Revuforj (revumenib) / Syndax Pharma - LARVOL DELTA

Detection of KMT2A partial tandem duplication (PTD) in AML by whole genome sequencing (WGS): Addressing limitations of traditional techniques in the era of revumenib approval. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM"

Whole genome sequencing • Acute Myelogenous Leukemia • KMT2A

A PHASE 1 STUDY OF REVUMENIB + INTENSIVE CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA HARBORING GENETIC ALTERATIONS IN KMT2A, NPM1, OR NUP98 (SNDX-5613-0708) (EHA 2025) - P1 | "Patients will receive induction therapy of revumenib in combination with cytarabine 200 mg/m2 and either daunorubicin 60 mg/m2 or idarubicin 12 mg/m2. Exploratory endpoints include the percentage of patients who achieve complete remission (CR), rate of composite CR, objective response rate, time to response, duration of response, relapse-free survival, event-free survival, and OS. As of March 1, 2025, this study is actively recruiting patients in the United States, Australia, and the United Kingdom, with additional sites opening in Canada, the Netherlands, and Spain."

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1 • NUP98

REVUMENIB ACTIVITY IN PATIENTS WITH ACUTE LEUKEMIA WITH NUP98R: RESULTS FROM THE AUGMENT-101 PHASE 1 STUDY (EHA 2025) - P1/2, P2 | "The safety profile of revumenib in pts with AL with NUP98r was consistent with previous reports, with no new safety signals observed (Issa et al, Nature. 2023; Issa et al, J Clin Oncol. 2025)."

Clinical • P1 data • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • KMT2A • NPM1 • NUP98

Budget Impact Analysis of Revumenib for the Treatment of Relapsed or Refractory Acute Leukemias With a KMT2A Translocation in the United States (ISPOR 2025) - "Including revumenib on a formulary for adult patients with R/R KMT2Ar acute leukemias was approximately cost neutral and offers patients access to a targeted treatment with potential for improved clinical outcomes."

HEOR • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A

PLINABULIN AND SELUMETINIB INDUCE AAMS REPROGRAMMING INTO M1-LIKE MACROPHAGES AND REDUCE AML CELL VIABILITY (EHA 2025) - "We then evaluated gene expression changes under the combination treatment of AZD6244 and revumenib (a Menin inhibitor) to assess AAM repolarization. In conclusion, we found that BPI-2358 and AZD6244 can reprogram AAMs into M1-like macrophages, enhancing their pro-inflammatory features and phagocytic capacity while reducing AAM-CD163⁺ levels and AML viability, representing a promising therapeutic approach in combination with targeted therapies in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD163 • CD34 • CD80 • KIT • MN1 • MRC1 • NOS2 • TNFA

UPDATED RESULTS AND LONGER FOLLOW-UP FROM THE AUGMENT-101 PHASE 2 STUDY OF REVUMENIB IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) KMT2AR ACUTE LEUKEMIA (EHA 2025) - P1/2 | "Pts were heavily pretreated: 51 (44%) received ≥3 prior therapies, 73 (63%) received prior venetoclax, and 59 (51%) underwent prior hematopoietic stem cell transplant (HSCT).In the efficacy population (n=97), 22 pts (23%; 95% CI, 15%-32%) achieved CR+CRh with a median DOR of 6.4 mo (95% CI, 1.9 mo-NR). Revumenib provides clinically meaningful responses in heavily pretreated pts with R/R KMT2Ar AL across various subgroups and has a manageable safety profile."

Clinical • P2 data • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • KMT2A

VENETOCLAX AND AZACYTIDINE IN CHILDHOOD MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA: THE AIEOP EXPERIENCE (EHA 2025) - "Among 11 patients with KMT2A-rearranged AML, 7 achieved CR, 2 PR, while 2 presented a blast increase and were rescued with revumenib, achieving CR. We report a nationwide experience with ven/aza in pediatric high-risk myeloid diseases, showing a relatively favorable outcome in patients bridged to HCT, with manageable toxicity. Our findings support future prospective protocols using ven/aza for MDS-EB and t-MDS/AML. Further biological characterization of specific genetic subgroups, such as KMT2A-rearranged malignancies, may help refine the role of Bcl-2 inhibition and the prediction of treatment response."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pediatrics • FLT3 • KMT2A

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. (PubMed, Blood) - P1/2 | "The protocol-defined efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 prior lines of therapy, 35.9%; prior venetoclax, 75.0%). The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as NCT04065399."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • NPM1

Dispersive solid-phase extraction as sample pretreatment for determination of chemotherapeutic agents revumenib and venetoclax by HPLC-DAD. (PubMed, Anal Bioanal Chem) - "Under optimized chromatographic conditions, the detection, identification, and determination of both anticancer agents and trazodone (internal standard) were done in less than 8 min of analysis. The preconcentration factor achieved was 1.7 so the limits of detection and quantification were 0.8 μg L-1 and 2.6 μg L-1 for revumenib and 0.7 μg L-1 and 2.3 μg L-1 for venetoclax in serum samples. The proposed strategy stands up as an interesting approach for therapeutic drug monitoring in AML patients moving away from a "one-size-fits-all" approach."

