4 February 2025
Syncona
Limited
Spur
announced positive data from Phase I/II trial of FLT201 in Gaucher
disease
Syncona Ltd, ("Syncona"), a leading
life science investor focused on creating, building and scaling a
portfolio of global leaders in life science, today notes that its portfolio company, Spur Therapeutics
("Spur") announced positive new data from its Phase I/II
GALILEO-1 study of FLT201, its novel gene therapy candidate, in
Gaucher disease at the 21st Annual WORLDSymposium in San Diego, CA,
USA.
Six patients have been treated in
GALILEO-1 with a single infusion of FLT201 at a low dose of 4.5e11
vg/kg and have been followed for between nine and 17 months after
dosing. All six patients are included in the safety analysis; one
patient with detectable pre-existing neutralising antibodies to the
AAVS3 capsid was excluded from the efficacy analysis. Prior to the
trial all of the patients had been treated with existing therapies
enzyme replacement therapy (ERT) or substrate reduction therapy
(SRT).
These data follow yesterday's
announcement that Spur had received positive feedback from its
end-of-Phase II meeting with the US Food and Drug Administration
(FDA), with alignment on the potential to seek accelerated
approval[1] based on reductions in
glucosylsphingosine (lyso-Gb1), an established biomarker of
clinical response in Gaucher disease. Full approval would be based
on a primary endpoint of maintenance or improvement in haemoglobin
at one year in the Phase III study. The completion of the pivotal
stage of the Phase III trial in CY2027 is a key value inflection
point for Syncona[2].
Data as of 6 December 2024
demonstrated:
· Continued
favourable safety and tolerability profile, with no infusion
reactions, dose limiting toxicities or treatment-related severe
adverse events
· Durable reductions in lyso-Gb1, ranging from 33% to 96% in
patients who entered the trial with high levels
o Stable lyso-Gb1 levels for more than a year after the
withdrawal of prior therapy in the one patient who entered the
trial with well-controlled levels.
· Maintenance of normal haemoglobin levels (Phase III primary
endpoint) beyond a year after withdrawal of ERT or SRT
· Sustained improvements or maintenance in platelet counts and
spleen and liver volume after withdrawal of ERT or SRT
· Improvements in
bone marrow burden (BMB) in four of the five patients, indicating
the clearance of substrate and reappearance of healthy marrow, and
maintenance of BMB in the fifth patient. Previously reported BMB
scores have been updated to correct a reporting error by an outside
clinical research organisation[3]
Chris Hollowood, Chief Executive Officer of Syncona Investment
Management Limited and Chair of Spur Therapeutics,
said: "These data further reinforce our belief that
FLT201 has the potential to be a first- and best-in-class gene
therapy for Gaucher disease. Through a single infusion, FLT201 has
shown improvements to symptoms that had been persistent in patients
receiving approved therapies for years and in some cases decades.
We look forward to the initiation of Spur's Phase III FLT201 trial
later this year, following the company's recent successful
end-of-Phase II meeting with the US FDA."
Spur's announcement is copied below
and can be accessed on the company's website
at https://spurtherapeutics.com/.
[ENDS]
Enquiries
Syncona Ltd
Natalie Garland-Collins / Fergus
Witt
Tel: +44
(0)20 3981 7912
FTI
Consulting
Ben Atwell / 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, building and
scaling companies to deliver transformational treatments to
patients in areas of high unmet need.
We aim to build and maintain a
diversified portfolio of 20-25 globally leading life science
businesses, across development stage, modality and therapeutic
area, for the benefit of all our stakeholders. We focus on
developing treatments that deliver patient impact by working in
close partnership with world-class academic founders and
experienced 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.
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.
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.
Notes
About Key Value Inflection Points
A key value inflection point is a
material de-risking event for a portfolio company that has the
potential to drive significant NAV growth for Syncona, for example
by increasing the possibility of a realisation event, such as
M&A. These milestones can also enable companies to access
significant capital including through financings and IPOs, which
may take place at valuation uplifts and underpin progression to a
subsequent key value inflection point which has the potential to
drive greater value. M&A or capital access is unlikely to occur
immediately following a key value inflection point.
Spur Therapeutics Announces
Positive Data from Phase 1/2 GALILEO-1 Trial of FLT201, Its Gene
Therapy Candidate for Gaucher Disease, at WORLDSymposium™
Oral and poster
presentations highlight FLT201's potential to set a new standard of
care
LONDON, February 4, 2025 - Spur
Therapeutics today announced
data from its Phase 1/2 GALILEO-1 trial of FLT201, an
adeno-associated virus (AAV) gene therapy candidate for Gaucher
disease type 1, showing rapid and sustained improvements in
glucosylsphingosine (lyso-Gb1), one of the best predictors of
clinical response in Gaucher disease, as well as improvement or
maintenance of blood counts, organ volume and bone marrow burden in
patients treated with a single infusion of FLT201. FLT201 continues
to demonstrate a favorable safety and tolerability profile in all
patients treated in the study. These data are being showcased this
week in oral and poster presentations at the 21st Annual
WORLDSymposium.
"Gaucher disease is a debilitating
chronic disorder, and despite treatment with currently approved
therapies, many patients continue to have serious symptoms," said
Pamela Foulds, M.D., Spur's Chief Medical Officer. "Data from our
Phase 1/2 study being presented at the WORLDSymposium show that a single infusion
of FLT201 led to improvements in persistent symptoms and disease
involvement in patients who have been on approved therapies for
years. These improvements, together with the favorable safety
profile and durability of responses, highlight FLT201's potential
to provide better efficacy and dramatically reduce the treatment
burden for people with Gaucher disease."
