emavusertib (CA-4948) / Curis, Dr. Reddy’s - LARVOL DELTA

Preliminary pharmacokinetic and MRD results from AML patients treated with 7- and 14-day dosing schedule of emavusertib added to combination therapy with azacitidine and venetoclax (ASH 2025) - "Optimization of dosing regimens in triplet combination continue to be investigated. Theseinitial findings support further investigation of the addition of emavusertib to this regimen in order toimprove patient outcomes in a hard-to-treat population."

Clinical • Combination therapy • PK/PD data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • IRAK4

Phase I trial of emavusertib (CA-4948) in combination with FOLFOX/PD-1 inhibitor +/- trastuzumab for untreated, unresectable gastric and esophageal cancer. (ASCO-GI 2026) - P1 | "Funded by V Foundation Clinical Trial Registration Number: NCT05187182 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Combination therapy • P1 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology

Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases (SNO 2025) - P1/2 | "Targeted IRAK-4 inhibition with emavusertib reprograms suppressive TAMs and enhances response to anti-PD-1 therapy in MBM models. These findings support emavusertib as a promising adjuvant to ICB in MM, providing the foundation for a first in human clinical trial (NCT05669352)."

IO biomarker • Melanoma • Solid Tumor • IFNG • IRAK4 • MYD88

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (SNO 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Promising efficacy signal in secondary CNS lymphoma patients treated with emavusertib and ibrutinib (SNO 2025) - "Subsequently, the dose of emavusertib was decreased to 150 mg BID due to Grade 4 neutropenia, then increased to 200 mg AM and 150 mg PM once resolved. This patient achieved CRu within 60 days on treatment.The 2 patients presented here are supportive data for using the combination of emavusertib and ibrutinib in SCNSL."

Clinical • CNS Lymphoma • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypoglycemia • Infectious Disease • Lymphoma • Neutropenia • Secondary Central Nervous System Lymphoma • Septic Shock

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (SNO 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Preliminary safety and efficacy of emavusertib (CA-4948) in combination with ibrutinib in relapsed/refractory primary central nervous system lymphoma patients (SNO 2025) - P1/2 | "This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues."

Clinical • Combination therapy • CNS Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma (ASH 2023) - P1/2 | "Key exclusion criteria: intraocular PCNSL without brain lesion or CSF involvement or significant co-morbidity. Key clinical assessments include brain imaging, CSF- and ocular examinations."

Clinical • IO biomarker • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • FLT3 • IRAK4 • MYD88

Promising efficacy signal in secondary CNS lymphoma patients treated with emavusertib and ibrutinib (WFNOS 2025) - "Subsequently, the dose of emavusertib was decreased to 150 mg BID due to Grade 4 neutropenia, then increased to 200 mg AM and 150 mg PM once resolved. This patient achieved CRu within 60 days on treatment.The 2 patients presented here are supportive data for using the combination of emavusertib and ibrutinib in SCNSL."

Clinical • CNS Lymphoma • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypoglycemia • Infectious Disease • Lymphoma • Neutropenia • Secondary Central Nervous System Lymphoma • Septic Shock

Preliminary safety and efficacy of emavusertib (CA-4948) in combination with ibrutinib in relapsed/refractory primary central nervous system lymphoma patients (WFNOS 2025) - P1/2 | "This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues."

Clinical • Combination therapy • CNS Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Takeaim Lymphoma: An Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Combination with Ibrutinib in Patients with Relapsed or Refractory Hematologic Malignancies (ASH 2023) - P1/2 | "The combination of emavusertib plus ibrutinib (ema+ibr) is well tolerated with an acceptable long-term safety profile and promising efficacy, showing several objective responses in heavily pretreated and/or BTK inhibitor resistant patients. Emavusertib may have the potential to overcome BTK inhibitor resistance and the combination of ema+ibr has the potential to show increased anti-cancer activity compared to ibrutinib monotherapy."

Clinical • Combination therapy • Chronic Lymphocytic Leukemia • CNS Lymphoma • Dental Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Stomatitis • FLT3 • IL1R1 • IRAK4 • MYD88

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (WFNOS 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (WFNOS 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases (WFNOS 2025) - P1/2 | "Targeted IRAK-4 inhibition with emavusertib reprograms suppressive TAMs and enhances response to anti-PD-1 therapy in MBM models. These findings support emavusertib as a promising adjuvant to ICB in MM, providing the foundation for a first in human clinical trial (NCT05669352)."

