Machine learning reveals metabolic pathways disrupted by the drugs, offering new targets to combat resistance

phys.org | May 09, 2019

Most antibiotics work by interfering with critical functions such as DNA replication or construction of the bacterial cell wall. However, these mechanisms represent only part of the full picture of how antibiotics act. In a new study of antibiotic action, MIT researchers developed a new machine-learning approach to discover an additional mechanism that helps some antibiotics kill bacteria. This secondary mechanism involves activating the bacterial metabolism of nucleotides that the cells need to replicate their DNA. "There are dramatic energy demands placed on the cell as a result of the drug stress. These energy demands require a metabolic response, and some of the metabolic byproducts are toxic and help contribute to killing the cells," says James Collins, the Termeer Professor of Medical Engineering and Science in MIT's Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering, and the senior author of the study.

Spotlight

It’s generally known that what makes us unique are the genes we inherit from our parents. While it’s fascinating to learn why we inherit certain traits such as height, eye color or athletic talent, scientists have recently shown that our genetic differences also determine how we metabolize different foods and nutrients. With today’s global epidemic of obesity and its link to 53 life-threatening diseases, it’s no wonder the field of nutrigenomics is getting unprecedented attention from the world’s top geneticists, scientists and physicians. People want to know why one person does well on a certain diet while other diets fail. We have intuitively known that the one-size-fits-all approach to nutrition, diet and exercise is flawed, but it’s only within the last few years that we have been able to peer into our genes and understand why.

Spotlight

It’s generally known that what makes us unique are the genes we inherit from our parents. While it’s fascinating to learn why we inherit certain traits such as height, eye color or athletic talent, scientists have recently shown that our genetic differences also determine how we metabolize different foods and nutrients. With today’s global epidemic of obesity and its link to 53 life-threatening diseases, it’s no wonder the field of nutrigenomics is getting unprecedented attention from the world’s top geneticists, scientists and physicians. People want to know why one person does well on a certain diet while other diets fail. We have intuitively known that the one-size-fits-all approach to nutrition, diet and exercise is flawed, but it’s only within the last few years that we have been able to peer into our genes and understand why.

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INDUSTRIAL IMPACT

Sirona Biochem Signs International Partnership Agreement with Wanbang Biopharmaceuticals

Sirona Biochem Corp. | November 24, 2022

Sirona Biochem Corp. announces that, subsequent to the LOI, Sirona and Wanbang Biopharmaceuticals have signed an expanded, international partnership agreement to collaborate on licencing Sirona’s SGLT2 inhibitor, TFC-039, as a pharmaceutical treatment in both animal and human health. The agreement adds human health to the partnership as a result of new licencing opportunities currently in due diligence. Wanbang and Sirona initially signed a licensing agreement for TFC-039, whereby Wanbang obtained the rights to develop the compound as a diabetes treatment in China and Sirona retained the global rights. Sirona has since been in discussions with animal health companies to advance TFC-039 as a treatment for diabetes and chronic kidney disease in companion animals. SGLT2 inhibitors provide an opportunity to treat inflicted animals with an oral medication as opposed to the traditional method of daily insulin injections. More recently, Sirona has entered into due diligence with a large pharmaceutical company with a regional interest in developing the compound for human diabetes. Together, Sirona and Wanbang share extensive knowledge and scientific results of TFC-039. Partnering will significantly increase the speed to third-party partnerships and commercialization. The shared data spans over 12 years of research and development, and includes in vitro and in vivo preclinical work, multiple clinical studies, advanced manufacturing process development and the ability to commercially manufacture TFC-039. “We have a long-standing relationship with Wanbang and are excited to combine our two companies’ expertise to license TFC-039. Wanbang has invested millions of dollars into the clinical stage research and development of the manufacturing processes for TFC-039. These pieces of data are critical to large organizations and will greatly increase the opportunities to move forward. The probability of a successful licensing agreement has been made much stronger by leveraging our alliance with Wanbang. We have had a successful year building Sirona’s pipeline, with positive movement on all projects and we’re looking forward to continuing this success with our SGLT2 inhibitor as well as our antiviral and anti-aging projects in 2023.” Dr. Howard Verrico, CEO About Wanbang Biopharmaceuticals and Fosun Pharmaceuticals Wanbang Biopharmaceuticals develops, manufactures, and markets drugs with indications for chronic disease treatment, antibiotics, and other endocrine diseases in China. Founded in 1981, the company is headquartered in Xuzhou, China, and is a subsidiary of Shanghai Fosun Pharmaceutical Group. Fosun is a leader in the pharmaceutical industry and is regarded as one of the top five domestic pharmaceutical companies in China. About Sirona Biochem Corp. Sirona Biochem is a cosmetic ingredient and drug discovery company with a proprietary platform technology. Sirona specializes in stabilizing carbohydrate molecules with the goal of improving efficacy and safety. New compounds are patented for maximum revenue potential. Sirona’s compounds are licensed to leading companies around the world in return for licensing fees, milestone fees and ongoing royalty payments. Sirona’s laboratory, TFChem, is located in France and is the recipient of multiple French national scientific awards and European Union and French government grants.

