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Archive - 2020

December 25th

Ocugen & Bharat Biotech to Co-Develop COVAXIN™, A Whole-Virion Inactivated COVID-19 Vaccine Candidate, for US Market; COVAXIN Is in Phase 3 Trial Now in India

On December 22, 2020, Ocugen, Inc., (NASDAQ: OCGN), a leading biopharmaceutical company, and Bharat Biotech, a global leader in vaccine innovation, announced that the companies have signed a binding letter of intent (LOI) to co-develop Bharat Biotech’s COVID-19 vaccine candidate, COVAXIN™, an advanced-stage whole-virion inactivated vaccine candidate, for the United States market. COVAXIN has been evaluated in approximately 1,000 subjects in Phase 1 and Phase 2 clinical trials in India, with promising safety and immunogenicity data. The vaccine candidate is currently part of a Phase 3 clinical trial in India involving 26,000 volunteers. Per the LOI, Ocugen will have US rights to the vaccine candidate and, in collaboration with Bharat Biotech, will be responsible for clinical development, registration, and commercialization for the US market. The companies have begun collaborating and will finalize details of the definitive agreement in the next few weeks. This collaboration leverages Ocugen’s vaccine expertise, and its R&D and regulatory capabilities in the US. In preparation for the development of COVAXIN™ in the US, Ocugen has assembled a Vaccine Scientific Advisory Board featuring leading academic and industry experts to evaluate the clinical and regulatory path to approval in the US market. “COVAXIN™ utilizes a historically proven approach to vaccine design. The adjuvanted inactivated virus vaccine candidate elicited strong IgG responses against spike (S1) protein, receptor-binding domain (RBD) and the nucleocapsid (N) protein of SARS-CoV-2, along with strong cellular responses in Phase 1 and 2clinical trials.

December 24th

New Class of Antibiotics Active Against a Wide Range of Bacteria; Inhibitors of Key Enzyme Kill Bacteria Directly & Also Elicit Rapid Immune Response; “Dual Acting Immuno-Antibiotics” Possible Landmark in World’s Fight Against Antimicrobial Resistance

Wistar Institute (Philadelphia) scientists have discovered a new class of compounds that uniquely combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combatting antimicrobial resistance (AMR). These finding were published online on December 23, 2020 in Nature. The article is titled “IspH inhibitors Kill Gram-Negative Bacteria and Mobilize Immune Clearance.” The World Health Organization (WHO) has declared antimicrobial resistance (AMR) as one of the top 10 global public health threats against humanity. It is estimated that by 2050, antibiotic-resistant infections could claim 10 million lives each year and impose a cumulative $100 trillion burden on the global economy. The list of bacteria that are becoming resistant to treatment with all available antibiotic options is growing and few new drugs are in the pipeline, creating a pressing need for new classes of antibiotics to prevent public health crises. “We took a creative, double-pronged strategy to develop new molecules that can kill difficult-to-treat infections while enhancing the natural host immune response,” said Farokh Dotiwala, M.B.B.S., Ph.D., Farokh Dotiwala (https://wistar.org/our-scientists/farokh-dotiwala), MBBS, PhD, Assistant Professor in the Vaccine & Immunotherapy Center and lead author of the effort to identify a new generation of antimicrobials named dual-acting immuno-antibiotics (DAIAs). Existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, building of the cell membrane, and metabolic pathways. However, bacteria can acquire drug resistance by mutating the bacterial target the antibiotic is directed against, inactivating the drugs, or pumping them out.

Lysine Methyltransferase SETD2 Plays Key Role in Modifying Actin Cytoskeleton; This Has Implications for Two Important Functions of Cancer Cells--Cell Migration & Autophagy; SETD2 Interacts with Huntingtin and Actin-Binding Adapter HIP1R to Modify Actin

