evofosfamide (IMGS-101) / ImmunoGenesis - LARVOL DELTA

Self-amplifying hypoxia cascade in covalent organic framework/metal organic framework nanoreactors for synergistic cancer therapy. (PubMed, J Colloid Interface Sci) - "Hypoxia-activated prodrugs (HAPs) like TH-302 exploit this niche, yet their efficacy is often limited by insufficient hypoxia levels...This coordinated action of chemodynamic therapy, photothermal therapy, PDT, and hypoxia-activated chemotherapy resulted in effective tumor suppression both in vitro and in vivo with minimal systemic toxicity. This work presents a novel strategy for leveraging the TME to achieve self-enhanced synergistic therapy."

Journal • Oncology

A mathematical framework to optimize combination therapy for triple-negative breast cancer in obese mice (SABCS 2025) - "However, obesity-driven intratumoral hypoxia presents additional challenges for treatment, motivating the use of evofosfamide (a hypoxia-activated prodrug) as a therapeutic adjunct...The optimized schedules point to the possibility of achieving significantly better tumor control with less total drug dose, potentially translating into reduced toxicity while preserving benefit. These optimized regimens should be regarded as hypothesis-generating; their safety and therapeutic benefit must be experimentally confirmed."

Combination therapy • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Hypoxia reduction remodels the glioblastoma immune microenvironment to enhance therapeutic sensitivity (SNO 2025) - "Together, these findings establish hypoxia as a central regulator of immune suppression in GBM and validate hypoxia-targeting strategies as powerful adjuncts to immunotherapy. Evofosfamide emerges as a potent immunomodulatory agent capable of reprogramming the GBM TME and unlocking new avenues for therapeutic intervention."

IO biomarker • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD8 • CD80 • GZMB • HAVCR2 • LAG3 • PD-L1

Hypoxia reduction remodels the glioblastoma immune microenvironment to enhance therapeutic sensitivity (SNO 2025) - "Together, these findings establish hypoxia as a central regulator of immune suppression in GBM and validate hypoxia-targeting strategies as powerful adjuncts to immunotherapy. Evofosfamide emerges as a potent immunomodulatory agent capable of reprogramming the GBM TME and unlocking new avenues for therapeutic intervention."

IO biomarker • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD8 • CD80 • GZMB • HAVCR2 • LAG3 • PD-L1

Hypoxia reduction remodels the glioblastoma immune microenvironment to enhance therapeutic sensitivity (WFNOS 2025) - "Together, these findings establish hypoxia as a central regulator of immune suppression in GBM and validate hypoxia-targeting strategies as powerful adjuncts to immunotherapy. Evofosfamide emerges as a potent immunomodulatory agent capable of reprogramming the GBM TME and unlocking new avenues for therapeutic intervention."

IO biomarker • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • CD8 • CD80 • GZMB • HAVCR2 • LAG3 • PD-L1

Hypoxia reduction remodels the glioblastoma immune microenvironment to enhance therapeutic sensitivity (WFNOS 2025) - P2 | "Together, these findings establish hypoxia as a central regulator of immune suppression in GBM and validate hypoxia-targeting strategies as powerful adjuncts to immunotherapy. Evofosfamide emerges as a potent immunomodulatory agent capable of reprogramming the GBM TME and unlocking new avenues for therapeutic intervention."

IO biomarker • Brain Cancer • Glioblastoma • Solid Tumor • CD8 • CD80 • GZMB • HAVCR2 • LAG3 • PD-L1

Development of hypoxia-activated prodrugs of AMPK inhibitors and evaluation in acute myeloid leukemia (AACR-NCI-EORTC 2025) - "Several HAPs have been developed, including Evofosfamide (TH-302) and Tarloxotinib (TH-4000), that utilize a nitroimidazole trigger that can be bioreduced under hypoxic conditions to release the active agent. In addition, we evaluated cellular target engagement in the MOLM-13 cell line by monitoring the phosphorylation of acetyl-CoA carboxylase (ACC) at Ser79 under both normal and hypoxic culture conditions. The development of HAPs of AMPK inhibitors have the potential to selectively sensitize drug resistant LSC to standard of care therapy or eliminate metabolically vulnerable LSCs as a single agent therapy."

