TakeAim Lymphoma data for the combination of
emavusertib plus ibrutinib show tumor reduction in 8 of 9 evaluable
patients, including 2 complete responses and 2 partial
responses
Potential for overcoming ibrutinib resistance
demonstrated with a complete response in a patient who had prior
treatment with ibrutinib
TakeAim Leukemia data, top-line data
previously released in January, highlight emavusertib's
single-agent activity in heavily pretreated AML and HR-MDS
patients
LEXINGTON, Mass., June 4, 2022
/PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company
focused on the development of innovative therapeutics for the
treatment of cancer, today announced the presentation of
encouraging clinical data from both the TakeAim Lymphoma and
TakeAim Leukemia studies at the 2022 American Society of Clinical
Oncology (ASCO) Annual Meeting currently taking place in
Chicago and online until
June 7, 2022.
"We are excited to share data with the oncology community from
our TakeAim Lymphoma and TakeAim Leukemia studies at ASCO,
including the first release of clinical data investigating the use
of emavusertib in combination with ibrutinib in patients with
Non-Hodgkin's Lymphoma," said James
Dentzer, President and Chief Executive Officer of Curis.
"These data demonstrate encouraging signs of anti-cancer activity,
including a complete response in a primary CNS lymphoma patient who
had prior treatment with ibrutinib. We also presented a poster with
data from the TakeAim Leukemia study, previously disclosed in a
January 2022 press release,
demonstrating emavusertib's encouraging monotherapy activity in
patients with relapsed or refractory (R/R) acute myeloid leukemia
(AML) or high-risk myelodysplastic syndrome (MDS)."
"In addition to the data from Curis's studies, there are
presentations at the meeting this year by our collaborators at
Washington University and the
University of Florida, which help more
fully explore emavusertib's use in tumor types outside of the
company's current focus in hematologic malignancies," said
Robert Martell, M.D., Ph.D., Head of
Research and Development.
TakeAim Lymphoma:
The TakeAim Lymphoma study is a Phase 1/2 open-label, dose
escalation, dose expansion clinical trial investigating emavusertib
as monotherapy and in combination with ibrutinib in patients with
R/R hematologic malignancies, such as non-Hodgkins's lymphoma and other B cell
malignancies. The poster presentation (#7575) made by Dr.
Grzegorz Nowakowski, Division of
Hematology, Mayo Clinic-Minnesota, today at ASCO includes clinical
data from a May 6, 2022 data cutoff,
on 13 patients who received the combination, 9 of whom had
post-baseline response assessments and were evaluable for
response.
Key findings in patients treated with the combination
included:
- The combination appeared to be well tolerated
- No dose-limiting toxicities (DLTs) at 200mg of emavusertib; 2
DLTs observed at 300mg (stomatitis and syncope)
- 8 of 9 evaluable patients experienced reduction in tumor
burden, including:
-
- 2 complete responses (CR) (primary CNS lymphoma and mantle cell
lymphoma)
- 2 partial responses (PR) (chronic lymphocytic leukemia and
mantle cell lymphoma)
- One of the CRs was in a patient who had received prior
treatment with ibrutinib, suggesting that the combination may be
able to overcome ibrutinib resistance
Next steps for the TakeAim Lymphoma study include further dose
expansion in order to determine the Recommended Phase 2 Dose for
the combination.
TakeAim Leukemia:
The TakeAim Leukemia study is a Phase 1/2 dose escalation and
dose expansion study examining emavusertib use as both monotherapy
and in combination with azacitidine or venetoclax in patients with
R/R AML or high risk MDS. The poster presentation (#7016)
made by Dr. Guillermo Garcia-Manero,
Chief of the Section of Myelodysplastic Syndromes within the
Department of Leukemia at The University of
Texas MD Anderson Cancer Center, today at ASCO, include
clinical data from a December 16,
2021 data cutoff for the 49 patients who had been treated
with emavusertib in monotherapy as of that date.
Key safety findings included:
- Emavusertib was well-tolerated across multiple dose levels,
including at the Recommended Phase 2 Dose of 300 mg BID
- No dose-limiting myelosuppression observed
- No cumulative toxicities observed
These attributes of emavusertib's emerging safety profile may
provide an advantage compared to current standard of care therapies
in monotherapy and may also make emavusertib an attractive
candidate for addition to combination therapy regimens.
