University of Palermo

New business unit is focused on "undruggable" targets for age-related indications and genetically inherited diseases. MOUNT LAUREL, N.J., Sept. 20, 2023 /PRNewswire/ -- CCM Biosciences, a pharmaceutical discovery and development company that recently confirmed its launch from stealth, today announced its latest business unit — CCM Protein Upregulation — dedicated to advancing first-in-class drug leads for age-related conditions such as Alzheimer's, Parkinson's, and infertility as well as for genetically inherited diseases such as cystic fibrosis, using highly differentiated technology platforms for improving the enzymatic activity or expression level of critical proteins implicated in the pathogenesis of such disorders. Continue Reading Enhancement of the activity or expression level of proteins is important for the treatment of many age-related and genetically inherited conditions. However, whereas reduction of enzymatic activity or protein expression level can be achieved for a very broad class of protein targets by inhibitors — which comprise the vast majority of small molecule drugs — and protein degraders, respectively, enhancement of the activity or expression level of protein targets is notoriously difficult. Protein targets susceptible to enzymatic activity enhancement have historically been almost entirely restricted to those with naturally evolved, so-called allosteric binding sites, and enhancement of protein expression by orally bioavailable drug molecules generally requires interaction between the drug and the cellular machinery for protein synthesis at the genetic level. CCM Protein Upregulation's technology platform is comprised of methods for the design of drugs that can enhance enzyme activity in the absence of allosteric binding sites, as well as drugs that can enhance translation of messenger RNAs (mRNAs) for genes bearing nonsense mutations to enable efficient production of functional proteins. CCM's sirtuin-activating drug leads were discovered in-house using its proprietary, patented drug discovery platform. Tweet this Advances aimed at improving human healthspan and lifespan are arguably among the most coveted targets in healthcare but also among the most scientifically complex ones. A class of enzymes known as sirtuins has been shown to play a central role in the regulation of human longevity and age-related diseases. However, most of these enzymes are considered "undruggable" because of the challenge of improving the activity of these enzymes in the absence of known allosteric sites. Among the seven mammalian sirtuin enzymes SIRT1-7, only SIRT1 has a known allosteric site. To date, sirtuin activation has been pursued pharmaceutically for SIRT1 by allosteric activation and for other sirtuins by nutraceutical supplements that are not drugs. CCM's sirtuin-activating drug leads were discovered in-house using its proprietary, patented drug discovery platform, which combines computational biophysics and DNA-Encoded Libraries, building upon publications by CCM scientists in the Proceedings of the National Academy of Sciences, Bioorganic and Medicinal Chemistry, the Journal of Chemical Physics, and PLoS. Application of the platform led to the discovery of novel first-in-class hits for activation of SIRT3, the major sirtuin enzyme in mitochondria – the energy production powerhouses of cellular metabolism that become less efficient with age, in part due to loss of sirtuin activity. "Characterization of the novel sirtuin activators uncovered for the first time the mechanism whereby they can activate enzymes without allosteric sites. In particular, these compounds were shown to increase up to two-fold the catalytic efficiency of SIRT3 under conditions wherein the essential metabolic cofactor NAD+ is depleted, as it is in old age. Such compounds have the potential to rejuvenate the activity of SIRT3 to levels observed in youth," said Dr. Raj Chakrabarti, CEO of CCM Biosciences. Preclinical studies are underway on evaluating the efficacy of such non-allosteric sirtuin activators for conditions stemming from the decline of mitochondrial function and NAD+ levels with age, such as Parkinson's and the reduction of fertility in females of advanced maternal age. Genetically inherited diseases affect hundreds of millions of people worldwide. An estimated 30 million of those patients are impacted by a nonsense mutation, which results in making an incomplete, nonfunctional protein product. CCM Protein Upregulation's drug leads represent a first-in-class opportunity to treat multiple diseases caused by nonsense mutations. The company's drug leads for nonsense mutation translational readthrough were discovered using computer-aided drug discovery methods, and acquired through exclusive licensing rights from the University of Palermo and the Italian Cystic Fibrosis Foundation. With promising preclinical animal study results, IND-enabling studies for the lead indication of cystic fibrosis are underway. About CCM Biosciences CCM Biosciences is a biotechnology company dedicated to discovering and developing novel drugs, including small molecules, gene therapies, biologics, and nanomedicines. CCM's patented drug discovery platforms were developed at Chakrabarti Advanced Technology, a privately funded R&D institute founded in 2010 with scientists in the US, France and India and with publications in leading scientific journals including PNAS, Nucleic Acids Research, American Chemical Society journals and Nature Publishing Group journals. These platforms are complemented by the contract research, development, and manufacturing organizations (CRDMO) at PMC Group, developed through acquisitions of industry-leading companies. Contact: Anisha Ghosh Email: [email protected] SOURCE CCM Biosciences

