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Archive - Jul 14, 2020

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Moderna Announces Publication in NEJM of Interim Results from Phase 1 Study of Its mRNA Vaccine (mRNA-1273) Against COVID-19; Neutralizing Antibody Titers Observed in 100% of Evaluated Participants; Phase 3 Study to Begin July 27

On July 14, 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 the publication of an interim analysis of the open-label Phase 1 study of mRNA-1273, its vaccine candidate against COVID-19, in The New England Journal of Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home). The open-acccess article, published online today (July 14, 2020) is titled “An mRNA Vaccine Against SARS-CoV-2--Preliminary Report.” This interim analysis evaluated a two-dose vaccination schedule of mRNA-1273 given 28 days apart across three dose levels (25, 100, 250 µg) in 45 healthy adult participants ages 18-55 years, and reports results through Day 57. Results from participants in the initial dose cohorts who received both vaccinations and were evaluated at pre-specified timepoints reaffirm the positive interim data assessment announced (https://investors.modernatx.com/news-releases/news-release-details/moder...) on May 18th and show that mRNA-1273 induced rapid and strong immune responses against SARS-CoV-2. The study was led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). mRNA-1273 was generally safe and well-tolerated, with no serious adverse events (SAEs) reported through Day 57. Adverse events (AEs) were generally transient and mild to moderate in severity. The most notable adverse events were seen at the 250 µg dose level, with three of those 14 participants (21%) reporting one or more severe events.

Extracellular Vesicles Displaying ACE2 Can Prevent Infection by SARS-CoV-2 Spike-Protein-Pseudotyped Lenti Virus; ACE2-EVs Are Up to 1500X As Effective As Soluble ACE2; Infection Prevention Further Enhanced by Inclusion of TMPRRS2 in EV Surface

In a non-final, non-peer-reviewed, pre-print* article, published online on July 8, 2020 on the pre-print portal bioRxiv,* researchers in Paris, France, have shown that extracellular vesicles (EVs) bearing the surface receptor ACE2 (angiotensin-converting enzyme 2), to which the spike (S) protein of SARS-CoV-2 virus binds when infecting human cells, may serve as decoys to the invading virus because such EVs effectively prevent infection of ACE2-bearing cells by a SARS-Co-V2 S-protein-pseudotyped lenti virus in vitro. The authors note that SARS-CoV-2 entry is mediated in COVID-19 by binding of the viral S protein to the host cell surface receptor ACE2 and subsequent priming by host cell TMPRRS2 (transmembrane protease, serine 2) that allows membrane fusion and viral entry to the cell. The researchers said that the reduction of infectivity correlates positively with the level of EV ACE2 This reduction in infectivity is 500X to 1500X more efficient than is achieved with soluble ACE2, and is further enhanced by inclusion of TMPRRS2 in the EV surface. The researchers conclude that ACE2-EVs represent a potential versatile therapeutic tool to block, not only SARS-CoV-2 infection, but also infections by other coronaviruses that use ACE2 for host cell entry. The open-access article on the bioRxiv portal is titled “Extracellular Vesicles Containing ACE2 Efficiently Prevent Infection by SARS-Cov-2 Spike Protein-Containing Virus” (https://www.biorxiv.org/content/10.1101/2020.07.08.193672v1?fbclid=IwAR0...). The co-senior and co-corresponding authors of this open-access article are Mercedes Tkach, PhD; Clotilde Thery, PhD; and Lorena Martin-Jaular, PhD, each of INSERM U932, Institut Curie Centre de Recerche, PSL Research University, Paris, France.

Scientists Identify Oncogene (AVIL) That Drives Glioblastoma; Discovery Offers Promising New Treatment Target for Possible Treatment of a Cancer That Is Always Fatal

