REG - Syncona Limited - Achilles provides clinical data update

SynconaAnnouncement

04/04/2024 12:00

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RNS Number : 3471J  Syncona Limited  04 April 2024

Syncona Limited

Achilles provides clinical data update

04 April 2024

Syncona Ltd, a leading healthcare investor focused on creating, building and
scaling a portfolio of global leaders in life science, notes that its
portfolio company, Achilles Therapeutics plc (Nasdaq: ACHL) ("Achilles"),
has provided interim Phase I/IIa data on the use of clonal neoantigen reactive
T cells (cNeT) from the CHIRON study in advanced unresectable or metastatic
non-small cell lung cancer (NSCLC) and the THETIS study in recurrent or
metastatic malignant melanoma.

·      Update includes data from 18 additional patients since the last
interim update in December 2022 across Achilles' Phase I/IIa trials in NSCLC
and melanoma

·      Key data presented includes:

o  Continued favourable tolerability profile of cNeT compared to other
tumour-infiltrating lymphocyte (TIL) therapies

o  At the higher Process 2 dose level, 3 out of 12 patients across CHIRON and
THETIS demonstrated stable disease with some reduction in tumour volume

o  No additional objective responses observed since previous interim update,
which may relate to limited cNeT persistence

o  To improve cNeT persistence the company has initiated a new cohort of
patients who have received enhanced chemo-conditioning and IL-2 dosing aligned
to standard TIL therapy; all three patients dosed to date in this process have
seen improvement in cNeT engraftment and some tumour reduction in one case

·      Further data expected in H2 CY2024, including from further
patients in the new cohort

Chris Hollowood, CEO of Syncona Investment Management Limited, said: "Whilst
we are pleased to see further data from 18 patients since the last interim
update from Achilles, we also note that Achilles has not seen any further
objective responses over this time period, including at the higher dose level.
In order for Achilles to be competitive we believe that it will need to show
an ability to routinely manufacture its products at high dose and significant
numbers whilst delivering superior efficacy to comparable treatments. We look
forward to engaging with the company and will continue to support it as it
seeks to maximise value for shareholders."

The announcement can be accessed on Achilles' website at:
https://ir.achillestx.com/ (https://ir.achillestx.com/) and the full text of
the announcement from Achilles is contained below.

  ENDS 

Enquiries

Syncona Ltd

Annabel Clark / Fergus Witt

Tel: +44 (0) 20 3981 7940

 

FTI Consulting

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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.

 

Achilles Therapeutics Provides Interim Phase I/IIa Update on Clonal Neoantigen
Reactive T Cells in Advanced NSCLC and Melanoma Including First Patients Dosed
with Enhanced Host Conditioning

 

- Improved VELOS(TM) manufacturing process delivering higher cNeT doses -

 

- Protocols updated to evaluate the benefit of enhanced host conditioning,
with further data expected in 2H 2024 -

 

- First three patients dosed in CHIRON and THETIS with enhanced host
chemo-conditioning, along with IL-2 aligned to standard TIL therapy, show
improved cNeT persistence and engraftment -

 

London, UK 4 April 2024 - Achilles Therapeutics plc (NASDAQ: ACHL), a
clinical-stage biopharmaceutical company developing AI-powered precision T
cell therapies targeting clonal neoantigens to treat solid tumors, today
announced interim Phase I/IIa data on the use of clonal neoantigen reactive T
cells (cNeT) from the CHIRON study in advanced unresectable or metastatic
non-small cell lung cancer (NSCLC) and the THETIS study in recurrent or
metastatic malignant melanoma. The update includes data from 18 patients
across CHIRON (n=12) and THETIS (n=6) dosed since the previous interim update
in December 2022, with two CHIRON patients and one THETIS patient having
received enhanced chemo-conditioning and IL-2 dosing aligned to standard tumor
infiltrating lymphocyte (TIL) therapy (enhanced host conditioning) in a new
Cohort C. This new Cohort C will allow the impact of enhanced host
conditioning on cNeT engraftment and persistence beyond 28 days to be
evaluated.

 

All trial participants were late-stage, checkpoint refractory patients with
progressive disease at the time of lymphodepletion. The observed tolerability
profiles remain favorable and similar to standard TIL therapy.

 

The VELOS™ manufacturing process continued to improve with a median 172
million cNeT dosed across the eighteen patients in the update compared to 18
million cNeT in the December 2022 update, with 10 products over 100 million
cNeT and five over one billion cNeT.

 

"The updated safety, tolerability and translational science data presented
today from checkpoint refractory patients continue to be encouraging and
reveal important mechanistic learnings about the factors driving durable T
cell engraftment and the impact of immune evasion mechanisms at an antigen
level.  These learnings will inform the development of cNeT and related
neoantigen vaccine and TCR-T therapies," said Dr Iraj Ali, CEO of Achilles
Therapeutics. "We have made important progress in the optimization of our
VELOS manufacturing process with a significant improvement in cNeT doses
delivered and are developing our understanding of the relationship between
host conditioning and the engraftment of infused cNeT. The next step is to
evaluate cNeT persistence and clinical activity in patients with enhanced host
conditioning, and we plan to report a meaningful data update in the second
half of 2024."

