STARMAP (Study
Treating Acquired Resistance:
MAPK Amplifications) is a
first-in-human, 3-part, Phase 1/2 study of BBI-825 as a single
agent and in combination with select targeted cancer therapies
BBI-825 is a novel, oral, selective
ribonucleotide reductase (RNR) inhibitor and Boundless Bio’s second
extrachromosomal DNA (ecDNA)-directed therapy (ecDTx) to enter
clinical development
Preclinically, BBI-825 has demonstrated tumor
growth inhibition, including regressions, in both prevention and
treatment of amplification-mediated resistance in MAPK
pathway-activated tumors
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, today announced that the first patient
has been dosed with BBI-825 in a first-in-human, Phase 1/2 clinical
trial for patients with locally advanced or metastatic cancer with
resistance gene amplifications (NCT06299761). ecDNA are a key
driver of high copy number amplification in cancer, and Boundless
has validated multiple drug targets that are essential for ecDNA
function in cancer cells. BBI-825, the Company's second
ecDNA-directed therapy (ecDTx) to enter clinical trials, is a
novel, selective, oral small molecule inhibitor of ribonucleotide
reductase (RNR), a rate-limiting enzyme responsible for the de novo
synthesis of deoxyribonucleotides, the building blocks of DNA.
Boundless has identified an essential role for RNR in ecDNA
assembly and repair and in the survival of certain oncogene
amplified cancer cells.
“We are excited to announce dosing of the first patient in our
first-in-human study of BBI-825, our second program to enter the
clinic,” said Klaus Wagner, M.D., Ph.D., Chief Medical Officer at
Boundless Bio. “BBI-825 represents a new approach in the potential
treatment of oncogene amplifications, particularly in resistance
associated with targeted therapy treatment of MAPK
pathway-activated cancers.”
"Rapid resistance is a major limitation for targeted therapies,
particularly in colorectal cancer, as patients with colorectal
cancer often progress within about 6 months of initiating targeted
treatment,” said Rona Yaeger, M.D., Gastrointestinal Oncologist and
Early Drug Development Specialist at Memorial Sloan Kettering
Cancer Center. “We have observed firsthand that tumors in patients
treated with KRASG12C or BRAFV600E targeted therapies develop
resistance via MAPK pathway and receptor tyrosine kinase gene
amplifications, and those with pre-existing amplifications have an
overall worse outcome. There remains an incredible need for
therapies that can prevent amplification-driven resistance or treat
patients that have already acquired such resistance.”
“Advancing our second ecDTx into clinical development is an
important milestone for Boundless Bio and underscores the power of
our Spyglass platform to identify synthetic lethal targets
essential to ecDNA formation and function in oncogene amplified
cancers,” said Zachary Hornby, President and Chief Executive
Officer at Boundless Bio. “We are excited to enroll patients in
this first-in-human Phase 1/2 study, focused initially on patients
with KRASG12C and BRAFV600E mutated colorectal cancer with
resistance gene amplifications. If data are supportive, we may have
the opportunity to expand into broader patient populations,
including pan-tumor, pan-RAS, and pan-RAF indications, potentially
addressing these populations of cancer patients with very high
unmet need.”
About the STARMAP Trial
STARMAP (“Study Treating Acquired
Resistance: MAPK Amplifications”) is an open-label, non-randomized,
three-part Phase 1/2 clinical trial to evaluate the safety,
pharmacokinetics, pharmacodynamic biomarkers, preliminary antitumor
activity, and identify the maximum tolerated dose and recommended
Phase 2 dose (RP2D) of BBI 825 administered as a single agent or in
combination with select targeted therapies (NCT06299761). Part 1 is
a dose escalation of BBI-825 as a monotherapy in patients with
solid tumors. Part 2 is a combination dose escalation of BBI-825
and targeted therapies, encorafenib and cetuximab, or adagrasib and
cetuximab, in patients with advanced or metastatic colorectal
cancer with BRAFV600E or KRASG12C mutations, respectively, and
co-occurring resistance gene amplifications. Part 3 is a
combination dose expansion to evaluate preliminary anti-tumor
activity at the RP2D of BBI-825 and each targeted therapy
combination from Part 2.
About BBI-825
Boundless Bio’s second ecDNA-directed therapy (ecDTx), BBI-825,
is a novel, oral, selective small molecule inhibitor of
ribonucleotide reductase (RNR) being studied in the currently
enrolling, first-in-human, Phase 1/2 STARMAP trial in cancer
patients with resistance gene amplifications. In preclinical
studies, BBI-825 demonstrated low double digit nanomolar RNR
inhibition and tumor growth inhibition, including regressions, in
both the prevention and treatment of amplification-mediated
resistance in mitogen-activated protein kinase (MAPK)
pathway-activated tumors. RNR is a rate-limiting enzyme responsible
for cellular de novo synthesis of deoxynucleotide triphosphates
(dNTPs), the building blocks of DNA, and is essential to the
assembly and repair of ecDNA. BBI-825 was shown to starve
ecDNA-reliant cancer cells of dNTPs, deplete ecDNA, and was
synthetic lethal in multiple oncogene amplified preclinical cancer
models.
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
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 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; the ability of
our Spyglass platform to identify synthetic lethal targets
essential to ecDNA formation and function in cancer; and the
potential opportunity to expand into broader patient populations.
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; 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/20240410633469/en/
James Lee, Boundless Bio jlee@boundlessbio.com
Media 1AB Dan Budwick dan@1abmedia.com
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