Study presents drug candidate for reversing mucosal barrier damage by HIV

medicalxpress | May 06, 2019

A vaginal microbicide that could prevent sexual transmission of HIV-1 in women has tremendous potential for saving lives and helping staunch an epidemic. But the delicate milieu of microbes that naturally colonize the vagina and maintain a healthy mucosal barrier have made the search for such a microbicide challenging, thwarting clinical trials of the most promising candidates. Investigators at Brigham and Women's Hospital led by Raina Fichorova, MD, Ph.D., in collaboration with an international team, tested a laboratory-made version of a naturally occurring protein (recombinant fragment of human Surfactant Protein D or rfhSP-D) on bioengineered vaginal tissues, immune cells and microbes to determine if the drug candidate could help prevent HIV transmission safely. In a paper published in Frontiers in Immunology, the team reports on the technique's success in preclinical testing, establishing it as a promising anti-HIV-1 vaginal microbicide.

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Luciano Rossetti, MD, head of global research and development, EMD Serono, Merck, KGaA, Darmstadt Germany, highlights the dedication and perseverance biopharmaceutical research scientists need to translate research into new medicines for patients.


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Saudi Ministry of Investment and Insilico Medicine sign agreement to expand region’s biotechnology capabilities

Insilico Medicine | September 15, 2022

Saudi Arabia’s Ministry of Investment and clinical stage artificial intelligence (AI)-driven drug discovery company Insilico Medicine have signed a memorandum of understanding (MoU) to support the development of a robust AI-driven biotech industry in the Kingdom. The agreement was signed during the Global AI Summit, held from the 13th through the 15th of September in Riyadh, which featured over 200 speakers representing 90 countries discussing the future of AI, including Insilico Medicine founder and CEO Alex Zhavoronkov, PhD. Sara Althari, PhD, senior researcher and MISA advisor, spearheaded the agreement. MISA and Insilico Medicine will work on shared initiatives that build on the capabilities of Insilico’s end-to-end AI-powered drug discovery platform, PharmaAI. Drawing on trillions of data points, the platform has three distinct but interconnected elements – novel AI target discovery novel AI drug design and AI clinical trial prediction. Under the terms of the MoU, Insilico will share its expertise and software platform with local biotech companies to support and accelerate their research and drug development efforts. Through the partnership, the MoU also seeks to spur the development of new biotech companies. Insilico will also work with Saudi companies on robotics-aided drug design and clinical trial design and best practices. The Company is launching a fully autonomous AI-run robotics lab that will perform experiments, capture data, and further validate its AI-discovered and designed drugs later this fall. The Company’s clinical trial prediction tool, InClinico, is designed to help researchers and companies plan trials with greater statistical likelihood of Phase 2 success. There will be additional partnership opportunities in other areas where Insilico’s AI platform has shown promise, including the support and initiation of projects related to healthy longevity and support for green chemistry initiatives, including the development of sustainable chemicals and crop protection solutions. “As someone who decided to dedicate his life to extending healthy productive longevity for everyone on the planet, I applaud Saudi Arabia’s new initiatives in this most impactful area of research. As a company, we are encouraged by Saudi Arabia’s vision to increase its digital economy and play a meaningful role in the future of drug discovery using AI and robotics. We look forward to working together to expand the region’s biotech sector and partnering with established and emerging companies as well as academic and research institutions in order to explore the full potential of our end-to-end AI platform.” Alex Zhavoronkov, PhD, founder and CEO of Insilico Medicine Over the past year, MISA has signed MoUs with a number of pharmaceutical and technology companies to grow its biotech sector, including Novartis, Janssen, AstraZeneca, GSK and Roche, as well as Amazon Saudi Arabia. Insilico Medicine, a company which bridges pharma and tech, is the first AI-driven drug discovery company to sign such an agreement in the region. About Insilico Medicine Insilico Medicine, a clinical stage end-to-end artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to discover novel targets and to design novel molecular structures with desired properties. Insilico Medicine is delivering breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases and aging-related diseases.

