On June 4, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported the presentation of encouraging clinical data from both the TakeAim Lymphoma and TakeAim Leukemia studies at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting currently taking place in Chicago and online until June 7, 2022 (Press release, Curis, JUN 4, 2022, View Source [SID1234615562]).

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"We are excited to share data with the oncology community from our TakeAim Lymphoma and TakeAim Leukemia studies at ASCO (Free ASCO Whitepaper), 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 (Free ASCO Whitepaper) 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 (Free ASCO Whitepaper), 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.