About 13,000 years ago, a climate crisis caused a global drop in temperatures in the northern hemisphere. This episode of intense cold, known as the Younger Dryas, also caused severe aridity across the Mediterranean basin, which had a major impact on terrestrial and marine ecosystems. But what do we know about the impact of this climate change on water circulation in the Mediterranean? About 13,000 years ago, a climate crisis caused a global drop in temperatures in the northern hemisphere. This episode of intense cold, known as the Younger Dryas, also caused severe aridity across the Mediterranean basin, which had a major impact on terrestrial and marine ecosystems. But what do we know about the impact of this climate change on water circulation in the Mediterranean? During the Younger Dryas, the flow of water masses from the eastern Mediterranean to the Atlantic Ocean through the Strait of Gibraltar doubled, according to a study published in Nature's Communications Earth & Environment journal. The work has applied the innovative technique of neodymium (Nd) isotopes to reconstruct the conditions in the Mediterranean since the last deglaciation, some 14,000 years ago. The study is part of the doctoral thesis being carried out by Sergio Trias-Navarro, under the supervision of Professor Leopoldo Pena and Professor Isabel Cacho, from the consolidated research group in Marine Geosciences (GCR Marine Geosciences) of the Faculty of Earth Sciences of the University of Barcelona. The study presents some of the most relevant results of the European Research Council's TIMED project (ERC-Consolidator), and has an outstanding participation of members of the GCR Marine Geosciences, and experts from La Sapienza University of Rome, the University of Palermo (Italy), and the Swiss Federal Institute of Technology in Zurich (Switzerland). The most intense climate change in 13,000 years The Younger Dryas was the most intense climate change of the last 13,000 years and the most far-reaching on a planetary scale. Its end marked the end of the Holocene, the interglacial period in which we find ourselves today. "There has also been climate variability during the Holocene, such as the episodes known as the Little Ice Age, the Medieval Climatic Anomaly or the Roman Warm Period. However, this climate variability had a lower relative intensity with different regional climatic expressions, without the capacity to generate changes on a global scale," says Professor Isabel Cacho, from the UB Department of Earth and Ocean Dynamics. The paper also analyses the last sapropel, a Holocene episode after the Younger Dryas linked to an extraordinary increase in rainfall in the Mediterranean region, especially in North Africa. The study provides the first quantification of changes in the deep circulation of the eastern Mediterranean during this episode, and it has estimated that it was reduced by up to a quarter compared to the Younger Dryas. Still, the experts explain that the impact this event may have had on the oceanography of the North Atlantic is unknown. The new study supports the hypothesis that increased salt input from the Mediterranean into Atlantic waters during the Younger Dryas was key to reactivating the North Atlantic circulation: this led to a rapid warming in Europe and the Mediterranean, which marked the beginning of the Holocene. "Mediterranean water masses are one of the primary sources of salt in the North Atlantic. Water salinity is an important factor in oceanography, as it determines the density of water masses. It is therefore a key process in the formation of deep waters in the Atlantic Ocean and is the driver of global ocean circulation," says researcher Sergio Trias-Navarro. A technical innovation to study the oceans of the past As in other previous studies conducted by the GRC Marine Geosciences, the team has applied the innovative technique of neodymium radiogenic isotopes as geochemical tracers to reconstruct the oceanographic conditions of the past. This analytical study has been carried out in the LIRA and PANTHALASSA laboratories, unique research support facilities in Catalonia located in areas of the Faculty of Earth Sciences and the UB's Scientific and Technological Centres (CCiTUB) and coordinated by experts Leopoldo Pena and Isabel Cacho. "Compared to other types of geochemical tracers, Nd isotopes have the great advantage of being conservative. Therefore, they do not interact with or are not affected by biological processes, for example, biological productivity or the degradation of organic matter," says Professor Leopoldo Pena, co-author of the paper. "This technique allows us to go beyond time and it can be applied to oceanographic reconstructions of both the present and the past. It allows us to understand the dynamics of the ocean and reconstruct oceanography long before we could observe or measure it ourselves with other scientific tools," adds the expert. Younger Dryas: a mirror for the Mediterranean of the future? There are still many enigmas about the potential impact of Mediterranean waters on the North Atlantic circulation. Despite the scientific interest, "much of the oceanographic studies focusing on the Atlantic Ocean do not consider the Mediterranean, and perhaps the role of Mediterranean waters in the Atlantic circulation has been downplayed," note the authors. The latest report of the Intergovernmental Panel on Climate Change (IPCC) presents the Younger Dryas as an example of the predictable changes in rainfall that will take place in the Mediterranean as a consequence of an expected reduction in the circulation of the North Atlantic. "On the other hand, according to projections for the end of the 21st century, the Mediterranean circulation will weaken and, consequently, so will its contribution to the Atlantic Ocean," says Isabel Cacho, coordinator of the TIMED project. In the current context of climate change, studies such as this one are increasingly necessary to better understand the sensitivity of the Mediterranean circulation to different climatic situations. "The Younger Dryas is not a perfect analogue for future changes, as we are currently facing a much more amplified greenhouse effect. Still, our study reveals that the change in aridity which is expected by the end of the century is capable of inducing an intensification of the Mediterranean circulation, although the projected warming could counteract this effect. For this reason, we need to better understand the relative weight that these two variables -- temperature and humidity -- have had on the evolution of the Mediterranean circulation," concludes the research team.