Late-breaking abstract • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AMPK

Bimodality imaging as a companion to evaluate antitumour efficacy of TH-302 in experimental chondrosarcoma. (PubMed, EJNMMI Res) - "TH-302 shows an in vivo anti-tumour activity in chondrosarcoma. Our multimodal imaging approach allows monitoring complex exchanges between tumour cells and their neighboring under therapy."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • SLC2A1

Spatiotemporally Ultrasound-Activatable Self-Amplifying Biomimetic Liposomes for Imaging-Guided Synergistic Cancer Sonodynamic Chemotherapy. (PubMed, Nano Lett) - "Herein, we develop a biomimetic liposomal platform (DiR-VT@cmLipo) coencapsulating the sonosensitizer verteporfin (VP) and hypoxia-activated prodrug evofosfamide (TH302), which synergistically inhibits tumor progression via fluorescence imaging-guided ultrasound-activated spatiotemporally selective sonodynamic-chemotherapy. This biomimetic nanoplatform represents an innovative strategy for overcoming microenvironmental limitations in SDT, establishing a paradigm for synergistic tumor microenvironment remodeling and precision-controlled combination therapy. The cascaded self-amplifying activation mechanism and spatiotemporally tumor-selective therapeutic amplification position DiR-VT@cmLipo as a promising candidate for clinical translation in solid tumor management."

Journal • Oncology • Solid Tumor

Multifunctional nanoliposome-loaded hypoxia-activated evofosfamide: improving antitumor activity and ferroptosis in pancreatic adenocarcinoma. (PubMed, Int J Pharm) - "The EFA can be activated by reductase in cancer cell lines under a hypoxic milieu, which diminishes free radicals through the reductase enzyme and disrupts the adjacent biomacromolecules' structure, thereby facilitating the synergistic therapy of chemotherapy and ferroptosis in Panc-1 cells. This study integrates improved ferroptosis with hypoxia-activated chemotherapy to generate an effective and targeted tumoricidal impact, perhaps offering a promising treatment for pancreatic adenocarcinoma (PDAC) in the future."

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Evofosfamide Enhances Sensitivity of Breast Cancer Cells to Apoptosis and Natural-Killer-Cell-Mediated Cytotoxicity Under Hypoxic Conditions. (PubMed, Cancers (Basel)) - "Evofosfamide is converted into bromo-isophosphoramide mustard, a potent DNA cross-linking agent that is expected to enhance the killing of cancer cells under hypoxic conditions, where these cells typically exhibit resistance. qPCR analysis revealed that Evofosfamide was capable of restoring type I interferon signaling in hypoxic breast cancer cells, leading to the subsequent cytolytic activity of NK cells against the tumor cells. Thus, conditioning the breast cancer cells with Evofosfamide resulted in enhanced cell killing under hypoxia, further underscoring its potential as a sensitizer to target hypoxia-driven tumors."

Journal • Breast Cancer • Oncology • Solid Tumor • CASP3 • CASP7

Evofosfamide Enhances Sensitivity of Breast Cancer Cells to Apoptosis and Natural-Killer-Cell-Mediated Cytotoxicity Under Hypoxic Conditions (Multidisciplinary Digital Publishing Institute) - "Evofosfamide enhanced cell killing in both MCF-7 and MDA-MB-231 cells under hypoxic conditions compared to normoxic conditions. Cell killing was accompanied by increased cellular reactive oxygen species (ROS), diminished mitochondrial membrane potential, and induction of apoptosis, as demonstrated by the fragmentation or laddering of genomic DNA, the activation of caspase 3/7, and the cleavage of PARP."

Preclinical • Breast Cancer

TH-302 (evofosfamide) monotherapy exerts anticancer activity in Ewing's sarcoma cells under hypoxia. (PubMed, Clin Transl Oncol) - "These in vitro findings suggest that TH-302 may be efficacious in ES. This provides a rationale for further in vivo investigations into the potential of TH-302 as a treatment for ES."

