Epic Bio Presents New Data Highlighting Potential of EPI-321 for FSHD and Epigenetic Editing Platform Leadership at ASGCT Annual Meeting
2024年4月23日 - 10:00PM
Epic Bio, a leading epigenetic editing company that plans to have
its FSHD program enter the clinic this year, today shared details
of data being presented at the Annual Meeting of the American
Society of Gene & Cell Therapy (ASGCT), taking place May 7-11,
2024, in Baltimore, Maryland. Across three oral presentations and
three poster presentations, Epic Bio will present new data
demonstrating the differentiation of the company’s epigenetic
editing platform and the promise of lead candidate EPI-321 for the
treatment of facioscapulohumeral muscular dystrophy (FSHD).
“We’re proud of the robust presence Epic Bio will have at this
year’s ASGCT, reflecting the high degree of excitement and interest
in epigenetic editing we’re seeing across the biopharma industry as
well as Epic Bio’s leading position within this space,” said Amber
Salzman, Ph.D., chief executive officer of Epic Bio. “We are
laser-focused on translating these capabilities into medicines that
can make a meaningful difference for patients, starting with our
lead candidate EPI-321 for FSHD, which will enter the clinic later
this year.”
Best-in-class epigenetic activators
In an oral presentation at the conference, the company will
present new data demonstrating the best-in-class profile of its
proprietary epigenetic activators. While epigenetic gene silencing
has been widely successful, robust and persistent activation of
genes remains a significant challenge, and an area where epigenetic
editing may offer the greatest therapeutic potential compared to
other genetic medicines.
New data on Epic Bio’s epigenetic activators show that they can
produce long-term activation of IL-21 — an interleukin crucial
for enhancing CAR-T function — at levels far exceeding those
produced by one of today’s gold-standard activators, VPR.
A second study evaluated the use of proprietary epigenetic
activators to boost transcription of the LDL Receptor (LDLR) gene.
Mutations in one copy of LDLR are the most common cause of familial
hypercholesterolemia, and thus epigenetic activation of LDLR is a
highly promising potential treatment approach. In liver cells, Epic
Bio’s epigenetic activators produced sustained LDLR expression.
Critically, this activation was shown to persist for 70 days though
the activator itself was only transiently expressed. Furthermore,
in a humanized mouse model the proprietary activators boosted LDLR
expression by twofold, sustained for up to 5 weeks, even though the
activator was transiently delivered — far exceeding all
previously reported outcomes of in vivo testing of a CRISPR-based
epigenetic activator. These insights will inform Epic Bio’s ongoing
preclinical efforts to develop an epigenetic editing therapy for
heterozygous familial hypercholesterolemia (HeFH) utilizing one or
more mechanisms of action.
Establishing the standard for off-target
characterization in epigenetic editing
In a second oral presentation, Epic Bio is presenting the design
and results of its whole-genome off-target assessment for the
company’s lead candidate, EPI-321. As a leader in the field of
epigenetic editing, Epic Bio has done pioneering work to craft a
comprehensive off-target assessment platform to ensure the safety
of epigenetic editing therapies for human testing. This analysis,
designed with inputs from regulators in the U.S. and elsewhere,
leverages genome-wide methylation profiling, genome-wide
transcriptomic profiling, in silico prediction, and targeted
validation assays across various model systems in order to robustly
identify putative off-target effects.
In the application of this off-target assessment to EPI-321, the
company found that there are no direct off-target events caused by
EPI-321 treatment, supporting the clinical initiation for EPI-321
later this year.
A tool to expand access to hypercompact Cas
proteins
A third oral presentation at ASGCT spotlights a novel, freely
available tool recently developed by Epic Bio to assist researchers
who wish to use the hypercompact dCasMINI protein for epigenetic
editing. The small size of dCasMINI — less than half the size of
dCas9 — makes it ideally suited for single-vector delivery,
regardless of cargo capacity. However, unlike Cas9 or Cas12a, there
are no available computational tools for designing CasMINI guides,
which presents a significant barrier to its ease-of-use by academic
and industry researchers as well as drug developers.
Epic Bio developed a web-based application to support design,
selection, and comprehensive off-target prediction of guide RNAs
for epigenetic activation and suppression (CRISPRa/i) using the
catalytically inactivated dCasMINI CRISPR-Cas system against any
gene in the human genome. The tool should enable researchers to
easily employ dCasMINI in their investigations, and thereby foster
continued scientific and medical innovation.
Poster presentations In addition to the above
oral presentations, the company will present posters on:
- The complete nonclinical data package for lead candidate
EPI-321, including supplemented efficacy and safety data since the
company’s oral presentation at ASGCT last year, along with new data
on functional measures using 3-D engineered human muscle
tissue.
- Details of a generative AI approach to design de novo
transcriptional activators, and
- Results of work to characterize and optimize Epic Bio’s
proprietary Cas proteins.
About Epic BioEpic Bio is a leading epigenetic
editing company, leveraging the power of CRISPR without cutting
DNA. The company’s proprietary Gene Expression Modulation System
(GEMS) includes the smallest Cas protein known to work in human
cells, enabling in vivo or ex vivo delivery via a single viral
vector. Epic plans to begin dosing patients in a clinical trial of
its lead program — EPI-321 for the treatment of
facioscapulohumeral muscular dystrophy (FSHD) — in 2024; additional
programs seek to address alpha-1 antitrypsin deficiency (A1AD),
heterozygous familial hypercholesterolemia (HeFH), and retinitis
pigmentosa (RP). Visit www.epic-bio.com for more
information or follow us
on X and LinkedIn.
Investor ContactShawn M. CoxEpic BioManager,
Investor Relations, and Corporate
Communicationsshawn.cox@epic-bio.com
Media ContactLisa RaffenspergerTen Bridge
Communicationslisa@tenbridgecommunications.com(617) 903-8783