Progenra and the Frederick National Laboratory for Cancer Research Establish a contractor Cooperative Research and Development Agreement (cCRADA) to Develop KRAS Degraders for Cancer Therapy
Scientists at Progenra Inc and the Frederick National Laboratory, Frederick, MD, have agreed to collaborate to produce and test PROTACs, which are heterobifunctional protein degrader molecules that connect a target protein ligand to an E3 ubiquitin ligase (E3)-recruiting ligand with an optimal linker. Degradation is initiated when the PROTAC promotes the formation of a ternary complex associating the target protein, in this case mutant KRAS, with a ubiquitin E3 ligase. The collaboration was announced in a press release from the Frederick National Laboratory:
The Frederick National Laboratory for Cancer Research and biotech company Progenra, Inc., recently signed a contractor Cooperative Research and Development Agreement (cCRADA) to develop a novel therapy that could be capable of degrading KRAS.
The human KRAS gene is one of the most elusive and potentially promising cancer therapy targets. KRAS mutations drive multiple cancers, including pancreatic, colorectal, and non-small-cell lung cancers.
On May 28, the FDA approved the first targeted therapy for tumors with a specific type of KRAS mutation. The FNL-Progenra study aims to affect a broader range of indications.
“The rapid approval of Amgen’s KRAS inhibitor Lumakras (sotorasib) by the FDA highlights the importance of KRAS-dependent cancer, which is considered the most undruggable target in cancer therapy,” said Tauseef R. Butt, Ph.D., CEO of Progenra, Inc. “However, the escape mutations of KRAS will remain a challenge and will limit the efficacy of the drug. This is the main reason for developing a new approach to degrade KRAS.”
“Taking into account drug resistance mechanisms, the most effective strategy to target KRAS-driven cancers is to specifically degrade KRAS. Such an approach would greatly benefit patients over a larger range of cancer indications than Lumakras,” explained Frantz Jean-Francois, Ph.D., FNL principal investigator in the partnership and team lead for the RAS degradation project, part of the RAS Initiative.
The concept for this collaboration began a little over a year ago, when Jean-Francois discovered a compound that had had promising binding properties. These properties suggested that the compound would be a good KRAS handle for designing KRAS PROteolysis-TArgeting Chimeras (PROTACs) when linked to a ubiquitin ligase. Ubiquitin ligases are enzymes that participate in protein homeostasis.
“The cell has a built-in protein clearing process; its own way of disposing of proteins that are no longer useful,” said Jean-Francois. “PROTAC is a way of hijacking this normal process and targeting it toward proteins that you do not want. You can literally pick and choose proteins to eliminate.”
The FNL partnership to design the PROTACs will leverage Progenra’s experience using the ubiquitin proteasome system for drug discovery. The company is among the first to develop small molecule inhibitors of ubiquitin-specific proteases and to demonstrate that they have anticancer activity. Currently, the company is testing novel PROTAC molecules for their ability to selectively degrade KRAS.
“We are very excited to work with the RAS Initiative team, and we believe that their discovery and expertise coupled with our innovative PROTAC strategy will enable us to identify a clinical candidate,” said Butt.
The collaboration leverages both partners’ expertise. The FNL will coordinate the biology, biophysics, structural analysis, and mass spectrometry studies. Progenra will synthesize and provide the novel ubiquitin ligase ligand binder and lead the chemistry efforts. Progenra will also synthesize multiple PROTACs and identify and optimize the lead PROTACs for degrading KRAS.
The investigators will evaluate the PROTACs for antitumor activity in multiple cancer cell lines, but they are particularly interested in pancreatic cancer. KRAS mutations are the most prevalent oncogene mutation in pancreatic cancer, and the current five-year survival rate is just 10% for patients with pancreatic cancer—illustrating a substantial need for improved therapies.
During the Pandemic-induced Scientific Conference Hiatus, Progenra Scientists Are Active in Online Meetings on Protein Degraders
Since early 2020, when it became obvious that in-person meetings of any kind would be inadvisable, the scientific community geared up to replace their traditional national and international conferences with virtual meetings. This format will probably persist through 2021, and perhaps even into 2022. Progenra’s field – protein degradation-based drug discovery – is still expanding rapidly, and numerous meetings organized by CHI, Hanson Wade, and others have become available to researchers, business people, and clinicians to maintain the flow of scientific information and facilitate discussions. Progenra scientists have served as invited presenters at several of these meetings; six out of nine scientific meetings featuring Progenra speakers in 2020 and six out of six in 2021 are virtual/digital events. The topics covered include the generation and assay methodology for the detection of novel PROTACs and other protein degrader molecules and the utility of these molecules as new drugs for cancer, SARS-CoV-2 infection, and neuronal disease.
