Krystal Biotech Announces Initial Clinical Update for Rare Respiratory Disease Programs KB408 and KB407 Including Early Clinical Evidence of Gene Delivery to the Lung of AATD Patients and Increase in Lung AAT to Therapeutic Levels
Krystal Biotech (NASDAQ: KRYS) announced clinical updates for its inhaled genetic medicine programs KB408 and KB407. The KB408 Phase 1 SERPENTINE-1 study showed successful SERPINA1 gene delivery and AAT expression in AATD patients. In two patients receiving bronchoscopies, conducting airway epithelial cells showed significant increases in AAT expression (35-39%) after KB408 dosing. One patient demonstrated an 8-fold increase in lung AAT levels and over 50% reduction in active neutrophil elastase.
The KB407 Phase 1 CORAL-1 study for cystic fibrosis received conditional sanctioning from CFF TDN. Five patients have been enrolled, with three receiving single doses and three receiving two daily doses. Both KB408 and KB407 demonstrated favorable safety profiles with only mild to moderate, transient adverse events reported. Additional data updates are expected in 2025.
Krystal Biotech (NASDAQ: KRYS) ha annunciato aggiornamenti clinici per i suoi programmi di medicina genetica inalata KB408 e KB407. Lo studio di Fase 1 SERPENTINE-1 per KB408 ha mostrato una riuscita consegna del gene SERPINA1 e espressione di AAT nei pazienti con AATD. In due pazienti sottoposti a broncoscopie, le cellule epiteliali delle vie aeree hanno mostrato aumenti significativi nell'espressione di AAT (35-39%) dopo la somministrazione di KB408. Un paziente ha dimostrato un aumento di otto volte nei livelli di AAT polmonare e oltre il 50% di riduzione dell'elastasi neutrofila attiva.
Lo studio di Fase 1 CORAL-1 per la fibrosi cistica ha ricevuto l'approvazione condizionata da CFF TDN. Cinque pazienti sono stati arruolati, tre dei quali hanno ricevuto dosi singole e tre hanno ricevuto due dosi giornaliere. Sia KB408 che KB407 hanno mostrato profili di sicurezza favorevoli con solo eventi avversi lievi a moderate e transitori riportati. Aggiornamenti aggiuntivi sui dati sono attesi nel 2025.
Krystal Biotech (NASDAQ: KRYS) anunció actualizaciones clínicas para sus programas de medicina genética inhalada KB408 y KB407. El estudio de Fase 1 SERPENTINE-1 de KB408 mostró una exitosa entrega del gen SERPINA1 y expresión de AAT en pacientes con AATD. En dos pacientes que recibieron broncoscopias, las células epiteliales de las vías respiratorias mostraron aumentos significativos en la expresión de AAT (35-39%) después de la administración de KB408. Un paciente mostró un aumento de ocho veces en los niveles de AAT en los pulmones y una reducción de más del 50% en la elastasa neutrofílica activa.
El estudio de Fase 1 CORAL-1 para la fibrosis quística recibió aprobación condicional de CFF TDN. Se han inscrito cinco pacientes, de los cuales tres recibieron dosis únicas y tres recibieron dos dosis diarias. Tanto KB408 como KB407 mostraron perfiles de seguridad favorables, con solo eventos adversos leves a moderados y transitorios reportados. Se esperan actualizaciones adicionales de datos en 2025.
크리스탈 바이오텍 (NASDAQ: KRYS)는 흡입 유전자 치료제 프로그램 KB408 및 KB407의 임상 업데이트를 발표했습니다. KB408 1상 SERPENTINE-1 연구는 AATD 환자에서 SERPINA1 유전자 전달 및 AAT 발현에 성공했음을 보여주었습니다. 기관지경 검사를 받은 두 환자에서 기도 상피 세포는 KB408 투여 후 AAT 발현이 유의미하게 증가(35-39%)했습니다. 한 환자는 폐 AAT 수치가 8배 증가하고 활성 중성구 엘라스타제는 50% 이상 감소했습니다.
