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Sensei Biotherapeutics Presents First Preclinical Data on SNS-723 CAR-T and Long-Term Results on SNS-301 Data at the 2019 American Association for Cancer Research (AACR) Annual Meeting

April 1, 2019 Off By BusinessWire

-Multiple SNS-723 CAR constructs demonstrated significant expression
of ASPH-specific CARs on T-cells, dose-dependent cell killing, and
cytokine responses

-Dose-dependent and durable ASPH-specific immune responses observed
in patients dosed with SNS-301, consistent with earlier findings

GAITHERSBURG, Md.–(BUSINESS WIRE)–Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company
developing precision immuno-oncology therapies, today announced new data
from two programs targeting a novel tumor specific embryonic antigen,
human aspartate β-hydroxylase (ASPH), including preclinical data on
SNS-723, a first-in-class CAR-T cell therapy demonstrating effective
killing of tumor cells by a series of ASPH-specific CAR-Ts as well as
additional data from its Phase 1 study on the long-term effects of
SNS-301, a first-in-class cancer immunotherapy demonstrating that all
patients experienced dose-dependent and durable ASPH-specific immune
responses. These data were presented in two poster presentations at the
American Association for Cancer Research (AACR) Annual Meeting in
Atlanta, Georgia from March 29 – April 3, 2019.

“We are excited to share these first preclinical data for SNS-723,” said
Hossein Ghanbari, Ph.D., Chief Scientific Officer of Sensei
Biotherapeutics. “This novel CAR-T is designed to elicit tumor cell
destruction where ASPH is expressed, which includes both solid tumors
and hematological malignancies. Given that ASPH is not found on the
surface of normal tissues at any detectable levels, we believe SNS-723
offers a substantial opportunity to improve on the safety profile of
today’s approved cell therapies.”

“These long-term data from our phase 1 study of SNS-301 are consistent
with our earlier findings of strong dose-dependent APSH-specific
immunogenicity in patients and provide additional insights into our
Phase 2 dosing strategy,” said Ildiko Csiki, M.D., Ph.D., Chief Medical
Officer of Sensei Biotherapeutics. “Given the promise of targeting ASPH
as a new strategy for treating cancer, we remain focused on initiating
Phase 2 trials of SNS-301 in various hematological malignancies and
solid tumors in 2019.”

In a poster titled “CAR-T Cell Therapies Targeting Aspartyl
β-hydroxylase (ASPH),” Sensei researchers examined multiple
ASPH-specific CAR constructs for CAR expression, cell-killing efficacy
and cytokine response. Key SNS-723 data (poster #2306) highlights
included:

Significant expression of three different evaluated ASPH-specific CARs
was observed in human T-cells.
Dose-dependent cell-killing of ASPH-expressing H460 lung carcinoma
cells by two of the ASPH-specific CAR constructs was observed
concomitant with cytokine release. In contrast, untransduced T-cells
or T-cells transduced to express a non-relevant CAR did not kill
target cells of or activate cytokine production.
CARs binding two different, non-overlapping epitopes on ASPH both
displayed cell killing efficacy.

In a poster titled “Long-term Immunogenicity Results from a
First-in-human Study Evaluating the Anti-ASPH Cancer Vaccine, SNS-301,”
Sensei researchers examined both short- and long-term immune
responses to SNS-301. Previous data from the Phase 1 clinical trial of
SNS-301 were presented in 2018, demonstrating rapid and significant
antigen-specific B-cell and T-cell responses induced by SNS-301. In the
extension of the Phase 1 study, the 12 enrolled patients received
between 8 and 23 doses of the vaccine delivered via an intradermal
injection every 21 days. The additional key SNS-301 data (poster #1454)
highlights included:

All patients continued to experience long-term, dose-dependent and
durable ASPH-specific immune responses, including B-cell, T-cell, and
antibody responses.
A fluctuation in the peak immune responses following the first six
cycles was seen, suggesting the possibility of immune fatigue and a
potential benefit from increased spacing between boosting doses after
the first 6 cycles.
Anti-phage antibody responses were generally much lower at the low-
and mid-doses than the high dose. Based on the ratio of ASPH-specific
immune response to anti-phage immune response, the mid-dose is the
recommended Phase 2 dose.

Based on the data presented today, Sensei plans to initiate multiple
multi-site Phase 2 clinical trials in mid-2019 to evaluate the
immunogenicity and preliminary clinical activity of SNS-301 in various
malignancies. Sensei also plans to continue preclinical development and
begin IND-enabling studies for SNS-723 in the second half of 2019.

About SNS-723

SNS-723 is a first-in-class CAR-T cell therapy that is currently in
preclinical development targeting human aspartate β-hydroxylase (ASPH),
a cell surface enzyme that is normally expressed during fetal
development. The recognition domain of the CAR is the scFv portion of a
high affinity, fully human, anti-ASPH antibody. SNS-723 is designed to
overcome one of the major hurdles in T-cell therapy, targeting T-cells
to tumors in the absence of non-tolerable and/or off-target toxicities
to essential tissues and organs. Experiments to further characterize
ASPH-targeted CAR-T cells are ongoing with the goal of moving these
promising therapeutics into clinic.

About SNS-301

SNS-301 is a first-in-class cancer immunotherapy targeting human
aspartate β-hydroxylase (ASPH), a cell surface enzyme that is normally
expressed during fetal development. Following fetal development, the
protein is no longer expressed. Expression of ASPH is uniquely
upregulated in more than 20 different cancer types and promotes cancer
cell growth, cell motility and invasiveness. ASPH expression levels in
various tumors are inversely correlated with tumor resistance and
patient survival. Through enhanced antigen presentation and other
engineered immunotherapeutic features, SNS-301 is designed to overcome
self- tolerance and induce robust and durable ASPH-specific humoral and
cellular immune responses. SNS-301 is paired with a companion diagnostic
to select antigen-positive patients and is delivered intradermally for
ease of administration.

About Sensei Biotherapeutics

Sensei Biotherapeutics is a clinical-stage biopharmaceutical company
developing precision immuno-oncology therapies to transform the cancer
treatment landscape. The company is using its proprietary drug discovery
platform, called SPIRIT, to discover and develop both vaccines and
T-cell therapies, including SNS-301, its clinical stage cancer vaccine,
and SNS-723, its cell therapy program in preclinical development for
solid tumors and hematological cancers. These programs target ASPH, a
novel embryonic antigen. Sensei’s precision medicine approach in
immuno-oncology includes the use of companion diagnostics to select
patients who are most likely to respond to its tumor-specific antigen
therapies. Sensei Biotherapeutics is located in Gaithersburg, MD. For
more information, please visit www.senseibio.com.