Krystal Biotech, Inc. · NASDAQ:KRYS
Krystal Biotech — Investor Presentation (November 2020)
34 slides from Krystal Biotech's investor presentation, Nov 9, 2020
Slide 1: Medicines for Rare Diseases – An HSV-1 Based Gene Therapy Company
Medicines for Rare Diseases – An HSV-1 Based Gene Therapy Company CORPORATE PRESENTATION November 2020 Exhibit 99.3
Slide 2: Forward-Looking Statements
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 abo
Slide 3: Krystal Overview
A fully integrated, clinical stage gene therapy company powered by proprietary HSV-1 vector technology Krystal Overview Differentiated viral vector platform enables in vivo, repeat dose gene therapies Platform powered by proprietary, engineered replication incompetent HSV-1 vector Pre-clinical and c
Slide 4: Differentiated HSV-1 Based Platform Enables In Vivo, Repeat Dose Gene Therapies
Differentiated HSV-1 Based Platform Enables In Vivo, Repeat Dose Gene Therapies
Slide 5: HSV-1 is Positively Differentiated vs. Other Gene Therapy Technologies
HSV-1 is Positively Differentiated vs. Other Gene Therapy Technologies Targeted mutagenesis resulting in platform that is well suited 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 Therape
Slide 6: Clinically Validated Platform Targeting Skin; Ongoing Investment in Next-Gen Technology
Clinically Validated Platform Targeting Skin; Ongoing Investment in Next-Gen Technology to Broaden Platform Applicability Topical Intradermal Inhaled The current vector has been clinically validated to target skin cells. Preclinical exploration of its ability to target additional epithelial cell typ
Slide 7: Pipeline
Pipeline Product Indication Discovery Preclinical Phase I/II B-VEC†¤•Δ‡§ Dystrophic EB KB105†¤•‡ TGM1-deficient ARCI Phase III Key Upcoming Milestone †: FDA Orphan Drug Designation ¤: FDA Rare Pediatric Disease Designation KB301 Wrinkles & Acne Scars Netherton Syndrome KB104 Chronic Skin Diseases KB
Slide 8: Initial Focus on Rare Skin Diseases Led to Rapid Clinical POC and Pipeline
Initial Focus on Rare Skin Diseases Led to Rapid Clinical POC and Pipeline
Slide 9: Dystrophic Epidermolysis Bullosa (DEB)
“Butterfly Children” is used to describe young DEB patients because their skin is as fragile as a butterfly’s wings 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 Pfend
Slide 10: Beremagene Geperpavec (B-VEC) for DEB
B-VEC is a topically administered, replication-deficient HSV-1 vector containing two functional COL7A1 genes applied directly to DEB patient wounds in an outpatient setting. Beremagene Geperpavec (B-VEC) for DEB Blister Untreated DEB Patient Skin B-VEC-treated Skin 1 Keratinocytes Dermoepidermal Jun
Slide 11: Topical B-VEC Was Evaluated in a Phase 1/2 Study at Stanford
Topical B-VEC Was Evaluated in a Phase 1/2 Study at Stanford 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.
Slide 12: In Ph1/2 Topical B-VEC was safe and well tolerated; COL7 expression observed
In Ph1/2 Topical B-VEC was safe and well tolerated; COL7 expression and molecular correction observed 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 administ
Slide 13: Statistically Significant Reduction in Wound Area achieved in Weeks 8, 10 and 12
Statistically Significant Reduction in Wound Area achieved in Weeks 8,10 and 12 Efficacy was observed in both recurrent and chronic wounds Patient 2 Patient 3 Wound 1: B-VEC Wound 2: Placebo Wound 3: B-VEC Median change in wound area across Phase 1/2 study B-VEC is an investigational therapy being s
Slide 14: Wound Closure for B-VEC vs. Placebo at Weeks 8 and 12
Wound Closure (>75% and 100%) for B-VEC vs. Placebo at Weeks 8 and 12 *p-values are based on Cochran-Mantel Haenszel (CMH) Test Without Adjusting for Week-to-Week Placebo Variability Change from baseline wound area ≥75% Change from baseline wound area = 100% B-VEC is an investigational therapy being
Slide 15: The Pivotal GEM-3 Study is Currently Enrolling
The Pivotal GEM-3 Study is Currently Enrolling 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 u
Slide 16: Phase 3 Design Optimized for Clinical and Commercial Success
Phase 3 Design Optimized for Clinical and Commercial Success 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 f
Slide 17: Autosomal Recessive Congenital Ichthyosis Associated With TGM1 Mutations
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 th
Slide 18: KB105 for TGM1 associated ARCI
KB105 for TGM1 associated ARCI KB105 is a replication-deficient HSV-1 vector that delivers multiple copies of human transglutaminase 1 (“TGM1”) via intradermal injection or topical application 3 TGM1 transcripts are generated, which allows the cell to produce functional TGM1 protein that localizes t
Slide 19: KB105 is Being Evaluated in a Phase 1/2 Study
KB105 is Being Evaluated in a Phase 1/2 Study The Ph1/2 trial (NCT04047732) is an open label, intra-patient comparison of KB105 and placebo Each patient on-study for approximately six months; 3 months of on-site visits followed by 3-month at-home imaging period Study PI: Dr. Amy Paller Design Enroll
Slide 20: Ph1 Data Shows KB105 safe; Molecular and Phenotypic Improvement Evident
Ph1 Data Shows KB105 safe; Molecular and Phenotypic Improvement Evident Repeat dosing with KB105 was well-tolerated with no drug related AEs and no immune response to HSV or TGM1 No vector shedding detected in swabs, blood or urine in all three patients KB105 treatment restored functional TGM1 prote
Slide 21: In-House GMP Manufacturing to Support both Clinical and Commercial Needs
In-House GMP Manufacturing to Support both Clinical and Commercial Needs
Slide 22: 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 Platform Supported by In-House Manufacturing Capaci
Slide 23: Leveraging Platform to Target New Tissues and Larger Indications
Leveraging Platform to Target New Tissues and Larger Indications
Slide 24: HSV-1 Has Potential Beyond Rare Skin
HSV-1 Has Potential Beyond Rare Skin B-VEC (COL7A1) for DEB KB105 (TGM1) for TGM1-ARCI KB104 (SPINK5) for Netherton’s Disease Additional preclinical candidates Wild-type HSV-1 Krystal’s Current Platform HSV-1 has natural affinity for epithelial cells, in addition to several other cell types, with fa
Slide 25: KB301 for Facial Wrinkles and Acne Scars
KB301 is designed to functional full-length human type III collagen (COL3) via injection KB301 for Facial Wrinkles and Acne Scars Many Characteristics of skin aging are due to aberrant collagen homeostasis The skin is largely composed of collagen-rich connective tissue, with dermal collagen, compose
Slide 26: Preclinical Data Supports KB301 Development
Preclinical Data Supports KB301 Development Aesthetic Indications A dose dependent increase in COL3A1 observed in young and aged mice A Similar dose dependent effect was observed in primary human dermal fibroblasts KB301 is an investigational therapy being studied in preclinical trials Human COL3A1
Slide 27: KB301 in Phase 1/2 with Initial Safety Data Expected Early 2021
KB301 in Phase 1/2 with Initial Safety Data Expected Early 2021 PEARL-1 (NCT04540900) is an intra-patient comparison of KB301 or placebo 22 patients will be enrolled cross 3 cohorts: Cohort 1 (n=6): Open label, dose ranging cohort will evaluate the safety and tolerability of two different dose level
Slide 28: KB407 for Cystic Fibrosis
We are developing KB407 as an inhalable, repeat dose gene therapy that delivers the full human CFTR gene KB407 for Cystic Fibrosis Gene therapy is an attractive modality for cystic fibrosis, though prior attempts have been unsuccessful Viral (adenovirus and AAV) and non-viral (DNA plasmids and stabi
Slide 29: Efficient Cell Targeting, CFTR Expression and Function In Vitro
Efficient Cell Targeting, CFTR Expression and Function In Vitro Robust, dose-dependent CFTR expression and functional correction in 2D Airway Epithelial Cell Culture KB407-expressed human CFTR properly localizes to the plasma membrane of transduced cells KB407-mediated functional correction of CF ph
Slide 30: CFTR Protein Expression Distributed Throughout the Lung In Vivo
CFTR Protein Expression Distributed Throughout the Lung In Vivo KB407 was effectively delivered to the lungs of mice using a clinically approved nebulizer Two repeat doses of KB407 in a nonhuman primate were well tolerated and distributed broadly throughout the lung Group No. Mouse Strain Test Artic
Slide 31: Financials and Milestones
Financials and Milestones YK Krystal
Slide 32: Krystal Summary: Current Status and Milestones
A fully integrated, clinical stage gene therapy company powered by proprietary HSV-1 vector technology Krystal Summary Current Status and Milestones Rare Skin B-VEC: Pivotal GEM-3 Trial currently enrolling; topline data expected 2021. Commercial planning in US and EU underway KB105: 4th patient (fir
Slide 33: Medicines for Rare Diseases – An HSV-1 Based Gene Therapy Company
Medicines for Rare Diseases – An HSV-1 Based Gene Therapy Company CORPORATE PRESENTATION November 2020
Slide 34: Links to Scientific Presentations
Links to Scientific Presentations Appendix B-VEC May 2020: Complete Phase 1/2 at SID 2020 – Link October 2019: Phase 1/2 Data Update – Link June 2019: Phase 1/2 Data Update – Link May 2018: Preclinical Poster at IID 2018 – Link September 2017: In vitro preclinical data at EB2017 - Link KB105 May 202
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