REG - Syncona Limited - Freeline reports 2022 priorities and guidance

SynconaAnnouncement

14/12/2021 08:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20211214:nRSN5137Va&default-theme=true

RNS Number : 5137V  Syncona Limited  14 December 2021

Syncona Limited

 

Freeline reports 2022 corporate priorities and guidance

 

14 December 2021

 

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"), has announced
its 2022 corporate priorities as well as providing updated guidance across its
programmes. The key updates are as follows:

 

·      The company anticipates data across all programmes by mid-2022

o  The Phase I/II B-LIEVE dose-confirmation trial of FLT180a in haemophilia B
launched in Q4 2021, one quarter ahead of its latest guidance

o  The Phase I/II dose-finding trial of FLT201 in Gaucher disease Type 1 is
on track for trial site initiation by year-end 2021 and first patient dosed in
Q1 2022

o  The Phase I/II MARVEL-1 dose-finding trial of FLT190 in Fabry disease is
progressing in the clinic, with the next patient expected to be dosed in H1
2022

 

·      Freeline has decided to discontinue further development of its
pre-clinical work for FLT210 in hemophilia A, as it continues to prioritise
its investments on the highest value activities

 

·      To streamline its operations, Freeline has proposed implementing
an approximate 25% reduction in the size of its workforce

 

·      As a result of these changes, the company expects that its cash
runway will be extended by an additional quarter to Q2 2023

 

The announcement can be accessed via the Investors
(https://www.freeline.life/investors/newsroom/) section of the Freeline
website. A copy of the announcement is also set out 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

 

Annabel Clay / 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
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 Announces 2022 Corporate Priorities and Guidance

Promising execution in the clinic with programs in hemophilia B, Fabry disease
and Gaucher disease; potential to deliver transformative therapies driven by
Freeline's differentiated platform

Data anticipated across all programs by mid-2022

FLT180a B-LIEVE trial for hemophilia B launched in Q4 2021, one quarter ahead
of latest guidance

FLT201 Phase 1/2 trial for Gaucher disease Type 1 on track for trial site
initiation by year-end 2021; dosing in Q1 2022; FLT190 MARVEL-1 trial for
Fabry disease progressing in the clinic;

next patient expected to be dosed in H1 2022

Company continues to prioritize investments on the highest value activities;
hones corporate focus with deprioritization of hemophilia A program and
proposed 25% workforce reduction

LONDON, December 13, 2021 - Freeline Therapeutics Holdings plc (Nasdaq: FRLN)
(the "Company" or "Freeline"), a clinical-stage biotechnology company
developing transformative AAV-mediated gene therapies for patients suffering
from inherited systemic debilitating diseases, today announced its 2022
corporate priorities and provided updated guidance.

"Today we are announcing a tightening of our focus to deliver on the promise
of Freeline to advance therapies that have the highest potential to transform
the lives of patients suffering from debilitating diseases. Leveraging our
highly potent capsid and unique platform capabilities, we believe we can
deliver best-in-class or first-in-class treatments, positioning Freeline for
long-term success as a leader in gene therapy," said Michael Parini, Chief
Executive Officer of Freeline. "2021 was a transformational year at Freeline
as we made progress across our three strategic priorities - execution,
prioritization and innovation - to lay the foundation for success in 2022 and
beyond."

"Starting with execution, we are on track to initiate our Phase 1/2
dose-finding study of FLT201 in Gaucher disease by year-end, in line with
prior guidance, and look forward to dosing the first patient in the first
quarter of 2022. Our compelling preclinical data suggest that the potency of
our AAVS3 capsid combined with our proprietary protein engineering positions
FLT201 as a potentially transformative therapy for Gaucher disease Type 1, a
serious, life-long disease with significant unmet medical need. FLT201 will be
our third program in the clinic and is poised to be the first AAV gene therapy
program for Gaucher disease Type 1 to enter the clinic."

"We continue to make strong progress in hemophilia B, initiating our Phase 1/2
dose-confirmation B-LIEVE study one quarter ahead of latest guidance. We are
rapidly advancing FLT180a for hemophilia B, having already identified a
sufficient number of patients to fully enroll the trial via the ECLIPSE run-in
study. We look forward to dosing patients in the first quarter of 2022. The
most recent data we released at the American Society of Hematology (ASH)
Annual Meeting strengthens our belief that FLT180a has the potential to be a
best-in-class gene therapy treatment for hemophilia B."

"We also will advance FLT190 for Fabry disease throughout 2022, with
additional patients to be dosed and data expected through the year. Based on
the encouraging data from the first two patients dosed in our ongoing MARVEL-1
trial, we continue to believe that FLT190 has the potential to deliver high
levels of α-Gal A expression to keep Fabry patients off enzyme replacement
therapy at relatively low doses compared to other treatments. We expect to
dose the third patient in our ongoing clinical trial in the first half of
2022."

Mr. Parini continued, "Successful execution of these programs requires focused
and strategic allocation of resources. To drive continued advancement of
FLT180a, FLT190 and FLT201, all of which have the potential to be first or
best-in-class, Freeline has undertaken a detailed strategic review of our
programs and operations. Following this review, the Company has decided to
halt further development of our preclinical work for FLT210 in hemophilia A,
given the additional work needed. Freeline will seek to explore potential
third-party partnership opportunities to progress this important work, which
will allow us to focus our time and resources on the programs most likely to
return transformative benefits for patients.

