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August 6th, 2020

SARS-CoV-2 RNA May Move Through Tiny Pore in Peculiar Intracellular Double-Membraned Replication Vesicles into Cytosol for Packaging into Complete, Infectious Virus; Pore in Double-Membraned Vesicle Revealed by Electron Tomography

By visualizing coronavirus replication in an infected host cell, researchers may have answered a long-standing question about how newly synthesized coronavirus components are able to be incorporated into fully infectious viruses. The scientists’ work uncovers a coronavirus-specific structure in cells that may be a target for much-needed antiviral strategies against this family of viruses. Coronaviruses replicate their large genomes in the host cell's cytoplasm. They do this by transforming host cell membranes into peculiar double-membrane vesicles (DMVs). Newly made viral RNA needs to be exported from these DMVs to the cytosol to be packaged into complete, infectious forms of the virus. To date, however, no openings to the cytosol have been detected in the DMV replication compartments. Here, seeking to understand how viral RNA is exported from sealed DMVs, Georg Wolff (photo), PhD Candidate, Department of Cell and Chemical Biology, Section Electron Microscopy, Leiden University Medical Center, Leiden, The Netherlands, and colleagues used electron tomography to visualize the middle stage of infection of a cell by mouse hepatitis coronavirus, used instead of SARS-CoV-2 due to biosafety constraints for in situ cryo-electron microscopy studies. They identified a coronavirus-specific crown-shaped structure--a molecular pore spanning the two DMV membranes--that likely plays a role during RNA release from the compartment. In further work using pre-fixed samples of SARS-CoV-2-infected cells, the researchers showed that the structure is also present in SARS-CoV-2-induced DMVs. The authors "surmise" that this structure may be a generic complex with a pivotal role in the coronavirus replication cycle, facilitating the export of newly synthesized viral RNA from the DMVs to the cytosol.

Study Will Examine If Concentrated Formulation of Leronlimab, an Anti-CCR5 Monoclonal Antibody, Could Prevent Simian Version of HIV in Non-Human Primates, with Less Frequent Treatment

A new study will examine whether a concentrated version of an experimental drug can prevent HIV infection with less frequent treatment. Oregon Health & Science University (OHSU) is leading the five-year, $3-million study (https://projectreporter.nih.gov/project_info_description.cfm?aid=1006493...) to explore if a new formulation of the drug leronlimab can prevent infection of the monkey version of HIV in rhesus macaques. If the new formulation works, the injectable drug could potentially be taken every three months instead of weekly, as is recommended with the drug’s current design. Jonah Sacha, PhD, a Professor at OHSU’s Oregon National Primate Center and Vaccine & Gene Therapy Institute, is leading the study. Leronlimab is a monoclonal antibody that blocks HIV from entering immune cells through a surface protein called CCR5. Following a Phase 3 clinical trial, Vancouver, Washington-based biotechnology firm CytoDyn is seeking FDA approval to use their current formula of leronlimab to treat humans infected with HIV. Clinical trials to evaluate leronlimab’s use for pre-exposure prophylaxis, or PrEP, to prevent human infection from the virus that causes AIDS are also planned. Some PrEP drugs are already available, but they can lead to adverse side effects such as liver, heart, and bone problems, and some people are resistant to them. Existing PrEP options typically require frequent use, such as taking a pill daily or must be given at a clinic. Leronlimab is designed to be a self-administered injection. This study will evaluate concentrated microparticle formulations of leronlimab that are designed to last longer and be delivered through a single injection.

August 2nd

Two Stirring Plenaries, Stunning News of Exosome-Based Clinical Trial in Pancreatic Cancer, & Announcement of Award Winners Highlight Last Day of International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting; Next Year, On to Lyon !!

