Early non-human primate (NHP) data for
P-KLKB1-101 demonstrate successful liver gene editing approaching
human therapeutic range with a favorable safety and tolerability
profile
Preclinical P-FVIII-101 data highlight
sustained Hemophilia A correction following a single dose and
support potential for repeat dosing and precise tuning of Factor
VIII levels
Promising early data further validate
Company's fully non-viral delivery platform and transposon
technologies
SAN
DIEGO, May 9, 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 and rare diseases,
today highlights new preclinical data supporting the potential of
its fully non-viral lead genetic medicines programs and related
platform technologies. The data was included in three oral and
three poster presentations at the American Society of Gene and Cell
Therapy (ASGCT) 2024 Annual Meeting, being held in Baltimore, MD and virtually on May 7-11, 2024.
"Poseida's unique and proprietary toolkit, which
enables non-viral gene insertion, high-fidelity gene editing, and
associated delivery and manufacturing technologies, has been the
driving force behind our emerging genetic medicines programs and
our clinical stage allogeneic CAR-T pipeline," said Blair Madison, Ph.D., Chief Scientific Officer,
Gene Therapy at Poseida
Therapeutics. "Starting with our recent R&D Day, and continuing
with ASGCT, we have showcased the maturity and power of our tools
specific to enabling a fully non-viral and potentially tunable
approach to in vivo genetic medicine. We believe this could provide
our medicines with a superior profile featuring a minimized risk of
off-target effects that can be customized to each patient, when
appropriate. Taken together, these data give us confidence as we
continue to validate our non-viral approach, seeking to achieve
durable correction in patients suffering from rare diseases such as
Hereditary Angioedema and Hemophilia A."
Oral Presentations
Title: Highly Specific Non-Viral Gene Editing
with P-KLKB1-101 for Hereditary Angioedema
Presenting Author: Blair Madison, Ph.D., Poseida
Therapeutics, Inc.
Session Title: Correction of Genetic Disorders of the
Blood and Immune System
Presentation Date/Time: Thursday, May 9, 2024,
1:30 - 1:45 PM ET
Location: Room 314-317
Abstract Number: 170
Hereditary Angioedema (HAE) is a rare inherited
disorder characterized by recurrent episodes of fluid accumulation
outside of blood vessels, causing rapid swelling of tissues. HAE
patients have significant unmet need for 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 pre-kallikrein,
or KLKB1, for targeted correction of HAE. It utilizes the
Cas-CLOVER™ nuclease to achieve clean site-specific gene editing
that is engineered for high specificity. In pre-clinical studies,
P-KLKB1-101 demonstrates excellent efficiency editing liver cells
with off-target edits <0.1% over a wide range of lipid
nanoparticle (LNP) concentrations. Poseida's gene editing delivery
technologies, including novel ionizable lipid and LNP, enable a
highly controlled dose response. Interim non-human primate (NHP)
data demonstrate favorable tolerability and liver editing
approaching the desired therapeutic range. Development of
P-KLKB1-101 is ongoing, including continuation of dose-finding
studies in NHPs, CMC manufacturing, scale-up, and additional
preparations for IND-enabling studies.
Title: Sustained FVIII Expression with a
Tolerable, Titratable, Fully Non-Viral Gene Therapy for Hemophilia
A
Presenting Author: Brian Truong, Ph.D., Poseida
Therapeutics, Inc.
Session Title: Liver Genetic Diseases
Presentation Date/Time: Thursday, May 9, 2024,
5:00 - 5:15 PM ET
Location: Room 324-326
Abstract Number: 210
P-FVIII-101 is a fully non-viral gene
insertion-based therapy for the treatment of Hemophilia A, an
X-linked bleeding disorder caused by a deficiency in coagulation
Factor VIII (FVIII). It utilizes Poseida's proprietary transposon
technology combined with nanoparticle delivery to achieve
site-specific gene insertion into DNA. Data demonstrate that a
single dose of P-FVIII-101 achieves Hemophilia A disease correction
with sustained FVIII expression observed over the 13-month duration
of the mouse study. The pre-clinical data also support the
potential for repeat dosing, enabled by the fully non-viral
approach. P-FVIII-101 can also be combined with Poseida's new
proprietary modulator switch, which allows inducible
down-regulation to enable patient-specific fine tuning of FVIII
levels, which is seen as an important product attribute by the
hemophilia community.
Development of P-FVIII-101 is ongoing with final
optimization of the nanoparticle delivery modality to be validated
in NHPs.
Title: A Durable Gene Therapy with a Robust
AAV-LNP Delivery System Allowing for a Reduced AAV Dose
Presenting Author: Jack Rychak, Ph.D., Poseida
Therapeutics, Inc.
Session Title: AAV Vectors - Preclinical and
Proof-of-Concept: Technology Focus
Presentation Date/Time: Friday, May 10, 2024,
1:45 - 2:00 PM ET
Location: Ballroom 2
Abstract Number: 248
This presentation highlights data from studies
exploring the feasibility of combining existing adeno-associated
virus delivery vectors (AAVs) with Poseida's piggyBac DNA insertion
system. This approach is intended to achieve stable integration of
a transgene into a large percentage of hepatocytes for maximal
therapeutic benefit, which cannot be readily achieved using an AAV
or episomal approach. Pre-clinical data demonstrate exceptional
efficacy in mouse models of severe Ornithine Transcarbamylase
Deficiency (OTCD). Additionally, robust potency is observed in
mouse models of Phenylketonuria (PKU), using low AAV doses, and
enabled by the integration of a therapeutic transgene with the SPB
transposase. These data highlight the utility of the hybrid
platform for enabling effective treatment with lower AAV doses,
even in the growing liver early in life. With Poseida's current
internal focus on fully non-viral approaches, as announced at the
Company's recent R&D Day, the Company may opportunistically
consider partnering transactions with respect to its P-PAH-101 and
P-OTC-101 programs.
Poster Presentations
Title: Advanced Gene Editing with an Enhanced
Site-Specific Nuclease for Knock-Out and Knock-In
Applications
Presenting Author: Oscar Alvarez, Ph.D., Poseida
Therapeutics, Inc.
Session Title: Wednesday Posters: Gene Targeting and
Gene Correction New Technologies
Session Date/Time: Wednesday, May 8, 2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 717
Poseida's Cas-CLOVER nuclease system represents a
key advancement in gene editing technology with high-fidelity
performance that significantly exceeds that of traditional
nucleases. Poseida developed its Cas-CLOVER system by incorporating
an S44P mutation which confers a two to three-fold improvement in
on-target Cas-CLOVER editing efficiency, while fully preserving
fidelity and with no increase in off-target editing. The enhanced
Cas-CLOVER system exhibits remarkable capabilities for
site-specific insertion of genes, as evidenced by the successful
integration of a therapeutic transgene in mouse liver cells and
associated phenotypical disease rescue in a PKU mouse model.
The Company plans to evaluate
homology-independent targeting using its rapidly advancing fully
non-viral DNA delivery technology for the precise insertion of
genes and related gene expression regulators to specific sites in
the genome.
Title: Optimizing Lipid Nanoparticle Formulations
for Enhanced Non-Viral Gene Therapy: Overcoming DNA Delivery
Challenges and Achieving High-Efficiency Transgene
Integration
Presenting Author: George Wang, Ph.D., Poseida
Therapeutics, Inc.
Session Title: Thursday Posters: Other Nonviral
Delivery
Session Date/Time: Thursday, May 9, 2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 1239
This study demonstrates the optimization of DNA
delivery to hepatocytes, in vivo, and genomic integration using
Poseida's piggyBac DNA insertion system. Poseida has synthesized
and evaluated novel terpene-based lipids exhibiting unique DNA
encapsulation and delivery properties in vivo. Poseida also
identified a class of amphipathic small molecules called Poseida
Delivery Excipients (PDEs) with unique capabilities for enhancing
DNA delivery. Data demonstrated that inclusion of these PDEs in
LNPs improved the insertion of targeted genes and decreased
pro-inflammatory cytokine release. LNPs comprising novel ionizable
lipids and PDEs also significantly enhanced genomic insertion of
therapeutically relevant transgenes in vivo. These unique
combinations of LNPs and PDEs could further enhance the potential
of Poseida's non-viral DNA platform technology and piggyBac DNA
insertion system for treating serious genetic disorders.
Title: Novel Biodegradable Lipid Nanoparticles
(LNP) for Co-Encapsulation of Complex Nucleic Acid Payloads for In
Vivo Genome Editing
Presenting Author: Alicia
Davis, Ph.D., Poseida Therapeutics
Session Title: Friday Posters: Other Nonviral Delivery
Session Date/Time: Friday, May 10,
2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 1737
This presentation highlights the development of
an LNP capable of robustly co-encapsulating and delivering
Poseida's Cas-CLOVER nuclease system to the liver, while avoiding
unintended uptake. Poseida has identified and characterized a novel
class of biodegradable ionizable lipids for in vivo mRNA delivery.
The Company has identified lipid S, which demonstrated potent mRNA
delivery potency and improved clearance from the liver. These
studies demonstrate Poseida's discovery chemistry and formulation
capabilities to generate high-performing LNPs for the efficient
delivery of next-generation genetic medicine platforms such as
Cas-CLOVER.
About P-KLKB1-101
P-KLKB1-101 is an investigational liver-directed
non-viral gene editing approach designed using Cas-CLOVER™
Site-Specific Gene Editing System, Poseida's proprietary
high-fidelity nuclease, for site-specific gene editing of the KLKB1
gene, for the treatment of Hereditary Angioedema (HAE). HAE is a
rare, inherited disorder that results in the swelling of the skin,
intestinal tract, and airways, which can be both debilitating and
life-threatening. Preclinical data demonstrate therapeutically
relevant reduction of pre-kallikrein levels in both mouse and NHP
models.
About P-FVIII-101
P-FVIII-101 is an investigational liver-directed
gene insertion program combining Poseida's non-viral transposon
platform and nanoparticle delivery technologies for the in vivo
treatment of Hemophilia A. Hemophilia A is a hereditary bleeding
disorder caused by a deficiency in Factor VIII production with a
high unmet need, resulting in excessive bleeding occurring either
spontaneously or due to trauma and leading to pain and permanent
joint damage in patients. P-FVIII-101 utilizes the piggyBac gene
integration system delivered via lipid nanoparticle, which has
demonstrated the potential to correct Factor VIII deficiency in
juvenile and adult animal models using Poseida's fully non-viral
insertion system that is capable of whole gene correction.
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 certain
cancers and rare diseases. The Company's pipeline includes
investigational allogeneic CAR-T cell therapies for both solid
tumors and hematologic cancers 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 piggyBac® 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,
expected plans with respect to clinical trials, including timing of
regulatory submissions and approvals and clinical data updates;
anticipated timelines and milestones with respect to the Company's
development programs and manufacturing activities and capabilities;
the potential capabilities and benefits of the Company's technology
platforms and product candidates, including the tolerability and
efficacy and safety profile of such product candidates; 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 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; the fact that interim data from
the Company's clinical trials may change as more data become
available and remain subject to audit and verification procedures
that could result in material differences from the final data; and
the other risks described in the Company's filings with the
Securities and Exchange Commission. 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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