Bolt Biotherapeutics Highlights Comprehensive Clinical Data from Phase 1 Dose-Escalation Trial of BDC-1001 as Monotherapy and in Combination with Nivolumab in HER2-Expressing Tumors at 2023 ASCO Annual Meeting
25 Maggio 2023 - 11:05PM
Bolt Biotherapeutics, Inc. (Nasdaq: BOLT) today announced the data
from its Phase 1 dose-escalation clinical trial of BDC-1001 that
will be presented in a poster session at the American Society of
Clinical Oncology (ASCO) 2023 Annual Meeting, being held at
McCormick Place in Chicago, Illinois and virtually from June 2-6,
2023.
BDC-1001 is an investigational Immune-Stimulating Antibody
Conjugate (ISAC) in development for the treatment of patients with
human epidermal growth factor receptor 2 (HER2)-expressing cancer.
BDC-1001 comprises a HER2-targeting biosimilar of trastuzumab
conjugated with a non-cleavable linker to a proprietary TLR7/8
agonist. The Phase 1 dose-escalation trial enrolled 131 patients
with 16 different HER2-expressing solid tumor types across 18 dose
levels in two arms, monotherapy and in combination with nivolumab.
At enrollment, all patients entered in the study had evidence of
tumor progression following prior standard of care treatments, and
a majority of the patients were heavily pre-treated.
“BDC-1001 has demonstrated a favorable safety profile and
encouraging efficacy including multiple objective responses and
long-term stable disease, as well as biomarker evidence of immune
activation that support our ISAC mechanism of action,” said Edith
A. Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics.
“Furthermore, these data support the initiation of our Phase 2
clinical program in four HER2-positive tumor types this year.”
“BDC-1001 represents a promising new therapeutic modality in
oncology,” said Bob T. Li, M.D., Ph.D., MPH, medical oncologist and
principal investigator at Memorial Sloan Kettering Cancer Center
(MSK). “The findings from the Phase 1 dose-escalation study
demonstrate the potential of BDC-1001 to treat patients with
HER2-expressing tumors and provide initial clinical validation of
ISACs as a therapeutic approach. I look forward to presenting these
data and engaging with the medical community during ASCO.”
Key findings from the recently completed BDC-1001
dose-escalation study are summarized below.
- The most clinically meaningful efficacy was observed at 20
mg/kg q2w, the dose level and frequency of administration selected
as the RP2D for both monotherapy and combination therapy and which
achieved the target drug exposure of >10 ug/ml. Four confirmed
partial responses (PRs) were observed at the RP2D; two in the
monotherapy arm in colorectal and biliary tract tumors, and two in
the combination arm in colorectal and ovarian tumors. The response
rate at the RP2D was 29% in evaluable patients with HER2-positive
tumors, both in monotherapy (2/7, 29%) and in combination with
nivolumab (2/7, 29%).
- At the RP2D, among evaluable patients with HER2-positive
tumors, 43% (3/7) in the monotherapy arm and 57% (4/7) in
combination experienced PRs or at least 24 weeks of disease
control.
- The 20 mg/kg q2w dose level achieved the serum exposure target
of more than 10 µg/mL throughout the dosing period. This dose level
demonstrated the best efficacy, was well tolerated, and
demonstrated evidence of pharmacodynamic changes, making it the
clear choice for the RP2D.
- BDC-1001 was well tolerated through 20 mg/kg dosed weekly as
both monotherapy and in combination with nivolumab. The most
frequent drug-related AEs were grade 1 or 2 infusion-related
reactions, which were observed in 29% of subjects. Grade 3 or
higher treatment-related AEs were seen in nine subjects (6.9%),
with only one grade 4 and no grade 5 drug-related AEs.
- Pharmacodynamic responses in both plasma and tissue were
consistent with the mechanism of action for an ISAC. BDC-1001
treatment resulted in increases in dendritic cells, macrophages,
and CD8+ T cells, as assessed in fresh biopsies. Dose-dependent
peak plasma increases were observed for multiple cytokines and
chemokines, including MIP-1β and IP-10. Levels of IL-6, a biomarker
of inflammation, were low at all dose levels.