Scientists have identified an oncogene (a cancer-causing gene) responsible for glioblastoma, the deadliest brain tumor. The discovery offers a promising new treatment target for a cancer that is always fatal. The researchers say the oncogene is essential to the survival of the cancer cells. Without it, the cancer cells die. Scientists have already developed many targeted therapies for other cancers with a similar "oncogene addiction." "Glioblastoma is one of the deadliest cancers. Unfortunately, there is no effective treatment option for the disease. The current standard option, radiation plus temozolomide, which displayed a 2.5-month better survival rate, was hailed as a great success. Clearly, better understanding and new therapeutic targets are urgently needed," said researcher Hui Li, PhD, of the University of Virginia (UVA) School of Medicine and the UVA Cancer Center. "The novel oncogene we discovered promises to be an Achilles' heel of glioblastoma, with its specific targeting potentially an effective approach for the treatment of the disease." Oncogenes are naturally occurring genes that spiral out of control and cause cancer. The oncogene that Dr. Li and his colleagues identified, avilllin (AVIL), normally helps cells maintain their size and shape. But the gene can be shifted into overdrive by a variety of factors, the researchers found. This causes cancer cells to form and spread. Blocking the gene's activity completely destroyed glioblastoma cells in lab mice but had no effect on healthy cells. This suggests targeting the gene could be an effective treatment option.

A Balancing Act Between Immunity and Longevity; Mutation in Splicing Factor RNP-6 Inhibits Immune Response in C. elegans, But Increases Lifespan, Barring Infection; RNP-6 Human Orthologue, Splicing Factor PUF60, May Also Be Involved in Immunity & Lifespan

As we age, the immune system gradually becomes impaired. One aspect of thisA Balancing Act Between Immunity and Longevity; Mutation in Splicing Factor RNP-6 Inhibits Immune Response in C. elegans, But Increases Lifespan, Barring Infection; RNP-6 Human Orthologue Splicing Factor PUF60 May Also Be Involved in Immunity & Lifespan impairment is chronic inflammation in the elderly, which means that the immune system is constantly active and sends out inflammatory substances. Such chronic inflammation is associated with multiple age-related diseases including arthritis and Alzheimer's disease, and impaired immune responses to infection. One of the questions in aging research is whether chronic inflammation is a cause of aging, or a consequence of the aging process itself? Scientists in the laboratory of Adam Antebi, PhD, Director of the Max Planck Institute for Biology of Aging in Cologne, Germany, have found evidence suggesting that increased inflammation causes the aging process to speed up, and that there is a fine balance between maintaining immune system function and longevity. From their work in the tiny roundworm, Caenorhabditis elegans, the scientists discovered a mutation in an evolutionarily conserved gene [the RNP-6 (ribonucleoprotein 6) gene in C. elegans, whose orthologous gene in humans is called PUF60 (poly U binding splicing factor 60)], which made the worms long-lived, but, at the same time, dampened their immune response. Worms with this mutation lived about 20% longer than normal worms, but when they were infected with certain bacteria, they succumbed more quickly to the infection. This suggests that an overactive immune system also has a price: it shortens life span. Conversely, a less active immune system pays off in a longer life span--as long as the animal does not die from an infection.

Biocon Describes Clinical Study Enabling Approval of Itolizumab for COVID-19 in India; Novel Anti-CD6 Monoclonal Antibody Reduces Release of Pro-Inflammatory Cytokines, Controls “Cytokine Storm,” & Reduces COVID-19 Mortality

On July 13, 2020, Biocon Ltd. (BSE code: 532523, NSE: BIOCON), an innovation-led global biopharmaceuticals company, headquartered in Bengaluru, Karntaka, India, presented key insights into the results of the pivotal study that demonstrated its novel biologic, itolizumab, significantly reduced mortality in moderate to severe ARDS (acute respiratory distress syndrome) patients hospitalized with COVID-19, in India. This led to the Drug Controller General of India (DCGI) approving this novel biologic therapy for restricted emergency use in India. Kiran Mazumdar-Shaw, Executive Chairperson, Biocon, said: “Itolizumab is a ‘Made in India,’ ‘Innovated in India,’ first-in-class anti-CD6 monoclonal antibody, which has a seven-year proven track record of safety as doctors in India have been prescribing this biologic therapy to treat acute psoriasis. As itolizumab has been approved in India and given that we are in the middle of a medical emergency, the regulator has approved Biocon’s product for emergency use based on compelling data from a pivotal clinical trial involving a cohort of 30 patients. The two-arm, randomized study met both the primary and secondary endpoints, with the Itolizumab arm demonstrating statistically significant advantage over the control arm, culminating in the drug’s approval for restricted emergency use by the DCGI. The study results show that itolizumab’s unique mechanism of action can bring down mortality in moderate to severe ARDS patients due to COVID-19.”