Slide 1: Rare Respiratory Pipeline Interim Clinical Update
© Copyright 2024 Krystal Biotech, Inc. All rights reserved. Rare Respiratory Pipeline Interim Clinical Update December 2024
Slide 2: Forward Looking Statements and Disclosures
Krystal | 2 Forward Looking Statements and Disclosures Forward Looking Statements This presentation and the accompanying oral presentation that are collectively referred to as this presentation contain forward-looking statements that involve substantial risks and uncertainties. Any statements about
Slide 3: Krystal's HSV-1 Based Approach for Lung Gene Delivery
Krystal | 3 Krystal’s HSV-1 Based Approach for Lung Gene Delivery Developing redosable, non-invasive, inhaled gene therapies to address monogenic disorders of the lung Historical Challenges with Inhaled Gene Therapy1 Inhaled gene therapy has been explored for decades, with little success Focus t
Slide 4: KB408 in Development as Redosable, Non-Invasive, Inhaled Gene Therapy for AATD
Krystal | 4 1. Greene CM, et al. Nat Rev Dis Primers 2016;2:16051; 2. Brantly ML, et al. Int J Chron Obstruct Pulmon Dis. 2019;6:100–114; 3. Aboussouan LS, et al. Respir Med. 2009;103:335-341; 4. Stoller JK, et al. Int J Chron Obstruct Pulmon Dis. 2013;10:26-24; 5. Blanco I, et al. Int J Chron Obstr
Slide 5: Inhaled Candidate KB408 for AATD Lung Disease
Krystal | 5 AAT, alpha-1 antitrypsin; AATD, alpha-1 antitrypsin deficiency; GLP, good laboratory practices; HSV-1, herpes simplex virus 1; IND, investigational new drug; NOAEL, no observed adverse effect level ; SERPINA1, serpin family A member 1 Inhaled Candidate KB408 for AATD Lung Disease Genetic
Slide 6: KB408 Phase Study SERPENTINE-1
Krystal | 6 KB408 Phase 1 Study SERPENTINE-1 Open-label, single dose escalation study in adult patients with AATD with a PI*ZZ genotype Key Enrollment Criteria • Key Inclusion Criteria • Age ≥18 to ≤70 • PI*ZZ or Pi*ZNull genotype • Serum AAT < 11μM - Cohort 3b only • Key Exclusion Criteria • ppFEV1
Slide 7: Scope of First SERPENTINE-1 Interim Readout
Krystal | 7 Observation** D29D1-D3 D8 D15 D57 Scope of First SERPENTINE-1 Interim Readout Safety data from seven patients across two dose levels, and initial molecular data from two Cohort 2 patients Cohort 2 No Bronchoscopy 1010 PFU n = 2* Cohort 1 109 PFU n = 3* Cohort 2 Bronchoscopy 1010 PFU n =
Slide 8: Patient Demographics and Augmentation Therapy Status
Krystal | 8 Patient Demographics and Augmentation Therapy Status Study population predominantly elderly with variable augmentation therapy use, all Pi*ZZ genotype Cohort 2 No Bronchoscopy 1010 PFU n = 2* Cohort 1 109 PFU n = 3* Cohort 2 Bronchoscopy 1010 PFU n = 2* Safety Assessments Only Safety and
Slide 9: KB408 Well Tolerated in All Patients Dosed To Date
Krystal | 9 KB408 Well Tolerated in All Patients Dosed To Date No serious adverse events or dose-limiting toxicities observed All KB408-related adverse events reported have been mild-to-moderate and transient No evidence of significant neutralizing antibody response following KB408 administrat
Slide 10: Bronchoscopy Sampling Plan and Molecular Data in Interim Readout
Krystal | 10 Bronchoscopy Sampling Plan and Molecular Data in Interim Readout Multiple assessments conducted to mitigate inherent variability in sample collection across patients Cohort 2 Bronchoscopy Timing Tissue Biopsies Bronchial Brushings Bronchoalveolar Lavage Assessments Included in Int
Slide 11: Clear Evidence of Transduction and AAT Expression in KB408 Treated Lungs
Krystal | 11 H&E DAPI AAT Merge CAS CAS CAS Baseline After KB408 Clear Evidence of Transduction and AAT Expression in KB408 Treated Lungs Patient 07, no background augmentation; clinically meaningful proportion of airway cells positive for AAT after single dose * Based on quantification of DAPI posi
Slide 12: Secreted AAT Reached Clinically Meaningful Levels after Single KB408 Dose
