REG - Syncona Limited - Freeline presents data in Fabry disease

SynconaAnnouncement

08/02/2022 13:05

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220208:nRSH0196Ba&default-theme=true

RNS Number : 0196B  Syncona Limited  08 February 2022

Syncona Limited

 

Freeline presents data in Fabry disease

 

8 February 2022

 

Syncona Ltd, a leading healthcare company focused on founding, building and
funding global leaders in life science, notes that its portfolio company,
Freeline Therapeutics Holdings plc (Nasdaq: FRLN) ("Freeline"), will present
encouraging new data from its ongoing Phase I/II MARVEL-1 dose-finding
clinical trial of FLT190 in Fabry disease at the 18(th) Annual
WORLDSymposium(TM) taking place on February 7-11, 2022 in San Diego,
California.

 

Highlights from the data:

 

·    FLT190 continues to be well tolerated with previously observed mild
myocarditis found not to be associated with enduring clinical sequelae

·    Results from the first dose cohort continue to demonstrate promising
efficacy with a potential dose-dependent increase in levels of the key enzyme
(α-Gal A), which is absent or markedly deficient in Fabry patients. Durable
levels of α-Gal A sustained up to two years following dosing in Patient 1,
with Patient 2 continuing to remain off enzyme replacement therapy more than
26 weeks post-dosing 1  (#_ftn1)

 

Freeline will also separately present further detail on the trial design of
the Phase I/II GALILEO-1 study of FLT201 in Gaucher disease.

 

Chris Hollowood, Chief Investment Officer of Syncona Investment Management
Limited and Chair of Freeline said: "We are pleased to see this data from the
Fabry study, which further demonstrates that the therapy has an encouraging
safety and efficacy profile. Continued α-Gal A expression in the first
patient following dosing in 2019 suggests good durability in response to the
initial dose level, suggesting this could be a potentially transformative
treatment for patients with Fabry disease. We look forward to seeing further
data published later in the year in the Fabry study."

 

The poster presentations will be available on the Investors
(https://www.freeline.life/investors/) section of Freeline's website following
presentation at the WORLDSymposium™ conference. Freeline has issued a
release to introduce the presentations, which is also available on the company
website, with the full text contained below.

 

 

 ENDS 

 

Copies of this press release and other corporate information can be found on
the company website at: www.synconaltd.com (http://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.

 

 

Enquiries

 

Syncona Ltd

 

Natalie Garland-Collins / Fergus Witt

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
founding and building companies to deliver transformational treatments to
patients in areas of high unmet need.

 

Our strategy is to found, build and fund companies around exceptional science
to create a diversified portfolio of 15-20 globally leading healthcare
businesses 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.

 

 

Freeline Presents on Its Fabry and Gaucher Disease AAV-Based Gene Therapies at
the 18(th) Annual WORLDSymposium(TM)

FLT190 well-tolerated with promising early efficacy in Fabry disease including
sustained α-Gal A expression up to two years

GALILEO-1, a first-in-human, open-label, international, multicenter Phase 1/2
clinical trial evaluating FLT201 in Gaucher disease Type 1 initiated

LONDON, February 8, 2022 - Freeline Therapeutics Holdings plc (Nasdaq: FRLN)
(the "Company" or "Freeline"), a clinical-stage biotechnology company
developing transformative AAV-mediated gene therapies for people with
inherited systemic debilitating diseases, will present updated data from the
ongoing Phase 1/2 MARVEL-1 clinical trial evaluating FLT190 for the treatment
of patients with Fabry disease, and the clinical trial design for GALILEO-1, a
Phase 1/2 safety and efficacy study of FLT201 in adult patients with Gaucher
disease Type 1 at the 18(th) Annual WORLDSymposium(TM) taking place February 7
- 11, 2022 in San Diego, California.

"Freeline's proprietary AAVS3 capsid has the potential to deliver
transformative treatments for patients with challenging diseases including
Fabry disease and Gaucher disease," said Pam Foulds, MD, Freeline's Chief
Medical Officer. "It is highly encouraging to observe early signals of
durability and efficacy in MARVEL-1 in Fabry disease, with sustained
expression up to two years as of our last data reading. Advancing the study
will allow further exploration of the potential of FLT190 to provide a
functional cure for Fabry disease, which may eliminate the need for enzyme
replacement therapy and improve patient outcomes. With FLT201 in Gaucher
disease Type 1 advancing to first-in-human studies, I believe the Freeline
approach, which leverages a novel capsid and engineered, stable GCase variant,
has the potential to overcome the limitations of currently available
treatments for Gaucher by addressing difficult-to-reach tissues including bone
marrow and lung."