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INDUSTRIAL IMPACT

XtalPi and CK Life Sciences to collaborate in AI-empowered tumour vaccine research and development, opening a new paradigm for scientific innovation

XtalPi Inc. | November 25, 2022

XtalPi announced today that they are embarking on a strategic collaboration with CK Life Sciences, a member of the CK Hutchison Group. XtalPi and CK Life Sciences will leverage their respective expertise to jointly develop a novel AI tumour vaccine R&D platform to improve the discovery and design capabilities of tumour vaccines and accelerate the development of more vaccine types. The goal of this collaboration is to realize precision treatment for patients worldwide. According to public information, there were nearly 20 million newly diagnosed cancer patients worldwide in 2021, of which about 4.5 million cases came from China. Many cancer types lead to detrimental outcomes, with high morbidity and mortality, and there remains a large unmet clinical need. Tumour vaccines targeting different tumour neoantigens, tumour-associated antigens and tumour-specific antigens in patients can be designed for use as immunotherapy, to activate the patient's own specific immune responses. Currently, there are only two therapeutic tumour vaccines— sipuleucel-T for melanoma and Bacillus Calmette-Guérin for bladder cancer, as well as preventive tumour vaccines against human papillomavirus infection and hepatitis B infection approved by the U.S. Food and Drug Administration. Recently, several other tumour vaccines have entered clinical development and evidence of efficacy has begun to emerge. According to Mordor Intelligence, the global cancer vaccine market size was US$6.79 billion in 2021 and will increase at a compound annual growth rate of 11.53% from 2022 to 2026. The expected market size by 2026 will be approximately US$12 billion. Currently, the design and preclinical development process for tumour vaccines is complex and lengthy, hindering the efficiency and success rate of tumour vaccine research and development. Incorporating XtalPi's industry expertise in AI computation and robotic automation, this collaboration aims to build an AI tumour vaccine R&D platform that applies advanced AI algorithms and high-precision molecular modeling to predict and design a variety of tumour vaccines that can activate specific immune responses to kill tumours. The tumour vaccines will be screened and verified through automated experiments, and through integrating algorithmic feedback to optimise activity and efficacy, the platform is expected to generate preclinical tumour vaccine candidate compounds with robust immune activity. "As a company headquartered in the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone, XtalPi is committed to realising the synergies between Shenzhen and Hong Kong by creating a new paradigm for innovation in the Greater Bay Area. Empowered by the latest technological advancements in automation, artificial intelligence is accelerating more innovative and diverse areas in drug research and development. Together with CK Life Sciences, we are committed to overcome conventional limitations and discover diverse applications for cutting-edge technologies. We believe the AI cancer vaccine platform jointly developed by CK Life Sciences and XtalPi will inspire the global scientific community to progress vaccine research and development and fast-track key development milestones for cancer vaccines. We are confident that this collaboration will significantly facilitate the scientific research exchange in the Greater Bay Area." Dr. Shuhao Wen, co-founder and chairman of XtalPi Dr. Melvin Toh, Vice President and Chief Scientific Officer of CK Life Sciences, comments: "The R&D of tumour vaccines is one of the key development directions of CK Life Sciences. The cooperation with XtalPi will apply XtalPi's AI algorithm, molecular modeling and automated experiments to speed up the R&D process, improve the success rate, and increase the efficacy of tumour vaccines." About XtalPi Founded in 2014, XtalPi founders recognized a common hurdle in drug development having to do with solid polymorphism, which could be successfully tackled with quantum physics predictions. Since then, XtalPi has maintained its focus on identifying and then attacking traditional bottlenecks in biopharmaceutical R&D through innovative technologies. Through considerable capital investments in automation and personnel, XtalPi now has four locations worldwide and employs approximately 1000 employees. XtalPi has engaged in collaboration research with nearly all top-20 pharmaceutical companies in the world. Its ID4 platform combines physics-based simulations with experimental validation and refinement, automation for rapid synthesis, and machine learning to continuously improve prediction accuracy and process efficiency. About CK Life Sciences CK Life Sciences is listed on the Stock Exchange of Hong Kong. Bearing the mission of improving the quality of life, CK Life Sciences is engaged in the business of research and development, manufacturing, commercialisation, marketing, sale of, and investment in, products and assets which fall into three core categories - nutraceuticals, pharmaceuticals and agriculture-related. CK Life Sciences is a member of the CK Hutchison Group.

