Slide 1: PEARL-1 Durability Results
A GENE-BASED AESTHETICS COMPANY November 2022 1 PEARL-1 Durability Results
Slide 2: Forward Looking Statement
Forward Looking Statement 2 This presentation contains forward-looking statements that involve substantial risks and uncertainties. Any statements in this presentation about future expectations, plans and prospects for Krystal Biotech, Inc. and its wholly-owned subsidiary, Jeune Aesthetics, Inc. (co
Slide 3: Agenda
Agenda 3 1 Introduction • September Riharb, SVP, Jeune Aesthetics, Inc. 2 PEARL - 1 Durability Trial Results • Dr. Hubert Chen, SVP Clinical Development 5 Q&A 4 Next Steps / PEARL-2 Study • September Riharb, SVP, Jeune Aesthetics, Inc.
Slide 4: Introduction
a. | \ ~ “Lg = Nt A __Introduétion NA) |! iy a = —_— 7; A Oy JEUNE
Slide 5: Aging Skin is Caused by Declining Levels of Collagen and Elastin
Aging Skin is Caused by Declining Levels of Collagen and Elastin • Skin aging is caused, in part, by a reduction of the skin’s key proteins: collagen and elastin • Impaired collagen and elastin synthesis leads to the degradation of the extracellular matrix, affecting overall skin quality and functio
Slide 6: KB301 is Designed to Increase Production of Type III Collagen
KB301 is Designed to Increase Production of Type III Collagen 6 • Collagen 3 provides tensile strength, and influences other functions such as cell adhesion, migration, proliferation, and differentiation through its interaction with integrins, which are cell surface receptors1 1 Kim JK, Xu Y, Xu X,
Slide 7: KB301 Key Product Differentiation
KB301 Key Product Di f ferent ia t ion F e a t u r e B e n e f i t Novel MOA naturally produces patient’s own Collagen-3 Reduced wrinkles and improved skin quality attributes Applicable for all skin types Can be added to every patient’s skin care program Physician (injector) controlled placement Tar
Slide 8: KB301 Treatment Market Uptake Beyond the Current Aesthetic Market
Stage 1: Aging Skin Concerns Non-Aesthetic Consumers KB301 Trea tment M a r ke t U p t a ke B eyo n d t h e C u r re n t A e s t h e t i c M a r ke t 8 Stage 2: Retinol and Sunscreen Usage Stage 3: Genetic Skin Rejuvenation with KB301 Treatments Stage 1: Aging Skin Concerns Despite Current Treatment
Slide 9: Improvement in Skin Quality has Potential Beyond the Face
Photo rejuvenation Botulinum toxin Hyaluronic acid Micro-ablative resurfacing / Full field ablative Chemical Peel Global Facial Rejuvenation Market1 $19B $44B 2019 by 2026 Global Skincare Devices Market2 $18B $50B 2018 by 2028 Trunk Chest / décolletage Neck (1) Hands Knee / legs Knee / legs Sign
Slide 10: Robust Pipeline Addresses Multiple Aspects of Skin Quality
Robust P ipe l ine Addresses Mul t ip le Aspects o f Sk in Qual i ty 10 PROGRAM INDICATION GENE PRE-CLINICAL CLINICAL KB301 Improved Skin Quality Attributes type III collagen (COL3) KB303 TBD elastin (ELN) KB302 TBD COL3 + ELN KB304 TBD Type 1 collagen (COL1) KB305 TBD type IV collagen (COL4)
Slide 11: KB301 Leverages Experience with Vector and Manufacturing Infrastructure
KB301 Leverages Experience with Vector and Manufacturing Infrastructure • KB301 uses same HSV-1 vector backbone as B-VEC, Krystal’s rare skin disease product currently under FDA review for licensure • Preclinical and clinical data generated for B-VEC, as well as manufacturing infrastructure, de-risk
Slide 12: KB301
KB301 12
Slide 13: PEARL-1: KB301 Phase 1 Program Overview