Progenra Drug Discovery Head Describes Company’s Use of Membrane Associated Ubiquitin E3 Ligases to Expand Scope of PROTAC Based Therapy.
Dr. Suresh Kumar, Senior Director and Head of Drug Discovery at Progenra Inc., was recently interviewed for an article in Genetic Engineering and Biotechnology News entitled “Targeted Protein Destruction: Advances in PROTACs Other Degraders.” In this article, lead scientists from several companies active in the PROTAC field discussed methods they are developing to increase the utility of the basic protein degradation mechanism demonstrated for the classic PROTAC heterobifunctional molecules, which link together a ligand for a ubiquitin E3 ligase and a ligand specific for a therapeutically relevant target protein. Ubiquitination catalyzed by the ligase results in selective degradation of the target protein, permitting the expansion of pharmacological action to targets that have historically been considered “undruggable.” Progenra is currently developing PROTACs that can attack membrane-associated targets by incorporating a membrane-associated ligase ligand into the bifunctional molecule. Dr. Kumar explained that “If your target is a membrane protein, and you want to degrade that protein with a PROTAC, “that job is better done with a membrane-targeted E3 ligase than with a nuclear-located ligase.” The inclusion of membrane associated targets will increase the scope of PROTAC therapy. As an example, Kumar revealed that Progenra is targeting K-Ras, a membrane protein that has been an anticancer target for many years with no approved drug resulting from the considerable time and effort expended.
Progenra receives funding from the Michael J Fox Foundation to develop Parkin activators to treat Parkinson’s disease.
Progenra has received new funding for its Michael J. Fox Foundation Therapeutic Pipeline Award, Discovery and Development of Novel Parkin Activators. Progenra’s novel Parkin activator molecules are undergoing preclinical development, and this funding will support chemical optimization and other early preclinical activities necessary to advance the program to clinical trial for treatment of Parkinson’s disease.
Progenra Scientists publish a chapter in the ACS 2019 Medicinal Chemistry Reviews.
Ubiquitin-specific proteases (USPs), the major class of deubiquitinating enzymes, or DUBs, remove conjugated ubiquitin from proteins in cells and in so doing help to regulate the content, location, or activity of the target protein. Approximately 80 USPs are expressed in humans, and many are linked genetically and biochemically with various diseases including cancer, cardiovascular disease, neurodegeneration, inflammation and asthma, and metabolic diseases. Pathology-linked USPs have become actively investigated therapeutic targets for the development of new medicines in these and other diseases. Despite all this work, not any DUB based drugs have entered clinical trials, and DUBs are regarded by some as undruggable because their common mechanism of hydrolysis and the active site (a conserved catalytic triad) shared with other cysteine protease classes. Nevertheless, the search for a USP-based drug continues as increasing evidence suggests that potent and highly selective inhibitors of individual DUBs can be developed. This evidence comes primarily from structural studies employing NMR and X-ray crystallography. In addition, the therapeutic utility of irreversible inhibitors is gaining acceptance. Progenra has been engaged in developing DUB inhibitors for several years, and three of the company’s researchers, medicinal chemists Jian Wu and Xu Wang and head of drug discovery Suresh Kumar, recently summarized the state of modulators of various USPs in drug development in a chapter in Medicinal Chemistry Reviews (Volume 54, Chapter 17) entitled Advances in the Development of De-ubiquitinase (DUB) Inhibitors.
Read the Full Chapter in 2019 Medicinal Chemistry Reviews, Volume 54, Chapter 17. Advances in the Development of De-ubiquitinase (DUB) Inhibitors. J. Wu et al.
Progenra CEO, Dr. Tauseef R Butt invited to speak at the PROTACs and Beyond Conference in London, on March 8-9th.
The field of PROTACs is rapidly increasing, and Progenra’s novel PROTACs program will be highlighted by its CEO, Dr. Tauseef Butt. He will speak on “How to Exploit the Ubiquitin Signal for PROTACs that Go Beyond Degradation” Nature synthesizes multiple poly-ubiquitin chains that extend from seven lysines on the ubiquitin surface. Lys 48 and Lys 63 poly-ubiquitin are primary degradation signals for PROTACs, driven by ubiquitin ligases cerebelon, VHL and HDM2. Little is known about the roles of mono-ubiquitin or atypical poly-ubiquitin chains or their cognitive ubiquitin ligases. The roles of classic ubiquitin ligases and atypical ubiquitylation will be discussed with the aim of expanding the horizon of PROTAC drugs beyond protein degradation.