Bolt has initiated a Phase 2 program encompassing four
HER2-positive solid tumor types. The original Phase 1/2 clinical
trial will move into Phase 2 dose expansions in three separate
cohorts evaluating colorectal, endometrial, and gastroesophageal
cancers. Following demonstration of monotherapy anti-tumor activity
in an indication, a separate cohort will be initiated to evaluate
BDC-1001 in combination with nivolumab in that indication. In
addition, a randomized two-arm Phase 2 clinical trial will
investigate BDC-1001 as monotherapy and in combination with
pertuzumab in patients with HER2-positive metastatic breast cancer
whose disease has progressed following treatment with Enhertu®.
Details about the presentation can be found below and on the
ASCO website. Additionally, a copy of the poster will be available
on the Publications page of the Bolt Biotherapeutics
website following the poster session.
- Title: A phase 1/2 study of a first-in-human
immune-stimulating antibody conjugate (ISAC) BDC-1001 in patients
with advanced HER2-expressing solid tumors
- Presenter: Bob Li, M.D., Ph.D., MPH,
medical oncologist, and principal investigator at MSK
- Abstract Presentation Number: 2538
- Poster Session: Developmental
Therapeutics—Immunotherapy
- Details: Saturday, June 3, 2023, 8:00
a.m. - 11:00 a.m. CDT
About the Boltbody™ Immune-Stimulating Antibody
Conjugate (ISAC) PlatformBolt Biotherapeutics’ Boltbody
ISAC platform harnesses the precision of antibodies with the power
of the innate and adaptive immune system to reprogram the tumor
microenvironment to generate a productive anti-cancer response.
Each Boltbody ISAC candidate comprises a tumor-targeting antibody,
a non-cleavable linker, and a proprietary immune stimulant. The
antibody is designed to target one or more markers on the surface
of a tumor cell and the immune stimulant is designed to recruit and
activate myeloid cells. Activated myeloid cells initiate a positive
feedback loop by releasing cytokines and chemokines, chemical
signals that attract other immune cells and lower the activation
threshold for an immune response. This increases the population of
activated immune system cells in the tumor microenvironment and
promotes a robust immune response, with the goal of generating
durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc.Bolt
Biotherapeutics is a clinical-stage biopharmaceutical company
developing novel immunotherapies for the treatment of cancer. Bolt
Biotherapeutics’ pipeline candidates are built on the Company’s
deep expertise in myeloid biology and cancer drug development. The
Company’s pipeline includes BDC-1001, a HER2-targeting Boltbody
Immune-Stimulating Antibody Conjugate (ISAC), BDC-3042, a
myeloid-modulating antibody, and multiple Boltbody ISAC
collaboration programs. BDC-1001 has completed a Phase 1
dose-escalation study demonstrating tolerability and early clinical
efficacy, and the Company plans to initiate Phase 2 studies in
2023. Bolt Biotherapeutics is advancing BDC-3042, an agonist
antibody targeting Dectin-2, through IND-enabling activities and
expects to initiate a Phase 1 trial in the second half of 2023. In
preclinical development, BDC-3042 demonstrated the ability to
convert tumor-supportive macrophages to tumor-destructive
macrophages. Bolt Biotherapeutics is leveraging its ability to
engineer and optimize novel applications of its Boltbody ISACs to
develop multiple immuno-oncology candidates through strategic
collaborations with leading biopharmaceutical companies. For more
information, please visit https://www.boltbio.com/
Forward-Looking Statements This 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 the
poster presentation at ASCO 2023, the advancement and success of
our clinical trials and the expansion of our clinical trials across
Europe, and the success of our collaborations are forward-looking
statements. In some cases, you can identify forward-looking
statements because they contain words such as “anticipate,”
“believe,” “could,” “estimate,” “expect,” “intend,” “may,” “on
track,” “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; and our ability to
maintain our current collaborations and establish further
collaborations. 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,
2022. 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.
Dr. Li has provided uncompensated advisory board services to
Bolt Biotherapeutics.
Investor Relations and Media Contacts:Karen L.
BergmanVice President, Communications and Investor RelationsBolt
Biotherapeutics, Inc.650-665-9295kbergman@boltbio.com
Sarah McCabeStern Investor Relations,
Inc.212-362-1200sarah.mccabe@sternir.com
David MelamedRusso Partners,
LLC212-845-4225david.melamed@russopartnersllc.com
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