Michael Parini, Chief Executive Officer of Freeline, said, "We are proud of
our steady execution in the clinic and believe this continued progress
showcases the Freeline team's dedication to advancing new therapies for
patients with great unmet need. Both the MARVEL-1 and GALILEO-1 studies
leverage the strengths of the proprietary Freeline platform, with a highly
potent AAVS3 capsid, robust CMC, and protein engineering expertise. We will
continue to push forward cutting-edge science, and lead the way in safety, to
deliver new medicines to patients with the potential to change the
standard-of-care."

Highlights from the presentation titled, "Safety and efficacy of FLT190 for
the treatment of patients with Fabry disease: Results from the MARVEL-1 Phase
1/2 clinical trial," presented by Derralynn A. Hughes, include:

·    FLT190 has been well-tolerated; a novel prophylactic immune
management regimen may have prevented vector-related transaminitis in Patient
2

·    Results from the first dose cohort (7.5 x 10(11) vg/kg) demonstrate
promising efficacy with a potential dose-dependent increase in plasma α-Gal A
levels, durable α-Gal A levels sustained for up to two years in Patient 1,
and with Patient 2 continuing to remain off ERT more than 26 weeks post-dosing
as of the data cut-off date of December 22, 2021

·    Mild, transient myocarditis was observed in both patients
approximately 6-8 weeks post-dose of FLT190 which was not associated with
enduring clinical sequelae on cardiac MRI and suggests that cardiac monitoring
may be valuable in gene therapy trials for conditions like Fabry disease with
known underlying cardiac manifestations

Highlights from the presentation titled "Design of GALILEO-1, a Phase 1/2
safety and efficacy study of FLT201 in adult patients with Gaucher disease
Type 1," presented by Derralynn A. Hughes include:

·    FLT201 consists of a rationally designed AAV capsid (AAVS3)
containing an expression cassette that encodes for a novel glucocerebrosidase
variant (GCase(var85)) under the control of a liver-specific promotor. FLT201
produces robust and sustained secretion of GCase in preclinical models, as
well as increased stability at lysosomal and physiological pH in human serum

·    GCase(var85) contains two novel amino acid substitutions that result
in a 6-fold increase in half-life in human serum, and 20-fold increase in
half-life at lysosomal pH conditions

·    GALILEO-1 is a first-in-human, open-label, international, multicenter
Phase 1/2 clinical trial evaluating a single intravenous infusion of FLT201
with a novel prophylactic immune management regimen to prevent vector-related
transaminitis

·    Study objectives include evaluating the safety and tolerability of
FLT201, investigating the relationship of FLT201 dose to production of
endogenous GCase and determining the potential to improve clinical phenotype
by reduction in the GCase substrate

·    The adaptive dose-escalation study will identify a dose of FLT201 for
further development in a Phase 3 clinical trial, and will include two parts:
Part 1, in patients previously treated with enzyme replacement therapy (ERT)
or substrate reduction therapy (SRT), and Part 2, previously untreated
patients

The poster presentations will be available on the Investors
(https://www.freeline.life/investors/newsroom/?type=presentations) section of
Freeline's website following presentation at the WORLDSymposium™ conference.

About Freeline Therapeutics

Freeline is a clinical-stage biotechnology company developing transformative
adeno-associated virus (AAV) vector-mediated systemic gene therapies. The
Company is dedicated to improving patient lives through innovative, one-time
treatments that provide functional cures for inherited systemic debilitating
diseases. Freeline uses its proprietary, rationally designed AAV vector, 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 the patient's
bloodstream. The Company's integrated gene therapy platform includes in-house
capabilities in research, clinical development, manufacturing, and
commercialization. The Company has clinical programs in hemophilia B, Fabry
disease, and Gaucher disease Type 1. Freeline is headquartered in the UK and
has operations in Germany and the US.

