Forward-looking statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. Any statements in this presentation about future expectations, plans and prospects for Kr

The Leader in Redosable Gene Therapy

Forward-looking statements 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 beremagene geperpavec ("B-VEC"), KB105, KB104, KB301 and KB407 and the Company's

other product candidates; conduct and timelines of clinical trials, the clinical utility of B-VEC, KB105, KB104, KB301 and KB407 and the Company's other product candidates; plans for and timing of the review of regulatory filings, efforts to

bring B-VEC, KB105, KB104, KB301 and KB407 and the Company's other product candidates to market; the market opportunity for and the potential market acceptance of B-VEC", KB105, KB104, KB301 and KB407 and the Company's other

product candidates, the development of B-VEC, KB105, KB104, KB301 and KB407 and the Company's other product candidates for additional indications; the development of additional formulations of B-VEC, KB105, KB104, KB301 and KB407 and the

Company's other product candidates; plans to pursue research and development of other product candidates, 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 performance and the future performance of the markets in which we

Krystal overview Proprietary,

engineered replication incompetent HSV-1 based platform Clinical data shows maintenance of safety and transgene expression after repeat dosing Positive external clinical and regulatory precedent with in vivo HSV-1 based therapy Differentiated viral

vector platform enables in vivo, repeat dose gene therapies A fully integrated, clinical stage gene therapy company powered by proprietary HSV-1 vector technology Lead program, B-VEC (formerly KB103) went from IND to Phase 3 in less than 3 years;

pivotal data anticipated in 2021 Two lead dermatologic pipeline programs, KB104 and KB105, leverage the same vector Initial focus on rare, dermatologic indications led to rapid clinical proof of concept and pipeline Stable producer cell lines

developed for each program have cost, scale, and regulatory benefits Current ~7,500 sqft GMP facility near company headquarters in Pittsburgh is producing pivotal material at commercial scale, and BLA readiness is underway Investing in additional

capacity via construction of an ~150,000 sqft facility which is expected to be operational in 2022 In-house GMP manufacturing to support clinical and commercial needs Ongoing Phase 1 trial in acne scars and wrinkles with KB301, under our wholly

owned subsidiary Jeune, Inc. Positive pre-clinical data from KB407 for cystic fibrosis demonstrates potential to target lung tissue; pre-IND studies underway Continue to drive innovation by investing in next-gen platform capabilities Broadening

Key 2021 Milestones Progress across

pipeline will yield pivotal data for B-VEC, a 4th clinical stage program and a new respiratory candidate in 2021 Timing Program Event 1Q21 B-VEC for DEB Complete enrollment in pivotal GEM-3 study in DEB 1Q21 KB301 for aesthetic indications Announce

Initial safety data from cohort 1 of Phase 1 study in facial wrinkles and acne scars 1Q21 KB301 for aesthetic indications Provide update on strategy for KB301 and aesthetic pipeline (under Jeune Inc.) 1H21 KB105 for TGM1-ARCI Announce initial Phase

2 data and update on next Phase 2 cohorts 1H21 KB407 for CF Announce data from IND enabling toxicology study in nonhuman primates 1H21 KB407 for CF Initiate Phase 1/2 study 1H21 Respiratory pipeline Announce development candidate for new genetic

lung disease 2H21 B-VEC for DEB Announce top line data from the pivotal GEM-3 study 2H21 KB104 for Netherton File IND All pipeline compounds are investigational, being evaluated in clinical or pre-clinical studies. Copyright 2021 Krystal

Our technology platform enables

HSV-1 is positively differentiated vs.

