Slide 1: Research & Development Oncology Program Announcement July 2023
© Copyright 2023 Krystal Biotech, Inc. All rights reserved. Research & Development Oncology Program Announcement July 2023
Slide 2: Speakers
Krystal | 2 Speakers Suma Krishnan President, Research & Development Trevor Parry, PhD VP, Research and Scientific Affairs David Chien, MD SVP, Clinical Development – Oncology Jason J. Luke, MD, FACP • Associate Professor of Medicine in the Division of Hematology/Oncology at the University of Pittsb
Slide 3: Forward-Looking Statements and Disclosures
Krystal | 3 Forward-Looking Statements and Disclosures Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties and are based on the current expectations and beliefs of Krystal Biotech, Inc. (the “Company”). Any statements in t
Slide 4: Agenda
Krystal | 4 Agenda Introduction Krish Krishnan; Chairman and CEO Krystal Oncology Program Therapeutic Approach & Target Indications Preclinical Overview Clinical Program Suma Krishnan, MS, MBA; President, Research & Development Samuel Broder, MD Trevor Parry, PhD; VP, Research and Scientific Affairs
Slide 5: Oncology Program Therapeutic Approach & Target Indications
Krystal Oncology Program Therapeutic Approach & Target Indications
Slide 6: Oncology Program is Building on Our Foundation in Gene Delivery
Krystal | 6 Oncology Program is Building on Our Foundation in Gene Delivery Lung • First Patient Dosed in cystic fibrosis clinical trial6 • Multiple inhaled delivery programs in or entering clinic in 2023 • Demonstrated in multiple animal models, including NHPs, that local delivery results in broad
Slide 7: Major Unmet Needs in Checkpoint Inhibitor (CPI) Refractory Solid Tumors
Krystal | 7 Major Unmet Needs in Checkpoint Inhibitor (CPI) Refractory Solid Tumors 1. NCI SEER. 2023; https://seer.cancer.gov/statfacts/html/common.html [accessed July 20, 2023], combined estimates for incident cases and deaths from cancers of the anus, bladder, bone and joint, brain and nervous sy
Slide 8: HSV-1 Based Vector Coded for the Local Delivery of Both IL-2 and IL-12 Cytokines
Krystal | 8 HSV-1 Based Vector Coded for the Local Delivery of Both IL-2 and IL-12 Cytokines with synergistic functions and therapeutic potential IL-2 IL-12 Reinforce Cytotoxic Effector Functions4,5 Complementary cytokine known to promote lymphocyte effector functions and IFN-gamma secretion + Expan
Slide 9: Advantages of Replication-Defective HSV-1 Based Cytokine Delivery Platform
Krystal | 9 Advantages of Replication-Defective HSV-1 Based Cytokine Delivery Platform well suited to accomplish dual goals of targeted but sustained delivery of IL-2 and IL-12 to the tumor Optimal vector platform to maximize cytokine expression and immune activation ✓ Efficiently transduces a wide
Slide 10: Potential KB707 Target Indications for the Skin
Krystal | 10 Potential KB707 Target Indications for the Skin KB707 Intratumoral KB707 Estimated 2023 US Melanoma Deaths1 8K Estimated Gorlin Pts in US5 10K+ Median Survival RDEB-SCC9* 2.4 Years CPI Refractory Melanoma • Over 97K new US melanoma cases expected in 2023; 14K classified as regional or d
Slide 11: Potential KB707 Target Indications for the Lung
Krystal | 11 Potential KB707 Target Indications for the Lung Inhaled KB707 Nebulizer KB707 44.3% PD-L1 Mid • Over 238K new lung cancer cases and over 127K deaths estimated in US in 20232 • CPI are increasingly used first-line but benefits from CPI transient and vary by PD-L1 expression level2-4 • In
Slide 12: Oncology Program KB707 Preclinical Update
Oncology Program KB707 Preclinical Update
Slide 13: Preclinical Research Objectives
