Progenra discusses role of small molecules and USP7 in immune oncology on Cambridge Healthtech Institue podcast
Recently, Dr. Tauseef Butt, President and CEO, spoke with Joel Hornby of Cambridge Healthtech Institute. Dr. Butt spoke of the role that small molecules, specifically inhibitors of ubiquitin protease 7 (USP7), play in immune oncology. In addition, Dr. Butt discussed animal model data generated using Progenra's USP7i compounds, as well as Progenra's unique Drug Discovery Platform. Dr. Butt will further discuss these topics during Immunomodulatory Small Molecules and Targeting the Ubiquitin Proteasome System at the Discovery on Target conference, September 27-28.
Listen to the podcast here.
MALVERN, PA, May 10, 2017 --(BUSINESS WIRE) -- Progenra, Inc. announced that it has received the Official Notice of Allowance (dated March 30, 2017) of its patent application entitled “Methods of treating cancer through the inhibition of USP7 and immune system modulation.” The patent, based on work described in a recent publication, is related to a new immune oncology therapy based on the inhibition of the ubiquitin-deconjugating enzyme USP7 by a small molecule. USP7 is a master positive regulator of cancer as it both directly supports the growth and survival of cancer cells and prevents the patient’s immune cells from recognizing and eradicating the tumor. Progenra is developing small molecule inhibitors of USP7 for clinical trial and, according to its President, Dr. Tauseef Butt, hopes to initiate Phase I in early 2018. He stated that “we continue to obtain data showing that our USP7 inhibitors have the potential to eliminate cancer by both direct cytotoxic and indirect immunological mechanisms. This class of drug could become a powerful alternative to the biological immune checkpoint inhibitors currently on the market (such as Opdivo and Keytruda), as well as a component of combination therapy with these agents.” In animal efficacy models, Progenra compounds have demonstrated anti-cancer activity that was superior to that of Yervoy, Opdivo, or Keytruda. These results point to a potentially radical development in cancer treatment -- a small molecule single agent that works as well as or better than combination protocols.
Progenra (www.progenra.com) aims to develop high value medicines exploiting protein regulatory pathways. Its early product portfolio addresses unmet needs in cancer, inflammation, and neurodegeneration. Utilizing its UbiPro™ Drug Discovery Platform, Progenra identifies novel modulators of its protein regulatory targets for drug development; its discovery platform is complemented by internal target validation, cell proof of concept, and medicinal chemistry.
June 18-22, 2017. San Diego, CA. Progenra President Dr. Tauseef Butt is the organizer and a participant of a panel discussion entitled “Immune Oncology Drugs: Ready for First Line Therapy?” This panel, which is comprised of leaders of immune oncology from the pharmaceutical industry and academic medicine, will address whether the new immune oncology drugs will, as currently predicted in many quarters of both the scientific/medical and investment communities, supplant tumoricidal drugs and radiation as first line therapies in many cancers. Other topics to be considered are: the affordability of immune oncology treatments; the existence and utility of biomarkers to identify treatable patients and monitor therapy; the utility of combination protocols involving other immune oncology drugs or traditional anticancer drugs to achieve maximum efficacy; and ways to manage immune side effects resulting from immune therapy of cancer.
January - July, 2017
Progenra Discovers Novel Immune Oncology Drug
MALVERN, PA, Dec 15, 2016 -- (BUSINESS WIRE) -- Progenra, Inc. announced a new immune-oncology drug whose mechanism differs from available cancer immunotherapies Opdivo and Keytruda. The findings, published by Progenra with Dr. Wayne Hancock, University of Pennsylvania School of Medicine, support a new immune-oncology antitumor strategy by inhibiting USP7, an enzyme that prevents immune activity against cancer in addition to supporting the growth of cancer cells. According to a commentary on this publication, inhibiting USP7 works on T cells to diminish immunosuppression, permitting the patient’s own immune system to eliminate cancer (“the data by Wang and colleagues proposes a potential immunotherapy against tumors by targeting USP7, which … breaks the immune tolerance in the tumor microenvironment”… “these preclinical findings suggest that USP7 targeting … as well as directly induce tumor cell apoptosis, could have practical significance in clinical applications”).