other gene therapy technologies Lundstrom, K. Viral Vectors in Gene Therapy. Diseases 2018, 6, 42. Generation Bio (GBIO) Prospectus. (2020, June 11). Retrieved September 4, 202020,

https://www.sec.gov/Archives/edgar/data/1733294/000119312520167812/d924849d424b4.htm LV = lentivirus AAV = adeno-associated virus LNP = lipid nanoparticle Targeted mutagenesis resulting in platform that is both safe and effective for localized,

repeat delivery of genetic payload Wild-type HSV-1 Krystal's Modified HSV-1 Platform Insertion of one or more therapeutic effectors of interest into the vector Therapeutic Vector HSV-1 has natural affinity for epithelial cells (in addition to

several other cell types) with favorable immune-evasion mechanisms Replication incompetent HSV-1 vector that can be administered repeatedly for chronic dosing Large carrying capacity allows insertion of large transgenes, multiple copies of the

transgene of interest and/or multiple different transgenes LV AAV HSV-1 LNP In vivo dosing? No Yes Yes Yes Baseline antibody exclusion criteria? No (if ex vivo) Yes No No Repeat-dose capabilities? Yes (if ex vivo) No Yes Yes Carrying capacity? 8 kb1

Clinically validated platform targeting

skin; broad tropism of HSV-1 could unlock additional target tissues Clinical Experience In development Research / Platform Development Efforts Topical Intradermal Inhaled The current vector has been clinically validated to target skin cells.

Preclinical exploration of its ability to target additional epithelial cell types is under way Formulation / Route of Admin Additional potential routes of administration under investigation B-VEC KB105 KB104 Early stage research projects KB301 KB104

Current pipeline : FDA Orphan

Drug Designation; : FDA Rare Pediatric Disease Designation; : Fast-track Designation; : FDA RMAT designation; : EMA Orphan Drug Designation; : EMA PRIME Designation. Product Indication Discovery Preclinical Phase I/II

B-VEC Dystrophic EB KB105 TGM1-deficient ARCI Phase III Key Upcoming Milestone KB301 Wrinkles & Acne Scars Netherton Syndrome KB104 Chronic Skin Diseases KB5XX Cystic

Fibrosis KB407 Top line pivotal data in 2H21 Ph2 data and next steps in 1H21 Cohort 1 safety data in 1Q21 File IND in 2H21 Initiate clinical study in 1H21 All pipeline compounds are investigational, being evaluated in clinical or

pre-clinical studies. Jeune Inc. a wholly owned subsidiary of Krystal Biotech Other Rare Lung KB4XX Aesthetic Skin Conditions KB3XX Jeune Inc. a wholly owned subsidiary of Krystal Biotech WW Rights Rare Skin Rare Lung Other Skin Copyright

Initial focus on rare skin diseases led

Dystrophic epidermolysis bullosa

(DEB) DEBRA International, http://www.debra-international.org/epidermolysis-bullosa/causes-and-subtypes.html; http://www.debra-international.org/what-is-eb/causes-and-subtypes/deb.html Pfendner EG, Lucky AW. Dystrophic Epidermolysis Bullosa. 2006

Aug 21 [Updated 2015 Feb 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. 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 Dystrophic Epidermolysis Bullosa A rare,

genetic skin disease that causes skin to tear or blister from minor contact Mutations in the COL7A1 gene lead to absent or dysfunctional COL7 protein, without which the epidermis does not anchor to the dermis The recessive form (RDEB) is the

classic, most severe form of the condition. Dominant DEB (DDEB) has a broader range in severity and is often characterized by blistering on the hands, feet, knees, and elbows Epidemiology Prevalence: Up to 125,000 people are affected by DEB

worldwide1 We believe that there are, at present, approximately 3,000 DEB patients in the US Incidence: The incidence of DEB is 6.5 per million births in the US2 Current Standard of Care There are no approved treatments for DEB Existing therapies

limited to expensive and time-consuming palliative treatments Palliative treatments cost $200k - $400k annually3,4 "Butterfly Children" is often used to describe young DEB patients because their skin is as fragile as a

Beremagene geperpavec (B-VEC) for

DEB 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 Topically applied B-VEC gel is designed to deliver local COL7 expression and molecular

Topical B-VEC was evaluated in a

Phase1/2 study GEM1/2 (NCT03536143) was an intra-patient comparison of wounds randomized to receive either topical B-VEC or placebo. Each patient on-study for ~6 months; 3 months of on-site visits followed by 3-month at-home imaging period Study PI:

Dr. Peter Marinkovich (Stanford University) Design Enrollment Key Endpoints A total of 9 RDEB patients (adult and pediatric) were enrolled in the study; 3 subjects re-enrolled later in the study and were re-randomized for a total of 12 subjects

