Mustang Bio Announces Positive Opinion from the European Medicines Agency on Orphan Drug Designation for Its Lentiviral Gene Therapy for the Treatment…

November 24, 2020 08:00 ET | Source: Mustang Bio, Inc.

WORCESTER, Mass., Nov. 24, 2020 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, today announced that the European Commission (EC) issued a positive opinion on its application for Orphan Drug Designation for Mustangs lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency (XSCID), also known as bubble boy disease. The Designation applies both to MB-107 for the treatment of newly diagnosed infants between two months and two years of age and to MB-207 for the treatment of patients who have been previously treated with hematopoietic stem cell transplantation (HSCT) and for whom re-treatment is indicated. The European Medicines Agency (EMA) previously granted Advanced Therapy Medicinal Product classification to MB-107 in April 2020. The U.S. Food and Drug Administration (FDA) also previously granted Rare Pediatric Disease and Orphan Drug Designations to MB-107 and MB-207, as well as Regenerative Medicine Advanced Therapy Designation to MB-107.

Orphan Drug Designation in the European Union (EU) is granted by the European Commission based on a positive opinion issued by the European Medicines Agency Committee for Orphan Medicinal Products (EMA COMP). To qualify, an investigational medicine must be intended to treat a seriously debilitating or life-threatening condition that affects fewer than five in 10,000 people in the EU, and there must be sufficient non-clinical or clinical data to suggest the investigational medicine may produce clinically relevant outcomes. EMA Orphan Drug Designation provides companies with certain benefits and incentives, including protocol assistance, differentiated evaluation procedures for Health Technology Assessments in certain countries, access to a centralized marketing authorization procedure valid in all EU member states, reduced regulatory fees and 10 years of market exclusivity.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, We are very pleased to receive a positive opinion from the EC on Orphan Drug Designation for our lentiviral gene therapy for XSCID. It is an important milestone for Mustang as we approach the initiation of our pivotal MB-107 and MB-207 clinical trials, which we anticipate will support regulatory filings in both the U.S. and EU. We look forward to working closely with the EMA as we continue our progress to make MB-107 and MB-207 available for patients suffering with XSCID.

MB-107 is currently being assessed in a Phase 1/2 clinical trial for XSCID in newly diagnosed infants under the age of two at St. Jude Childrens Research Hospital (St. Jude), UCSF Benioff Childrens Hospital in San Francisco and Seattle Childrens Hospital. Mustang submitted an investigational new drug application (IND) to the FDA to initiate a pivotal multi-center Phase 2 clinical trial of MB-107 in this same patient population. The trial is expected to enroll 10 patients who, together with 15 patients enrolled in the current multi-center trial led by St. Jude, will be compared with 25 matched historical control patients who have undergone HSCT. The primary efficacy endpoint will be event-free survival. The initiation of this trial is expected soon. Mustang is targeting topline data from this trial in the second half of 2022.

Earlier this month, Mustang signed an agreement with Minaris Regenerative Medicine GmbH (Minaris), a leading contract development and manufacturing service provider for the cell and gene therapy industry, to enable technology transfer and GMP clinical manufacturing of Mustangs MB-107 lentiviral gene therapy program for the treatment of XSCID in newly diagnosed infants in Europe. Under the terms of the agreement, Minaris will perform technology transfer of the manufacturing and analytical processes, as well as their adoption to the European regulatory environment, for the GMP-compliant manufacturing of the drug product at its site in Ottobrunn, Germany, with the goal of supplying clinical trials in Europe.

MB-207 is currently being assessed in a Phase 1/2 clinical trial at the National Institute of Allergy and Infectious Diseases for XSCID patients who have been previously treated with HSCT and for whom re-treatment is indicated. Mustang expects to file an IND with the FDA to initiate a pivotal multi-center pivotal Phase 2 clinical trial of MB-207 in this same patient population in the first quarter of 2021 and is targeting topline data from this trial in the second half of 2022.

About X-linked Severe Combined Immunodeficiency (XSCID) X-linked severe combined immunodeficiency is a rare genetic disorder that occurs in approximately 1 per 225,000 births. It is characterized by the absence or lack of function of key immune cells, resulting in a severely compromised immune system and death by one year of age if untreated. Patients with XSCID have no T-cells or natural killer cells. Although their B-cells are normal in number, they are not functional. As a result, XSCID patients are usually affected by severe bacterial, viral or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea and failure to thrive.

The specific genetic disorder that causes XSCID is a mutation in the gene coding for the common gamma chain (c), a protein that is shared by the receptors for at least six interleukins. These interleukins and their receptors are critical for the development and differentiation of immune cells. The gene coding for c is known as IL-2 receptor gamma, or IL2RG. Because IL2RG is located on the X-chromosome, XSCID is inherited in an X-linked recessive pattern, resulting in almost all patients being male.

About Mustang Bio Mustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (SEC). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking StatementsThis press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Company Contacts: Jaclyn Jaffe and William Begien Mustang Bio, Inc. (781) 652-4500 ir@mustangbio.com

Investor Relations Contact: Daniel Ferry LifeSci Advisors, LLC (617) 430-7576 daniel@lifesciadvisors.com

Media Relations Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com

Read the rest here:
Mustang Bio Announces Positive Opinion from the European Medicines Agency on Orphan Drug Designation for Its Lentiviral Gene Therapy for the Treatment...

Study Finds Racial and Ethnic Disparities in Treatment of AL Amyloidosis – DocWire News

Racial and ethnic minorities comprise only a small percentage of patients seen at specialized treatment centers for light-chain (AL) amyloidosis, despite being at increased risk for this disease.

AL amyloidosis is a condition marked by the production of abnormal proteins from antibodies called light chains, which can then deposit in organs. The disease is commonly associated with multiple myeloma, the most frequent hematologic cancer among Black Americans.

Researchers from the Boston University School of Medicine (BUSM) examined disease characteristics, treatments, and outcomes according to self-reported race/ethnicity of patients with AL amyloidosis referred to the Amyloidosis Center at BUSM between 1990 and 2020. They found that only 14% of the more than 2,400 patients seen during this 30-year period were racial or ethnic minorities, a figure much lower than in the general population.

The investigators observed similarities in disease manifestation across all patient populations but found younger age and more severe illness among racial and ethnic minorities. Fewer minority patients received treatment with stem cell transplantation compared with non-Hispanic white patients. This treatment difference was largely explained by lower educational level and more advanced heart disease among patients of racial or ethnic minorities, according to the researchers.

These findings indicate that, in order to mitigate disparities, earlier disease detection and efforts to reduce economic and/or language barriers are key. After controlling for disease severity and treatment, race/ethnicity did not independently impact survival, senior author Vaishali Sanchorawala, MD, professor of medicine and director of the Amyloidosis Center at BUSM and Boston Medical Center, explained in a press release.

These disparities can be mitigated, according to the research team, by increasing healthcare providers awareness of manifestations of this disease, such as structural heart changes, nephrosis, and neuropathy, which are symptoms that can mimic common disorders like hypertension and diabetes.

Findings from this study were published in Nature.

