roducitabine (PCS3117) / Opus Genetics, BioSense Global, Processa Pharma - LARVOL DELTA

Trifluoromethylation on a Nucleoside Sugar Scaffold: Design and Synthesis of 6'-Trifluoromethylcyclopentenyl-purine and -pyrimidine Nucleosides. (PubMed, Org Lett) - "Based on the promising biological activity of 6'-fluorocyclopentenyl-cytosine and -adenine, we report the design and synthesis of 6'-trifluoromethylcyclopentenyl-pyrimidine and -purine as potential antiviral agents. The introduction of a trifluoromethyl (CF3) group onto a sugar scaffold has been achieved using methyl fluorosulfonyldifluoroacetate (Chen's reagent) as a key step. The resulting trifluoromethylated sugar intermediate provides an efficient pathway for synthesizing various nucleoside analogues, facilitating the expansion of structure-activity relationship studies for neplanocin A analogues."

Journal

Processa Pharmaceuticals Provides Product Pipeline and Financial Update (GlobeNewswire) - "Processa is evaluating the potential of NGC-Gem in patients with pancreatic and other cancers, as well as ways to identify patients who are more likely to respond to NGC-Gem than gemcitabine alone. The Company plans to meet with the FDA in late 2024 or early 2025 to discuss potential trial designs, including implementation of the Project Optimus initiative....The Company is currently evaluating the manufacturing process and potential sites for NGC-Iri. In addition, Processa is defining the potential paths to approval, which include defining the target patient population and the type of cancer, with the expectation to conduct IND-enabling toxicology studies in 2025."

FDA event • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Nucleo(s)tide metabolism as basis for drug development; the Anne Simmonds award lecture. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "This background was fundamental in our studies on how to optimize application of existing drugs (5-fluorouracil [5FU], thiopurines, antifolates such as methotrexate) but also to support development of novel drugs such as gemcitabine, novel antifolates, S-1, TAS-102 and fluorocyclopentenylcytosine. Knowledge of their metabolism helped to design rational combinations such as of gemcitabine with cisplatin, one of the most widely used drug combinations for various cancers. The combination of 5FU with uridine, led to the development of triacetyluridine registered for emergency treatment of patients with lethal 5FU toxicity...The latter actually led to the most interesting results. Investigation of (nucleoside/nucleotide) metabolism remains an exciting field of research."

Journal • Cardiovascular • Infectious Disease • Oncology • Pediatrics • Rheumatology

Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies. (PubMed, Curr HIV Res) - "A drug screening system using Rev-A3R5-GFP reporter cells with pseudoviruses (pNL4-3) is highly efficient. This study provided potential hit compounds for new HIV drug research."

Journal • Human Immunodeficiency Virus • Infectious Disease

RX-3117, an oral hypomethylating agent to treat advanced solid tumors (st): Interim results from an ongoing phase 2a study in advanced urothelial cancer (ESMO 2017) - P1/2; "RX-3117 shows efficacy in various xenograft models, including those of gemcitabine resistant bladder and colorectal cancers. Single agent RX-3117 appears to be safe and well tolerated and shows evidence of preliminary tumor activity. The predefined efficacy criteria was met in Stage 1, and Stage 2 is ongoing. Results from Stage 1 of the phase 2a will be presented."

P2 data • Bladder Cancer • Colorectal Cancer

Activity of RX-3117, an oral antimetabolite nucleoside, in subjects with advanced urothelial cancer: Preliminary results of a phase IIa study. (ASCO-GU 2019) - P1/2; "Twenty subjects had received 3 or more prior therapies; 30 received gemcitabine/cisplatin and 25 received a checkpoint inhibitor. RX-3117 appears to be safe and well-tolerated in chemotherapy and immunotherapy refractory advanced urothelial cancer with acceptable toxicities. Preliminary results show anti-tumor activity in heavily pre-treated patients."

Clinical • P2a data

A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results. (ASCO-GI 2019) - P1/2; "RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing."

Clinical • Combination therapy • P1/2 data • Bladder Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Urothelial Cancer

Activity of RX-3117, an oral antimetabolite nucleoside, in patients with pancreatic cancer: Preliminary results of stage 1 of the phase 1a/2b. (ASCO-GI 2017) - P1/2; "RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled."

