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. (the "C

AAD GEM-3 Phase 3 Data Conference Call

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. (the "Company"), including but not limited to

statements about the development of the Company's product candidates, such as the future development or commercialization of B-VEC (beremagene geperpavec), and the Company's other product candidates; conduct and timelines of preclinical

and clinical trials, the clinical utility of B-VEC and the Company's other product candidates; plans for and timing of the review of regulatory filings, efforts to bring B-VEC and the Company's other product candidates to market; the

market opportunity for and the potential market acceptance of B-VEC; plans to pursue research and development of product candidates and the Company's technology; the sufficiency of the Company's existing cash resources; and other

statements containing the words "anticipate", "believe", "estimate", "expect", "intend", "may", "plan", "predict", "project",

"target", "potential", "likely", "will", "would", "could", "should", "continue" and similar expressions, constitute forward-looking statements within the

meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the content and timing of decisions

made by the U.S. Food and Drug Administration, European Medicines Agency and other regulatory authorities; the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials; whether

results of early clinical trials or studies in different disease indications will be indicative of the results of ongoing or future trials; uncertainties associated with regulatory review of clinical trials and applications for marketing approvals;

the availability or commercial potential of product candidates; the ability to retain and hire key personnel; the sufficiency of cash resources and need for additional financing; and such other important factors as are set forth in the

Company's annual and quarterly reports and other filings on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this presentation represent the Company's views as of the date of

this presentation. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims

any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presentation. This presentation also contains estimates and other statistical

data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we

nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, projections, assumptions and estimates of our future

Agenda 1 Introductory Comments Krish

Krishnan - Chairman and CEO 2 DEB Background and GEM-3 Results (AAD Late-Breaking Presentation) Dr. Hubert Chen - SVP, Clinical Development 3 Market Opportunity and Commercial Preparations Andy Orth - Chief Commercial Officer 4

Krystal Biotech: Bringing

Transformative, Redosable Gene Therapies to Underserved Patient Populations Cash position as of December 31, 2021 Leader in the science of redosable gene therapies - powered by proprietary HSV-1 vector technology Initial focus on rare

dermatologic diseases established clinical POC and a broad pipeline Expanded focus on larger indications, new tissue types and alternative routes of administration Fully integrated, commercial-ready/pivotal gene therapy company Well funded with cash

Lead Program: B-VEC (beremagene

2,500 patients diagnosed across the US, Europe and ROW1 Global commercial & medical teams with deep expertise in rare diseases Topline Phase 3 data announced in Nov 2021; Detailed data presented at AAD in March 2022 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 MAA filing in 2H22 Evaluate path forward in other markets Europe Japan + Other BLA filing in 2Q22 United States Internal data on file

Dr. Hubert Chen SVP, Clinical

Dystrophic Epidermolysis Bullosa and

B-VEC Dystrophic epidermolysis bullosa (DEB) is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene which lead to skin fragility and wounds1-3 Patients with DEB are at increased risk for serious complications,

including aggressive squamous cell carcinoma4-6; management is currently supportive in nature7,8 Beremagene geperpavec (B-VEC) is an investigational HSV-1-based topical, redosable gene therapy designed to restore functional COL7 protein by

delivering the COL7A1 gene B-VEC utilizes a differentiated HSV-1 vector platform that allows for episomal delivery, high payload capacity, tropism for skin cells, and evades the immune system enabling repeat delivery 1. Fine J-D, et al. J Am Acad

Dermatol. 2014;70(6):1103-1126; 2. Fine J-D. JAMA Dermatol. 2016;152(11):1231-1238; 3. Bardhan A, et al. Nat Rev Dis Primers. 2020 Sep 24;6(1):78; 4. Condorelli A, et al. Int J Mol Sci. 2019;20(22):5707; 5. Montaudi H, et al. Orphanet J Rare

Dis. 2016;11(1):117; 6. Fine J-D, Mellerio JE. J Am Acad Dermatol. 2009;61:367-384; 7. Denyer J, et al. Accessed March 16, 2022. https://www.woundsinternational.com/download/resource/5921; 8. Bruckner AL, et al. Orphanet J Rare Dis. 2020;15(1):1.

B-VEC, beremagene geperpavec; COL7, type VII collagen; COL7A1, collagen type VII alpha 1 chain; DEB, dystrophic epidermolysis bullosa; HSV-1, herpes simplex virus type 1 7

GEM-3 Study Design B-VEC, beremagene

geperpavec; DEB, dystrophic epidermolysis bullosa GEM-3 (NCT04491604) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled intra-patient study evaluating the efficacy and safety of B-VEC in patients with DEB B-VEC Placebo

Randomized, double-blind 6-month treatment period Open-label 6-month treatment period Secondary Wounds 31 Patients Enrolled Age 6 months Genetically confirmed DEB Two cutaneous wounds similar in size, appearance, and anatomical regions

Primary Wound Pair 30-day safety period Once weekly treatment until wound closure; treatment resumed if wound reopened Dosing continues after safety period Open-label extension period B-VEC Remaining weekly dose used to treat up to four secondary

wounds Secondary Efficacy Endpoints Complete wound healing* at Weeks 8 & 10 or Weeks 10 & 12 (3 months) Mean change in pain severity associated with wound dressing changes Primary Efficacy Endpoint Complete wound healing* at Weeks 22 &

24 or Weeks 24 & 26 (6 months) *Complete wound healing defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage 8

Patient Disposition 31 patients were

randomized and made up the intent-to-treat (ITT) population used for all primary and secondary efficacy analyses The safety population was the same as the ITT population and used for all safety analyses Three patients withdrew from the study for

nondrug-related reasons B-VEC, beremagene geperpavec; ITT, intent-to-treat 31 patients screened and enrolled 30 patients completed through Week 12 One primary wound pair per patient randomized 1:1 28 patients completed through Week 26 1 withdrawal

after Week 6 31 primary wounds received B-VEC 31 primary wounds received placebo 1 withdrawal after Week 12 1 withdrawal after Week 24 9

Baseline Demographics and Clinical

Characteristics *In a small number of patients, the pre-defined threshold values for wound area/size category fell in between the size of the two wounds B-VEC, beremagene geperpavec; DDEB, dominant dystrophic epidermolysis bullosa; RDEB, recessive

dystrophic epidermolysis bullosa; SD, standard deviation Total patients (n=31) Age, years Mean (SD) 17.2 (10.7) Range 1 - 44 Age category, n (%) 12 years 10 (32.3) >12 and 18 years 9 (29.0) >18 years 12 (38.7) Sex, n (%)

Male 20 (64.5) Female 11 (35.5) Race, n (%) White 20 (64.5) Asian 6 (19.4) American Indian or Alaska Native 5 (16.1) Total patients (n=31) Genotype, n (%) DDEB 1 (3.2) RDEB 30 (96.8) Primary wound B-VEC (n=31) Placebo (n=31) Wound area/size, cm2

Mean (SD) 14.4 (12.7) 15.6 (12.1) Range 2.3 - 57.3 2.3 - 51.5 Wound area/size category*, n (%) <20 cm2 23 (74.2) 22 (71.0) 20 - <40 cm2 6 (19.4) 8 (25.8) 40 - 60 cm2 2 (6.5) 1 (3.2) 10

Significantly Greater Complete Wound

Healing with B-VEC Treatment The proportion of primary wounds with complete wound healing was significantly greater with B-VEC than placebo at both 3- and 6-month timepoints (p <0.005) In the patient with DDEB, primary endpoint of complete wound

healing at 6 months was achieved by the B-VEC treated wound, but not by the placebo treated wound At 6 months, 15 of 17 discordant pairs showed response to B-VEC but not placebo Discordant pair defined as when one wound meets complete wound healing

responder definition and other does not Data as of database lock on 19Nov2021; data in figure based on ITT population (imputed); p-values and CIs are based on exact McNemar's test B-VEC, beremagene geperpavec; CI, confidence interval; DDEB,

dominant dystrophic epidermolysis bullosa; ITT, intent-to-treat 67.4% 21.6% 70.3% 20.0% 45.8% absolute difference (95% CI 23.6 - 68.0%) p < 0.005 50.3% absolute difference (95% CI 28.7 - 72.0%) p < 0.005 B-VEC Placebo Proportion of

Primary Wounds with Complete Wound Healing in the ITT Population (n= 31) 6 Months (Primary Endpoint) 3 Months (Key Secondary Endpoint) 11

Primary Wound Pairs (15 - 30

cm2) at Baseline and 6 Months Baseline 6 Months Baseline 6 Months Patient A Knee Patient A Knee Patient B Lower abdomen Patient B Sternum Patient C Lower trapezius Patient C Upper paraspinal B-VEC, beremagene geperpavec 12 B-VEC Placebo

Treatment with B-VEC Demonstrated

Durability of Response 49.7% of B-VEC treated wounds compared to 7.1% of placebo treated wounds demonstrated durability of response, defined as wounds that met complete wound healing at both 3 months (key secondary endpoint) and 6 months (primary

endpoint) Nearly half of all B-VEC treated wounds demonstrated complete wound healing for three consecutive visits Data as of database lock on 19Nov2021 B-VEC, beremagene geperpavec; CI, confidence interval Responder, n (%) Absolute

Difference, % (95% CI) B-VEC (n=31) Placebo (n=31) Durability of response 15.4 (49.7) 2.2 (7.1) 42.6 (22.6, 62.6) Complete wound healing Weeks 8, 10, and 12 14.8 (47.7) 5.1 (16.5) 31.3 (10.6, 51.9) Weeks 22, 24, and 26 13.4 (43.2) 2.0

(6.5) 36.8 (19.8, 53.7) Durability of response was defined as meeting the responder definition for complete wound healing both at 3 months (Weeks 8 & 10 or Weeks 10 & 12) and at 6 months (Weeks 22 & 24 or Weeks 24 & 26)

Percentages are based on the number of subjects in the intent-to-treat (ITT) population; CIs are based on McNemar's test Missing endpoint data were imputed assuming the data are missing at random and using multiple imputation methodology Of

the total B-VEC wounds closed at 3 months, 66.7% (14/21) of B-VEC-treated wounds were also closed at 6 months, as compared to 33.3% (2/6) for placebo treated wounds (p=0.02) 13 Copyright 2022 Krystal Biotech, Inc. All rights

Consistent Evidence of a Treatment

Response with B-VEC Across Subgroups Treatment response was in favor of B-VEC for all gender, age, and wound area/size subgroups, however the individual subgroups were not powered to demonstrate statistical significance Data as of database lock on

19Nov2021; data in figures based on ITT population (imputed); p-values and CIs are based on exact McNemar's test; gender and age subgroups were pre-specified B-VEC, beremagene geperpavec; CI, confidence interval; ITT, intent-to-treat Favors

B-VEC Favors placebo Gender Male (n=20) Female (n=11) 12 years (n=10) >12 and 18 years (n=9) >18 years (n=12) Absolute Difference, % (95% CI) Complete Wound Healing at 6 Months by Gender and Age Subgroups Age Baseline primary

wound area/size category* B-VEC Placebo N Complete wound healing at 6 months, n (%) N Complete wound healing at 6 months, n (%) <20 cm2 23 14 (60.9) 22 5 (22.7) 20 - <40 cm2 6 4 (66.7) 8 1 (12.5) 40 - 60 cm2 2 1 (50.0) 1 0 (0) *In a

small number of patients, the pre-defined threshold values for wound area/size category fell in between the size of the two wounds Complete Wound Healing at 6 Months by Baseline Primary Wound Area/Size Category 14

Pain and PRO Assessments

Demonstrated Improvement Consistent with a Wound Healing Response Baseline VAS score of enrolled patients were approximately 2 to 3 on average A trend towards decreased pain in B-VEC treated versus placebo treated wounds was observed across Weeks