See the original post:
Study Finds Racial and Ethnic Disparities in Treatment of AL Amyloidosis - DocWire News

New Virtual Reality Tool, Domestic Cats are SARS-CoV-2 Carriers, Combination Therapy Advances: COVID-19 Updates – Bio-IT World

November 20, 2020 I St. Jude discovers hyperinflammatory pathway, hepatitis C drugs are potential treatment, non-human primate model identifies features of virus, IL-10 production is a marker for severity, recommendations on re-use of data, molecular structure of key E-protein, and early antibody evolution predicts outcomes. Plus: Disrupting SKI complex prevents viral replication, why COVID-19 spares children, and how smoking causes more severe infection.

Research News

Two collaborative studies, published in the journal Emerging Microbes & Infections, show that domestic cats can be asymptomatic carriers of SARS-CoV-2, but pigs are not likely to be significant carriers of the virus. Researchers from Kansas State University conducted an in-depth study at the K-State Biosecurity Research Institute (BRI) and determined that domestic cats may not have obvious clinical signs of the virus, but they still shed the virus through their nasal, oral and rectal cavities and can spread it to other cats within two days. Authors of the study highlight its importance in understanding risks of animal to human transmission. DOI:10.1080/22221751.2020.1833687

St. Jude Childrens Research Hospital scientists have discovered the process behind the life-threatening hyperinflammatory immune response associated with COVID-19 and potential therapeutics to disrupt this process. In mice models, they determined a combination of two cytokines that triggered this inflammatory cell death pathway: TNF-alpha and IFN-gamma. Neutralizing antibodies against these cytokines are currently used to treat inflammatory diseases, and researchers found that treatment with these antibodies protected mice from death associated with SARS-CoV-2 infection and other inflammatory conditions caused by cytokine storm. These findings are published in Cell. DOI:10.1016/j.cell.2020.11.025

In a new study, published in JACC: Basic to Translational Research, researchers used publicly available gene expression data to determine how COVID-19 impacts cardiovascular tissue and endothelial cells. They determined that cardiorenal tissue and endothelial cells express higher or comparable levels of SARS-CoV-2 associated genes to those found in the lungs or airway epithelium, supporting the hypothesis that COVID-19 may infect the vasculature. DOI:10.1016/j.jacbts.2020.09.010

Research led at the University of Tennessee Health Science Center (UTHSC) has identified three drugs that can potentially be repurposed for treatment of COVID-19. Based on virtual and in vitro experiments conducted at the UTHSC Regional Biocontainment Laboratory (RBL), the researchers found zuclopenthixol (an antipsychotic drug), nebivolol (an antihypertensive drug), and amodiaquine (an older antimalarial) to be good candidates for future clinical trials. They found these three drugs to act similarly to hydroxychloroquine, in some cases safer, and efficacy may be improved with combination therapy using remdesivir. This research is published in ACS Pharmacology & Translational Science. DOI:10.1021/acsptsci.0c00131

In vitro combination therapy of remdesivir and human recombinant soluble ACE2 (hrsACE2) shows promising results for the treatment of COVID-19 in a new study led by researchers at Karolinska Institutet. The research group tested this drug combination in cell cultures and organoids and found a reduced viral load of SARS-CoV-2 and inhibited viral replication. They achieved these results with a relatively lose dose of each drug, which reduced toxicity and risk for potential side effects. The authors of this study, which is published in EMBO Molecular Medicine, hope these findings will lead to successful clinical trials for combination therapy. DOI:10.15252/emmm.202013426

New research led at UCLA reveals how smoking causes more severe COVID-19 infection in the airways. The research team used a model of airway tissue created from human stem cells that were donated from the lungs of five young, healthy nonsmokers and exposed the airway cultures to cigarette smoke. The group then infected the cigarette smoke exposed cultures with SARS-CoV-2, along with cultures that were not exposed to smoke. The researchers found that the cultures exposed to smoke had two to three times more infected cells and determined that the blocking of interferons due to smoking was the cause for this finding. This study is published in Cell Stem Cell. DOI:10.1016/j.stem.2020.11.010

SARS-CoV-2 specific antibodies likely provide protection against reinfection of the virus, according to new research from the University of Freiburg. The scientists examined characteristics of the SARS-CoV-2 specific T-cells and determined that they differentiate into memory T-cells that are comparable to the flu. The authors of the study, published in Nature Medicine, are confident that this immunological memory means that vaccines currently being tested will provide significant protection against COVID-19. DOI:10.1038/s41591-020-01143-2

Experiments led by researchers at the Department of Energys Oak Ridge National Laboratory have identified hepatitis C drugs with the potential to treat COVID-19. The team performed an X-ray study that revealed promising results for the hepatitis C drugs boceprevir and narlaprevir, which exhibited the ability to bind and inhibit the SARS-CoV-2 main protease that enables the virus to reproduce. The study also discovered the proteases ability to change or adapt its shape according to the size and structure of the inhibitor molecule it binds to. This research is published in Structure, and the team suggests consideration of hepatitis C inhibitors as potential repurposing candidates for the treatment of COVID-19. DOI:10.1016/j.str.2020.10.007

A nonhuman primate model developed at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) has identified features of the SARS-CoV-2 virus that may help in vaccine development and treatment for COVID-19. The research team showed in this primate study that the virus causes vascular inflammation and that this persisted for 3 days following infection. They also confirmed immunosuppression as the viral load increased during the first 2 days of infection and observed rapid replication of the virus in the upper and lower respiratory tract for the first 2 days, followed by a rapid decrease with no viral activity detected 7 days post-infection. These findings are published in the Journal of Infectious Disease. DOI:10.1093/infdis/jiaa486

Vanderbilt University Medical Center researchers have uncovered why COVID-19 seems to spare children. The research team identified an enzyme, called TMPRSS2, that allows the virus to gain entry into airway epithelial cells and is found at lower levels in children. In the study, published in the Journal of Clinical Investigation, the researchers obtained and analyzed human lung specimens collected from donors of different ages and found that the expression of TMPRSS2 went up significantly with age. The team also analyzed autopsy samples for three patients who died from COVID-19 and found the virus in three types of cells that express the enzyme. Drugs that block TMPRSS2, which have been approved for the treatment of prostate cancer, are currently being tested clinically as a potential treatment for COVID-19. DOI:10.1172/JCI140766

Interleukin 10 (IL-10) production may act as a marker for severity of COVID-19, finds new research published in Clinical and Translational Immunology. A team of immunology experts examined immunological features associated with the development of severe COVID-19 disease by comparing the immune system response to COVID-19 in patients showing mild to moderate or severe symptoms, using a subset of healthy individuals as a control group. The researchers, surprisingly, found few differences in T cell response in the blood of severe COVID-19 patients when compared to the healthy individuals. They did, however, identify a significant increase in T cells producing IL-10 in patients with severe disease compared to the healthy group. The authors note that larger-scale studies are needed to confirm these findings. DOI:10.1002/cti2.1204

Researchers at the University of Maryland School of Medicine have identified new drug compounds to potentially treat novel coronaviruses, such as COVID-19. The study, published in PNAS, found that disrupting the SKI complex prevents the virus from replicating, which essentially destroys it. The team also identified compounds that target the SKI complex which not only inhibit coronaviruses, but also influenza and Ebola. The authors of the study hope these findings lead to development of new broad-spectrum antiviral drugs. DOI:10.1073/pnas.2012939117