The International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/) ended its live-streamed events triumphantly on Wednesday, July 22, with an all-time record attendance of 1,600, and the last of over 600 presentations of various types (Plenary Addresses, “Hot-Topic” Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, Education Sessions, & Sponsor Presentations), both live-streamed and on-demand. The final live day featured two fantastic plenary addresses, the last of four Featured Abstracts from young investigators (selected on a merit basis from over 700 applicants), the final two of six hugely informative Education Sessions, and the last two of four “Hot-Topic” Panels. The enormously successfully ISEV 2020 closed with wrap-ups of clinical and basic science highlights from the meeting, announcement of the 39 Junior Member Scholarships awarded to young investigators from 17 countries, announcement of the four Featured Abstract winners, presentation of the ISEV 2020 Awards for Outstanding Oral Presentations and for Outstanding Poster Presentations. Also included were remarks from the incoming Co-Chairs of the ISEV International Organization Committee (IOC) 2021 describing the selection of Lyon, France, as the site for the ISEV 2021 Annual Meeting, which will hopefully be held in person.

Education Session 2 ("EV Methods & Techniques") at International Society for Extracellular Vesicls (ISEV) 2020 Virtual Annual Meeting; Materails Available On-Demand Until Sept 21

[This article was written for BioQuick News by Yolanda Watson, Assistant Principal, Klein Independent School District (Klein Forest High School) Houston, Texas; MS, San Francisco State University; BA (Molecular Biology), UC-Berkeley.] [Much of this material has been reviewed for accuracy by speakers, but not all. If you should have any questions, please contact Mike O’Neill, Editor & Publisher, BioQuick News, at logophile2000@yahoo.com. This material was produced by BioQuick News and does not imply endorsement by the ISEV.] Among its myriad stimulating and timely offerings, the International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/)meeting offered 23 Educational Presentations, featured in 6 different sessions during the 3-day meeting and also available on-demand until September 21. These sessions are intended to convey significant background information on the ever-widening impact of extracellular vesicles (EVs), including exosomes, on virtually all of biology and medicine The 23 10-minute educational presentations were delivered by world leaders in their fields. Education Session 2 (EV Methods & Techniques) was also presented on Monday (JuIy 20), and was briefly introduced by Alain Brisson, PhD, Emeritus Professor at the University of Bordeaux, Extracellular Vesicles & Membrane Repair Team, French National Center for Scientific Research (Centre National de la Recherche Scientifique, CNRS) Unit, Institut de Chimie & Biologie des Membranes et des Nano-objets (CBMN), Bordeaux, France.

Education Session 1 ("Introduction & EV Position Papers) at International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22); Materials Available On-Demand Until Sept 21

[This story was written for BioQuick News by Yolanda Watson, Assistant Principal, Klein Independent School District (Klein Forest High School) Houston, Texas; MS, San Francisco State University; BA (Molecular Biology), UC-Berkeley.] [Much of this material has been reviewed for accuracy by speakers, but not all. If you should have any questions, please contact Mike O’Neill, Editor & Publisher, BioQuick News, at logophile2000@yahoo.com. This material was produced by BioQuick News and does not imply endorsement by the ISEV.] Among its myriad stimulating and timely offerings, the International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/)meeting offered 23 Educational Presentations, featured in 6 different sessions during the 3-day meeting and also available on-demand until September 21. These sessions are intended to convey significant background information on the ever-widening impact of extracellular vesicles (EVs), including exosomes, on virtually all of biology and medicine. The 23 10-minute educational presentations were delivered by world leaders in their fields. Education Session 1 (Introduction & EV Position Papers), on Monday (June 20), featured a brief introduction by Edit Buzas, MD, PhD, ISEV Executive Chair for Education; Core Member, TRAIN-EV; Professor & Chair, Department of Genetics, Cell Biology, and Immunobiology; Head, Extracellular Vesicles Group; Semmelweis University, Budapest, Hungary. This was followed by 10-minute presentations of three EV position papers.

