REG - Syncona Limited - Freeline Announces Positive Initial Clinical Data

SynconaAnnouncement

04/10/2023 12:15

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20231004:nRSD6844Oa&default-theme=true

RNS Number : 6844O  Syncona Limited  04 October 2023

Syncona Limited

 

Freeline Announces Positive Initial Clinical Data

 

 

04 October 2023

 

Syncona Ltd, a leading healthcare company focused on creating, building and
scaling global leaders in life science, notes that its portfolio company,
Freeline Therapeutics Holdings plc (Nasdaq: FRLN) ("Freeline") has announced
positive initial safety, tolerability and enzyme activity data from the
ongoing phase I/II GALILEO-1 trial evaluating FLT201, its novel gene therapy
candidate, in Gaucher disease.

 

Highlights include:

 

·      Gaucher disease is a debilitating genetic disorder caused by a
deficiency of the GCase enzyme

·      First two patients treated with Freeline's gene therapy
demonstrated a robust increase and normalisation of GCase enzyme levels and
activity; an important indication of the candidate's therapeutic potential

·      The data from the first two patients also showed a favorable
safety and tolerability profile with 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

·      Given the compelling safety profile and robust enzyme activity, a
third patient has been scheduled for dosing in the first cohort

·      Freeline will host a webcast presentation today, at 8:00 am ET/
1:00 pm BST, to discuss these initial clinical data for FLT201 in Gaucher
disease

 

Chris Hollowood, CEO of Syncona Investment Management Limited and Chair of
Freeline, said: "We are very pleased to see this positive data from Freeline
which demonstrates a compelling safety profile and robust enzyme activity for
its gene therapy programme for the treatment of Gaucher disease. This data
strengthens our belief that FLT201 has the potential to be first- and
best-in-class gene therapy for Gaucher disease, a debilitating condition where
there is a clear need for better treatment options. We look forward to the
dosing of additional patients and to the further encouraging data readouts
from the study."

 

Pamela Foulds, MD, Chief Medical Officer of Freeline, said: "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. 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."

 

Freeline management will host a webcast presentation today, at 8:00 am ET/
1:00 pm BST, 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 (http://www.freeline.life/)
.

 

The announcement can be accessed on Freeline's website at
https://freeline.life/investors/newsroom/
(https://freeline.life/investors/newsroom/) and the full text of the
announcement from Freeline is contained below.

 

 

 ENDS 

 

Enquiries

 

Syncona Ltd

Annabel Clark

Tel: +44 (0) 7714 916615

 

FTI Consulting

Ben Atwell / Natalie Garland-Collins / Tim Stamper

Tel: +44 (0) 20 3727 1000

 

About Syncona

 

Syncona's purpose is to invest to extend and enhance human life. We do this by
creating and building companies to deliver transformational treatments to
patients in areas of high unmet need.

 

Our strategy is to create, build and scale companies around exceptional
science to create a diversified portfolio of 20-25 globally leading healthcare
businesses, across development stage and therapeutic areas, for the benefit of
all our stakeholders. We focus on developing treatments for patients by
working in close partnership with world-class academic founders and management
teams. Our balance sheet underpins our strategy enabling us to take a
long-term view as we look to improve the lives of patients with no or poor
treatment options, build sustainable life science companies and deliver strong
risk-adjusted returns to shareholders.

 

Copies of this press release and other corporate information can be found on
the company website at: www.synconaltd.com Forward-looking statements - this
announcement contains certain forward-looking statements with respect to the
portfolio of investments of Syncona Limited. These statements and forecasts
involve risk and uncertainty because they relate to events and depend upon
circumstances that may or may not occur in the future. There are a number of
factors that could cause actual results or developments to differ materially
from those expressed or implied by these forward-looking statements. In
particular, many companies in the Syncona Limited portfolio are conducting
scientific research and clinical trials where the outcome is inherently
uncertain and there is significant risk of negative results or adverse events
arising. In addition, many companies in the Syncona Limited portfolio have yet
to commercialise a product and their ability to do so may be affected by
operational, commercial and other risks.

 

Freeline Reports Positive Initial Clinical Data from First Cohort of Phase 1/2
GALILEO-1 Trial of FLT201, Its Novel Gene Therapy Candidate, in Gaucher
Disease

 

Robust increases of up to 700-fold over baseline in plasma GCase enzyme
activity in first two patients treated with FLT201

 

Normalization of leukocyte GCase in both patients demonstrates cellular uptake
from plasma

 

FLT201 has been well tolerated, with no serious adverse events

 

Company to host conference call today at 8 a.m. ET

 

LONDON, October 4, 2023 - Freeline Therapeutics Holdings plc
(https://www.freeline.life/) (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 FLT201

The 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 4.5x10(11) 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 mmol/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 mmol/L/h as of four weeks
post-dosing. Normal plasma GCase levels range from 0.3 to 1.2 mmol/L/h (mean:
0.58 mmol/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
4.5x10(11) 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 Information

Freeline 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 (https://wsw.com/webcast/cc/frln3/1432638) . 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 Disease

Gaucher 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
(https://clinicaltrials.gov/ct2/show/NCT05324943?term=galileo-1&draw=2&rank=1)
(NCT05324943).

 

About Freeline Therapeutics

Freeline 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 (http://www.freeline.life) or connect with Freeline on
LinkedIn (https://www.linkedin.com/company/freelinelife/) and Twitter
(https://twitter.com/FreelineLife) .

 

Forward-Looking Statements

This 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 (http://www.sec.gov) .

 

Media and Investor Contact:

Naomi Aoki
naomi.aoki@freeline.life
(https://www.globenewswire.com/Tracker?data=4nPenuYvOBzpaHtJGKs93JV-SstDIW0q1Z9sVIPRaQZ16_YZYW6eR2IqtB8eXPu2Pe4d5rW0L0mDjYrhupJcVVEfwGmy5GsaS6XHJz9rMmw=)

Senior Vice President, Head of Investor Relations & Corporate
Communications

+ 1 617 283 4298

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  PFUFIFVAILLSIIV