The Leader in Redosable Gene Therapy for Rare Disease Topline GEM-3 Trial Results Call © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Exhibit 99.2
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© Copyright 2021 Krystal Biotech, Inc. All rights reserved. Call Agenda Introductory Comments Krish Krishnan – Chairman and CEO Dystrophic Epidermolysis Bullosa Background Dr. Peter Marinkovich GEM-3 Results and Next Steps Suma Krishnan – Founder and COO Commercial Preparations Andy Orth – Chief Commercial Officer Q&A 1 2 3 4 5
Chairman and CEO Krish Krishnan © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Novel viral vector platform positively differentiated from other viral vector technologies Robust tropism to target cells of interest upon local administration Large payload capacity allows for delivery of two copies of large gene Immune evasive properties of proprietary vectors enables redosability 1 2 3 © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
GEM-3 results provide significant platform validation Engineered HSV-1 Vector Platform GEM-3 Study Confirms safety and efficacy of VYJUVEKTM* (beremagene geperpavec) for dystrophic EB Most advanced clinical application of platform Validates therapeutic vector in dermatologic applications Skin pipeline covers rare and aesthetic conditions (via wholly owned subsidiary Jeune Aesthetics) Potential to deliver diverse genetic cargo Validates therapeutic vector for broader redosable gene delivery Tropism to lung and additional types under exploration Potential to deliver diverse of genetic cargo with a variety of delivery mechanisms 1 2 3 Platform fully integrated from research to development to manufacturing to commercialization *VYJUVEK is the current proprietary name for beremagene geperpavec, formerly known as B-VEC © Copyright 2021 Krystal Biotech, Inc. All rights reserved. VYJUVEK is an investigational therapy being studied in clinical trials
Associate Professor of Dermatology at Stanford University Blistering Disease Clinic Director Dr. Peter Marinkovich Disclosures: Principal investigator in GEM-3 trial © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Images courtesy of Dr. Peter Marinkovich © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Epidermolysis Bullosa is a group of rare diseases associated with fragile skin, causing skin to blister easily Dystrophic EB One of four inherited forms of EB Dystrophic EB can be inherited dominantly (DDEB) or recessively (RDEB); the recessive form of Dystrophic EB is the most severe, chronic type of EB Blisters occur in the lower layer of the skin, just beneath the lamina densa in the most superficial portion of the dermis Produces debilitating scarring to hands and other parts of the body Constant cycle of blistering, wounding and re-healing greatly increases risk of squamous cell carcinoma (SCC) which can be fatal Diagnosis has traditionally been made based on skin biopsy and is often incorrect; genetic testing provides the most accurate diagnosis Epidermolysis Bullosa (EB) Dystrophic EB Junctional EB Kindler Syndrome EB Simplex EB Acquisita
Images courtesy of Dr. Peter Marinkovich © Copyright 2021 Krystal Biotech, Inc. All rights reserved. The dystrophic form of EB is caused by mutations in the COL7A1 gene The location of the blisters (below the lamina densa) corresponds to level of the “anchoring fibrils” Anchoring fibrils are the molecular glue that holds the dermis to the epidermis, and are mainly composed of type VII collagen protein (COL7) Mutations in the COL7A1 gene lead to missing or dysfunctional forms of the protein; mutations can be dominant (DDEB) or recessive (RDEB) Without functional anchoring fibrils, the skin is fragile and easily shears with even slight friction (holding a pencil, putting on a shirt)
© Copyright 2021 Krystal Biotech, Inc. All rights reserved. There are currently no approved corrective treatments for dystrophic EB Current treatment options for dystrophic EB are largely palliative in nature, involving wound care regimens similar to the care provided to burn victims Blistered areas are wrapped in special bandages which must be changed frequently, often daily, which is time consuming and painful The goal of treatment is to promote wound healing, prevent infection, and protect the skin form trauma to minimize blister formation Multidisciplinary care is often needed, and includes pain management, nutritional support, physical therapy, and other supportive care Palliative treatments cost $200k – $400k annually1,2 Rashidghamat E., Mellerio J.E., Management of chronic wounds in patients with dystrophic epidermolysis bullosa: challenges and solutions, Chronic Wound Care Management and Research Volume 2017:4, 45-54 GENEGRAFT Report Summary. (2015, February 16). Retrieved December 13, 2016, from http://cordis.europa.eu/result/rcn/156078_en.html