낭포성 섬유증을 위한 KB407 1상 CORAL-1 연구는 CFF TDN으로부터 조건부 승인을 받았습니다. 5명의 환자가 등록되었으며, 3명은 단일 용량, 3명은 하루 2회 용량을 받았습니다. KB408과 KB407 모두 경증에서 중증의 일시적인 부작용이 보고되었을 뿐 안전성 프로필이 양호하게 나타났습니다. 추가 데이터 업데이트는 2025년에 예상됩니다.
Krystal Biotech (NASDAQ: KRYS) a annoncé des mises à jour cliniques pour ses programmes de médecine génétique inhalée KB408 et KB407. L'étude de phase 1 SERPENTINE-1 pour KB408 a montré une réussite de la livraison du gène SERPINA1 et de l'expression d'AAT chez les patients atteints d'AATD. Chez deux patients ayant reçu des bronchoscopies, les cellules épithéliales des voies aériennes ont montré des augmentations significatives de l'expression de l'AAT (35-39%) après l'administration de KB408. Un patient a démontré une augmentation huit fois plus élevée des niveaux d'AAT dans les poumons et une réduction de plus de 50 % de l'élastase neutrophile active.
L'étude de phase 1 CORAL-1 pour la fibrose kystique a reçu une approbation conditionnelle de la part de CFF TDN. Cinq patients ont été enrôlés, dont trois ont reçu des doses uniques et trois ont reçu deux doses quotidiennes. Tant KB408 que KB407 ont montré des profils de sécurité favorables, avec seulement des événements indésirables légers à modérés et transitoires signalés. Des mises à jour supplémentaires des données sont attendues en 2025.
Krystal Biotech (NASDAQ: KRYS) hat klinische Updates für seine inhalativen Gentherapie-Programme KB408 und KB407 angekündigt. Die Phase-1-Studie SERPENTINE-1 zu KB408 zeigte eine erfolgreiche Genübertragung des SERPINA1-Gens und AAT-Expression bei AATD-Patienten. Bei zwei Patienten, die sich einer Bronchoskopie unterzogen, zeigten die Epithelzellen der Atemwege signifikante Zunahmen der AAT-Expression (35-39%) nach der Dosierung von KB408. Ein Patient zeigte einen 8-fachen Anstieg der AAT-Werte in der Lunge und eine über 50%ige Reduktion der aktiven neutrophilen Elastase.
Die Phase-1-Studie CORAL-1 zu KB407 für Mukoviszidose erhielt eine bedingte Genehmigung von CFF TDN. Fünf Patienten wurden eingeschrieben, wobei drei eine Einzeldosis und drei zwei Dosen pro Tag erhielten. Sowohl KB408 als auch KB407 wiesen günstige Sicherheitsprofile auf, mit nur milden bis moderaten, vorübergehenden unerwünschten Ereignissen. Zusätzliche Datenaktualisierungen werden für 2025 erwartet.
- Clear evidence of successful gene delivery in AATD patients with 35-39% of cells showing AAT expression post-KB408 treatment
- 8-fold increase in lung AAT levels and 50% reduction in neutrophil elastase in one patient
- Serum AAT increases observed in all Cohort 2 patients, with increases ranging from 270 nM to 5.3 µM
- Both KB408 and KB407 demonstrated favorable safety profiles with only mild to moderate adverse events
- CFF TDN granted conditional sanctioning for KB407 Phase 1 study
- Lavage samples couldn't be collected from one patient, preventing AAT quantification
Insights
Clear evidence of SERPINA1 gene delivery and AAT expression following KB408 administration in AATD patients
Both KB408 for AATD patients and KB407 for patients with cystic fibrosis were safe and well tolerated at all dosing regimens evaluated to date
Conditional sanctioning of the KB407 Phase 1 CF Study CORAL-1 protocol by CFF TDN
Investor call and webcast to be held December 12 at 8:30 am ET to discuss data update
PITTSBURGH, Dec. 12, 2024 (GLOBE NEWSWIRE) -- Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS), a commercial-stage biotechnology company, announced today clinical data updates for both KB408 and KB407, the Company’s clinical-stage, inhaled genetic medicine programs in Phase 1 for the treatment of rare respiratory diseases. Today’s updates include molecular data from multiple patients demonstrating SERPINA1 delivery and alpha-1 antitrypsin (AAT) expression within the respiratory tract following KB408 administration as well as safety and tolerability data for both KB407 and KB408 that, taken together, highlight the potential of the Company’s platform to safely deliver genetic cargo to the lung.