Journal • Acute Myelogenous Leukemia • Oncology

OUTCOMES OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA AFTER MENIN INHIBITION (EHA 2025) - "Prior to MENINi, 84% (n=43) of patients had received intensive chemotherapy (IC) and 73% (n=37) had received venetoclax (VEN)-based therapy...The most used MENINi was revumenib (n=40, 78%), followed by ziftomenib (n=9, 18%)...Of these 4 responders, 3 received AZA (azacitidine)/VEN, 1 received FLAG-IDA/VEN, and all 4 were VEN-naïve...No patients with FLT3-ITD after MENINi responded to further therapy, including 8 treated with gilteritinib (GILT), despite 4 of them being GILT-naïve... MENINi are promising in AML, but outcomes after failure are poor. Responses to post-MENINi therapy can be seen with VEN-based regimens in VEN-naïve patients. Studies focused on sequencing as well as preventing and overcoming MENINi resistance are needed."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • MEN1 • NPM1 • NUP98 • WT1

AZACITIDINE, VENETOCLAX, AND REVUMENIB FOR NEWLY DIAGNOSED OLDER ADULTS WITH ACUTE MYELOID LEUKEMIA (AML) AND NPM1 MUTATION OR KMT2A REARRANGEMENT: UPDATED RESULTS FROM THE BEAT AML CONSORTIUM (EHA 2025) - P1/2, P3 | "AVR has demonstrable clinical activity with manageable safety in ND older adults with NPM1m or KMT2Ar AML with ORR of 88% in all pts and 100% in response-evaluable pts within 2 cycles of treatment. A randomized phase 3 study (NCT06652438) of AVR vs. AV-placebo in ND older adults with NPM1m is in development based on these findings."

Clinical • Acute Myelogenous Leukemia • Cardiovascular • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Septic Shock • KMT2A • NPM1

PATIENTS WITH RELAPSED OR REFRACTORY (R/R) NUCLEOPHOSMIN 1-MUTATED (NPM1M) ACUTE MYELOID LEUKEMIA (AML): UPDATED RESULTS FROM THE PHASE 2 AUGMENT-101 STUDY (EHA 2025) - P1/2 | "The prognosis for R/R NPM1m AML is poor, with only 16% of pts expected to survive 1 y; outcomes after salvage therapy with venetoclax are low, with overall response rates (ORRs) ranging from 6% to 23%, demonstrating a high unmet medical need. Revumenib continues to demonstrate clinically meaningful responses in this heavily pretreated, older population with R/R NPM1m AML. The safety profile remains consistent with previous reports. These findings support further investigation of revumenib as a treatment in earlier lines of therapy and in combination."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • KMT2A • NPM1

SEQUENTIAL ALLOGENEIC STEM CELL TRANSPLANTATION FOR VENETOCLAX-EXPOSED RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH INCREASED BLASTS-2 (EHA 2025) - "Three different 10-day preconditioning backbone regimens were used: ACTIVE (actinomycin D 12.5 mcg/kg (days 1-3), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10), De-ACTIVE (decitabine 20 mg/m2 (days 1-10) added to ACTIVE) or De-CAVE (decitabine 20 mg/m2 (days 1-10), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10)...Gilteritinib, revumenib, and BCR-ABL1 inhibitor exposure was reported in 16 % (4/25), 12 % (3/25), and 8 % (2/25), respectively...Cladribine (40 %, 10/25), gilteritinib (12 %, 3/25), trametinib (16 %, 4/25), navitoclax (28 %, 7/25), and ponatinib (8 %, 2/25) were added to the preconditioning... Upfront sequential alloSCT demonstrates high antileukemic efficacy in poor-risk, R/R AML, or MDS-IB2 patients with previous venetoclax exposure."

