REG - Syncona Limited - Freeline presents data in haemophilia B

SynconaAnnouncement

13/12/2021 15:05

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20211213:nRSM3587Va&default-theme=true

RNS Number : 3587V  Syncona Limited  13 December 2021

Syncona Limited

 

Freeline presents long-term follow-up data in haemophilia B and

initiates dose-confirmation trial

 

13 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"), presented data
from its long-term follow-up study of its Phase I/II B-AMAZE dose-finding
trial of FLT180a for the treatment of haemophilia B during the 63(rd) American
Society of Hematology (ASH) Annual Meeting & Exposition, being held
between December 11-14, 2021.

 

The results presented demonstrated sustained factor IX (FIX) expression up to
3.5 years, and supported selection of a dose of 7.7e11 vg/kg and an immune
management regimen that has the potential to deliver FIX activity in the
normal range (50-150%) for patients with haemophilia B. Additionally, the
company announced initiation of the first trial site in the Phase I/II B-LIEVE
dose-confirmation trial of FLT180a, one quarter ahead of its latest guidance.
Freeline expects the B-LIEVE study will finalise a dose for the planned
pivotal Phase III trial and anticipates an interim data readout from B-LIEVE
in mid-2022.

 

Chris Hollowood, Chief Investment Officer of Syncona Investment Management
Limited and Chair of Freeline said: "We are pleased to see this long-term data
in severe haemophilia B patients, showing sustained expression of FIX for up
to three and half years after dosing. The ability of this gene therapy product
candidate to deliver durable FIX activity in the normal range, using
relatively low doses, suggests its potential to provide a functional cure for
patients with this disease. It is encouraging that Freeline has initiated its
dose-confirmation study earlier than previously guided, and we look forward to
seeing an update in 2022."

 

The announcement and poster presentation are available on the Investors
(https://www.freeline.life/investors/) 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 Presents Long-Term Follow-Up Data from Phase 1/2 B‑AMAZE Trial in
Hemophilia B at the 2021 ASH Annual Meeting and Announces

Early Initiation of Phase 1/2 B-LIEVE Dose-Confirmation Trial

 

B-AMAZE long-term follow up data demonstrate sustained FIX expression up to
3.5 years; potential for expression levels in the normal range with relatively
low vector doses

 

B-LIEVE trial to confirm dose and immune management for planned Phase 3
pivotal trial launched one quarter ahead of latest guidance

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 presents 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 and Exposition. The event is being held from December 11
- 14, 2021 at the Georgia World Congress Center. Freeline also announced the
first trial site in the Phase 1/2 B-LIEVE dose-confirmation trial of FLT180a
has been initiated, one quarter ahead of its latest guidance. The Company
anticipates an interim data readout from the B-LIEVE trial in the middle of
2022.

"The data presented today at ASH demonstrate that FLT180a gene therapy has the
potential to deliver a durable, functional cure for hemophilia B," said
Michael Parini, Chief Executive Officer of Freeline. "Patients in the first
cohort experienced sustained expression of Factor IX out to 3.5 years
following treatment with FLT180a. The data from our B-AMAZE study also
informed our B-LIEVE dose-confirmation study, enabling us to identify a dose
and prophylactic immune management regimen that we believe can get and keep
hemophilia B patients in the normal range of Factor IX expression. These
results provide an important proof-of-concept for the Freeline platform,
demonstrating the proprietary, rationally designed AAVS3 capsid has the
potential to normalize FIX activity in patients with relatively low dosing due
to its high potency."

 

Mr. Parini continued, "We continue to execute across our programs, initiating
the B-LIEVE study, our Phase 1/2 dose confirmation trial, ahead of schedule.
We are excited to get this trial started and completed to enable a Phase 3
pivotal study. Enrollment in the ECLIPSE run-in study for the B-LIEVE trial
has proceeded more quickly than expected and, as a result, we believe we have
identified a sufficient number of patients to fully enroll the B-LIEVE
trial. We look forward to continued progress with FLT180a as we work toward
improving the lives of patients with hemophilia B."

 

ASH Presentation Highlights

Key Findings

·    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
FIX activity in the normal range (50-150%). and thereby prevent spontaneous
bleeds and normalize hemostasis in the event of traumatic bleeds.

·    Median follow up of 27.2 months (range 19.1-42.4) post-dosing across
10 patients.

·    Dose-dependent increase in FIX activity observed and FIX expression
sustained in nine of 10 patients.

·    Annualized exogenous FIX consumption and bleeding declined after gene
therapy. Across the nine of 10 patients with sustained FIX expression after
FLT180a treatment, only one reported traumatic bleed was treated with FIX
replacement; it occurred in a patient who had an endogenous FIX level of 57%
at the time.

·    The data cutoff date was September 20, 2021.

Safety

·    FLT180a was generally well tolerated with a favorable safety profile.

·    No infusion or allergic reactions and no evidence of FIX inhibitors
were reported.

·    Transient transaminitis with or without an associated decline in FIX
was the most common FLT180a-related adverse event (AE).

B-LIEVE Trial Site Initiation

Freeline has begun to apply these findings to advance the B-LIEVE trial, a
Phase 1/2 dose-confirmation trial of FLT180a manufactured at commercial scale
and using a starting dose of 7.7e11 vg/kg and a short course of prophylactic
immune management. The first trial site was initiated on December 6, 2021.

The starting dose of FLT180a in B-LIEVE was selected based on the results of
B-AMAZE and multiple modeling approaches. Freeline expects the B-LIEVE trial
will finalize a dose for the planned Phase 3 pivotal trial that is intended to
consistently enable FIX expression in the normal range for patients with
hemophilia B.

Freeline is currently evaluating the timing of its Phase 3 pivotal trial and
filing of a Biologics License Application and will provide more concrete
guidance next year.

ASH Poster Presentation Details

Title:                            Factor IX
Expression within the Normal Range Prevents Spontaneous Bleeds Requiring
Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B:
Long-term Follow-up Study of the B-AMAZE Program

Presenter:                Pratima Chowdary, MD, MRCP, FRCPath,
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital and
University College London

Date & Time:            December 13, 2021, 6:00 pm - 8:00 pm ET

Publication #:           3967

Session Name:        801. Gene Therapies: Poster III

 

The poster presentation is available online on the Investors section of the
Freeline website.

 

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 and
hemophilia A. Freeline is headquartered in the UK and has operations in
Germany and the US.

 

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 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.

 

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 initiation, timing, progress and results of the Company's
clinical trials, including data readouts from the Phase 1/2 B-LIEVE
dose-confirmation clinical trial of FLT180a, whether the Company has
identified a sufficient number of patients to fully enroll the B-LIEVE trial;
and whether a dose of 7.7e11 vg/kg will be successful in preserving FIX
activity levels in the normal range. 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. We 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  UPDFFFVIFVLFLIL