P1/2 data • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Activity of RX-3117, an oral antimetabolite nucleoside, in subjects with metastatic bladder cancer resistant to gemcitabine: Preliminary results of a phase Ia/IIb study. (ASCO 2017) - P1/2; "RX-3117 demonstrated an excellent safety profile, and prolonged stable disease was seen in 1 subject who failed prior cisplatin/gemcitabine and FGFR3 inhibition. Activity persisted despite development a putative resistance alteration detected by ctDNA."

P1/2 data • Biosimilar • Bladder Cancer • Colorectal Cancer

The Metabolic and Non-Metabolic Roles of UCK2 in Tumor Progression. (PubMed, Front Oncol) - "By harnessing the catalytic activity of UCK2, several cytotoxic ribonucleoside analogs, such as TAS-106 and RX-3117, have been developed for UCK2-mediated cancer chemotherapy. These findings suggest that UCK2 may serve as a potential therapeutic target for cancer treatment. In this mini-review, we introduced the genomic localization and protein structure of UCK2, described the role of UCK2 in tumor development, discussed the application of UCK2 in anti-tumor treatment, and proposed concurrent targeting of the catalytic and non-catalytic roles of UCK2 as a potential therapeutic strategy for cancer treatment."

Journal • Review • Developmental Disorders • Hematological Malignancies • Lung Cancer • Oncology • Solid Tumor • EGFR

A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma. (PubMed, Invest New Drugs) - "All patients experienced a treatment emergent adverse event (TEAE) with the most common diarrhea, nausea, and fatigue.10.9% of patients experienced a serious adverse event (SAE) related to the combination. Conclusion RX-3117 plus nab-Pac in newly diagnosed met-PC patients demonstrated tolerability, safety, and early treatment efficacy."

Clinical • Journal • P1/2 data • PK/PD data • Fatigue • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Preliminary results from an ongoing phase 2a study of RX-3117, an oral nucleoside analogue to treat advanced urothelial cancer (aUC). (ASCO 2018) - P1/2; "RX-3117 shows efficacy in various xenograft models, including those of gemcitabine resistant bladder cancer. RX3117 is safe and well tolerated and shows preliminary evidence of anti-tumor activity in heavily pretreated patients. The study continues to enroll subjects with aUC in Stage 2."

P2a data • Bladder Cancer

Activity of RX-3117, an oral antimetabolite nucleoside, in subjects with advanced urothelial cancer: Preliminary results of a phase IIa study. (ASCO-GU 2019) - P1/2; "Twenty subjects had received 3 or more prior therapies; 30 received gemcitabine/cisplatin and 25 received a checkpoint inhibitor. RX-3117 appears to be safe and well-tolerated in chemotherapy and immunotherapy refractory advanced urothelial cancer with acceptable toxicities. Preliminary results show anti-tumor activity in heavily pre-treated patients."

Clinical • P2a data

RX‐3117, an oral hypomethylating agent to treat advanced solid tumors: Interim results from an ongoing phase 2a study in advanced urothelial cancer (aUC). (ASCO-GU 2018) - P1/2; "RX-3117 shows efficacy in various xenograft models, including those of gemcitabine resistant bladder cancer. RX-3117 is safe and well tolerable and shows preliminary evidence of anti-tumor activity. The study continues to enroll patients with aUC in Stage 2."

P2a data • Bladder Cancer • Lung Cancer

RX­3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer—Preliminary results of stage II of the phase Ia/IIb study. (ASCO-GI 2018) - P1/2; "RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started."

Clinical • Bladder Cancer • Colorectal Cancer • Pancreatic Cancer

A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results. (ASCO-GI 2019) - P1/2; "RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing."