26 – 27 May 2020, Berlin, Germany. This meeting bring together Europe’s premier pharmaceutical organizations, biotech companies and academic institutions specializing in therapeutic areas. Progenra President Dr. Tauseef Butt has been invited to give one of the cutting-edge presentations, and he will speak on “PROTACs, Protein Targeting Chimeras, Bottle Necks and Success with Novel Ligases” Traditional ubiquitin ligases, such as cereblon, VHL, HDM2 and cIAPs and their ligands have been exploited as PROTAC drugs. There is dearth of tools to rapidly discover PROTAC molecules. Lack of innovation and poor IP position could result into loss of investment, time and opportunity to develop breakthrough PROTACs. Progenra has focused its attention to novel ubiquitin ligases and discovered entirely new class of PROTACs. Discovery platform and application of novel ligase PROTAC drugs in inflammation, oncology and neuroscience will be discussed.
Cambridge Healthtech Institute’s 3rd Annual Drug Discovery Chemistry Conference
Ubiquitin-Induced Targeted Protein Degradation Optimizing PROTACs and Small Molecule Degraders for Pursuing Undruggable Targets April 14-15, 2020. San Diego, CA. Dr Tauseef Butt, President of Progenra, will speak at this annual meeting on “PROTACs, Protein Targeting Chimeras, Bottle Necks and Success with Novel Ligases”. Only the well-known ligases (Cereblon, VHL, HDM2 and cIAPs) have been exploited by medicinal chemists. Too many resources are devoted to these ligases as vehicles for PROTACs. There is dearth of tools to rapidly discover PROTAC molecules. Lack of innovation and poor IP position could result into loss of investment, time and opportunity to develop breakthrough PROTACs. Progenra has focused its attention to novel ubiquitin ligases and discovered entirely new class of PROTACs. Application in the novel PROTACs in oncology, inflammatory and neuroscience will be discussed.
21-22 May 2020, London UK. This conference will feature sessions on immuno-oncology and autoimmunity/immunology, enabling attendees to share their insights and results and gain the latest information on these areas of immunology from the leading immunotherapy experts. Progenra’s President Dr. Tauseef Butt will speak at the Autoimmunity and Immunology session on “Ubiquitin Proteasome System, A Double Edge Sword: How to Sharpen the Edge against Autoimmunity”. Ubiquitin Proteasome System (UPS) plays is a key role in innate and adaptive immune systems mediating inflammation. Many companies have failed to discover selective molecules that target ubiquitin ligases or de-ubiquitylases (DUBs) for therapeutic benefit. Nedd4-family E3 ligases, including Itch, negatively regulate inflammatory immune responses by suppressing TH2 and TH17 differentiation and cytokine production. Small molecule activators of Nedd4-family E3 ligase can be used to selectively activate ubiquitylation cascades to limit TH2 and TH17 cytokine production and to dampen inflammation in a variety of inflammatory diseases. In this talk, he will present discovery and characterization of novel E3 ligase activators that suppress TH2 and TH17 differentiation and exhibit robust anti-inflammatory properties.
May 6, 2019 | News
Paris, France. ” Multiple clinical failures in the neurodegenerative field have sparked realization that there is a critical need for discussion and debate among neurodegenerative drug developers to drive clinical success. NDD Europe will overcome the translational challenges facing neurodegenerative drug developers by exploring the future biomarkers of neurodegeneration, improving preclinical modelling to increase clinical predictability and encouraging pre-competitive strategies and collaboration amongst drug developers. Dr. Tauseef Butt will speak about recent advancements in biomarker identification as a key step in the drug discovery process for neurodegenerative disease.
Progenra Inc. Receives Therapeutic Pipeline Award from The Michael J. Fox Foundation for Parkinson’s Research and Drug Development
Dec 14, 2018
Funding will support Progenra’s development of small molecules for treatment of Parkinson’s Disease
Malvern, PA (Dec 8, 2018) – Progenra Inc. announces the receipt of a 2018 Therapeutic Pipeline Award from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). The award supports Progenra’s program of small molecule drug discovery and development for Parkinson’s disease, which, after Alzheimer’s disease, is the second most common form of neurodegeneration. The MJFF’s Target Advancement and Therapeutic Pipeline Programs are aimed at uncovering the biology underpinning Parkinson’s disease and, exemplified by Progenra’s leadership in the ubiquitin proteasome system, evaluating new treatments, respectively.
