Olita (olmutinib) / Hanmi - LARVOL DELTA

Leveraging a novel, multi-modal platform to identify drug resistant clones with distinct mechanisms of resistance to EGFR inhibitors (SITC 2025) - "Tens of thousands of single lung cancer A549 cells were within semi-permeable hydrogel compartments called CellCage™ Enclosures (CCEs) and treated with EGFR inhibitors (Olmutinib) or antibody drug conjugate (Cetuximab-MMAE) (figure 1). This enables the generation of highly parallel, integrated single-CCE datasets.Abstract 178 Figure 2Request permissionsNovel cellular phenotypes were identified within drug-resistant clones using Cellanome's technology. Representative images of non-treated controls and distinct cellular phenotypes within drug-resistant clones"

Lung Cancer • Oncology • Solid Tumor • ABCC1 • ABCC2 • ABCC3 • ANXA5

Effect of ponatinib on the metabolism of cariprazine in vitro and in vivo and the underlying mechanism. (PubMed, Toxicol Appl Pharmacol) - "The objective of the present study was to examine the inhibitory impacts of three antitumor drugs (olmutinib, napabucasin and ponatinib) on the metabolism of cariprazine, and the molecular docking of cariprazine and ponatinib in relation to CYP3A4 was also evaluated. Molecular docking studies had demonstrated that both cariprazine and ponatinib could engage in hydrophobic interactions with residue PHE-304 on CYP3A4. Consequently, when ponatinib is employed in conjunction with cariprazine in a clinical setting, it is imperative to assess the efficacy and adverse effects, and adjust the dosage to attain the optimal efficacy."

Journal • Preclinical • CNS Disorders • Mental Retardation • Oncology • Psychiatry • Schizophrenia • CYP3A4

Thienopyrimidine: A promising scaffold in the development of kinase inhibitors with anticancer activities. (PubMed, Bioorg Med Chem) - "Some of these thienopyrimidines as anticancer kinase inhibitors have already been marketed or are currently undergoing clinical/preclinical studies for the treatment of cancers, such as Olmutinib, Pictilisib, SNS-314, PF-03758309, and Fimepinostat, highlighting the substantial advantages of the thienopyrimidine scaffold in the discovery of anticancer agents. This article reviews the discovery, activity, and structure-activity relationships of antitumor kinase inhibitors based on the thienopyrimidine scaffold, and partially discusses the binding modes between thienopyrimidine derivatives and their kinase targets. By elucidating the application of thienopyrimidine derivatives as anticancer kinase inhibitors, this review aims to provide new perspectives for the development of more effective and novel kinase inhibitors."

Journal • Review • Oncology

68Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe. (PubMed, Bioorg Chem) - "Additionally, PET/CT imaging with 68Ga-DOTA-Olmutinib showed significant tumor uptake at 60 min with 4 % ID/g post-injection, marking a breakthrough, though the uptake is not yet ideal. Overall, our results suggest that 68Ga-labeled Olmutinib holds promise as a potential PET tracer for detecting EGFR-positive cancers."

Journal • Oncology • EGFR

Design, synthesis and bioevaluation of dual EGFR-PI3Kα inhibitors for potential treatment of NSCLC. (PubMed, Bioorg Chem) - "A series of dual EGFR/PI3Kα inhibitors was synthesized using pharmacophore hybridization of the third-generation EGFR inhibitor olmutinib and the PI3Kα selective inhibitor TAK-117. Compound 30k exhibited a significant antiproliferative effect in NCI-H1975 cells with a higher selectivity profile than olmutinib. The potential antitumor mechanism, molecular binding modes, and in vitro metabolic stability of compound 30k were also clarified."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PIK3CA

Synthesis and in vitro antitumor evaluation of new thieno[2,3-d]pyrimidine derivatives as EGFR and DHFR inhibitors. (PubMed, Bioorg Chem) - "Compounds 6e, 7a, 7b, 7d, 10c and 10e displayed the highest antitumor activity against all tested cell lines compared to Doxorubicin. Docking results of compounds 6e and 10e into the pocket of EGFR active site showed their similar main binding features with Olmutinib, while compounds 7d and 10e showed only moderate fitting into DHFR compared to methotrexate. In silico studies revealed that most of the tested compounds obeyed Lipinski's RO5 and showed positive drug likeness scores."

Journal • Preclinical • Colorectal Cancer • Oncology • DHFR • EGFR

Olmutinib Reverses Thioacetamide-Induced Cell Cycle Gene Alterations in Mice Liver and Kidney Tissues, While Wheat Germ Treatment Exhibits Limited Efficacy at Gene Level. (PubMed, Medicina (Kaunas)) - " It was predicted that the increased expression of the MKi67 gene by TAA leads to the increase in TP53, which negatively regulates the cell cycle via increased CDKN3 expression in kidneys and the restoration of TP53 levels in the liver. These findings contribute to our understanding of the effects of olmutinib and WGO on TAA-induced gene expression changes and highlight their contrasting effects based on cell cycle alterations."

Journal • Preclinical • Hepatology • Liver Failure • Renal Disease • CDK3 • CDKN3 • MKI67 • TP53

Synthesis and initial in vitro evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer. (PubMed, Bioimpacts) - "The binding energy of OTB and I-OTB in complex with EGFR T790M are -8.7 and -7.9 kcal/mol, respectively. The cytotoxicity assay showed that I-OTB also has an affinity towards the EGFR L858R/T790M mutation with the IC50 10.49 ± 5.64"

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes. (PubMed, Medicina (Kaunas)) - "Molecular docking indicated strong binding of poziotinib and olmutinib to extrinsic and intrinsic apoptotic pathway markers, with binding energies of -9.4 kcal/mol and -8.5 kcal/mol, respectively, on interacting with STK-11. Combining poziotinib and olmutinib therapies may significantly improve drug tolerance and conquer drug resistance more effectively than using them individually in lung cancer patients, as suggested by this study's mechanisms."

IO biomarker • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BAX • BCL2 • EGFR • HER-2 • MIR7 • STK11

The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone. (PubMed, Biomed Pharmacother) - "When co-administration of lurasidone with olmutinib in rats, the AUC and AUC of lurasidone were significantly increased by 73.52 % and 69.68 %, respectively, while CL was observably decreased by 43.83 %. In conclusion, CYP3A4 genetic polymorphism and olmutinib can remarkably affect the metabolism of lurasidone."

Journal • Oncology • CYP3A4

Learning from COVID-19: How drug hunters can prepare for the next pandemic. (PubMed, Drug Discov Today) - "During this time, our very small company was able to contribute to antiviral drug discovery efforts through global collaborations with other researchers, which enabled the identification and repurposing of multiple molecules with activity against SARS-CoV-2 including pyronaridine tetraphosphate, tilorone, quinacrine, vandetanib, lumefantrine, cetylpyridinium chloride, raloxifene, carvedilol, olmutinib, dacomitinib, crizotinib, and bosutinib. Teaser: Through global collaborations, a very small company was able to identify computationally and experimentally numerous small molecules with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approaches may be instructive for future antiviral drug discovery efforts."

Journal • Ebola Virus Disease • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Discovery of PL and M Inhibitors for SARS-CoV-2. (PubMed, ACS Omega) - "There are very few small-molecule antivirals for SARS-CoV-2 that are either currently approved (or emergency authorized) in the US or globally, including remdesivir, molnupiravir, and paxlovid...A second inhibitor of PL was the selective estrogen receptor modulator raloxifene (IC = 3.28 ± 0.29 μM for PL and IC = 42.8 ± 6.7 μM for M). We additionally tested several kinase inhibitors and identified olmutinib (IC = 0.54 ± 0.04 μM), bosutinib (IC = 4.23 ± 0.28 μM), crizotinib (IC = 3.81 ± 0.04 μM), and dacominitinib (IC = IC 3.33 ± 0.06 μM) as PL inhibitors for the first time...The results suggest that approved drugs can be identified with promising activity against these proteases, and in several cases we or others have validated their antiviral activity. The additional identification of known kinase inhibitors as molecules targeting PL may provide new repurposing opportunities or starting points for chemical optimization."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An integrated transomics approach reveals significant differences between EGFR inhibitors with the potential to identify novel targets to overcome EGFR resistance (AACR 2023) - "Approved drugs included erlotinib, afatinib (first- and second-generation EGFRi, respectively), and osimertinib (third-generation drug that can overcome the T790M gatekeeper mutation that confers resistance to earlier drugs). The remaining drugs (maverlertinib, naquotinib, olmutinib, rociletinib) are unapproved third-generation inhibitors...Transomic analysis of EGFRi has the potential to identify important differences between successful drugs, drugs that failed in clinical development, and to identify non-EGFR targets that may overcome resistance to current drugs. This hypothesis is currently being investigated across various resistant and undruggable cancers to unlock novel therapeutic targets."

Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A global phase II study of olmutinib (HM61713) in patients with T790M-positive NSCLC after failure of first-line EGFR-TKI (ESMO Asia 2017) - "Olmutinib showed modest activity with tolerable safety profile in patients with T790M+ NSCLC who had previously received an EGFR TKI. Optimal dose of olmutinib is being determined by additional translational studies, to produce more improved therapeutic outcome in phase III clinical trials."