Clinical • Combination therapy • P1/2 data

PROCESSA PHARMACEUTICALS ENTERS INTO A LICENSING AGREEMENT WITH OCUPHIRE PHARMA, INC., FOR THE DEVELOPMENT OF RX-3117 (GlobeNewswire) - "Processa Pharmaceuticals, Inc...announced today that it has entered into a licensing agreement with Ocuphire Pharma, Inc...to license in RX-3117...Rx-3117 has a family of patents extending into 2036 as well as U.S. Food and Drug Administration (FDA) Orphan Designation for the treatment of Pancreatic Cancer. Processa will evaluate the potential benefit of RX-3117 for patients with such cancers as pancreatic or non-small cell lung cancer...Prior to conducting a pivotal trial, Processa will first conduct a Phase 2b trial in 2022 to assess the correlation of the biomarker measurements with the clinical benefit-risk of RX-3117 in patients with pancreatic cancer or non-small cell lung cancer."

Licensing / partnership • New P2b trial • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

RX-3117 promotes epigenetic effects in cancer cells through enhanced degradation of DNMT1 (AACR 2018) - "RX-3117 is a novel, investigational, oral, small molecule nucleoside compound that shows promising antitumor activity in xenografts including patient-derived xenografts resistant to gemcitabine...Incubation of A549 and SUIT-028 cells with 80 nM of the specific proteasome inhibitor bortezomib prevented RX-3117 mediated degradation of DNMT1 (at 24 and 24 hr exposure to 1 M RX-3117)...With confocal microscopy it was demonstrated that DNMT1 and the proteasome co-localized and translocated to the cytosol of A549 and SUIT-028 cells treated for 48 hours with 1 M RX-3117. With molecular modelling using QM and MD, changes in nucleophilicity of C4-C5 double bound were observed indicating that DNMT1 would initiate methyl transfer but cannot proceed.In summary we conclude that RX-3117 induces epigenetic changes in cancer cells by trapping DNMT1 in the nucleus followed by translocation of the protein to the proteasome for degradation."

IO Biomarker • Bladder Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Targeting SARS-CoV-2 Nsp12/Nsp8 interaction interface with approved and investigational drugs: an in silico structure-based approach. (PubMed, J Biomol Struct Dyn) - "RX-3117 (fluorocyclopentenyl cytosine) and Nebivolol had the highest binding affinities in both mutant and wild-type enzymes, therefore they were selected and resultant protein-ligand complexes were simulated for analysis of stability over 100 ns. Interruption of viral replication by drugs proposed in this study should be further tested to pave the way for in vivo studies towards the treatment of COVID-19. Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease

Rexahn: Corporate Factsheet (Rexahn Pharmaceuticals, Inc) - Anticipated completion of enrollment in P1 trial for solid tumors in Q1 2015

Anticipated enrollment status • Oncology

A novel small molecule cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to treatment with gemcitabine (AACR 2014) - Presentation time: Sunday, Apr 06, 2014, 1:00 PM - 5:00 PM; Abstract #819; "Not only has RX-3117 demonstrated potent efficacy in several cancer xenograft models but also oral treatment with RX-3117 results in dose-dependent tumor growth inhibition (TGI), even in tumors that are only moderately sensitive or resistant to gemcitabine."

Preclinical • Oncology

Rexahn: Rodman & Renshaw Global Investment Conference (Rexahn Pharmaceuticals, Inc, Rodman and Renshaw 18th Annual Global Investment Conference 2016) - Anticipated presentation of P1b/P2a trial (NCT02030067) in stage 1 pancreatic cancer at ESMO (Oct 7-11, 2016)

Anticipated P1/2 data • Oncology

Rexahn: Rodman & Renshaw Global Investment Conference (Rexahn Pharmaceuticals, Inc, Rodman and Renshaw 18th Annual Global Investment Conference 2016) - Anticipated presentation of P1b/P2a trial (NCT02030067) in stage 1 pancreatic cancer at ESMO (Oct 7-11, 2016)

Anticipated P1/2 data • Oncology

"Proud of @manuelmaiamd presenting RX3117 data in mUC at #ESMO17! Really nice work!" (@montypal)

Biosimilar • Oncology

Rexahn: Rodman & Renshaw Global Investment Conference (Rexahn Pharmaceuticals, Inc) - Anticipated initiation of proof-of-concept trial for cancer in 2016

Anticipated new trial • Oncology