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April 18th, 2020

Capricor Initiates Compassionate Use Program for Severe COVID-19 Patients Using CAP-1002, Its Novel Cell Therapy Based on Cardiosphere-Derived Cells; CDCs Release Exosomes That May Mitigate Severe Inflammatory Response Associated with COVID-19

On April 3, 2020, Capricor Therapeutics (NASDAQ: CAPR) a clinical-stage biotechnology company focused on the development of first-in-class biological therapeutics for the treatment or prevention of serious diseases, announced it is providing CAP-1002, its novel cell therapy to patients with advanced COVID-19 under the compassionate use pathway. Two patients were treated in the previous week at a leading healthcare center in Los Angeles, California with additional patients planned in the coming weeks. Infusions of CAP-1002 were administered safely and patients are currently clinically stable. “Physicians leading the fight against COVID-19 patients approached Capricor to discuss the use of CAP-1002 due to its strong immunomodulatory capabilities. They believe that the use of CAP-1002 for the treatment or attenuation of ARDS (acute respiratory distress syndrome) pneumonia in COVID-19 patients is based on solid scientific rationale and pre-clinical data. We know from previously published pre-clinical data that CAP-1002 mitigates the release of anti-inflammatory cytokines, as well as macrophage activation in a number of models of inflammation, including sepsis and autoimmune diseases. It is believed that COVID-19-induced ARDS pneumonia is a response to an exaggerated and sustained cytokine storm. As such, we are hopeful that CAP-1002 will be of value to patients with respect to the treatment of COVID-19,” said Linda Marbán, PhD, Capricor’s President and Chief Executive Officer. The compassionate use act allows the FDA to immediately collect information on experimental treatments and then make the appropriate decisions about the safety and efficacy of those treatments.

Orgenesis & Excella-Bio Announce Breakthrough Manufacturing Process for Bioxomes™ (Proprietary Synthetic Exosomes/Extracellular Vesicles); Patented Process Results in Uniform, Scalable Production & Ability to Deliver Specific Cargo to Targeted Cells

On March 31, 2020, Orgenesis Inc. (NASDAQ: ORGS) (“Orgenesis” or the “Company”), a pioneering, global biotech company committed to lowering costs, accelerating commercialization, and transforming the delivery of cell and gene therapies (CGTs), announced that it has developed a breakthrough and patented manufacturing process for Bioxomes™ (synthetic exosomes/extracellular vesicles), through its collaboration and licensing agreement with Excella-Bio Ltd. Exosomes, or extracellular vesicles (EVs), are small vesicles that can transfer DNA, RNA, and proteins from the cell of origin to other, often targeted cells, thereby enabling alteration of the function of the targeted cells. It is belieed that exosomes can provide the same therapeutic benefit of whole cells, without the risks and difficulties of administering entire cells to patients. Together, Orgenesis and Excella-Bio have developed Bioxomes, which are synthetic exosomes/EVs. Until now, exosome/EV production has been based on conventional ultracentrifugation or ultrafiltration. These are both complex and costly techniques. Bioxomes are engineered and produced through a patented method as membrane nanoparticles isolated from cell cultures of various sources. Orgenesis and ExcellaBio have now demonstrated the optimization and scale-up of Bioxomes™, while generating consistent and repeatable results, including uniform particles sizes. These Bioxomes have demonstrated the ability to fuse with cell membranes and deliver an intracellular cargo, in a similar manner to that of natural exosomes. Bioxomes can be sourced effectively from various cell cultures. These include mesenchymal stem cells, immortalized cells, immune cells, and epithelial cells.

Mysterious Tuft Cells Found to Play Role in Pancreatitis

Persistent inflammation of the pancreas (chronic pancreatitis) is a known risk factor for developing pancreatic cancer, the third-deadliest cancer in the United States. Tuft cells (cells sensitive to chemical (chemosensory) changes typically found in the intestines and respiratory tract) had previously been discovered in the pancreas, but their function has largely remained a mystery. Now, a team of Salk Institute scientists, led by Professor Geoffrey Wahl, PhD, and Staff Scientist Kathleen DelGiorno, PhD, has uncovered the formation of tuft cells during pancreatitis and the surprising role of tuft cells in immunity, using mouse models of pancreatitis. The findings, published online in Frontiers in Physiology on February 14, 2020, could lead to the development of new biomarkers to test for pancreatitis and pancreatic cancer. The open-access article is titled “Tuft Cell Formation Reflects Epithelial Plasticity in Pancreatic Injury: Implications for Modeling Human Pancreatitis.” "By understanding these early stages of pancreas disease, we hope our work will lead to the development of new strategies to diagnose and treat pancreatitis and pancreatic cancer early on," says Dr. Wahl, co-corresponding author and holder of the Daniel and Martina Lewis Chair in Salk's Gene Expression Laboratory. The pancreas is an abdominal organ that plays a role in digestion and blood sugar regulation. Yet, scientists know little about how the pancreas recovers from injuries, such as pancreatitis, or fights off pancreatic cancer. Most of the pancreas is composed of acinar cells, which produce and secrete digestive enzymes. Acinar cells also have the ability to transform into another type of cell called a tuft cell.

Male Ring-Tailed Lemurs Exude Fruity-Smelling Odorants from Their Wrists to Attract Mates

In an article published online in Current Biology on April 16, 2020, scientists reported that male ring-tailed lemurs (Lemur catta) become more attractive to females by secreting a fruity and floral aroma from their wrists. Using detailed chemical analysis, the researchers identified three compounds responsible for this sweet scent, marking the first time that pheromones have been identified in a primate. The open-access article is titled “Key Male Glandular Odorants Attracting Female Ring-Tailed Lemurs.” "During the yearly breeding season, male lemurs rub the glands on their wrists against their fluffy tails and then wave them at females in a behavior called 'stink flirting,'" says senior author Kazushige Touhara, PhD, Professor and biochemist at the University of Tokyo. Ring-tailed lemurs have well-developed scent glands on their shoulders and wrists. These glands are typically used to designate social rank, territory, and reproductive status. However, behavioral observations show they also use their scent glands to catch the attention of females. "Because only ring-tailed lemurs have these wrist glands and exhibit 'stink flirting' behavior, we reasoned that specific odorants for sexual communication must be involved," Dr. Touhara says. At the Japanese Monkey Center (JMC) in Aichi and The Research Institute of Evolutionary Biology in Tokyo, Japan, Dr. Touhara and his team tracked the behavior of a conspiracy of ring-tailed lemurs. They observed that female lemurs sniffed the scent markings left by males more often and for longer periods of time during the breeding season--when females are sexually receptive.

April 17th

Individual Genetic Variation in Immune System Genes (HLA) May Affect Differences in Severity of COVID-19 Infection and Susceptibility

Genetic variability in the human immune system may affect susceptibility to, and severity of infection by, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19). The research was published online on April 17, 2020 in the Journal of Virology, a publication of the American Society for Microbiology. The open-access article is titled “Human Leukocyte Antigen Susceptibility Map for SARS-CoV-2.” Individual genetic variation may explain differences in the strength of immune responses. Certain immune system genes, called human leukocyte antigen (HLA) genes that are involved in recognizing pathogens, vary from person to person. Variations can influence how well the immune system recognizes a given pathogen. Poor recognition of SARS-CoV-2 could cause a person to be more vulnerable to the virus. "In particular, understanding how variation in HLA [a component of the immune system containing multiple genes] may affect the course of COVID-19 could help identify individuals at higher risk from the disease," according to the authors of the new study, who are from Oregon Health & Science University, Portland, Oregon, and the Portland VA Research Foundation. The first author is PhD candidate Austin Nguyen, and the senior author is Reid F. Thompson, MD, PhD, both from the Oregon Health & Science University. The authors show that individual HLA, haplotype, and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and note that certain alleles in particular could be associated with more severe infection, as has previously been shown with SARS-CoV (the SARS virus).

Researchers Move Closer to Producing Heparin Anti-Coagulant in the Lab; UC San Diego Group Demonstrates Influence of Transcription Factor ZNF263 on Heparin Synthesis

In a recent study published online on April 10, 2020in the Proceedings of the National Academy of Sciences (PNAS), University of California (UC) San Diego researchers moved one step closer to the ability to make heparin (image) of structure) in cultured cells. The article is titled “ZNF263 Is a Transcriptional Regulator of Heparin and Heparan Sulfate Biosynthesis.” Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible. In particular, the researchers found a critical gene in heparin biosynthesis: ZNF263 (zinc-finger protein 263). The researchers believe this gene regulator is a key discovery on the way to industrial heparin production. The idea would be to control this regulator in industrial cell lines using genetic engineering, paving the way for safe industrial production of heparin in well-controlled cell culture. Heparin is currently produced by extracting the drug from pig intestines, which is a concern for safety, sustainability, and security reasons. Millions of pigs are needed each year to meet our needs, and most manufacturing is done outside the USA. Furthermore, ten years ago, contaminants from the pig preparations led to dozens of deaths. Thus, there is a need to develop sustainable recombinant production. The work in PNAS provides new insights on exactly how cells control synthesis of heparin. Heparin is a special subtype of a more general class of carbohydrates, called heparan sulfates, that are produced by a wide range of cells, both in the human body, as well as in cell culture. Yet, heparin is exclusively produced in a special type of blood cells called mast cells. To this day, heparin cannot be successfully produced in cell culture.

New Ebola Vaccine May Fight All Four Ebola Virus Species That Infect Humans

Infectious disease scientists report early development of a potential universal vaccine for Ebola viruses that preclinical tests show might neutralize all four species of these deadly viruses infecting people in recent outbreaks, mainly in Africa. Scientists at Cincinnati Children's Hospital Medical Center report their preclinical results in an article published online on February 19, 2020 in the Journal of Virology, published by the American Society for Microbiology. The article is titled “A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses Against Pathogenic Ebola Viruses in Rhesus Macaques.” Although still in early preclinical testing, the researchers report that their data indicate that the prospective vaccine has potential to be a stand-alone protection from Ebola. It also could broaden and extend the durability of protective immunity induced by current live vaccines already being tested in clinical trials against individual Ebola virus species, said Karnail Singh, PhD, the study's co-principal investigator in the Division of Infectious Diseases at Cincinnati Children’s. "This could be a significant advancement in the global effort to prevent or manage Ebola outbreaks, especially if this vaccine, used alone or in combination with another Ebola vaccine, results in long-term and durable protective immunity against different Ebola viruses," Dr. Singh said. A deadly Ebola outbreak in West Africa between 2013 and 2016 accelerated international efforts to develop vaccines for these highly infectious and harmful viruses. This led to development of recombinant Ebola vaccines in which glycoprotein from Zaire Ebola virus is engineered into another modified live viral vector.