Early antibody evolution may predict COVID-19 patient outcomes, according to new research published in Cell. The study used a systems serology approach to profile the antibody responses of 193 hospitalized COVID-19 patients and compared responses from patients with moderate and severe disease to those who died. Researchers found that all patients developed antibodies against the virus, but patients who passed away never fully developed an antibody response. In those died, there was a significant defect in the development of IgG antibodies and stunted development of the antibodies ability to strongly bind to Fc-receptors, which consequently never triggered a strong immune response against the virus. The team also found that of the survivors, the immune system recognized and targeted the S2 domain of the SARS-CoV-2 spike protein, suggesting a previous exposure to other coronaviruses and pre-existing immunity. DOI:10.1016/j.cell.2020.10.052

New research from Georgetown University Medical Center demonstrates the use of RNA molecules to successfully shut down the production of destructive proteins produced by COVID-19. The team showed that microRNAs (miRNAs) and silencing RNAs (siRNAs) can target messenger RNA inside a virus. SARS-CoV-2 uses messenger RNA to generate proteins essential for replication and infection. The authors of the study note that this ability to target the virus within cells, particularly through siRNA, could help shut the virus down. The researchers are working to aerosolize the RNA molecules to incorporate in an inhalable drug that would interfere with the production of the protein spikes associated with infectivity of the virus. This work is published in Gene Therapy. DOI:10.1038/s41434-020-00210-0

University of Bristol scientists have developed and demonstrated a new virtual (VR) reality tool, called Narupa, that allows researchers to virtually test COVID-19 drug candidates. In the study, published in the Journal of Chemical Information and Modeling, the team created a 3D model structure of the SARS-CoV-2 main protease (Mpro) and used interactive molecular dynamics in VR to visualize molecules binding to the enzyme in atomic detail. Their results showed that users were able to show how a drug molecule fits within the enzyme. The tool is an open source software framework that uses readily available VR equipment and enables virtual collaboration in the global fight against COVID-19. DOI:10.1021/acs.jcim.0c01030

The common D614G mutation may make SARS-CoV-2 more susceptible to a vaccine, finds a new study published in Science. Researchers of this study confirmed that this most common strain, which emerged in Europe, replicates and transmits quickly and efficiently but the mutation to the spike protein also makes it more sensitive to neutralizing antibody drugs. Hamster models investigating the original strain from China and the mutated strain showed that the mutated strain replicated about ten times faster and was more infectious, but the researchers did not find the mutated strain to cause more severe disease. The team explained that the D614G mutation also alters the spike protein in a way that creates a more vulnerable pathway to the virus core. DOI:10.1126/science.abe8499

Massachusetts Institute of Technology (MIT) scientists have discovered the molecular structure of a key protein found in the SARS-CoV-2 virus. This protein, named the envelope E protein, acts as an ion channel and plays an important role in viral replication and activation of the host cells inflammatory response. The MIT researchers also studied the binding sites of two drugs, amantadine and hexamethylene amiloride, that block the entrance of the E channel, but these drugs only bind weakly to the E protein. The authors of this study, published in Nature Structural and Molecular Biology, hope these findings help medicinal chemists to design new drugs that target this channel with high affinity. DOI:10.1038/s41594-020-00536-8

Researchers in China have developed a rhesus macaque model that mimics SARS-CoV-2 infection in humans via the nasal route. The study, published in PLOS Pathogens, revealed viral shedding in the nose and stool for up to 27 days and progression from mild disease to marked interstitial pneumonia, both of which resemble the manifestations of COVID-19 in humans. The research team also found that T-cells played an important role in viral disease progression and cytokine changes in the respiratory tract triggered inflammation, noting that treatments and vaccines should focus on these immune responses. DOI:10.1371/journal.ppat.1008949

A new study, published in PNAS, reveals models that detail binding and, for the first time, unbinding mechanisms that play key roles in the immune system response. The computational analysis shows the unbinding of peptides from the major histocompatibility complex (MHC) with atomic resolution. The research team found that in these secondary interactions, position 4 plays an important role in the stability of the complex and their model was able to predict the effect of mutations. The researchers believe that this work will have an impact on the fight against COVID-19, as the SARS peptide they investigated is very similar to the peptide in SARS-CoV-2, with the same binding pockets in positions 2, 4 and 9. DOI:10.1073/pnas.2007246117

Industry News

XPRIZE and Cognizant have announced a Pandemic Response Challenge that aims to safely reopen societies and restart economies through the power of data and artificial intelligence. Based on technology and AI models developed by Cognizant, and using data compiled by the Oxford COVID-19 Government Response Tracker, competing teams will build data-driven AI models that predict local COVID-19 transmission rates and prescribe intervention and measures to minimize infection rates, as well as negative economic impacts. This four-month competition will award a total prize of $500K at its conclusion. Press Release

In a special December issue, SLAS Discovery will feature research focusing on drug discovery efforts toward the COVID-19 pandemic. The issue will include four reviews that cover the commonly utilized approach of repurposing drugs to rapidly treat SARS-CoV-2, as well as targeting the virus using new vaccines and clinical drugs. The article, High-Throughput Screening for Drugs that Inhibit Papain-Like Protease in SARS-CoV-2, explores how an ultra-high throughput screening platform targeting PLPro was used to investigate over 13,000 clinically applicable drugs, and another article of original research tests drug-like ligands for their efficacy against the MAC domain of SARS2 Nsp3, a novel approach. Press Release

The December issue of SLAS Technology will feature a special collection of articles addressing COVID-19 and focuses on the advancing technological innovations being used to address the novel coronavirus. The special collection includes seven articles of original research, in addition to two reviews and the featured cover article, Advances in Technology to Address COVID-19. Press Release

The Governance Lab (GovLab) at the NYU Tandon School of Engineering has released recommendations for the re-use of data in response to the COVID-19 crisis. The guidance and a new Responsible Data Re-Use framework stem from The Data Assembly initiative in New York City. The GovLab co-hosted four months of remote deliberations with civil rights organizations, key data holders, and policymakers and this newly published release is the product of this combined effort to guide New York decision-makers on potential costs and benefits of re-using data while considering the sometimes contradictory needs of various stakeholders. Press Release

The Wellcome Sanger Institute and the COVID-19 Genomics UK (COG-UK) have received funding from the Department for Health and Social Care Testing Innovation Fund to expand whole genome sequencing of positive SARS-CoV-2 virus samples to track how COVID-19 is spreading and mutating. Since March 2020, COG-UK has generated more than 100,000 SARS-CoV-2 genomes, made available to the public and making up over 45 percent of the global total. The Sanger Institute has rapidly established new sequencing pipelines and developed supporting software to sequence and analyze the virus samples. The genomic data will be used to monitor the virus as new vaccines are deployed and identify any mutations that may impact vaccine efficacy. Press Release

Read more from the original source:
New Virtual Reality Tool, Domestic Cats are SARS-CoV-2 Carriers, Combination Therapy Advances: COVID-19 Updates - Bio-IT World

SEE | Smoking worsens Covid-19 infection in the airways, new study reveals – Health24

19 November 2020 SEE | Smoking worsens Covid-19 infection in the airways, new study reveals Using a model of airway tissue created from human stem cells, scientists recreated what happens when the airways of a smoker are infected with SARS-CoV-2.