“We are pleased that Progenra’s unique UbiPro™ Drug Discovery Platform is gaining traction outside the US and that a major pharmaceutical company such as Ono has agreed to collaborate with Progenra on the ubiquitin and ubiquitin-like protein pathways”
“We are pleased that Progenra’s USP7 inhibitors, tested in several laboratories worldwide, can eradicate cancers by both tumoricidal and immunological mechanisms,” said Tauseef Butt, President of Progenra. “We are excited to move USP7 inhibitors into clinical trial as single agents or combined with marketed immunological agents such as Opdivo and Keytruda.”
Dr. Hancock added,” Immunotherapy must do more than affect a single target, since those approaches help only about 20% of patients. Pharmacologic inhibition of USP7 allows direct targeting through the immune system, in a graded manner that has antitumor efficacy used alone or combined with one or more biologic agents.”.
Progenra (www.progenra.com) aims to develop high value medicines exploiting protein regulatory pathways. Its early product portfolio addresses unmet needs in cancer, inflammation, and neurodegeneration. Utilizing its drug discovery platform, Progenra identifies novel modulators of its protein regulatory targets for drug development; the company’s discovery platform is complemented by internal target validation, cell proof of concept, and medicinal chemistry.
Dr. Wayne Hancock is Professor of Pathology/Laboratory Medicine at The University of Pennsylvania School of Medicine and Chief, Division of Transplant Immunology at the Children’s Hospital of Philadelphia. His multidisciplinary team focuses on improving outcomes of organ transplantation and cancer immunotherapy by modulating immune cell production and function.
July - December, 2016
Dr. Tauseef Butt speaks at the Second International Conference on Clinical Science and Drug Design at the University of Dundee
July 27-29, 2016 Dundee, Scotland UK. Progenra’s President Dr Tauseef Butt gave an invited lecture at this second annual conference, which focuses on the translation of academic research findings into industry-driven drug development. Sessions featured invited speakers from industry and academia, as well as oral and poster presentations from submitted abstracts. In the past decade, epigenetic molecular targets have become the bases of development of new medicines for a variety of diseases, such work being exemplified by the Dundee University laboratory of Sir Philip Cohen, a leader in protein kinase research. Progenra’s President, Dr. Tauseef Butt, presented a talk at this conference summarizing the company’s drug discovery progress in utilizing the ubiquitin pathway, a second epigenetic field that is supplying multiple targets for drug development. In particular, Dr. Butt described Progenra’s current program to develop novel cancer treatments by pharmacologically manipulating the ubiquitin pathway to activate the native immune response to neoplastic disease.
Progenra’s Head of Drug Discovery speaks at the CHI Meeting on Cancer Immunotherapy and Combinations -- Exploring a New Generation of Immunomodulatory Agents and Combinations
January - June, 2016
June 15-16, 2016 Boston, MA. Invited to speak at this meeting in the session entitled “Small Molecule Inhibitors as Single and Checkpoint Combination Agents,” Dr. Suresh Kumar, Senior Director and Head of Drug Discovery at Progenra Inc., gave an update on Progenra’s pre-clinical ubiquitin protease inhibitors currently being developed as immunotherapy agents for cancer. These small molecules, which work through a unique mechanism to unleash the effector T cell antitumor responses, show promise in efficacy studies both as single agents and in combination with immune checkpoint biologicals. Potential advantages of combination protocols include cost effectiveness and increase in the range of treatable disease.
Progenra business development represented at the 2016 BIO International Convention
June 6th-9th, 2016 San Francisco, CA. The Progenra Business Development team were in attendance at the BIO International Convention 2016 to discuss the company’s progress and to explore collaborative opportunities in drug discovery.
Collaborative research on cystic fibrosis is presented by Progenra at Cold Spring Harbor Meeting on Protein Homeostasis in Health and Disease
April 18-22, 2016 Cold Spring Harbor, NY. This meeting, which marked the 25th anniversary of the first Cold Spring Harbor meeting in 1991 related to heat shock and the role of molecular chaperones, featured the latest research in this area with several keynote talks by leading investigators in the field. Dr. Christopher Riling and Ivan Sokirniy attended this meeting from Progenra and presented results of work on E3 ligases and mutant CFTR in the context of cystic fibrosis, in collaboration with colleagues at the University of Pittsburgh, the University of Alabama/Birmingham, and Emory University.