"Today we also announced that, in an effort to streamline our operations, the
Company is implementing an approximate 25% reduction in the size of our
workforce. This change follows our program optimization and will enable us to
better focus our time and resources on the highest value activities. We are
confident these steps will create a more efficient and sustainable company,
positioning Freeline for long-term success across its clinical programs and
platform technology. I would like to express my sincere gratitude to our
departing colleagues who are impacted by this decision. Their dedication and
contributions have been invaluable to advancing our mission, and we will honor
their work through continued focus on delivering our three core programs to
the patients waiting for functional cures for their diseases."

"We are excited about our programs and what's to come in 2022. These decisions
to focus our efforts will result in a reduction in operating expenses that
extends our cash runway by an additional quarter to the second quarter of 2023
and provides a solid financial foundation to support the future success of our
programs and Company. We are ready, with increased focus and commitment, to
deliver the next generation of innovations for patients," said Mr. Parini.

Recent Updates, Key 2022 Priorities and Program Guidance

Gaucher Disease Type 1

•    Phase 1/2 dose-finding trial of FLT201 on track to be initiated in
Q4 2021.

•    The Company expects to dose two patients in the first dose cohort in
the first half of 2022, with initial data expected in Q3 2022. Data from
additional patients expected prior to year-end 2022.

Hemophilia B

·    Reported long-term follow-up data from its Phase 1/2 B-AMAZE
dose-finding trial of FLT180a for the treatment of hemophilia B at the 63(rd)
American Society of Hematology (ASH) Annual Meeting. Results suggest that a
dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune
management, has the potential to achieve durable factor IX (FIX) activity in
the normal range (50-150%).

·    Initiated the B-LIEVE study, a Phase 1/2 dose-confirmation study of
FLT180a manufactured at commercial scale and using a starting dose of 7.7e11
vg/kg and a short course of prophylactic immune management, in Q4 2021.

·    The Company expects to complete dosing of the first dose cohort in
the B-LIEVE study and report data from the first dose cohort in the first half
of 2022.

Fabry Disease

•    Reported data from the lowest dose cohort in MARVEL-1 trial of
FLT190 for Fabry disease, demonstrating durable α-Gal A expression over two
years in the first patient and promising activity with near normal α-Gal A
levels in the second patient, who remains off enzyme replacement therapy more
than 16 weeks post-dosing.

•    The Company expects to dose the third patient at the at 7.5e11 vg/kg
dose level in H1 2022, with updated data from the first two patients dosed,
and initial data from the third, in the first half of 2022. Escalation to next
dose level is expected in H2 2022, along with updated data.

Corporate

The company intends to reduce expenses and extend its existing cash runway
through a prioritization of its programs and reduction in workforce:

•    The Company expects to incur charges relating to its proposed
workforce reduction between $2.1 and $2.6 million in the fourth quarter of
2021, which is expected to result in $1.3 to $1.6 million of cash expenditures
in the first quarter of 2022 and $0.8 to $1.0 million of cash expenditures in
the second quarter of 2022.

•    The Company estimates the proposed reduction in force will decrease
aggregate cash expenditures by between $4.7 and $5.1 million in 2022 and
between $7.0 and $7.6 million in 2023.

•    As a result of these initiatives, the Company expects its current
level of cash and cash equivalents will enable the Company to fund its
operating expenses into the second quarter of 2023.

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 and Fabry
disease, as well as preclinical programs in Gaucher disease Type 1. Freeline
is headquartered in the UK and has operations in Germany and the US.

About Hemophilia

Hemophilia is a genetic bleeding disorder caused by a deficiency in clotting
factor protein that impairs blood clot formation. In hemophilia B, there is a
deficiency of the clotting factor IX (nine) protein. Hemophilia B is an
X-linked disease that mainly affects boys and men; however, women who carry an
affected copy of the clotting factor gene may also experience symptoms.
Hemophilia B affects about one in every 30,000 males. Hemophilia is classified
as mild, moderate or severe, depending on the level of clotting factor VIII or
IX in the blood and is diagnosed through blood tests.

About FLT180a for Hemophilia B

The Freeline hemophilia B program, FLT180a, uses a potent, rationally designed
capsid (AAVS3) containing an expression cassette encoding a gain of function
Padua variant of human factor IX (FIX). FLT180a was studied in B-AMAZE, a
Phase 1/2 dose-finding trial in patients with severe and moderately severe
hemophilia B with the goal of normalizing FIX activity. Patients treated in
B-AMAZE are being followed in a long-term follow-up study. A Phase 1/2
dose-confirmation trial of FLT180a called B-LIEVE has been initiated.

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. Fabry
disease occurs in all ethnic groups and is estimated to affect one in every
40,000 people. 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 every two weeks, which is a significant
treatment burden on the patient.

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 (GCasevar85) under the control of a liver-specific promoter. The
GCasevar85 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. 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 endogenous GCase, thus
eliminating the need for ERT.

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, discussion of
the Company's strategies, anticipated operating and financial performance and
financial condition; the Company's expectations regarding its use of cash and
cash runway; statements regarding the initiation, dosing, timing, progress and
interim and final results of the Company's clinical trials, including the
Phase 1/2 B-LIEVE dose-confirmation clinical trial of FLT180a, the Phase 1/2
dose-finding clinical trial of FLT201 and the Phase 1/2 MARVEL-1 dose-finding
clinical trial of FLT190, whether the Company has identified a sufficient
number of patients to fully enroll the B-LIEVE trial; statements regarding the
expected timing of regulatory filings; and manufacturing, research, pipeline,
and clinical trial plans, including anticipated clinical development
milestones for the Company's product candidates. 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
(http://www.sec.gov) .

Contact

David S. Arrington

Vice President Investor Relations & Corporate Communications

Freeline Therapeutics

david.arrington@freeline.life

+1 (646) 668 6947

 

 

 

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  UPDUOUURAWUUAUA