B-VEC is an investigational, off-the-shelf, topical gene therapy designed to correct the underlying molecular defect in DEB wounds Blister Untreated DEB Patient Skin B-VEC-treated Skin 1 Keratinocytes Dermoepidermal Junction Fibroblasts Anchoring Fibrils (Collagen VII) B-VEC 2 3 Nucleus COL7 transcripts COL7 protein Keratinocyte (or Fibroblast) Cell 4 1 B-VEC enters the compromised skin of DEB patients and transduces both keratinocytes and fibroblasts 2 Once in the nucleus of transduced cells the vector genome is deposited (episomally) 3 As a result, COL7A1 transcripts are generated, allowing the cell to produce and secrete functional COL7 protein 4 The secreted COL7 protein assembles into anchoring fibrils which hold the epidermis and dermis together Anchoring fibrils B-VEC is an investigational therapy being studied in clinical trials © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Founder and COO Suma Krishnan © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
1 1 1 VYJUVEKTM represents important firsts VYJUVEK is an investigational therapy being studied in clinical trials © Copyright 2021 Krystal Biotech, Inc. All rights reserved. These data also position VYJUVEK to become the first-ever in vivo redosable gene replacement therapy VYJUVEK could be the first-ever topical gene therapy This was the first-ever placebo controlled, blinded study that evaluated a genetic therapy in DEB ST ST ST
Once-weekly treatment until wound closure Resumed if wound reopened Open-label Extension GEM-3 evaluated weekly VYJUVEKTM or Placebo in dystrophic EB patients 31 Patients VYJUVEK Placebo Primary Wound Pair Randomized, double-blind 6-month Treatment Period 30-day Safety Primary Efficacy Endpoints Complete wound healing at Week 22 and Week 24; or at Week 24 and Week 26 (six-month timepoints) Secondary Efficacy Endpoints Complete wound healing at weeks 8 and 10, or 10 and 12 (three-month timepoints) Mean change in pain severity (VAS or FLACC-R Scale) associated with wound dressing changes Demographics 31 patients, each with one primary wound pair were enrolled and included in the intent-to-treat (ITT) analysis Enrolled patients ranged from 1 year old to 44 years old at baseline; 61% of the patients enrolled were pediatric (≤18 years old) Less than ten percent 10% of enrolled patients had the dominant form of dystrophic epidermolysis bullosa (DDEB) Genetically confirmed dystrophic EB VYJUVEK Open label 6-month Treatment Period Secondary Wounds Dosing continues after safety period © Copyright 2021 Krystal Biotech, Inc. All rights reserved. VYJUVEK is an investigational therapy being studied in clinical trials
Topline Ph3 safety data summary © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Topical VYJUVEK was well tolerated with a safety profile consistent with prior studies No drug-related serious AEs or discontinuations due to treatment were reported Immunogenicity profile (as measured by anti-HSV-1 and anti-COL7 antibodies) was consistent with prior studies 1 2 3 VYJUVEK is an investigational therapy being studied in clinical trials One mild drug-related AE was reported during the trial
Topline Ph3 efficacy data summary © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Met primary endpoint of complete wound healing at 6-month timepoints Response Rate 67% 22% Absolute Difference 45.8% 95% Confidence Interval 23.6%-68.0% p-value* <0.005 0.0155 *based on McNemar test - In an ad-hoc analysis, the trial also demonstrated a statistical difference between the active and placebo groups for wounds that demonstrated complete wound healing at both the three and six-month timepoints (p<0.005) 45.8% absolute difference VYJUVEK is an investigational therapy being studied in clinical trials Met secondary endpoint of complete wound healing at 3-month timepoints Response Rate 71% 20% Absolute Difference 51.0% 95% Confidence Interval 29.3%-72.6% p-value* <0.005 0.0155 *based on McNemar test 51.0% absolute difference
Once-weekly treatment until wound closure Resumed if wound reopened Open-label Extension Secondary wounds received open-label VYJUVEKTM throughout the study 31 Patients VYJUVEK Placebo Primary Wound Pair Randomized, double-blind 6-month Treatment Period 30-day Safety Genetically confirmed dystrophic EB VYJUVEK Open label 6-month Treatment Period Secondary Wounds Dosing continues after safety period At baseline, the amount of VYJUVEK that was assigned to the primary wound pair was subtracted from the maximum weekly dose The remaining amount, which was also fixed throughout the study, was assigned to “secondary wounds” that were treated on an open label basis © Copyright 2021 Krystal Biotech, Inc. All rights reserved. VYJUVEK is an investigational therapy being studied in clinical trials
Secondary wound (Illustrative) © Copyright 2021 Krystal Biotech, Inc. All rights reserved. End of Study Baseline Large, chronic back wound in 21 year old RDEB patient VYJUVEK is an investigational therapy being studied in clinical trials
Secondary wound (Illustrative) © Copyright 2021 Krystal Biotech, Inc. All rights reserved. End of Study Baseline left foot Right foot left foot Right foot Recurring foot wound in 34 year old RDEB patient VYJUVEK is an investigational therapy being studied in clinical trials
Once-weekly treatment until wound closure Resumed if wound reopened Open-label Extension Open-label extension ongoing 31 Patients VYJUVEK Placebo Primary Wound Pair Randomized, double-blind 6-month Treatment Period 30-day Safety Genetically confirmed dystrophic EB VYJUVEK Open label 6-month Treatment Period Secondary Wounds Dosing continues after safety period Patients who completed the Phase 3 trial have option to enroll Also opening three new sites where new patients who meet Ph3 entry criteria - but did not complete the Phase 3 trial – are eligible to enroll © Copyright 2021 Krystal Biotech, Inc. All rights reserved. VYJUVEK is an investigational therapy being studied in clinical trials