Krystal | 13 Preclinical Research Objectives Research program built on stringent preclinical models to support clinical development Confirm expression, secretion, and bioactivity of vector-produced cytokines❑ ❑ ❑ Demonstrate safety and efficacy of repeated dosing of cytokine-expressing vectors in ch
Slide 14: KB707 Transduction and Cytokine Secretion by Mammalian Cells In Vitro
Krystal | 14 KB707 Transduction and Cytokine Secretion by Mammalian Cells In Vitro Vector-derived, secreted IL-12 and IL-2 equivalently bioactive to commercial recombinant proteins Krystal Biotech, Data on File. CD3, cluster of differentiation 3; CD8, cluster of differentiation 8; HEK, human embryon
Slide 15: Sustained Cytokine Expression After Intradermal Delivery to Mice
Krystal | 15 Sustained Cytokine Expression After Intradermal Delivery to Mice Vector genomes, cytokine transcripts, and protein detected out to seven days after single administration 1. Clinigen, 2019, Proleukin® (aldesleukin) FDA Label Krystal Biotech, Data on File. DNA, deoxyribonucleic acid; IL-1
Slide 16: Intratumoral IL-12 and IL-2 Effective in Cold Syngeneic Mouse Tumor Model
Krystal | 16 Intratumoral IL-12 and IL-2 Effective in Cold Syngeneic Mouse Tumor Model Clear antitumor effect and survival benefit in checkpoint inhibitor refractory B16F10 tumor model Single Flank B16F10 Melanoma Model • B16F10 is a subclone of the B16 cancer cell line originally derived from the s
Slide 17: Evidence of Systemic Immune Response with Intratumoral IL-12 and IL-2
Krystal | 17 Evidence of Systemic Immune Response with Intratumoral IL-12 and IL-2 Antitumor effect and survival benefit in dual flank B16F10 tumor model Peak systemic exposure lower than recombinant Dual Flank B16F10 Melanoma Model • Dual flank model mimics metastatic, checkpoint refractory melanom
Slide 18: Lung Delivery Effective in Metastatic Osteosarcoma Model
Krystal | 18 v Lung Delivery Effective in Metastatic Osteosarcoma Model Local delivery of IL-12 and IL-2 confers clear survival benefit in otherwise lethal, metastatic osteosarcoma 1. Khanna C, et al., Clin Exp Metastasis. 2000;18(3):261-271; 2. Lussier DM et al. J Immunother Cancer 2015;3(21) Kryst
Slide 19: Lung Delivery Also Confers Durable Protection from Tumor Rechallenge
Krystal | 19 v Lung Delivery Also Confers Durable Protection from Tumor Rechallenge Suggestive of memory adaptive immune response Krystal Biotech, Data on File. † KB703 encodes murine IL-12, KB704 encodes murine IL-2, and KB703 + KB704 is murine equivalent to KB707 IV, intravenous; PFU, plaque formi
Slide 20: Preclinical Summary
Krystal | 20 Preclinical Summary Robust efficacy in stringent, CPI-refractory preclinical models supports clinical development Transduces human cells in vitro leading to secretion of bioactive IL-2 and IL-12 ✓ ✓ ✓ ✓ ✓ Localized, durable cytokine expression in mouse skin after intradermal delivery Cl
Slide 21: Oncology Program KB707 Clinical Program
Oncology Program KB707 Clinical Program
Slide 22: KB707 Clinical Program Overall Phase 1/2 Approach
Krystal | 22 KB707 Clinical Program Overall Phase 1/2 Approach Deliver response to all solid tumor patients with immunotherapy Phase 1 first-in-human study with intratumoral administration • Evaluate the safety and tolerability of monotherapy in ascending dose • Demonstrate single agent anti-tumor a
Slide 23: KB707-01 Intratumoral Phase 1 Study
Krystal | 23 KB707-01 Intratumoral Phase 1 Study Open-label study to assess safety, tolerability, and preliminary efficacy DLT, dose limiting toxicity; EOT, end of treatment; MTD, maximum tolerated dose; ORR, objective response rate; OS, overall survival; PFS, progression free survival; PFU, plaque
Slide 24: KB707 Clinical Timeline