Since the early days of the pandemic, questions have been raised about the link between smoking and Covid-19, the disease caused by SARS-CoV-2.

In June this year, the World Health Organization statedthat, based on existing literature assessing the association between smoking and Covid-19, there was insufficient information to confirm any link between tobacco or nicotine in the prevention or treatment of Covid-19.

However, more recent studies have shown that while smokers are not at risk of contracting infection, their risk of severe disease and death, once infected, is higher than that of non-smokers, although the ways that cigarette smoke exposure affects airway cell infection by SARS-CoV-2 have not been very clear.

A new study by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California has helped understand how this happens by investigating SARS-CoV-2 infection on a cellular and molecular level using a model of airway tissue created from human cells.

Their report was published in Cell Stem Cell.

The study

To perform their study, the scientists employed a platform known as an air-liquid interface culture. Essentially, this is grown from human airway stem cells and closely replicates how the airways behave and function in humans.

The airways carry air breathed in through the nose and mouth to the lungs, also functioning as the body's first line of defence against airborne pathogens, such as viruses, the authors noted.

"Our model replicates the upper part of the airways, which is the first place the virus hits," said Brigitte Gomperts, a professor of pulmonary medicine and member of the UCLA Jonsson Comprehensive Cancer Center.

"This is the part that produces mucus to trap viruses, bacteria and toxins and contains cells with finger-like projections that beat that mucus up and out of the body."

This type of model, Gomperts explained, has previously been used to study lung diseases for over a decade and has been shown to mimic the changes in the airway that can be seen in someone that smokes.

'Smoking cigarettes is like creating holes in these walls'

The air-liquid cultures used in the study were grown from airway stem cells that were taken from the lungs of five young, healthy, non-smoking tissue donors.

To replicate the effects of smoking, the researchers exposed these airway interface cultures to cigarette smoke for three minutes per day over four days.

They then infected the cultures exposed to cigarette smoke (along with identical cultures that had not been exposed) with live SARS-CoV-2 viruses.

The two groups were compared. In the models exposed to smoke, the researchers saw between two and three times more infected cells.

A more in-depth analysis led to the conclusion that smoking resulted in more severe infection, at least in part, by blocking the activity of interferons (which play a critical role in the body's early immune response to fight the virus).

"If you think of the airways like the high walls that protect a castle, smoking cigarettes is like creating holes in these walls," Gomperts said.

"Smoking reduces the natural defences, and that allows the virus to set in."

READ |Covid-19 deaths: Surprise findings on smoking and other insights from study of 17m patients

READ |Covid-19 is more severe in smokers, an analysis of 19 studies show

READ |Why the cigarette ban during lockdown? Five medical experts weigh in

Image: Basil MK/Pexels

Compiled by Zakiyah Ebrahim

Original post:
SEE | Smoking worsens Covid-19 infection in the airways, new study reveals - Health24

Could Cell Therapy Be The Answer To COVID-19? – CBS Boston

AgenTus Immune Cell Therapy in Patients with COVID-19

Excessive inflammatory response in the most serious cases of COVID-19, along with surges in infection rates, has caused a healthcare crisis in many countries around the world.

Could cell therapy be the answer?

The public health crisis of COVID-19 has propelled and catalyzed investigations of therapies known to have potential in related disease states for their suitability in combating COVID-19. One such area is immune cell therapy.

To that end, AgenTus Therapeutics, the cell therapy subsidiary of Agenus, an immuno-oncology company advancing immune therapies for patients with cancer, announced the start of a clinical trial with its proprietary allogeneic iNKT cell therapy. iNKT cell therapy has the potential to eliminate the COVID-19 virus, dampen harmful inflammation, and promote protection from reinfection all particularly critical in combating COVID-19. The first patient was treated at Weill Cornell Medical Center and New York Presbyterian Hospital, and early trial results are expected later this year.

Most people who become infected with COVID-19 experience symptoms such as a dry cough and mild fever and recover without medical care, but around 15% develop more serious symptoms including pneumonia and shortness of breath. Approximately 5% of patients with more severe disease experience acute respiratory distress syndrome (ARDS). When this syndrome occurs, the patients lungs become severely inflamed and fluid seeps into the lung tissue from nearby blood vessels, making breathing increasingly difficult. Some of these patients can go on to develop septic shock and multi-organ failure, with more than half dying after reaching this stage.

Respiratory failure from COVID-19 is linked to excessive immune activation that causes a cytokine storm, in which the inflammatory immune protein in the lungs increase to dangerously high levels. This hyper-reaction of the immune system has been observed with other coronaviruses, like SARS and MERS. Cell therapy has previously shown promise for treating respiratory distress for the nearly 500,000 who are affected globally every year even without the COVID-19 pandemic.

Agenus, a US-based biotechnology company headquartered in Lexington, MA with the goal of advancing immune therapies for patients with cancer, recently announced that its proprietary allogeneic iNKT cell therapy will be evaluated for its potential to treat COVID-19 and cancer through its cell therapy subsidiary, AgenTus.

Invariant natural killer T cells (iNKT cells) are a unique cell type that combine features of two critical arms of the immune system, T cells (adaptive immunity) and NK cells (innate immunity), making them invaluable in combatting diseases like cancer and COVID-19. In the case of cancer, they travel to tumor tissue by detecting a protein known as CD1d. They also express a protein known as NKG2D, which recognizes tumor stress ligands. Importantly, these proteins are expressed in both solid and liquid tumors, making iNKT cells broadly applicable to all cancer patients. In preclinical models, iNKT cells have been shown to work alone and have also demonstrated curative potential when activated and combined with Agenus pipeline of immuno-oncology drug candidates.

Agenus has observed that the number of iNKT cells in the body is reduced in people with cancer and infectious diseases like COVID-19, and this reduction is associated with poorer response to disease. In preclinical models that bear similarities to SARS-COV-2, increasing the number or frequency of iNKT cells reduced viral shedding and prevented inflammation-driven lung injury. These specific attributes are of paramount importance in any therapy attempting to overcome COVID-19.

As a result of this research, AgenTus is advancing an iNKT cell therapy program towards clinical trials in both cancer and COVID-19. Beyond the curative potential of iNKT cells as addressed above, AgenTus cell therapy program has the potential to be more practical and more beneficial than currently approved cell therapies. Currently approved cell therapies require genetic manipulation, which increases their cost, manufacturing time and complexity. On the other hand, iNKT cells may be effective even without genetic manipulation and have the potential to be manufactured to treat large numbers of patients from a single batch, presenting the opportunity for lower costs. Further, iNKT cells have been tested in clinical trials and have been well-tolerated, thus decreasing the risk of serious side effects.

Encouraged by these compelling properties of this cell therapy, AgenTus announced today the start of a clinical trial to test iNKT cells in patients with moderate to severe symptoms of COVID-19. The study is being led by Dr. Koen van Besien, M.D., Ph.D., Professor of Medicine and Director of the Stem Cell Transplant program at Weill Cornell Medical Center and New York Presbyterian Hospital. The trial is designed to evaluate the benefit of infusing iNKT cells in patients who have moderate to severe symptoms of COVID-19. The outcome of the trial will provide insight into whether administering iNKT cells will help to eliminate the virus, dampen harmful inflammation, and promote protection from reinfection.

