Achilles Therapeutics plc (NASDAQ: ACHL), a clinical-stage
biopharmaceutical company developing precision T cell therapies to
treat solid tumors, today presented two posters at the Society for
Immunotherapy of Cancer (SITC) Annual Meeting demonstrating the
ability to detect, quantify, and track patient-specific clonal
neoantigen-reactive T cells (cNeT) and generate increased cNeT
doses from VELOS™ Process 2 manufacturing. cNeT target clonal
neoantigens, which are unique targets expressed on every cancer
cell within a patient but not on healthy tissue.
Samra Turajlic, MD, PhD, Chief Investigator for
Achilles’ Phase I/IIa THETIS trial for metastatic malignant
melanoma at the Royal Marsden NHS Foundation Trust in London, UK,
presented Poster 543, entitled ‘Sensitive quantification and
tracking of the active components of a clonal neoantigen T cell
(cNeT) therapy: From manufacture to peripheral circulation’ which
shows Achilles’ ability to detect, quantify and track
patient-specific cNeT pre- and post-infusion in the ongoing PI/IIa
CHIRON and THETIS clinical trials for non-small cell lung cancer
(NSCLC) and metastatic malignant melanoma, respectively. Joseph
Robinson, PhD, Senior Scientist, Process Development at Achilles
Therapeutics, presented Poster 193, ‘The Achilles VELOS™ Process 2
boosts the dose of highly functional clonal neoantigen-reactive T
cells for precision personalized cell therapies’ highlighting data
from a proof-of-concept study showing an 18-fold increase in median
cNeT generated from VELOS™ Process 2 compared to Process 1.
“The data we presented today continue to
illustrate the differentiated profile of our cNeT product and
overall platform that builds on standard TIL therapy by leveraging
clonal neoantigen targeting to deliver a more precise and potent
product,” said Dr Iraj Ali, Chief
Executive Officer of Achilles. “The ability to reliably
detect and quantify our active component is a key differentiator of
our world-class technology that is unique in the field and which we
believe will be critical for the successful development of
TIL-based therapies.”
Engraftment Kinetics, Quantification and
Tracking of cNeT in CHIRON and THETIS
Data presented from the first eight patients
dosed across the first-in-human PI/IIa CHIRON and THETIS trials
confirm the ability of Achilles’ VELOS manufacturing process to
generate fit, polyclonal cNeT that can target multiple cancer
neoantigens present on all tumor cells. Achilles’ platform can
detect, quantify and track the patient-specific cNeT during
manufacturing and post patient administration, allowing for
extensive product characterization and immune-monitoring.
At the data cut-off for this presentation, five
patients with melanoma (THETIS) and three patients with NSCLC
(CHIRON) had received their cNeT infusion. The median age of the
cohort was 57 years and patients had received a median of 2.5 lines
of prior therapy. 88% (7 of 8) of the cNeT products dosed targeted
multiple clonal neoantigens present on all tumor cells. In these
seven products, the number of individual reactivities ranged from
two to twenty-eight and cNeT were detected in the blood of 71% (5
of 7) of the patients following infusion at time points up to six
weeks post dosing. Best response in the eight dosed patients was
stable disease in 63% (5 of 8) in this initial, low-dose cohort
generated using VELOS Process 1. The tolerability profile was
generally similar to that of standard TIL products that have not
been enriched for cNeT reactivity, with none of the higher-grade
adverse events more commonly associated with the use of higher
doses of interleukin-2 (IL-2). There were no suspected unexpected
serious adverse reactions reported since the previous update
on the first six patients earlier in 2021. Overall, in the cohort
there were three events of cytokine release syndrome and one ICANS
event deemed to be possibly related to cNeT treatment. A previously
disclosed case of encephalopathy was subsequently deemed unlikely
related to cNeT treatment following an Independent Data Safety
Monitoring Committee review.