Acute Myelogenous Leukemia • Infectious Disease • Mucositis • Myelodysplastic Syndrome • Septic Shock • Transplantation • BCR • TP53

REM-422, A SMALL MOLECULE MYB MRNA DEGRADER, DEMONSTRATES ANTI-LEUKEMIC ACTIVITY AS A MONOTHERAPY AND IN COMBINATION WITH STANDARDS OF CARE IN PRECLINICAL MODELS OF AML (EHA 2025) - P1 | "REM-422's anti-proliferative activity was unchanged in the resistant models, which is consistent with the differentiated mechanism of action of REM-422 compared to these standards of care.The activity of REM-422 was assessed in vitro in combination with AML standards of care by co-treating leukemia cell lines with REM-422 and other agents including venetoclax, gilteritinib, revumenib, and azacitidine. These data support the therapeutic potential for REM-422 in AML patients both as monotherapy and in combination therapy."

Combination therapy • Monotherapy • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CD14 • FLT3 • ITGAM • KMT2A • MYB

DIRECT FUNCTIONAL HOXA9/DNA BINDING COMPETITORS VERSUS EPIGENETIC INHIBITORS OF HOXA9 EXPRESSION ON CELL PROLIFERATION, DEATH AND DIFFERENTIATION PROCESSES IN THE MODEL OF MLL-REARRANGED ACUTE MYELOID LEUKAEMIA (EHA 2025) - "For this purpose, we first focused on genes and pathways that were deregulated, utilizing transcriptomic data to identify both shared and distinct deregulated pathways across the approaches and then evaluated cellular effects based on global cell survival and further identified the impact of cell death, cell cycle and cell differentiation using direct HOXA9/DNA binding competitors (HOXA9i) or epigenetic MLL inhibitors of HOXA9 (Revumenib, MI-503, MM-102, Pinometostat/EPZ5676 and EPZ004777).The present work highlights common and different features from transcriptomic analysis following direct or indirect HOXA9 inhibition. In summary, the use of direct HOXA9 functional inhibitors that target the DNA binding domain, such as DB1055 and DB818, seems to be more effective in promoting differentiation of MLL-r cells compared to the epigenetic MLL inhibitors that operate at the level of HOXA9 expression. This observation offers compelling justification for advancing clinical..."

Epigenetic controller • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • CD40 • CD86 • CDKN1A • DOT1L • HOXA9 • IL1B • ITGAM • KMT2A • WDR5

TARGETING ZEB1 TO ENHANCE MENIN-INHIBITOR SENSITIVITY IN KMT2A-MLLT3 ACUTE MYELOID LEUKEMIA THROUGH MODULATION OF MICRORNA-204 (EHA 2025) - "Finally, we investigated 5-azacytidine (5-Aza) treatment as a strategy to restore miR-204 expression in AML.We identified Zeb1 expression exclusively in a subset of primitive leukemic cells anti-correlated with Hoxa9/Meis1, suggesting an alternative survival pathway in these cells...We then showed an increased sensitivity of these cells to MENIN inhibition (revumenib) mediated by miR-204, while 204-KO cells responded by activating Zeb1, demonstrating its potential as a resistance mechanism... This study establishes miR-204 as a key regulator of ZEB1 in KMT2A-MLLT3 AML, suppressing leukemic stemness and therapy resistance. We show miR-204 enhances MENIN inhibitor sensitivity, while its depletion may drive resistance via ZEB1 activation. Notably, 5-Aza reactivates miR-204 expression, offering a strategy to improve MENIN inhibitor responsiveness in KMT2A-MLLT3 AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • HOXA9 • KMT2A • MEIS1 • MIR204 • MLLT3 • ZEB1

UNCOVERING CD180 AS A NOVEL MARKER AND THERAPEUTIC TARGET OF CHEMORESISTANCE AND RELAPSE IN KMT2A-REARRANGED PAEDIATRIC AML. (EHA 2025) - "CD180+ cells were enriched in quiescent clusters (p<2.2e-16) persisting through relapse (33.2% of total cells) that had co-expression of CD33 and CD93 and were enriched in oxidative phosphorylation, inflammatory response, and TNF-α signaling pathways (NES=1.52, 1.67, 1.62; p-adj=0.006, 1.54e-04, 3.17e-04) known to contribute to chemoresistance.In vitro studies showed that CD180 was upregulated in cytarabine and mitoxantrone chemoresistant versus parental THP-1 (p<0.05)...Revumenib (SNDX-5613) menin-inhibitor significantly decreased CD180-expressing cells% (p=0.0006)... KMT2A-r PAML showed low expression of conventional MRD markers, including CD34. CD180 was highly expressed in KMT2A-r PAML but minimally in normal HSCs. CD180 identifies a chemoresistant, quiescent LSC population expanding at relapse, supporting its use in MRD tracking."