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PHARMACY MARKET

A novel azapeptide editing method provides potential for new drug development, Feinstein Institutes research shows

Feinstein Institutes | November 29, 2022

Peptides, short sections of proteins made up of chains of amino acids, are an important area of new drug development due to their potential for increased specificity and fewer side effects. Their main drawback is the rapid degradation by the body’s own enzymes, which has led to the need to develop longer-lasting peptide alternatives. Azapeptides are one type of peptide alternative that has shown great potential as therapeutics, exemplified by the HIV drug, Atazanavir. A new paper published in the journal Nature Communications by researchers at The Feinstein Institutes for Medical Research details proprietary reagents and methods that can selectively replace only those amino acids known to be targeted by enzymes with more stable versions to create azapeptides. The paper, authored by Yousef Al-Abed, PhD, co-director of the Institute of Bioelectronic Medicine at the Feinstein Institutes, describes the proprietary building blocks and method used to conduct systematic and robust peptide editing, replacing targeted amino acids with aza-amino acids to form more stable and efficient azapeptides. The azapeptides created could expedite the novel therapies to treat many diseases and conditions, including metabolic disease, influenza, pulmonary arterial hypertension, Crohn’s disease, arthritis, and irritable bowel diseases, among others. The paper, titled “Thiocarbazate building blocks enable the construction of azapeptides for rapid development of therapeutic candidates,” provides multiple examples of azapeptide construction, screening, and selection using a known peptide inhibitor of inflammation and bradykinin. “Peptides as drug candidates are easy to discover yet difficult to develop as final drugs because of their fast degradation in our body. A technology that circumvents these problems inherent to native peptides will change the future landscape of drug discovery. Our technology provides a platform of tools that enable minimal modification of any peptide at highly prone degradation sites, thereby increasing its life span in our body, allowing it more time to find its target and neutralize it.” Dr. Al-Abed Through peptide editing, going from peptide to azapeptide, using methods that Dr. Al-Abed and his team detail in the new paper, scientists can create potential therapies that have enhanced characteristics compared to natural peptides, like longer stabilities in a more efficient manner. Dr. Al-Abed and his team have precisely engineered thiocarbazates (a novel functional group) in the proprietary process to achieve an almost universal and more efficient means to selectively replace amino acids in a peptide chain. “Peptide drugs are a crucial resource for patients and the global pharmaceutical industry,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research. “Dr. Al-Abed and his team invented a fully automated chemical strategy using novel chemistry to make new peptide drugs which is an important new avenue for peptide drug discovery.” About the Feinstein Institutes The Feinstein Institutes for Medical Research is the research arm of Northwell Health, the largest health care provider and private employer in New York State. Home to 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine – a new field of science that has the potential to revolutionize medicine.

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Astellas Announces Topline Results from Phase 3 Long-Term Safety Study of Fezolinetant in Mainland China