“The encouraging data from this low-dose cohort
are important as they show how the Achilles platform can answer
potency questions, gives a first look at mechanism of action in a
TIL product, and adds confidence to now move to higher cell doses,”
said Dr Samra Turajlic, THETIS Chief
Investigator, Royal Marsden NHS Foundation Trust, London,
UK. “I look forward to exploring higher median doses from
VELOS Process 2 manufacturing that should more predictably be in
the anticipated therapeutic range, based on work done with other
cell therapies. As we move to higher cNeT doses I expect improved
cellular engraftment, both in terms of peak expansion and
durability, and hope to see greater evidence of anti-tumor
activity.”
The median cNeT dose in patients in this
low-dose, Process 1 cohort was 14.2 million cNeT, which is in line
with previous updates. VELOS Process 1 manufacturing generated
doses between 0.1 million and 287 million cNeT. cNeT reactivity,
defined as the percentage of clonal neoantigen-reactive cells in
the final dosed products, ranged from 5% to 77%. As the dataset
expands and matures, these metrics of detection and expansion will
be correlated with product, clinical and genomic characteristics to
determine variables associated with peripheral cNeT dynamics and
clinical response.
VELOS™ Process 2
Manufacturing
Achilles’ VELOS Process 2 manufacturing
generated an 18-fold increase in cNeT compared to Process 1 in this
proof-of-concept study. The increased cNeT contained multiple
polyclonal reactivities and key phenotypic features associated with
high cell fitness and reduced cell exhaustion. VELOS Process 2
improves upon Process 1 by introducing additional culture media
supplementation and an expansion-boosting stimulation cocktail
during the co-culture period, without adding any time to the
overall manufacturing process. Complementary GMP scale
manufacturing data from Process 2 will be presented at the ESMO
Immuno-Oncology Congress taking place December 8-11, 2021. This GMP
scale manufacturing is identical to the process for Achilles’
clinical studies and formed the basis of the Company’s regulatory
submissions to move the ongoing clinical studies to Process 2.
“We are thrilled to see that our Process 2
generated such a robust increase in cells while maintaining a
highly functional phenotype and we look forward to treating
patients with higher doses manufactured using VELOS Process 2,”
said Dr Sergio Quezada, Chief Scientific
Officer of Achilles. “Based on our experience with other
cell therapies, we are confident that Process 2 will deliver doses
able to elicit detectable clinical activity.”
Achilles’ proprietary potency assay enabled the
quantification of the proportion of tumor reactive cNeT within the
expanded TIL population. Both processes generated CD4+ and CD8+
cells able to recognize clonal neoantigens. Process 2 delivered a
polyclonal product with a median of five neoantigen reactivities
(range 3 to 18) detected per patient. The immunophenotype of cNeT
generated by Process 1 and 2 was largely similar, with the majority
of the cells bearing an effector memory phenotype. Cells generated
from both processes are also functionally similar as determined by
their ability to secrete INF-γ, IL-2 and TNF-α in response to
polyclonal stimulus.
Poster presentations are available in the Events
& Presentations section of the Company website.
Webcast and Conference Call
DetailsThe company will host a live webcast and conference
call today, Friday, November 12, 2021 at 8:30am ET / 1:30pm UK to
review the SITC presentations and provide a corporate update. A
slide presentation to accompany today’s webcast and conference call
will be available on the webcast and in the Events &
Presentations section of the Company’s website. The live webcast
can be accessed in the Events & Presentations section of the
Company’s website. The conference call dial-in for investors and
analysts are (833) 732-1204 (toll free within the USA), 0800
0288438 (toll free within the United Kingdom) or (720) 405-2169
(outside the USA) with the access code 4795875.
About Achilles
TherapeuticsAchilles is a clinical-stage biopharmaceutical
company developing 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
unresectable locally advanced and metastatic 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 StatementsThis
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. 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.
Further information:
Lee M. Stern – VP, IR & External
Communications+1 (332) 373-2634l.stern@achillestx.com
Consilium Strategic CommunicationsMary-Jane
Elliott, Sukaina Virji, Melissa Gardiner+44 (0) 203 709
5000achillestx@consilium-comms.com
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