Key tumor assessment findings included:
Collaborator Studies:
- In patients with spliceosome-mutated R/R AML:
-
- CR/CRh rate of 40% (2 out of 5 patients) (CRh=complete response
with partial hematologic recovery)
- Both patients who achieved CR/CRh have been on study > 6
months and achieved negative MRD (minimal residual disease)
status
- Consistent tumor burden reduction observed, 4 out of 5 patients
achieved blast reduction, 3 of whom by ≥ 50%
- In patients with spliceosome-mutated R/R MDS:
-
- Objective response rate of 57% (4 out of 7 patients)
- One of the patients who achieved a marrow CR (mCR) proceeded to
stem cell transplant after 1 cycle
- Consistent tumor burden reduction observed, with 4 out of 6
patients with elevated baseline blast counts achieving ≥ 50%
reduction in blast counts
- In patients with FLT3-mutated R/R AML:
-
- CR rate of 33% (1 out of 3 patients)
- 2 out of 3 patients showed eradication of FLT3 mutation
following treatment, indicating potential for disease modification
with emavusertib
- Consistent tumor burden reduction observed with 2 out of 3
patients with elevated blast counts achieving ≥ 50% reduction in
blast counts
Being presented today (#TPS4168) is work in gastric cancer by
Dr. Kian-Huat Lim's team at
Washington University School of
Medicine. Based on compelling preclinical work, Dr. Lim and his
team have developed a clinical study exploring combination of
emavusertib (CA-4948) in combination with FOLFOX chemotherapy plus
nivolumab or pembrolizumab. Preclinically, it has been established
that chemotherapy resistance can be driven by TLR9 activation and
IRAK4 dependent activation of pro-survival NF-kB signaling.
Inhibition of IRAK4 has been shown to block this signaling, and to
reduce tumor desmoplasia along with revitalization of intratumoral
T-cells, setting the stage for combination with immune checkpoint
inhibitors. This study is active, but not yet recruiting.
Being presented tomorrow (#2011), June
5, is preclinical work from Dr. Duane Mitchell's team at the University of Florida, which investigated
emavusertib (CA-4948) in melanoma brain metastasis where
IRAK4-dependent signaling is known to be high. Emavusertib exposure
in the brain and in brain tumors achieved therapeutically relevant
levels, resulted in substantial reduction of B16.F10 tumor volume
and prolonged survival of the mice.
About Emavusertib (CA-4948)
Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an
essential role in the toll-like receptor (TLR) and interleukin-1
receptor (IL-1R) signaling pathways, which are frequently
dysregulated in patients with cancer. TLRs and the IL-1R family
signal through the adaptor protein MYD88, which results in the
assembly and activation of IRAK4, initiating a signaling cascade
that induces cytokine and survival factor expression mediated by
the NF-κB protein complex. Additionally, third parties have
recently discovered that the long form of IRAK4 (IRAK4-L) is
oncogenic and preferentially expressed in over half of patients
with AML and MDS. The overexpression of IRAK4-L is believed to be
driven by a variety of factors, including specific spliceosome
mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4,
emavusertib was also designed to inhibit FLT3, a known oncologic
driver, which may provide additional benefit in patients with AML
and MDS.
About Curis, Inc.
Curis is a biotechnology company focused on the development of
innovative therapeutics for the treatment of cancer. In 2015, Curis
entered into a collaboration with Aurigene in the areas of
immuno-oncology and precision oncology. As part of this
collaboration, Curis has exclusive licenses to oral small molecule
antagonists of immune checkpoints including the VISTA/PDL1
antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as
the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is
currently undergoing testing in the Phase 1/2 TakeAim Lymphoma
trial, in patients with hematologic malignancies, such as
non-Hodgkins lymphoma and other B
cell malignancies, both as a monotherapy and in combination with
BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia trial
in patients with acute myeloid leukemia and myelodysplastic
syndrome, for which it has received Orphan Drug Designation from
the U.S. Food and Drug Administration. The FDA has placed a partial
clinical hold on the TakeAim Leukemia and TakeAim Lymphoma trials
during which no new patients will be enrolled, and current study
participants benefiting from treatment may continue to be treated
with emavusertib at doses of 300mg BID or lower. In addition, Curis
is engaged in a collaboration with ImmuNext for development of
CI-8993, a monoclonal anti-VISTA antibody, which is currently
undergoing testing in a Phase 1 trial in patients with solid
tumors. Curis is also party to a collaboration with Genentech, a
member of the Roche Group, under which Genentech and Roche are
commercializing Erivedge® for the treatment of advanced basal cell
carcinoma.
For more information, visit Curis's website at
www.curis.com.