As mentioned earlier, iNKT cell therapy offers promise for the fight against cancer as well as the fight against COVID-19. To that end, Agenus is also advancing iNKT cells into clinical trials for patients with cancer. Agenus recently presented data at two major cancer conferences, the Society of Immune Therapy for Cancer (SITC; #SITC19) and the American Association of Cancer Research (AACR; #AACR20), which revealed that in preclinical models AgenTus iNKTs can penetrate tissues, giving them a critical advantage in targeting solid tumors not currently served by approved cell therapies. These data also showed that the combination of checkpoint antibodies and iNKT cell triggering therapy shows curative potential in cancer models that are refractory to available therapies.

Agenus is the only company known to have a portfolio of checkpoint antibodies, cell therapy, and cancer vaccines. This gives the company enormous flexibility to develop novel combinations of agents with curative potential for patients with cancer and infectious disease at a significant cost advantage.

The potential benefits of iNKT cell therapy against both COVID-19 and cancer thus look very promising. Agenus is excited to investigate the possibilities of these treatments against these diseases that cause suffering and death for thousands of patients every year. By leveraging its unique capabilities and extensive pipeline against these diseases, Agenus hopes to provide significant benefit to these patients and a potential path to a cure.

_______________________________________________________________________________________________________________

1) https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

2) https://investor.agenusbio.com/2020-06-02-FDA-Clears-IND-for-iNKT-Cells-to-Treat-COVID-19-Patients

3) Exley et al., Clinical Cancer Research, 2017.

4) Tanne et al., American Association of Cancer Research, 2020.

5) Mavers et al., Frontiers in Immunology, 2017.

6) Nair and Dhodapkar, Frontiers in Immunology, 2017.

7) Wolf et al. Frontiers in Immunology, 2018.

8) Burcu et al., Society for Immunotherapy of Cancer, 2019.

_______________________________________________________________________________________________________________ Forward-Looking Statements: This article includes forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding Agenus and AgenTus abilities to produce effective allogeneic cell therapies to treat solid tumors, the anticipated clinical benefits and costs of such cell therapies, and future clinical development and regulatory plans. These statements are subject to risks and uncertainties, including those described in Agenus SEC filings.

Read more:
Could Cell Therapy Be The Answer To COVID-19? - CBS Boston

CA Prop 14 Explained: What To Know Before You Vote Election Day – Los Angeles, CA Patch

LOS ANGELES, CA Proposition 14, the only statewide bond measure on the general election ballot, asks voters to authorize $5.5 billion in bonds to fund stem cell research. If that sounds familiar, that's because it is. California approved a similar bond request 16 years ago, allowing the state to prop up what was then a fledgling and controversial area of research.

Prop 14's supporters contend the money is needed to fund cutting-edge research on the brink of discovering treatments and cures that could help save countless lives. Opponents say such promises are "shameless exaggerations" and that California isn't in a position to spend billions on stem cell research.

In 2004, Californians authorized $3 billion in bonds to create the California Institute for Regenerative Medicine, with the aim of making the Golden State a hub of cutting-edge stem cell research. It offset the George W. Bush administration's decision to halt federal funding for embryonic stem cell research. Sixteen years later, the California Institute for Regenerative Medicine is running out of money, forcing it to suspend new projects. Last year, the institute stopped accepting new applications, according to Ballotpedia.

If Prop 14 passes, it will authorize $5.5 billion in state general obligation bonds to support private, university and nonprofit stem cell research and therapy for diseases and conditions such as cancer, HIV/AIDS, Alzheimer's, Parkinson's, strokes, epilepsy and other neurological conditions. In addition to funding research, the measure would help fund treatment and physician training.

The measure caps the California Institute for Regenerative Medicine operating costs at 7.5 percent of the funding, with the rest going to grants. Over the last decade, the bulk of the institute's grants went to California universities and hospitals. It will cost the state about $260 million a year for 30 years to repay the bonds.

According to the text of the measure, the institute has generated more than $3 billion in matching funds, sponsored more than 1,000 research projects and treated thousands of patients. It claims to have promising treatments in the pipeline awaiting funding for final stages of research.

Check Out The CalMatters 2020 Election Guide

"This medical revolution holds the promise of restoring health and quality of life for many of California's individuals and families suffering from chronic disease and injury," Robert Klein, chairman of Americans for Cures, told the California Stem Cell Report blog. "However, the last tactical mile to bring this broad spectrum of therapies to patients will require more funding and the thoughtful support of California's public as the human trials and discoveries are refined and tested, overcome numerous obstacles or complications, and ultimately serve to improve the life and reduce the suffering of every one of us."

Opponents of the measure say that the California Institute for Regenerative Medicine is no longer necessary because the federal government now spends billions to support stem cell research and private entities are leading the way on advancements without the help of taxpayer-funded grants. They question the institution's track record, oversight and budget.

"We can't afford to waste billions. In the middle of an economic crisis, with soaring unemployment and budget shortfalls in the tens of billions of dollars, we don't have money to burn," reads the opposition on the Official Voter Information Guide. "Paying back Prop. 14's costs of $7.8 billion could mean huge tax increases at a time when our economy is on its knees. Or laying off thousands of nurses and other heroes who do the real work of keeping California healthy."

The measure has the support of the California Democratic Party and the University of California Board of Regents. More than $9 million has been spent on the Yes On 14 campaign, while there are no official opposition campaigns. However, several newspaper editorial boards have come out against the measure including The Orange County Register, the Mercury News and The Bakersfield Californian.

See the article here:
CA Prop 14 Explained: What To Know Before You Vote Election Day - Los Angeles, CA Patch

GMP Cell Banking Services Market Predicted to Accelerate the Growth by 2019-2029 – TechnoWeekly

Global GMP Cell Banking Services Market: Overview

A cell bank refers to a facility that helps in the storage of cells of certain genome for future use in medicinal needs or in some product. Cell banks often have large amount of base cell material that can be used in a number of projects. Cell banks are utilized for the generation of detailed characteristics of cell lines and it also assists in the mitigation of cross contamination of the same. Use of cell banks also diminishes the cost of processes of cell culture, thereby offering an economic alternative to continuous keeping of cells in culture. The growth of the global GMP cell banking services market is likely to be driven by the growing popularity of the procedure and emergence of rare diseases across the globe.

Get Exclusive PDF Sample Copy Of This Report:https://www.tmrresearch.com/sample/sample?flag=B&rep_id=6584

Cell banks are usually utilized in wide range of sectors, such as pharmaceuticals and stem cell research. The traditional procedure that is used in keeping the materials of cells intact is called cryopreservation. Cell banks are also capable of diminishing the prevalence of cell sample diversifying from the process of natural cell division over a period of time.

Increased funding for research and development activities in rare diseases is likely to encourage growth of the global GMP cell banking services market over the forecast period.

The global GMP Cell Banking Services market has been segmented based on end user and region. The main objective of providing such a comprehensive report is to provide a deep insight into the market.

