Curis scientists discover novel IRAK4 nuclear
localization and describe potential use as a biomarker
IRAK4 along with NF-kB p50/p65 localization to
the nucleus is associated with improved response to
emavusertib
Promising clinical and preclinical analysis
showcases the potential of emavusertib in treating pCNSL
LEXINGTON, Mass., June 10,
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 novel findings on biomarker development for IRAK4
inhibitor emavusertib, collaborative work from the University of Florida in primary CNS lymphoma
(pCNSL), and clinical data from the TakeAim Leukemia and TakeAim
Lymphoma studies at the 2022 European Hematology Association (EHA)
Hybrid Congress currently taking place in Vienna, Austria and online until June 12, 2022.
"We are delighted to share with our colleagues in Europe our findings regarding IRAK4's
previously undescribed localization in the nucleus of cancer cells.
It appears that when IRAK4 is found in the nucleus with active
NF-kB proteins p50 and p65, using a technique which we refer to as
'triple staining,' this triple nuclear presence is associated with
better responses to emavusertib," said James Dentzer, President and Chief Executive
Officer of Curis.
"Also at EHA this year, collaborative work by Dr. Duane Mitchell's team at the University of Florida is being presented on the
potential role of emavusertib in treating pCNSL, including data on
one patient who achieved a complete response following previous
treatment with ibrutinib," Mr. Dentzer continued. "And finally, in
addition to this foundational work on IRAK4 biology, we are
presenting data from our TakeAim Lymphoma and TakeAim Leukemia
studies as we continue to spread the word on IRAK4 and the utility
of inhibiting this important target to our European
colleagues."
- Curis scientists have discovered previously unknown nuclear
accumulation of IRAK4 selectively in acute myeloid leukemia (AML)
cells whereas nuclear IRAK4 was not detectable in mature myeloid
cells (#2609). IRAK4 nuclear accumulation is significantly
correlated with NF-kB activation in bone marrow samples from de
novo AML patients and in AML cell lines. The detection of IRAK4
and NF-kB (phospho-p50 and phospho-p65) using nuclear staining of
blasts in AML bone marrow samples was defined as 'triple-positive,'
and patients whose cells did not stain for the nuclear presence of
any of the three markers were termed 'triple-negative.' Treatment
with emavusertib led to a significant decrease in bone marrow blast
count in AML patients whose bone marrow sample was triple-positive,
whereas no significant decrease in bone marrow blast count was
detected in triple-negative cases. The goal of the Company's
biomarker work is to develop a companion diagnostic for emavusertib
that is broadly applicable and is intended to identify the patients
most likely to benefit from emavusertib treatment.
- Research from Curis collaborators at the University of Florida in pCNSL (#2715) show that,
in a patient treated on the TakeAim Lymphoma study in the
combination arm following a previous ibrutinib containing regimen,
the combination of emavusertib and ibrutinib resulted in a complete
response. The team also observed that IRAK-4 and NF-kB proteins
have elevated expression levels in human pCNSL. Further, in
preclinical work, the team showed that emavusertib achieves
therapeutically relevant concentrations in brain parenchyma and
shows single-agent activity in an aggressive model of pCNSL.
- Also presented at the EHA meeting were previously presented
data from the TakeAim Leukemia (#3975) and TakeAim Lymphoma (#3875)
studies. TakeAim Leukemia is being orally presented, and TakeAim
Lymphoma is the subject of a poster at the meeting. The data from
these studies were also presented at the American Society of
Clinical Oncology meeting last week in Chicago.
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 TakeAim Lymphoma
The TakeAim Lymphoma study (NCT03328078) 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. After dose escalation in both monotherapy and
combination therapy to determine the recommended Phase 2 dose
(RP2D), we plan to expand four cohorts for combination treatment:
marginal zone lymphoma, activated b-cell diffuse large b-cell
lymphoma, primary CNS lymphoma, and patients developing adaptive
resistance to ibrutinib monotherapy. The goals of the study are to
determine several parameters including safety, maximum tolerated
dose (MTD), RP2D and signals of activity.
About TakeAim Leukemia
The TakeAim Leukemia study (NCT04278768) 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. After dose escalation in
both monotherapy and combination therapy to determine the
recommended Phase 2 dose, we plan to expand five cohorts:
monotherapy in AML patients with spliceosome and FLT3 mutations,
monotherapy in patients with MDS and spliceosome mutations and
combination therapy with azacitidine or venetoclax in patients
without spliceosome or FLT3 mutations. The goals of the study are
to determine several parameters including safety, maximum tolerated
dose (MTD), RP2D and signals of activity.
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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