INCB057643 / Incyte - LARVOL DELTA

Preclinical efficacy of dual BET/HAT inhibitor–based combinations against post myeloproliferative neoplasm secondary AML cells (ASH 2025) - "Notably, treatment with BETi (e.g., OTX015) wasshown to reduce leukemia burden and improve survival in xenograft models of post-MPN sAML cells.However, BETi resistance and BETi-refractory disease develop uniformly...Compared to pan-BET inhibitor INCB057643,treatment with EP31670 induced significantly greater in vitro lethality in HEL92.1.7 and SET2 cells.Notably, in vitro treatment of cell lines and PD post-MPN sAML cells with EP31670 in combination withruxolitinib, for 72 to 96 hours induced synergistic lethality, as determined by SynergyFinder...Notably, co-treatment with EP31670 and SY-5609resulted in significantly greater reduction in leukemia burden and overall survival of the mice thantreatment with each agent alone (p < 0.05). These findings demonstrate promising preclinical activity ofEP31670 against cellular models of MPN-sAML and strongly support the rationale to further evaluate thein vivo efficacy of EP31670-based combinations against advanced MPN with..."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • ASXL1 • BCL2 • BRD4 • CALR • CDK6 • CDKN1A • DNMT3A • EP300 • HEXIM1 • IL6 • JAK2 • MYC • PIM1 • RUNX1 • STAT5 • STAT5AWqe • TP53

INCB057643, a bromodomain and extra-terminal protein inhibitor, in combination with ruxolitinib in patients with myelofibrosis: A phase 1 study of safety and efficacy (ASH 2025) - P1 | "INCB057643 combination therapy with RUX was generally well tolerated on a continuousdosing schedule, with few treatment-related serious TEAEs and no treatment-related fatal events, andwas associated with improvement in spleen size, marked improvement in symptom burden, and anemiaresponses. Dose expansion is ongoing for the 4- and 8-mg combination in both the add-on therapy groupand in JAKi-naive patients."

Clinical • Combination therapy • P1 data • Fibrosis • Hematological Malignancies • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia

Safety and efficacy of bromodomain and extra-terminal protein inhibitor INCB057643 monotherapy in patients with relapsed or refractory myelofibrosis and other advanced myeloid neoplasms: A phase 1 study (ASH 2025) - P1 | "INCB057643 monotherapy was generally well tolerated on a continuous dosing schedule,with few treatment-related serious TEAEs and no treatment-related fatal events. Improvement in spleensize, marked improvement in symptom burden, and anemia response were observed with monotherapy.Dose expansion is ongoing for the 6- and 10-mg INCB057643 dose cohorts in pts with MF. A phase 3study is being initiated to investigate INCB057643 monotherapy in pts with advanced MF following JAKinhibitor treatment."

Clinical • IO biomarker • Metastases • Monotherapy • P1 data • Fibrosis • Hematological Malignancies • Hepatology • Immunology • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • BCL2 • ITGB3 • MYC • TFRC

Details on Incyte data presentations at ASH include: Poster Presentations (Incyte Press Release)

Clinical data • Acute Graft versus Host Disease • Anemia • Chronic Graft versus Host Disease • Essential Thrombocythemia • Follicular Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera

Details on Incyte data presentations at ASH include: Oral Presentations (Incyte Press Release)

Clinical data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera

Bromodomain and Extra-Terminal Inhibitor INCB057643 (LIMBER-103) in Patients with Relapsed or Refractory Myelofibrosis and Other Advanced Myeloid Neoplasms: A Phase 1 Study (ASH 2023) - P1 | "INCB057643 monotherapy (4 and 8 mg qd) and combined (4 and 6 mg qd) with ruxolitinib was generally well tolerated, whereas the 12 mg qd monotherapy dose caused 2 DLTs. There were no treatment-related fatal events. Improvements in spleen size and symptom burden were observed in patients receiving ≥8 mg in the monotherapy group and 4 mg in the combination therapy group."