Safety measures AEs, including clinically significant changes in laboratory results, vitals, and physical exam findings Viral shedding was analyzed through the collection of blood, urine, and skin swabs, and antibodies to HSV and COL7 were analyzed

through collection of serum Efficacy measures Level of collagen VII (COL7) in B-VEC-administered skin as measured by immunofluorescence; presence of anchoring fibrils as measured by immunoelectron microscopy Wound closure (change in wound surface

area relative to baseline), time to wound closure, and duration of wound closure, all relative to placebo Dosing In the Ph1 portion (n=2) one wound was administered B-VEC and one wound was administered placebo at a dose of 1e8 PFU/wound with varying

frequency throughout the study period In Phase 2 portion (n=10) 2 wounds were administered B-VEC and one wound was administered placebo (except 1 patient who was 1:1) at doses of either 2e8, 3e8, 6e8 or 8e8 PFU/wound with varying frequency

Repeat doses of topical B-VEC were

well tolerated; COL7 expression and molecular correction established In the Ph1/2 trial, the number of repeat doses per wound ranged from 4 to 41; the PFU per wound ranged from 1e8 to 8e8 No treatment-related serious AEs were reported; AEs deemed

possibly related were mild (n=7) or moderate (n=1) and self-limiting No immune response or blistering observed around the sites of administration following first and repeat doses Blood and urine samples collected throughout the study revealed: No

systemic viral shedding No adverse events associated with routine labs (chemistry and hematology) Some patients had baseline COL7 and/or HSV-1 antibodies which did not impair efficacy or impact tolerance of therapy Increasing doses and dosing

frequency were well tolerated Molecular correction established and correlated with wound healing Expression and correct localization of full-length COL7 was observed following B-VEC therapy, evidenced by presence of both NC1 and NC2 domains and

visible anchoring fibrils on IEM. Baseline, Days 15 and 97 collagen VII expression using NC1 and NC2 specific antibodies (patient 10) Immunoelectron microscopy shows mature anchoring fibrils at day 97 (patient 10) Day 0 Day 15 Day 97 NC1 NC2 Arrows

indicate basement membrane zone Increased expression of NC1 (arrow) Increased expression of NC2 (black dots) Robust, mature anchoring fibrils (arrows) B-VEC is an investigational therapy being studied in clinical trials Copyright 2021 Krystal

B-VEC showed statistically

significant benefit in wound healing relative to placebo Percent change in wound area from (individual measurements and average) from Day 0 to 90 Percentage of wounds reaching 100% closure at weeks 8, 10 and 12 B-VEC 82.4% (14/17) 75.0% (12/16)

64.3% (9/14) Placebo 0.0% (0/8) 16.7% (1/6) 14.3% (1/7) p-value* 0.0001 0.0155 .0384 Combined p-value* <0.0001 *based on Cochran-Mantel Haenszel (CMH) Test Without Adjusting for Week-to-Week Placebo Variability ** based on the Breslow-Day for

The pivotal GEM-3 study is

enrolling; top line data expected in 2021 GEM-3 (NCT04491604) is a randomized, double-blind, intra-patient comparison of wounds randomized to receive either topical B-VEC or placebo. Each patient on-study for approximately 7 months: the 6-month

dosing period followed by a 30-day safety follow up Design Enrollment Efficacy Endpoints Approximately 30 DEB subjects (adult and pediatric) will be enrolled across 6 trial sites in the US Each subject provides at least 1 pair (up to 3) of primary

target wounds, 1 randomized to B-VEC and the other to placebo In addition to the primary target wound pair(s), additional wounds (secondary wounds) may be selected to be treated with B-VEC in an open-label manner Primary Complete wound healing,

determined by the Investigator, as compared to baseline in B-VEC treated wounds versus placebo treated at weeks 20, 22 and 24 Secondary Complete wound healing, determined by the Investigator, as compared to baseline in B-VEC treated wounds versus

placebo at weeks 8, 10 and 12 Mean change in pain severity (using either a VAS or FLACC-R Scale) per primary wound site associated with wound dressing changes The proportion of primary wound sites with 75% would healing as compared to

Phase 3 trial is well powered and

inclusive of a broad patient population Screening 6-month Treatment Period 30-day Safety OLE Dosing: Primary wounds will be treated once weekly with a fixed dose until wound closure; should a wound re-open, weekly dosing will resume at the assigned

dose until wound closure The fixed dose per wound is dependent on the size of the wound at baseline and ranges from 4x108 to 1.2x109 PFU per wound Each patient is allowed a maximum weekly dose of B-VEC; if that maximum is not reached in dosing

primary wounds, additional secondary wounds may be chosen and treated with B-VEC in an open label manner The maximum weekly dose, administered once weekly per patient, is defined by patient age (right) Wk 20 Wk 22 Wk 24 Wk 8 Wk 10 Wk 12 Maximum

Weekly Dose Per Subject: Age Max Weekly Dose 6 months to < 3 years 1.6x10^9 PFU/week 3 years to < 6 years 2.4x10^9 PFU/week 6 years 3.2x10^9 PFU/week The trial is designed to maximize chances of success while

maintaining potential for a broad label, inclusive of chronic and recurring wounds of any size in RDEB or DDEB patients Key Design Elements: No restriction on chronic or recurring wounds Maximum weekly dose allows for flexibility to treat multiple

Autosomal Recessive Congenital

Icthyosis associated with TGM1 mutations Autosomal Recessive Congenital Ichthyosis (ARCI) Associated with TGM1 The most common form of ARCI is caused by an inactivating mutation in the TGM1 gene encoding the enzyme transglutaminase-1, a protein that

is essential for the proper formation of the skin barrier The condition is characterized by thick, dry, scaly skin, increased trans-epidermal water loss (TEWL), risk for dehydration, sepsis, skin malignancies, etc Epidemiology1-8 Prevalence: There

are approximately 20,000 people affected by TGMI related icthyosis worldwide (~1,800 US; 3,000 EU; 18,000 ROW) Incidence: It is estimated that around 350-400 babies are born with the condition each year, worldwide Current Standard of Care There are

no approved treatments for ARCI associated with TGM1 Topical and systemic retinoids and time-consuming supportive treatments (up to 4 hours a day of skin care) are most often used 1. Rodriguez-Pazos et al. Actas Dermosifiliogr. 2013

May;104(4):270-284; 2. Dreyfus et al. Orphanet J Rare Dis. 2014 Jan 6;9:1; 3. Hernandez-Martin et al. J Am Acad Dermatol. 2012 Aug;67(2):240-244; 4. Pigg et al. Eur J Hum Genet. 1998 Nov-Dec;6(6):589-596. 5. Pigg et al. Acta Derm

Venereol. 2016 Nov 2;96(7):932-937; 6. Orphanet; 7. Foundation for Ichthyosis & Related Skin Types (FIRST); 8. National Organization for Rare Disorders (NORD). Transglutaminase-1 deficiency is associated with increased mortality in the

KB105 for TGM1 associated ARCI 3

TGM1 transcripts are generated, which allows the cell to produce functional TGM1 protein that localizes to the cell membrane 2 KB105 is transported into the nucleus of transduced cells and the vector genome is deposited (episomally) 1 KB105 enters

permeabilized skin and transduces keratinocytes (native TGM1-producing cells) 4 TGM1 crosslinks target proteins (e.g., filaggrin (FLG), involucrin (IVL), small proline-rich proteins (SPRs)) to aid in the formation of the cornified cell envelope 5

This layer, known as the stratum corneum, acts as a mechanical barrier to protect against transepidermal water loss (TEWL) and entry of infectious agents Untreated ARCI Patient Skin KB105-treated Skin 1 2 3 Nucleus Keratinocyte 5 4 TGM1 SPRs FLG IVL

TGM1 Basal Spinous Granular Cornified TEWL TEWL Pathogens Pathogens KB105 Topically applied KB105 delivers multiple copies of the human transglutaminase 1 ("TGM1") gene KB105 is an investigational therapy being studied in clinical trials