Global GMP Cell Banking Services market: Notable Developments

One such promising development of the global GMP cell banking services market is mentioned below:

Some of the key market players of the global GMP cell banking services market are

Buy This Report @https://www.tmrresearch.com/checkout?rep_id=6584<ype=S

Global GMP Cell Banking Services market: Growth Drivers

Increased for Research on Rare Diseases to Pave Way for Rapid Growth of the Market

There has been an increased funding for research and development projects in rare diseases, which is likely to pave way for the development of the global GMP cell banking services market over the period of analysis. A case in point is funding of research on rare diseases by Food and Drug Administration (FDA), the US. FDA makes use of programs mandated by congress, such as Orphan Products Grants Program, which funds studies of natural history and for conducting clinical trials for rare medical conditions.

In addition to that, establishment of several resource centers for stem cell banking is estimated to positively influence the global GMP cell banking services market. For instance, Kuala Lampur based cord blood bank, Stemlife Berhad started resource center for stem banking in Brunei-based private hospital, Jerudong Park Medical Center. Such strategies by leading market players is likely to propel growth of the global GMP cell banking services market in the years to come.

Global GMP Cell Banking Services market: Regional Outlook

In the global GMP cell banking services market, North America is regarded as one of the most promising regions due to the presence of substantial mammalian cell. This type of cells is estimated to generate most of the revenue in the North America market.

Asia Pacific is another important lucrative region in the market with mammalian cell type accounting for most of the revenue in the region. A rise in the research and development on rare diseases together with increased funding for the same is estimated to drive the market in Asia Pacific.

The global GMP cell banking services market is segmented as:

End User

To know more about the table of contents, you can click @https://www.tmrresearch.com/sample/sample?flag=T&rep_id=6584

About TMR Research

TMR Research is a premier provider of customized market research and consulting services to busi-ness entities keen on succeeding in todays supercharged economic climate. Armed with an experi-enced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

Read the rest here:
GMP Cell Banking Services Market Predicted to Accelerate the Growth by 2019-2029 - TechnoWeekly

Making Progress Against Relapsed/ Refractory DLBCL Without CAR T – OncLive

Approximately of patients with diffuse large B-cell lymphoma (DLBCL) experience refractory disease after initial treatment or have a relapse after achieving remission.1 Until the advent of chimeric antigen receptor (CAR) T-cell therapies, treatment options for these patients had been mostly palliative, especially for those ineligible for autologous stem-cell transplantation (ASCT) and those who relapsed after ASCT. Although CAR T-cell therapies have revolutionized the treatment landscape for relapsed/refractory (R/R) DLBCL, not all patients are candidates for this treatment. Of those who do receive it, 30% to 35% experience long-term benefit, demonstrating a great unmet need for others in the treatment landscape.

Emerging agents have started to shake up the R/R DLBCL armamentarium, but there is still a long road ahead to fully define their role. During an OncLive Peer Exchange, a panel of lymphoma experts discussed several novel agents for R/R DLBCL, some of which have been recently approved. They examined the clinical trial data, discussed how these agents compare with CAR T-cell therapy, and provided insights on how they might be used in clinical practice. Before long, well need more sophistication in how we approach patients, moderator John P. Leonard, MD, said. Hopefully, that means well be using treatments more effectively and have more tools at our disposal.

Tafasitamab-cxix (Monjuvi) is a humanized anti-CD19 monoclonal antibody that has been mostly studied as a combination therapy, particularly with lenalidomide (Revlimid). On July 31, 2020, the FDA granted accelerated approval to the combination for adult patients with R/R DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for ASCT.2

The Fc portion has been enhanced to increase ADCC [antibody-dependent cell-mediated cytotoxicity] and ADCP [antibody-dependent cellular phagocytosis], Kami J. Maddocks, MD, said. She noted that investigators initially examined tafasitamab in a single-arm study as monotherapy in patients with R/R non-Hodgkin lymphoma, the data from which demonstrated responses in DLBCL, including a few complete responses (CRs). In this phase 2a study (NCT01685008), investigators observed responses in 9 of the 35 patients (26%) with DLBCL (2 CRs and 7 partial responses [PRs]), with a median duration of response of 20.1 months (range, 1.1-26.5).3 [This study] signaled that there might be some activity with this agent in large cell lymphoma, Maddocks said. She proceeded to explain that the rationale for combining this agent with lenalidomide is that lenalidomide activates natural killer cells, thereby optimizing the tumor environment for tafasitamab.

Data from L-MIND (NCT02399085) provided the basis for the approval of tafasitamab in combination with lenalidomide. The phase 2, open label, multicenter, single-arm trial included 71 patients with DLBCL who received tafasitamab 12 mg/kg intravenously (days 1, 8, 15 and 22 of each 28-day cycle for 3 cycles, then days 1 and 15 only) with lenalidomide 25 mg orally (days 1-21) for a maximum of 12 cycles, followed by biweekly tafasitamab as monotherapy.4 It was really targeted at those patients who relapsed after their initial therapy or maybe received a first salvage and then were not candidates for ASCT, she said. All patients in the study had previously received 1 to 4 systemic regimens, at least 1 of which was an anti-CD20 therapy.4

Maddocks noted that the combination was well tolerated and that the adverse effects (AEs) were in line with expected AEs for lenalidomide monotherapy. The most common grade 3 or higher treatment-emergent AEs were hematologic abnormalities, including neutropenia (48%), thrombocytopenia (17%), and febrile neutropenia (12%).4 There were very few infusion-related reactions. Approximately three-quarters of the patients were able to stay on lenalidomide 20 mg or higher, Maddocks said.

Tafasitamab/Lenalidomide vs CAR T-Cell Therapy

The panelists proceeded to discuss tafasitamab plus lenalidomide in the context of CAR T-cell therapy and when it might be most useful. They noted that the patients in the L-MIND trial were not heavily pretreated, were not refractory to their first-line treatment, and did not have more aggressive disease subtypes, such as double- or triple-hit biology.

Subsequently, this population was different from those included in the CAR T-cell studies, such as ZUMA-1 (NCT02348216), JULIET (NCT02445248), and TRANSCEND-NHL-001 (NCT02631044), in which 77%, 54%, and 67% of patients, respectively, had primary refractoriness, and 69%, 51%, and 50% received more than 3 lines of therapy.5 Further, in reported data from the JULIET and TRANSCEND-NHL-001 studies, 27% and 22% of patients had double-hit lymphoma, respectively. [CAR T-cell therapy] doesnt care that youre a double-hit. You can still respond and have durability. Its the same thing if youre primary refractory, Matthew Lunning, DO, said. Thus far, there are no data to clarify whether this is also the case for tafasitamab plus lenalidomide.

It is also unknown whether tafasitamab plus lenalidomide can be used as a bridge to CAR T-cell therapy. National Comprehensive Cancer Network guidelines state, It is unclear if tafasitamab will have a negative impact on the efficacy of subsequent anti-CD19 CAR T-cell therapy.6 Lunning said that preclinical data have shown that there is no negative affect with tafasitamab.

