Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today reported
positive initial safety, tolerability and enzyme activity data from
the ongoing Phase 1/2 GALILEO-1 trial evaluating FLT201, its
adeno-associated virus (AAV) gene therapy candidate, in Gaucher
disease. Gaucher disease is a debilitating genetic disorder in
which a deficiency of the GCase enzyme leads to a buildup of
harmful substrates, causing symptoms including enlarged spleen and
liver, low blood counts, bone pain and reduced lung function. In
addition to demonstrating a favorable safety and tolerability
profile, data from the first two patients in GALILEO-1 show that a
single infusion of FLT201 led to several hundred-fold increases in
GCase activity in plasma and normalization of GCase activity in
leukocytes.
"These initial clinical data are very compelling,” said Pilar
Giraldo, M.D., Ph.D., hematologist at the Spanish Foundation for
the Study and Therapy of Gaucher Disease, Quirónsalud Hospital –
Zaragoza, and an investigator in the GALILEO-1 trial. “While
existing therapies have had a significant impact on the disease,
many patients continue to experience symptoms and current therapies
come with a heavy lifelong treatment burden. People with Gaucher
disease deserve better treatment options. FLT201 represents a
promising new approach as a one-time investigational gene therapy,
and based on the emerging clinical data, I am excited about its
potential.”
“FLT201 is a highly differentiated gene therapy candidate for
Gaucher disease with the opportunity to provide better outcomes for
patients, while dramatically reducing the burden that comes with
existing therapies,” said Pamela Foulds, M.D., Freeline’s Chief
Medical Officer. “The magnitude of the increases in plasma GCase
activity in the first two patients treated with FLT201, together
with the normalization of GCase activity in cells, further
strengthen our belief in its therapeutic potential. Given the
strong response and clean safety and tolerability to date, we have
decided to treat a third patient at this dose rather than a higher
dose as initially planned.”
“Our goal at Freeline is to unlock the true potential of gene
therapy by optimizing every component of our product candidates,”
said Michael Parini, Freeline’s Chief Executive Officer. “FLT201
exemplifies that approach. It leverages our proprietary capsid
designed to deliver high expression at low doses and our novel
GCase variant engineered to overcome the short half-life of
wildtype GCase. Our preclinical data for FLT201 show robust
increases in plasma GCase, which is then taken up by
disease-affected tissues, clearing harmful substrate more
effectively than the existing standard-of-care. These clinical data
show the preclinical data are starting to translate, and we are
committed to expeditiously advancing FLT201.”
Positive Initial Clinical Data for FLT201The
data reported today include assessments of safety, tolerability and
GCase activity from the first two patients in GALILEO-1, which is a
first-in-human, international, multicenter Phase 1/2 dose-finding
study in people with Gaucher disease Type 1. Both patients were
treated with a dose of 4.5x1011 vg/kg and have successfully come
off their prior therapies.
As of the September 27 data cutoff,
the data demonstrated:
- Favorable safety and tolerability, with no infusion reactions
and no serious adverse events as of 13 weeks post-dosing for
patient 1 and six weeks post-dosing for patient 2. All
treatment-related adverse events were Grade 1 and resolved without
intervention.
- No elevations in liver transaminase levels during the same time
periods. Alanine-transaminase (ALT) and aspartate-transaminase
(AST) levels remained in the normal range in both patients.
- Robust increases in plasma GCase levels. Patient 1 showed a
nearly 700-fold increase over baseline to more than 70 μmol/L/h as
of 12 weeks post-dosing. Patient 2 showed a similarly robust
response, with a greater than 300-fold increase over baseline to
approximately 30 μmol/L/h as of four weeks post-dosing. Normal
plasma GCase levels range from 0.3 to 1.2 μmol/L/h (mean: 0.58
μmol/L/h).
- Normalization of leukocyte GCase activity, demonstrating
cellular uptake of GCase from the plasma. Leukocyte GCase activity
reached normal levels in patient 1 within four weeks of dosing and
remained normal as of the last measurement. Similarly, leukocyte
GCase activity in patient 2 reached normal levels within four weeks
of dosing. Leukocytes are validated markers for broad cellular
uptake in Gaucher disease.
