Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio” or the
“Company”), a clinical-stage biotechnology company developing
next-generation cell and gene therapies using its proprietary Gene
Circuit platform, today reported positive initial clinical data
from a Phase 1 clinical trial of SENTI-202, a potential
first-in-class Logic Gated off-the-shelf chimeric antigen receptor
natural killer (“CAR-NK”) investigational cell therapy, for the
treatment of relapsed/refractory (“R/R”) hematologic malignancies
including acute myeloid leukemia (“AML”). SENTI-202 is designed to
selectively target and eliminate CD33 and/or FLT3- expressing
hematologic malignancies, including AML, while sparing healthy bone
marrow cells.
Three AML patients have been treated at the lowest dose level
(1.0 billion CAR+ NK cells per dose) and, as of the data cutoff
date of September 19, 2024, two achieved complete remission (“CR”),
confirmed by bone marrow biopsy, which includes blast reduction and
recovery of blood cells to normal ranges. In addition, both
patients were assessed as measurable residual disease (“MRD”)
negative after treatment, which is defined as no detectable cancer
cells present in a bone marrow sample by the most sensitive locally
available method. As of today, both patients continue to maintain
their remission (4+ months and 3+ months, respectively). In all
three patients, SENTI-202 was generally well-tolerated with an
adverse event profile consistent with the use of lymphodepleting
chemotherapy in patients with AML.
“R/R AML is a devastating disease that progresses rapidly with
no approved therapies once it has progressed past first-line
intensive or venetoclax-based treatment, or targeted agents in the
subset of patients with addressable mutations,” said Kanya
Rajangam, MD, PhD, President, Head of R&D and Chief Medical
Officer of Senti Bio. “In the trial, early and deep responses at
the first dose level were observed along with a generally
well-tolerated preliminary safety profile, which is very
encouraging. We look forward to reporting on additional response
and durability data in 2025 as we continue dose finding.”
Stephen A. Strickland, Jr., MD, MSCI, Director, Leukemia
Research for Sarah Cannon Research Institute, added, "Across the
Sarah Cannon Research Institute network, we care for thousands of
leukemia patients yearly and, given the limited treatment options
for patients with R/R AML, we are constantly hoping for new
therapies with novel mechanisms of action. I am very encouraged by
the initial findings—these early clinical results suggest that
SENTI-202 may potentially address the critical limitations of
existing therapies and provide hope to people living with AML."
Clinical Results Summary (September 19,
2024)
- As of the data cut, three patients
with R/R AML were enrolled at the 1.0 billion CAR+ NK cells/dose
level, administered three times, on days 0, 7, and 14 of a 28-day
cycle following lymphodepletion with fludarabine/cytarabine
(“Ara-C”)
- The lowest dose cohort was cleared
by the Safety Review Committee and dose escalation is continuing at
the 1.5 billion CAR+ NK cells/dose level
- Two patients achieved CR; one
after two cycles and the other after one cycle, both with absent
MRD by the most sensitive methods available for the patients at the
respective clinical sites. With an additional two months of
follow-up since the data cut, both patients are continuing to
maintain MRD negative CR status (4+ months and 3+ months,
respectively). One patient had no response after one cycle of
treatment and was refractory to therapy
- SENTI-202 was generally
well-tolerated with no dose limiting toxicities (“DLTs”) and an
adverse event profile consistent with other investigational NK cell
therapies and patients with underlying AML receiving
lymphodepleting chemotherapy
- SENTI-202 transgene was detected
in the peripheral circulation of all 3 patients and in all cycles,
with a pharmacokinetic (“PK”) profile generally consistent with
other investigational CAR-NK therapy levels
SENTI-202 Efficacy Data
3 doses/cycle (day 0, 7, 14) |
Number of Patients |
1.0 billion CAR+ NK per dose |
2/3 patients achieved CR 2/2 CRs are MRD negative* |
* One assessed by Next Generation Sequencing and another by
Multi-Parametric Flow Cytometry |
SENTI-202 Safety Data
|
Key Adverse Events* |
Patient 1 |
Grade 4 hematologic toxicity (thrombocytopenia)^Grade 1 fever^ /
Grade 2 bacteremia / Grade 3 upper respiratory infection (SAE)No
DLT/ AEI |
Patient 2 |
Grade 4 hematologic toxicity (neutropenia & leukopenia)^Grade 2
fever (reported as CRS)No DLT / SAE |
Patient 3 |
Grade 4 hematologic toxicity (pancytopenia)^Grade 1 fever (reported
as CRS)No DLT / SAE |
* Treatment emergent adverse events, regardless of relationship to
SENTI-202; SAE (“Serious Adverse Event”); DLT (“Dose Limiting
Toxicity”); Adverse Events of Interest (“AEI”) includes Cytokine
Release Syndrome (“CRS”)^ related to lymphodepletion |
SENTI-202 Next Steps
The Company expects to enroll a total of approximately 20
patients in the Phase 1 trial, based on the current clinical trial
design. A higher dose cohort of 1.5 billion CAR+ NK cells/dose is
actively enrolling. Additional safety and efficacy data, including
initial durability data, are expected to follow in 2025.
