MRX34 / Synlogic - LARVOL DELTA

Nanotechnology-enabled miRNA delivery systems next-generation molecular strategies in cancer therapy. (PubMed, Biochem Biophys Res Commun) - "We conclude with a concise roadmap that prioritizes platform selection for near-term translation and integration with tumor-specific miRNA signatures to advance personalized therapy. Our translation-first synthesis links barriers to design solutions (pKa-tuned LNPs; exosome-mimetic/hybrid vesicles) and highlights AI/ML-guided formulation; lessons from MRX34/TargomiRs inform safety, scalability, and CMC-together yielding a practical 24-36-month roadmap toward clinical readiness, with functionalized LNPs best positioned for near-term translation."

Journal • Review • Oncology

Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer. (PubMed, Small) - "However, the clinical translation of miR-34a has been hindered by challenges such as poor stability, inefficient cytoplasmic delivery, and immune-related toxicities, as evidenced by the failure of MRX34 in trials...This dual mechanism promoted macrophage phagocytosis, enhanced CD8+ T-cell activation, and induced apoptosis, resulting in significant tumor inhibition without systemic toxicity. These findings demonstrate the transformative potential of aCD47-C-miR34a in overcoming TNBC's oncogenic and immune-evasive mechanisms, paving the way for innovative treatments in TNBC and other heterogeneous, aggressive cancers."

IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • MIR34A • PD-L1 • PGR

Oligonucleotide-Based Modulation of Macrophage Polarization: Emerging Strategies in Immunotherapy. (PubMed, Immun Inflamm Dis) - "Optimizing delivery platforms, enhancing molecular stability, and rigorous safety profiling are critical. Integration with emerging modalities-such as engineered CAR‑macrophages-will enable precise, disease‑specific interventions, and advance oligonucleotide‑guided macrophage modulation toward clinical translation."

Journal • Review • Infectious Disease • Oncology

MicroRNAs and Long Non-coding RNAs as Novel Targets in Anti-cancer Drug Development. (PubMed, Curr Pharm Biotechnol) - "In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described."

Journal • Oncology

Functional and Clinical Significance of Dysregulated microRNAs in Liver Cancer. (PubMed, Cancers (Basel)) - "Clinical treatment drugs have been developed based on miR-34 and miR-122 (MRX34 and Miravirsen, respectively), but their side effects have not yet been overcome. Future research is needed to address these weaknesses and establish a feasible microRNA-based treatment strategy for liver cancer."

Clinical • Journal • Review • Gastrointestinal Cancer • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Cancer • Oncology • Solid Tumor • MIR122 • MIR21 • MIR214 • MIR34A

MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic. (PubMed, Front Cell Dev Biol) - "We shall briefly discuss potential reasons behind the failure of the first-in-class clinical trial of MRX34, a liposomal miR-34a mimic. Finally, we offer several clinical settings where miR-34a can potentially be deployed to therapeutically target CSCs and advanced, therapy-resistant, and p53-mutant tumors in order to overcome therapy resistance and curb tumor relapse."

Cancer stem cells • IO biomarker • Journal • Review • Oncology • BCL2 • CD44 • MIR34A • MYC • TP53

Down-regulation of target gene expression in human white blood cells (hWBCs) by MRX34, a liposomal miR-34 mimic: Next generation sequencing (NGS) results from a first-in-human trial of microRNA cancer therapy (ESMO 2016) - P1; "This NGS analysis of hWBC samples from patients treated with MRX34 in a first-in-human clinical trial of miRNA cancer therapy showed dosedependent modulation of expression for validated and predicted miR-34a target genes, including key oncogenes. Our work suggests that MRX34 effectively delivers active miR-34a mimics to hWBCs in patients with cancer, and provides a potentially useful method to evaluate biomarkers of response to MRX34 therapy."

Biomarker • Cancer stem cells • Clinical • Tumor microenvironment • Biosimilar • Oncology

Shousha, Naglaa Zayed, Mahmoud N El-Rouby, Ahmed O Kaseb, Ashraf - "...Ahmed O. Kaseb...Veliparib Hydrophobic bile acids, such as deoxycholic acid (DCA), are know to modulate the expression of several apoptosis-related proteins, including c-Jun N-terminal kinase (JNK), leading to cell death. In addition, microRNAs (miRNAs or miRs) are being increasingly implicated in cell death and in the pathogenesis of human liver diseases."

Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. (PubMed, Br J Cancer) - P1 | "MRX34 treatment with dexamethasone premedication demonstrated a manageable toxicity profile in most patients and some clinical activity. Although the trial was closed early due to serious immune-mediated AEs that resulted in four patient deaths, dose-dependent modulation of relevant target genes provides proof-of-concept for miRNA-based cancer therapy."

Clinical • Journal • P1 data

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance. (PubMed, Cells) - "Several EMT inhibitory mechanisms are instrumental in reversing EMT or targeting EMT cells. Currently, these mechanisms are also significant for clinical use."

Journal • Review • CD8 • IL6

Expanding the Biotherapeutics Realm via miR-34a: "Potent Clever Little" Agent in Breast Cancer Therapy. (PubMed, Curr Pharm Biotechnol) - "These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond."

IO Biomarker • Journal

MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. (PubMed, J Exp Clin Cancer Res) - P1; "...Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized...Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected."

Journal • Review