April 11th

Trial Drug (Soluble Form of ACE2) Can Significantly Impact Early Stages of COVID-19 Infection in Engineered Human Tissues; Drug Interferes with Viral Spike Binding to ACE2 Receptor on Cell Surfaces

An international team led by University of British Columbia (UBC) researcher Dr. Josef Penninger has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts. The findings, published online on April 2, 2020 in Cell, hold promise as a treatment capable of stopping early infection of the novel coronavirus that, as of April 2, 2020, had affected more than 981,000 people and claimed the lives of 50,000 people worldwide. The study provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19, and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys. The open-access article is titled "Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2." We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic," says Dr. Penninger, Professor in UBC's Faculty of Medicine, Director of the Life Sciences Institute and the Canada 150 Research Chair in Functional Genetics at UBC. "This work stems from an amazing collaboration among academic researchers and companies, including Dr. Ryan Conder's gastrointestinal group at STEMCELL Technologies in Vancouver; Nuria Montserrat in Spain; Drs. Haibo Zhang and Art Slutsky from Toronto; and especially Ali Mirazimi's infectious biology team in Sweden, who have been working tirelessly day and night for weeks to better understand the pathology of this disease and to provide breakthrough therapeutic options." ACE2 (angiotensin-converting enzyme 2)-- a protein on the surface of the cell membrane -- is now at center-stage in this outbreak as the key receptor for the spike glycoprotein of SARS-CoV-2. In earlier work, Dr.

March 22nd

FDA Approves 45-Minute Point-of-Care COVID-19 Test; First Rapid, Near-Patient Molecular Test for Detection of Virus that Causes COVID-19 Developed by California’s Cepheid

On March 21, 2020, California-based Cepheid announced that it has received Emergency Use Authorization (EUA) from the FDA for its Xpert® Xpress SARS-CoV-2, a rapid molecular diagnostic test for qualitative detection of SARS-CoV-2, the virus causing COVID-19. The test has been designed to operate on any of Cepheid's more than 23,000 automated GeneXpert® Systems worldwide, with a detection time of approximately 45 minutes with less than a minute of hands on time to prepare the sample. "During this time of increased demand for hospital services, Clinicians urgently need an on-demand diagnostic test for real-time management of patients being evaluated for admission to health-care facilities. An accurate test delivered close to the patient can be transformative — and help alleviate the pressure that the emergence of the 2019-nCoV outbreak has put on healthcare facilities that need to properly allocate their respiratory isolation resources," said Dr. David Persing, MD, PhD, Chief Medical and Technology Officer at Cepheid. "By leveraging the design principles of our current Xpert Xpress Flu/RSV cartridge technology, in which multiple regions of the viral genome are targeted to provide rapid detection of current and potential future variants of SARS-CoV-2, we have developed a test that provides reference lab-quality results in multiple settings where actionable treatment information is needed quickly." "Cepheid currently has nearly 5,000 GeneXpert® Systems in the US capable of point-of-care testing and for use in hospitals," said Cepheid President Warren Kocmond.

March 19th

NIH Clinical Trial of Gilead's Remdesivir to Treat COVID-19 Begun in Nebraska

In a February 25, 2020 press release, the FDA announced that a randomized, controlled clinical trial to evaluate the safety and efficacy of the investigational antiviral remdesivir in hospitalized adults diagnosed with coronavirus disease 2019 (COVID-19) has begun at the University of Nebraska Medical Center (UNMC) in Omaha. The trial regulatory sponsor is the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. This is the first clinical trial in the United States to evaluate an experimental treatment for COVID-19, the respiratory disease first detected in December 2019 in Wuhan, Hubei Province, China. The first trial participant is an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan and volunteered to participate in the study. The study can be adapted to evaluate additional investigative treatments and to enroll participants at other sites in the U.S. and worldwide. There are no specific therapeutics approved by the Food and Drug Administration (FDA) to treat people with COVID-19, the disease caused by the newly emergent SARS-CoV-2 virus (formerly known as 2019-nCoV). Infection can cause mild to severe respiratory illness, and symptoms can include fever, cough, and shortness of breath. As of February 24, the World Health Organization (WHO) had reported 77,262 confirmed cases of COVID-19 and 2,595 deaths in China and 2,069 cases of COVID-19 and 23 deaths in 29 other countries. There had been 14 confirmed COVID-19 cases reported in the United States and an additional 39 cases among persons repatriated to the United States, according to the Centers for Disease Control and Prevention (CDC) at that time.