Human Gene Therapy - April 2023 - 257

GENE THERAPY BRIEFS
257
ORCHARD THERAPEUTICS
ATTRACTS UP TO $188M
IN STRATEGIC FINANCING
Orchard Therapeutics
has
entered into a securities purchase
agreement for the sale of ordinary
shares and warrants in a private
placement that could bring in up to
$188 million, tied to achieving U.S.
regulatory milestones for its metachromatic
leukodystrophy (MLD)
gene therapy candidate OTL-200.
The financing was led by RA
Capital Management, and attracted
new and existing investors Deep
Track Capital, Cowen Healthcare
Investments, Woodline Partners
LP, and Zentree Investments Ltd.,
among others.
OTL-200 has been approved in
Europe as a treatment for early-onset
MLD, under the name Libmeldy
(atidarsagene autotemcel).
Orchard said it intends to use
the net proceeds from the offering
to support its growing commercial
capabilities, including expanding
its commercialization efforts of
Libmeldy in Europe; preparing for
a potential Biologics License Application
(BLA) submission and
approval for OTL-200 in the United
States; advancing its clinical and
preclinical stage programs; servicing
its existing outstanding debt; and
funding general corporate purposes.
''The financing will provide
important capital to accelerate the
commercialization of Libmeldy and
advance the other programs in our
HSC [hematopoietic stem cell] gene
therapy platform,'' said Frank Thomas,
president and chief operating
officer of Orchard Therapeutics.
''We believe the deal's innovative
structure provides additional committed
capital at progressively higher
valuations as OTL-200 advances
towards potential regulatory approval
in the United States.''5
Orchard raised $34 million in
upfront proceeds from the
financing-which combined with
existing cash, cash equivalents, and
investments are expected to fund the
company's anticipated operating,
debt service, and capital expenditure
requirements into 2025, with
the potential for additional runway
extension upon subsequent closings.
Guggenheim Securities acted as
the sole placement agent for the private
placement.
CHROMA RAISES STAKES
IN EPIGENETIC EDITING
WITH $135M SERIES B
With $135 million in new financing
to draw upon, Chroma Medicine
says it will spend this year
presenting promising proof of concept
data for its epigenetic genome
editing platform, advancing its pipeline
of single-dose therapies discovered
through the platform, and
growing its workforce.
Chroma completed its $135 million
Series B financing earlier this
month, bringing the company's total
capital raised to $260 million. The
new capital, Chroma says, will help
it build out a platform designed to
develop programmable epigenetic
editors that precisely turn genes on
or off, or can alter the expression of
several genes at once.
By seamlessly silencing, activating,
and multiplexing genes in a
single platform intended to mimic
the cell's innate mechanisms for
controlling gene expression, Chroma
reasons, its epigenetic technology
can become the leading approach for
gene regulation.
''The technology can best address
any disease where changes in the
amount of gene expression are
important to the pathogenesis of the
disease,'' Chroma CEO Catherine
Stehman-Breen, MD, told GEN
Edge. ''We don't correct genes. We
change gene expression. We don't
need to change the sequence of the
DNA in order to change gene expression.
We can do this leveraging
this endogenous system that was
actually intended to regulate gene
expression.''6
Chroma's programmable epigenetic
editors-or epieditors-are
designed to target genes and control
chromatin conformation by coupling
a DNA-binding domain with epigenetic
effector domains. The DNAbinding
domain specifically targets
one or more genes to be silenced
or activated, whereas the effector
domains create specific and durable
methylation patterns that control
chromatin conformation and govern
whether a gene is accessible or
inaccessible for transcription.
Chroma's approach contrasts with
current genome editing technologies
that indirectly regulate gene expression
by cutting DNA, as a result
activating DNA repair pathways and
potentially producing immunogenic
truncated or mutant proteins, both
potentially generating unpredictable
results.7
FDA EXTENDS DECISION
DATE ON BIOMARIN'S
ROCTAVIAN
The U.S. Food and Drug
Administration (FDA) has extended
its target date under the Prescription
Drug User Fee Act
(PDUFA) for a decision on BioMarin
Pharmaceutical's BLA of BioMarin
Pharmaceutical said that ROCTAVIAN
(valoctocogene roxaparvovec
or ''val rox''), the company's
one-time gene therapy candidate for
adults with severe hemophilia A.
According to BioMarin, the FDA
has determined that the company's
submission of a 3-year data analysis
from the ongoing Phase III
GENEr8-1 trial (NCT03370913)
constituted a major amendment due
to the substantial amount of additional
data furnished to the agency.
The FDA set a new PDUFA target
action date of June 30.
GENEr8-1 is the largest and longest
global Phase III study to date for
any gene therapy in hemophilia with
134 participants.
''We are continuing to work closely
with FDA and appreciate the
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