PEARL-1: KB301 Phase 1 Program Overview Safety (Cohort 1/1a) 13 Efficacy (Cohort 2) Durability (Cohort 2E) Objectives • Establish preliminary safety • Evaluate for COL3A1 transgene expression Design • Open-label treatment of buttocks • Skin biopsies Objectives • Demonstrate preliminary efficacy • Do
Slide 14: PEARL-1: Cohort 2 Efficacy Results
PEARL-1: Cohort 2 Efficacy Results 14 Difference in Mean Change from Baseline between High Dose KB301 and Placebo is Clinically Meaningful 0.8 0.6 0.8 0.8 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Visit 5 Visit 6 M EA N C HA N G E FR O M B AS EL IN E Subject Satisfaction Score - Below the Zygomati
Slide 15: PEARL-1: Cohort Extension Study for Assessment of Durability
PEARL-1: Cohort 2 Extension Study for Assessment of Durability 15 • 9 subjects not eligible (received low dose) • 4 subjects did not enroll N = 7 Subjects • Previously received high dose to one cheek and placebo to the other cheek and determined to be uneven N = 3 Subjects • Previously received high
Slide 16: Assessment of Durability in Cohort Extension
Assessment of Durability in Cohort 2 Extension 16 Visit 1 Month 1 Durability Assessed Month 2 Durability Assessed Month 3 Durability Assessed 1 month 1 month 1 month Visit 1Last Dose Cohort 2 5 to 6 months between last dose in Cohort 2 and first visit of Cohort 2E ~7 months after last dose Efficacy
Slide 17: Mean Change in Subject Satisfaction Scores during Cohort 2 Extension
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 Baseline (n=13) Visit 5 (n=13) Visit 6 (n=12) Month 1 (n=13) Month 2 (n=13) Month 3 (n=10) M ea n C ha ng e in S SS fr om B as el in e Change in Subject Satisfaction Score Mean Change in Subject Satisfaction Scores during Cohort 2 Extension 17 Cohort 2 (Efficacy
Slide 18: Sustained Treatment Response during Cohort 2 Extension
0 10 20 30 40 50 60 70 80 90 100 Month 1 (n=13) Month 2 (n=13) Month 3 (n=10) % o f R es po nd er s Ba se d on S SS Visit Subject Satisfaction Score Responders 2 point improvement or greater 1 point improvement 0 10 20 30 40 50 60 70 80 90 100 Month 1 (n=13) Month 2 (n=13) Month 3 (n=10) % o f C he
Slide 19: Lower Cheek Observation Arm: Baseline and Nine Month Extension Assessment
Lower Cheek Observation Arm: Cohort 2 Baseline and Nine Month Extension Assessment 19 Baseline 9 Months Subject Age: 65
Slide 20: Lower Cheek Observation Arm: Baseline and Nine Month Extension Assessment
Lower Cheek Observation Arm: Cohort 2 Baseline and Nine Month Extension Assessment 20 Baseline 9 Months Subject Age: 65
Slide 21: Lower Cheek Observation Arm: Baseline and Nine Month Extension Assessment
Lower Cheek Observation Arm: Cohort 2 Baseline and Nine Month Extension Assessment 21 Baseline 9 Months Subject Age: 61
Slide 22: Conclusions
22 • Results from open-label PEARL-1 Cohort 2 Extension demonstrate evidence of durable treatment response approximately 7, 8, and 9 months after last dose as indicated by: • Sustained change in Subject Satisfaction Scores compared to pre-treatment • Percent of responders by Subject Satisfaction Sco
Slide 23: Next Steps
| ‘N BZ Next Steps \Vt | eX JEUNE
Slide 24: Next Steps: PEARL-2 Study
Next Steps: PEARL-2 Study 24 • PEARL-2 study design is based on positive results from PEARL-1 Study and FDA guidance on KB301 fine lines and wrinkles scale • Study design will be a prospective, multicenter, randomized, double-blind, placebo-controlled study to assess improvement of fine lines in tar
Slide 25: Closing and Q&A
\ Closthg ant > Q&A JEUNE