Findings support the ongoing development of
BBI-355, a novel, oral, selective inhibitor of checkpoint kinase 1
(CHK1) in Phase 1/2 development, as a differentiated treatment
approach for ecDNA-enabled oncogene amplified cancers
Third poster presentation to highlight the
potential role of ecDNA-based resistance to chemotherapy
Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company
interrogating extrachromosomal DNA (ecDNA) biology to deliver
transformative therapies to patients with previously intractable
oncogene amplified cancers, presents preclinical and clinical
pharmacodynamic data on its lead ecDNA-directed therapy (ecDTx),
BBI-355, and research on ecDNA-mediated acquired resistance to
chemotherapy at the American Association for Cancer Research (AACR)
Annual Meeting 2024. BBI-355 is a novel, oral, selective inhibitor
of checkpoint kinase 1 (CHK1) being studied in the ongoing,
first-in-human, Phase 1/2 POTENTIATE clinical trial in patients
with oncogene amplified cancers.
“Extrachromosomal DNA afford unique advantages to tumors,
typically rendering existing therapies ineffective and correlating
with poor patient outcomes,” said Chris Hassig, Ph.D., Chief
Scientific Officer of Boundless Bio. “Our first poster presented
this year at AACR demonstrated that BBI-355 overcame ecDNA-mediated
targeted therapy resistance in preclinical tumor models by
leveraging the enhanced reliance of ecDNA-driven tumor cells on
CHK1 for survival. BBI-355 showed substantial antitumor activity,
including complete and durable regressions, in preclinical oncogene
amplified models.
Dr. Hassig continued, “Today we present preclinical and
preliminary clinical pharmacodynamic biomarker assay data that
showed detection of CHK1 inhibition-associated replication stress
in both patient skin and tumor tissue following administration of
BBI-355. In addition, we report a possible role for ecDNA in
acquired resistance to chemotherapy observed in preclinical models,
extending the potential applicability of ecDNA-directed strategies
beyond targeted therapy resistance. We are encouraged by these
findings as we continue to advance BBI-355 through the ongoing
Phase 1/2 POTENTIATE clinical trial.”
Details of the presentations are as follows:
Title: Oral CHK1 inhibitor BBI-355 allows flexibility of
dose and schedule with demonstration of monotherapy and
combinational antitumor activity in extrachromosomal DNA
(ecDNA)-driven oncogene amplified preclinical models Abstract
Number: 613 Session Category: Experimental and Molecular
Therapeutics Session Title: Kinase and Phosphatase
Inhibitors 1 Session Date and Time: Sunday Apr 7, 2024, 1:30
PM – 5:00 PM PT Location: Poster Section 25 Poster Board
Number: 23
BBI-355 showed inhibition of CHK1 in a host of tumor cell lines
and demonstrated in vivo single agent tumor growth inhibition,
including complete tumor regressions, across a range of tumor
models representing multiple different oncogene amplifications and
tumor types. BBI-355 also demonstrated synergistic tumor growth
inhibition, including durable regressions, when combined with
targeted therapies across multiple oncogene amplified tumor
models.
Title: Preclinical and clinical pharmacodynamic
characterization of BBI-355, a novel, orally bioavailable, and
selective CHK1 inhibitor being evaluated in the first-in-human
Phase 1/2 POTENTIATE clinical trial of patients with cancer
harboring oncogene amplifications Number: 3631 Session
Category: Clinical Research Session Title: Biomarkers in
Clinical Trials Session Date and Time: Monday Apr 8, 2024,
1:30 PM - 5:00 PM PT Location: Poster Section 40 Poster
Board Number: 9
Historically, clinical CHK1 inhibitor programs have lacked
effective clinical PD biomarker assays. The findings showed that
phosphorylated-CHK1 Ser345 (pCHK1-S345) is a useful pharmacodynamic
(PD) biomarker for confirming clinical on-target activity of
BBI-355 and could potentially inform the pharmacologically active
range of BBI-355 in clinical development. In addition to
preclinical data, increased pCHK1-S345 expression by
immunohistochemistry in skin biopsies from patients treated with
BBI-355 in the ongoing POTENTIATE clinical study were also
observed, marking the first, real-time analysis of PD activity from
a CHK1 inhibitor in humans.
