CELL AND GENE THERAPY
Tiziana Life Sciences Ltd. | September 16, 2022
Tiziana Life Sciences Ltd. a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announces that a Lawrence & Isabel Barnett Drug Development Program Grant will be awarded to the Ann Romney Center for Neurologic Diseases at the Brigham and Women’s Hospital by the ALS Association for the study of an intranasal anti-CD3 monoclonal antibody in an animal model of Amyotrophic Lateral Sclerosis (ALS).
Howard L. Weiner, M.D., Co-Director of the Ann Romney Center for Neurologic Diseases at BWH and Chairman of Tiziana's Scientific Advisory Board, stated, “This prestigious research grant will be used to further study the role of intranasal anti-CD3 mAb in dampening the microglial activation which amplifies ALS disease progression. This research follows our recently presented positive findings on intranasal anti-CD3 mAb in Alzheimer’s Disease preclinical models of neuroinflammation. Additionally, we are currently studying foralumab, the first entirely human anti-CD3 mAb, in patients with secondary progressive multiple sclerosis.”
Gabriele Cerrone, Executive Chairman and interim Chief Executive Officer of Tiziana, remarked, “Intranasal foralumab has demonstrated potential across multiple Central Nervous System (CNS) indications. We are encouraged by the preclinical research using an intranasal anti-CD3 mAb in the neuroinflammatory related diseases of ALS and Alzheimer’s, as well as the impressive clinical benefits we have already shown for foralumab in patients with multiple sclerosis. While our initial focus is on our ongoing MS program which will continue to generate clinical read-outs, we are excited by foralumab’s potential to help highly debilitated ALS patients with limited therapeutic options and high unmet need.”
“We have now seen the potential of intranasal foralumab to dampen microglial activation in three major neuroinflammatory-related diseases, which creates significant optionality for exploring its benefits in some of the most important and burdensome medical conditions of our time.”
Matthew W. Davis, M.D., RPh, Chief Medical Officer of Tiziana
About the Barnett Drug Development Grant
The ALS Association’s Barnett Drug Development grant program supports preclinical drug discovery and development of new or repurposed treatments for ALS. There is an urgent need for new and improved therapies for ALS, as there is still no cure. The Lawrence and Isabel Barnett Drug Development Program is open to industry and academic investigators proposing to develop novel or repositioning approaches for ALS. The Association seeks applications for the preclinical assessment of therapeutics for ALS that have a high probability of reaching the clinic within three years.
Foralumab the only entirely human anti-CD3 mAb, has shown reduced release of cytokines after IV administration in healthy volunteers and in patients with Crohn's disease. In a humanized mouse model it was shown that while targeting the T-cell receptor, orally administered foralumab modulates immune responses of the T-cells and enhances regulatory T-cells thereby providing therapeutic benefit in treating inflammatory and autoimmune diseases without the occurrence of potential adverse events usually associated with parenteral mAb therapy. Once a day treatment for 10 consecutive days with intranasal foralumab was both well tolerated and produced clinical responses in COVID-19 patients. Based on these studies, the intranasal and oral administration of Foralumab offers the potential to become a well-tolerated immunotherapy for autoimmune and inflammatory diseases by the induction of Tregs.
About Tiziana Life Sciences
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal, oral and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
CELL AND GENE THERAPY
TEMBEXA and Smallpox | September 27, 2022
Emergent BioSolutions Inc. announced that it has completed its acquisition of exclusive worldwide rights to TEMBEXA® the first oral antiviral approved by the U.S. Food and Drug Administration for all age groups for the treatment of smallpox, from Chimerix. TEMBEXA was approved in June 2021 and is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates.
The completion of the acquisition follows the satisfaction or waiver by the parties, as applicable, of all closing conditions, including expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act), as amended, and receipt of consent from the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, for a sub-contract agreement between Chimerix and Emergent.
“The addition of TEMBEXA to our smallpox medical countermeasure franchise, which consists of our smallpox vaccine and therapeutic for smallpox vaccine complications, creates a more comprehensive offering to combat this deadly public health threat. We look forward to supporting the U.S. government’s smallpox preparedness strategy on a broader scale by executing on this BARDA contract.”
Paul Williams, SVP government/MCM business at Emergent
The 10-year contract valued at up to $680 million, to supply up to 1.7 million treatment courses of tablet and suspension formulations of TEMBEXA® to the U.S. government, was awarded to Chimerix on August 29, 2022. The contract includes an initial product procurement valued at approximately $115 million, with optional future procurement, valued at up to approximately $551 million, exercisable at the sole discretion of BARDA. In addition to product procurement, the contract includes reimbursed post marketing activities of approximately $12 million.
Based on the terms of the final BARDA agreement, Emergent is expected to pay Chimerix
An upfront payment of $238 million;
Potential milestone payments of up to $124 million contingent on the potential exercise by the U.S. government of procurement options following the base period;
15% royalty on gross profit from sales of TEMBEXA outside the U.S.;
20% royalty on gross profit from sales of TEMBEXA in the U.S. that are in excess of the 1.7 million treatment courses as contemplated in the existing BARDA contract; and
Up to an additional $12.5 million upon achievement of certain development-based milestones.
