Data to be highlighted in a Distinguished
Industry Oral Abstract presentation at the American College of
Allergy, Asthma & Immunology (ACAAI) 2024 Scientific
Meeting
SAN
DIEGO, Oct. 24, 2024 /PRNewswire/ -- Poseida
Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell
therapy and genetic medicines company advancing differentiated
non-viral treatments for patients with cancer, autoimmune, and rare
diseases, today announced the upcoming presentation of new
preclinical data supporting the potential of P-KLKB1-101, a
liver-directed genetic medicine that uses the
Company's Cas-CLOVER™ Site-Specific Gene Editing System, for
the treatment of patients with hereditary angioedema (HAE). The
data showed high-fidelity KLKB1 gene editing for the targeted
correction of HAE, the ability for controlled dose response,
favorable tolerability and liver editing within the predicted
therapeutic range.
"The newest preclinical data for P-KLKB1-101
support our goal to develop a gene editing treatment option for HAE
with encouraging early tolerability, safety and efficacy results,"
said Blair Madison, Ph.D., Chief
Scientific Officer, Gene Therapy at
Poseida Therapeutics. "We achieved a highly effective,
therapeutically relevant reduction of kallikrein in our new
humanized pre-clinical mouse model at a low 0.125 mg/kg dose,
marking an improvement in our lipid nanoparticle delivery
efficiency. These tools could potentially enable therapeutic gene
editing in other liver-relevant targets, considering the high
fidelity editing of Cas-CLOVER and the promising delivery
efficiency we are seeing with our proprietary lipid and LNP in
pre-clinical studies."
HAE is a rare inherited disorder characterized by
recurrent episodes of fluid accumulation outside of blood vessels,
causing rapid swelling of tissues. The swelling is caused by
unchecked activation of the kallikrein-bradykinin cascade due to
deficiency of the C1 esterase inhibitor, a protein that is involved
in regulating vascular permeability and the contact system.
Patients with HAE are in need of a durable, effective, and
convenient treatment option that eliminates recurrent attacks.
P-KLKB1-101 is a fully non-viral investigational
gene editing therapy designed to enable high fidelity editing at
the pre-kallikrein gene, or KLKB1, for correction of HAE. It
utilizes the Cas-CLOVER nuclease, which is engineered for high
specificity, to achieve site-specific gene editing.
Key Highlights from P-KLKB1-101 Data to be
Presented at ACAAI
- P-KLKB1-101 enabled highly efficient KLKB1 editing and
reduction of kallikrein in cultured primary human hepatocytes, with
all off-target edits consistently at or below 0.1%, including at
high dose levels.
- P-KLKB1-101 yielded controlled, dose-dependent reductions in
kallikrein protein levels and activity in a new humanized mouse
model. The reduction in plasma kallikrein levels was stable and
persisted for at least 180 days (latest time point assessed). In
this model, the targeted therapeutic level of KLKB1 editing was
achieved with a single dose, and a 58% reduction of kallikrein
levels at the minimally effective dose of 0.125 mg/kg.
- Interim non-human primate (NHP) data demonstrate that
P-KLKB1-101 had favorable tolerability and achieved liver editing
approaching the desired therapeutic range. Ongoing lead
optimization of P-KLKB1-101 yielded a 29% increase in potency (as
measured by on-target KLKB1 editing) relative to a historical
dose-matched benchmark.
- Poseida's novel ionizable lipid and lipid nanoparticle (LNP)
enables potent in vivo delivery of P-KLKB1-101 and a controlled
dose response.
Presentation Details
The data will be
presented on Saturday, October 26 by
Dr. Madison at the American College of Allergy, Asthma &
Immunology (ACAAI) 2024 Scientific Meeting in Boston:
Title: Highly Specific
Non-Viral Gene Editing with P-KLKB1-101 for Hereditary
Angioedema
Abstract #: 8063
Session: Distinguished Industry & Late-breaking Oral
Abstracts – Session 1
Session Date/Time: Saturday, October 26, 4:30-6:00 p.m. ET (presentation at 5:03 p.m. ET)
About P-KLKB1-101
P-KLKB1-101 is an
investigational liver-directed non-viral gene editing approach
designed using the Cas-CLOVER™ Site-Specific Gene Editing
System, Poseida's proprietary high-fidelity nuclease. P-KLKB1-101
is designed for site-specific gene editing of the KLKB1 gene for
the treatment of hereditary angioedema (HAE). This rare inherited
disorder results in the swelling of the skin, intestinal tract, and
airways, which can be both debilitating and life-threatening.
Preclinical data demonstrates therapeutically relevant reduction of
pre-kallikrein levels in both mouse and non-human primate
models.
About Cas-CLOVER
The
Cas-CLOVER™ Site-Specific Gene Editing System employs dual
RNA-guided DNA targeting for high fidelity editing. The dual guide
RNA targeting provides spatial restrictions on each of two
Cas-CLOVER molecules after interacting with specific DNA sequences.
This interaction then allows Clo051 cutting at the target site. The
result is a highly specific edit by the Cas-CLOVER nuclease, and a
low incidence of unwanted off-target edits, with 25-fold greater
fidelity than CRISPR/Cas9.
About Poseida Therapeutics,
Inc.
Poseida Therapeutics is a clinical-stage
biopharmaceutical company advancing differentiated allogeneic cell
therapies and genetic medicines with the capacity to cure. The
Company's pipeline includes investigational allogeneic CAR-T cell
therapies for hematologic cancers, autoimmune diseases, and solid
tumors, as well as investigational in vivo genetic medicines that
address patient populations with high unmet medical need. The
Company's approach is based on its proprietary genetic editing
platforms, including its non-viral transposon-based DNA delivery
system, Cas-CLOVER™ Site-Specific Gene Editing System, Booster
Molecule and nanoparticle gene delivery technologies, as well as
in-house GMP cell therapy manufacturing. The Company has formed
strategic collaborations with Roche and Astellas to unlock the
promise of cell therapies for cancer patients. Learn more
at www.poseida.com and connect
with Poseida on X and LinkedIn.
Forward-Looking Statements
Statements contained in this press release regarding matters that
are not historical facts are "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995. Such forward-looking statements include statements regarding,
among other things, the potential capabilities and benefits of the
Company's technology platforms and product candidates, including
P-KLKB1-101; the quote from Dr. Madison; and the Company's plans
and strategy with respect to developing its technologies and
product candidates. Because such statements are subject to risks
and uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. These
forward-looking statements are based upon the Company's current
expectations and involve assumptions that may never materialize or
may prove to be incorrect. Actual results could differ materially
from those anticipated in such forward-looking statements as a
result of various risks and uncertainties, which include, without
limitation, the fact that interim data from the Company's
preclinical trials may change as more data become available; the
Company's reliance on third parties for various aspects of its
business; risks and uncertainties associated with development and
regulatory approval of novel product candidates in the
biopharmaceutical industry; the Company's ability to retain key
scientific or management personnel; whether any of the Company's
product candidates will be shown to be effective, safe and
reliable; and the other risks and uncertainties described in the
Risk Factors section of Poseida's Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission (SEC)
on August 5, 2024, and in other filings Poseida makes with
the SEC from time to time. All forward-looking statements
contained in this press release speak only as of the date on which
they were made. The Company undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made, except as required by
law.
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SOURCE Poseida Therapeutics, Inc.