[Cell line studies show] that it does engage the same CD19 antigen that youd expect the CAR T cell to go after but, at least in cell lines, it did not appear to affect the CAR T cells, he said. Maddocks added that there was 1 patient enrolled in the L-MIND trial who received CAR T-cell therapy after progression on tafasitamab plus lenalidomide and who has been in remission for more than a year. However, she warned that you cannot draw conclusions based on 1 patient. As this combination becomes available to people, well hopefully know more about whether there is an effect on the efficacy of CAR T, she said.

Despite the unknown effect of tafasitamab plus lenalidomide as a bridging therapy to CAR T, the panelists agreed this may be a reasonable use. If it takes a couple of weeks to get patients to their apheresis and then another 3 weeks to get them [to delivery], maybe tafasitamab is the best option. Its 8 weekly doses early on and youre getting drug exposure with the intent to go to CAR T-cell therapy or a patient could say no, and you havent lost anything if theyre responding, Lunning said.

Lunning suspects tafasitamab plus lenalidomide will get a lot of use because it is an IV [intravenous] therapy, given weekly for a lot of doses up front, and lenalidomide is an oral therapy that people are very comfortable using in lymphoma and multiple myeloma. Subsequently, he emphasized the importance of capturing the data for those patients previously exposed to tafasitamab/lenalidomide who do not respond or who get a PR and go on to CAR T-cell therapy to determine the true durability of the combination. Thats only going to come out with real-world experience data rather than a commercially funded experience, Lunning said.

The FDA granted selinexor (Xpovio) accelerated approval on June 22, 2020, as a single agent for adult patients with R/R DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.7 The oral agent represents a whole new class of drugs. Its unlike anything that we have for large cell lymphoma or any other cancers. Its called a SINE [selective inhibitor of nuclear export] and it targets certain proteins that are exported out of the nucleus that give cells a prosurvival advantage. It is not necessarily specific to large cell lymphoma, but it targets the mechanism that large cell lymphoma probably uses to keep itself alive and potentially resistant, Nathan H. Fowler, MD, said.

The drugs approval was based on data from SADAL (NCT02227251), a multicenter, single-arm, open-label phase 2b trial in which 134 patients received selinexor 60 mg orally on days 1 and 3 of each week. All patients in the study had previously received 2 to 5 systemic regimens. Thirty-nine patients (29%) responded, with 18 (13%) achieving a CR and 21 (16%) achieving a PR.8 Unlike the L-MIND study, SADAL included patients with double- or triple-expressor status and data showed responses in these patients. If you think about [selinexor in the context of] CAR T-cell data and others, its not quite as good, but its a single drug so its fairly easy to give. It is effective in a subset of patients with large cell lymphoma that is pretty difficult to treat, including patients who have double-hit lymphoma, Fowler said. He also noted that responses appear durable. If you look at patients who have PR or better, the duration of response is over 2 years, [so] there is a select group of patients who do achieve durable benefit with the drug, he explained.

A challenge with selinexor is its toxicity. The most common grade 3 and 4 AEs observed in the SADAL study included thrombocytopenia (49% and 18%, respectively), neutropenia (21% and 9%), fatigue (grade 3/4, 15%), and nausea (grade 3/4, 6%).7 Maddocks said that in her experience gastrointestinal toxicity was most problematic but once this was addressed with antiemetics, it became less concerning. The FDA recommends that selinexor be administered with antiemetic prophylaxis.7

The panelists emphasized that selinexor is not a replacement for CAR T-cell therapy but added that it may help fill an unmet need for patients who have limited treatment options. For patients who are failing [ASCT or CAR T], we dont have a lot of options. We can do lenalidomide and lenalidomide plus a CD19-targeted agent. Patients who fail CAR T-cell therapy, those who would not qualify [for CAR T], and those who are not near a [CAR T] center are the obvious population [for selinexor], Fowler said. Maddocks and Lunning agreed.

The panelists noted that many other agents are in clinical trials for R/R DLBCL, including bispecific antibodies such as glofitamab and epcoritamab. [These are] going to be generating data but not a lot of data will follow [treatment with] CAR T, Lunning said. Nevertheless, he is excited to see what kind of durability these drugs will ultimately show. In contrast, another investigational bispecific antibody, mosunetuzumab, has shown favorable efficacy in a phase 1/1b study that included patients with heavily pretreated R/R DLBCL, including those with disease progression after CAR T-cell therapy. Of the 7 evaluable patients with DLBCL who received prior CAR T-cell therapy, 2 achieved a CR.9

When we were looking at the BiTE [bispecific T-cell engager] molecules a couple of years ago, there was some sense that they would maybe displace CAR Ts. But a lot of the data that were seeing now are immature. I dont think the durable CR rate appears to be at the same level that were seeing with CAR T, at least in large cell lymphoma. So, I dont see these replacing CAR T-cell therapy, but I agree with Drs Maddocks and Lunning that they will probably follow CAR T as a salvage for these patients, Fowler said.

The other treatment the panelists discussed were anti-CD19 antibody-drug conjugates (ADCs). There are 3 CD19 ADCs that have been developed, all showing pretty similar responses; however, 2 are no longer being developed due to toxicity, Maddocks said. She remarked that the third ADC had good initial responses but they were not durable. Subsequently, she noted this agent would probably have to be used as part of a combination therapy to achieve good remissions.

A major challenge in treating DLBCL is that there are no biological markers to guide treatment decision-making. We really need to define the biology by some assay and then use that to put patients into different treatment groups. Thats the holy grail because a one-size-fits-all approach can only move the bar so much in large cell lymphoma, Fowler said.

Its great that were getting all of these new drug classesmore drugs to have the discussions about, Lunning said. Its a chess match against large cell lymphoma and its important to know what piece to play next. You may be moving 1 piece to make a move 3 turns down the road.

References

1. Skrabek P, Assouline S, Christofides A, et al. Emerging therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma. Curr Oncol. 2019;26(4):253-265. doi:10.3747/co.26.5421

2. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. Updated August 3, 2020. Accessed October 9, 2020. https://bit.ly/3nmOT43

3. Jurczak W, Zinzani PL, Gaidano G, et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkins lymphoma. Ann Oncol. 2018;29(5):1266-1272. doi:10.1093/annonc/mdy056

4. Monjuvi. Prescribing information. MorphoSys US Inc; 2020. Accessed October 9, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761163s000lbl.pdf

5. Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther Adv Hematol. 2019;10:2040620719841581. doi:10.1177/2040620719841581

6. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 4.2020. Accessed October 9, 2020. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

7. FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphoma. FDA. June 22, 2020. Accessed October 9, 2020. https://bit.ly/36Am12o

8. Xpovio. Prescribing information. Karyopharm Therapeutics Inc; 2020. Accessed October 9, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212306s001lbl.pdf

9. Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell (CAR-T) therapies, and is active in treatment through multiple lines. Blood. 2019;134(suppl 1):6. doi:10.1182/blood-2019-123742

Read the rest here:
Making Progress Against Relapsed/ Refractory DLBCL Without CAR T - OncLive

Orchard Therapeutics to Host Virtual R&D Investor Event on Friday, November 13, 2020 – GlobeNewswire

November 02, 2020 07:00 ET | Source: Orchard Therapeutics (Europe) Limited

BOSTON and LONDON, Nov. 02, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the company will webcast a virtual R&D event New Horizons in Gene Therapy on Friday, November 13, 2020 from 9:00 a.m. to 11:00 a.m. ET.