Clinical • Metastases • P1 data • Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • MYC

Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitor INCB057643 in Patients with Relapsed or Refractory Myelofibrosis and Other Advanced Myeloid Neoplasms: A Phase 1 Study (ASH 2024) - P1 | "In a previous phase 1/2 clinical trial, INCB057643 (an oral, small-molecule BET inhibitor) evaluated as monotherapy or combination (combo) with the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib (RUX) showed favorable tolerability and encouraging clinical activity in patients (pts) with advanced MF. Improvements in anemia, spleen size, and symptom burden were observed in pts receiving monotherapy and combo therapy. Dose expansion is ongoing for 6 mg and 10 mg monotherapy; ongoing dose escalation for combo therapy is expected to be completed, with data presentation at ASH 2024."

Clinical • Metastases • P1 data • Acute Myelogenous Leukemia • Anemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombocytosis

Machine Learning in Predicting Longitudinal Platelet Counts: Applications in Dose Optimization (ASH 2024) - P1, P1/2 | "Our ML framework predicts that safety events vary with INCB057643 dosage and dosing regimens. This information can be used to inform dose optimization for patients."

Machine learning • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • Thrombocytopenia

MODULE 4: Novel Agents Under Investigation for MF (ASH 2025) - "This program is supported by educational grants from Blueprint Medicines, Bristol Myers Squibb, GSK, and Incyte Corporation. Rationale for the inhibition of BET proteins in MF; mechanism of action of pelabresib Key efficacy and safety findings from the Phase III MANIFEST-2 study combining pelabresib with ruxolitinib for patients with JAK inhibitor-naïve disease; potential role of BET inhibition as monotherapy and/or in combination with JAK inhibition Similarities and differences between pelabresib and investigational BET inhibitors (INCB57643); available data and ongoing evaluation of these agents Mechanism of antitumor activity of navtemadlin and biological rationale for its evaluation for patients with MF Design, eligibility criteria and key efficacy and safety endpoints of the Phase III BOREAS trial evaluating navtemadlin monotherapy for patients with MF whose disease was resistant or refractory to JAK inhibitors Ongoing Phase III POIESIS study of adding..."

Anemia • Hematological Disorders

Corporate and Business Development Updates (Businesswire) - "Based on ongoing pipeline prioritization efforts, the Company has paused further development of the INCA034460 (anti-CD122) and INCB57643 (BET inhibitor) programs, as well as the development of povorcitinib in chronic spontaneous urticaria (CSU)."

Discontinued • Chronic Spontaneous Urticaria • Myelodysplastic Syndrome • Myelofibrosis • Vitiligo

INCB 57643-103: Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=231 ➔ 140

Enrollment change • Enrollment closed • Atypical Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis

Safety and Efficacy of Bromodomain and Extra-Terminal (BET) Inhibitor INCB057643 in Patients With Relapsed or Refractory Myelofibrosis (MF) and Other Advanced Myeloid Neoplasms: A Phase 1 Study (SOHO 2025) - P1 | " This ongoing phase 1, open-label 3+3 dose-escalation/expansion study (NCT04279847) is evaluating INCB057643 monotherapy (part 1; 4mg→12 mg once daily [qd]) in adults with relapsed/refractory MF, essential thrombocythemia, myelodysplastic syndrome (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome; or combination therapy (part 2; 4 mg qd→part 1 maximum tolerated dose) with ruxolitinib in adults with MF and suboptimal response to ruxolitinib or who were Janus kinase inhibitor (JAKi) naive. INCB057643 monotherapy or combination therapy was generally well tolerated, with improvements observed in anemia, spleen size, and symptom burden. Dose expansion is ongoing for 6- and 10-mg monotherapy and 4- and 8-mg combination therapy (add-on and JAKi naive)."

