September 22-23, 2015, New York, NY. Third Annual CHI Discovery on Target – Targeting the Ubiquitin Proteasome System: Exploring the Therapeutic Potential of Ubiquitin Ligases and Deubiquitinases (DUBs). Although the ubiquitin pathway remains a highly attractive source of new medicines for a variety of diseases, progress to the clinic for all ubiquitin-based experimental therapies except proteasome inhibitors has been slow. Dr. Tauseef Butt, CEO of Progenra, described the company’s recent progress in developing selective inhibitors of ubiquitin pathway enzymes (E3 ligases, which conjugate ubiquitin to target proteins, and deubiquitylases, which de-conjugate ubiquitin). Focusing on USP7, an oncogenic protein that sustains tumor growth by a variety of molecular mechanisms, Dr. Butt described studies showing that Progenra’s novel inhibitors of this enzyme exert direct antitumor activity in a number of p53-positive and p53-negative animal models and, equally important, block cancer growth in immunocompetent mice by impairing the host animals’ regulatory T cell functions, thereby allowing effector T cells to eradicate implanted tumors. He presented evidence laying out the molecular mechanisms of these inhibitors in various cellular and in vivo settings. Progenra is developing these USP7 inhibitors as single agents or for combination treatments with established cancer immunotherapies to achieve durable clinical responses.
September 16-19, 2015, New York, NY. CRI-CIMT-EATI-AACR - The Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival. The field of immune-oncology has exploded in the past year with the FDA approval of Opdivo and Keytruda, new drugs which harness the cancer patient’s immune cells to fight the disease. Various combinations with these approved drugs and other biologicals are now being sought to improve patient coverage and efficacy, and to lower treatment costs. Dr. Suresh Kumar, head of drug discovery at Progenra, presented data from a collaboration between Progenra and Dr. Wayne Hancock, Children’s Hospital, Perelman School of Medicine (University of Pennsylvania) demonstrating the ability of Progenra’s irreversible and selective small molecule inhibitors of the de-ubiquitylating enzyme USP7 to kill tumors by both inducing apoptosis, or programmed cell death, and blocking the ability of tumors to evade surveillance and killing by the patient’s own immune system. Dr. Kumar’s poster focused on cellular biomarker and mechanism studies confirming that the experimental USP7 inhibitors from Progenra act through the predicted apoptotic and immune-stimulatory routes. Progenra is currently developing selected, chemically optimized USP7 inhibitors for treatment of cancer.
August 2-7, 2015. New London, NH. Gordon Research Conference: Recent Advances in Drug Discovery: Pathways, Targets and Molecules. Inhibitors of the oncogenic deubiquitylating enzyme USP7 can exert antitumor activity by 1) inducing apoptosis via the tumor suppressor p53 and p53-independent mechanisms; and 2) promoting T cell mediated tumor cell killing. Progenra medicinal chemists Dr. Joseph Weinstock and Dr. Jian Wu presented a talk and poster, respectively, describing the synthesis and anticancer mechanisms of novel Progenra compounds that bind selectively to USP7 leading to irreversible inhibition of the enzyme. In in vivo biomarker and efficacy studies the compounds behaved as predicted in immunocompetent and immunocompromised animals, and initial results suggested that the USP7 inhibitors can augment the antitumor efficacy of vaccines. Progenra is currently completing chemical optimization and initiating candidate selection for development of USP7 inhibitors as anticancer agents.
Progenra is chairing a Ubiquitin Symposium on “The Latest on Ubiquitin Pathway and Neurodegeneration Disease” This symposium brings together leaders in ubiquitin pathway research applied to translational medicine and drug discovery in neuroscience. The ubiquitin pathway, which governs the half-life, activity, and cell localization of most proteins, has emerged as an important means of controlling both normal brain function and dysregulated function manifested in disorders such as Alzheimer's disease, Parkinson's disease, polyQ disease, synaptic impairment, and neuroinflammation. Researchers who have defined these roles for ubiquitin will evaluate them in terms of their therapeutic potential in neuronal disease.