Astellas Pharma Inc. | September 05, 2022

Astellas Pharma Inc. announced topline results from the Phase 3 MOONLIGHT 3™ clinical trial in women in mainland China evaluating the long-term safety and tolerability of fezolinetant, an investigational oral, nonhormonal compound being studied for the treatment of moderate to severe vasomotor symptoms associated with menopause. VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause. MOONLIGHT 3 is a 52-week single-arm Phase 3 clinical trial investigating the long-term safety and tolerability of fezolinetant 30 mg taken once daily in 150 women in mainland China seeking treatment for relief of VMS associated with menopause. The study's primary endpoint is the frequency and severity of adverse events which were generally consistent with previous Phase 3 studies of fezolinetant. Detailed results will be submitted for publication in the near future. "The topline results from the MOONLIGHT 3 study are very encouraging and, upon initial review, further support the long-term safety of fezolinetant. We are evaluating the full MOONLIGHT data sets and remain committed to developing innovative treatments in this therapeutic area with the hope of delivering a first-in-class, nonhormonal treatment option for women with moderate to severe VMS." Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas Fezolinetant is an investigational selective neurokinin-3 receptor antagonist and is not approved anywhere in the world. In the U.S., a New Drug Application for fezolinetant for the treatment of moderate to severe VMS associated with menopause is under review. The NDA submission is based on results from two pivotal Phase 3 clinical trials, SKYLIGHT 1™ and SKYLIGHT 2™, and the Phase 3 long-term safety study, SKYLIGHT 4™. About the MOONLIGHT Phase 3 Clinical Trials MOONLIGHT 1™ is designed to investigate the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS associated with menopause in women in Asia. The study is double-blinded and placebo-controlled for the first 12 weeks, followed by a 12-week non-controlled extension treatment period. A total of 302 women with moderate to severe VMS associated with menopause were enrolled at nearly 60 sites in mainland China, Korea and Taiwan. MOONLIGHT 3™ is a 52-week single-arm Phase 3 clinical trial designed to investigate the long-term safety and tolerability of fezolinetant in women in mainland China with VMS associated with menopause. A total of 150 women were enrolled at 34 sites in mainland China. About the BRIGHT SKY™ Phase 3 Program The BRIGHT SKY pivotal trials, SKYLIGHT 1™ and SKYLIGHT 2™ enrolled over 1,000 women with moderate to severe VMS. The trials are double-blinded, placebo-controlled for the first 12 weeks followed by a 40-week treatment extension period. Women were enrolled at over 180 sites within the U.S., Canada and Europe. SKYLIGHT 4™ is a 52-week double-blinded, placebo-controlled study designed to investigate the long-term safety of fezolinetant. For SKYLIGHT 4, over 1,800 women with VMS were enrolled at over 180 sites within the U.S., Canada and Europe. About VMS Associated with Menopause VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause.1,2 Worldwide, more than 50% of women 40 to 64 years of age experience VMS and, in East Asia, the prevalence of VMS has been estimated to be around 80% of women 40 to 65 years of age, with 55% having moderate to severe VMS.3,4 VMS can have a disruptive impact on women's daily activities and overall quality of life.1 About Fezolinetant Fezolinetant is an investigational oral, nonhormonal therapy in clinical development for the treatment of moderate to severe VMS associated with menopause. Fezolinetant works by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron to moderate neuronal activity in the thermoregulatory center of the brain (the hypothalamus) to reduce the frequency and severity of moderate to severe VMS associated with menopause.5,6,7 The safety and efficacy of fezolinetant are under investigation and have not been established. There is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated. About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients.

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Lifespin Launches Commercial Access to its Metabolic Profiler Software and Database for Pharma and Biobank Services

Lifespin | September 16, 2022

Lifespin GmbH, based in Regensburg with offices in Boston, Massachusetts, announced that it has launched a new commercial service that, for the first time, will provide the pharmaceutical and biobanking industry with access to Lifespin’s proprietary metabolic database, along with its advanced interpretive software to assist in various phases of drug research, development, and manufacturing. Immediate applications of Lifespin’s commercial services will include quality control for synthetic/natural compounds, quantitative profiling of metabolites in liquid samples, monitoring of drug responses and organ-specific metabolic phenotyping, and precision nutrition to therapeutic drug monitoring and longitudinal treatment monitoring. “Making our technology platform accessible to the pharma and biobanking industry will provide the field with deeper clinical insights and improve stratification of patient data in clinical trials, enabling pharmaceutical companies and others in the field to perform a range of precision phenotyping of cell or animal models and patient cohorts. Our goal is to provide the pharma and biobank scientists with yet another powerful resource in their development toolbox, including our advanced algorithms and database, to enhance their earlier phase analysis and to help better identify the strengths and weaknesses of compounds in study during research through clinical trials.” Dr. Ali Tinazli, CEO of Lifespin GmbH Lifespin, a deep data company that maps human health based on snapshots of metabolic states, has built one of the largest and most comprehensive databases of metabolic health profiles across healthy and diseased individuals covering multiple age and gender groups as well as specific diseases in neurology, oncology, and inflammation. Utilizing proprietary technology, Lifespin is performing quantitative in-house measurements of metabolomes, digitizing metabolic profiles that include billions of metabolic relationships. These digital metabolic profiles allow systematic mapping across various health conditions and may enable differential diagnosis and early detection of health conditions, staging of diseases, monitoring of treatment success and personalized medicine. Lifespin’s advisory board consists of key opinion leaders such as James Rothman (Nobel Laureate in Physiology/Medicine, Sterling Professor of Cell Biology, Yale University, New Haven, CT USA) and other prominent leaders in the relevant fields of study.

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Spotlight

Luciano Rossetti, MD, head of global research and development, EMD Serono, Merck, KGaA, Darmstadt Germany, highlights the dedication and perseverance biopharmaceutical research scientists need to translate research into new medicines for patients.

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