Syncona
Limited
Freeline
presents clinical data update
9 May 2024
Syncona Ltd, a leading life science
investor focused on creating, building and scaling global leaders
in life science, announces that its portfolio company Freeline
Therapeutics ("Freeline") today presented positive new data from
its Phase I/II GALILEO-1 study of FLT201, its novel gene therapy
candidate, in Gaucher disease at the American Society of Gene and
Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore,
Maryland.
Gaucher disease is a debilitating
genetic disorder caused by a deficiency of the GCase enzyme. The
data reported is from the four patients in the trial who have come
off their prior therapies as of the 19 February 2024 data cutoff.
These four patients have remained off their prior therapies and
range in follow up from 14 to 32 weeks after dosing. All patients
were treated with a single dose of 4.5x1011
vg/kg.
Highlights from the presentation
include:
· FLT201
demonstrates a favourable safety and tolerability profile, with no
infusion reactions and no severe adverse events.
· FLT201
generates robust and continuous expression of the GCase enzyme in
the plasma, with clear evidence of uptake of GCase into the cells;
an important indication of the candidate's therapeutic
potential.
· Lyso-Gb1, an established biomarker of clinical response, was
substantially reduced in patients with persistently high lyso-Gb1
levels, despite years on prior treatment with enzyme replacement
therapy (ERT) or substrate reduction therapy (SRT).
· Maintenance of haemoglobin levels and improvement or
maintenance of platelet counts were also seen post withdrawal of
treatment with ERT or SRT.
Emerging late-breaking data as of 8
April 2024 also demonstrated early signs of clinical
benefit:
· In the
first four patients as of 12 to 38 weeks post-dosing, bone marrow
burden improved, indicating clearance of substrate and reappearance
of healthy, fatty marrow. Furthermore, a clinically meaningful
improvement in fatigue, leading to increased ability to perform
daily activities, was seen in a patient who entered the trial with
extreme fatigue
Chris Hollowood, CEO of Syncona
Investment Management Limited and Chair of Freeline, said:
"We are very encouraged by the data generated from
FLT201 which demonstrates a favourable safety and tolerability
profile and significant enzyme activity. We are confident this
treatment has the potential to challenge the standard of care in
Gaucher disease, where current treatments are life-long and do not
fully alleviate the disease. After a decade on ERT, 60% of
patients still experience symptoms,
including bone pain, lung dysfunction, enlarged organs, fatigue and
low platelet counts. Freeline's treatment not only
sustains GCase expression, but data presented at ASGCT suggests
that FLT201 could potentially transform the quality of life for
these patients. The company expects to publish further data this
year, which we view as a key value inflection point, and is
advancing FLT201 towards a Phase III trial next year. We look
forward to working with the company closely to deliver on
this."
Separately, Freeline also presented
promising in vitro and in
vivo data from its Parkinson's disease research programme,
which leverages the same mechanism as the Gaucher programme.
Freeline is developing a gene therapy candidate for a subset of
patients with GBA1 gene mutations, which are associated with
earlier onset, symptom severity and likelihood of progression to
dementia.
The company has also announced that
FLT201 has been granted Regenerative Medicine Advanced Therapy
(RMAT) designation by the US Food and Drug Administration and
Priority Medicines (PRIME) Designation by the European Medicines
Agency (EMA). Both RMAT and PRIME designations are designed to
expedite the drug development and review process for
investigational therapies intended to treat, modify, reverse or
cure a serious or life-threatening disease.
Freeline's announcement is copied
below, whilst a summary of data from both programmes can be
accessed on the company's website at https://freeline.life/investors/newsroom/.
[ENDS]
Enquiries
Syncona Ltd
Annabel Clark / Fergus
Witt
Tel: +44 (0) 20 3981 7940
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.
Syncona Limited seeks to
achieve returns over the long term. Investors should seek to ensure
they understand the risks and opportunities of an investment
in Syncona Limited, including the information in our published
documentation, before investing.
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. Freeline 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
X.