IO biomarker • Melanoma • Solid Tumor • IFNG • IRAK4 • MYD88

Targeting of Various Inflammatory Circuits Does Not Ameliorate Ineffective Hematopoiesis: Results of the Lucas and Canfire Studies Investigating IRAK4 or IL-1β Blockade to Target Anemia in Lower-Risk MDS (ASH 2024) - "Emavusertib treatment was associated with a reduction in neutrophil counts...Canakinumab treatment was well-tolerated with no reported SAEs...Despite the observed anti-inflammatory effects in the bone marrow, in LUCAS there was a paradoxical increase in inflammatory markers in peripheral blood, potentially due to compensatory mechanisms. These findings suggest that targeting multiple inflammatory pathways simultaneously may offer a more promising therapeutic strategy, such as the combination of IL-1β and IRAK4 inhibitors."

Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • ASXL1 • CSF1 • IL10 • IL15 • IL1B • IL1R1 • IL7 • IRAK4 • SETBP1 • U2AF1

Curis to Present at Upcoming 30th Annual SNO Meeting (PRNewswire) - "...Curis will report emavusertib and BTKi clinical data in Primary CNS Lymphoma (PCNSL) and Secondary CNS Lymphoma (SCNSL) in three presentations and preclinical data on emavusertib in an oral presentation..."

Clinical data • Preclinical • CNS Lymphoma

Kme-0584, a Highly Potent IRAK1/IRAK4/panFLT3 Inhibitor, Is a Promising Clinical Candidate for Hypomethylating Agent Plus Venetoclax Resistant AML/MDS Patients (ASH 2023) - "In primary patient cell lines from FLT3 wildtype (WT) patients, KME-0584 inhibits leukemia stem cell progenitor function as measured by the colony formation assay in methylcellulose with higher potency than IRAK4 inhibitor compounds that lack IRAK1 activity such as CA-4948 (Emavusertib)...Given that monocytic-like subtypes of AML are resistant to Venetoclax plus Azacitidine (VEN/AZA) (S Pei et...KME-0584 exhibits superior potency and efficacy to gilteritinib in the FLT3-ITD (D835Y) xenograft model after QD oral dosing, with sufficient PK and oral bioavailability across multiple species to support QD or BID dosing in the clinic. KME-0584 does not inhibit any of the major or minor cytochrome P450 enzymes at anticipated clinical concentrations and early indication from ongoing GLP toxicology studies suggest that it could be safely administered in humans. A clinical study of KME-0584 in relapsed/refractory AML and HR-MDS is currently planned to start in 1H 2024."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • FLT3 • GLI2 • IRAK4 • PDGFRB • SF3B1 • U2AF1

Trial in Progress: A Phase 1b Single-Arm, Open-Label Study of Emavusertib (CA-4948) in Combination with Azacitidine and Venetoclax in Acute Myeloid Leukemia Patients in Complete Response with Measurable Residual Disease (ASH 2023) - "In this Phase 1b trial, MRD can be evaluated by local testing of bone marrow. Key exclusion criteria include residual toxicities and significant comorbidities."

Clinical • Combination therapy • P1 data • Residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • FLT3 • IRAK4

Preliminary Safety, Efficacy and Molecular Characterization in Patients with Higher-Risk Myelodysplastic Syndrome Treated with Single Agent Emavusertib (CA-4948) (ASH 2024) - P1/2 | "Aim We present preliminary efficacy data of emavusertib hrMDS patients with SFm who failed prior treatment with either venetoclax (VEN) or hypomethylating agents (HMA) based regimens, either as monotherapy or in combination. Enrollment in this monotherapy trial is ongoing at 300 mg BID in hrMDS patients with < 3 lines of prior anti-cancer therapies. Combination trials across the emavusertib program are ongoing with HMA, BCL2 and BTK-inhibitors."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • BCL2 • BCOR • FLT3 • IRAK4 • RUNX1 • SF3B1 • SRSF2 • TET2 • U2AF1

