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Archive - Jul 2020

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.

Moderna Announces Beginning of Phase 3 COVE Study of mRNA Vaccine Against COVID-19 (mRNA-1273); Study Expected to Enroll 30,000 Participants in US

On July 27, 2020, Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced that the Phase 3 study of its mRNA vaccine candidate (mRNA-1273) against COVID-19 has begun dosing participants. The Phase 3 study, called the COVE (Coronavirus Efficacy) study, is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services. “We are pleased to have started the Phase 3 COVE study,” said Stephane Bancel, MBA, CEO at Moderna. “We are grateful to the efforts of so many inside and outside the company to get us to this important milestone. We are indebted to the participants and investigators who now begin the work of the COVE study itself. We look forward to this trial demonstrating the potential of our vaccine to prevent COVID-19, so that we can defeat this pandemic.” The Phase 3 study protocol follows the U.S. FDA guidance on clinical trial design for COVID-19 vaccine studies. The randomized, placebo-controlled trial is expected to include approximately 30,000 participants in the United States, testing an mRNA-1273 dosage of 100 µg. The primary endpoint will be the prevention of symptomatic COVID-19 disease. Key secondary endpoints include prevention of severe COVID-19 disease (as defined by the need for hospitalization) and prevention of infection by SARS-CoV-2, regardless of symptomology. SARS-CoV-2 is the virus that causes COVID-19.

July 24th

Gene in Fat Plays Key Role in Insulin Resistance; “Getting Better Grasp on Function of KBTBD2 Could Open Completely New Window into How Insulin Sensitivity Is Regulated,” Says Nobelist Who Made Seminal “Innate Immunity” Discovery of Toll-Like Receptors

Deleting a key gene in mice in just their fat made tissues throughout these animals insulin-resistant, in addition to other effects, a new study by University of Texas Southwestern (UTSW) researchers shows. The findings, initially published online on May 7, 2020 in PNAS (https://www.pnas.org/content/117/21/11829), could shed light on Type 2 diabetes and other insulin-resistance disorders, which remain poorly understood, despite decades of study. The open-access article is titled “Tissue-Specific Disruption of Kbtbd2 Uncovers Adipocyte-Intrinsic and -Extrinsic Features of the teeny Lipodystrophy Syndrome.” In 2016, UTSW immunologist and geneticist and Nobel Laureate Bruce Beutler (photo), MD, (https://profiles.utsouthwestern.edu/profile/10593/bruce-beutler.html, Zhao Zhang, PhD (https://profiles.utsouthwestern.edu/profile/155419/zhao-zhang.html, and their colleagues reported a new mouse mutant that they named teeny (https://www.pnas.org/content/113/42/E6418), which resulted from inactivating a gene known as KBTBD2 that is widely expressed throughout the body in mice and humans. In addition to these animals’ small size – about half that of normal “wild-type” mice – the scientists quickly noticed that teeny mice produce a lot of urine, often a sign of diabetes. Dr. Beutler is a Regental Professor and Director of the Center for the Genetics of Host Defense (https://www.utsouthwestern.edu/education/medical-school/departments/gene...). Dr. Zhang is an Assistant Professor of Internal Medicine who also has an appointment in the Center. Sure enough, tests showed that these teeny animals had extremely high blood sugar, severe insulin resistance, and high insulin levels that peaked at 8 weeks of age and then gradually declined. They also had abnormally low amounts of body fat, but had fatty livers.

July 22nd

Election of Next President & Riveting Plenary Address Highlight Day 2 of International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22)

Tuesday, July 21, witnessed the election of new ISEV President Clotilde Théry (photo) (https://en.wikipedia.org/wiki/Clotilde_Th%C3%A9ry), PhD, of the Institut Curie in Paris, and an electrifying scientific presentation on work involving exosomes, cardiology, and Duchenne muscular dystrophy (DMD), as two of many highlights of an action-packed Day 2 of the International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/). This year’s ISEV meeting has successfully gone virtual with 1,600 virtual attendees from 52 countries around the world, and is offering ~600 presentations of various types (Plenary Addresses, “Hot-Topic” Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions), both live-streamed and on-demand, to its large international group of participants. Tuesday’s activities included the meeting’s third Plenary Address, presentation of the third of four ISEV Featured Abstracts, the ISEV General Assembly meeting at which new ISEV President Clotilde Thery was elected and three ISEV Special Achievement Awards were presented, the holding of highly informative Education Sessions 3 & 4, and presentations of key current technology by ISEV 2020’s Gold Sponsors. The meeting’s third Plenary Address, “Deconstructing Regenerative Medicine: From Cells to Exosomes and Defined Factors,” was delivered by Eduardo Marbán, MD, PhD, Founding Director, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles. Dr. Marbán is an international leader in cardiology and a pioneering heart researcher. His 30-plus years of experience in patient care and research have led to key discoveries in gene and stem cell therapies for heart disease. Those discoveries have formed the basis for multiple startup companies. Dr.

July 22nd

“EVs in Neurological Diseases,” with Focus on Rett Syndome, Is Second Plenary Address on Opening Day of International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) for 1,600 Virtual Attendees from 52 Countries

(Written for BioQuick News by Michael A. Goldman, PhD, Professor & Former Chair, Biology, San Francisco State University, https://faculty.sfsu.edu/~goldman/) The International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), with a record 1,600 virtual attendees from 52 countries around the world, and offering ~600 presentations of various types (Plenary Addresses, “Hot-Topic” Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions), both live-streamed and on-demand, showcased its second Plenary Address on Monday, July 20. This address was titled “EVs in Neurological Diseases,” and was delivered by Hollis Cline (photo), PhD, the Hahn Professor of Neuroscience and Co-Chair of the Department of Neuroscience at Scripps Research in La Jolla, California, USA. Dr. Cline (https://www.scripps.edu/faculty/cline/) is also a Counselor for the National Institute of Neurological Disorders and Stroke (NINDS) and a Past President of the Society for Neuroscience. She received her BA from Bryn Mawr College and her PhD from the University of California at Berkeley, followed by postdoctoral training at Yale University and Stanford University. Dr. Cline has served on the faculty of the University of Iowa and the Cold Spring Harbor Laboratory, where she served as the Director of Research from 2002-2006. Dr. Cline’s research has demonstrated the roles of a variety of activity-dependent mechanisms in controlling structural plasticity of neuronal dendrites and axons, synaptic maturation, and topographic map formation. This body of work has helped to generate a comprehensive understanding of the role of experience in shaping brain development.

Fourth Featured Abstract at ISEV 2020 Virtual Annual Meeting Reports That, Following Endocytosis by Acceptor Cells, Extracellular Vesicles (EVs) Release Their Cargo from Endosomes; New Analytical Methodology Enables Key Finding

Today (Wednesday, June 22), in the last of four Featured Abstracts presented by graduate students during the ISEV 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), Bhagyashree Joshi (photo), of the Department of Biomedical Engineering, University of Groningen, University Medical Center Groningen, The Netherlands, presented her group’s abstract (FA03) “Genetically Encoded Probes Provide Insight into Extracellular Vesicle Cargo Release in Cells.” Ms. Joshi is a PhD candidate in the laboratory of Inge Zuhorn, PhD, Associate Professor, Department of Biomedical Engineering, University of Groningen, University Medical Center Groningen University Medical Center Groningen. In her introduction, Ms. Joshi noted that extracellular vesicles (EVs) are known to modulate tissue development, regeneration, and disease through the transfer of proteins, nucleic acids, and lipids between cells. Currently, however, the mechanism of cytosolic delivery of EV cargo is largely unknown, she said. It has been speculated that EVs undergo back fusion at multi-vesicular bodies (MVBs) in recipient cells to release their functional cargo. However, Ms. Joshi said, evidence for this is lacking. She remarked that tracing the cellular uptake of EVs with high resolution, as well as acquiring direct evidence for the release of EV cargo, is challenging, chiefly because of technical limitations. To address this problem, Ms. Joshi and colleagues developed an analytical methodology that combined state-of-the-art molecular tools and correlative light and electron microscopy (CLEM) to identify the intracellular site for EV cargo release. Green fluorescent protein (GFP) was loaded inside EVs through the expression of GFP-CD63, a fusion of GFP to the cytosolic tail of CD63, in EV producer cells.

Third Featured Abstract at ISEV 2020 Virtual Annual Meeting Reports That Expression of Tetraspanin 8 (Tspan8) Causes Nuclear Proteins to Be Incorporated into Tumor-Derived Extracellular Vesicles (EVs); Results Suggest New Mechanism of Action for Tspan8

On Tuesday, June 21, in the third of four Featured Abstracts being presented by junior investigators during the ISEV 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), Elena Grueso Navarro (photo), a Marie Curie Fellow at TRAIN-EV* at the Institute for Infection Prevention and Hospital Epidemiology, Medical Center-University of Freiburg, Breisgau, German, presented her group’s abstract (FA02) “Nuclear Proteins Are Recruited into Tumor-Derived Extracellular Vesicles Upon Expression of Tetraspanin Tspan8.” Ms. Navarro is a PhD candidate in the laboratory of Irina Nazarenko, PhD, Head, Exosomes & Tumor Group, Institute for Infection Prevention and Hospital Epidemiology, Medical Center-University of Freiburg. In her introduction, Ms. Grueso Navarro noted that tetraspanin 8 (Tspan8) is a transmembrane protein that exhibits a unique expression pattern, being overexpressed in many cancer types, but undetectable in a majority of healthy tissues. When overexpressed, Tspan8 facilitates cell motility, and, in tumor models, it supports invasion and metastasis. In addition, Tspan8 is recruited to the extracellular vesicles (EVs). Previous work in Dr. Nazarenko's laboratory has shown that Tspan8 affects EV content and mediates the EVs’ function in metastasis and angiogenesis. These data suggest that Tspan8 may be a promising therapeutic target in cancer.