Krystal Biotech, Inc. · NASDAQ:KRYS

Krystal Biotech — North American Cystic Fibrosis Conference (NACFC) 2022

14 slides from Krystal Biotech's conference presentation, Nov 3, 2022

  1. Slide 1: Respiratory cell-type affinity and absolute CFTR expression in the primate airway upon nebulization of KB407

    Respiratory cell-type affinity and absolute CFTR expression in the primate airway upon nebulization of KB407 T r e v o r P a r r y , S a r a A r t u s i , J o r g e G u z m a n - L e p e , M a r y J a n e D u e r m e y e r , S u m a K r i s h n a n K r y s t a l B i o t e c h , I n c .

  2. Slide 2: Disclosures

    Krystal | 2 T. Parry, S. Artusi, J. Guzman-Lepe, M. Duermeyer and S. Krishnan are employees of, and have equity interest in, Krystal Biotech, Inc. Disclosures

  3. Slide 3: Cystic Fibrosis: Significant Unmet Need Despite Recent Approvals

    Krystal | 3 Cystic Fibrosis: Significant Unmet Need Despite Recent Approvals Approximately 10% of CF patients have mutations that are not amenable to current small molecule approaches Cystic Fibrosis  Known as a life-threatening inherited disease, with an incidence of ~1/2,500 live births, affectin

  4. Slide 4: KB407: A Differentiated Vector

    Krystal | 4 KB407: A Differentiated Vector An investigational inhaled gene therapy designed with the ability to redose HSV-1 In vivo dosing Yes Potential baseline neutralizing immunity No Repeat-dose capabilities Yes Carrying capacity ≥30 kb Integrates payload into host cell DNA No Efficiency of del

  5. Slide 5: KB407 Corrected CFTR Defect in 3D Patient-Derived Intestinal Organoids

    Krystal | 5  In healthy patient derived organoids (PDOs, top left), CFTR protein functions properly and enables water transport across the membrane leading to plump, round appearing PDOs  In PDOs derived from CF patients (bottom left, center, and right), CFTR does not work properly and water is no

  6. Slide 6: Nebulized KB407 in Nonhuman Primates (NHPs)

    Krystal | 6 Nebulized KB407 in Nonhuman Primates (NHPs) Repeat doses of KB407 well tolerated and broadly distributed throughout lung tissue in NHPs  No abnormal cage-side of clinical observations  No changes in food consumption, bodyweight, or behavior during dosing period  KB407 was distributed

  7. Slide 7: KB407 Repeat Dose (Weekly) GLP Toxicology Study in NHPs

    Krystal | 7 KB407 Repeat Dose (Weekly) GLP Toxicology Study in NHPs Study Design Group n Duration of Exposure (minutes) Avg. Dose Deposited in Lungs (PFU/administration) Dosing Days Necropsy Days Air 6 90 - 1, 8, 15 16 Vehicle 10 90 - 1, 8, 15 16, 43 Low Dose KB407 10 18 1.81x108 (male) 1, 8, 15 16,

  8. Slide 8: KB407 Cell-Type Affinity in NHP Lungs: Ciliated cells

    Krystal | 8 KB407 Cell-Type Affinity in NHP Lungs Ciliated cells (AC-Tubulin+), 24-hours after last dose administered (Day 16 of GLP toxicology study) 1. Okuda, K. et al. Am J Respir Crit Care Med. 2021 203(10): 1275-1289. GLP, good laboratory practice; NHP, nonhuman primate.  A majority of KB407-p

  9. Slide 9: KB407 Cell-Type Affinity in NHP Lungs: Club cells

    Krystal | 9 KB407 Cell-Type Affinity in NHP Lungs Club cells (SCGB1A1+), 24-hours after last dose administered (Day 16 of GLP toxicology study) GLP, good laboratory practice; NHP, nonhuman primate.  KB407-positive club cells identified in the airways of NHPs after repeated nebulization 17.4% (38/21

  10. Slide 10: KB407 Cell-Type Affinity in NHP Lungs: Goblet cells

    Krystal | 10 KB407 Cell-Type Affinity in NHP Lungs Goblet cells (MUC5AC+), 24-hours after last dose administered (Day 16 of GLP toxicology study)  KB407-positive goblet cells also observed in the airways of NHPs after repeated nebulization GLP, good laboratory practice; NHP, nonhuman primate. 8.0%

  11. Slide 11: KB407 Cell-Type Affinity in NHP Lungs: Macrophages

    Krystal | 11 KB407 Cell-Type Affinity in NHP Lungs Macrophages (CD163+), 24-hours after last dose administered (Day 16 of GLP toxicology study)  Significant majority of KB407-positive cells are CD163-negative  No significant colocalization of the viral and basal cell markers was detected, indicati

  12. Slide 12: KB407 Expresses Human CFTR ≥ Endogenous CFTR in NHP Lungs

    Krystal | 12 0.00E+00 5.00E+04 1.00E+05 1.50E+05 2.00E+05 2.50E+05 Right Cranial Right Caudal Right Caudal Lung Lobe Biopsy CF TR RN A co pi es /5 0n g to ta l R N A Absolute CFTR Transcription Human NHP KB407 Expresses Human CFTR ≥ Endogenous CFTR in NHP Lungs Absolute quantitation of exogenous hum

  13. Slide 13: Assessment of Inflammatory Induction in Human CF Cells

    Krystal | 13 Assessment of Inflammatory Induction in Human CF Cells No significant cytokine induction, even at MOI 10 and in presence of high levels of KB407-mediated CFTR expression, in CF colorectal epithelial cells 48 hours post-transduction IL-10, IL-12p70, IP-10, GM-CSF, IFN-λ1/2/3 also assesse

  14. Slide 14: Summary

    Krystal | 14 Summary  Expression and localization of CFTR in CF primary small airway cells  Post-translation glycosylation of CFTR protein  Functional correction in 3D organoid model  KB407 is stable after nebulization  KB407 expresses human CFTR in airways of mice and NHPs upon nebulization 

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