Krystal Biotech Provides Update on the Clinical Trial Evaluating Topical KB105 for the Treatment of TGM-1 Associated Ichthyos...
July 01 2021 - 4:15PM
Krystal Biotech Inc., (“Krystal”) (NASDAQ: KRYS), the leader in
redosable gene therapies for rare diseases, today announced updated
results from the Phase 1/2 clinical trial evaluating topical
administration of KB105 in patients with autosomal recessive
congenital ichthyosis (ARCI) associated with mutations in the TGM1
gene. These data show that repeat doses of KB105 continue to be
well tolerated with no adverse events and with no evidence of
immune response, systemically or at the sites of application.
Phenotypic improvement, based on the IGA scale, was observed at
each KB105 dosing site at varying time points throughout the 30-day
dosing period, with the maximum effect observed in the treatment
areas that received the highest KB105 dose.
These results build on previous data showing a dramatic increase
in KB105-mediated TGM-1 expression and activity in 3 patients,
which correlated with an improvement on the IGA scale after KB105
topical treatment, with or without pretreatment of the area through
micro-needling. No drug-related adverse effects were reported.
“The totality of the data from our Phase 1/2 trial is
encouraging, showing that topical application of KB105 to
exfoliated skin results in detectable and correctly localized and
functionally active TGM-1 enzyme,” said Suma Krishnan, Chief
Operating Officer of Krystal Biotech. “With this data in hand, we
look forward to having continued discussions with patients and
physicians to determine the optimal dosing regimen and endpoints to
take forward into the next Phase 2 cohort, which we expect will
include pediatric patients, in 2022.”
Initial Phase 2 DataAn adult subject, aged 63,
was enrolled and four 100cm2 treatment areas were identified. Each
treatment area was assigned to receive repeat doses of 4.0x109 PFU
(n=2 treatment areas) or 1.0x1010 PFU (n=2 treatment areas). Each
area was dosed on Day 1 and 3, after which dosing continued either
every 3 days (n=2 treatment areas) or every 6 days (n=2 treatment
areas) up to day 30. Treatment areas were clinically evaluated at
pre- and post-KB105 application timepoints, using a 5-point IGA
scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 =
very severe).
Repeated topical doses of KB105 were well tolerated, and no
drug-related adverse effects were reported. No vector shedding or
systemic viral exposure was detected at any time point. Improvement
on the IGA scale was observed in each treatment area, with the
maximum effect observed in TA3 and TA4 that received the highest
dose; at day 27, the investigator assigned an IGA score of 2, which
was improved as compared to baseline score of 4 in each area.
Variable 1-point improvements were observed at other time points
and in the treatment areas that received the lowest dose. As in the
Phase 1 portion of the trial, TGM1 turnover was observed to be
variable but relatively rapid, and the observed IGA improvements
were not sustained through day 60.
More detailed data is available in the Company’s corporate
presentation, which is available at https://ir.krystalbio.com/.
Phase 1 ReviewThe Phase 1 portion of the study
enrolled 3 adult subjects, on whom four 20cm2 treatment areas were
identified. One site received placebo, and three sites each
received topical doses of 2.0x109 PFU at varying frequencies, up to
5 or 6 repeat doses throughout the 90-day study period. All 3
subjects showed a dramatic increase in KB105-mediated TGM-1
expression and activity, which correlated with an improvement in
scaling with KB105 topical treatment, with or without pretreatment
of the area through micro-needling. No drug-related adverse effects
were reported. Pre-existing immunity to HSV-1 had no impact on
KB105 efficacy, and repeat dosing with KB105 did not exacerbate
immune response to HSV-1. KB105-mediated TGM-1 was correctly
localized and functionally active based on an in situ activity
assay. KB105 treated areas showed reduced reversion to ichthyotic
scaling phenotype which correlated with molecular correction. These
data were previously presented at the Society for Investigative
Dermatology (SID) 2020 annual meeting. The presentation is
available here.
In these subjects, TGM1 turnover was observed to be variable and
rapid, and pharmacokinetic data suggested that the optimal dosing
frequency may be more frequent. Further, phenotypic evaluation was
limited by small treatment areas. Based on these Phase 1 results,
the dose, dosing frequency, and size of the treatment areas were
adjusted for Phase 2.
Next StepsKrystal intends to discuss these data
with patients and key opinion leaders to help inform next steps. In
particular, the company will assess the optimal dosing frequency as
well as additional clinical endpoints, including a novel scale
designed for ichthyosis. The Company intends to complete these
discussions by the end of the year, and continue dosing in the
Phase 2 trial, in 2022.
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 KB105 and the clinical utility of KB105 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 will be indicative of the
results of ongoing or future trials, uncertainties associated with
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 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.
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