Biocryst Pharmaceuticals, Inc. · NASDAQ:BCRX

Biocryst Pharmaceuticals — Technical Presentation (November 2012)

15 slides from Biocryst Pharmaceuticals's technical presentation, Nov 12, 2012

  1. Slide 1: Effect of BCX4208 (Ulodesine) Add-on Therapy to Allopurinol 300 mg on Plasma Hypoxanthine and Xanthine

    Effect of BCX4208 (Ulodesine) Add-on Therapy to Allopurinol 300 mg on Plasma Hypoxanthine and Xanthine Concentrations in Gout Patients Shanta Bantia, Leigh Harman, Cynthia Parker, Damon Papac, Andreas Maetzel, Brian Taubenheim, Alan S. Hollister November 12, 2012

  2. Slide 2: Background: BCX4208 (Ulodesine)

    Background: BCX4208 (Ulodesine)  Purine nucleoside phosphorylase (PNP) Ulodesine inhibitor  Ulodesine is currently in clinical trials for Gout  PNP inhibitors form a new class of therapy for Gout − Oral, once daily dosing − T1/2 steady state: 17h PNP IC50 = 0.0005 µM − Clearance: renal 2 © BioCry

  3. Slide 3: Background: Ulodesine's mechanism of action

    Background: Ulodesine’s mechanism of action  Inhibition of PNP reduces serum uric acid , hypoxanthine and xanthine Purine nucleotide metabolism (deoxy) Inosine (deoxy) Guanosine PNP inhibitor: Ulodesine Hypoxanthine Guanine XO inhibitors: Xanthine allopurinol, febuxostat Inhibitory Uric acid effect

  4. Slide 4: Ulodesine has a dose-dependent effect on reducing serum uric acid as a monotherapy

    Background: Ulodesine has a dose-dependent effect on reducing serum uric acid as a monotherapy Study 201: Ulodesine monotherapy in patients with gout1 20 % change in sUA from baseline 0 -20 (mean) -40 -60 -80 1 8 15 22 29 36 43 50 Days 1.Fitz-Patrick D, Drummond W, Pappas J, Hollister A. Effects of

  5. Slide 5: Ulodesine has a synergistic effect in lowering serum uric acid in combination with allopurinol

    Background: Ulodesine has a synergistic effect in lowering serum uric acid in combination with allopurinol Study 202: Ulodesine in combination with allopurinol in gout patients1 Ulodesine dose (mg/d) 1. Hollister A, Becker M, Terkeltaub R, Waugh A, Lyman S, Flynt A, Fitz-Patrick D. BCX4208 Shows Syn

  6. Slide 6: Role of plasma hypoxanthine and xanthine in gout

    Background: Role of plasma hypoxanthine and xanthine in gout  Plasma xanthine (X) & hypoxanthine (HX) concentrations are significantly higher in untreated gout patients compared to hyperuricemic and normal subjects1.  Kidney stones, as observed in xanthine-oxidase Elevated deficient patients and m

  7. Slide 7: Role of plasma hypoxanthine and xanthine in gout

    Background: Role of plasma hypoxanthine and xanthine in gout  Xanthine-Oxidoreductase (XOR) knock-out mice demonstrate accumulation of crystals in renal tubules and increase in triglycerides1 1: Ohtsubo T, et al Hypertension 2009;54;868-876; 7 © BioCryst Pharmaceuticals, Inc.

  8. Slide 8: Method: Stability of xanthine & hypoxanthine in whole blood

    Method: Stability of xanthine & hypoxanthine in whole blood  Study in 3 healthy donors (volunteers)  Blood collected into heparin tubes with or without BCX-34 (PNP inhibitor) − Incubated for 0, 1, 2, 4 hrs at room temperature and centrifuged to collect plasma − Plasma samples were immediately froz

  9. Slide 9: Results: Stability of xanthine & hypoxanthine in whole blood

    Results: Stability of xanthine & hypoxanthine in whole blood  Xanthine and Hypoxanthine increase rapidly in whole blood left at room temperature  PNP inhibitor, BCX-34, prevents the breakdown of purine nucleosides in whole blood kept at room temperature  These results explain the large variabilit

  10. Slide 10: Methods: Study 203 evaluated ulodesine added on to allopurinol in inadequate responders

    Methods: Study 203 evaluated ulodesine added on to allopurinol in allopurinol inadequate responders  1o endpoint: % patients with serum uric acid (sUA) < 6mg/dL at week 12, with 24- week and 52-week extension Study 203: design Day 1 week 12 week 24 week 52 Randomized1 n=279 n=160 n=119 n=81 Pbo All

  11. Slide 11: Methods: Plasma xanthine and hypoxanthine levels in Phase 2b

    Methods: Plasma xanthine and hypoxanthine levels in Phase 2b  Blood samples collected at baseline and week 12 into heparin tubes containing BCX- 34 (PNP inhibitor) − Processed within 1hr to prevent purine metabolism  LC/MS/MS to quantitate plasma xanthine (X) and hypoxanthine (HX) levels  Cold la

  12. Slide 12: Gout patients on allopurinol demonstrate high levels of plasma xanthine and hypoxanthine

    Gout patients on allopurinol treatment demonstrate high levels of plasma xanthine and hypoxanthine levels Baseline xanthine and hypoxanthine levels Population Xanthine Hypoxanthine Studied (ng/ml) (ng/ml) Healthy volunteers 56 ± 13 < 25 (n = 10) Gout patients* 500 ± 408 301 ± 293 (203 study; n = 275

  13. Slide 13: Results: Ulodesine produced dose dependent decrease in plasma xanthine levels

    Results: Ulodesine added on to allopurinol produced dose dependant decrease in plasma xanthine levels Plasma xanthine, change from baseline After 12 Weeks of Treatment Xanthine, change from baseline 200 ng/mL (LSM + SEM) 100 0 -100 * -200 ** *P< 0.005, **P < 0.001 vs. placebo ** -300 n= 36 - 41 ** 0

  14. Slide 14: Results: Ulodesine produced dose dependent decrease in plasma hypoxanthine levels

    Results: Ulodesine added on to allopurinol produced dose dependant decrease in plasma hypoxanthine levels Plasma hypoxanthine, change from baseline after 12 weeks of treatment 0 Hypoxanthine, change from baseline -50 ng/mL (LSM + SEM) -100 -150 -200 -250 * *P< 0.005 vs. placebo n= 36 - 41 * -300 0 5

  15. Slide 15: Summary

    Summary  Ongoing purine metabolism in whole blood left at room temperature renders incorrect estimates of xanthine & hypoxanthine levels − This finding explains the variability of xanthine and hypoxanthine levels reported in the literature − Spiking collection tubes with PNP-inhibitor (BCX-34) is n

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