“To achieve meaningful AAT expression levels and functionality with the first dose of KB408 is a very exciting development for this program and for our alpha-1 antitrypsin deficiency (AATD) patients,” said Robert A. Sandhaus, MD, PhD, FCCP, Professor of Medicine at the National Jewish Health in Denver, Executive Vice President and Senior Medical Director of AlphaNet, as well as Clinical Director of the Alpha-1 Foundation. “Even though the first intravenous augmentation therapy was approved decades ago, we still don’t have a good understanding of the impact these therapies are having on lung disease. A safe, effective, non-invasive therapy that is less burdensome on patients and supported by molecular evidence of function in the lung is needed, and we look forward to additional clinical updates on KB408 in the months to come.”
The Company will host an investor conference call and webcast today, Thursday, December 12, 2024, at 8:30 am ET, to discuss the clinical data updates. Investors and the general public can access the live webcast at: https://www.webcaster4.com/Webcast/Page/3018/51767. For those unable to listen to the live webcast, an archived version will also be available on the Investors section of the Company’s website for at least 30 days.
KB408 for the treatment of alpha-1 antitrypsin deficiency (AATD) lung disease
KB408 is being evaluated in the Company’s Phase 1 SERPENTINE-1 study. SERPENTINE-1 is an open label, single dose escalation study in adult patients with AATD with a Pi*ZZ or a Pi*ZNull genotype. SERPENTINE-1 is designed to include up to three dose escalation cohorts evaluating single administrations of 109, 1010, and 1011 PFU of KB408 via inhalation. Additional details of the SERPENTINE-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06049082.
As of the December 6, 2024 data cut-off, a total of seven (7) patients had been enrolled in SERPENTINE-1, including 3 patients in Cohort 1 who had received the 109 PFU KB408 dose and 4 patients in Cohort 2 who had received the 1010 PFU KB408 dose. One patient in each of Cohort 1 and Cohort 2 were receiving background intravenous (IV) augmentation therapy.
Two patients in Cohort 2 also received bronchoscopies to assess SERPINA1 delivery and AAT levels in the lung. Both a baseline bronchoscopy and a post-dose bronchoscopy, conducted 24 to 48 hours after KB408 dosing, were completed. One of the two patients who received bronchoscopies was receiving background IV augmentation therapy.
Clear evidence of successful gene delivery was observed in both patients, including high rates of transduction and AAT expression in the conducting airways of both patients as assessed via bronchoscopy. Key molecular findings for each patient are summarized below:
Patient Not on Background IV Augmentation
- A clinically meaningful proportion of conducting airway epithelial cells were transduced following administration of a single dose of KB408, with the percentage of cells positive for AAT expression increasing from
0% at baseline to39% after KB408 dosing. - Free AAT levels in lung epithelial lining fluid increased over 8-fold, rising from 85 nM at baseline to 729 nM after KB408 dosing.
- AAT functionality was also confirmed by detection of AAT-NE binding, with the percentage of active, unbound neutrophil elastase in epithelial lining fluid dropping from
97.2% at baseline to40.2% – an over50% absolute reduction achieved within 48 hours after dosing.
Patient on Background IV Augmentation
- Again, a clinically meaningful proportion of conducting airway epithelial cells were transduced following administration of a single dose of KB408, with the percentage of cells positive for AAT expression increasing from
3% at baseline to35% after KB408 dosing. - Lavage samples could not be successfully collected from this patient, preventing accurate quantification of AAT and neutrophil elastase binding in lung epithelial lining fluid. However, both KB408 genomes and SERPINA1 RNA transcripts were detected in multiple bronchial brushing samples, with an average of 4 x 103 genome copies and 4 x 102 transcript copies detected, providing further support of successful gene delivery and expression in the KB408 treated lung.