"FLT201 is the result of our
unwavering focus on developing gene therapies that change people's
lives," said Michael Parini, Spur's Chief Executive Officer. "We
purposefully designed FLT201 to overcome the shortcomings of
currently approved therapies, engineering a more stable version of
the GCase enzyme deficient in people with Gaucher disease and
packaging it in a capsid that is highly efficient at transducing
cells to produce the enzyme. We are seeing that work translate into
benefits beyond what current therapies provide at a low dose that
we believe could offer an important safety advantage over other
gene therapies in development. We are moving quickly to initiate a
Phase 3 study of FLT201."
Compelling Safety and Efficacy Data for
FLT201
Building on previously reported
data, the oral and poster presentations at the WORLDSymposium demonstrate the durable
benefits and longer-term safety profile of FLT201. In addition to
updated safety and tolerability data, the presentations include
recent assessments of biomarker and efficacy endpoints from the
GALILEO-1 study, a first-in-human, international,
multicenter dose-finding study in adults with Gaucher disease type
1, and the GALILEO-2 long-term follow up study.
Six patients
were treated in GALILEO-1 with a single infusion of FLT201 at a low
dose of 4.5e11 vg/kg. Patients have been followed for
between nine and 17
months after dosing and have all rolled over into
GALILEO-2. All six patients are included in the safety analysis;
one patient with detectable pre-existing neutralizing antibodies to
the AAVS3 capsid was excluded from the efficacy analysis. Prior to
the trial, patients had been on a stable dose of either enzyme
replacement therapy (ERT) or substrate reduction therapy (SRT) for
between four and 24 years. All patients taken off ERT or SRT remain
off those therapies.
The data as of December 6, 2024 cut-off
date demonstrated:
·
Favorable safety and tolerability, with no
infusion reactions or dose limiting toxicities. All
treatment-related adverse events were mild to moderate in
nature.
·
Durable reductions in lyso-Gb1, ranging from
33% to 96%, in patients who entered the
trial with high levels; stable lyso-Gb1 levels for more than a year
after the withdrawal of prior therapy in the one patient who
entered the trial with well-controlled levels. Lyso-Gb1 levels in
the blood are highly correlated with substrate levels in
disease-affected tissues as well as with
treatment response.
·
Maintenance of normal hemoglobin levels beyond a
year after withdrawal of ERT or SRT.
·
Sustained improvements or maintenance in platelet
counts and spleen and liver volume after withdrawal ERT or
SRT.
·
Improvements in bone marrow burden (BMB) in four
of the five patients, indicating the clearance of substrate and
reappearance of healthy marrow, and maintenance of BMB in the fifth
patient. Previously reported BMB scores
have been updated to correct a reporting error by an outside
clinical research organization.[4]
As announced yesterday, Spur has
gained alignment with the U.S. Food and Drug Administration on the
design of a single-arm Phase 3 study to support potential
accelerated approval of FLT201 based on reductions in lyso-Gb1 and
full approval based on improvement or maintenance of hemoglobin
levels. Secondary endpoints will include platelet counts and organ
volume, with exploratory endpoints including bone health
assessments and patient-reported outcomes. Spur expects to dose the
first patient in the Phase 3 study in the second half of
2025.
About
FLT201
FLT201 is an
adeno-associated virus (AAV) gene therapy candidate in clinical
development as a potential one-time treatment for Gaucher disease.
FLT201 leverages Spur's proprietary and potent AAVS3 capsid to
deliver GCase85, a rationally engineered longer-acting version of
the enzyme deficient in people with Gaucher disease, with the goal
of stopping disease progression, reducing or eliminating symptoms,
and allowing patients to come off current lifelong treatments. Data
from the completed Phase 1/2 GALILEO-1 clinical trial of FLT201
have shown improvements across a number of key biomarkers and
clinical assessments, including substantial reductions in the toxic
buildup of substrate that results from the enzyme deficiency, as
well as a favorable safety and efficacy profile. A Phase 3 trial
for FLT201 is expected to start in the second half of
2025.
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, which then accumulate in tissues and
organs throughout the body, causing inflammation and dysfunction.
Despite treatment with currently approved therapies, many people
with Gaucher disease continue to experience debilitating symptoms,
including enlarged organs, fatigue, bone pain and reduced lung
function. Gaucher disease affects approximately 18,000 people in
the United States, United Kingdom, France, Germany, Spain, Italy
and Israel.
About Spur Therapeutics
Spur Therapeutics is a clinical-stage
biotechnology company focused on developing life-changing gene
therapies for debilitating chronic conditions. By optimizing every
component of its product candidates, Spur aims to unlock the true
potential of gene therapy to realize outsized clinical
results.
Spur is advancing a breakthrough gene therapy
candidate for Gaucher disease and a potential first-in-class gene
therapy candidate for adrenomyeloneuropathy, as well as a research
strategy to move gene therapy into more prevalent diseases,
including forms of Parkinson's, dementia, and cardiovascular
disease. Expanding our impact, and advancing the practice of
genetic medicine.
Toward life-changing therapies, and brighter
futures. Toward More™
For more information, visit
www.spurtherapeutics.com
or connect with Spur on LinkedIn
and X.
Investor Contact
Naomi Aoki
naomi.aoki@spurtherapeutics.com
+ 1 617 283 4298
Media Contact
Carolyn Noyes
carolyn.noyes@spurtherapeutics.com
+ 1 617 780 2182