Title: Extrachromosomal DNA (ecDNA) amplification of
multi-drug resistance genes results in acquired resistance to
taxane-based chemotherapy Abstract Number: 5870 Session
Category: Experimental and Molecular Therapeutics Session
Title: Mechanisms of Drug Resistance 3 Session Date and
Time: Tuesday Apr 9, 2024, 1:30 PM - 5:00 PM PT
Location: Poster Section 24 Poster Board Number:
14
Early insights into the role of ecDNA in driving resistance to
paclitaxel, a taxane chemotherapy, are revealed and highlight the
importance of ecDNA-directed therapies as a potential treatment
option for many patients that have chemotherapy-resistant disease.
Chemotherapy remains standard of care for many cancer patients,
however, resistance to chemotherapy often develops and has been
associated with the emergence of multi-drug resistance (MDR) gene
amplification, such as ABCB1. These preclinical findings showed
that ecDNA-enabled MDR gene amplification can cause short-and
long-term resistance to paclitaxel, potentially driving resistance
to chemotherapy in patients and underscoring the broad need for
ecDTx for chemotherapy-resistant patient populations.
About BBI-355
Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is
a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1)
being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE
clinical trial (NCT05827614) in patients with oncogene amplified
cancers. CHK1 is a master regulator of cells’ response to
replication stress (RS). RS is elevated in ecDNA-enabled oncogene
amplified cancer cells and, because of this, represents a key
vulnerability of those cells. BBI-355 was designed to exploit the
elevated RS in ecDNA-enabled oncogene amplified cancer cells by
disrupting proper CHK1 function in regulating RS and thereby
facilitating catastrophic RS to preferentially kill cancer cells
relative to healthy cells.
About Boundless Bio
Boundless Bio is a clinical-stage oncology company dedicated to
unlocking a new paradigm in cancer therapeutics to address the
significant unmet need of patients with oncogene amplified tumors
by targeting extrachromosomal DNA (ecDNA), a root cause of oncogene
amplification and observed in more than 14% of cancer patients.
Boundless Bio is developing the first ecDNA-directed therapy
(ecDTx), BBI-355, which is an oral inhibitor of checkpoint kinase 1
(CHK1) and is being evaluated in a Phase 1/2 clinical trial in
patients with oncogene amplified cancers. Boundless Bio’s second
ecDTx, BBI-825, is an oral inhibitor of ribonucleotide reductase
(RNR) and recently entered a Phase 1/2 clinical trial in cancer
patients with resistance gene amplifications. Leveraging its
Spyglass platform, Boundless Bio has additional programs advancing
through preclinical development and discovery. Boundless Bio is
headquartered in San Diego, CA.
For more information, visit www.boundlessbio.com.
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Forward-Looking Statements
Boundless Bio cautions you that statements contained in this
press release regarding matters that are not historical facts are
forward-looking statements. The forward-looking statements are
based on our current beliefs and expectations and include, but are
not limited to: the potential therapeutic benefits of our ecDTx in
treating patients with oncogene amplified cancers; and the
possibility to extend potential applicability of ecDTx beyond
targeted therapy resistance. Actual results may differ from those
set forth in this press release due to the risks and uncertainties
inherent in our business, including, without limitation: we are
early in our development efforts and our approach to discover and
develop ecDTx directed against ecDNA in oncogene amplified cancers
is novel and unproven; results from preclinical studies or early
clinical trials not necessarily being predictive of future results;
potential delays in the commencement, enrollment, data readouts or
completion of clinical trials or preclinical studies; our
dependence on third parties in connection with clinical trials,
preclinical studies, ecDNA diagnostic development, and
manufacturing; unfavorable results from clinical trials or
preclinical studies; unexpected adverse side effects or inadequate
efficacy of our ecDTx that may limit their development, regulatory
approval, and/or commercialization; regulatory developments in the
United States and foreign countries; and other risks described in
our filings with the Securities and Exchange Commission (SEC),
including under the heading “Risk Factors” in the final prospectus
dated March 27, 2024 that we filed with the SEC and any subsequent
filings with the SEC. You are cautioned not to place undue reliance
on these forward-looking statements, which speak only as of the
date hereof, and we undertake no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date hereof. All forward-looking statements are qualified
in their entirety by this cautionary statement, which is made under
the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995.
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version on businesswire.com: https://www.businesswire.com/news/home/20240407867079/en/
James Lee, Boundless Bio jlee@boundlessbio.com Media 1AB
Dan Budwick dan@1abmedia.com
Boundless Bio (NASDAQ:BOLD)
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