Clinical • Metastases • P1 data • Essential Thrombocythemia • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

SAFETY AND EFFICACY OF BROMODOMAIN AND EXTRA-TERMINAL (BET) INHIBITOR INCB057643 IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY MYELOFIBROSIS (MF) AND OTHER ADVANCED MYELOID NEOPLASMS: A PHASE 1 STUDY (EHA 2025) - P1 | "This ongoing phase 1, open-label 3+3 dose-escalation/expansion study (NCT04279847) is evaluating INCB057643 monotherapy (part 1; 4 mg→12 mg once daily [qd]) in adults with relapsed or refractory MF, essential thrombocythemia, myelodysplastic syndrome (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome; or combination therapy (part 2; 4 mg qd→part 1 maximum tolerated dose) with ruxolitinib (RUX) in adults with MF and suboptimal response to RUX or who were Janus kinase inhibitor (JAKi) naive. INCB057643 monotherapy or combination therapy with RUX was generally well tolerated, with no tx-related fatal events. Improvements in anemia, spleen size, and symptom burden were observed with monotherapy and combination therapy. Dose expansion is ongoing for 6- and 10-mg monotherapy and 4- and 8-mg combination therapy groups (add-on and JAKi naive)."

Clinical • Metastases • P1 data • Acute Myelogenous Leukemia • Anemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombocytosis

BROMODOMAIN AND EXTRA-TERMINAL (BET) PROTEIN INHIBITOR, INCB057643, IMPROVES BONE MARROW FUNCTION AND SHIFTS MEGAKARYOPOIESIS TO ERYTHROPOIESIS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS (MPNS) (EHA 2025) - P1, P1/2 | "INCB057643, a novel, orally bioavailable BET inhibitor, is being evaluated in clinical trials as monotherapy and in combination with ruxolitinib in patients with MPNs (NCT02711137; NCT04279847). Results show that INCB057643 specifically inhibits pathogenic MK differentiation, reduces inflammatory cytokine production, and decreases fibrosis. INCB057643 treatment also improves bone marrow function, which results in increased erythroid differentiation and reduced anaemia symptoms."

Clinical • Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • ITGB3 • JAK2 • TFRC • TIMP3

INCB057643, A BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR, HAS NOVEL ROLES IN MYELOID CELL REGULATION AND IMMUNOSUPPRESSIVE TUMOUR ENVIRONMENT REMODELLING IN MYELOFIBROSIS (EHA 2025) - P1, P1/2 | "In ex vivo assays, INCB057643 decreased the proportion of malignant MK precursors that drive MF. Although RNAseq data confirmed INCB057643 regulated epigenetic gene expression globally, selective inhibition of myeloid and MK cells, but not other lineages, was observed. INCB057643 inhibited myeloid cells by downregulating immunosuppressive receptors and proinflammatory cytokines, leading to tumour microenvironment remodelling and reduced inflammation."

IO biomarker • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • CXCL5 • CXCL8 • IL18 • MGST1 • MYC • PRF1

A Study to Evaluate the Relative Bioavailability of New Formulations of INCB057643 Tablets Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Incyte Corporation | Recruiting ➔ Completed

Trial completion

A Phase 2 Study of INCB57643 (BET Inhibitor) in Combination With Ruxolitinib in JAK Inhibitor-naïve Patients With Myelofibrosis (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=30 ➔ 0 | Trial completion date: Apr 2029 ➔ May 2025 | Initiation date: Mar 2025 ➔ Sep 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Apr 2027 ➔ May 2025

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Myelofibrosis

Incyte Announces Multiple Presentations, Including New Late-Breaking Data for its mutCALR-Directed Monoclonal Antibody (INCA033989), Accepted for Presentation at EHA 2025 (Businesswire) - "Late-breaking oral presentation will highlight new data from a trial of INCA033989, an anti-mutant calreticulin (mutCALR)-directed monoclonal antibody, in patients with essential thrombocythemia (ET); Incyte to host an in-person analyst and investor event highlighting the mutCALR data at EHA on Sunday, June 15, 2025, from 6:00 - 7:30 a.m. EDT (12:00 - 1:30 p.m. CEST)."

Clinical data • Chronic Graft versus Host Disease • Essential Thrombocythemia • Follicular Lymphoma • Marginal Zone Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm

Safety and efficacy of bromodomain and extra-terminal (BET) inhibitor INCB057643 in patients (pts) with relapsed or refractory myelofibrosis (r/r-MF) and other advanced myeloid neoplasms: A phase (Ph) 1 study. (ASCO 2025) - P1 | " This ongoing Ph 1, open-label 3+3 dose-escalation/expansion study (NCT04279847) is evaluating INCB057643 monotherapy (mono; part 1; 4 mg→12 mg once daily [qd]) in adults with r/r-MF, essential thrombocythemia (ET), myelodysplastic syndrome (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, or combination therapy (combo; part 2; 4 mg qd→part 1 maximum tolerated dose) with ruxolitinib (RUX) in adults with MF and suboptimal response to RUX or who were Janus kinase inhibitor (JAKi) naive. INCB057643 mono or combo with RUX was generally well tolerated, with no tx-related fatal events. Improvements in anemia, spleen size, and symptom burden were observed with mono and combo. Dose expansion is ongoing for 6- and 10-mg mono and 4- and 8-mg combo groups (add-on and JAKi naive)."

Clinical • Metastases • Acute Myelogenous Leukemia • Anemia • Essential Thrombocythemia • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Thrombocytopenia • Thrombocytosis

A Study to Evaluate the Relative Bioavailability of New Formulations of INCB057643 Tablets Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Relative Bioavailability of New Formulations of INCB057643 Tablets Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Incyte Corporation

New P1 trial

Incyte to Showcase New Data from its Oncology Portfolio at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - "Incyte...that multiple abstracts featuring new data from its oncology portfolio will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30 – June 3, 2025, in Chicago."

Clinical data • Platinum resistant • Anal Squamous Cell Carcinoma • Endometrial Cancer • Glioblastoma • Merkel Cell Carcinoma • Myelofibrosis • Ovarian Cancer

INCB057643, a bromodomain and extra-terminal (BET) protein inhibitor, improved bone marrow function and shifted megakaryopoiesis to erythropoiesis in patients with myeloproliferative neoplasms (MPNs) (AACR 2025) - P1, P1/2 | "INCB057643, a novel, orally bioavailable BET inhibitor, is being evaluated in clinical trials as monotherapy and in combination with ruxolitinib in patients with MPNs (NCT02711137; NCT04279847). In conclusion, the results show that INCB057643 specifically inhibits pathogenic MK differentiation, reduces inflammatory cytokine production, and decreases fibrosis. INCB057643 treatment also improves bone marrow function, which results in increased erythroid differentiation and reduced anemia symptoms."

Clinical • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • ITGB3 • JAK2 • TFRC • TIMP3

Novel role of INCB057643, a bromodomain and extra-terminal (BET) protein inhibitor, in myeloid cell regulation and immunosuppressive tumor environment remodeling in myelofibrosis (MF) (AACR 2025) - P1, P1/2 | "Although data confirmed INCB057643 regulates epigenetic gene expression globally, selective inhibition of myeloid and MK cells, but not other lineages, was observed. INCB057643 inhibited myeloid cells by downregulating immunosuppressive receptors and proinflammatory cytokines, leading to tumor microenvironment remodeling and reduced inflammation."

IO biomarker • Myelofibrosis • Oncology • CD34 • CXCL5 • CXCL8 • IL18 • MGST1 • MYC • PRF1

Incyte to Highlight Early-Stage Oncology Data at American Association for Cancer Research Annual Meeting 2025 (Businesswire) - "Incyte...announced that the Company will present new early-stage data from its oncology portfolio at the American Association of Cancer Research (AACR) Annual Meeting 2025 in Chicago, IL, from April 25–30."

Clinical data • Preclinical • Myelofibrosis • Myeloproliferative Neoplasm • Ovarian Cancer