Acute Myelogenous Leukemia • Inflammation • Pediatrics • CD123 • CD33 • CD34 • CD93 • IL3RA • KIT • KMT2A • MLLT3 • TNFA

Insights into KMT2A rearrangements in acute myeloid leukemia: from molecular characteristics to targeted therapies. (PubMed, Biomark Res) - "Menin inhibitors (e.g., Revumenib, Ziftomenib) disrupt the Menin-KMT2A interaction, suppressing HOXA/MEIS1 and promoting differentiation. DOT1L inhibitors (e.g., Pinometostat) show promise in combination therapies, while novel approaches like WDR5 inhibitors and PROTAC-mediated degradation are expanding treatment options. Despite progress, challenges remain, including optimizing minimal residual disease monitoring, overcoming resistance, and validating biomarkers. This review emphasizes the imperative to translate molecular insights into personalized therapeutic regimens, offering renewed hope for patients afflicted by this historically refractory malignancy."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • DOT1L • KMT2A • MEIS1 • WDR5

Syndax Announces Data Presentations at EHA 2025 Showcasing Revuforj (revumenib) (GlobeNewswire) - "Key data being presented at EHA 2025 include: An oral presentation reporting updated results from the Phase 1 BEAT AML trial evaluating the combination of revumenib with venetoclax and azacitidine in newly diagnosed mutant NPM1 (mNPM1) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients aged 60 years or older; A poster presentation reporting data from the 77 patients with relapsed or refractory (R/R) mNPM1 AML who met the efficacy evaluable criteria in the Phase 2 cohort of the AUGMENT-101 trial of revumenib; A poster presentation reporting outcomes in patients with R/R NUP98r acute leukemias in the Phase 1 portion of the AUGMENT-101 trial."

Clinical data • Acute Myelogenous Leukemia

Evaluation of Revumenib in Participants With Colorectal Cancer and Other Solid Tumors (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: Syndax Pharmaceuticals | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Revuforj: "Continued expansion of breadth and depth of Revuforj prescribing and formulary coverage" (Syndax) - Q1 2025 Results

Commercial • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Syndax Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Completed the submission of a supplemental New Drug Application (sNDA) to the U.S. FDA in April 2025, seeking Priority Review for the approval of Revuforj for the treatment of R/R mutant NPM1 (mNPM1) AML. The sNDA was submitted under the FDA’s Real-Time Oncology Review (RTOR) program, which allows for a more efficient review and close engagement between the sponsor and FDA throughout the submission process. The sNDA is supported by the previously reported positive pivotal data from the AUGMENT-101 trial."

Evidence highlight • FDA filing • Priority review • Acute Myelogenous Leukemia • NPM1

Syndax Announces Publication of Pivotal Revumenib Data in Relapsed or Refractory mNPM1 Acute Myeloid Leukemia in the Journal Blood (GlobeNewswire) - P1/2 | N=413 | AUGMENT-101 (NCT04065399) | Sponsor: Syndax Pharmaceuticals | "Syndax Pharmaceuticals...announced that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor, in patients with relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML) have been published in Blood....The protocol-defined efficacy-evaluable population for the primary analysis included the first 64 adult patients with R/R mNPM1 AML....The study met the primary efficacy endpoint with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% (15/64; 95% confidence interval [CI]: 14%-36%; one-sided p-value =0.0014). The median time to first CR+CRh was 2.76 months (range: 1.8-8.8) and the median duration of CR+CRh was 4.7 months (95% CI: 1.2-8.2)....The overall response rate (ORR) was 47% (30/64)."

P2 data • Acute Myelogenous Leukemia

Syndax Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Recent Business Highlights and Anticipated Milestones:...(i) Opened enrollment in the EVOLVE-2 trial, a pivotal, randomized, double-blind, placebo-controlled trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2A-rearranged (KMT2Ar) AML patients who are unfit for intensive chemotherapy in the first quarter of 2025...; (ii) The Company plans to initiate multiple trials of revumenib in combination with standard of care regimens in newly diagnosed acute leukemia patients who are fit to receive intensive chemotherapy, starting in the second half of 2025."

Enrollment open • New trial • Acute Myelogenous Leukemia

Syndax Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Multiple trials evaluating revumenib in mNPM1 and KMT2Ar acute leukemia across the treatment landscape are ongoing. These trials include: (i) BEAT AML: A Phase 1 trial evaluating the combination of revumenib with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2Ar AML patients....The Company anticipates that an update on the trial will be available at a medical meeting in the second quarter of 2025; (ii) Intensive chemotherapy: A Phase 1 trial evaluating the combination of revumenib with intensive chemotherapy (7+3) followed by revumenib maintenance treatment in newly diagnosed mNPM1 or KMT2Ar acute leukemia patients. The Company expects to report data in the fourth quarter of 2025."

P1 data • Acute Myelogenous Leukemia