22, 24, and 26; improvement in pain was consistent with wound healing PRO measures (EQ-5D-5L and Skindex-29) assessed before and after treatment with B-VEC demonstrated improvement across multiple domains directionally, consistent with a wound

healing response Data as of database lock on 19Nov2021 B-VEC, beremagene geperpavec; ITT, intent-to-treat; PRO, patient reported outcomes; VAS, Visual Analog Scale Change from baseline in pain severity associated with wound dressing changes, as

measured by Visual Analog Scale, at Weeks 22, 24, and 26 for the ITT population, ages 6 and above Least square mean difference, 95% CI (shown as error bars), and p values were generated from analysis of covariance linear model with treatment and

subject as the fixed effects and the baseline value as the covariate and change from baseline as the dependent variable Change from Baseline in Pain following B-VEC Treatment Week 22 Week 24 Week 26 15 p = 0.02 p = 0.06 p = 0.07

B-VEC was Generally Well-Tolerated

Total Patients (n=31) Total number of adverse events (AEs) 45 Patients with 1 AE, n (%) 18 (58.1) Serious AEs 3 (9.7) Severe AEs 2 (6.5) Drug-related AEs 1 (3.2) AE leading to treatment discontinuation 0 (0) Death 0 (0) Data as of database

lock on 19Nov2021 AEs, adverse events; B-VEC, beremagene geperpavec; COL7, type VII collagen; HSV-1; herpes simplex virus type 1; SAEs, serious adverse events The majority of AEs were mild; there were no AEs leading to treatment discontinuation or

death One AE, mild erythema, was considered possibly related to study drug as assessed by the investigator Three patients experienced a total of 5 SAEs during the study: cellulitis, anemia (2 events), diarrhea, and positive blood culture None were

considered related to study drug No clinically significant immunologic reactions were reported during the study Treatment response to B-VEC was not associated with HSV-1 serostatus at baseline or with COL7 seroconversion 16

Andy Orth Chief Commercial Officer

Dystrophic EB Patient Population and

B-VEC Opportunity B-VEC is an investigational therapy being studied in clinical trials Genetic prevalence suggests ~3,000 patients in the US Initial claims data mining points to >1,000 known patients diagnosed with DEB in the US and >2500

patients worldwide Payer mix expected to be ~80% commercially insured in the US Palliative care alone costs the healthcare system $200,000-$400,000 today B-VEC vial pricing to be informed by significant variability in patient level vial consumption;

driven by disease severity and duration of treatment Patient costs (vial consumption) to the payer expected to decrease over time until they reach steady state. Proactively partnering with US payers for budget predictability Copyright 2022

Preparing for U.S. Launch Education

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 Payer education and engagement

Initial Launch Focused on >1,000 patients identified by claims database analytics Primarily treating more severe patients at Centers of Excellence Access to treatment at convenient sites of care Longer-term Launch Identifying and educating HCPs

and patients in order to identify remaining Dystrophic EB patient population Patient finding activities - focusing on individuals currently not diagnosed or with localized -to-moderate diagnosis Drive patient disease awareness via sponsored genetic

testing and disease education Internal Preparation Profiling HCPs to ensure we know where the patients are and raise awareness/educate Laying groundwork for site-of-care strategy (goal to allow patients to get treatment in their own zip code)

No-charge genetic testing program

available to eligible U.S. 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

DEB Disease Awareness Update

DEBFacts Web Sites Launched early 2022 DEB Caused by COL7 Dysfunction Importance of accurately diagnosing DEB Patients Every Wound Matters/Has Consequences DDEB RDEB For internal use only >1,000 visits since launch. Media investment and other

websites traffic drivers launching early Q2

Medical affairs booth focused on

disease state and Krystal Biotech awareness, highlighting: Patient journey cases Decode DEB genetic testing program Mechanism of disease and mechanism of action animations/videos Pipeline and clinical trial information Engaging HCPs serving the

dystrophic EB community Better understand practice dynamics, patient unmet needs, and dystrophic EB landscape Highlight Krystal scientific research Proactive Education at American Academy of Dermatology Learn More About Dystrophic Epidermolysis

Existing ANCORIS Facility New ASTRA