zefamenib (BN104) / BioNova Pharma, Servier - LARVOL DELTA

Evolving Frontiers in Targeted Therapy: Menin Inhibition in AML (ICKSH 2026) - "Clinically, two menin inhibitors have been approved by the U.S. Food and Drug Administration for relapsed/refractory (R/R) disease in the United States: revumenib for KMT2Ar and NPM1- mutant acute leukemia, and ziftomenib for NPM1m acute leukemias. Additional menin inhibitors, including blexime nib, enzomenib, and BN104, are also being evaluated in clinical trials for R/R acute leukemia with KMT2Ar and NPM1m...Similarly, combining menin inhibitors with standard -of-care therapies, such as azacitidine/venetoclax or intensive chemotherapy, pa rticularly in newly diagnosed KMT2Ar and NPM1m AML, may help mitigate the resistance observed with single -agent therapy...A distinctive feature of menin inhibitor –associated DS is that, unlike DS induced by all -trans retin oic acid (ATRA), arsenic, or IDH inhibitors, corticosteroids are sometimes ineffective. This highlights the need to better understand the pathogenesis of menin inhibitor –associated DS, identify patients at..."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Respiratory Diseases • KMT2A • NPM1

BN104-101: A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov) - P1/2 | N=66 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier (I.R.I.S.) | Trial completion date: Jun 2027 ➔ Dec 2027 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEIS1 • NPM1 • NUP98

Menin inhibitors for adult acute myeloid leukemia: 2025 update. (PubMed, Expert Opin Investig Drugs) - "Menin inhibitor approval/use is expanding into other HOX-driven subtypes (e.g. NPM1, NUP98r), as frontline option and in combination settings. Monitoring for differentiation syndrome, QT interval prolongation, recognizing pseudo-progression, and supportive care needs remains essential to maximize patient benefit."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HOXA9 • KMT2A • MEIS1 • MEN1 • NPM1 • NUP98

Phase 1/2, multi-center, open-label clinical study to evaluate the safety, pharmacokinetics, and efficacy of Zefamenib combined with chemotherapy or targeted Agents in patients with Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Menin inhibitor revumenib combined with venetoclax and azacitidine have shown complete remission (CR) rate of 88.4% in newly diagnosed AML patients harboring these aberrations...Cohort A and D will enroll untreated AML patients, who will receive zefamenib combined with standard 7+3 chemotherapy for induction and zefamenib combined with high dose cytarabine for consolidation...This study will be the first to clarify the feasibility of zefamenib with intensive chemotherapy or targeted agents in the frontline treatment of AML patients or the efficacy and safety of zefamenib with targeted agents in R/R AML patients harboring NPM1 mutation or KMT2A/NUP98 rearrangements. Results of this study will provide ideas and evidence to improve the prognosis of Chinese AML patients with these genetic aberrations."

Clinical • P1/2 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • KMT2A • MEIS1 • NPM1 • NUP98

Phase 1/2, multi-center, open-label clinical study to evaluate the safety, pharmacokinetics, and efficacy of zefamenib in patients with relapsed/refractory acute leukemia (ASH 2025) - P1/2 | "Key secondary endpoints include CR, CR+CRh, objective responserate, MRD negative remission rate, duration of response, duration of CR+CRh, duration of CRc, EFS, OS,cumulative relapse rate, cumulative mortality, safety, and pharmacokinetics. Based on the phase 1results of this study, a global phase 2 study assessing the efficacy and safety of zefamenib monotherapyin acute leukemias with NUP98r, HOXA9r, or mNPM1 will be started in Q2 2026."

Clinical • P1/2 data • PK/PD data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • HEY1 • HOXA9 • KMT2A • MEIS1 • NPM1 • NUP98

A First-in-Human Phase 1/2 Study of the Menin-KMT2A(MLL1) Inhibitor BN104 in Adult Patients with Relapsed or Refractory Acute Leukemia (ASH 2024) - P1/2 | "The median number of prior lines of treatment was 3 (range : 1-8), including all pts had been treated with Venetoclax, and 4 (20%) pts had allogeneic stem cell transplant. Conclusions : Based on preliminary results from the dose escalation part, the 400 mg bid and 600 mg bid dose groups were selected for dose optimization. This FIH Phase 1/2 study preliminary data have demonstrated that BN104 monotherapy has a tolerable safety profile and promising antileukemic activity in heavily pretreated R/R AML pts harboring KMT2Ar or NPM1m."