Journal • Monotherapy • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • CASP3 • CASP7

Amplifying Anti-Tumor Immune Responses via Mitochondria-Targeting Near-Infrared Photodynamic Therapy. (PubMed, Adv Sci (Weinh)) - "Simultaneously, the exacerbated hypoxia induced by PDT activates a TH302 prodrug, resulting in cell cycle arrest in highly proliferative tumor cells...Moreover, the NIR-PDT-induced immune activation markedly improves the immune checkpoint blockade (ICB) therapy efficacy. This strategy offers a robust modality for immune activation in cancer therapy, paving the way for effective treatment of deep-seated tumors and preventing recurrence."

Journal • Liver Cancer • Oncology • Solid Tumor

Neovascular pruning by IDO1 inhibitors can potentiate immunogenic cytotoxicity of ischemia-targeted agents to synergistically enhance anti-PD-1 responsiveness. (PubMed, J Immunother Cancer) - "Improving therapeutic outcomes for patients with lung tumors, arising either as primary lesions or metastatic colonies, is of vital clinical importance. Building on preclinical evidence for IDO1's role in promoting inflammatory neovascularization of lung tumors, this study demonstrates how the intratumoral ischemic stress elicited by IDO1 inhibition can potentiate the immunogenic cytotoxicity of ischemia-targeted agents to effectively leverage immune checkpoint blockade responsiveness to confer a synergistic survival benefit. These findings provide a novel perspective on how IDO1 inhibitors can impact tumor biology and open up new possibilities for therapeutic applications."

IO biomarker • Journal • Breast Cancer • Cardiovascular • Lung Cancer • Oncology • Solid Tumor • IFNG • PERK

Measured intrapatient radiomic variability as a predictor of treatment response in multi-metastatic patients (ESTRO 2025) - P3 | "Material/ A retrospective analysis was conducted on 350 multi-metastatic patients from a Phase III trial (TH CR-406/SARC021, NCT01440088; details in [1]) comparing Doxorubicin Monotherapy with Doxorubicin plus Evofosfamide for advanced soft-tissue sarcoma. MIRV shows promise as a predictive tool for differential treatment response. Integrating MIRV into predictive models may enhance personalized treatment planning across various cancer types, ultimately improving patient outcomes. Our approach is likely disease-agnostic, highlighting the importance of lesion-specific analysis in personalized treatment strategies, with further extensions to other malignancies warranted for future research."

Clinical • Metastases • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Antibacterial compounds against non-growing and intracellular bacteria. (PubMed, NPJ Antimicrob Resist) - "Ten compounds - solithromycin, rifabutin, mitomycin C, and seven fluoroquinolones-have strong bactericidal activity against non-growing P. aeruginosa, killing >4 log10 of bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, and satraplatin are unique in their ability to selectively target non-growing bacteria, exhibiting poor efficacy against growing bacteria. Finally, 31 hit compounds inhibit the growth of intracellular Shigella flexneri in a human enterocyte infection model, indicating their ability to permeate the cytoplasm of host cells. The identified compounds hold potential for treating persistent infections, warranting further comparative studies with current standard-of-care antibiotics."

Journal • Infectious Disease • Oncology

Gemcitabine Plus Docetaxel, Dacarbazine, Doxorubicin Combinations, or Doxorubicin Alone as First-Line Treatment for Advanced/Metastatic Leiomyosarcoma: A Retrospective Analysis at a Sarcoma Center. (PubMed, Diseases) - "These findings reaffirm the efficacy of doxorubicin-based combination regimens as a first-line treatment for locally advanced and metastatic LMS, particularly in non-uterine LMS."