Progenra scientists describe novel small molecule immune-oncology agents from the ubiquitin pathway at the American Association for Cancer Research (AACR) Annual Meeting
April 16-20, 2016, New Orleans, LA. Updates to Progenra's characterization of its preclinical inhibitors of a deubiquitinating enzyme and an E3 ligase were presented in posters by discovery scientists Drs. Suresh Kumar and Christopher Riling, who attended this meeting . These small molecules show promise as immuno-oncology antitumor agents either singly or in combination with approved biological immune checkpoint inhibitors such as Yervoy, Keytruda, Opdivo, and others. Progenra is currently working to identify clinical candidate inhibitors of these two and other novel immune-oncology targets.
Progenra CEO presents at 2016 J P Morgan Healthcare Conference in San Francisco.
January 11-16, 2016, San Francisco, CA. Dr. Tauseef Butt, President and CEO of Progenra, presented the company to investors and potential partners at the annual J.P. Morgan Healthcare Conference, the industry’s oldest and largest gathering of healthcare and biotech companies and investors, with more than 300 companies in attendance. Dr. Butt had discussions with several potential partners regarding Progenra’s compound assets in immune-oncology and rare diseases. The company expects to have a compound in clinical development in late 2016-early 2017.
July - December, 2015
October 8-10 2015, Results of recent work on experimental therapeutics for cystic fibrosis conducted by Progenra and collaborating research groups headed by leading scientists in cystic fibrosis research – Dr. Eric Sorscher of the University of Alabama at Birmingham (now at Emory University) and Dr. Jeffrey Brodsky of the University of Pittsburgh – were presented in a talk by Dr. Wook Joon Chung (University of Alabama Birmingham) at the North American Cystic Fibrosis Conference in October, 2015, in Phoenix, AZ. The title of Dr. Chung’s presentation was” Increasing the pool of CFTR available for correction by disrupting ubiquitination.” In it he described compounds from Progenra that prevent ubiquitin-mediated degradation of a CFTR ion transport protein (CFTRDF508) that is mutated, though partially functional, in many cystic fibrosis patients. These compounds are expected to act as protectors which increase the pool of CFTRDF508 for subsequent modulation by correctors such as lumacaftor, thereby providing therapeutic benefit. The compounds were evaluated for their ability to increase CFTRDF508 content of appropriate model cells; several of them were found to increase CFTRDF508 levels compared to control, and to enhance CFTRDF508 ion transport synergistically following lumacaftor treatment in human bronchial epithelial monolayers. These results establish that preventing degradation of CFTR can serve as a valuable drug development strategy and promote “repairable” CFTRDF508. Progenra and collaborators are evaluating chemically optimized versions of these protector molecules for drug metabolism/pharmacokinetic properties, with the goal of identifying clinical candidates that could become transformative therapeutic agents for cystic fibrosis.
October 5-6 2015. Progenra CEO Dr. Tauseef Butt and senior discovery scientist Dr. Jack Wang attended the 16th international conference on Alzheimer’s drug discovery Oct 5-6. This annual conference brings together academic and industry scientists intent on accelerating the development of innovative treatments for Alzheimer’s disease and related dementias. The ADDF’s funded investigators and top-level scientists in the field described their current research progress and stimulated discussion among the attendees. Progenra has been conducting a drug discovery program exploiting the regulatory roles of various ubiquitin pathway enzymes in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s Diseases, and has identified small cell modulators of ubiquitin conjugating and deconjugating enzymes that are genetically and/or biochemically linked to these pathologies. The company believes that at least one of these small molecules will enter preclinical development in 2016 for treatment of Alzheimer’s Disease.
Progenra CEO speaks in the ubiquitin drug discovery section of the Third Annual CHI Discovery on Target Conference on Progenra’s anticancer strategy for USP7 inhibitors.
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. Inin 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.
November 11, 2014 - 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.
August 15, 2014 - Progenra, Inc. announced today that Dr. Wayne Hancock, 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.
Progenra receives patent on novel anti-cancer compound.
March 25, 2014 - 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.
Progenra's Novel USP7 Inhibitors are Shown to Exert Multiple Anti-Tumor Effects
October 8, 2012 - 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 - 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 - 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, 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. 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, 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 6, 2010 - 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 23, 2010 - 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 30, 2010 - 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.