Correct antibiotic dosing could preserve lung microbial diversity in cystic fibrosis

Medical Xpress | February 22, 2019

Children and young adults with cystic fibrosis (CF) whose lung infections were treated with suboptimal doses of antibiotics had fewer changes in lung microbial diversity during the IV treatment, and their microbial diversity levels were higher 30 days later, a multi-institutional study that includes Children's researchers shows. By contrast, patients who were treated with therapeutic doses had greater decreases in lung microbial diversity and significantly lower diversity levels when the antibiotic treatment ended as well as 30 days later. "With the subtherapeutic treatment group, this could represent a 'basement effect' where it is harder to decrease diversity when it is already low to start. Also, patients in the subtherapeutic group had more advanced disease than those in the therapeutic group, which may influence the findings," explains Andrea Hahn, M.D., MS, an infectious disease specialist at Children's National Health System and the study's lead author. The findings, published online Feb. 22, 2019, in Scientific Reports, clearly establish the importance of the interplay between baseline microbial diversity and lung function and have the potential to improve clinical practices, the research team writes.

Spotlight

There are many parenteral dosage forms from which the pharmaceutical scientist can choose to develop their drug product. For primary pack choices, there are traditional vials, ampoules, cartridges, pre-filled syringes and complex containers such as the various types of dual chamber syringes. Additionally, there are newer dosage forms such as wearable injection devices or pump patches. Each have their own merits and advantages, but these advantages may not be realized until the product is marketed.

Spotlight

There are many parenteral dosage forms from which the pharmaceutical scientist can choose to develop their drug product. For primary pack choices, there are traditional vials, ampoules, cartridges, pre-filled syringes and complex containers such as the various types of dual chamber syringes. Additionally, there are newer dosage forms such as wearable injection devices or pump patches. Each have their own merits and advantages, but these advantages may not be realized until the product is marketed.

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CELL AND GENE THERAPY

Casma Therapeutics Raises $46.0 M in Series C Funding

Casma Therapeutics, Inc. | November 21, 2022

Casma Therapeutics, Inc., a biotechnology company engaging the autophagy system to provide innovative new medicines, announced the closing of a Series C financing round of $46.0 million. New investors participating in the round include Amgen Ventures, LLC, Astellas Venture Management, Eisai Co., Ltd., Euclidean Capital, Mirae Asset, and Ono Venture Investment. Current investors Eventide Asset Management, LLC, Schroders Capital, The Column Group, Third Rock Ventures, and other funds also participated in the financing. Dr. Hiromichi Kimura, Investment Director of Astellas Ventures, has joined the board of directors. Dr. Tomotaka Okino of Ono Venture Investment and Amgen Ventures have joined as board observers. Casma will use proceeds to advance its lead program for MYD88 mutant lymphoma through preclinical and into IND enabling studies. “The closing of this financing has strengthened our resources to continue advancing our drug pipeline focused on autophagy-based degradation. We are thrilled to welcome several top-tier investors who recognize the potential of our biological platforms and therapeutic assets targeting well-known high-value and traditionally undruggable targets.” Keith Dionne, Ph.D., Chief Executive Officer of Casma Therapeutics, Inc "Casma’s autophagy-based degradation platform, PHLYT™, is unique and impressive,” commented Dr. Kimura. “Along with a rich pipeline of autophagy degraders, the company has also established a highly qualified team with extensive scientific experience in drug development. We expect that this round of funding will accelerate development of Casma’s pipeline assets, especially its degrader for MYD88 mutant tumors.” About Casma Therapeutics, Inc. Casma Therapeutics, Inc. is developing novel cellular degradation approaches based on the autophagy pathway to open new target areas for drug discovery and development that will profoundly impact the lives of patients. Autophagy is a conserved cellular process that contributes to overall cellular homeostasis. The autophagy machinery targets large and complex disease targets such as organelles, protein aggregates and large signaling complexes and before directing them to the lysosome for elimination. By selectively degrading disease targets by autophagy, Casma expects to arrest or reverse the progression of disease in multiple oncology, inflammation, neurodegeneration, and metabolic disorders.

