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/
and the full text of the announcement
from Achilles is contained below.
[ENDS]
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About Syncona
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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 VELOSTM 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
Media:
ICR Consilium
Sukaina Virji, Tracy Cheung, Emmalee Hoppe
+44 (0) 203 709 5000
achillestx@consilium-comms.com