Progenra, Inc. announced today that Dr. Wayne Hanock, Professor of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine has joined their Scientific Advisory Board. Dr. Hancock is a world-renowned expert in immunology, inflammation, and mechanisms of disease pathologies, and his addition to the board will add strength to Progenra's immuno-oncology drug development program. He has served as an expert consultant and collaborator and in these capacities has helped to expand Progenra's compound pipeline. As an advisor, Dr. Hancock will guide Progenra's immuno-oncology program and help to commercialize novel medicines targeting ubiquitin related enzymes.
March 25, 2014 Progenra receives patent on novel anti-cancer compound
Progenra, Inc. has been awarded a composition of matter patent covering their first series of small molecule USP7 inhibitors. The highly conserved ubiquitin pathway plays an important role in the regulation of cellular activity and prior work by Progenra and others identified the deubiquitylating enzyme USP7 as a key regulator of this pathway. Dysregulated USP7 activity has been implicated in cancer, inflammation and other diseases. The issued patent, entitled "Anti-neoplastic compounds, compositions and methods" (US 8,680,139), covers the small molecule USP7 inhibitor P0005091 and related structures.
Researchers at Progenra, Inc. announce the advanced online publication of the article “Selective Dual Inhibitors of the Cancer-related Deubiquitylating Proteases USP7 and USP47” (Weinstock, J. et al, ACS Medicinal Chemistry Letters).
September 17, 2012 New Study Demonstrating Progenra’s Novel Anti-Tumor Compound Overcome VELCADE®(bortezomib) Resistant Multiple Myeloma Cells
Researchers at the Dana Farber Cancer Institute and Progenra, Inc. announce the publication of a research article entitled “A Small Molecule Inhibitor of Ubiquitin-Specific Protease-7 Induces Apoptosis in Multiple Myeloma Cells and Overcomes Bortezomib Resistance” (Chauhan et al, Cancer Cell).
November 27, 2011, New Study Demonstrating the Intracellular Selectivity of Progenra’s Novel Anti-Tumor Compound
Researchers at the University of Oxford and Progenra, Inc. are pleased to announce the publication of a research article entitled “Activity-Based Chemical Proteomics Accelerates Inhibitor Development for Deubiquitylating Enzymes” (Altun et al, Chemistry & Biology, Volume 18, Issue 11, 1401-1412, 23 November 2011) that details a novel proteomics based method to detect inhibition of intracellular deubiquitylating enzymes (DUBs).
October 14, 2011, Progenra and Tokyo Medical University Form Rheumatoid Arthritis Research Collaboration
Progenra, Inc. announced today it has entered in to a research collaboration with Dr. Toshihiro Nakajima, Professor, Institute of Medical Science, Tokyo Medical University. Professor Nakajima discovered the Rheumatoid Arthritis (RA) biomarker and therapeutic target Synoviolin/Hrd1, a ubiquitin E3 ligase overexpressed in RA patients. Under the collaboration, Progenra will work with Professor Nakajima to bring existing inhibitors to market and to utilize Progenra’s UbiPro™ Drug Discovery Platform to identify additional inhibitors.
October 11, 2011, Progenra, Inc. and Ono Pharmaceutical Co., Ltd. Enter into Research Collaboration.
Progenra, Inc. announced today that it has entered into a research collaboration with Ono Pharmaceutical Co., Ltd. Under the agreement, Progenra will collaborate with Ono to conduct assay development and high throughput screening by using Progenra’s proprietary technology on multiple targets in the ubiquitin pathway. Terms of the agreement were not disclosed.
August 8, 2011, Progenra Announces the Availability of its UbiProTM Drug Discovery Platform for Licensing
Progenra, Inc., announced today that their UbiPro™ Drug Discovery Platform is available for licensing to partners interested in discovering drugs that modify the ubiquitin-proteasome pathway. The UbiPro™ Drug Discovery Platform encompasses all of Progenra’s current and future proprietary technology discoveries used for identifying novel modulators of deubiquitylase and E3 ubiquitin ligases.