Krystal | 24 2023 2024 1H 2H 1H 2H KB707-01 Intratumoral KB707-02 Inhaled KB707 Clinical Timeline Both routes of administration under evaluation in Phase 1 by 1H 2024 FDA, US Food and Drug Administration; FPD, first patient dosed; IND, investigational new drug; US, United States Other than VYJUVEK,
Slide 25: Cutaneous oncology landscape for refractory disease
Cutaneous oncology landscape for refractory disease Jason J. Luke, MD, FACP Associate Professor Director of the Immunotherapy and Drug Development Center Associate Director for Clinical Research
Slide 26: Treatment flow chart across melanoma stages
Treatment flow chart across melanoma stages @jasonlukemd
Slide 27: 5-year survival with anti-PD1 +/- CTLA4 in melanoma
5-year survival with anti-PD1 +/- CTLA4 in melanoma 5 year overall survival Pembro: 38.7% Ipi: 31.0% 5 year overall survival Ipi+Nivo: 52% Nivo: 44% Ipi: 26% Anti-PD1 or Anti-PD1 + Anti-CTLA4 Robert et al. Lancet Onc. 2019; Larkin et al. N Engl J Med. 2019; Luke and Hodi. Oncologist. 2013; Luke and
Slide 28: Confirmed ORR by BICR NIVO + RELA
Confirmed ORR by BICR NIVO + RELA (n = 355) NIVO (n = 359) ORR % (95% CI) 43.1 (37.9-48.4) 32.6 (27.8-37.7) DBL date: October 28, 2021. Median follow-up: 19.3 mo Updated PFS by BICR OS NIVO + RELA (n = 355) NIVO (n = 359) mPFS, mo (95% CI) 10.22 (6.51–14.75) 4.63 (3.48-6.44) HR (95% CI) 0.78 (0.64–0
Slide 29: Majority of patients who progress to stage IV now eligible for peri-operative systemic therapy
Luke et al. Lancet. 2022; Weber et al. NEJM 2021; Long et al. NEJM 2021; Patel et al. ESMO. 2022 Majority of patients who progress to stage IV now eligible for peri- operative systemic therapy @jasonlukemd BRAF-MEK Stage IIB/C – anti-PD1 Stage III – anti-PD1 Stage IIIB/C/IV – anti-PD1
Slide 30: Melanoma Vignette
Melanoma Vignette • Patient with a 3.2 mm melanoma on the right leg undergoes resection and nodal evaluation identifying 2 nodes involved. Tumor is BRAF WT • Adjuvant treatment with nivolumab is given for eight months with progression in new nodes and lung. • Nivo + ipi vs Nivo + rela are considered
Slide 31: Anti-PD1 in cutaneous squamous cell carcinoma
@jasonlukemd Midgen et al. NEJM. 2018; Gross et al. NJEM. 2023 Anti-PD1 in cutaneous squamous cell carcinoma Anti-PD1 (cempilimab in locally advanced cSCC) Neoadjuvant cempilimab in cSCC)
Slide 32: Basal cell carcinoma treatment options
Basal cell carcinoma treatment options @jasonlukemd Sekulic et al. N Engl J Med. 2012; Midgen et al. Lancet Oncology. 2015 “Chronic grade 1-2 toxicity is worse for the patient than an episode of grade 3-4” Len Saltz, MD - MSKCC Hedgehog inhibitor efficacy and toxicity Anti-PD1 efficacy
Slide 33: cSCC Vignette
cSCC Vignette • Patient with history of multiple early stage non-melanoma skin cancers develops a bleeding ulcer on the scalp. • Moh’s procedure removes the lesion but within 4 months the skin graft erodes and the ulcer returns • A second resection attempt is considered but aborted when margins are
Slide 34: Conclusions
Conclusions • In melanoma, unmet needs remains after progression on anti-PD1 • KB707 has high upside potential for combinations with anti-PD1 in earlier lines of therapy given arming with IL2 and IL12 • Therapeutic landscape open in non-melanoma skin cancers • Anti-PD1 is SOC but 50% do not respond
Slide 35: Q&A Panelists
Krystal | 35 Q&A Panelists Suma Krishnan President, Research & Development Trevor Parry, PhD Vice President, Research and Scientific Affairs Jason J. Luke, MD, FACP David Chien, MD Senior Vice President, Clinical Development – Oncology Krish Krishnan Chairman and CEO Samuel Broder, MD
Slide 36: © Copyright 2023 Krystal Biotech, Inc. All rights reserved.
© Copyright 2023 Krystal Biotech, Inc. All rights reserved.