23 Educational Talks Among Over 600 Presentations During Jam-Packed International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22); Materials Available On-Demand Until Sept 21

Among its myriad stimulating and timely offerings, the ISEV 2020 Virtual Annual Meeting ((https://www.eventscribe.com/2020/ISEV/) ), live-streamed July 20-22, and on-demand until September 21, offered 23 Educational Presentations, featured in 6 different sessions during the 3-day live-streamed meeting. These sessions were intended to convey significant background information on the ever-widening impact of extracellular vesicles (EVs), including exosomes, on virtually all of biology and medicine. The 23 10-minute educational presentations were delivered by world leaders in their fields. Below is an outline of the Education Sessions, with descriptions of the 23 different presentations and backgrounds on the distinguished presenters and session moderators. Each of the six Education Sessions will include a 15-minute Q&A discussion at its end. Although the live-streamed sessions ended July 22, all meeting presentations are available to all registrants until September 21. You can still register and access all meeting material at the following link: https://www.isev.org/mpage/2020Registration. The first education session "Introduction & EV Position Papers" was presented on Monday and was briefly introduced by Edit Buzás, MD, PhD, ISEV Executive Chair for Education; Core Member, TRAIN-EV; Professor & Chair, Department of Genetics, Cell Biology, and Immunobiology; Head, Extracellular Vesicles Group; Semmelweis University, Budapest, Hungary. This was followed by 10-minute presentations of three EV position papers.

July 28th

Pfizer & BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 & Commence Phase 2/3 Global Study of Up to 30,000 Participants, Starting in US and to Include Approximately 120 Sites Globally; 100 Million Doses Anticipated by End of 2020

On July 27, 2020, Pfizer Inc. (NYSE: PFE) (https://www.pfizer.com/) and BioNTech SE (Nasdaq: BNTX) (https://biontech.de/) announced the start of a global (except for China) Phase 2/3 safety and efficacy clinical study to evaluate a single nucleoside-modified messenger RNA (modRNA) candidate from their BNT162 mRNA-based vaccine program against SARS-CoV-2. After extensive review of preclinical and clinical data from Phase 1/2 clinical trials, and in consultation with the U.S. FDA’s Center for Biologics Evaluation and Research (CBER) and other global regulators, Pfizer and BioNTech announced that they have chosen to advance their BNT162b2 vaccine candidate into the Phase 2/3 study, at a 30 µg dose level in a 2-dose regimen. BNT162b2, which recently received U.S. FDA Fast Track designation, encodes an optimized SARS-CoV-2 full length spike glycoprotein (S), which is the target of virus neutralizing antibodies. “Our selection of the BNT162b2 vaccine candidate and its advancement into a Phase 2/3 study are the culmination of an extensive, collaborative and unprecedented R&D program involving Pfizer, BioNTech, clinical investigators, and study participants with a singular focus of developing a safe and effective COVID-19 RNA vaccine. The Phase 2/3 study protocol follows all the U.S. FDA guidance on clinical trial design for COVID-19 vaccine studies,” said Kathrin U. Jansen, PhD, Senior Vice President and Head of Vaccine Research & Development, Pfizer. “The initiation of the Phase 2/3 trial is a major step forward in our progress toward providing a potential vaccine to help fight the ongoing COVID-19 pandemic, and we look forward to generating additional data as the program progresses.” “Today, we are starting our late-stage global study, which will include up to 30,000 participants.

Seer, Inc., Announces Publication in Nature Communications Demonstrating Performance, Scalability, and Utility of its Platform Technology for Deep, Unbiased Proteomics