December 6th, 2010, Progenra announces the publication of a paper in Assay and Drug Development Technologies expanding the CHOP reporter platform family. The new publication by Tian et al entitled "Characterization of Selective Ubiquitin and Ubiquitin-Like Protease Inhibitors Using a Fluorescence-based Multiplex Assay Format" decribles two novel CHOP reporters, Ubl-Enterokinase (CHOP2) and Ubl-Granzyme-B (CHOP3). Furthermore, the combination of multiple CHOP reporters in the same well in a multiplex format is decribed.
September 23rd, 2010, Progenra announces the publication of a manuscript describing its proprietary E3 ligase screening platform. Progenra Inc, is pleased to announce the publication of an article by Jeffrey Marblestone et al. entitled "Novel Approach for Characterizing Ubiquitin E3 Ligase Function" in the Journal of Biomolecular Screening describing the development of a novel high throughput compliant E3 ligase assay platform based on ubiquitin binding domains.
August 30th, 2010, Progenra announces its sponsorship of the third annual Philadelphia Ubiquitin Drug Discovery and Diagnostics Conference, June 20-22nd, 2011. Progenra Inc announced it will continue its sponsorship of the recently inaugurated conference series that uniquely brings together researchers and business experts from the pharmaceutical industry and academic sectors to report on recent progress in developing drugs and diagnostic/prognostic technologies based on the ubiquitin pathway. Ubiquitin Drug Discovery and Diagnostics 2011 will be held June 20-22, 2011 in Philadelphia.
July 26th, 2010, Progenra announced today their receipt of an Official Notice of Allowance, dated June 15th, 2010 of U.S. Patent Application No. 11/156,707, "Diagnostic and Screening Methods and Kits Associated with Proteolytic Activity". Click here to read more.
October 10th, 2009. Dr. Dharminder Chauhan (Dana Farber Cancer Institute, Boston, MA) presented exciting new data on the activity of Progenra's USP7 inhibitor, P5091 against cell based and in vivo models of multiple myeloma at the 51st ASH Annual Meeting and Exposition. Dr. Chauhan's oral presentation entitled "Deubiquitylating Enzyme USP-7, a Novel Therapeutic Target in Multiple Myeloma" will be presented in the Myeloma - pathophysiology and preclinical studies excluding therapy: targeting intracellular proteolysis and the cell surface session at 3:30pm on Monday December 7th, 2009.
October 6th, 2009, Progenra announces sponsorship of the second annual Ubiquitin conference, October 4th, 5th, and 6th, 2010. Progenra Inc is one of the sponsors of the second conference series focused on ubiquitin, ubiquitin-like proteins, and drug discovery (Ubiquitin Drug Discovery and Diagnostics 2010), to be held in Philadelphia in October, 2010.
July 6th, 2009. Progenra licenses UBL-CHOP reporter assay platform (formerly known as IsoPRO) to LifeSensors, Inc. Progenra's proprietary Ub-CHOP deubiquitylation assay is unique in that deubiquitylation liberates a reporter enzyme. Upon liberation, the reporter enzyme acts on its substrate, designed to yield a fluorescent product. Progenra has licensed the CHOP reporter technology to LifeSensors, Inc. Attachment of different reporters to the C-terminus of ubiquitin enables Progenra's technology to mimic most closely the physiological ubiquitylated DUB substrates. This feature of Progenra's platform is single-handedly responsible for the discovery of novel and selective molecules that target DUBs. CHOP is superior to off the shelf assay technologies, which measure the cleavage of a small molecule from a protein and thus do not probe all of the structural features of DUBs, which in nature cleave fusions of two large proteins. Thus, the chemical space discovered by such assays has been limited, as demonstrated by the lack of selective compounds reported. Currently, two different CHOP reporters are available, CHOP1 (PLA2) and CHOP2, via LifeSensors Inc.
June 15th, 2009. Progenra enters second year of medicinal chemistry service collaboration with Jubilant ChemSys, Ltd. Progenra has completed its first year of a medicinal chemistry services agreement with Jubilant ChemSys, a full service contract research organization based in Noida, India. "The Jubilant agreement represents an important step in establishing an internal medicinal chemistry program at Progenra; we recently in-house medicinal chemistry and our chemists are now working jointly with Jubilant to achieve synergy and scale of operation in moving Progenra's drug discovery programs forward," stated Progenra CEO Tauseef Butt. Significant chemical optimization has been achieved in Progenra's lead anticancer program, testifying to the success of the collaboration."
