Krystal Biotech, Inc. · NASDAQ:KRYS
Krystal Biotech — Technical Presentation (November 2020)
20 slides from Krystal Biotech's technical presentation, Nov 9, 2020
Slide 1: KB407 for the treatment of cystic fibrosis
KB407 for the treatment of cystic fibrosis November 2020 Exhibit 99.2
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: Despite recent approvals, there remains significant unmet need in CF
Despite recent approvals, there remains significant unmet need in CF Epidemiology of cystic fibrosis1 CF Prevalence & Incidence2 >70,000 patients with CF worldwide >30,000 patients in US CF registry2 ~1,000 new cases of CF diagnosed each year in the US 1: World Health Organization (2004). “The molec
Slide 4: Gene therapy is an attractive approach; our vector is uniquely positioned
Gene therapy is an attractive approach; our vector is uniquely positioned to overcome prior limitations CF is a monogenic disease; replacing the missing or dysfunctional protein could fundamentally correct the defect Various gene therapy approaches have been tried and ultimately failed in their atte
Slide 5: KB407 is an inhaled gene therapy for the treatment of CF
KB407 is an inhaled gene therapy for the treatment of CF Nebulizer KB407 product characteristics: Replication incompetent HSV-1 Delivers two copies of full length, human CFTR protein (mutation agnostic approach) Duration of nebulization expected to be under 30 minutes, using a commercially available
Slide 6: In vitro data shows KB407 can be nebulized and transduce target lung cells
In vitro data shows KB407 can be nebulized, successfully transduce target lung cells and induce expression of fully functional and properly localized CFTR
Slide 7: KB407 is amenable to aerosolization without loss of titer
KB407 is amenable to aerosolization without loss of titer ns ns ns: not significant ns Our vector can be formulated and delivered via nebulizer with no significant change in activity KB407 is an investigational therapy being studied in preclinical trials
Slide 8: Dose dependent expression observed in CF patient derived airway epithelial cells
Dose dependent expression observed in CF patient derived airway epithelial cells Protein activity determined using a CFTR-dependent fluorescent dye uptake assay. KB407 infects primary CF cells in a dose-dependent manner, resulting in robust expression of human CFTR at the transcript and protein leve
Slide 9: KB407-Expressed CFTR is Properly Glycosylated in Mammalian Cells
KB407-Expressed CFTR is Properly Glycosylated in Mammalian Cells Proper glycosylation indicates the protein has been produced and processed correctly into mature CFTR CFTR protein is assembled on the endoplasmic reticulum-associated ribosome and is eventually trafficked to the cell membrane where it
Slide 10: Preliminary in vitro data supports KB407 ability to penetrate CF mucus
Preliminary in vitro data supports KB407 ability to penetrate CF mucus Collaboration with Epithelix using MucilAirTM system derived from F508del CF patient biopsy The MucilAirTM system provides an in vitro replication of the CF airway, including active mucus production After 7 days of mucus producti
Slide 11: KB407 corrects CF phenotype in clinically translatable organoid model
KB407 corrects CF phenotype in clinically translatable organoid model
Slide 12: Efficacy in patient derived organoids correlates with clinical efficacy
Efficacy in patient derived organoids correlates with clinical efficacy Van Mourik et al. (2019). “Intestinal organoids to model cystic fibrosis”. Berkers et al. (2019). “Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis”. Organoids have proven to be valuable disease models in CF The
Slide 13: Treatment with KB407 corrected PDO morphology within hours
Treatment with KB407 corrected PDO morphology within 24 hours CF PDOs Healthy PDOs In healthy patient derived organoids (left), CFTR protein functions properly and enables water transport across the membrane leading to plump, round appearing PDOs In PDOs derived from CF patients (right), CFTR does n
Slide 14: In vivo studies demonstrate successful nebulization of KB407 with broad lung distribution
In vivo studies (mice and nonhuman primate) demonstrate successful nebulization of KB407 with broad distribution throughout the lung; no toxicity or significant safety findings were observed
Slide 15: KB407 is effectively delivered to the lungs of healthy and CFTR-/- mice
KB407 is effectively delivered to the lungs of healthy and CFTR-/- mice Group No. Mouse Strain Test Article Route of Administration Termination 1 C57BL/6J Vehicle Nebulization 48h 2 C57BL/6J KB407 Nebulization 48h 3 Cftrtm1UncTg(FABPCFTR)1 Jaw/J KB407 Nebulization 48h 3 groups of 4 mice were simulta
Slide 16: Nebulized KB407 does not induce inflammation or cell infiltration
Nebulized KB407 does not induce inflammation or cell infiltration Qualitative (right) and quantitative (below) analysis shows no evidence of local immune activation Certified pathologist found no adverse safety findings (fibrosis, necrosis, immune cell infiltration or immune activation) in any exami
Slide 17: KB407 was safe and well tolerated in a nonhuman primate
KB407 was safe and well tolerated a nonhuman primate A single cynomolgus macaque received 2 doses of KB407 two weeks apart A single monkey received 3 serial doses of vehicle alone, KB407 low dose and KB407 high dose over 19 days At day 19 (2 days following high dose KB407) animals were sacrificed an
Slide 18: Program Summary
KB407 Program Summary KB407 infects cells derived from CF patient airways in a dose-dependent manner, resulting in robust expression of human CFTR at the transcript and protein levels The vector efficiently produces functional, full-length CFTR protein that properly traffics to the cell membrane KB4
Slide 19: Next Steps
KB407 Next Steps GLP toxicity study in 40 nonhuman primates ongoing Clinical trial initiation anticipated in 2021
Slide 20: KB407 for the treatment of cystic fibrosis
KB407 for the treatment of cystic fibrosis November 2020
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