Dr. Karl Peggs, Chief Medical Officer of Achilles Therapeutics commented, "We
have not seen any new objective responses since our last update, which may
relate to limited cNeT persistence. With the aim of extending the duration of
engraftment and prolonging the early significant peaks of cNeT seen in the
blood of these patients, we introduced Cohort C to evaluate enhanced host
conditioning in both studies, intensifying lymphodepletion and IL-2 dosing."

Dr. Sergio Quezada, Chief Scientific Officer of Achilles Therapeutics added,
"Emerging translational data from the three patients dosed with the enhanced
conditioning show improved cNeT engraftment levels and persistence."

 

·    Summary of new patients treated since the previous update

o  18 new patients treated since the last update (12 NSCLC in CHIRON, 6
melanoma in THETIS) with a median of two prior lines of therapy

o  Data update includes two CHIRON Cohort C (enhanced host conditioning), one
THETIS Cohort C and two THETIS Cohort B patients (checkpoint combination)

o  Median cNeT dose of 172 million in the 18 patients reported since the last
update with 10 of 18 patients dosed with over 100 million cNeT, including five
products over one billion cNeT

·    Continued favorable tolerability profile for cNeT

o  Tolerability observations for cNeT compare well with standard TIL therapy

o  Lymphopenia and neutropenia were the most common adverse events, which are
principally associated with the conditioning regimen, and no dose limiting
high-grade toxicities were observed

·    25% of higher dose (>100M cNeT) patients in CHIRON and THETIS (3
of 12) demonstrated stable disease with some reduction in tumor volume

o  No new objective responses were observed, which is believed to relate to a
lack of cNeT persistence with the previous host-conditioning regimen using
lower lymphodepletion and IL-2 compared to standard TIL therapy

o  Early and significant peaks of cNeT, similar to standard TIL therapy, were
observed in the blood of patients receiving reduced intensity conditioning,
though with a lack of consistent cNeT persistence beyond 28 days

·    Enhanced host conditioning cohort opened in CHIRON and THETIS

o  Enhanced host conditioning protocol Cohort C has been added to CHIRON and
THETIS to evaluate an enhanced regimen of increased lymphodepletion intensity
and increased IL-2 dosing on cNeT persistence and hence potentially clinical
activity

o  All three patients dosed using the enhanced host conditioning regimen have
shown improvement in cNeT engraftment and some tumor reduction in one case

o  TCR tracking shows more durable cNeT engraftment beyond week six in the
first patient treated with enhanced host-conditioning regimen

o  A further eight patients are currently under observation with products
ready for dosing with a cNeT product

·    VELOS Manufacturing process further enhanced

o  172 million median cNeT dose for the last 18 patients in this update
compared to a median of 18 million cNeT in the December 2022 update

o  The last 10 products manufactured have delivered a median cNeT dose of 611
million

 

About Achilles Therapeutics

Achilles is a clinical-stage biopharmaceutical company developing AI-powered
precision T cell therapies targeting clonal neoantigens: protein markers
unique to the individual that are expressed on the surface of every cancer
cell. The Company has two ongoing Phase I/IIa trials, the CHIRON trial in
patients with advanced non-small cell lung cancer (NSCLC) and the THETIS trial
in patients with recurrent or metastatic melanoma. Achilles uses DNA
sequencing data from each patient, together with its proprietary PELEUS™
bioinformatics platform, to identify clonal neoantigens specific to that
patient, and then develop precision T cell-based product candidates
specifically targeting those clonal neoantigens.

 

Forward Looking Statements

This press release contains express or implied forward-looking statements that
are based on our management's belief and assumptions and on information
currently available to our management. Forward-looking statements in this
press release include, but are not limited to, statements regarding the timing
of the Company's clinical and translational data updates and the Company's
beliefs about recent data updates, and expectations related to the Company's
operating expenses and capital expense requirements. Although we believe that
the expectations reflected in these forward-looking statements are reasonable,
these statements relate to future events or our future operational or
financial performance, and involve known and unknown risks, uncertainties and
other factors that may cause our actual results, performance, or achievements
to be materially different from any future results, performance or
achievements expressed or implied by these forward-looking statements. The
forward-looking statements in this press release represent our views as of the
date of this press release. We anticipate that subsequent events and
developments will cause our views to change. However, while we may elect to
update these forward-looking statements at some point in the future, we have
no current intention of doing so except to the extent required by applicable
law. You should therefore not rely on these forward-looking statements as
representing our views as of any date subsequent to the date of this press
release.

For further information, please contact:

Investors:

Meru Advisors

Lee M. Stern

lstern@meruadvisors.com (mailto:lstern@meruadvisors.com)

Media:

ICR Consilium

Sukaina Virji, Tracy Cheung, Emmalee Hoppe

+44 (0) 203 709 5000
achillestx@consilium-comms.com (mailto:achillestx@consilium-comms.com)

 

 

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