Freeline Presents Positive
New Data from Phase 1/2 Trial of FLT201, Its Novel Gene Therapy
Candidate for Gaucher Disease, in Late-Breaking Oral Presentation
at ASGCT 27th Annual Meeting
Substantial reductions seen
in lyso-Gb1, an established biomarker of clinical response, in
patients with persistently high levels despite years of treatment
with currently approved therapies
Early signs of clinical
improvement observed in bone marrow burden and fatigue, supporting
FLT201's potential to improve patient outcomes over standard of
care with a one-time therapy
FLT201 granted Regenerative
Medicine Advanced Therapy designation by FDA and Priority Medicines
Designation by EMA
Freeline also presenting
promising in vitro and in vivo data on its GBA1 Parkinson's disease
gene therapy program, leveraging same longer-acting engineered
GCase enzyme as FLT201
LONDON, May 9, 2024 - Freeline Therapeutics
today announced new clinical data from its ongoing
Phase 1/2 GALILEO-1 trial of FLT201, its adeno-associated virus
(AAV) gene therapy candidate for Gaucher disease, showing
substantial reductions in glucosylsphinogsine (lyso-Gb1), one of
the best predictors of clinical response, in patients with
persistently high levels despite years of treatment with currently
approved therapies, as well as early signs of clinical improvements
in bone marrow burden and fatigue. FLT201 continues to demonstrate
a favorable safety and tolerability profile. These data are being
showcased in a late-breaking oral presentation at the American
Society of Gene and Cell Therapy (ASGCT) 27th Annual
Meeting taking place in Baltimore, Maryland.
Gaucher disease is caused by a
mutation in the GBA1 gene,
which leads to a deficiency of the glucocerebrosidase (GCase)
enzyme. As a result, substrates build up in cells and organs
throughout the body, causing symptoms including enlarged spleen and
liver, low blood counts, bone pain, fatigue and reduced lung
function. FLT201 delivers a rationally engineered version of the
GCase enzyme (GCase85) with greater stability than wildtype GCase,
designed to stay in cells longer to more effectively clear
substrates and penetrate difficult-to-reach tissues, including
bone, that currently approved therapies poorly address. Reductions
in lyso-Gb1 levels in the blood are highly correlated with
substrate reduction in disease-affected tissues and positive
clinical outcomes in Gaucher disease.
"Gaucher disease, the most common
lysosomal storage disorder, is severe and progressive when not
treated. Currently approved treatments have made a significant
difference for people with Gaucher disease, but there is not an
existing cure. Patients require life-long treatment and many
continue to experience symptoms, including enlarged organs, chronic
bone pain and fatigue," said Ozlem Goker-Alpan, M.D., founder and
CEO of the Lysosomal and Rare Disorder Research and Treatment
Center (LDRTC) and an investigator in the Phase 1/2 GALILEO-1 trial
of FLT201. "A gene therapy that could deliver the same or better
efficacy than currently available treatments, while freeing people
from an ongoing treatment burden, would mark a significant advance
in the treatment paradigm for Gaucher disease. I am very encouraged
by the clinical data to date for FLT201."
Positive New Clinical Data for FLT201
Today's presentation will include
updated data on safety, tolerability, GCase activity
and lyso-GB1, hemoglobin and
platelet levels, as well as new data on bone marrow burden and
fatigue from GALILEO-1, a
first-in-human, international, multicenter dose-finding study in
adults with Gaucher disease Type 1. The data being reported
are from the four patients in the trial who have come off their
prior therapies as of the February 19, 2024 data
cutoff. These four patients have remained
off their prior therapies and range in follow up
from 14 to 32 weeks after dosing. All patients
were treated with a single dose of 4.5x1011 vg/kg.
The data demonstrated:
·
Favorable safety and tolerability, with no
infusion reactions and no serious adverse events. Modest
alanine-transaminase (ALT) elevations in some patients were managed
with immune therapy, with no impact to efficacy. Non-serious
adverse events were all mild or moderate in severity.
·
Robust and continuous expression in plasma GCase,
with clear evidence of cellular uptake of GCase from the plasma as
measured by GCase activity in the leukocytes. Leukocytes are
established indicators for broad cellular uptake in Gaucher
disease.
·
Substantial reductions in lyso-Gb1 in patients who
entered the trial with persistently high lyso-Gb1 levels despite
years on prior treatment with enzyme replacement therapy (ERT) or
substrate reduction therapy (SRT). Low lyso-Gb1 levels were
maintained in one patient who entered the trial with
well-controlled levels.
·
Maintenance of hemoglobin levels, an established
endpoint for Gaucher disease clinical trials, was observed post
withdrawal of treatment with ERT or SRT. Improvement or maintenance
of platelet counts was also seen post withdrawal of treatment with
ERT or SRT.
Emerging late-breaking data as of
April 8, 2024, also demonstrated:
·
Reductions in bone marrow burden in the first four
patients as of 12 to 38 weeks post-dosing, indicating clearance of
substrate from the bone marrow and reappearance of healthy, fatty
marrow.