Evaluating approaches in these markets Known patient populations in rest-of-world (i.e. China) Japan in progress Orphan Drug Designation PRIority MEdicines (PRIME) Designation Orphan Drug Designation Rare Pediatric Disease Designation Regenerative Medicine Advanced Therapy (RMAT) designation Fast Track Designation VYJUVEKTM regulatory next steps © Copyright 2021 Krystal Biotech, Inc. All rights reserved. MAA filing in mid-2022 Evaluate path forward in other markets Europe Japan + Other BLA filing in 1H22 United States VYJUVEK is an investigational therapy being studied in clinical trials
CCO Andy Orth © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Dystrophic EB patient population and VYJUVEKTM opportunity © Copyright 2021 Krystal Biotech, Inc. All rights reserved. VYJUVEK is an investigational therapy being studied in clinical trials
Launch readiness / efforts © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Education + Awareness Patient and Caregiver facing Community Educational Liaisons in the field Health Care Professional and Patient focused Disease State Awareness programming underway Medical Affairs Key Opinion Leader engagement underway Exploring all access pathways in Europe No-charge genetic testing available to eligible US residents who are suspected of having EB and have not yet been genetically confirmed. Comprehensive testing panel to identify Dystrophic EB or conditions with similar phenotypes, including other EB types and some non-EB genetic blistering conditions. Excellent EB community response to date Payer / Reimbursement Early engagement with US payer partners to educate on Dystrophic EB, Krystal and B-VEC Will pursue an aggressive and progressive value-based strategy to ensure timely and open access for B-VEC VYJUVEK is an investigational therapy being studied in clinical trials
Platform supported by in-house manufacturing capacity and expertise Established process conducted at Krystal’s end-to-end GMP facility (Ancoris) Maintains control of IP/trade secrets relating to manufacturing process Adheres to internal process and production schedules, avoiding use of high demand gene therapy CMOs Upstream process using stable producer cell lines has cost & regulatory benefits Stable complementary cell lines developed in-house are used in established methods for production of consistent batches Eliminates the need for multiple cGMP qualifications of plasmids and variability in transfection efficiency from batch to batch Scalable from clinical phase to commercial Successfully developed a robust and reproducible downstream process Work conducted in an aseptic closed system process The same process is leveraged across pipeline with minimal redevelopment effort between product candidates Compliant with global regulatory requirements © Copyright 2021 Krystal Biotech, Inc. All rights reserved. ASTRA Operational in 2022 Size: ~150,000 sq. ft. Facility operational
Chairman and CEO Krish Krishnan © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Pipeline upcoming events †: FDA Orphan Drug Designation; ¤: FDA Rare Pediatric Disease Designation; •: Fast-track Designation; Δ: FDA RMAT designation; ‡: EMA Orphan Drug Designation; §: EMA PRIME Designation. All pipeline compounds are investigational, being evaluated in clinical or pre-clinical studies. © Copyright 2021 Krystal Biotech, Inc. All rights reserved. Product Protein Indication Discovery Preclinical Phase 1/2 Phase 3 Key Upcoming Milestone Ownership VYJUVEKTM †¤•Δ‡§ Type VII collagen (COL7) Dystrophic EB File BLA in 1H22 Wholly owned KB105†¤•‡ Transglutaminase 1 (TGM1) TGM1-deficient ARCI Initiate next Phase 2 cohort in 2022 Wholly owned KB104¤ Serine Peptidase Inhibitor Kazal Type 5 (SPINK5) Netherton Syndrome File IND in 2022 Wholly owned KB1XX Undisclosed programs Wholly owned KB5XX Vectorized antibodies Chronic conditions Wholly owned KB301 Type III collagen (COL3) Aesthetic skin conditions Ph1 efficacy data in 1Q22 KB407†¤‡ Cystic fibrosis transmembrane conductance regulator (CFTR) Cystic fibrosis Initiate Ph1 study in 4Q21 Wholly owned KB408 Alpha-1 antitrypsin (AAT) Alpha-1 antitrypsin deficiency Wholly owned KB4XX Undisclosed programs Wholly owned Respiratory Dermatology
Routes of Administration Redosable gene delivery technology has broad potential Engineered HSV-1 Platform Vector can deliver variety of therapeutic modalities and be administered repeatedly Provides multiple potential pathways to address different tissue types, with options for route of administration Broad potential for rare, non-rare and aesthetic conditions Topical gel Intradermal injection Nebulization Eyedrop Additional routes of administration and target tissues being explored Mix-and-Match Modality & Tissue Target Lungs Cornea Other Skin Therapeutic gene replacement Vectorized cytokines Gene silencing (RNA, gene editing) Vectorized antibodies © Copyright 2021 Krystal Biotech, Inc. All rights reserved.
Questions & Answers © Copyright 2021 Krystal Biotech, Inc. All rights reserved.