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CELL AND GENE THERAPY

Emergent BioSolutions Completes Acquisition of Exclusive Worldwide Rights to TEMBEXA® First FDA-Approved Smallpox Oral Antiviral for All Ages

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. Financial Terms 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. ABOUT TEMBEXA 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. About Smallpox 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. 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INDUSTRIAL IMPACT

ImaginAb Executes New License and Supply Agreement for CD8 ImmunoPET Technology with TriSalus Life Sciences

ImaginAb | November 23, 2022

ImaginAb Inc., a global biotechnology company developing 89Zr crefmirlimab berdoxam imaging agent and radiopharmaceutical therapy products, is pleased to announce the signing of a new non-exclusive License and Supply Agreement with TriSalus Life Sciences, Inc. an oncology therapeutics company integrating immunotherapy with disruptive delivery technology to transform the treatment paradigm for patients with liver and pancreatic tumors. Under the terms of the agreement, ImaginAb will license and supply clinical doses of ImaginAb's investigational CD8 ImmunoPET to TriSalus for use in its clinical trials using its proprietary Pressure-Enabled Drug Delivery™ method for intravascular delivery of its investigational SD-101 compound. "We are delighted that TriSalus will use our investigational CD8 ImmunoPET technology in an imaging sub-study within its PERIO-01 clinical trial which leverages its PEDD™ methodology and SD-101, a novel therapeutic candidate designed to re-activate the immune system within the liver and pancreas. Our agreement with TriSalus highlights our expanding partnership network and showcases the increasing adoption of our CD8 ImmunoPET technology." Ian Wilson, Chief Executive Officer of ImaginAb About ImaginAb ImaginAb is a clinical stage, revenue-generating global biotechnology company developing the next generation of imaging agents and radiopharmaceutical therapy products through its proprietary minibody and cys-diabody platforms. The lead candidate 89Zr crefmirlimab berdoxam imaging agent is currently in Phase II clinical trials and has been licensed by numerous pharmaceutical and biotech companies for imaging in their immunotherapy clinical trials, primarily in oncology. About 89Zr crefmirlimab berdoxam CD8 ImmunoPET is an 89Zr-labelled minibody that has been designed to bind to the CD8 receptor on human T cells for quantitative, non-invasive PET imaging of CD8+ T cells. CD8+ T cells are the main effector cells involved in the immune response against tumour cells induced by immunotherapies and they also play a key role in multiple autoimmune diseases. As such, quantitative imaging of CD8+ T cells is currently being researched to determine whether it may be used to diagnose the immune status of a patient, to measure the efficacy of immunotherapies and predict patient outcomes. About TriSalus Life Sciences TriSalus Life Sciences® is an oncology therapeutics company integrating immunotherapy with disruptive delivery technology to transform the treatment paradigm for patients with liver and pancreatic tumors. The company works to enable more patients to benefit from established and emerging cancer treatments by overcoming intratumoral pressure and immunosuppression, significant barriers that can limit delivery and efficacy. The proprietary TriSalus delivery method—Pressure-Enabled Drug Delivery™—modulates pressure and flow within blood vessels to improve therapy uptake and tumor response in ways traditional approaches cannot. Two FDA-cleared devices utilize TriSalus' proprietary approach to delivery of therapeutics: the TriNav® Infusion System and the Pancreatic Retrograde Venous Infusion™ System. Currently, in clinical trials across multiple indications, the TriSalus™ Platform uses PEDD™ to administer the company's investigational immunotherapy, SD-101, through a regional intravascular approach with the goal of strengthening immunotherapy responses for liver and pancreatic cancer patients. In partnership with leading cancer centers across the country, and by leveraging deep immuno-oncology expertise and inventive technology development, TriSalus is committed to advancing innovation that improves outcomes for patients. About PERIO-01 The Pressure-Enabled Regional Immuno-Oncology™ PERIO™-01 clinical trial is studying a new investigational drug, SD-101, delivered intravascularly by the TriNav® Infusion System using the Pressure-Enabled Drug Delivery™ method of administration. The study will evaluate if this platform approach can improve the performance of systemic checkpoint inhibitors in treating uveal melanoma with liver metastases.

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