Clinical • P2 data • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Integrating computational, in vitro and in vivo approaches for SARS-CoV-2 drug discovery (ACS-Fall 2022) - "It was not until later in the year when we were able to test in mammalian cells lines such as A549-ACE2 that we demonstrated these compounds had similar nM activity as remdesivir...We also identified bosutinib, crizotinib and olmutinib with activity against PLpro and vandetanib with in vitro activity against SARS-CoV-2...Perhaps our biggest accomplishment was to encourage a South Korean pharmaceutical company to undertake a clinical trial with Pyramax (pyronaridine and artesunate), which is now in Phase III trials. There are still challenges for the future such as the need to find treatments for the millions affected by long COVID which is not addressed by any existing treatments and may require further collaborations. 2 years on and we are ready to address the next pandemic virus with our collaborator network and integrated approaches."

Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL10 • IL6 • TNFA

Evaluation of the Effect of Wheat Germ Oil and Olmutinib on the Thioacetamide-Induced Liver and Kidney Toxicity in Mice. (PubMed, Life (Basel)) - "At the same time, WGO efficiently alleviated TAA and TAA-olmutinib toxicity in Groups IV and V. The histological studies also showed reduced damage with WGO in the animal model. Hence, it was concluded that WGO could significantly reduce liver and kidney damage caused by TAA and olmutinib in mice."

Journal • Preclinical • Hepatology • Renal Disease • IL1B • IL6

Beyond osimertinib: The development of 3-generation EGFR Tyrosine Kinase Inhibitors. (PubMed, J Thorac Oncol) - P3 | "In this review, we profiled many of the third-generation EGFR TKIs in late stage clinical development (e.g. almonertinib, lazertinib, alflutinib, rezivertinib, ASK120069, SH-1028, D-0316 and abivertinib) of their interim results of phase 1-3 trials and their chemical structures when publicly available. Additionally, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, maverlertinib) including phase 3 results of rociletinib and naquotinib. We further profiled the next-generation combination clinical trial design of third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704) and ACROSS2 (NCT04500717)."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study. (PubMed, Cancer) - "Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non-small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy."

Clinical • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Elucidation of the interaction mechanism of olmutinib with human α-1 acid glycoprotein: insights from spectroscopic and molecular modeling studies. (PubMed, J Biomol Struct Dyn) - "The data also proved that olmutinib preferably bound to the hydrophobic cavity of HAG and the binding distance between the two was 2.21 nm. In addition, it can be found that the presence of some metal ions such as Zn, Ca, Ni and Cu would exert a certain extent effect on the olmutinib-HAG complexation process.Communicated by Ramaswamy H. Sarma."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and Interactions into EGFR. (PubMed, Molecules) - "The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs."

Journal • EGFR

Spectroscopic, molecular docking and dynamic simulation studies of binding between the new anticancer agent olmutinib and human serum albumin. (PubMed, J Biomol Struct Dyn) - "OMB binds to HSA at site I (IIA). Electrostatic forces and H-bonding were the main binding forces of main bonding between HSA and OMB as revealed by docking and thermodynamic results.Communicated by Ramaswamy H. Sarma."

Journal • Oncology

Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer (Review). (PubMed, Int J Oncol) - "Other 3rd‑generation EGFR‑TKIs, such as abivertinib, rociletinib, nazartinib, olmutinib and alflutinib, are also at various stages of development. The mechanisms of acquired resistance mainly include an altered EGFR signaling pathway (EGFR tertiary mutations and amplification), activation of aberrant bypassing pathways (hepatocyte growth factor receptor amplification, human epidermal growth factor receptor 2 amplification and aberrant insulin‑like growth factor 1 receptor activation), downstream pathway activation (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) and histological/phenotypic transformations (SCLC transformation and epithelial‑mesenchymal transition). The combination of targeted therapies is a promising strategy to treat osimertinib‑resistant patients, and multiple clinical studies on novel combined therapies are ongoing."

Journal • Review • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2 • MET

Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety. (PubMed, Molecules) - "Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents."

Journal • Oncology • EGFR

Antineoplastic kinase inhibitors: A new class of potent anti-amoebic compounds. (PubMed, PLoS Negl Trop Dis) - "This resulted in the identification of dasatinib, bosutinib, and ibrutinib as amoebicidal agents at low-micromolar concentrations...Testing of these additional twelve drugs led to the identification of ponatinib, neratinib, and olmutinib were identified as highly potent, with EC50 values in the sub-micromolar range...Ibrutinib thus possesses both amoebicidal and cysticidal properties, in contrast to all drugs used in the current therapeutic strategy. These findings together reveal antineoplastic kinase inhibitors as a highly promising class of potent drugs against this widespread and devastating disease."

Journal • Oncology

Phase II Trial of HM61713 for the Treatment of ≥2nd Line T790M Mutation Positive Adenocarcinoma of the Lung (clinicaltrials.gov) - P2; N=162; Terminated; Sponsor: Hanmi Pharmaceutical Company Limited; Trial completion date: Aug 2020 ➔ Dec 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Aug 2020 ➔ Dec 2020; Study termination by the Sponsor

Clinical • Trial completion date • Trial primary completion date • Trial termination • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR