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December 30th, 2020

Codiak BioSciences Reports Positive Initial Phase 1 Results for Its Exosome-Based IL-12 Vehicle (exoIL-12™) Demonstrating Tolerability and Absence of Systemic IL-12 Exposure in Healthy Volunteers

On Decembr 30, 2020, Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, announced that the primary objectives were met in the initial part of its Phase 1 trial, which evaluated a single ascending dose of exoIL-12 in healthy volunteers. In this randomized, placebo controlled, double-blind study, exoIL-12 demonstrated a favorable safety and tolerability profile, with no local or systemic treatment-related adverse events and no detectable systemic exposure of IL-12. “This is an important milestone, as these results show that exoIL-12 acts in humans as we had expected, based on our preclinical evaluations. The safety and tolerability profile observed here support the target profile that we are hoping to achieve with this candidate,” said Benny Sorensen, MD, PhD, Senior Vice President and Head of Clinical Development, Codiak. “We’re looking forward to advancing exoIL-12 into the multi-dose part of the study in cutaneous T-cell lymphoma patients and presenting the detailed results from the healthy volunteer part of this study at an upcoming medical conference.”

December 29th

Scientists in Russia Synthesize Variants of Toxic Pesticide That Are Effective Against ESKAPE Panel of Antibiotic-Resistant Bacteria; Human Toxicity May Be Reduced by Careful Optimization of Molecular Periphery Around Nitro Heteroaromatic “Warhead”

N-aryl-C-nitroazoles are an important class of heterocyclic compounds. They are used as pesticides and fungicides. However, these substances could be toxic to humans and cause mutations. As they are not frequently used, there is little data about them in the medicinal chemistry literature. However, it has been suggested recently that the groups of compounds that are traditionally avoided may help to fight pathogenic bacteria. Yet, to reduce toxic effects, a great amount of work must be carried out at the molecular level, accurate optimization of the molecular environment of the nitro-heteroaromatic "warhead.” The validity of this approach was demonstrated in the early 2000s through the development of anti-tuberculosis drugs delamanid and pretomanid, currently approved for medical use. They act like prodrugs, that is, the substance itself is inactive, but acquires effective new properties when it enters the human body. In terms of the new work described here, scientists from the Immanuel Kant Baltic Federal University in Kaliningrad, together with colleagues from St. Petersburg State University, the L. Pasteur Research Institute of Epidemiology and Microbiology, and the Research Institute of Phthisiopulmonology, all in St. Petersburg (photo), are looking for new effective antibacterial drugs, studying various nitrogen heteroaromatic compounds with a nitro group which might be used in medicine further. The compound OTB-021 was found to work well against drug-sensitive strains of tuberculosis pathogens, but was powerless against strains of pathogens that belong to the so-called ESKAPE panel.

Hemoglobins in Different Species Evolved from Same Ancestral Gene, New Study Suggests

Thanks to the marine worm Platynereis dumerilii (image), an animal whose genes have evolved very slowly, scientists from the French National Centre for Scientific Research (CNRS), Université de Paris, and Sorbonne Université, in association with others at the University of Saint Petersburg and the University of Rio de Janeiro, have shown that while hemoglobin appeared independently in several species, it actually descends from a single gene transmitted to all by their last common ancestor. These findings were published online on December 29, 2020 in BMC Evolutionary Biology. The open-access article is titled “Globins in the Marine Annelid Platynereis dumerilii Shed New Light on Hemoglobin Evolution in Bilaterians.” Having red blood is not peculiar to humans or mammals. This color comes from hemoglobin, a complex protein specialized in transporting the oxygen found in the circulatory system of vertebrates, but also in annelids (a worm family whose most famous members are earthworms), molluscs (especially pond snails), and crustaceans (such as daphnia or “water fleas”). It was thought that for hemoglobin to have appeared in such diverse species, it must have been “invented” several times during evolution. But recent research has shown that all of these hemoglobins, thought to have been born “independently,” actually derive from a single ancestral gene. Researchers from the Institut Jacques Monod (CNRS/Université de Paris), the Laboratoire Matière et Systèmes Complexes (CNRS/Université de Paris), the Station Biologique de Roscoff (CNRS/Sorbonne Université), the Universities of Saint Petersburg (Russia) and Rio de Janeiro (Brazil), conducted this research on Platynereis dumerilii, a small marine worm with red blood.

Novavax Announces Initiation of PREVENT-19 Pivotal Phase 3 Efficacy Trial of COVID-19 Vaccine in the United States and Mexico

On December 28, 2020, Novavax, Inc. (Nasdaq: NVAX), a late-stage biotechnology company developing next-generation vaccines for serious infectious diseases, announced initiation of PREVENT-19, its pivotal Phase 3 study in the United States and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373, the company’s COVID-19 vaccine candidate. The trial builds on research from Phase 1/2 studies demonstrating that the vaccine provoked a robust immune response, generated highly neutralizing antibodies against the virus, and was generally well-tolerated. “With the COVID-19 pandemic raging around the globe, this trial is a critical step in building the global portfolio of safe and effective vaccines to protect the world’s population,” said Stanley C. Erck, MBA, President and Chief Executive Officer, Novavax. “We thank our colleagues and partners who continue to work with us to urgently advance our commercial-scale manufacturing processes, and we are grateful for the hard work and assistance from Operation Warp Speed, the U.S. FDA, and the government of Mexico on this program.” NVX-CoV2373 contains a full-length, prefusion spike protein made using Novavax’ recombinant nanoparticle technology and the company’s proprietary saponin-based Matrix-M™ adjuvant. The purified protein is encoded by the genetic sequence of the SARS-CoV-2 spike (S) protein and is produced in insect cells. It can neither cause COVID-19 nor can it replicate, is stable at 2°C to 8°C and is shipped in a ready-to-use liquid formulation that permits distribution using standard vaccine supply chain channels.

December 28th

Gut Cells (Enterocytes) Sound First Alarm When Cryptosporidium Parasites Invade; Inflammasome Is Key

To effectively combat an infection, the body first has to sense it's been invaded, then the affected tissue must send out signals to marshal resources to fight the intruder. Knowing more about these early stages of pathogen recognition and response may provide scientists with crucial clues when it comes to preventing infections or treating inflammatory diseases resulting from overactive immunity. That was the intent behind a new study, led by researchers at the University of Pennsylvania School of Veterinary Medicine (Penn Vet), examining infection with the parasite Cryptosporidium (image). When the team looked for the very first "danger" signals emitted by a host infected with the parasite, they traced them not to an immune cell, as might have been expected, but to epithelial cells lining the intestines, where Cryptosporidium sets up shop during an infection. Known as enterocytes, these cells take up nutrients from the gut, and here they were shown to alert the body to danger via the molecular receptor NLRP6, which is a component of what's known as the inflammasome (https://en.wikipedia.org/wiki/Inflammasome). "You can think about the inflammasome as an alarm system in a house," says Boris Striepen, PhD, a Professor in the Department of Pathobiology at Penn Vet and senior author on the paper, which was published online on December 28, 2020 in PNAS. "It has various components--like a camera that watches the door, and sensors on the windows--and once triggered it amplifies those first signals to warn of danger and send a call for help.

New England Journal of Medicine Publishes Positive Initial Regeneron Antibody Cocktail Results in Non-Hospitalized Patients with COVID-19

On December 17, 2020, Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that the New England Journal of Medicine (NEJM) has published initial clinical data from an ongoing seamless Phase 1/2/3 trial of the Regeneron antibody cocktail casirivimab and imdevimab in non-hospitalized patients with COVID-19 (https://www.nejm.org/doi/full/10.1056/NEJMoa2035002). "The peer-reviewed NEJM publication of our first set of clinical data in recently infected COVID-19 patients showed that casirivimab and imdevimab effectively reduced viral load and the need for medically-attended visits, with the greatest benefit in patients who had not yet mounted their own effective immune response or had high viral load at baseline," said David Weinreich, MD, Senior Vice President and Head of Global Clinical Development at Regeneron and lead author of the publication. "The investigational cocktail is now available to indicated high-risk U.S. patients under an Emergency Use Authorization, and we also continue a robust clinical development program." "Building on these initial findings, we were gratified to recently report follow-on data from the next-stage analysis of this ongoing trial, which prospectively replicated these results in a rigorous and statistically significant manner. These follow-on data provided the first definitive prospective evidence demonstrating anti-viral activity for a treatment regimen now available for COVID-19, and also further documented the ability of this treatment to decrease the need for further medical attention," said George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer at Regeneron.

Discovery About How Cancer Cells Evade Immune Defenses Inspires New Treatment Approach; Inhibiting Action of Scissor-Like ENPP1 Protein May Strike at Cancer in Two Different Ways, Sloan-Kettering Study Indicates

Cancer cells are known for spreading genetic chaos. As cancer cells divide, DNA segments and even whole chromosomes can be duplicated, mutated, or lost altogether. This is called chromosomal instability, and scientists at Memorial Sloan Kettering Cancer Center (MSKCC) have learned that it is associated with cancer's aggressiveness. The more unstable chromosomes are, the more likely that bits of DNA from these chromosomes will end up where they don't belong: outside of a cell's central nucleus and floating in the cytoplasm. Cells interpret these rogue bits of DNA as evidence of viral invaders, which sets off their internal alarm bells and leads to inflammation. Immune cells travel to the site of the tumor and churn out defensive chemicals. A mystery has been why this immune reaction, triggered by the cancer cells, does not spell their downfall. "The elephant in the room is that we didn't really understand how cancer cells were able to survive and thrive in this inflammatory environment," says Samuel Bakhoum (https://www.mskcc.org/research-areas/labs/samuel-bakhoum),MD, PhD, a physician-scientist at MSKCC and a member of the Human Oncology and Pathogenesis Program. According to a new study from Dr. Bakhoum's lab, published online on December 28, 2020 in Cancer Discovery (https://cancerdiscovery.aacrjournals.org/content/early/2020/12/23/2159-8...), the reason has to do, in part, with a molecule sitting on the outside of the cancer cells that destroys the warning signals before they ever reach neighboring immune cells. The findings help to explain why some tumors do not respond to immunotherapy, and--equally important--suggest ways to sensitize them to immunotherapy. The warning system Dr.

Big Bumblebees Take Time to Memorize Locations of Best Flowers; Big Bumblebees Have Longer Flight Range and Higher Carrying Capacity Than Smaller Bumblebees, Which Do Not Alter Their Location Learning Efforts on Basis of Flower’s Nectar Richness

Big bumblebees take time to learn the locations of the best flowers, new research shows. Meanwhile, smaller bumblebees--which have a shorter flight range and less carrying capacity--don't pay special attention to flowers with the richest nectar. University of Exeter (UK) scientists examined the "learning flights" which most bees perform after leaving flowers. Honeybees are known to perform such flights-- and the study shows bumblebees do the same, repeatedly looking back to memorize a flower's location. "It might not be widely known that pollinating insects learn and develop individual flower preferences, but, in fact, bumblebees are selective," said Natalie Hempel de Ibarra, PhD, Associate Professor of Neuroethology at Exeter's Centre for Research in Animal Behavior (https://psychology.exeter.ac.uk/staff/profile/index.php?web_id=Natalie_H...). "On leaving a flower, they can actively decide how much effort to put into remembering its location. The surprising finding of our study is that a bee's size determines this decision-making and the learning behavior." In the study, captive bees visited artificial flowers containing sucrose (sugar) solution of varying concentrations. The larger the bee, the more its learning behavior varied depending on the richness of the sucrose solution. Smaller bees invested the same amount of effort in learning the locations of the artificial flowers, regardless of whether sucrose concentration was high or low. "The differences we found reflect the different roles of bees in their colonies," said Professor Hempel de Ibarra. "Large bumblebees can carry larger loads and explore further from the nest than smaller ones.

Discovery Boosts Theory That Life on Earth Arose from RNA-DNA Mix; Undercuts “RNA World” Hypothesis & Suggests Enzyme-Free Chemical Reactions That May Prove Superior to PCR in Some Cases

Chemists at Scripps Research in La Jolla, California, have made a discovery that supports a surprising new view of how life originated on our planet. In a study published online on December 15, 2020 in the chemistry journal Angewandte Chemie, the scientists demonstrated that a simple compound called diamidophosphate (DAP), which was plausibly present on Earth before life arose, could have chemically knitted together tiny DNA building blocks called deoxynucleosides into strands of primordial DNA. The finding is the latest in a series of discoveries, over the past several years, pointing to the possibility that DNA and its close chemical cousin RNA arose together as products of similar chemical reactions, and that the first self-replicating molecules--the first life forms on Earth--were mixes of the two. The discovery may also lead to new practical applications in chemistry and biology, but its main significance is that it addresses the age-old question of how life on Earth first arose. In particular, it paves the way for more extensive studies of how self-replicating DNA-RNA mixes could have evolved and spread on the primordial Earth and ultimately seeded the more mature biology of modern organisms. The Angewandte Chemie article is titled “Prebiotic Phosphorylation and Concomitant Oligomerization of Deoxynucleosides to form DNA.” "This finding is an important step toward the development of a detailed chemical model of how the first life forms originated on Earth," says study senior author Ramanarayanan Krishnamurthy, PhD, Associate Professor of Chemistry at Scripps Research.

QUAZAR Global Trial of Drug (Oral Azacytidine, CC-486) Shows Significantly Extended Survival of Patients Over 55 with Acute Myeloid Leukemia; Drug “Likely to Establish New Standard of Care for Older Patients with AML,” First Author of NEJM Article States

A landmark paper published online on December 23, 2020 in the New England Journal of Medicine describes the results from a global trial across 148 sites in 23 countries, showing a 30 per cent improvement in survival in patients with acute myeloid leukemia (AML). The Phase 3 clinical trial called QUAZAR, showed that a drug, called CC-486 (oral azacytidine) (image), significantly improved survival in older patients, over the age of 55, with the disease. AML is the most acute blood cancer in adults and its incidence increases with age, with a poor prognosis. With current treatments, the majority of older patients will die of their disease within 2 years of diagnosis. Approximately 20,000 people in the United States are diagnosed with AML every year. The global trial, led by Professor Andrew Wei from Monash University's Australian Centre for Blood Diseases and a hematologist at Alfred Health, focused on people with AML over 55 years of age, "because of an unmet need to identify new agents able to improve outcome in patients after completing chemotherapy," he said. "After intensive chemotherapy, the risk of AML relapse is high. Many older patients are not eligible to receive a stem cell transplant and so a less toxic option to reduce disease recurrence is desirable, rather than just being monitored and waiting for the disease to come back," he said. "Based on the results of the QUAZAR study, it is very exciting to think that, by taking a tablet that is relatively well-tolerated, we can help reduce relapse risk and improve survival." The NEJM article was published online on December 24, 2020 and is titled “Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.” The trial involved 472 patients, with an average age 68 years, who were either given CC-486 or a placebo.