Cautionary Note Regarding Forward-Looking Statements:
This press release contains forward-looking statements within
the meaning of the U.S. Private Securities Litigation Reform Act of
1995, including, without limitation, any statements with respect to
Curis's plans, strategies, objectives or financial results;
statements concerning product research, development, clinical
trials and studies and commercialization plans, timelines,
anticipated results or the therapeutic potential of drug candidates
including any statements regarding the initiation, progression,
expansion, use, efficacy, dosage and potential benefits of CA-4948
in clinical trials as a monotherapy and/or as a combination
therapy, the progression, use and potential benefits of CI-8993,
Curis's plans and timelines to provide preliminary, interim and/or
additional data from its ongoing or planned clinical trials, any
statements concerning Curis's expectations regarding its
interactions with the FDA or its ability to resolve the partial
clinical hold of the TakeAim Leukemia study or the partial clinical
hold of the TakeAim Lymphoma study, and statements with respect to
mutations or potential biomarkers; and statements of assumptions
underlying any of the foregoing. Forward-looking statements
may contain the words "believes," "expects," "anticipates,"
"plans," "intends," "seeks," "estimates," "assumes," "predicts,"
"projects," "targets," "will," "may," "would," "could," "should,"
"continue," "potential," "focus," "strategy," "mission," or similar
expressions. These forward-looking statements are not guarantees of
future performance and involve risks, uncertainties, assumptions
and other important factors that may cause actual results to be
materially different from those indicated by such forward-looking
statements. For example, the FDA may not remove the partial
clinical hold on the Phase 1/2 TakeAim Leukemia trial or the
partial clinical hold on the Phase 1/2 TakeAim Lymphoma trial, or
may take further regulatory action with regard to such trials;
Curis may experience adverse results, delays and/or failures in its
drug development programs and may not be able to successfully
advance the development of its drug candidates in the time frames
it projects, if at all. Curis's drug candidates may cause
unexpected toxicities, fail to demonstrate sufficient safety and
efficacy in clinical studies and/or may never achieve the requisite
regulatory approvals needed for commercialization. Favorable
results seen in preclinical studies and early clinical trials of
Curis's drug candidates may not be replicated in later trials.
There can be no guarantee that the collaboration agreements with
Aurigene and ImmuNext will continue for their full terms, or the
CRADA with NCI, that Curis or its collaborators will each maintain
the financial and other resources necessary to continue financing
its portion of the research, development and commercialization
costs, or that the parties will successfully discover, develop or
commercialize drug candidates under the collaboration. Regulatory
authorities may determine to delay or restrict Genentech's and/or
Roche's ability to continue to develop or commercialize Erivedge in
BCC. Erivedge may not demonstrate sufficient or any activity to
merit its further development in disease indications other than
BCC. Competing drugs may be developed that are superior to
Erivedge. In connection with its agreement with Oberland Capital,
Curis faces risks relating to the transfer and encumbrance of
certain royalty and royalty-related payments on commercial sales of
Erivedge, including the risk that, in the event of a default by
Curis or its wholly-owned subsidiary, Curis could lose all retained
rights to future royalty and royalty-related payments, Curis could
be required to repurchase such future royalty and royalty-related
payments at a price that is a multiple of the payments it has
received, and its ability to enter into future arrangements may be
inhibited, all of which could have a material adverse effect on its
business, financial condition and stock price. Curis will require
substantial additional capital to fund its business. If it is not
able to obtain sufficient funding, it will be forced to delay,
reduce in scope or eliminate some of its research and development
programs, including related clinical trials and operating expenses,
potentially delaying the time to market for, or preventing the
marketing of, any of its product candidates, which could adversely
affect its business prospects and its ability to continue
operations, and would have a negative impact on its financial
condition and its ability to pursue its business
strategies. Curis faces substantial competition. Curis and its
collaborators face the risk of potential adverse decisions made by
the FDA and other regulatory authorities, investigational review
boards, and publication review bodies. Curis may not obtain or
maintain necessary patent protection and could become involved in
expensive and time-consuming patent litigation and interference
proceedings. Unstable market and economic conditions, natural
disasters, public health crises, political crises and other events
outside of Curis's control could significantly disrupt its
operations or the operations of third parties on which Curis
depends and could adversely impact Curis's operating results and
its ability to raise capital. For example, the COVID-19 pandemic
may result in closures of third-party facilities, impact enrollment
in clinical trials or impact sales of Erivedge by
Genentech and/or Roche. The extent to which the COVID-19
pandemic may impact Curis's business or operating results is
uncertain. Other important factors that may cause or contribute
to actual results being materially different from those
indicated by forward-looking statements include the factors set
forth under the captions "Risk Factor Summary" and "Risk Factors"
in our most recent Form 10-K and Form 10-Q, and the factors that
are discussed in other filings that we periodically make with the
Securities and Exchange Commission ("SEC"). In addition, any
forward-looking statements represent the views of Curis only as of
today and should not be relied upon as representing Curis's views
as of any subsequent date. Curis disclaims any intention or
obligation to update any of the forward-looking statements after
the date of this press release whether as a result of new
information, future events or otherwise, except as may be required
by law.
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