Krystal | 12 Secreted AAT Reached Clinically Meaningful Levels after Single KB408 Dose Patient 07, no background augmentation; increase in AAT to high nanomolar range supports further exploration of mid dose 1. Average values from 2 lobes (pre-dose samples). Only 1 post-dose sample was evaluable due
Slide 13: Clear Evidence of Transduction and AAT Expression in KB408 Treated Lungs (Patient 06)
Krystal | 13 Clear Evidence of Transduction and AAT Expression in KB408 Treated Lungs Patient 06, on background augmentation; also detected meaningful proportion of airway cells positive for AAT after single dose 35% AAT Positive Cells After Single KB408 Dose* 3% AAT Positive Cells at Baseline [Plac
Slide 14: Increased SERPINA1 in Brushings Consistent with KB408 Mechanism
Krystal | 14 Increased SERPINA1 in Brushings Consistent with KB408 Mechanism Lavages not successfully collected in Patient 06 but increased SERPINA1 levels provide further evidence of successful delivery 1 10 100 1000 10000 SERPINA1 RNA Copies SERPINA1 DNA Copies Average Copy Number SERPINA1 DNA and
Slide 15: Clear Evidence of Successful and Safe Gene Delivery with KB408
Krystal | 15 Clear Evidence of Successful and Safe Gene Delivery with KB408 Positive initial data supports acceleration of KB408 and has positive read-through implications for pipeline KB408 delivery via inhalation well tolerated at both dose levels tested to date Free AAT levels in ELF of
Slide 16: Cystic Fibrosis Disease Overview
Krystal | 16 Cystic Fibrosis Disease Overview A life-span shortening progressive disease of the lung 1. U.S. Cystic Fibrosis Foundation – About Cystic Fibrosis, accessible at: About Cystic Fibrosis | Cystic Fibrosis Foundation (cff.org); 2. U.S. Cystic Fibrosis Foundation – 2022 CFF Patient Registry
Slide 17: Target Segments for KB407
Krystal | 17 10K 19K 5K All 105K Target Segments for KB407 Patients ineligible for CFTR modulator therapy including CFTR null patients 10%+ of all CF patients11 Upside: Combination therapy or direct competition with TRIKAFTA if demonstrating superior dosing, efficacy, and/or safety+ Alternate regime
Slide 18: Robust Preclinical Data Package Supports Clinical Evaluation of KB407
Krystal | 18 CF, cystic fibrosis; CFF, Cystic Fibrosis Foundation; CFTR / CFTR, cystic fibrosis transmembrane conductance regulator; GLP, good laboratory practices; IND, investigational new drug; NHP, non-human primate; NOAEL, no observed adverse effect level; TDN, Therapeutic Development Network Ro
Slide 19: KB407 Phase 1 Study CORAL-1
Krystal | 19 Observation Cohort 3 n = 6 Cohort 2 n = 3 KB407 Cohort 1 n = 3 KB407 KB407 Phase 1 Study CORAL-1 Ongoing study to assess safety and transduction efficiency of ascending doses of KB407 in adults with CF Study Objectives • Evaluate safety and tolerability of ascending doses of nebulized K
Slide 20: Scope of CORAL-1 Interim Safety Data Update and Patient Demographics
Krystal | 20 Scope of CORAL-1 Interim Safety Data Update and Patient Demographics Safety data available from five patients dosed once or twice with KB407* *One patient rolled over from Cohort 1 to Cohort 2 Data cutoff date of December 6, 2024 CFTR / CFTR, cystic fibrosis transmembrane conductance re
Slide 21: KB407 Well Tolerated in All Patients Dosed To Date
Krystal | 21 KB407 Well Tolerated in All Patients Dosed To Date No serious adverse events or dose-limiting toxicities observed All KB407-related adverse events reported have been mild-to-moderate and transient No evidence of significant neutralizing antibody response following KB407 administra
Slide 22: Working Towards a Highly Differentiated Respiratory Franchise
Krystal | 22 Working Towards a Highly Differentiated Respiratory Franchise Safe delivery of genetic cargo in Phase 1 is a key derisking event for the platform with read-through to broader pipeline First direct clinical evidence of safe gene delivery using HSV-1 Well-tolerated by patient populati
Slide 23: Developing Genetic Medicines to Treat Diseases with High Unmet Medical Needs
Developing Genetic Medicines to Treat Diseases with High Unmet Medical Needs © Copyright 2024 Krystal Biotech, Inc. All rights reserved.