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Adaptimmune Announces Data From Clinical Study of NY-ESO Affinity Enhanced T-Cell Therapy in Synovial Sarcoma at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer

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Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in the use of TCR
engineered T-cell therapy to treat cancer, today presents updated data
on its lead clinical program, an affinity enhanced T-cell receptor
therapy targeting the NY-ESO-1 cancer antigen in synovial sarcoma, at
the 2015 Annual Meeting of the Society of Immunotherapy for Cancer
(SITC).

Also being presented are an extended follow-up and correlative data from
Adaptimmune's study of its T-cell therapy targeting NY-ESO in patients
with multiple myeloma, and preclinical safety assessments of its next
affinity enhanced T-cell therapy product directed at MAGE A-10, for
which a clinical trial is expected to initiate later this year.

The data presented demonstrate the following:

-- In the primary efficacy analysis, 50 percent of synovial sarcoma
patients
receiving Adaptimmune's affinity enhanced T-cell therapy targeting
NY-ESO
responded, and 75 percent remain alive and on long term-follow up. Sixty

(60) percent of patients receiving the target dose responded, and 90
percent remain alive and on long term-follow up;

-- Adaptimmune's affinity enhanced T-cell therapy targeting NY-ESO in
multiple myeloma generated responses that were better than expected for
autologous stem cell transplant (ASCT) alone, despite the patients
having
advanced stage disease with 60 percent of patients having tumor
chromosomal abnormalities; and

-- Adaptimmune's platform technology enables the generation of multiple
TCRs
to a large number of cancer targets. Once affinity engineered, these
TCRs
are subjected to an extensive preclinical safety and efficacy package.

In the synovial sarcoma poster presentation, entitled: "Optimizing
engineered TCR T-cell therapy for synovial sarcoma," Sandra P. D'Angelo,
M.D., Assistant Attending, Sarcoma Medical Oncology / Immunotherapeutics
Core at Memorial Sloan-Kettering Cancer Center is providing an update on
Adaptimmune's NY-ESO-1 synovial sarcoma study, including all patients in
the original cohort (n=12), and longer follow-up and time-to-event, as
well as updated correlative and safety data, and characterization of the
product pre- and post-infusion. All patients enrolled in the study had
metastatic or relapse inoperable synovial sarcoma, and failed prior
ifosfamide and/or doxorubicin therapy. The authors of the poster
conclude:

-- Adaptimmune's affinity enhanced T-cell therapy targeting NY-ESO
demonstrated robust clinical responses in synovial sarcoma, including a
50 percent (6/12) overall response rate (ORR) in patients receiving
T-cells, and a 60 percent (6/10) response rate in a subset of patients
who received the target dose of one to six billion total engineered
T-cells. Two patients received below the target dose, and neither
responded. This compares favorably to a historical partial response rate

of approximately four percent observed with pazopanib, which is the only

approved drug in this patient population.

-- Seventy-five (75) percent (9/12) of all subjects who received any dose
of
NY-ESO-1 T cells - and 90 percent (9/10) of subjects who received the
minimum intended cell dose - are alive and on long term follow-up.
Forty-two (42) percent (5/12) of patients who received any dose have
survival data beyond one year.

-- NY-ESO-1 T-cells durably persist and maintain function without
accumulation of exhaustion markers; persistence detected at up to 21
months in those receiving the minimum intended cell dose. Poor
persistence was observed in subjects receiving less than 1 billion
NY-ESO-1 T-cells, with no detectable cells beyond day 25.

-- The encouraging anti-tumor activity considered in the context of a
generally manageable safety profile is supportive of a favorable
benefit:risk for NY-ESO-1 T-cells in this patient population. Most
treatment related adverse events resolve within 30 days of treatment.
The
most common adverse events include: nausea, anemia, pyrexia,
lymphopenia,
and neutropenia. There were no treatment related deaths. Cytokine
release
syndrome was seen in 4 subjects; Grade 3 cytokine release syndrome was
observed in 2/4 subjects, no grade 4 events were observed.

