Supinoxin (RX-5902) / Opus Genetics - LARVOL DELTA

Supinoxin blocks small cell lung cancer progression by inhibiting mitochondrial respiration through DDX5. (PubMed, iScience) - "Finally, we find that Supinoxin inhibits expression of mitochondrial genes and effectively blocks respiration. These studies suggest that Supinoxin functions in anti-tumor progression by reducing cellular energy levels through DDX5."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DDX5

Inhibiting β-catenin in AML by targeting DDX5 (AACR 2023) - "Indeed, concurrent treatment using RX-5902 and Venetoclax, a BCL-2 inhibitor, synergistically induced apoptosis in AML cells. Collectively, therapeutic targeting of DDX5 may be a novel and effective approach in AML and warrants further study."

IO biomarker • Acute Myelogenous Leukemia • Oncology • Solid Tumor • CASP3 • CCND1 • CTNNB1 • DDX5 • MYC

Phase 1 study of RX-5902, a novel orally bioavailable inhibitor of phosphorylated P68, which prevents β-catenin translocation in advanced solid tumors (ESMO 2017) - P1; "Data from this study support that RX-5902 is safe and well-tolerated at the doses and schedules tested. The RP2D of 250 mg of RX-5902 administered daily for 5 consecutive days for 4 weeks is being studied further in metastatic triple negative breast cancer in the Phase 2 portion of this study."

Clinical • P1 data • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Neuroendocrine Tumor • Triple Negative Breast Cancer

Phase 1b/2a study of RX-5902, a novel Orally Bioavailable Inhibitor of Phosphorylated P68, which prevents nuclear _-catenin Translocation in patients with Triple Negative Breast Cancer (ESMO 2018) - P1/2; "Exploratory endpoints include biochemical levels of drug targets. Approximately 40 evaluable subjects will be enrolled in stage 2 of the phase 2."

Clinical • P1/2 data • Triple Negative Breast Cancer

Preliminary report of a phase 1b/2a trial, an oral inhibitor of phosphorylated P68 (P-p68) which mediates -catenin nuclear translocation in advanced triple-negative breast cancer (TNBC). (ASCO 2018) - P1/2; "Preliminary evidence suggests that oral administration of RX-5902 at 250 mg/day appears safe and well tolerated. Early anti-tumor activity was observed in 1 patient. Recruitment to Phase 2 is ongoing."

Melanoma • Triple Negative Breast Cancer

Pharmacokinetic Characterization of Supinoxin and Its Physiologically Based Pharmacokinetic Modeling in Rats. (PubMed, Pharmaceutics) - "Supinoxin was mainly eliminated via NADPH-dependent phase I metabolism (i.e., 58.5% of total clearance), while UDPGA-dependent phase II metabolism appeared negligible in the rat liver microsome. Supinoxin was most abundantly distributed in the adipose tissue, gut, and liver among the nine major tissues studied (i.e., the brain, liver, kidneys, heart, lungs, spleen, gut, muscles, and adipose tissue), and the tissue exposure profiles of supinoxin were well predicted with physiologically based pharmacokinetics."

Journal • PK/PD data • Preclinical • Oncology • DDX5

RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer. (PubMed, BMC Cancer) - " RX-5902 enhanced the efficacy of nivolumab in a humanized, preclinical model of TNBC. Several changes in immunologic profiles were noted in mice treated with RX-5902 and the combination, including an increase in activated TILs and a decrease in human myeloid populations, that are often associated with immunosuppression in a tumor microenvironment. RX-5902 also was shown to potentiate the effects of checkpoint inhibitors of CTLA4 and the PD-1 inhibitor in the 4 T-1 murine TNBC model. These findings indicate that RX-5902 may have important immunomodulatory, as well as anti-tumor activity, in TNBC when combined with a checkpoint inhibitor."

Checkpoint inhibition • Journal • Preclinical • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Transplantation • Triple Negative Breast Cancer

First-in-class phosphorylated-p68 inhibitor RX-5902 inhibits β-catenin signaling and demonstrates anti-tumor activity in triple-negative breast cancer. (PubMed, Mol Cancer Ther) - "Target engagement was confirmed with decreases in nuclear β-catenin and MCL-1 observed, confirming the proposed mechanism of action. This study supports the continued investigation of RX-5902 in TNBC and combinations with immunotherapy."