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) is a protein well known as a chromatin remodeler, one that helps turn genes on or off by modifying histone proteins in the nucleus of the cell. When researchers discovered that SETD2 is mutated or lost in several cancer types, most commonly a type of kidney cancer called clear-cell renal cell carcinoma, all eyes turned toward SETD2 function in the nucleus of the cell to explain these cancers. In 2016, the lab of Cheryl Walker (photo), PhD, Director of the Center for Precision Environmental Health at Baylor College of Medicine, made the unexpected discovery that SETD2 not only remodels chromosomes in the nucleus, but also microtubules of the cytoskeleton outside the nucleus. The cytoskeleton is a dynamic network of interlinking protein thread-like structures, including filaments and microtubules that extend throughout the cell. It gives a cell its shape and internal organization and provides mechanical support that enables cells to carry out essential functions like division and movement. The Walker team found that SETD2 tags cytoskeleton microtubules with a methyl group. Loss of SETD2 resulted in defective delivery of chromosomes and problems with the separation of daughter cells during cell division. "Our findings suggested that defects in SETD2 could not only affect gene expression but also functions controlled by the cytoskeleton, such as movement, metastasis, and migration, which are very important for cancer cells," Dr. Walker said. "We wondered whether SETD2 might target other cytoskeletal proteins." Actin proteins, which form the filaments of the cytoskeleton, stood out as a prime target for SETD2.

December 23rd

French Exosome Company CILOA Creates GMP-Compliant Production Unit; This Unit Ensures Autonomy of CILOA in Development of Its Biomanufacturing Infrastructuren and Progress Toward Future Clinical Studies of Exosome-Based Vaccines & Biomedicines

On December 8, 2020, Ciloa, a pioneer French company specialized in the in-vivo customization of exosomes, announced the implementation of a production unit designed to meet GMP (Good Manufacturing Practices) standards. This new unit will allow Ciloa to have a complete manufacturing control and independence, starting by the initiation of the clinical phases. Ciloa’s future biomedicines and vaccines based on exosomes (TEM image here) will thus comply with the requirements of the regulatory agencies. Since its foundation in 2011 by Dr. Robert Mamoun, former Director of Research at INSERM, and Dr. Bernadette Trentin, both experts in molecular virology, Ciloa has been developing its expertise in the customization, production, and purification of exosomes. Stemming from two families of patents from the CNRS (French National Centre for Scientific Research) and the University of Montpellier, this breakthrough technology positions Ciloa as a precursor in the fast-evolving field of exosome innovation. Exosomes are natural nanovesicles secreted by cells into the extracellular medium. They can act as intercellular messengers and deliver specifically functional proteins (and other molecules) to targeted cells. Moving throughout the body, they can transmit natural signals that can be used therapeutically to regenerate, modify, multiply, or induce apoptosis of the targeted cells. The technology developed by Ciloa acts on the cellular machinery involved in exosome production. It is the sole technology that allows the in-vivo production of exosomes customized with any proteins.

New Drug Inhibits Growth of Cancer Cells; Small Molecule Blocks Gene Expression in Mitochondria in Mice & Stops Cancer Cells from Growing; Article Published in Nature

A newly developed compound starves cancer cells by attacking their "power plants"--the so-called mitochondria (image). The new compound prevents the genetic information within mitochondria from being read. Researchers from the Max Planck Institute for Biology of Ageing in Cologne, the Karolinska Institute in Stockholm, and the University of Gothenburg report in their study that this compound could be used as a potential anti-tumor drug in the future; not only in mice, but also in human patients. The article describing this work was published in the December 16, 2020 issue of Nature (https://www.nature.com/articles/s41586-020-03048-z). The article is titled “Small Molecule Inhibitors of Human Mitochondrial DNA Transcription.” Mitochondria provide our cells with energy and cellular building blocks necessary for normal tissue and organ function. For a long time, the growth of cancer cells was assumed to be independent of mitochondrial function. However, this long-standing dogma has been challenged in recent years. Especially, cancer stem cells are highly dependent on mitochondrial metabolism. Due to the central role of mitochondria for normal tissue function, and because drugs that target mitochondrial functions are usually very toxic, it has so far proven difficult to target mitochondria for cancer treatment. Now an international team of researchers has found a way to overcome these difficulties. "We managed to establish a potential cancer drug that targets mitochondrial function without severe side effects and without harming healthy cells", explains Nina Bonekamp, PhD, one of the lead authors of the study. Mitochondria contain their own genetic material, the mitochondrial DNA molecules (mtDNA), whose gene expression is mediated by a dedicated set of proteins.

December 22nd

FDA Resumes eIND Approval for Severe-to-Critical COVID-19 Patients Use of Vyrologix™ (Leronlimab) Following Full Enrollment in CytoDyn’s Phase 3 Trial for Severe-to-Critical COVID-19

On December 22, 2020, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing Vyrologix™ (leronlimab-PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that a treating physician has received authorization from the U.S. Food and Drug Administration (“FDA”) to administer leronlimab for a COVID-19 patient under emergency investigational new drug IND (eIND) authorization. Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn, commented, “We are very thankful the FDA is allowing severe-to-critical COVID-19 patients access to Vyrologix™ (leronlimab) again under eIND while we await the unblinding of data from our recently completed Phase 3 registrational trial. We are receiving daily requests from families seeking our drug for a loved one with COVID-19. In recent months, leronlimab received more than 60 eIND authorizations from the FDA, and during the pendency of our COVID-19 trials, we deferred seeking authorizations for eINDs in order to accelerate the pace of enrollment. Now that enrollment has been completed, we are pleased to be able to assist once again and remain hopeful the upcoming results of our Phase 3 trial will enable leronlimab to be more readily available for severe-to-critical COVID-19 patients.” CytoDyn’s Phase 2b/3 trial to evaluate the efficacy and safety of leronlimab for patients with severe-to-critical COVID-19 indications is a two-arm, randomized, double-blind, placebo-controlled, adaptive design multicenter study. Patients are randomized to receive weekly doses of 700 mg leronlimab, or placebo. Leronlimab and placebo are administered via subcutaneous injection. The study has three phases: Screening Period, Treatment Period, and Follow-Up Period. The primary outcome measured in this study is: all-cause mortality at Day 28.

Stability of Ebola Virus Nucleocapsid Studied Via Supercomputer Simulations to Identify Possible Targets of Therapeutic Attack

In the midst of a global pandemic with COVID-19, it's hard to appreciate how lucky those outside of Africa have been to avoid the deadly Ebola virus disease. It incapacitates its victims soon after infection with massive vomiting or diarrhea, leading to death from fluid loss in about 50 percent of the afflicted. The Ebola virus transmits only through bodily fluids, marking a key difference from the COVID-19 virus and one that has helped contain Ebola's spread. Ebola outbreaks continue to flare up in West Africa, although a vaccine developed in December 2019 and improvements in care and containment have helped keep Ebola in check. Supercomputer simulations by a University of Delaware team that included an undergraduate supported by the XSEDE (Extreme Science and Engineering Discovery Environment) EMPOWER program are adding to the mix and helping to crack the defenses of Ebola's coiled genetic material. This new research could help lead to breakthroughs in treatment and improved vaccines for Ebola and other deadly viral diseases such as COVID-19. "Our main findings are related to the stability of the Ebola nucleocapsid," said Juan R. Perilla, PhD, an Assistant Professor in the Department of Chemistry and Biochemistry at the University of Delaware. Dr. Perilla co-authored a new study published in online on October 20, 2020 in the AIP Journal of Chemistry Physics. It focused on the nucleocapsid, a protein shell that protects against the body's defenses the genetic material Ebola uses to replicate itself. The open-access article is titled "Molecular Determinants of Ebola Nucleocapsid Stability from Molecular Dynamics Simulations.” "What we've found is that the Ebola virus has evolved to regulate the stability of the nucleocapsid by forming electrostatic interactions with its RNA, its genetic material," Dr.

December 21st

Codiak’s Novel Engineered Exosome Therapeutic Candidate (ExoIL-12) Being Investigated in Phase 1 Clinical Trial As Single Agent for Treatment of Early-Stage Cutaneous T Cell Lymphoma (CTCL) and, Potentially, Other Cancers

