Cabaletta Bio Presents New Interim Data from the DesCAARTes™ Phase 1 Trial at the 31st EADV Congress
September 10 2022 - 07:00AM
GlobeNewswire Inc.
Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology
company focused on the discovery and development of targeted cell
therapies for patients with autoimmune diseases, today presented
updated clinical and translational data through 6 months of
follow-up in cohorts A1 through A4 as well as 28-day safety data
and DSG3-CAART persistence data through day 29 for cohorts A1
through A5 from the DesCAARTes™ trial at the 31st European Academy
of Dermatology and Venereology (EADV) Congress, which is being held
in Milan, Italy from September 7-10, 2022.
“The new data continue to support the favorable safety profile
of DSG3-CAART, with no dose-limiting toxicities, and one grade 1
cytokine release syndrome through cohort A5, at a dose of up to 7.5
billion DSG3-CAART cells. No clear trends in antibody levels or
disease activity reduction were observed, though one subject in
cohort A4 had no disease activity by three months post-infusion
while reducing steroid usage during that period, an antibody titer
that dropped more than 20% by three months post-infusion, and was
the only patient in the first four cohorts that had detectable
DSG3-CAART persistence at the 3 month time point following initial
DSG3-CAART infusion,” said David J. Chang, M.D., Chief Medical
Officer of Cabaletta. “The 2 to 3 fold increase in infusion dose in
cohort A5 relative to cohort A4 did not result in a dose-dependent
increase in one month DSG3-CAART persistence, suggesting strategies
beyond single dose escalation may be required to potentially
further increase DSG3-CAART in vivo exposure and generate durable
clinical responses. We believe these data support a multiple
infusion approach, and provide a rationale to prioritize the
combination sub-study, which will employ pre-treatment with
intravenous immunoglobulin and cyclophosphamide to potentially
increase the in vivo expansion, persistence and activity of
DSG3-CAART.”
The updated interim data included 16 treated subjects, four
cohorts with three patients per cohort and one cohort with four
patients, with twelve having completed six months of follow-up
after DSG3-CAART infusion, and four having completed 28-day
follow-up after DSG3-CAART infusion. The presentation is available
on the Company’s website
at https://www.cabalettabio.com/technology/posters-publications.
The data demonstrate:
- Doses up to 7.5 billion DSG3-CAART cells (cohort A5) were
generally well tolerated, with no DLTs, and one grade 1 CRS.
- There was a dose-dependent increase in DSG3-CAART persistence
through day 29 in cohorts A1 to A4. DSG3-CAART persistence through
day 29 in cohort A5 was similar to that observed in cohort A4.
- In cohorts A1 to A4:
- Through six months post DSG3-CAART infusion, no clear pattern
was observed in changes in anti-DSG3 Ab levels (ELISA) or disease
activity (PDAI) through cohort A4.
- One subject in cohort A4 demonstrated a transient improvement
in several assessments of efficacy, including DSG3-CAART
persistence at 3 months, decrease of anti-DSG3 Ab levels >20% at
2- and 3-months post-infusion, improvement in PDAI score and
decreased steroid usage.
The rationale for prioritization of the next planned dosing
cohorts is as follows:
- Combination sub-study: A4 dose (2.5x109 cells) combined with
cyclophosphamide (CY) and intravenous immunoglobulin (IVIg)
pre-treatment has been prioritized based on leveling off of
DSG3-CAART persistence through day 29 from cohorts A4 to A5.
- CY may reduce cells that compete for cytokines necessary for
DSG3-CAART activation & proliferation.
- This combination is designed to reduce anti-DSG3
autoantibodies, which may block DSG3-CAART.
- CY may reduce pathogenic autoantibody-secreting B cells.
- IVIg may facilitate this reduction through several mechanisms,
including binding and blocking the autoantibodies.
- Cohort A6m: 2-fold higher than A5 dose (1-1.5x1010 cells): Two
A5 infusions will be administered 3 weeks apart to potentially
increase the duration of in vivo exposure and persistence of
DSG3-CAART.
The trial is currently being conducted across multiple clinical
sites throughout the United States and is enrolling patients in the
combination sub-study. If no DLTs are observed, 28-day safety and
persistence data through day 29 for the combination sub-study
cohort are anticipated to be shared at a scientific or medical
meeting during the first quarter of 2023.
About the DesCAARTes™ Phase 1 TrialCabaletta’s
DesCAARTes™ Phase 1 trial is an open-label, dose escalation,
multi-center study of DSG3-CAART in adults with mucosal-dominant
pemphigus vulgaris (mPV). The trial is designed to determine the
maximum tolerated dose of DSG3-CAART in adult subjects with active,
anti-DSG3 Ab positive, biopsy confirmed mPV that is inadequately
managed by one or more standard therapies. The primary endpoint is
incidence of adverse events (AEs), including dose-limiting
toxicities (DLTs), such as certain events of cytokine release
syndrome (CRS) and neurotoxicity, related to DSG3-CAART within
three months of infusion. Secondary endpoints include CAART
persistence (qPCR), anti-DSG3 Ab levels (ELISA) and disease
activity (PDAI).