Journal • Retrospective data • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

ImmunoGenesis to Present in Innovation Track of the 2025 NeauxCancer Oncology Conference in New Orleans (PRNewswire) - "ImmunoGenesis...announces its participation in the 2025 NeauxCancer Conference organized by the Cancer Advocacy Group of Louisiana (CAGLA), being held March 27 – 29, 2025 in New Orleans...President and CEO James Barlow will discuss how ImmunoGenesis plans to transform immuno-oncology with its pipeline of products designed to overcome immune resistance. He will provide an update on the active Phase 1a/1b study of their lead compound, IMGS-001, including preliminary data on enrolled subjects....Mr. Barlow will also discuss the recently initiated phase 2 trial for the company's second clinical asset, IMGS-101 (evofosfamide), a hypoxia reversal agent being studied in combination with checkpoint inhibition."

P1 data • Trial status • Solid Tumor

Design, synthesis, and biological evaluation of hypoxic activation prodrug TH-302 derivatives. (PubMed, Bioorg Med Chem Lett) - "The results of CCK-8 assay indicate that the steric hindrance and electronic effects of substituents on N have significant impacts on the activity, while changes in nitro group positions have minimal effects on the activity, and Bromo-phosphoramide mustard exhibits better activity than Chloro-phosphoramide mustard. Compounds 15c and 16d exhibit significantly superior antitumor activity compared to TH-302, with IC50 values of 42 μM and 32 μM for SKOV3 cells, and IC50 values of 47 μM and 41 μM for U87MG cells, respectively."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Ovarian Cancer • Solid Tumor

Temperature-Sensitive Nano-GOx Combined with Downregulation of Tumor Stemness to Initiate Robust Antitumor Efficacy. (PubMed, ACS Nano) - "Ulteriorly, VTNG was obtained by NG coloading with verteporfin (VP) and evofosfamide (TH-302). Notably, VTNG had a significant antitumor effect in melanoma models compared with first-line melanoma therapy and formed an immune memory effect. In conclusion, VTNG provided an effective approach to enhance the therapeutic effect of GOx for tumor treatment."

Journal • Melanoma • Oncology • Solid Tumor

ImmunoGenesis Doses First Patient in Phase 1/2 Clinical Trial of IMGS-101 in Combination With Balstilimab (anti-PD-1) and Zalifrelimab (anti-CTLA-4) in Relapsed or Refractory Advanced Prostate, Pancreatic, and HPV(-) Head & Neck Tumors (PRNewswire) - "ImmunoGenesis...announced the first patient has been dosed in the company's Phase 1/2 clinical trial of its hypoxia reversal agent IMGS-101 (evofosfamide) in combination with Balstilimab (anti-PD-1) and Zalifrelimab (anti-CTLA-4) at The University of Texas MD Anderson Cancer Center in Houston, Texas....The Phase 1/2, open-label, multicenter study (NCT06782555) consists of a dose escalation and expansion portion to evaluate the safety, pharmacokinetics, and anti-tumor activity of IMGS-101 in combination with Balstilimab and Zalifrelimab in adult patients with locally advanced or metastatic castration-resistant prostate cancer (CRPC), pancreatic cancer, and human papillomavirus-(HPV) negative squamous cell carcinoma of the head and neck (SCCHN)."

Trial status • Castration-Resistant Prostate Cancer • Pancreatic Cancer • Squamous Cell Carcinoma of Head and Neck

Coenzyme Q10 as an Inhibitor of Effector Release from One-Electron-Reduced Bioreductive Anticancer Prodrugs. (PubMed, Molecules) - "Evidence is put forward suggesting that radical anions can undergo an electron transfer to ubiquinone (CoQ10, UQ) in competition with the fragmentation of the radical anions releasing effectors. The prior inhibition of the synthesis of UQ in cells is put forward as a possible approach to increase the effectiveness of such prodrugs in killing hypoxic tumor cells."

Journal • Oncology

EVO: Clinical Trial to Test Efficacy of Targeting Hypoxia Combined With ARSI After First-line ARSI Therapy for Castrate Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: University Health Network, Toronto

New P2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab (clinicaltrials.gov) - P1/2 | N=71 | Recruiting | Sponsor: ImmunoGenesis

New P1/2 trial • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck