Gomekli (mirdametinib) / EMD Serono - LARVOL DELTA

Long-term analysis of mirdametinib treatment in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma (NF1-PN): updated phase 2b ReNeu trial findings (EANO 2026) - P2 | "Long-term mirdametinib treatment in ReNeu demonstrated increased confirmed objective response rates, additional deep responses, and decreased TRAE rates over time in adults and children with NF1-PN."

Clinical • P2b data • Oncology • Solid Tumor • NF1

The impact of mirdametinib on pain medication use in adult patients from a United States (US) claims dataset (SNO 2026) - No abstract available

Clinical • Pain

Iodide Availability Controls Thyroid Cell Identity, ERK Signaling, and Redox Balance (ETA 2026) - "To evaluate the role of the MAPK/ERK signaling pathway on ID-induced effects, cells were treated with the MEK inhibitor PD0325901... ID directly modulates thyroid cell differentiation, epigenetic regulatory pathways, redox-related enzymes, and intracellular signaling pathways independently of TSH. These data reinforce the concept that iodide is not only required for thyroid hormone synthesis, but also actively participates in the maintenance of thyroid follicular cell identity and cellular homeostasis."

AMPK • GPX1 • HAT1 • HDAC3 • KDM5C • KDM6A • PAX8 • SOD2

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma. (PubMed, J Clin Oncol) - "In ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children."

Journal • P2b data • Dermatitis • Dermatology • Genetic Disorders • Immunology • Neurofibromatosis • Oncology • Pain • Solid Tumor • NF1

An NF1 patient with a very heavy burden of plexiform neurofibromas with remarkable symptomatic improvement following mirdametinib (SNO 2026) - No abstract available

Clinical • Neurofibromatosis • Solid Tumor • NF1

Mirdametinib and Other MEK Inhibitors in NF1-Associated High-Grade Glioma: Outcomes From a Single-Institution Cohort and Literature Review (SNO 2026) - No abstract available

Clinical • Review • Brain Cancer • Glioma • High Grade Glioma • Solid Tumor • NF1

Pain outcomes in patients with/without volumetric tumor response: post hoc from the ReNeu trial of mirdametinib in adults & children with neurofibromatosis type 1-associated plexiform neurofibroma (NF1-PN) (SNO 2026) - No abstract available

Clinical • Retrospective data • Genetic Disorders • Neurofibromatosis • Oncology • Pain • Solid Tumor • NF1

Pain outcomes in patients with and without volumetric tumor response: post hoc analysis from the ReNeu trial of mirdametinib in adults and children with neurofibromatosis type 1-associated plexiform neurofibroma (NF1-PN) (EANO 2026) - P2 | "Patients with NF1-PN previously reported pain improvement with mirdametinib, but the contribution of target PN response was unknown. This analysis demonstrates that adults and children may derive symptomatic benefit in pain outcomes with mirdametinib treatment independent of radiographic response."

Clinical • Retrospective data • Oncology • Solid Tumor • NF1

ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1) associated symptomatic inoperable plexiform neurofibroma (PN) (EANO 2024) - P2 | "Conclusions : In ReNeu, the largest multicenter NF1 PN trial reported to date, mirdametinib demonstrated a statistically significant ORR by BICR, with deep and durable PN volume reductions, significant improvements in pain severity, pain interference, and HRQoL, and a manageable safety profile in both adults and children. Together with a dispersible tablet formulation, these results underscore the potential of mirdametinib to become an important new treatment option for NF1 PN pts across all ages."

Clinical • P2b data • Oncology • Solid Tumor • NF1

PPARGC1A as an Epigenetic Biomarker of Differentiation in Differentiated Thyroid Cancer (ETA 2026) - "Similarly, thyroid cancer redifferentiation models, including treatments with LY294002 (PI3K inhibitor), PD325901 (ERK/MAPK inhibitor), Trichostatin A (histone deacetylase inhibitor) and 5-azacytidine (DNA methyltransferase inhibitor), also resulted in an increased PPARGC1A expression alongside the TDS, reinforcing the link between PPARGC1A and differentiation state. In conclusion, we have identified PPARGC1A as an epigenetic factor with a great potential as a biomarker of differentiation in DTC. Understanding its role may provide new insights into tumour dedifferentiation and open new avenues for therapeutic strategies in advanced thyroid carcinomas."

Biomarker • Oncology • Solid Tumor • Thyroid Gland Carcinoma • PPARGC1A

ZUP1 as a Novel Potential Oncogenic Driver and Prognostic Biomarker in Breast Cancer. (PubMed, Comb Chem High Throughput Screen) - "Our findings suggest that ZUP1 is a novel multifaceted biomarker with significant implications for personalized treatment strategies in breast cancer."

Biomarker • Journal • Breast Cancer • Gene Therapies • Hematological Disorders • Oncology • Solid Tumor

Gomekli: Newly added patents in Orange Book (Orange Book) - Expiry on Feb 17, 2041, Mar 16, 2043 and Mar 15, 2044

Patent • Genetic Disorders • Neurofibromatosis

Clinical experience with mirdametinib in the treatment of pediatric low-grade gliomas: a case series (SNO 2026) - No abstract available

Clinical • Brain Cancer • Glioma • Low Grade Glioma • Pediatrics • Solid Tumor

Long-term analysis of mirdametinib treatment in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma (NF1-PN): Updated phase 2b ReNeu trial findings (SNO 2026) - No abstract available

Clinical • P2b data • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

New treatment recommended for inoperable plexiform neurofibromas in children (Doctors.net.uk) - "The National Institute for Health and Care Excellence has recommended that mirdametinib, which is made by Merck Serono and sold under the brand name Ezmekly, be used for tumours caused by NF1. In its final draft guidance, NICE said around 200 patients up to the age of 17 could benefit from using the treatment."

NICE • Neurofibromatosis

Use of mirdametinib for the treatment of neurofibromatosis type 1–associated plexiform neurofibromas (NF1-PN) in patients with prior mitogen-activated protein kinase (MAPK) kinase inhibitor (MEKi) exposure (SNO 2026) - No abstract available

Clinical • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

TEAD inhibitors re-sensitize drug-resistant NF1 MPNST cells to MEK inhibitors. (PubMed, MicroPubl Biol) - "NF1 neurofibromas are treated with MEK inhibitors, such as mirdametinib and selumetinib, because they are driven by activation of the Ras/Raf/MEK/ERK signaling pathway. The cells were resistant to 15 other MEK inhibitors in a high-throughput screen but were re-sensitized by co-treatment with a TEAD inhibitor. These results suggest that TEAD inhibitors synergize with MEK inhibitors to overcome resistance and enhance therapeutic efficacy in MPNSTs."

Journal • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • NF1

SOCS3 deficiency drives the primed to naive pluripotency transition by sustaining STAT3 activation. (PubMed, Front Genet) - "CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) -mediated Socs3 knockout (KO) was generated in mouse EpiSCs, followed by primed-to-naive reprogramming induction in 2i/LIF [LIF (leukemia inhibitory factor), PD0325901 and CHIR99021) culture system...SOCS3 acts as a pivotal inducible barrier to the primed-to-naive pluripotency transition. Eliminating SOCS3-mediated negative regulation to sustain STAT3 activation is an effective strategy to overcome stem cell reprogramming barriers, providing a key target for the precise manipulation of pluripotent stem cell (PSC) fate."

Journal • Hematological Malignancies • Leukemia • Oncology • LIF • SOCS3 • STAT3

Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction. (PubMed, J Clin Transl Hepatol) - "4EBP1A4 enhances Nrf2 ubiquitination and degradation via the HSP90β/Keap1 axis, relieving mTOR-mediated ferroptosis suppression and synergistically improving rapamycin efficacy. Additionally, rapamycin, MLN0128, and PD901 suppress HCC progression by inducing ferroptosis, with their combination showing superior potency."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CDC37 • CTNNB1 • EIF4EBP1 • KEAP1 • MET • RPS6

Comprehensive analysis of POLD2 as a potential biomarker for modulating the immune microenvironment and predicting immunotherapy response in lung adenocarcinoma. (PubMed, J Thorac Dis) - "As an extended exploratory analysis to further explore POLD2's therapeutic potential, molecular docking and MD simulations revealed strong binding interactions between POLD2 and MEK inhibitors, including PD0325901, selumetinib and trametinib. Our results identify POLD2 as a promising prognostic biomarker and a potential therapeutic target in LUAD, with particular relevance to predicting immunotherapy response-consistent with the core focus of this study. This finding not only provides important insights into the mechanisms underlying LUAD progression and treatment resistance but also lays a preliminary foundation for subsequent research on both immunotherapeutic optimization and targeted therapy (via MEK inhibitors) for LUAD."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • POLD1 • POLD2

IMMUNOMEK: Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %. (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Centre Georges Francois Leclerc | Trial completion date: May 2028 ➔ May 2029

Trial completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Human Biopsy-Defined IRI-Selective Reperfusion Signature Prioritizes Reperfusion-Timed MEK Inhibition After DCD Liver Transplantation. (PubMed, Am J Transplant) - "A representative MEK inhibitor, PD-0325901, reduced hepatocyte OGD/R injury and, when administered at reperfusion in a rat DCD liver transplantation model (5-20 mg/kg), attenuated histologic and biochemical injury, apoptosis, and redox-inflammatory readouts and improved 7-day survival. Collectively, this biopsy-anchored ΔΔ interaction-phenotype framework, with cross-cohort concordance as a prespecified robustness gate, nominates reperfusion-timed MEK inhibition as a mechanism- and window-aligned strategy to blunt early post-liver transplant IRI."

Journal • Cardiovascular • Hepatology • Liver Failure • Reperfusion Injury • Transplantation

Unanticipated radiographic response with decreased cerebellar enhancement in patient with NF1 with Mirdametinib (ISPNO 2026) - "This case demonstrates differential responses to two MEK inhibitors in an NF-1-associated cerebellar contrast-enhancing lesion suspected to be a low-grade glioma. Although both selumetinib and mirdametinib are approved for NF1-related PN, mirdametinib led to a marked reduction in enhancement and obviated planned surgical intervention. These findings suggest that a trial of different MEK inhibition may be considered prior to invasive procedures in select NF-1 patients, with continued long-term monitoring of radiographic response."

Clinical • Brain Cancer • Genetic Disorders • Glioma • Low Grade Glioma • Neurofibromatosis • Solid Tumor • NF1

Trametinib in neurofibromatosis type 1-associated plexiform neurofibroma Real data from the SACHA study (ISPNO 2026) - "Trametinib demonstrated efficacy in improving clinical symptoms and stabilizing tumor progression in children with NF-1-associated PNs, though tumor volume reduction was limited. The safety profile was manageable and consistent with prior reports[5]. This study represents the largest real-world cohort of Trametinib-treated pediatric NF-1 patients."

Genetic Disorders • Neurofibromatosis • Solid Tumor

Effectiveness of Mirdametinib in Infants with Low-Grade Glioma (LGG) with BRAF alterations – A Series of 3 Cases. (ISPNO 2026) - "In the short term, mirdametinib was well tolerated by 3 infants. Two showed progressive reduction in tumor volume, and one showed sustained partial response. More longitudinal follow-up and patients are needed to better report the safety and efficacy of mirdametinib in infants."

Clinical • Astrocytoma • Brain Cancer • Glioma • Low Grade Glioma • Pilocytic Astrocytoma • Solid Tumor • BRAF • KIAA1549