IO Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

RX-5902 Treatment of Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Rexahn Pharmaceuticals, Inc.; Trial primary completion date: Sep 2016 ➔ Apr 2017

Trial primary completion date • Biosimilar • Oncology

Rexahn to present clinical data at 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P2a, N=72; NCT02030067; "Rexahn Pharmaceuticals...will present two posters with clinical data on RX-5902 and RX-3117 [Preliminary results from an ongoing phase 2a study of RX-3117, an oral nucleoside analogue to treat advanced urothelial cancer (aUC)] at the upcoming 2018 American Society of Clinical Oncology (ASCO) Annual Meeting to be held June 1–5 in Chicago."

Clinical data • P2a data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Rexahn Pharmaceuticals announces presentations at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting (Rexahn Press Release) - "An interim analysis of the first 10 evaluable patients in a Phase 2a trial of RX-5902 in TNBC [NCT02003092] showed five patients exhibited a clinical response including one patient who had an 18% reduction in tumor size and two patients experiencing progression free survival (PFS) greater than 200 days....Updated interim data from a Phase 2a clinical trial of RX-3117 monotherapy for the treatment of advanced bladder cancer [NCT02030067] showed that, of the 24 evaluable patients enrolled into the study, one patient had a complete response (100% tumor reduction) and an additional four patients had tumor reductions of greater than 15%."

P2a data • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Rexahn bails on cancer candidate RX-5902 in triple negative breast cancer (SeekingAlpha) - "Rexahn Pharmaceuticals...discloses that it is terminating its clinical trial collaboration and supply agreement with Merck....related to a Phase 2 study evaluating RX-5902, a small molecule phosphorylated p68 inhibitor, and Keytruda (pembrolizumab) in patients with metastatic triple negative breast cancer."

Licensing / partnership • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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RX-5902 Treatment of Subjects With Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2; N=18; Terminated; Sponsor: Rexahn Pharmaceuticals, Inc.; Active, not recruiting ➔ Terminated

Clinical • Trial termination

RX-5902 Treatment of Subjects With Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2; N=18; Active, not recruiting; Sponsor: Rexahn Pharmaceuticals, Inc.; Trial completion date: Jan 2019 ➔ Nov 2019; Trial primary completion date: Dec 2018 ➔ Oct 2019

Clinical • Trial completion date • Trial primary completion date

RX-5902 exhibits direct and immunomodulatory anti-tumor activities in melanoma PDX models (AACR 2019) - "There was evidence of an immune contribution to the TGI in those tumors derived from subjects who did not benefit from I/O (Nivolumab) therapy. RX-5902 provided greater TGI in the two melanoma PDX models derived from subjects who were resistant to I/O therapy compared to the models from I/O naïve subjects and, regardless, is greater in BRAF WT vs mutant tumors. The RX-5902 immune-mediated anti-tumoral activity may benefit the majority of melanoma subjects with limited response to BRAF-directed and/or I/O therapy."

IO Biomarker • PD(L)-1 Biomarker

The anticancer effects of RX-5902 result from inhibition of phosphorylated p68-mediated β-catenin nuclear translocation (AACR 2019) - "Furthermore, an in vivo study of the MDA-MD-231 xenograft model demonstrated the ability of RX-5902 to inhibit the tumor growth by decreasing p-p68, β-catenin, cyclin D1 and c-myc proteins. Collectively our findings in both in vitro and in vivo studies support the potential therapeutic effect of RX-5902 in multiple cancer indications through the disruption of the phospho-p68/nuclear β-catenin interaction and blocking the nuclear translocation of β-catenin."

Rexahn Announces Multiple Presentations at the 2019 American Association for Cancer Research Annual Meeting (GlobeNewswire, Rexahn Pharmaceuticals) - "Rexahn Pharmaceuticals, Inc...today announced that it will present four scientific posters at the 2019 American Association for Cancer Research (AACR) Annual Meeting, which will be held from March 29 – April 3, 2019 in Atlanta, Georgia."

Biomarker • Clinical • Preclinical

Rexahn Pharmaceuticals Reports 2018 Financial Results (GlobeNewswire, Rexahn Pharmaceuticals) - “RX-5902 – Announced a clinical collaboration with Merck in August 2018 to evaluate RX-5902 in combination with KEYTRUDA® (pembrolizumab) for triple negative breast cancer (TNBC). Rexahn is currently evaluating the development strategy for RX-5902 and may or may not proceed with this trial.”

Trial status

Rexahn announces proposed public offering of common stock and warrants (GlobeNewswire) - "Rexahn intends to use the net proceeds of the offering for further development of its lead clinical programs, including the funding of its clinical development programs for RX-3117 and RX-5902, and for working capital and general corporate purposes."

Financing