Clinical • First-in-human • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • FLT3 • ITGAM • KMT2A • MEIS1 • NPM1 • NUP98

A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov) - P1/2 | N=66 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier (I.R.I.S.) | Recruiting ➔ Active, not recruiting | N=266 ➔ 66

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • KMT2A • NPM1

A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov) - P1/2 | N=266 | Recruiting | Sponsor: BioNova Pharmaceuticals (Shanghai) LTD. | N=90 ➔ 266

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • KMT2A • NPM1

The Effect of Food on the Pharmacokinetics of BN104 Tablets (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: BioNova Pharmaceuticals (Shanghai) LTD. | Not yet recruiting ➔ Completed

Trial completion

Phase 2 Trial of BN104 as Post-HSCT Maintenance in Acute Leukemia (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P2 trial • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting. (PubMed, J Hematol Oncol) - "Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEIS1 • NPM1 • NUP98

MENIN inhibitor-based therapy in acute leukemia: latest updates from the 2024 ASH annual meeting. (PubMed, Exp Hematol Oncol) - "At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Furthermore, the therapeutic effects of venetoclax plus azacitidine or "3 + 7" regimens were further enhanced by the addition of MENINis in KMT2Ar- and NPM1m-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • HOXA9 • KMT2A • MEIS1 • NPM1

Servier To Acquire a Potential Best-in-Class Precision Therapy for Acute Leukemias, from BioNova Pharmaceuticals (Servier Press Release) - "Servier...and BioNova Pharmaceuticals...announce that the companies have entered into a definitive agreement under which Servier will acquire BN104, a potential best-in-class menin inhibitor currently in Phase 1/2 development for the treatment of acute leukemias....In line with its 2030 strategy, Servier aims to accelerate the global clinical development of BN104 in mutated AML as well as acute lymphoblastic leukemia (ALL) where the unmet medical need is high, especially for safer therapies in relapse/refractory conditions....Under the terms of the agreement, BioNova Pharmaceuticals will receive a cash payment for its sale of BN104 with development and regulatory earn-outs. The transaction is subject to customary closing conditions."

Commercial • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia

A multicenter, open phase I/ II clinical study to evaluate the safety, pharmacokinetics and efficacy of menin inhibitor BN104 in the treatment of patients with acute myeloid leukemia (ChiCTR) - P1/2 | N=135 | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AFF1 • KMT2A • MEIS1 • MLLT10 • MLLT3 • NPM1 • NUP98

BN104 in Combination With Chemotherapy or Targeted Agents for Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=135 | Recruiting | Sponsor: Chen Suning

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • HOXA9 • MEIS1

Yehui Pharmaceutical's Category 1 new drug for leukemia is planned to be included in the breakthrough therapy category [Google translation] (bydrug.pharmcube.com) - "On December 16, the website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that BN104 tablets, a Class 1 new drug applied by Yehui Pharmaceutical, is planned to be included in the breakthrough therapy category, and the proposed indication is for the treatment of relapsed/refractory acute leukemia with KMT2A rearrangement and/or NPM1 mutation."

Breakthrough therapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Leukemia

The Effect of Food on the Pharmacokinetics of BN104 Tablets (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: BioNova Pharmaceuticals (Shanghai) LTD.

New P1 trial

A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov) - P1/2 | N=90 | Recruiting | Sponsor: BioNova Pharmaceuticals (Shanghai) LTD. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • KMT2A • NPM1

A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov) - P1/2 | N=90 | Not yet recruiting | Sponsor: BioNova Pharmaceuticals (Shanghai) LTD.

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • HOXA9 • ITGAM • KMT2A • MEIS1 • NPM1 • NUP98 • TP53