April 20th, 2009, Progenra announces sponsorship of the first annual Ubiquitin conference, October 13th and 14th, 2009. Progenra Inc is one of the sponsors of the first in what is intended to be a series of conferences focused on ubiquitin and ubiquitin-like proteins and drug discovery (Ubiquitin Drug Discovery and Diagnostics 2009), to be held in Philadelphia in October, 2009. The conference will bring together researchers and pharma business experts from academic and industry sectors to report on recent progress in developing drugs and diagnostic/prognostic technologies based on the ubiquitin pathway and to chart the course of further progress.
March 15th, 2009, Progenra to present updates on their deubiquitylases drug discovery program at Target World Congress, August 4-5, 2009. In a podium presentation, Dr. KG Suresh Kumar, Senior Scientist will present updates on Progenra's isopeptidase drug discovery program, in particular he will discuss preclinical proof of concept of data for the prototype USP7 inhibitor P5091 and related analogs.
February 2009, Progenra to present a review on the development of their ubiquitin pathway inhibitors at Thomas Jefferson University. Dr. Craig Leach, Assistant Director will discuss Progenra's advances in targeting the ubiquitin pathway for drug discovery. The seminar will take place at 3:30pm on February 12th in the Department of Molecular Physiology and Biophysics.
December 24th, 2008, Progenra announces the publication of detailed protocols for the SUMO-PLA2 assay platform. To enhance the utility of Progenra's novel isopeptidase assay platform, Dr. Leach and colleagues provide four detailed protocols utilizing the SUMO-PLA2 assay platform to measure SUMO protease activity, perform kinetic analysis of SUMO proteases and profile modulators of SUMO proteases in a high throughput compliant assay platform. For more information please see Detection and characterization of SUMO-protease activity using a sensitive enzyme-based reporter assay, Leach, CA et al Methods in Molecular Biology: SUMO protocols 497: 269-281.
September 10th, 2008, Progenra and Temple University establish a collaboration to study modulators of Praja 1. In order to characterize potential inhibitors of ubiquitin E3 ligase Praja1, Progenra has established a collaboration with Temple University Medical School's Dr. Fayez F. Safadi, an expert in bone formation pathways. Cell-based secondary assays are being developed as part of Progenra's NIH-funded SBIR project "Functional Assays for Osteoporosis Therapeutics."
August 2008, Publication of work describing a role for ubiquitin in the regulation of PEPC in castor oil seeds. Progenra announces the publication of a journal article describing the effect of mono-ubiquitylating phosphoenolpyruvate carboxylase. In collaboration with Dr. William Plaxton of Queen's University, researchers discovered that mono-ubiquitylation of PEPC influences the kinetic and regulatory properties of the enzyme. Please see Uhrig, RG et al J Biol Chem (2008) 283: 29650-29657.
April 18th, 2008, Publication of paper describing a new highly sensitive isopeptidase reporter assay platform. In paper published today, Progenra describes a readily quantifiable novel isopeptidase assay platform consisting of ubiquitin (Ub) or ubiquitin like protein fused to the reporter enzyme phospholipase A2 (PLA2). Direct comparisons with the ubiquitin-AMC assay demonstrated that the Ub-PLA2 assay is an effective tool for characterizing modulators of isopeptidase activity. For further details please refer to Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities, Nicholson, B et al Protein Science (2008) 17: 1035-1043. The entire paper can be accessed for free via PubMed Central.
April, 2007, Publication of a review highlighting the importance of deubiquitylases in cancer. Progenra announces the publication of a comprehensive review detailing the crucial role that deubiquitylating enzymes play in neoplastic disease. In particular, the oncogenic roles of USP2a, USP7, USP20, USP33 and AMSH are discussed as well as the tumor suppressor role of CYLD. For further information please see Deubiquitylating enzymes as novel anticancer targets, Nicholson, B et al Future Oncology (2007) 3: 191-199. The full paper can be accessed for free via PubMed Central.