In addition to evidence of KB408 transduction and AAT expression in the lungs of these two patients, increases in serum AAT levels were also detected in all four Cohort 2 patients after KB408 dosing, suggestive of broad dissemination of KB408-encoded AAT following expression in the lung. Increases in serum AAT relative to baseline ranged from 270 nM to 5.3 µM in the three patients that were not on confounding background IV augmentation, including in one case increases in serum AAT from 4.4 µM at baseline to 9.7 µM after KB408 dosing.
KB408-related adverse events for all seven patients treated in Cohort 1 and Cohort 2 were mild to moderate and transient. No serious adverse events have been reported.
“With clear evidence of gene delivery, including detection of high nanomolar concentrations of AAT in lung epithelial lining fluid, as well as corresponding reductions in the percentage of unbound, active neutrophil elastase by over
The Company will enroll two additional patients in Cohort 2 of SERPENTINE-1 and expects to provide additional data updates in 2025. In parallel, the Company will open Cohort 3 to explore safety and gene delivery at the highest dose of KB408.
KB407 for the treatment of cystic fibrosis (CF)
Based on preclinical data submitted to date by the Company, the Cystic Fibrosis Foundation (CFF) Therapeutic Development Network (TDN) Clinical Research Executive Committee has granted conditional sanctioning of the Company’s KB407 Phase 1 CORAL-1 study protocol subject to review of the data monitoring committee charter, if required, to align with CFF TDN standards. No additional preclinical updates for KB407 are required, and the Company expects to be fully sanctioned and open sites within the CFF TDN shortly.
KB407 is being evaluated in the Phase 1 CORAL-1 study. CORAL-1 is an open label, dose escalation study in adult patients with CF. CORAL-1 is designed to include up to three dose escalation cohorts evaluating either one, two, or four daily administrations of 109 PFU of KB407 via inhalation. Additional details of the CORAL-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
As of the December 6, 2024 data cut-off, a total of five (5) patients had been enrolled in CORAL-1. Three patients received a single 109 PFU KB407 dose in Cohort 1 and three patients, including one roll-over from Cohort 1, received two daily 109 PFU KB407 doses in Cohort 2. All but one patient was on background modulator therapy.
The initial focus of Cohorts 1 and 2 was safety of single and repeat inhaled administration of KB407 in patients with CF. As observed with KB408, KB407 has been well tolerated in all patients dosed to date. KB407-related adverse events for all five patients treated in Cohort 1 and Cohort 2 were mild to moderate and transient. No serious adverse events have been reported. The Company expects to report data from Cohort 3 in 1H 2025, including data on CFTR gene delivery and expression in patients with cystic fibrosis.
About Krystal Biotech, Inc.
Krystal Biotech, Inc. (NASDAQ: KRYS) is a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEK® is the Company’s first commercial product, the first-ever redosable gene therapy, and the first medicine approved by the FDA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and X (formerly Twitter).
Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc., including statements about the potential of the Company’s platform to safely deliver genetic cargo to the lung; the Company’s clinical-stage, inhaled genetic medicines programs in Phase 1 for the treatment of rare respiratory diseases; the Company’s plans to enroll two additional patients in Cohort 2 of its SERPENTINE-1 study and provide additional data updates in 2025; the Company’s plans to open Cohort 3 of its SERPENTINE-1 study to explore safety and gene delivery at the highest dose of KB408; the Company’s expectation to be fully sanctioned and open sites within the CFF TDN shortly; the Company’s expectation that it will report data from Cohort 3 of its CORAL-1 study in 1H 2025, including data on CFTR gene delivery and expression in cystic fibrosis patients; 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 uncertainties inherent in the initiation and conduct of clinical trials, as well as regulatory review of clinical trials and applications for marketing approvals; and such other important factors as are set forth under the caption “Risk Factors” in the Company’s annual and quarterly reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements included in this press release represent the Company’s views as of the date of this press release. 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 press release.
CONTACT
Investors and Media:
Stéphane Paquette, PhD
Krystal Biotech
spaquette@krystalbio.com
FAQ
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