADH1 Wild type ADH1 Wild type CaSR that can decrease CaSR Ca2+ Excretion PTH Secretion sensitivity to extracellular calcium C

  6. 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 Individualized Outpatient Long-term dose escalation dose titration extension extension (LTE) 5 days, inpatient (N=6) 5 days, inpatient (N=13) 24 weeks, outpatient (N=13) Outpatient (N=12) Month 36 LTE Re

  7. 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

  8. Slide 8: Phase 2B Oral Encaleret Dosing Summary

    Phase 2B Oral Encaleret Dosing Summary Individual Patient Dosing Encaleret sulfate dose (mg/day) 360 Period 3 (n=13) Optimized dose adjustments 270 Week 24 Mean+SD: 172±140 mg/day 180 LTE (n=12) Maintenance dose 90 Month 36 Mean+SD: 151±133 mg/day 0 W 12 W 16 W 20 M 4 W 1 W 2 W 3 W 4 W 6 W k8 M 3 M

  9. Slide 9: Encaleret was overall well-tolerated

    Encaleret was overall well-tolerated Periods 2 and 3 LTE N=13 N=13 Number of subjects experiencing any Serious Adverse Event 0 (0%) 2 (15%) Post-operative right shoulder pain 1 Chest pain 1 Number of subjects experiencing any Treatment-Emergent 13 (100%) 13 (100%) Adverse Event (TEAE) Mild 13 (100%)

  10. Slide 10: Encaleret normalized mean iPTH and blood calcium over a 42-month period

    Encaleret normalized mean iPTH and blood calcium over a 42-month period 100 75 (pg/mL) iPTH 50 ** ** 25 0 0 8 16 24 48 6 72 12 96 18 120 24 144 30 168 36 11 10 Blood cCa ** ** (mg/dL) 9 8 7 6 0 8 16 24 48 6 72 12 96 18 24 120 30 144 168 36 Period 3 LTE Weeks Months Data reported as mean+SD. Values b

  11. Slide 11: Encaleret decreased mean urine calcium into the normal range with no change in eGFR

    Encaleret decreased mean urine calcium into the normal range with no change in eGFR over 42 months 800 (mg/24 h) Urine Ca 600 400 ** ** 200 0 0 8 16 24 6 48 12 72 18 96 24 120 30 144 36 168 (mL/min/1.73m²) 120 90 eGFR 60 30 0 0 8 16 24 48 6 72 12 96 18 120 24 30 144 168 36 Period 3 LTE Weeks Months

  12. 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 6 48 12 72 18 96 24 120 30 144 36 168 3 Magnesium ** ** (mg/dL) 2 1 0 0 8 16 24 48 6 72 12 96 18 120 24 144 30 168 36 Period 3 LTE Weeks Months Data reported as mean+SD. Gray sh

  13. Slide 13: Encaleret increased bone turnover markers

    Encaleret increased bone turnover markers CTX Relative to ULN 4 3 (CTX/ULN) ** ** 2 1 0 -1 0 8 16 24 6 48 12 72 18 96 24 120 30 144 36 168 P1NP Relative to ULN 4 3 ** ** (P1NP/ULN) 2 1 0 -1 0 8 16 24 48 6 72 12 18 96 120 24 144 30 168 36 Period 3 LTE Weeks Months Data reported as mean+SD after corre

  14. Slide 14: On encaleret, DXA Z-scores decreased at Month 24 but stabilized at Month 36

    On encaleret, DXA Z-scores decreased from baseline at all sites at Month 24 but stabilized at Month 36 6 6 AP Lumbar Spine Z-Score Whole Body Z-score 4 4 * * * * 2 2 0 0 0 24 12 72 18 96 24 120 30 144 36 168 0 24 12 72 18 96 24 120 30 144 36 168 -2 -2 -4 -4 6 6 1/3 Distal Radius Z-score * * * * Tota

  15. Slide 15: Summary

    Summary ▪ In patients with ADH1, encaleret administered twice daily rapidly corrects and maintains mineral homeostasis within the normal range, as demonstrated by: ✓ Increase in PTH ✓ Correction of hypocalcemia ✓ Normalization of mean 24-hr urine calcium ✓ Reduction in mean blood phosphate ✓ Increas

  16. 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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