Dr. Tauseef Butt, CEO of Progenra, stated: “Progenra is pleased to have been selected by The Michael J. Fox Foundation to contribute to bringing Parkinson’s and other major neurodegenerative diseases under control by introducing new therapeutic agents. Since its inception, Progenra has been dedicated to developing novel therapeutics by targeting enzymes from the ubiquitin proteasome system (UPS). The UPS plays a fundamental role in neuronal health, and dysfunction in this pathway is responsible for neuronal diseases. We believe that augmenting the activity of a native enzyme known to be beneficial in combating neurodegeneration will provide both mechanistic information and the potential for breakthrough treatment, and we look forward to working with the many excellent researchers in the foundation’s consortium.”
About Progenra Inc.
Progenra (www.progenra.com) aims to discover and develop novel medicines exploiting the ubiquitin proteasome system. Progenra has achieved leadership in ubiquitin proteasome system by utilizing the company’s UbiPro™ Drug Discovery Platform. Progenra has identified novel therapeutically relevant molecules for Parkinson’s disease by targeting ubiquitin proteasome system. For Progenra contact Tauseef Butt, Phone 610-644-6974 x 301, firstname.lastname@example.org.
About The Michael J. Fox Foundation for Parkinson’s Research
As the world’s largest nonprofit funder of Parkinson’s research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson’s disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson’s patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $800 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson’s research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson’s disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson’s awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. For more information, visit us at michaeljfox.org, on Facebook or Twitter.
Drug Discovery Chemistry, April 4-5, 2018. San Diego, CA.
First-generation cancer immunotherapy agents have been primarily biologicals — monoclonal antibodies that block protein-protein interactions between T cell checkpoint receptors and their ligands. Recently, discovery efforts have focused on the development of immune-modulatory small molecules addressing a wide array of new immune-modulatory targets that can be used in combination with the biologicals. The Cambridge Healthtech Institute’s Drug Discovery Chemistry conference brought together developers and discovery scientists to share new targets, novel immune-modulatory inhibitors, and preclinical and clinical studies in combination with checkpoint antibodies. Progenra President Dr. Tauseef Butt spoke at this conference on “Small Molecule Ubiquitin Protease (USP7) Inhibitors with Immune Cell-Based Anti-Tumor Activity Superior to That of Biologicals” in the Ubiquitin Proteasome Inhibitors section. Dr. Suresh Kumar, Senior Director and Head of Discovery at Progenra, presented Progenra’s work on “Targeting the Tumor Microenvironment with Deubiquitinase Inhibitors for Cancer Immunotherapy” in the Small Molecules for Cancer Immunotherapy section of the meeting.
American Chemical Society National Meeting and Exposition March 18-22, 2018. New Orleans, LA.
Dr. Jian Wu, Associate Director at Progenra, presented a talk entitled ” Small molecules as frontline therapy for immune oncology: Experience from ubiquitin pathway targets ” at medicinal chemistry section. The ACS National Meeting brings together more than 10,000 professionals to present and discuss recent publications as well as technological advancements. The spring conference highlighted Advanced Materials, Technologies, Systems and Processes.
Progenra discusses role of small molecules and USP7 in immune oncology on Cambridge Healthtech Institute 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.
Progenra Receives Second Immune Oncology Patent
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.
Progenra invited to host an Immune Oncology Session at BIO International Convention 2017
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.
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.
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
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.
Data from Progenra and collaborators presented at the North American Cystic Fibrosis Conference, Phoenix, AZ.
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.
Progenra scientists attend 16th international conference on Alzheimer’s drug discovery, Jersey City, NJ.
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.
Progenra head of biology describes antitumor activity of the company’s deubiquitylating enzyme USP7 inhibitors at the inaugural International Cancer Immunotherapy Conference.
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.
Progenra chemists describe the synthesis and antitumor activity of novel USP7 inhibitors at the 2015 Gordon Research Conference on Medicinal Chemistry.
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.
Progenra Chairs Ubiquitin Symposium at the Society for Neuroscience Conference, November 15-19, Washington, DC.
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.
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).
New Study Demonstrating Progenra’s Novel Anti-Tumor Compound Overcome VELCADE®(bortezomib) Resistant Multiple Myeloma Cells.
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.
Progenra Announces the Availability of its UbiProTM Drug Discovery Platform for Licensing.
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.
Progenra announces the publication of a paper in Assay and Drug Development Technologies expanding the CHOP reporter platform family.
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.
Progenra announces the publication of a manuscript describing its proprietary E3 ligase screening platform.
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.
Progenra announces its sponsorship of the third annual Philadelphia Ubiquitin Drug Discovery and Diagnostics Conference, June 20-22nd, 2011.
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.
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”.
July 26, 2010. Progenra announced 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”.
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