nuvisertib (TP-3654) / Sumitomo Pharma - LARVOL DELTA

Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis (ASH 2025) - P1/2 | "Nuvisertib (NUVI, TP-3654), an oralinvestigational highly selective PIM1 kinase inhibitor, alone and in combination with ruxolitinib (RUX)showed spleen size reduction and bone marrow (BM) fibrosis improvement in JAK2V617F and MPLW515LMF mouse models. NUVI + MMB combo appeared to be well tolerated. Preliminary data showed early clinicalactivity including 60% TSS50 response and absolute symptom improvement, 40% SVR25 response,cytokine modulation and anemia improvement in R/R MF pts with anemia. Preliminary data supportsfurther development of NUVI + MMB combo for pts with MF."

Clinical • Combination therapy • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1 • PIM1

Nuvisertib, an oral investigational selective PIM1 kinase inhibitor, showed clinical responses strongly correlating with cytokine modulation in patients with relapsed/refractory myelofibrosis in the ongoing global phase I/II study (ASH 2025) - P1/2 | "Nuvisertib monotherapy appeared well tolerated with no DLTs. Preliminary data in pts withR/R MF showed that nuvisertib treatment leads to significant modulation of cytokine profiles,demonstrating a strong correlation with clinical responses, including SVR25 and TSS50 responses, andimprovements in Hgb, PLT and BM fibrosis, suggesting that selective PIM1 inhibition may offer disease-modification with limited hematologic toxicity. Emerging data supports ongoing clinical development ofnuvisertib in combination with ruxolitinib and momelotinib (NCT04176198, Arms 2 and 3, respectively)."

Clinical • P1/2 data • Fibrosis • Hematological Malignancies • Immunology • Myelofibrosis • Thrombocytopenia • IL1R1 • PIM1 • TNFRSF1A • VCAM1

For the first time, clinical data were presented from the ongoing global Phase 1/2 study evaluating the safety and efficacy of nuvisertib in combination with momelotinib (MMB) in 18 patients with R/R MF with anemia. (PRNewswire) - "Preliminary data showed that the treatment with nuvisertib and MMB combination appeared well tolerated, with early clinical activity observed, including ³50% total symptom score reduction (TSS50 response) in 58% of patients with an absolute reduction in all individual symptoms, a spleen volume reduction 25% (SVR25 response) in 50% of patients, anemia improvement, and cytokine modulation in patients with relapsed or refractory MF with anemia. These preliminary data, collected as of October 15, 2025, support further development of nuvisertib in combination with MMB as a potential treatment option for patients with MF."

P1/2 data • Anemia • Myelofibrosis

Additionally, data presented from the ongoing global Phase 1/2 study of nuvisertib in patients with relapsed or refractory MF (N=77) showed that nuvisertib monotherapy continued to be well tolerated with no DLTs and limited myelosuppression. (PRNewswire) - "The results showed that treatment with nuvisertib monotherapy led to SVR25 response in 20% of patients, TSS50 response in 45% of patients with absolute reduction in all individual symptoms. Data also showed that treatment with nuvisertib resulted in significant cytokine modulation over time, correlating with spleen and symptom responses and one-year overall survival rate of 81%."

P1/2 data • Myelofibrosis

Highlights of JTCC Research to be presented at ASH 2025: Myeloproliferative Neoplasms (PRNewswire) - "Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis (ABSTRACT 25-3882); Safety and efficacy results from A phase 1b study of R289, a dual irak 1/4 inhibitor, in patients with Relapsed/Refractory (R/R) lower risk myelodysplastic syndrome (LR-MDS) (ABSTRACT 25-13480); Nuvisertib, an oral investigational selective PIM1 kinase inhibitor, showed clinical responses strongly correlating with cytokine modulation in patients with relapsed/refractory myelofibrosis in the ongoing global phase I/II study (ABSTRACT 25-2614)."

Clinical data • Myelodysplastic Syndrome • Myelofibrosis

A Phase 1/2 Study of Nuvisertib (TP-3654), an Investigational Selective PIM1 Kinase Inhibitor, in Combination with JAK Inhibitors Ruxolitinib or Momelotinib in Patients with Myelofibrosis (ASH 2024) - P1/2 | "Recent Phase 3 combination studies of RUX with Pelabresib (Rampal R, 2023) or Navitoclax (Pemmaraju N, 2023) in treatment naïve MF pts with platelet (PLT) count ≥100 x 109/L showed significant increase only in spleen responses; however, did not improve symptoms response, also were limited by overlapping toxicities of thrombocytopenia. For TP-3654 in combination with MMB (Arm 3), pts that have been previously treated with an approved JAK inhibitor (except MMB) for ≥12 weeks, or ≥4 weeks if JAK inhibitor therapy was complicated by a transfusion requirement of ≥4 units of RBC in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma. Combination arms are currently recruiting pts."

Clinical • Combination therapy • P1/2 data • Anemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • Thrombocytopenia • PIM1

Nuvisertib (TP-3654), an Investigational Selective PIM1 Kinase Inhibitor, Showed Durable Clinical Response and Sustained Hematological Improvement in Relapsed/Refractory Myelofibrosis Patients (ASH 2024) - P1/2 | "Preliminary data of TP-3654 in relapsed/refractory MF pts showed clinical activity including SVR25, symptom improvement correlating with cytokines reduction, BM fibrosis reduction, and Hgb and PLT responses. Current monotherapy and preclinical data support the development of TP-3654 in combination with JAK inhibitors ruxolitinib and momelotinib (NCT04176198, Arms 2 and 3, respectively); enrollment ongoing in all 3 arms."

Clinical • Anemia • Fatigue • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Musculoskeletal Pain • Myelofibrosis • Oncology • Pain • PIM1

Cytokine Modulation Correlates Strongly with Symptom Improvement in Patients with Myelofibrosis Treated with Nuvisertib (TP-3654), an Investigational Selective PIM1 Kinase Inhibitor (ASH 2024) - P1/2 | "In preclinical murine MF models, TP-3654 alone and in combination with ruxolitinib, showed reduced spleen size, bone marrow (BM) fibrosis and, importantly, cytokine response genes. ENRAGE and adiponectin levels were significant predictors of SVR, TSS50 responses and specific symptom improvement for fatigue, itching and satiety. Translational studies are ongoing to further explore potential disease modification activity of TP-3654."

Clinical • Anemia • Fatigue • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Pruritus • Thrombocytopenia • CD40LG • EGFR • IL18 • IL1R1 • PIM1 • TIMP1 • TNFRSF1A

Phase 1/2 Study of TP-3654, a Selective PIM1 Kinase Inhibitor: Preliminary Data Showed Clinical Activity and Cytokine Reductions in Relapsed/Refractory Myelofibrosis Patients (ASH 2023) - P1/2 | "In preclinical studies, TP-3654 alone and in combination with ruxolitinib showed spleen size and bone marrow (BM) fibrosis reduction in murine MF models. This preliminary data of TP-3654 in relapsed/refractory MF pts showed early signs of clinical activity including spleen volume reduction, TSS improvement, and correlating cytokine reductions. TP-3654 is well tolerated with limited myelosuppressive adverse events. Enrollment is ongoing as monotherapy and current data support the development of TP-3654 in combination with JAK inhibitors given the preliminary clinical activity and minimal cytopenia."

Clinical • IO biomarker • P1/2 data • Fibrosis • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • CD40 • CXCL8 • IL18 • PIM1 • TGFB1

New clinical data from the Phase 1/2 study evaluating the safety and efficacy of nuvisertib in combination with MMB demonstrate early clinical activity and show that the treatment combination was well-tolerated supporting further development in patients with MF. (PRNewswire)

P1/2 data • Myelofibrosis

Nuvisertib shows single-agent anti-tumor activity in multiple myeloma nonclinical models (AACR-NCI-EORTC 2025) - P1/2 | "Nuvisertib demonstrated potent, dose-dependent cytotoxicity in vitro, with an IC₃₀ value of 1.11 µM, comparable to those of established MM drugs including dexamethasone (1.32 µM), cyclophosphamide (1.01 mM), lenalidomide (95.1 µM), and pomalidomide (16.5 µM). These results support nuvisertib as a potential therapeutic agent for MM, both as a monotherapy and in combination with currently used treatments. Further studies using preclinical human MM PDX models are warranted to evaluate drug interactions and impact on overall survival."

Hematological Malignancies • Multiple Myeloma • Myelofibrosis • Oncology • PIM1

Sumitomo Pharma Presents Latest Clinical Data on Investigational Anti-Cancer Agent Enzomenib (DSP-5336) at the 2025 Annual Meeting of the Japanese Society of Hematology (JSH) (Sumitomo Pharma Press Release) - "The safety analysis set of the study included 84 patients with acute leukemia, of whom 94% (79/84) had acute myeloid leukemia (AML)....Preliminary efficacy data from the dose optimization cohort (200 mg and 300 mg twice daily) were also presented. This included patients with KMT2A rearrangements or nucleophosmin 1 (NPM1) mutations who had received at least one dose of enzomenib and had not previously been treated with menin inhibitors. Among these, the overall population (n=40) showed an objective response rate (ORR) of 62.5% (25/40) and a complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate of 37.5% (15/40). In the Japanese population (n=12), ORR was 75.0% (9/12) and CR+CRh was 41.7% (5/12)...At JSH2025, Sumitomo Pharma also presented clinical data from a Phase 1/2 study of nuvisertib....targeting relapsed or refractory myelofibrosis."

P1/2 data • Acute Myelogenous Leukemia • Myelofibrosis

Sumitomo Pharma America Announces that the European Medicines Agency Has Granted Orphan Drug Designation to Nuvisertib (TP-3654) for the Treatment of Myelofibrosis (PRNewswire) - "Sumitomo Pharma America, Inc...announced that the European Medicines Agency (EMA) granted Orphan Drug Designation to nuvisertib (TP-3654), an oral investigational highly selective inhibitor of PIM1 kinase, for the treatment of patients with myelofibrosis (MF)....This designation comes on the heels of the recent U.S. Food and Drug Administration (FDA) Fast Track Designation granted to nuvisertib, and following the oral presentation of updated preliminary Phase 1/2 data at the European Hematology Association (EHA) 2025 Congress in Milan, Italy."

Orphan drug • Myelofibrosis

Nuvisertib: "Improvements in important efficacy measures were observed even in patients who did not respond to JAK inhibitors and in those with poor prognostic factors such as low hemoglobin and platelet counts"; Myelofibrosis (Sumitomo Dainippon) - Q1 FY2025 Results

P1/2 data • Hematological Malignancies • Myelofibrosis • Oncology

PRELIMINARY DATA FROM PHASE I/II STUDY OF NUVISERTIB, AN ORAL INVESTIGATIONAL SELECTIVE PIM1 INHIBITOR, SHOWED CLINICAL RESPONSE CORRELATING WITH CYTOKINE MODULATION IN PATIENTS WITH MYELOFIBROSIS (EHA 2025) - P1/2 | "Nuvisertib monotherapy appeared well tolerated with no DLTs. Preliminary data showed clinical activity including SVR25, symptom improvement correlating with cytokines modulation, BM fibrosis reduction, and Hgb and PLT responses in relapsed/refractory (R/R) MF pts. Emerging data support clinical development of nuvisertib in combination with JAK inhibitors ruxolitinib and momelotinib (NCT04176198, Arms 2 and 3, respectively)."

Clinical • P1/2 data • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • Thrombocytopenia • PIM1

Silencing PIM1 inhibits ENO1-induced AKT activation and attenuates fibrillogenesis during spinal cord injury-induced skeletal muscle atrophy. (PubMed, J Biol Chem) - "We then explored the effects of the selective PIM1 inhibitor TP-3654 on fibrosis...Downregulation of PIM1 expression in fibroblasts using drugs or siRNA leads to decreased ENO1 expression, concurrent with AKT phosphorylation reduction and suppressor of mothers against decapentaplegic (Smad)2/3 dephosphorylation within the TGF-β classical pathway. In summary, PIM1 might be an important target gene for future skeletal muscle atrophy treatments."

Journal • CNS Disorders • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Muscular Atrophy • Oncology • Orthopedics • ENO1 • SMAD4 • TGFB1

Sumitomo Pharma America Announces that Nuvisertib (TP-3654) Has Received FDA Fast Track Designation for the Treatment of Myelofibrosis (PRNewswire) - P1/2 | N=240 | NCT04176198 | Sponsor: Sumitomo Pharma America, Inc. | "Sumitomo Pharma America...announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to nuvisertib (TP-3654) for the treatment of patients with intermediate or high-risk myelofibrosis (MF).....Updated data from the ongoing Phase 1/2 study of nuvisertib in patients with relapsed/refractory MF were presented at the EHA Congress on June 12, 2025. Preliminary data showed that nuvisertib monotherapy appears to be well tolerated with no dose-limiting toxicities (DLTs). Evaluable patients showed clinical activity including a ≥25% spleen volume reduction (SVR25) in 22.2% of patients and a ≥50% reduction in total symptom score (TSS50) of 44.4% of patients, as well as improvement of bone marrow fibrosis (42.9% patients), hemoglobin (24% patients) and platelet count (26.7% patients)."

Fast track • P1/2 data • Myelofibrosis

AUM-302, A NOVEL TRIPLE PIM/PI3K/MTOR INHIBITOR, SYNERGIZES WITH KRAS INHIBITION AND IMPEDES THE GROWTH OF PANCREATIC DUCTAL ADENOCARCINOMA SPHEROIDS AND ORGANOIDS (DDW 2025) - "Single- and dual kinase inhibitors TP-3654, GDC-0941, and BEZ-235, and DMSO were used as controls...Finally, combinatorial assays revealed synergy between AUM-302 and the KRAS inhibitor RMC-6236 in reducing the growth of hT1 and hM1A organoids. By blocking kinase activity, AUM-302 demonstrates potent inhibitory activity in PDAC cell lines and organoids in two different 3D culture formats. Treatment with this novel triple PIM/PI3K/mTOR inhibitor may also sensitize PDAC to other therapies, such as KRAS inhibitors."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Nuvisertib: Presentation of efficacy and safety data from P1/2 trial (NCT04176198) for myelofibrosis at EHA (Jun 12-15, 2025) (Sumitomo Dainippon) - FY2024 Results

P1/2 data • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Nuvisertib: Regulatory submission for myelofibrosis in FY 2027 (Sumitomo Dainippon) - FY2024 Results: Launch in US/Japan for myelofibrosis in FY 2028

Filing • Launch Japan • Launch US • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

PIM inhibition increases membrane expression of TNFRSF10B(DR5) and combination with recombinant human TRAIL synergizes to reduce renal cell carcinoma cell viability (AACR 2025) - "To investigate synergism between PIM inhibitors and recombinant human TRAIL (rhTRAIL), RCC cell lines were treated with increasing concentrations of SGI-1776 or TP-3654 and rhTRAIL (TLY012) for 24 hours and assessed for viability via Cell Titer Glo assay. These results reveal novel therapeutic strategies for the treatment of RCC, highlighting PIM kinases as targets to potentiate TRAIL induced apoptosis. Current studies are ongoing to understand the mechanism of PIM kinase involvement in DR5 regulation and sensitivity to TRAIL in RCC."

Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Oncology • Renal Cell Carcinoma • Solid Tumor • PIM1 • TNFRSF10B

PIM1 contributes to tumor progression, immune evasion and metastasis of triple-negative breast cancer (AACR 2025) - "Gene Set Enrichment Analysis (GSEA) revealed significant downregulation of genes related to cell proliferation, translation, EMT and metastasis in PIM1-deleted or TP-3654-treated TNBC cells compared to control TNBC cells. Collectively, our results suggest that PIM1 plays an important role in tumor progression, immune evasion and metastasis of TNBC, and inhibition of PIM1 with TP-3654 might be potentially useful for treatment of TNBC."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MET • PIM1 • SNAI2 • VIM

REDD1 is a determinant of the sensitivity of renal cell carcinoma cells to autophagy inhibition that can be therapeutically exploited by targeting PIM activity. (PubMed, Cancer Lett) - "Repurposing FDA approved drugs with off-target autophagy inhibition such as chloroquine/hydroxychloroquine (CQ, HCQ) has produced modest anticancer activity in clinical trials, due in part, to a failure to define predictive biomarkers that enable the selection of patients that best respond to this treatment strategy. Inhibition of autophagy with CQ synergistically enhanced the in vitro and in vivo anticancer activity of TP-3654. Our findings identify REDD1 as a novel determinant of the sensitivity of RCC cells to autophagy inhibition and support further investigation of PIM kinase inhibition as a precision strategy to drive sensitivity to autophagy-targeted therapies through REDD1 upregulation."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AMPK • DDIT4

Nuvisertib: Launch in US/Japan for myelofibrosis in FY 2027 (Sumitomo Dainippon) - Q3 FY2024 Results

Launch Japan • Launch US • Hematological Malignancies • Myelofibrosis • Oncology

Nuvisertib: “Improvements in important efficacy measures were observed even in patients who did not respond to JAK inhibitor and in those with poor prognostic factors such as low hemoglobin and platelet counts”; Myelofibrosis (Sumitomo Dainippon) - Q3 FY2024 Results

P1/2 data • Hematological Malignancies • Myelofibrosis • Oncology