- Both patients had normal hemoglobin levels at baseline and have
remained in the normal range at each weekly assessment, including
those taken after coming off enzyme replacement therapy or
substrate replacement therapy.
Given the compelling safety profile
and robust enzyme activity at the 4.5x1011 vg/kg dose, a third
patient has been scheduled for dosing in this first cohort to
gather additional data before deciding whether to continue at the
current dose or explore a higher dose. Three additional study
patients have been identified and are in the process of being
scheduled for dosing.
Webcast/Conference Call InformationFreeline
Therapeutics will host a webcast presentation at 8 a.m. ET today to
discuss these initial clinical data for FLT201 in Gaucher
disease.
A live webcast of the event will be available on the Investors
section of Freeline’s website at www.freeline.life. Participants
may access the event by registering here. While not required, it is
recommended that participants join 10 minutes prior to the
scheduled start. An archived replay will be available on Freeline’s
website for at least 90 days.
About Gaucher
DiseaseGaucher disease is caused by a mutation in the GBA1
gene that results in abnormally low levels of glucocerebrosidase
(GCase), an enzyme needed to metabolize a certain type of lipid. As
a result, harmful substrates glucosylceramide (Gb-1) and
glucosylsphingosine (lyso-Gb1) build up in cells that then
accumulate in various organs, causing inflammation and dysfunction.
Gaucher disease is hereditary and presents in various subtypes.
Freeline is currently focused on Gaucher disease Type 1, the most
common form of the disease, which affects the health of the spleen,
liver, bone and lung. Despite treatment with existing therapies,
many people with Gaucher disease continue to experience symptoms
and disease progression. Gaucher disease affects approximately
18,000 people in the United States, United Kingdom, France,
Germany, Spain, Italy and Israel.
About FLT201 FLT201
is an adeno-associated virus (AAV) gene therapy candidate that is
currently being investigated in the Phase 1/2 GALILEO-1 clinical
trial in adults with Gaucher disease Type 1. FLT201 is designed to
generate durable increases in glucocerebrosidase (GCase) and reduce
the accumulation of harmful substrates, with the aim of providing a
one-time treatment that can stop disease progression, improve
outcomes, and free people from lifelong treatment. FLT201 uses
Freeline’s proprietary AAVS3 capsid to introduce a novel transgene
into liver cells to produce a rationally engineered GCase variant.
In preclinical studies, the GCase variant has demonstrated a
greater than 20-fold increase in half-life at lysosomal pH
conditions compared to wildtype human GCase. Preclinically, FLT201
has shown robust GCase expression, leading to significant GCase
uptake and substrate reduction in key tissues. For more information
about the GALILEO-1 trial, please visit clinicaltrials.gov
(NCT05324943).
About Freeline
TherapeuticsFreeline is a clinical-stage biotechnology
company focused on developing transformative gene therapies for
chronic debilitating diseases. Freeline uses its proprietary,
rationally designed AAV vector and capsid (AAVS3), along with novel
promoters and transgenes, to deliver a functional copy of a
therapeutic gene into human liver cells, thereby expressing a
persistent functional level of the missing or dysfunctional protein
into a patient’s bloodstream. The company is currently advancing
FLT201, a highly differentiated gene therapy candidate that
delivers a novel transgene, in a Phase 1/2 clinical trial in people
with Gaucher disease type 1. Freeline has additional programs in
research, including one focused on GBA1-linked Parkinson’s disease
that leverages the same novel transgene as FLT201. Freeline is
headquartered in the UK and has operations in the United States.
For more information, visit www.freeline.life or connect with
Freeline on LinkedIn and Twitter.
