New vulnerability found in major human viruses

phys.org | June 11, 2019

Discovery of a new feature of a large class of pathogenic viruses may allow development of new antiviral medications for the common cold, polio, and other illnesses, according to a new study publishing June 11 in the open-access journal PLOS Biology by Rana Abdelnabi and Johan Neyts of the University of Leuven, Belgium, and James Geraets and Sarah Butcher of the University of Helsinki and their colleagues. Picornaviruses include rhinoviruses and enteroviruses. Rhinoviruses cause millions of cases of upper respiratory infections ("colds") yearly and contribute to asthma, and enteroviruses are responsible for millions of infections including cases such as meningitis, encephalitis and polio. There are currently no antivirals that can be used for the treatment or prevention of any of the rhino- or enteroviruses. To replicate, viruses must interact with host cells, and in doing so, often need to change shape; stabilizing the virus particle is therefore thought to be a promising strategy for preventing replication. In a search for potential antiviral candidates, the authors found a compound that stabilized a model picornavirus. They performed cryo-electron microscopy (cryo-EM) of the drug-virus complex to determine how the drug exerted its effect. Cryo-EM involves combining thousands of two-dimensional images to develop a highly detailed three-dimensional image of the target.

Spotlight

Advances in imaging techniques have been instrumental in many aspects of cancer research; from screening and diagnosis to the guidance of cancer treatments and the monitoring of its recurrence. Insights provided by these advanced imaging techniques have been pivotal in enabling scientists to make these breakthroughs and save so many lives. This flipbook showcases a selection of spectacular images from The Cell Image Library that have been produced by scientists from around the world.

Spotlight

Advances in imaging techniques have been instrumental in many aspects of cancer research; from screening and diagnosis to the guidance of cancer treatments and the monitoring of its recurrence. Insights provided by these advanced imaging techniques have been pivotal in enabling scientists to make these breakthroughs and save so many lives. This flipbook showcases a selection of spectacular images from The Cell Image Library that have been produced by scientists from around the world.

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CELL AND GENE THERAPY

Terumo Blood and Cell Technologies to Collaborate with CSL Plasma on U.S. FDA Clearance of Plasma Collection Technology

CSL Plasma | March 11, 2022

CSL Plasma, a division of global biotherapeutics pioneer CSL Behring, announced the Rika Plasma Donation System created by Terumo Blood and Cell Technologies, a medical technology company based in Lakewood, Colorado, has received regulatory approval. The new plasmapheresis system is expected to provide technologies to support a safe, efficient, and better experience for plasma donors and an improved experience for CSL Plasma personnel, according to Terumo Blood and Cell Technologies. Additional characteristics of the new Rika system, according to CSL Plasma, will allow for the collection of more plasma in less time, hence improving quality and safety and, in turn, better serving patients who rely on plasma-based therapies. These advantages include: On average, Rika completes one plasma collection in 35 minutes or less: Compared to previous average CSL Plasma donation timings, this might mean a nearly 30% reduction in donor donation time. It assures that no more than 200 milliliters of blood are ever removed from the donor's body. This is believed to make the donor more comfortable during the donation process and lessen the risk of red cell loss deferral. It has a sophisticated user interface that helps CSL Plasma front-line personnel operate the equipment. This milestone helps bring to life how we demonstrate innovation, collaboration, and patient-focus, part of the CSL Values that underpin our commitment to manufacturing and delivering life-saving and life-extending medicines around the world, We continue to evolve as a leading biotechnology company, investing in our core plasma business. Continued innovation that benefits our employees and plasma donors speak to how we are driven by our promise to save and improve lives around the world." CSL Chief Operating Officer Paul McKenzie. CSL Plasma will begin installing the new technology at locations in the Denver, Colorado, area in the following months. There is a critical and ongoing need for human plasma to produce life-saving medicines for people with serious and rare diseases, CSL Plasma's decision to work with Terumo Blood and Cell Technologies is consistent with our business goals to improve the donor and employee experience through innovation and remain the plasma donation center of choice. We look forward to rolling out this new technology." CSL Plasma General Manager Michelle Meyer.

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MEDTECH

Patritumab Deruxtecan Granted U.S. FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

Daiichi Sankyo | December 24, 2021

Daiichi Sankyo Company, Limited announced that the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to patritumab deruxtecan, a potential first-in-class HER3 directed antibody drug conjugate, for the treatment of patients with metastatic or locally advanced EGFR-mutated non-small cell lung cancer with disease progression on or after treatment with a third-generation tyrosine kinase inhibitor and platinum-based therapies. Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide, with 80% to 85% classified as NSCLC.1,2,3 While the efficacy of targeted therapy with EGFR TKIs is well-established in the treatment of advanced EGFR-mutated NSCLC, which comprises approximately 30% of patients, the development of a broad range of resistance mechanisms commonly leads to disease progression.4,5,6 After failure of an EGFR TKI, platinum-based chemotherapy has limited efficacy with progression-free survival (PFS) of approximately 4.4 to 6.4 months.7 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have PFS of 2.8 to 3.2 months.8 The U.S. FDA’s BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines. The FDA granted the BTD based on data from the dose escalation portion and two expansion cohorts of a three-cohort phase 1 study of patritumab deruxtecan. Extended follow-up data from the dose escalation portion and dose expansion cohort 1 of the study were recently presented at the 2021 American Society of Clinical Oncology annual meeting and published in Cancer Discovery. This is the first BTD for patritumab deruxtecan and the seventh BTD across Daiichi Sankyo’s oncology portfolio. “The Breakthrough Therapy Designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer. We are proud that the FDA has once again recognized our innovative science and technology and we look forward to bringing this potential first-in-class HER3 directed antibody drug conjugate to patients with this specific type of lung cancer as quickly as possible.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo About Non-Small Cell Lung Cancer Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide, with 80% to 85% classified as NSCLC.1,2,3 There were an estimated 2.2 million new cases of lung cancer and 1.8 million deaths in 2020.9 NSCLC is diagnosed at an advanced stage in more than 50% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy.10,11,12 The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC. For patients with advanced EGFR-mutated NSCLC, targeted therapy with EGFR TKIs offer higher response rates and PFS compared to chemotherapy.13 However, most patients eventually develop resistance to these therapies and subsequent therapy after EGFR TKI with platinum-based chemotherapy have limited efficacy with PFS of approximately 4.4 to 6.4 months.7,14 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have PFS of 2.8 to 3.2 months.8 New treatment approaches are needed to overcome resistance and improve survival in this subtype of NSCLC. About HER3 HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival.15 Approximately 25% to 30% of lung cancers have an EGFR-activating mutation, and it is estimated that about 83% of all NSCLC tumors express the HER3 protein, which can be associated with an increased incidence of metastases, reduced survival and resistance to standard of care treatment.16,17,18 Currently, no HER3 directed medicines are approved for the treatment of cancer. About the Phase 1 Non-Small Cell Lung Cancer Study The global, multicenter, open label, two-part phase 1 study is evaluating patritumab deruxtecan in previously treated patients with metastatic or unresectable NSCLC. The dose escalation part of the study evaluated patients with EGFR-mutated disease either with progression on osimertinib or T790M-negative after progression on erlotinib, gefitinib or afatinib. The primary objective of this part of the study was to assess the safety and tolerability of patritumab deruxtecan and determine the recommended dose for expansion. The dose expansion part of the study is evaluating patritumab deruxtecan at the RD in three cohorts. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking one or more EGFR TKIs and one or more platinum-based chemotherapy regimens. Cohort 2 includes patients with squamous or non-squamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and following an anti-PD-1 or anti-PD-L1 antibody regimen. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and non-small cell lung cancer; patients in Cohort 3 are randomized 1:1 to receive the 5.6 mg/kg RDE regimen or an escalating up-titration regimen of patritumab deruxtecan. The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate assessed by blinded independent central review. Secondary study endpoints include investigator-assessed ORR, safety and pharmacokinetics. The study enrolled patients at multiple sites in Asia, Europe and North America. For more information, visit ClinicalTrials.gov. About Patritumab Deruxtecan Patritumab deruxtecan is one of three lead DXd ADCs in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is comprised of a fully human anti-HER3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC. Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo in Oncology The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon, our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025. About Daiichi Sankyo Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.”

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CELL AND GENE THERAPY

Neurophth and AAVnerGene Announces Strategic AAV Capsids Partnership for Next-Generation Ophthalmic Gene Therapy

Neurophth | January 19, 2021

Neurophth Therapeutics, Inc., a subsidiary of Wuhan Neurophth Biotechnology Ltd. gene therapy organization, and AAVnerGene Inc., a practicing AAV innovation organization, reports a strategic partnership to provide Neurophth with overall rights to commonly choose adeno-associated virus (AAV) capsids for the next generation ophthalmic gene therapy. AAVnerGene's Tissue-specific, Highly-transductive and Expressive New AAVs (ATHENA) screening stage can productively choose the best AAV vector for every cell type in a high-throughput (HTP) way. Significant difficulties in AAV-based gene therapy are the transduction productivity, conceivable resistance to the capsid and complex assembling measures. The capacity to distinguish appropriate cutting edge AAV vectors that could beat the limits of before generation AAV vectors is basic to a patient for accomplishing adequate helpful articulation of the moved gene in the most minimal portion dose regular strategy, for example, intravitreal (IVT) injection with reasonable cost. "AAVnerGene's proprietary technology may create capsid libraries derived from artificial intelligence machine learning, DNA shuffling or directed evolution allowing a significant increase in AAV genetic payload capacity, production, and transduction with the ability to penetrate through the inner limiting membrane of the retina, thus potentially enhance the overall transduction efficiency of capsid library-derived AAV vectors," said Alvin Luk, Ph.D., M.B.A., Chief Executive Officer of Neurophth. "Importantly, if proven successful, the administration of the selected AAVnerGene capsid variant(s) in gene therapy may enable repeated dosing AAVs in both adults and pediatric patients, potentially improving the clinical efficacy at a lower vector dose with better penetration of the barriers in eyes using a safer and less invasive procedure such as intravitreal injection which lower the risk of immune response to the capsid."

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