Conference Call InformationSenti Bio management
and Dr. Strickland will discuss the SENTI-202 results on December
3, 2024 at 7:30am ET. To access the live webcast, please register
online on the Events and Presentations page of Senti
Bio’s website. The webcast may also be accessed as
follows:
Conference ID: 1202759 United States - New York +1.646.968.2525
USA & Canada - Toll-Free +1.888.596.4144 Live webcast:
https://edge.media-server.com/mmc/p/q37k42qa
An archived webcast and accompanying slides will be available on
the Company’s website approximately one hour after the event.
About the Clinical TrialThe Phase 1 clinical
trial of SENTI-202 (NCT06325748) is enrolling adult patients with
R/R CD33 and/or FLT3 expressing hematologic malignancies, including
AML, at multiple sites in the United States and Australia. The dose
finding trial is currently evaluating two dose levels, either 1.0
billion or 1.5 billion SENTI-202 cells. SENTI-202 is administered
in 3 weekly doses (Days 0, 7, 14) of a 28-day treatment cycle
following a lymphodepletion conditioning regimen of fludarabine and
cytarabine. Patients will receive a minimum of one and maximum of
three treatment cycles. Patients may continue to receive multiple
cycles of treatment based on safety and efficacy data. This trial
is funded in part by the California Institute for Regenerative
Medicine (“CIRM”).
About SENTI-202SENTI-202 is a Logic Gated
off-the-shelf CAR-NK cell therapy product candidate designed to
selectively target and eliminate CD33 and/or FLT3 expressing
hematologic malignancies, such as AML and myelodysplastic syndrome
(“MDS”), while sparing healthy bone marrow cells. SENTI-202 has
three main components. First, SENTI-202 contains an OR GATE, which
is an activating CAR that recognizes CD33 and FLT3. By targeting
either or both of these antigens, SENTI-202 is designed to
effectively kill both leukemic blasts and leukemic stem cells,
which constitute a difficult-to-eradicate reservoir of AML disease.
Second, SENTI-202 contains a NOT GATE, which is an inhibitory CAR
that is designed to recognize healthy cells and protect those
healthy cells from being killed, thus potentially widening the
therapeutic window. Third, SENTI-202 contains calibrated-release
IL-15, which is designed to significantly increase cell
persistence, expansion and activity of both the CAR-NK cells and
host immune cells. The NK cells used to construct SENTI-202 are
sourced from healthy adult donors, which have been screened based
on a set of criteria that reflect manufacturability and product
quality, and are then cryopreserved prior to use in manufacturing
to minimize variability. Senti Bio is currently enrolling adult
patients with R/R CD33 and/or FLT3 expressing heme malignancies in
a Phase 1 clinical trial for SENTI-202, which can be a potential
first-in-class allogeneic treatment for AML/MDS patients.
Senti Bio has published SENTI-202 preclinical data demonstrating
the potential of Logic Gated CAR-NK cell therapy for the treatment
of AML.
About AMLAML is a cancer of the blood and bone
marrow and is the most common type of acute leukemia in adults. It
is estimated there will be 20,800 new cases of AML in the United
States in 2024. The five-year survival rate for these patients is
approximately 30%. AML is currently treated with chemotherapy,
targeted therapies, and/or allogeneic or autologous stem cell
transplant. For patients with R/R AML, there are few treatment
options and median overall survival is typically less than seven
months.
About Senti BioSenti Bio is a clinical-stage
biotechnology company developing a new generation of cell and gene
therapies for patients living with incurable diseases. To achieve
this, Senti Bio is leveraging a synthetic biology platform called
Gene Circuits to create therapies with enhanced precision and
control. These Gene Circuits are designed to precisely kill cancer
cells, spare healthy cells, increase specificity to target cells
and control the expression of drugs even after administration. The
Company’s wholly-owned pipeline includes off-the-shelf CAR-NK
cells, outfitted with Gene Circuits, to target challenging liquid
and solid tumor indications. Senti Bio has also preclinically
demonstrated that its Gene Circuits can function in T cells.
Additionally, Senti Bio has preclinically demonstrated the
potential breadth of Gene Circuits in other cell and gene therapy
modalities, diseases outside of oncology, and continues to advance
these capabilities through partnerships with Roche/Spark
Therapeutics and Bayer/BlueRock Therapeutics.
Forward-Looking StatementsThis press release
and document contain certain statements that are not historical
facts and are considered forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933, as amended,
and Section 21E of the Securities Exchange Act of 1934, as amended.
These forward-looking statements generally are identified by the
words “believe,” “could,” “predict,” “continue,” “ongoing,”
“project,” “expect,” “anticipate,” “estimate,” “intend,”
“strategy,” “future,” “opportunity,” “plan,” “may,” “should,”
“will,” “would,” “will be,” “will continue,” “will likely result,”
“forecast,” “seek,” “target” and similar expressions that predict
or indicate future events or trends or that are not statements of
historical matters. Forward-looking statements are predictions,
projections, and other statements about future events that are
based on current expectations of Senti Bio’s management and
assumptions, whether or not identified in this document, and, as a
result, are subject to risks and uncertainties. Forward-looking
statements in this release include, but are not limited to,
expectations regarding Senti Bio’s growth, strategy, progress and
timing of its clinical trials for SENTI-202; the timing of
availability of data from the ongoing Phase 1 clinical trial of
SENTI-202; the ability of any product candidate to perform in
humans in a manner consistent with nonclinical, preclinical or
previous clinical study data; expectations regarding the
anticipated dosing of patients and availability of data from
clinical trials, and the timing thereof; the ability to initiate
new clinical programs; as well as statements about the potential
attributes and benefits of Senti Bio’s platform technology and the
progress and continuation of its collaborations with certain
collaboration and strategic partners. These forward-looking
statements are provided for illustrative purposes only and are not
intended to serve as and must not be relied on by any investor as,
a guarantee, an assurance, a prediction, or a definitive statement
of fact or probability. Actual events and circumstances are
difficult or impossible to predict and will differ from
assumptions. Many actual events and circumstances are beyond the
control of Senti Bio. Many factors could cause actual future
results to differ materially from the forward-looking statements in
this document, including but not limited to: (i) changes in
domestic and foreign business, market, financial, political and
legal conditions, (ii) changes in the competitive and highly
regulated industries in which Senti Bio operates, variations in
operating performance across competitors, changes in laws and
regulations affecting Senti Bio’s business, (iii) the ability to
implement business plans, forecasts and other expectations, (iv)
the risk of downturns and a changing regulatory landscape in Senti
Bio’s highly competitive industry, (v) risks relating to the
uncertainty of any projected financial information with respect to
Senti Bio, (vi) risks related to uncertainty in the timing or
results of Senti Bio’s clinical trial start up, clinical studies,
patient enrollment, and GMP manufacturing startup activities, (vii)
Senti Bio’s dependence on third parties in connection with clinical
trial startup, clinical studies, and GMP manufacturing activities,
(viii) risks related to delays and other impacts from macroeconomic
and geopolitical events, increasing rates of inflation and rising
interest rates on business operations, (ix) risks related to the
timing and utilization of the grant from CIRM, and (x) the success
of any future research and development efforts by Senti Bio. The
foregoing list of factors is not exhaustive. You should carefully
consider the foregoing factors and the other risks and
uncertainties described in the “Risk Factors” section of Senti
Bio’s most recent periodic report filed with the U.S. Securities
and Exchange Commission (“SEC”), and other documents filed by Senti
Bio from time to time with the SEC. These filings identify and
address other important risks and uncertainties that could cause
actual events and results to differ materially from those contained
in the forward-looking statements in this document. There may be
additional risks that Senti Bio does not presently know, or that
Senti Bio currently believes are immaterial that could also cause
actual results to differ from those contained in the
forward-looking statements in this document. Forward-looking
statements speak only as of the date they are made. Senti Bio
anticipates that subsequent events and developments may cause Senti
Bio’s assessments to change. Except as required by law, Senti Bio
assumes no obligation to update publicly any forward-looking
statements, whether as a result of new information, future events,
or otherwise.
Availability of Other Information About Senti
Biosciences, Inc.For more information, please visit the
Senti Bio website at https://www.sentibio.com or follow Senti Bio
on X (formerly Twitter) (@SentiBio) and LinkedIn (Senti
Biosciences). Investors and others should note that we communicate
with our investors and the public using our company website
(www.sentibio.com), including, but not limited to, company
disclosures, investor presentations and FAQs, Securities and
Exchange Commission filings, press releases, public conference call
transcripts and webcast transcripts, as well as on X and LinkedIn.
The information that we post on our website or on X or LinkedIn
could be deemed to be material information. As a result, we
encourage investors, the media and others interested to review the
information that we post there on a regular basis. The contents of
our website or social media shall not be deemed incorporated by
reference in any filing under the Securities Act of 1933, as
amended.
Senti Bio Contacts
Investors: investors@sentibio.com
Media: media@sentibio.com
Senti Biosciences (NASDAQ:SNTI)
過去 株価チャート
から 11 2024 まで 12 2024
Senti Biosciences (NASDAQ:SNTI)
過去 株価チャート
から 12 2023 まで 12 2024