On December 21, 2020, Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today announced the December 21, 2020 online publication of a new manuscript, “Exosome Surface Display of IL-12 Results In Tumor-Retained Pharmacology With Superior Potency and Limited Systemic Exposure Compared to Recombinant IL-12,” in Molecular Cancer Therapeutics (https://mct.aacrjournals.org/content/early/2020/12/18/1535-7163.MCT-20-0484), a journal of the American Association for Cancer Research. exoIL-12 is a novel engineered exosome therapeutic candidate currently being investigated in a Phase 1 clinical trial as a single agent for the treatment of early-stage cutaneous T cell lymphoma (CTCL) and potentially other cancers. This publication details the findings from the preclinical development program and highlights the potential of exoIL-12 to inhibit tumor growth by facilitating potent local pharmacology, precisely quantified doses, undetectable systemic exposure, and the robust generation of systemic anti-tumor immunity superior to that of recombinant IL-12 (rIL-12).“We believe exoIL-12 represents a potentially first-in-class approach for a number of cancers that have previously shown clinical responses to IL-12, a potent anti-tumor cytokine for which prior development has been limited due to unwanted systemic exposure and related toxicity,” said Sriram Sathyanarayanan, PhD, Senior Vice President, Preclinical Research, Codiak.

December 18th

Artificial SARS-CoV-2-Like Particles Very Sensitive to Warmer Temperatures, Study Suggests; Particle Exterior Degrades in 30 Minutes on Surfaces at 93 F; Little Effect Seen at 71 F; Surface Humidity Effect Appears Negligible

Winter is coming in the northern hemisphere and public health officials are asking how the seasonal shift will impact the spread of SARS-CoV-2, the virus that causes COVID-19. A new study (https://pubmed.ncbi.nlm.nih.gov/33272571/) tested how temperatures and humidity affect the structure of individual SARS-CoV-2 virus-like particles on surfaces. University of Utah scientists and colleagues found that just moderate temperature increases broke down the virus' structure, while humidity had very little impact. In order to remain infectious, the SARS-CoV-2 membrane needs a specific web of proteins arranged in a particular order. When that structure falls apart, it becomes less infectious. The study findings suggest that as temperatures begin to drop, particles on surfaces will remain infectious longer. This is the first study to analyze the mechanics of the virus on an individual particle level, but the findings agree with large-scale observations of other coronaviruses that appear to infect more people during the winter months. "You would expect that temperature makes a huge difference, and that's what we saw. To the point where the packaging of the virus was completely destroyed by even moderate temperature increases," said Michael Vershinin, PhD, Assistant Professor at the University of Utah and co-senior author of the paper. "What's surprising is how little heat was needed to break them down--surfaces that are warm to the touch, but not hot. The packaging of this virus is very sensitive to temperature." The paper (https://pubmed.ncbi.nlm.nih.gov/33272571/) reporting these temperature results was published online on November 28, 2020, in the journal Biochemical Biophysical Research Communications.

December 17th

Physician/Molecular Geneticist Richard A. Gatti Honored with Lifetime Achievement Award for Decades of Service to Those with the Rare Genetic Disease Ataxia-Telangiectasia (A-T) and Their Families

As one of the highlights of the 2018* biennial Ataxia-Telangiectasia (A-T)** Clinical Research Conference, held this year in Naples, Italy (November 29-December 1), a lifetime achievement award was presented to UCLA Professor-in-Residence of Genetics Richard A. Gatti (photo), MD, who for over 40 years has continuously advanced the world’s scientific understanding of this rare, but devastating neurodegenerative disease, largely of children (see additional pics from event at end). In addition to his own numerous scientific achievements in the area of A-T, Dr. Gatti has stimulated hundreds of graduate students to pursue further studies of A-T and he has inspired numerous scientific colleagues to work as hard as they can to better understand this disease and to bring us ever closer to possible treatments and even an eventual cure. And Dr. Gatti, not only carries out scientific research at the highest level, but he sees and treats A-T patients and their families, so he is never far from the ultimate driving motivation of trying to do his best to help real patients and families who are struggling with an extremely difficult disease. Approximately 120 A-T experts from around the world attended the three-day conference in Naples, which was held at the University of Naples Federico II, right on the shore of the Bay of Naples, and with the daunting vista of Mount Vesuvius standing spectacularly right across the Bay. After a very full day of scientific sessions on Saturday, almost all the conference attendees boarded the evening buses that would take them high into the hills of Naples for the wonderful award dinner for Dr. Gatti, which featured spectacular vistas of the beautiful lights and waters of historic Naples.