On July 22, 2020, Seer, Inc. (https://seer.bio/) announced the publication in Nature Communications (https://www.nature.com/articles/s41467-020-17033-7) of a study demonstrating the power of its proprietary, engineered nanoparticle technology platform to discover novel proteins and biomarkers through an unprecedented combination of unbiased, deep, rapid, large-scale proteomics. The study brought together an interdisciplinary team of scientists, engineers and physicians from MIT, Harvard Medical School, Seer, and other organizations. The open-access article, entitled “Rapid, Deep and Precise Profiling of the Plasma Proteome with Multi-Nanoparticle Protein Corona,” establishes the novel technology’s ability to interrogate the plasma proteome across many orders of magnitude spanning highly abundant to rare proteins, and reproducibly capture and robustly quantify proteins in a rapid, automated workflow without the need for additional sample-processing steps. Omid Farokhzad, MD, Chief Executive Officer at Seer, commented on the significance of the findings, “Measuring the vast amount of proteomic information across many individuals, many time points, and many diseases has long been a goal of scientific and industry researchers. But, that goal has not been achievable due to the complexity of the proteome and inherent challenges in measuring it. Essentially, researchers have had to sacrifice depth of profiling either for number of proteins or for speed. As the study published today demonstrates, this is the first technology to eliminate that trade-off – and, importantly, offer an unbiased view of the proteome.” The technology described in the Nature Communications paper forms the foundation for Seer’s Proteograph™ suite of products, including reagents, instruments, and software, which the company plans to begin commercializing next year.

Proteomics Company "Seer" Announces $55M Financing Led by Fidelity Management and Research Company

On July 22, 2020, Seer, Inc., a life sciences company focused on empowering exceptional scientific outcomes through the power of rapid, deep, unbiased proteomics information, announced that it has raised $55 million in a new funding round. This latest equity financing was led by Fidelity Management and Research Company, and included a new investor, HBM Healthcare Investments. All existing investors also participated in the round, including funds and accounts advised by T. Rowe Price Associates, Invus, aMoon, and Maverick Ventures. “We’re thrilled by the high caliber of investors we continue to attract who share Seer’s vision to transform proteomics and empower researchers to exponentially advance our understanding of human health and disease,” said Omid Farokhzad, MD, Chief Executive Officer and Founder of Seer. “We are paving the road for researchers to measure hundreds of thousands of distinct protein variants that make up the human proteome at population scale and provide the missing functional context to genomic data sets. This will have a fundamental impact on our understanding of biology and disease, including the selection of more precise biomarkers for early disease detection and the elucidation of novel targets for disease treatment.” Seer will use the proceeds from this financing to expand its research and development activities and to prepare for the planned 2021 commercial launch of its Proteograph™ suite of products, comprising reagents, instruments, and software. The Proteograph suite of products leverage Seer’s proprietary engineered nanoparticles to enable an entirely new way of accessing the proteome.

July 27th

NIH Selects Humanigen’s Lenzilumab for its COVID-19 Big Effect Trial (BET), Sponsored by NIAID to Advance High-Priority Therapeutic Candidates for COVID-19; Humanigen’s Monoclonal Antibody Will Be Tested in Combination with Gilead’s Antiviral Remdesivir

On July 27, 2020, Humanigen, Inc., (HGEN) (https://www.humanigen.com/), a clinical-stage biopharmaceutical company focused on preventing and treating “cytokine storm,” announced that the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which is part of the United States Government Department of Health and Human Services (HHS) as represented by the Division of Microbiology and Infectious Diseases (DMID), and Humanigen have executed a clinical trial agreement for lenzilumab, the company’s proprietary Humaneered®anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody drug candidate, as an agent to be evaluated in the NIAID-sponsored Big Effect Trial (BET) in hospitalized patients with COVID-19. BET will help advance NIAID’s strategic plan for COVID-19 research, which includes conducting studies to advance high-priority therapeutic candidates.1 Identification of agents with novel mechanisms of action for therapy is a strategic priority. This trial builds on initial data from NIAID’s Adaptive COVID-19 Treatment Trial (ACTT) that demonstrated Gilead’s investigational antiviral, remdesivir, may improve time to recovery in hospitalized patients with COVID-19. BET will evaluate the combination of lenzilumab and remdesivir on treatment outcomes versus placebo and remdesivir in hospitalized COVID-19 patients. The trial is expected to enroll 100 patients in each arm of the study with an interim analysis for efficacy after 50 patients have been enrolled in each arm.