Bolt Biotherapeutics Announces AACR 2021 Presentation of Boltbody™ Platform Mechanism of Action and Clinical Properties of ...
April 10 2021 - 8:30AM
Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage
biotechnology company pioneering a new class of immuno-oncology
agents that combine the targeting precision of antibodies with the
power of both the innate and adaptive immune systems, today
announced that an online oral presentation with live Q&A and a
Trial in Progress poster presentation for lead agent BDC-1001 are
being presented at the American Association for Cancer Research
(AACR) Annual Meeting 2021 being held virtually from April 10-15th.
The oral presentation explores immunosuppression mediated by
various cells in the tumor microenvironment (TME), as well as the
tumor-supportive nature of antigen presenting cells (APCs) in the
TME in preclinical models. Reawakening these immunosuppressed APCs
may result in a productive and durable anti-tumor immune response.
Bolt is utilizing its Boltbody™ platform to create
immune-stimulating antibody conjugates (ISACs), such as BDC-1001,
that invoke this mechanism and provided complete tumor regression
in preclinical tumor models.
“In murine models we have seen efficacy in a variety of tumors
that are immunologically cold and well-established. Furthermore,
consistent with our proposed mechanism of action for ISACs, we see
evidence of increased myeloid and T cell infiltration in the tumor
microenvironment mediated by BDC-1001 surrogate ISACs,” said David
Dornan, Ph.D., Chief Scientific Officer at Bolt Biotherapeutics.
“We’re excited to share our rationale for selecting the
linker-payload for BDC-1001 to optimize anti-tumor activity while
minimizing the potential for the formation of anti-drug
antibodies.”
BDC-1001 is comprised of a tumor antigen-targeting monoclonal
antibody (mAb), a trastuzumab biosimilar and an immune-stimulating
agent (a TLR7/8 agonist) conjugated to each other with a
non-cleavable linker. In a series of preclinical studies with
BDC-1001, Bolt demonstrated the mechanism of action for their
HER2-targeted ISAC. BDC-1001 surrogate was able to eliminate
established, treatment-resistant tumors through the engagement of
both innate and adaptive immunity. There were no adverse findings
in toxicology studies of BDC-1001.
A Trial in Progress poster is also being presented by Manish R.
Sharma, M.D. of START Midwest, a principal investigator in Bolt’s
ongoing BDC-1001 Phase 1/2 trial. The poster details the design of
the study: a four-part study with two dose-escalation parts and two
dose-expansion parts. The study is evaluating BDC-1001 administered
intravenously with or without an immune checkpoint inhibitor
targeting PD-1 in up to 390 patients with HER2-expressing or
HER2-amplified advanced or metastatic solid tumors. The dose
escalation parts will evaluate sequential doses of BDC-1001 as a
monotherapy or in combination with a PD-1 checkpoint inhibitor in a
3+3 design, with the ability to backfill up to an additional 12
patients in each dose cohort. The dose expansion parts will
evaluate the recommended Phase 2 dose as monotherapy or in
combination with a PD-1 checkpoint inhibitor in four cohorts of
patients.
The primary objective of the dose escalation portion of the
study is to assess safety as measured by the incidence of adverse
events and serious adverse events; dose-limiting toxicities within
the 3+3 design; and potential immune-related toxicities and
determine the recommended phase 2 dose. Secondary objectives will
evaluate pharmacokinetic parameters and pharmacodynamic biomarkers
in tumor tissue and in peripheral blood associated with drug
exposure. These exploratory studies will help reinforce the ISAC
mechanism of action in humans and seek to identify biomarkers
associated with BDC-1001 biological activity with or without an
immune checkpoint inhibitor.
In January, Bolt presented a preliminary clinical update on the
first 20 patients that showed early signs of clinical activity,
including stable disease in several patients and a confirmed
partial response by RECIST, and acceptable safety with all 20
patients completing their dose-limiting toxicity (DLT) evaluation
period without DLTs or drug-related serious adverse events.
Treatment-emergent adverse events deemed to be related to BDC-1001
have been mild or moderate in severity, including mild
infusion-related reactions without interruption to dosing. Bolt
expects to provide an update on the trial sometime in the second
half of 2021.
About Bolt Biotherapeutics’ Immune Stimulating Antibody
Conjugate (ISAC) Platform Technology The Boltbody™ ISAC
platform technology harnesses the ability of innate immune agonists
to convert cold tumors into immunologically hot tumors, thereby
illuminating tumors to the immune system and allowing them to be
invaded by tumor killing cells. Boltbody ISACs have demonstrated
the ability to eliminate tumors following systemic administration
as monotherapy in preclinical models and have also led to the
development of immunological memory, which is predicted to
translate into more durable clinical responses for patients.
About the Ongoing BDC-1001 Phase 1/2 Study in Patients
with HER2-Expressing Solid Tumors The Phase 1/2,
multi-center, open-label study is evaluating the safety,
pharmacokinetics, pharmacodynamics and proof of mechanism of
BDC-1001 in patients with HER2-expressing solid tumors. The first
portion of the study includes a monotherapy dose-escalation phase
in which cohorts of patients will receive ascending intravenous
doses of BDC-1001 to determine the maximum tolerated dose and/or
the recommended dose to advance into expansion cohorts and Phase 2
based on safety and tolerability. The second portion of the study
is a dose expansion phase in which patients will receive BDC-1001
monotherapy to further evaluate the safety, tolerability and
clinical antitumor activity of the recommended Phase 2 dose. Please
refer to www.clinicaltrials.gov NCT04278144 for additional clinical
trial information.
About Bolt Biotherapeutics, Inc.Bolt
Biotherapeutics, Inc. is a clinical-stage biotechnology company
pioneering a new class of immuno-oncology agents that combine the
targeting precision of antibodies with the power of both the innate
and adaptive immune systems Bolt’s proprietary Boltbody™
Immune-stimulating Antibody Conjugates (ISACs) approach uses
immunostimulants to engage and activate myeloid cells that directly
kill tumor cells. This leads to the conversion of immunologically
“cold” tumors to “hot” tumors. Bolt’s lead candidate, BDC-1001, is
a Boltbody ISAC comprised of a HER2-targeting biosimilar of
trastuzumab conjugated to one of Bolt’s proprietary TLR7/8 agonists
for the treatment of patients with HER2-expressing solid tumors.
Bolt is also advancing additional Boltbody ISAC product candidates
targeting CEA and PD-L1.
For more information, visit https://www.boltbio.com/.
Forward Looking StatementsThis press release
contains forward-looking statements about us and our industry that
involve substantial risks and uncertainties and are based on our
beliefs and assumptions and on information currently available to
us. All statements other than statements of historical facts
contained in this press release, including statements regarding our
clinical trials, the timing of enrollment for our Phase 1/2 trial
for BDC-1001 for the treatment of patients with HER2-expressing
solid tumors, the potential of BDC-1001’s anti-tumor activity while
minimizing the formation of anti-drug antibodies, the potential
that APCs may result in a productive and durable anti-tumor immune
response, and the prediction that Boltbody ISACs may translate into
more durable clinical responses for patients. In some cases, you
can identify forward-looking statements because they contain words
such as “anticipate,” “believe,” “could,” “estimate,” “expect,”
“intend,” “may,” “plan,” “potential,” “predict,” “project,”
“should,” “will,” or “would,” or the negative of these words or
other similar terms or expressions. Forward-looking statements
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 the forward-looking
statements. Forward-looking statements represent our current
beliefs, estimates and assumptions only as of the date of this
press release and information contained in this press release
should not be relied upon as representing our estimates as of any
subsequent date. These statements, and related risks,
uncertainties, factors and assumptions, include, but are not
limited to: the potential product candidates that we develop may
not progress through clinical development or receive required
regulatory approvals within expected timelines or at all; clinical
trials may not confirm any safety, potency or other product
characteristics described or assumed in this press release; such
product candidates may not be beneficial to patients or become
commercialized. These risks are not exhaustive. Except as required
by law, we assume no obligation to update these forward-looking
statements, or to update the reasons actual results could differ
materially from those anticipated in the forward-looking
statements, even if new information becomes available in the
future. Further information on factors that could cause actual
results to differ materially from the results anticipated by our
forward-looking statements is included in the reports we have filed
or will file with the Securities and Exchange Commission, including
our Annual Report on Form 10-K for the year ended December 31,
2020. These filings, when available, are available on the investor
relations section of our website at investors.boltbio.com and on
the SEC’s website at www.sec.gov.
Media Contacts:Maggie Beller or David
SchullRusso Partners,
LLC646-942-5631maggie.beller@russopartnersllc.comdavid.schull@russopartnersllc.com
Investor Relations Contact:Sarah McCabeStern
Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.com
Bolt Biotherapeutics (NASDAQ:BOLT)
Historical Stock Chart
From Mar 2024 to Apr 2024
Bolt Biotherapeutics (NASDAQ:BOLT)
Historical Stock Chart
From Apr 2023 to Apr 2024