TEMBEXA is an oral antiviral approved by the FDA in June 2021 for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates. TEMBEXA is formulated as 100 mg tablets and 10 mg/mL oral suspension dosed once weekly for two weeks. The oral suspension formulation is particularly important for patients who have difficulty swallowing due to age or medical status. TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease.
The effectiveness of TEMBEXA for the treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible and inducing smallpox disease in humans to study the drug’s efficacy is not ethical. TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals. TEMBEXA has a BOXED WARNING for increased risk for mortality when used for longer duration.
Smallpox is a highly contagious disease caused by the variola virus. Historically, smallpox was one of the deadliest diseases in history with a case fatality rate of approximately 30%. Despite successful eradication of smallpox in the 1970s, there is considerable concern that variola virus could reappear, either through accidental release or as a weapon of bioterrorism. According to the U.S. Centers for Disease Control and Prevention variola virus is ranked in the highest risk category for bioterrorism agents due to its ease of transmission, high mortality rate, and potential to cause public panic and social disruption. Based on a recent report – The Department of Health and Human Services Fiscal Year 2023 Public Health and Social Services Emergency Fund Justification of Estimates for Appropriations Committee – smallpox remains a threat of high concern to both the domestic and international community.
About Emergent BioSolutions
At Emergent, our mission is to protect and enhance life. For over 20 years, we’ve been at work defending people from things we hope will never happen—so we are prepared just in case they ever do. We provide solutions for complex and urgent public health threats through a portfolio of vaccines and therapeutics that we develop and manufacture for governments and consumers. We also offer a range of integrated contract development and manufacturing services for pharmaceutical and biotechnology customers.
CELL AND GENE THERAPY
Genscript Biotech Corporation | September 23, 2022
GenScript USA Inc., the world's leading life-science research tools and services provider, is collaborating with researchers at the Gladstone-UCSF Institute of Genomic Immunology to advance the development of new, non-viral cell therapies that modify genomic sequences in the pursuit of more effective cell therapy products while limiting the cellular toxicity that is typically associated with previously available methods.
A new study, published in Nature Biotechnology, details methods for achieving highly efficient non-viral knock-in using GenScript's GenExact™ single-strand DNA modified with Cas9-target sequences. This method achieved up to ˜40% knock-in efficiency in primary immune cell types.
One powerful application of CRISPR/Cas genome editing technology involves the precise insertion of DNA sequences via the HDR pathway. Traditionally, researchers have relied on viral vectors to deliver DNA insertion templates used for gene therapy into cells. However, difficulties manufacturing large amounts of clinical-grade viral vectors have delayed getting cell therapies to patients. Additionally, viral vectors can insert genes at any location within the genome, leading to safety concerns.
Previous research by the group at Gladstone and UCSF has shown that synthetic DNA templates can be delivered without the use of viral vectors, but high levels of double-stranded DNA can be toxic to cells, resulting in low efficiency. Efficiency can be improved using a modified version of the DNA templates that can bind to the Cas9 enzyme. However, additional work was required to improve the yield of successfully engineered cells and to make the process compatible with the manufacturing of future cell therapies. Those goals motivated the team's current study.
In this study, the team tested modified GenExact ssDNA designed with Cas9-targeted sequences to determine if the gene-editing efficiency could be improved with lower toxicity. First, synthetic sgRNA was complexed with Cas9 protein to form a RNP complex. Then the RNP and ssDNA template were delivered into the cell via electroporation, enabling efficient gene editing.
The team discovered that this combination of GenExact ssDNA with Cas9-targeted sequence offers up to 40% knock-in editing efficiency with minimal cellular toxicity. This approach can accelerate the development and manufacture of novel, high-yield non-viral gene therapies — and at lower cost.
"We are very proud to have collaborated on this groundbreaking scale-up work by the talented team at Gladstone and UCSF. GenScript is excited for the opportunities that this high-yield cell-line engineering process will provide to our customers," said Ray Chen, Ph.D, president of GenScript Life Science Group.
"We were very happy to partner with Genscript on critical experiments demonstrating high efficiency and yield of CAR knock-in cells at clinical scale. The long ssDNA produced by Genscript exceeded our expectations and helped us clearly demonstrate the potential for future therapeutic applications using these methods.",
Brian Shy, MD, PhD, a former clinical fellow in the lab of Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology
About GenScript Biotech Corporation
GenScript Biotech Corporation is a global biotechnology group. Based on its leading gene synthesis technology, GenScript has developed four major platforms including the global cell therapy platform, the biologics contract development and manufacturing organization platform, the contract research organization platform, and the industrial synthesis product platform.
GenScript was founded in New Jersey, USA in 2002 and listed on the Hong Kong Stock Exchange in 2015. GenScript's business operation spans over 100 countries and regions worldwide, with legal entities located in the USA, mainland China, Hong Kong, Japan, Singapore, the Netherlands, and Ireland. GenScript has provided premium, convenient, and reliable products and services for over 100,000 customers.