Forward-Looking
StatementsThis press release contains statements that
constitute “forward-looking statements” as that term is defined in
the United States Private Securities Litigation Reform Act of 1995,
including statements that express the opinions, expectations,
beliefs, plans, objectives, assumptions or projections of Freeline
Therapeutics Holdings plc (the “Company”) regarding future events
or future results, in contrast with statements that reflect
historical facts. All statements, other than historical facts,
including statements regarding FLT201’s potential to provide better
outcomes for patients while dramatically reducing the burden that
comes with existing therapies, that the preclinical data regarding
FLT201 are starting to translate into clinical data and that a
third patient has been scheduled for dosing and three additional
study patients are in the process of being scheduled for dosing are
forward-looking statements. In some cases, you can identify such
forward-looking statements by terminology such as “anticipate,”
“intend,” “believe,” “estimate,” “plan,” “seek,” “project,”
“expect,” “may,” “will,” “would,” “could” or “should,” the negative
of these terms or similar expressions. Forward-looking statements
are based on management’s current beliefs and assumptions and on
information currently available to the Company, and you should not
place undue reliance on such statements. Forward-looking statements
are subject to many risks and uncertainties, including the
Company’s recurring losses from operations; the uncertainties
inherent in research and development of the Company’s product
candidates, including statements regarding the timing of
initiation, enrollment, continuation, completion and the outcome of
clinical studies or trials and related preparatory work and
regulatory review, regulatory submission dates, regulatory approval
dates and/or launch dates, as well as risks associated with
preclinical and clinical data, including the possibility of
unfavorable new preclinical, clinical or safety data and further
analyses of existing preclinical, clinical or safety data; the
Company’s ability to design and implement successful clinical
trials for its product candidates; whether the Company’s cash
resources will be sufficient to fund the Company’s foreseeable and
unforeseeable operating expenses and capital expenditure
requirements for the Company’s expected timeline in light of
management’s substantial doubt regarding the Company’s ability to
continue as a going concern for at least 12 months from the
issuance date of its most recent quarterly financial statements;
the Company’s failure to demonstrate the safety and efficacy of its
product candidates; the fact that results obtained in earlier stage
clinical testing may not be indicative of results in future
clinical trials; the Company’s ability to enroll patients in
clinical trials for its product candidates; the possibility that
one or more of the Company’s product candidates may cause serious
adverse, undesirable or unacceptable side effects or have other
properties that could delay or prevent their regulatory approval or
limit their commercial potential; the Company’s ability to obtain
and maintain regulatory approval of its product candidates; the
Company’s limited manufacturing history, which could result in
delays in the development, regulatory approval or commercialization
of its product candidates; and the Company’s ability to identify or
discover additional product candidates, or failure to capitalize on
programs or product candidates. Such risks and uncertainties may
cause the statements to be inaccurate and readers are cautioned not
to place undue reliance on such statements. The Company cannot
guarantee that any forward-looking statement will be realized.
Should known or unknown risks or uncertainties materialize or
should underlying assumptions prove inaccurate, actual results
could vary materially from past results and those anticipated,
estimated, or projected. Investors are cautioned not to put undue
reliance on forward-looking statements. A further list and
description of risks, uncertainties, and other matters can be found
in the Company’s Annual Report on Form 20-F for the fiscal year
ended December 31, 2022, and in subsequent reports on Form 6-K, in
each case including in the sections thereof captioned “Cautionary
Statement Regarding Forward-Looking Statements” and “Item 3.D. Risk
factors.” Many of these risks are outside of the Company’s control
and could cause its actual results to differ materially from those
it thought would occur. The forward-looking statements included in
this press release are made only as of the date hereof. The Company
does not undertake, and specifically declines, any obligation to
update any such statements or to publicly announce the results of
any revisions to any such statements to reflect future events or
developments, except as required by law. For further information,
please reference the Company’s reports and documents filed with the
U.S. Securities and Exchange Commission (the “SEC”). You may review
these documents by visiting EDGAR on the SEC website at
www.sec.gov.
Media and Investor
Contact:Naomi Aokinaomi.aoki@freeline.lifeSenior Vice
President, Head of Investor Relations & Corporate
Communications+ 1 617 283 4298
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