·
Clinically meaningful improvement in fatigue in
the first patient dosed, which led to increased functioning and
ability to perform daily activities. The patient demonstrated a
21-point improvement on the Functional Assessment of Chronic
Illness Therapy (FACIT) fatigue scale, with a 2.8 to 6.8-point
improvement being considered clinically meaningful in chronic
illnesses. As of the data cut, this patient was the only patient
with sufficient follow-up data for a meaningful FACIT
assessment.
Freeline today also announced that
FLT201 has been granted Regenerative Medicine Advanced Therapy
(RMAT) designation by the US Food and Drug Administration and
Priority Medicines (PRIME) Designation by the European Medicines
Agency (EMA). Both RMAT and PRIME designations are designed to
expedite the drug development and review process for
investigational therapies intended to treat, modify, reverse or
cure a serious or life-threatening disease. The investigational
therapy must be supported by preliminary clinical evidence that the
therapy has the potential to address unmet medical needs for the
disease. RMAT and PRIME provide the benefits of intensive guidance
from the FDA and EMA, respectively, on efficient drug development,
including the ability for early interactions to discuss surrogate
or intermediate endpoints, potential ways to support accelerated
approval and satisfy post-approval requirements, and potential
priority review of the biologics license application.
"FLT201 is a potentially first- and
best-in-class gene therapy for Gaucher disease," said Pamela
Foulds, M.D., Freeline's Chief Medical Officer. "It is designed to
deliver a continuous supply of the enzyme missing in people with
Gaucher disease and to deliver a more stable version of that
enzyme, with the aim of getting enzyme into all disease-affected
tissues and increasing the amount of time the enzyme is in those
tissues to do its job of clearing harmful substrates. The clinical
data to date strengthen our conviction in the life-changing
potential of FLT201. They also support our strategy of extending
the therapeutic potential of our GCase85 enzyme into a genetically
linked subset of Parkinson's disease patients with GBA1 mutations, and we are excited to
share promising new data from that program."
Highlights from GBA1 Parkinson's Disease Research
Program
In a separate poster presentation at
ASGCT, Freeline is presenting in vitro and in vivo data from its Parkinson's
disease research program. The program builds on its work with
Gaucher disease, leveraging the enhanced stability of GCase85 to
develop a gene therapy candidate for a subset of Parkinson's
disease patients with mutations in the GBA1 gene. As in Gaucher disease, the
GBA1 mutations lead to a
deficiency of GCase and the accumulation of harmful substrates,
greatly increasing the risk of developing Parkinson's disease. GBA1
mutations are also associated with earlier onset of disease, more
severe symptoms and increased likelihood of progression to
dementia.
The findings demonstrate
that:
·
GCase85 results in an order of magnitude higher
GCase activity compared to wildtype in both in vitro and in vivo studies.
·
Direct injection into the caudate putamen region
of the brain using an AAV9 vector is effectively distributed to the
target cells of the substantia nigra, which is a key area of the
brain affected by Parkinson's disease.
·
An AAV9-GBA1-85 construct results in stronger
expression and broader GCase distribution in the brain than a
wildtype AAV9-GBA1 construct when directly injected into the brain
in mice.
Both the late-breaking oral
presentation and the poster presentation are now available on the
News & Events section of Freeline's
website.
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 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 GBA1-linked
Parkinson's Disease
Parkinson's disease (PD) is a progressive
neurodegenerative disorder that results in tremors, muscle
rigidity, difficulty walking, anxiety, depression and cognitive
impairments. Approximately 5-15% of PD patients have mutations in
the GBA1 gene, which encodes for
the glucocerebrosidase (GCase) enzyme. The most common genetic risk
factor for PD, GBA1 mutations increase the
risk of developing PD by 5- to
30-fold. GBA1 mutations
are also associated with earlier onset and more severe disease.
There are no approved disease-modifying therapies for PD, and
current treatments, which focus on managing symptoms, become less
effective over time. Freeline estimates GBA1-linked PD affects
approximately 190,000 patients in the United States, United
Kingdom, France, Germany, Spain and Italy.
About Freeline Therapeutics
Freeline is a clinical-stage biotechnology
company focused on developing transformative gene therapies for
chronic debilitating diseases. Freeline 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 X.
Media
Contact:
Naomi Aoki
naomi.aoki@freeline.life
+ 1 617 283 4298