Krystal Biotech Inc., (“Krystal”) (NASDAQ: KRYS), the leader in
redosable gene therapies for rare diseases, today announced
positive results of its IND-enabling good laboratory practice (GLP)
toxicology study of KB407, an inhaled gene therapy candidate for
the treatment of cystic fibrosis (CF), in nonhuman primates (NHPs).
In addition, the Company announced initial preclinical
proof-of-concept for its second genetic pulmonary disease
candidate, KB408, for the treatment of alpha-1 antitrypsin
deficiency (AATD).
“Successful completion of this GLP toxicology and
biodistribution study is an important milestone not only for KB407,
but also for our emerging pulmonary portfolio,” said Suma Krishnan,
founder and chief operating officer of Krystal Biotech. “We are
excited to expand our pulmonary pipeline with the addition of KB408
for the potential treatment of alpha-1 antitrypsin deficiency and
look forward to continued progress with our additional discovery
phase candidates.”
KB407 for Cystic FibrosisKB407 is an inhaled
(nebulized) formulation of an engineered HSV-1 based vector
designed to deliver two copies of the full-length CFTR gene for the
treatment of cystic fibrosis. Previously presented in vitro and in
vivo data demonstrate robust transduction efficiency in
patient-derived airway epithelial cells, correction of the CF
phenotype in patient-derived organoids irrespective of the
underlying CFTR mutation within 24 hours of infection, and
distribution throughout the lungs of mice and a single nonhuman
primate when dosed via nebulization.
To further characterize the safety profile of KB407, Krystal
conducted a repeat-dose GLP toxicology and biodistribution study in
36 nonhuman primates (NHPs) who received three weekly doses of
either KB407 high dose (n=10), KB407 low dose (n=10), vehicle
(n=10), or air (n=6). Results of the study were positive and
included:
- Repeat doses of KB407 in NHPs were well tolerated, and the
No-Observed-Adverse-Effect Level (NOAEL) was at the highest dose
tested;
- KB407 was distributed throughout the lung tissue, including the
bronchioles and alveoli, with little-to-no vector detected in all
other tissues and fluids tested;
- Tissue samples collected for immunofluorescent analysis show
specific transduction of airway epithelia, with little-to-no vector
detected in lung-resident macrophages; and
- Lung samples harvested 28 days after the last dose demonstrate
persistence of the vector and CFTR expression to at least that
timepoint.
Next Steps: The Company intends to initiate a Phase 1 study of
KB407 in 3Q21.
KB408 for Alpha-1 Antitrypsin Deficiency KB408
is an inhaled (nebulized) formulation of our novel vector designed
to deliver two copies of the SERPINA1 gene, that encodes for normal
human alpha-1 antitrypsin (AAT) protein, for the treatment of
alpha-1 antitrypsin deficiency (AATD). AATD is a genetic condition
caused by mutations that lead to decreased levels and/or decreased
functionality of the AAT protein. The predominant disease
manifestation of severe AAT deficiency is emphysema, as lower
levels of functional AAT are insufficient to fully protect the
lungs from the enzymatic activity of neutrophil elastase and
progressive destruction of the lung tissue. There are an estimated
90,000 to 100,000 people in the US with severe AAT deficiency.
Building on the positive preclinical experience with repeat-dose
gene delivery to the lungs with KB407, KB408 leverages the same
formulation and route of administration. Initial preclinical data
show:
- KB408 successfully transduces primary airway epithelial cells
in vitro, leading to production and secretion of full length,
normal human AAT protein;
- In healthy immunocompetent mice administered a single dose of
KB408 or vehicle control to the airways, analyses of lung tissue
samples 24 hours post-dose show efficient vector transduction and
human AAT transgene expression;
- Analysis of bronchoalveolar lavage fluid harvested at the same
24-hour timepoint shows secretion of full-length AAT protein in
dosed animals; and
- Quantitative analysis of lung fluid harvests at necropsy
reveals no evidence of local immune activation/toxicity.
Next steps:More detailed preclinical data will be presented at a
future scientific conference. In addition, the Company has
submitted a pre-IND (Investigational New Drug) briefing package and
is scheduled to meet with the U.S. Food and Drug Administration
(FDA) regarding the preclinical IND enabling study requirements in
2Q21, which will determine next steps and timelines for the
program.
About Krystal BiotechKrystal Biotech,
Inc. (NASDAQ:KRYS) is a pivotal-stage gene therapy company
leveraging its novel, redosable gene therapy platform and in-house
manufacturing capabilities to develop therapies to treat serious
rare diseases. For more information, please
visit http://www.krystalbio.com.
Forward-Looking StatementsAny statements in
this press release about future expectations, plans and prospects
for Krystal Biotech, Inc., including but not limited to statements
about the development of Krystal’s product candidates, such as
plans for the design, conduct and timelines of ongoing clinical
trials of beremagene geperpavec (“B-VEC”), KB105, KB104, KB301,
KB407, and KB408; the clinical utility of B-VEC, KB105, KB104,
KB301, KB407 and KB408, and Krystal’s plans for filing of
regulatory approvals and efforts to bring B-VEC, KB105, KB104,
KB301, KB407 and KB408 to market; the market opportunity for and
the potential market acceptance of B-VEC, KB105, KB104, KB301,
KB407 and KB408; plans to pursue research and development of other
product candidates; the sufficiency of Krystal’s existing cash
resources; the unanticipated impact of COVID-19 on Krystal’s
business operations, pre-clinical activities and clinical trials;
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
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 trials 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 including B-VEC, KB105,
KB104, KB301, KB407 and KB408, the sufficiency of cash resources
and need for additional financing and such other important factors
as are set forth under the caption “Risk Factors” in Krystal’s
annual and quarterly reports on file with the U.S. Securities and
Exchange Commission. In addition, the forward-looking statements
included in this press release represent Krystal’s views as of the
date of this release. Krystal anticipates that subsequent events
and developments will cause its views to change. However, while
Krystal 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 Krystal’s views as of any date subsequent to
the date of this release.
CONTACTS:
Investors:Whitney Ijemwijem@krystalbio.com
Media:Mary CoyleTellMed
Strategiesmary.coyle@tmstrat.com
Source: Krystal Biotech, Inc.
Krystal Biotech (NASDAQ:KRYS)
Historical Stock Chart
From Jun 2024 to Jul 2024
Krystal Biotech (NASDAQ:KRYS)
Historical Stock Chart
From Jul 2023 to Jul 2024