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CELL AND GENE THERAPY

Gamma Biosciences and Lonza Collaborate to Co-develop Reagents for Clinical Cell Selection in the Cocoon® Platform

Gamma Biosciences | October 13, 2022

Gamma Biosciences, a leading provider of tools and technologies for cell and gene therapy manufacturing, through their BioMagnetic Solutions business announced a strategic collaboration with Lonza. Under the multi-year agreement, BioMagnetic Solutions will supply its proprietary research and cGMP manufacturing grade FerroSelect™ reagents to Lonza for use in developing CAR-T and other immunotherapeutic products using Lonza's Cocoon® Platform. "We are looking forward to working together with the team at Gamma Biosciences to offer cell and gene therapy developers added cell selection functionality on the Cocoon® Platform. The BioMagnetic Solutions ferrofluid technology provides efficient, high-performance cell selection reagents for research, clinical, and commercial-scale cell separations in a workflow that can be easily integrated into our automated, closed-system Cocoon® manufacturing platform. This collaboration speaks to Lonza's commitment to expanding the flexibility and functionality of our automated manufacturing technology to address a broader range of needs for the cell therapy industry." Adam Bryan, Vice President of Personalized Medicines at Lonza "We are thrilled to collaborate with Lonza in further developing and adapting FerroSelect reagents for use with the Cocoon® Platform," said Phil Vanek, Chief Technology Officer at Gamma Biosciences. "The Lonza platform can be an alternative to our FerroSelect Array cell selection platform, demonstrating that our proprietary reagents can be applied to other automated manufacturing technologies. The agreement gives BioMagnetic Solutions technical direction on new applications, and access to some of the best process developers in the industry. In return, Lonza gains early access to certain BioMagnetic Solutions FerroSelect reagents to complement the growing demand for their Cocoon® Platform technology." Ted Liberti, Chief Commercial Officer at BioMagnetic Solutions concluded, "This is an exciting time for us. In late 2021, we achieved ISO 9001:2015 and 13485:2016 certification for our Quality Systems through NQA and have been working steadily to build out an extensive repertoire of cell specific antibodies. The alignment with Lonza helps both companies contribute to expanding access to therapeutic cell selection capabilities across the market with space to grow to meet evolving customer needs." The collaboration between Gamma Biosciences and Lonza provides a framework for additional clinical grade reagents to be developed. It also opens up the possibility of other collaborations as Gamma Biosciences expands its portfolio of tools and technologies supporting the bioprocessing, vaccine, cell and gene therapy industries. About BioMagnetic Solutions BioMagnetic Solutions develops advanced ferrofluid-based immunomagnetic cell selection systems for clinical and commercial applications. BioMagnetic Solutions' product platform leverages proprietary magnetic ferrofluids that enable superior performance as compared to existing immunomagnetic cell separation systems. About Gamma Biosciences Gamma Biosciences is a leading life sciences company providing products and services to support the development and manufacturing of advanced biologic therapies. Our operating companies are committed to advancing the science and art of bioprocessing by delivering market-ready innovation and expertise that helps our customers. Gamma Biosciences encompass biopharmaceutical companies, contract developers and manufacturing companies. Our goal is to safely bring therapies to patients quickly and efficiently. Gamma is a global company with offices and major manufacturing facilities in North America, the U.K. and Belgium. About Lonza Lonza is the preferred global partner to the pharmaceutical, biotech and nutrition markets. We work to enable a healthier world by supporting our customers to deliver new and innovative medicines that help treat a wide range of diseases. We achieve this by combining technological insight with world-class manufacturing, scientific expertise and process excellence. Our unparalleled breadth of offerings enables our customers to commercialize their discoveries and innovations in the healthcare industry.

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