-- The evidence of relapse seen in some patients provides rationale for
testing of combination approaches or second generation T-cells designed
to overcome the immune suppressive environment of selected tumors.

Dr. Rafael Amado, Adaptimmune's Chief Medical Officer, said,
"Adaptimmune's core focus is the development of affinity enhanced T-cell
therapies that may offer promising treatment options to patients with a
broad range of solid and hematologic malignancies. We are encouraged by
the response and survival data we are observing in patients with
chemotherapy refractory synovial sarcoma, and we have expanded this
trial as we progress the development of our NY-ESO T-cell therapy in
this disease. We also continue to see promising clinical outcomes with
our NY-ESO T-cell therapy in patients with relapsed or refractory
multiple myeloma. And importantly, we continue to refine our proprietary
in vitro predictive safety package, which we now utilize to assess each
of our candidate T-cell therapies."

In the myeloma update entitled, "Deep phenotypic characterization of
NY-ESO TCR engineered T cells and tumor in patients with advanced
myeloma", Eduardo Davila, Ph.D., Associate Professor of Microbiology and
Immunology at the University of Maryland School of Medicine, Program
Leader for Tumor Immunology and Immunotherapy Research Program at the
Greenebaum Cancer Center at the University of Maryland, is presenting
follow-up data from the Nature Medicine paper (published July 20, 2015)
reporting results of the first 20 patients. This update includes data
from the full 25 patient cohort, long term follow-up data, and details
on NY-ESO-1 T-cell phenotyping and functional data, as well as clinical
and basic correlative data in myeloma patients. Patients in this study
had an average of 3 prior therapies; 24 percent had received prior
transplant and 60 percent have tumors with chromosomal abnormalities.
Early studies indicate upregulation of PDL-1 in relapsing tumor. Relapse
occurs upon loss of NY-ESO-1(c259) T in the peripheral blood, suggesting
that therapies designed to improve persistence or enhance
multi-targeting of tumor would be beneficial. The authors conclude that
the depth of responses on study, including a complete response rate of
59 percent, are better than expected for ASCT alone, despite the
patient population being advanced with risk factors of tumor chromosomal
abnormalities, and prior ASCT. Median overall survival amongst treated
patients is 32 months, and median progression free survival is 19
months.

Adaptimmune also presents preclinical data supporting its next first in
human study in a poster entitled, "Preclinical safety testing of an
Optimized Enhanced-Affinity MAGE-A10 -specific T cell receptor for
adoptive T cell therapy". Andrew Gerry, Ph.D., Director of Preclinical
Research at Adaptimmune is providing a summary of the preclinical safety
testing of an affinity-enhanced T-cell therapy specific for MAGE-A10,
for which a dose escalation study in patients with non-small cell lung
cancer is expected to initiate shortly. The Investigational New Drug
(IND) application is open, and the study is expected to initiate in
2015. Adaptimmune has the ability to generate multiple TCRs against
cancer target antigens and select the optimal TCR based on specificity;
the company can then optimize the affinity of the TCR. Once affinity
optimized, the company has established an extensive, first-in-class in
vitro-based preclinical safety and efficacy package including molecular
peptide mapping, 2D and 3D primary cell line screening, and
alloreactivity screening, which capitalizes on the ability to map the
linear peptide target of the TCR. The authors of the poster conclude
that Adaptimmune's preclinical strategy has been shown to be able to
predict off target toxicity observed in a prior study with a MAGE-A3
TCR. This strategy, under continuing refinement, will be used for all
new candidate enhanced affinity TCRs for adoptive T cell therapy for
cancer and other diseases.

Adaptimmune's affinity enhanced T-cell candidates are novel cancer
immunotherapies that have been engineered to target and destroy cancer
cells by strengthening a patient's natural T-cell response. T-cells are
a type of white blood cell that play a central role in a person's immune
response. Adaptimmune's goal is to harness the power of the T-cell and,
through its multiple therapeutic candidate, significantly impact cancer
treatment and clinical outcomes of patients with solid and hematologic
cancers

Posted-In: News FDA Press Releases

 

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