Preliminary Safety, Efficacy, and Molecular Characterization of Emavusertib (CA-4948) in Relapsed/Refractory Acute Myeloid Leukemia Patients (ASH 2024) - P1/2 | "Patients with relapsed/refractory (R/R) AML who have failed standard therapies, including venetoclax (VEN), hypomethylating agents (HMA), and/or FLT3 inhibitors (FLT3i) have limited therapeutic options. Enrollment in this trial is ongoing at 300 mg BID in patients with < 3 lines of prior anti-cancer therapies. Combination trials across the emavusertib program are ongoing with HMA, BCL2 and BTK-inhibitors."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • BCL2 • BCOR • FLT3 • IRAK4 • NRAS • RUNX1 • SF3B1 • SRSF2 • U2AF1 • WT1

In Vivo Ablation of NFκB Cascade Effectors Alleviates Disease Burden in Myeloproliferative Neoplasms (ASH 2023) - "Through qRT-PCR and mass cytometry, we demonstrate that CA-4948 treatment dampened inflammatory cytokine production induced by IL-1β in primary MPN CD14+ monocytes. Overall, we demonstrate that targeting mediators including Rela, Myd88, and IRAK4 specifically alleviated MPN disease burden without toxicity to healthy tissue and further establish CA-4948 as a promising therapeutic avenue for the treatment of MPN."

Preclinical • Acute Myelogenous Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CD14 • CD34 • CDKN1A • CHEK2 • GPX4 • IL1B • IRAK4 • JAK2 • MIR146A • MYD88 • PTPRC • RELA • TP53INP1

Preliminary Safety and Efficacy of Emavusertib (CA-4948) in Acute Myeloid Leukemia Patients with FLT3 Mutation (ASH 2023) - P1/2 | "Two patients with prior gilteritinib exposure also received midostaurin therapy. In addition, mutational profiles are suggestive of disease-modifying activity of emavusertib. Enrollment in this trial is continuing at a dose of 300mg BID (phase 2 expansion cohort) for patients with ≤ 2 prior lines of therapy."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • IRAK4 • SF3B1 • U2AF1

Synthetic Lethal Interactions with IRAK4 Inhibition in Myeloid Malignancies (ASH 2023) - "In Phase-1 findings with a selective IRAK4 inhibitor (CA-4948; Curis Therapeutics), it was found that MDS and AML patients with splicing factor mutations responded best to monotherapy IRAK4 inhibition, although the overall response rate with monotherapy was modest...CC-90009 did not result in complete cell death up to concentrations of 10mM in both WT and IRAK4KO, suggesting that the selective sensitivity of IRAK4KO AML cells to CC-885 is not due to inhibition of GSPT1...These findings suggest that IRAK4 inhibition alters the pool of neosubstrates in AML cells for certain CELMoDs. Overall, our study demonstrates that IRAK4 is a therapeutic target in AML, but that combination therapies, such as with certain CELMoDs, will be necessary to achieve better clinical responses."

Synthetic lethality • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • ANXA5 • CASP3 • CRBN • GLI2 • GSPT1 • IKZF1 • IKZF2 • IKZF3 • IRAK4 • SF3B1 • U2AF1

Preliminary Safety and Efficacy of Emavusertib (CA-4948) in Combination with Ibrutinib in Relapsed/Refractory Primary Central Nervous System Lymphoma Patients with Prior Exposure to BTK Inhibitor (ASH 2024) - P1/2 | "The combination of emavusertib + ibrutinib may overcome BTKi resistance and has the potential to show improved anti-cancer activity. Enrollment in this trial is ongoing (NCT03328078)."

Clinical • Combination therapy • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • IL1R1 • IRAK4 • MYD88

Curis will be presenting initial clinical data from the ongoing frontline AML triplet study in a poster presentation at the 67th ASH Annual Meeting in December (PRNewswire) - "The AML triplet study is evaluating the addition of emavusertib to the combination of azacitidine and venetoclax (aza-ven) in AML patients who have achieved complete remission on aza-ven but remain MRD positive (MRD+)....The abstract, published on November 3, 2025, showed data with a July 2, 2025 data cut-off for 4 patients in the 7-day cohort and 6 patients in the 14-day cohort: (i) MRD conversion (positive to undetectable) was observed in 4 of 8 patients (50%); (ii) 1 additional patient achieved a 40% reduction in MRD from baseline as of data cut-off; (iii) No patients who remained MRD+ progressed on study."

P1 data • Acute Myelogenous Leukemia