About Fabry Disease

Fabry disease is a genetic lysosomal disease that leads to a deficiency in
α-galactosidase A (α-Gal A), which is a key enzyme needed to break down a
fatty substance called globotriaosylceramide (Gb3) and lyso-Gb3. Without the
enzyme, this fatty substance builds up throughout the body, affecting tissues
and organs including skin, kidneys, heart, and the nervous system. Freeline is
currently focused on classic Fabry disease where patients have little to no
functional α-Gal A enzyme. The current standard of care is lifelong
intravenous infusions of enzyme replacement therapy (ERT) or pharmacological
chaperone therapy (PCT). Certain treatments can carry a significant burden on
the patient. The aim of Freeline's investigational gene therapy program is to
deliver a one-time treatment of a long-lasting gene therapy that will provide
a sustained, therapeutically relevant level of α-Gal A that the Company
believes would eliminate the need for ERT or PCT.

About FLT190 for Fabry Disease

FLT190 is an investigational AAV gene therapy in development as a potential
treatment for patients with Fabry disease. FLT190 consists of a potent,
rationally designed capsid (AAVS3) containing an expression cassette with a
codon-optimized human α-Gal A cDNA under the control of a liver-specific
promoter. The Company's current MARVEL-1 Phase 1/2 dose-finding trial is
evaluating the potential safety and efficacy of FLT190 in Fabry patients, who
often have pre-existing cardiac manifestations due to underlying substrate
accumulation and disease progression in the heart. The treatment is
administered by intravenous infusion that lasts approximately one hour and
does not require the patient to undergo stem cell harvest or conditioning with
chemotherapy.

About Gaucher Disease

Gaucher disease is a genetic disorder in which a fatty substance called
glucosylceramide accumulates in macrophages in certain organs due to the lack
of functional glucocerebrosidase (GCase). The disorder is hereditary and
presents in various subtypes. Freeline is currently focused on Gaucher disease
Type 1, the most common type, which impacts the health of many organs of the
body including the spleen, liver, blood system, and bones. The current
standard of care is intravenous infusion of ERT or oral substrate reduction
therapy (SRT). The aim of Freeline's investigational gene therapy program is
to deliver a one-time treatment of a long-lasting gene therapy that will
provide a sustained, therapeutically relevant level of GCase that the Company
believes would eliminate the need for ERT or SRT.

About FLT201 for Gaucher Disease

FLT201 is an investigational gene therapy for the treatment of Gaucher disease
Type 1. It consists of a potent, rationally designed AAV capsid (AAVS3)
containing an expression cassette that encodes for a novel glucocerebrosidase
variant (GCase(var85)) under the control of a liver-specific promoter. The
GCase(var85) contains two novel amino acid substitutions to the wild-type
human GCase, which results in a 20-fold increase in GCase half-life at
lysosomal pH conditions, but similar catalytic parameters to those of
wild-type GCase and ERT. The Company's high-transducing AAVS3 capsid advances
its goal to address unmet needs for those affected by Gaucher disease by
potentially enabling sustained, endogenous production of GCase following a
one-time intravenous infusion.

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 Company's
opinions, expectations, beliefs, plans, objectives, assumptions or projections
regarding future events or future results, in contrast with statements that
reflect historical facts. Examples include, among other topics, statements
regarding the dosing, timing, progress and interim and final results of the
Company's Phase 1/2 MARVEL-1 dose-finding clinical trial of FLT190 and Phase
1/2 GALILEO-1 dose-finding clinical trial of FLT201 and statements regarding
the potential of the Company's product candidates to deliver transformative
treatments or change the standard-of-care for patients with challenging
diseases, including FLT190's potential to provide a functional cure for Fabry
disease, eliminate the need for enzyme replacement therapy and improve patient
outcomes, FLT201's potential to overcome the limitations of currently
available treatments for Gaucher disease by addressing difficult-to-reach
tissues including bone marrow and lung. In some cases, you can identify such
forward-looking statements by terminology such as "anticipate," "intend,"
"believe," "estimate," "plan," "seek," "project" or "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, 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; the recent departures of a number of executive officers of
the Company, and the Company's ability to fill open positions, implement an
orderly transition process and retain key talent; 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; the potential for a pandemic, epidemic or
outbreak of infectious diseases in the US, UK or EU, including the COVID-19
pandemic, to disrupt and delay the Company's clinical trial pipeline; 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 experience, 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, 2020 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.

IR Contact:

investor@freeline.life

 

Media Contact:

media@freeline.life

 

 

 

 

 1  (#_ftnref1) Data cut off date of December 22, 2021

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  PFUFIFFAFEITIIF