Members of Orchards management team and a world-leading gene therapy expert will present an overview of the companys development of hematopoietic stem cell (HSC) gene therapy in genetic subsets of frontotemporal dementia (FTD) and Crohns disease, as well as the latest innovations in lentiviral vector and drug product manufacturing.

Presentations will be given by:

A live webcast of the presentation will be available under "News & Events" in the Investors & Media section of the company's website at http://www.orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation. If you would like to RSVP, please contact orchard@privilege-events.it.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist. Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (TwitterandLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Contacts

Investors Renee Leck Director, Investor Relations +1 862-242-0764 Renee.Leck@orchard-tx.com

Continue reading here:
Orchard Therapeutics to Host Virtual R&D Investor Event on Friday, November 13, 2020 - GlobeNewswire

Editorial Article: Combating cancer: The incubation technology accelerating CAR-T cell therapy development – SelectScience

Gene and cell therapy expert Dr. Gerhard Bauer explores the powerful therapies that use a patient's own immune cells to treat cancer

In this article, we hear from Dr. Gerhard Bauer, Professor of Hematology-Oncology at the UC Davis Medical Center within the School of Medicine and Director and Designer of the UC Davis Good Manufacturing Practice Facility. Following his earlier research on stem cell gene therapy for HIV and severe combined immune deficiency (SCID), Bauer discusses his current work overseeing the development of life-saving CAR-T cells, highlights how new self-sterilizing instruments have been critical to his teams production of safe gene therapy products for patients, and shares his hopes for the future.

Tell us more about the Good Manufacturing Practice Lab at the UC Davis Institute, and your journey to becoming director

GB: In my early years, I helped operate a laboratory in Vienna testing laboratory blood products for HIV. Until finally, I thought, if I really want to do something about HIV and want to find a treatment or cure for it, then I need to do more than just testing test kits. I was subsequently hired by the University of Maryland at Baltimore to run the HIV laboratory. Whilst there I was able to find a predictor for HIV transmission, from mother to child, which at that time was a cell-based assay designed to predict the transmission rate. From this, we were able to demonstrate that higher viral load leads to more transmission.

I was then asked to move over to the Johns Hopkins University, where I started on the development of stem cell gene therapy for HIV. And then on to Dr. Donald Kohn's laboratory at Children's Hospital Los Angeles, where I was fortunate enough to be able to work on developing all the clinical-grade procedures to transport genes into hematopoietic stem and progenitor cells. This research led to the development of a completely new treatment for ADA-deficient SCID, severe combined immune deficiency.

After the success of the clinical-grade procedures, I was asked to go to Washington University in St. Louis, to build them a completely new Good Manufacturing Practice facility for cell and gene therapy. This was because I had built a GMP facility among the first academic GMP facilities at Children's Hospital Los Angeles. A few years later I moved to California to help build another GMP facility at University of California, Davis, where I am still conducting my research.

The UC Davis Medical Center is a manufacturing facility for cell and gene therapy products that are being used in clinical trials to help treat patients with currently incurable diseases. In this aspect, I overlook all the manufacturing efforts for novel clinical trials. Since 2010, we have been operating very successfully and have a whole pallet of applications, cell and gene therapy, and other applications that we manufacture here.

What are the main goals for your projects using homegrown CAR-T cell therapy approaches?

GB: A very interesting project that we have been tackling is CAR-T cells. Everybody talks about CAR-T cells these days because they have turned from an experimental project into commercialized applications. CAR-T cells are chimeric antigen receptor T cells. They are gene-modified immune cells from the patient. You can take a patient's immune cells, specifically T cells, out in a blood collection procedure, put them into a laboratory, and then insert genes that will produce a completely novel receptor on the cell surface that can recognize cancer cells. Chemotherapy and radiotherapy only kill the fast-growing tumor cells but often a patient will have a relapse. The relapse comes from cells that have survived the chemotherapy or radiation.

The immune system, if properly equipped, allows for the surveillance of all the cancer cells that may still be there even after chemotherapy. With CAR-T cells, we have developed such a weapon that allows the patient's own immune system to recognize the cancer and eliminate it. This can also be sustained elimination because the T cells develop memory T cells that will be reactivated when the cancer comes back.

In my career here at UC Davis, I have been involved in several CAR-T cell projects initiated by biotech companies. Also, another one initiated by UC Davis in collaboration with University of California, San Francisco. And we are manufacturing such CAR-T cells in the laboratory currently and we are initiating investigational new drug applications, INDs, with the FDA to apply these homegrown CAR-T cells as we call them to patients in San Francisco and also here at UC Davis.

What role do incubators play in cell and gene therapy development?

GB: Within a Good Manufacturing Practice laboratory, we need equipment that can be calibrated and that can maintain the operational status in a very precise way, from beginning to end of the process. Also, we must be able to clean these pieces of equipment appropriately. This means we maintain a very clean environment so as not to cross-contaminate or bring any other infections in. It is very important that we get laboratory equipment that can handle all of this.

I have had a good experience with the incubators that we have had over the years in our laboratories. Some had lasted for over 10 years until we replaced them with newer incubators with a unique feature. That feature is a self-sterilizing incubator, which has helped us tremendously in our efforts. We need to keep the time that we work on maintenance of the equipment low because our technicians are needed for making the products. We do not have to do an autoclaving step on the shelves and everything that is in there. We can leave everything in, and it sterilizes itself. It has saved us so much time and effort and our technicians are grateful for that.

Without these incubators, I do not think we would be able to efficiently produce as many products as we do currently. We also must make sure that we produce a safe and efficacious patient product if we do not have reliable incubators, we cannot make reliable products.

What is your vision for the future of gene therapy?

GB: Up to now we have been able to demonstrate that gene therapy is very safe. We have seen so many patients cured with ADA-deficient SCID safely. In CAR-T cell therapy, which is also a gene therapy, we have saved the lives of so many patients safely.

In the future, we need to expand these already working methods. We must make CAR-T cell therapy available for the many people that need it. Often scaling up is not possible because it is an autologous therapy. I would say scale out, not scale up. Scaling out means that you have many different laboratories where you can make these products and each product is being made in an efficient way. We are going to have to develop methods to efficiently manufacture these products side by side. This will be possible with automation.

Hopefully, in a few years down the road, we will be able to provide those who need it with cell and gene therapy. The second thing is that it is likely that genetic diseases will be curable with gene therapy, more of these cures are being worked on currently. Not only is cell therapy involved in that, but gene therapy vectors can also be administered directly into the patient to look for the cells they need to cure, and then illicit the cure directly without having to transplant cells. So, the future is very interesting, and having seen it from the very beginning to where we are now is something that I really enjoy.

More on the impact of PHCbi technology:

Find out more about Dr. Gerhard Bauers research here>>

Do you use PHCbi products in your lab? Write a review today for your chance to win a $400 Amazon gift card>>

Read the original:
Editorial Article: Combating cancer: The incubation technology accelerating CAR-T cell therapy development - SelectScience