About Cabaletta BioCabaletta Bio (Nasdaq: CABA)
is a clinical-stage biotechnology company focused on the discovery
and development of engineered T cell therapies that have the
potential to provide a deep and durable, perhaps curative,
treatment for patients with autoimmune diseases. The CABA™
platform, in combination with Cabaletta Bio’s proprietary
technology, has advanced a growing pipeline that currently includes
potential treatments for patients with mucosal pemphigus vulgaris,
MuSK-associated myasthenia gravis, PLA2R-associated membranous
nephropathy, mucocutaneous pemphigus vulgaris and hemophilia A with
FVIII alloantibodies. Cabaletta Bio’s headquarters are located in
Philadelphia, PA. For more information,
visit www.cabalettabio.com and follow us on LinkedIn and
Twitter.
Forward-Looking StatementsThis press release
contains “forward-looking statements” of Cabaletta Bio within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended, including without limitation, express or implied
statements regarding expectations regarding: the company’s business
plans and objectives; the progress and results of its DesCAARTes™
Phase 1 trial, including Cabaletta’s ability to enroll the
requisite number of patients, dose each dosing cohort in the
intended manner, and progress the trial; the expected significance
and impact around the clinical and translational data updates
provided at the scientific meeting described herein and the
expected timing and significance around additional clinical data
updates from the DesCAARTes™ trial at additional scientific
meetings throughout 2022 and 2023; the expectation that Cabaletta
may improve outcomes for patients suffering from mPV; Cabaletta’s
ability to escalate dosing as high as 10 to 15 billion cells in a
planned future cohort, initiate dosing in a combination cohort or
otherwise; Cabaletta’s plans to implement a pre-treatment regimen
and the potential ability to enhance in vivo DSG3-CAART exposure;
Cabaletta’s ability to advance dose escalation in the DesCAARTes™
Phase 1 trial at the current dose ranges for the current cohorts
and any projected potential dose ranges for future cohorts, and to
optimize its targeted cell therapy; Cabaletta’s ability to
evaluate, and the potential significance of, the relationship
between DSG3-CAART persistence and potential clinical responses in
patients with mPV; expectations regarding the design,
implementation, timing and success of its current and planned
clinical trials and the successful completion of nonclinical
studies; planned potential timing and advancement of its
preclinical studies and clinical trials and related regulatory
submissions; ability to optimize the impact of its collaborations
on its development programs; the impact of COVID-19 on the timing,
progress, interpretability of data, and results of ongoing or
planned preclinical and clinical trials; statements regarding the
timing of regulatory filings regarding its development programs;
the ability to accelerate Cabaletta’s pipeline and develop
meaningful therapies for patients, including in collaboration with
academic and industry partners; and the anticipated contribution of
the members of Cabaletta’s executives to the company’s operations
and progress.
Any forward-looking statements in this press release are based
on management’s current expectations and beliefs of future events,
and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those
set forth in or implied by such forward-looking statements. These
risks and uncertainties include, but are not limited to: the risk
that signs of biologic activity or persistence may not inform
long-term results; Cabaletta’s ability to demonstrate sufficient
evidence of safety, efficacy and tolerability in its preclinical
studies and clinical trials of DSG3-CAART; Cabaletta’s plans to
evaluate additional cohorts in the DesCAARTes™ trial, including a
cohort implementing a pre-treatment regimen; the risk that
persistence observed with effective CART-19 oncology studies in
combination with lymphodepletion is not indicative of, or
applicable to, clinical responses in patients with mPV; risks
related to clinical trial site activation or enrollment rates that
are lower than expected; risks related to unexpected safety or
efficacy data observed during clinical studies; risks related to
the impact of public health epidemics affecting countries or
regions in which Cabaletta has operations or does business, such as
COVID-19; Cabaletta’s ability to retain and recognize the intended
incentives conferred by Orphan Drug Designation and Fast Track
Designation for DSG3-CAART for the treatment of pemphigus vulgaris;
risks related to Cabaletta’s ability to protect and maintain its
intellectual property position; uncertainties related to the
initiation and conduct of studies and other development
requirements for its product candidates; the risk that any one or
more of Cabaletta’s product candidates will not be successfully
developed and commercialized; and the risk that the results of
preclinical studies or clinical studies will not be predictive of
future results in connection with future studies. For a discussion
of these and other risks and uncertainties, and other important
factors, any of which could cause Cabaletta’s actual results to
differ from those contained in the forward-looking statements, see
the section entitled “Risk Factors” in Cabaletta’s most recent
annual report on Form 10-K as well as discussions of potential
risks, uncertainties, and other important factors in Cabaletta’s
other filings with the Securities and Exchange Commission. All
information in this press release is as of the date of the release,
and Cabaletta undertakes no duty to update this information unless
required by law.
Contacts:
Anup MardaChief Financial Officerinvestors@cabalettabio.com
Sarah McCabeStern Investor Relations,
Inc.sarah.mccabe@sternir.com
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