Novartis Board of Directors approves the recommendation of Sandoz Chairman-designate for the future Sandoz Board of Directors, to start preparatory work in June, followed by formal constitution in H2 2023 Experienced and diverse group of corporate leaders with a track record of growing businesses and driving value for the organization and society will help set strategic direction for Sandoz and support its future development Basel, May 15, 2023 — Sandoz takes the next steps to prepare for the planned listing on the Swiss Stock Exchange (SIX): The Novartis Board of Directors has approved the recommendations of the Sandoz Chairman-designate, Gilbert Ghostine, on the structure of the to-be Board of Directors of Sandoz and has nominated all of its future members. The Sandoz Board of Directors will have 10 members in total and 3 sub-committees: a Science, Innovation & Development Committee, a Human Capital & ESG Committee and an Audit, Risk & Compliance Committee. The Sandoz Board of Directors will start preparatory work from June onwards and will be effective following the planned spin-off of Sandoz in the second half of 2023, subject to Novartis Board of Directors and shareholder approval. The new board members are: Dr. Karen J. Huebscher, non-executive board member in companies, institutions and former CEO of Solvias Group, a Swiss contract research firm, which she led between 2014 and 2021. Before joining Solvias Group, Karen held various senior leadership roles at Novartis, including global head investor relations from 2000 to 2006, head M&A and Executive Committee member, as well as site head for the Vaccines & Diagnostics division between 2006 and 2011. Karen holds a PhD in Natural Sciences from ETH Zurich, and an MBA from IMD, both in Switzerland. Since 2012, she serves as board member and currently as chair of the Audit Committee of Tecan Group, a Swiss listed company. She is also a board member at BBI Solutions, a UK based diagnostic reagents and a Novo Holdings company. Karen will be Vice Chair of the future Board of Directors of Sandoz as well as the ad interim Chair of its Science, Innovation & Development Committee. François-Xavier Roger, Chief Financial Officer of Nestlé S.A., the world’s largest food company, since 2015. Before joining Nestlé he served as CFO at Takeda Pharmaceuticals, one of the largest publicly listed companies in Japan, between 2013 and 2015, and CFO at Millicom, a NASDAQ listed global mobile phone operator based in Luxembourg, between 2008 and 2013. François-Xavier also worked in finance roles for global food company Danone in Asia and Paris and spent 14 years with predecessor companies of what today is Sanofi, one of the leading companies in the global pharmaceutical industry. He also served on 2 Boards of Directors at Takeda Pharmaceuticals between 2013 and 2015 and Britannia Industries, India, between 2000 and 2008. He will be Chair of the Audit, Risk & Compliance Committee of Sandoz. Urs Riedener, was CEO of Swiss consumer goods company EMMI Group between 2008 and 2022. Before joining EMMI Group as CEO, he was a Member of the Executive Board and Head of the Marketing Department at Migros-Genossenschafts-Bund. He holds a Master degree in Marketing and Trade from the University of St. Gallen (HSG), Switzerland. Urs also serves as President of the Board at Emmi AG, a Board member at Schwarz Group, Germany, and Bystronic AG, Switzerland. Urs will be Chair of the Human Capital & ESG Committee of Sandoz. Dr. Shamiram R. Feinglass, MD, MPH was most recently Chief Medical Officer for Life Sciences and Diagnostics and Vice President Global Medical Affairs and Policy, Life Sciences and Diagnostics, at Danaher, a global science and technology company. Shamiram holds an AB from Smith College and Doctor of Medicine as well as a Master of Public Health, both from Emory University, U.S.A. She also serves as Board Member of the Research and Innovation Advisory Board at Children's National Medical Center and a Fellow of the Aspen Institute Global Leadership Network, both in the US. Aarti Shah, PhD former Chief Information and Digital Officer & Senior Vice President at Eli Lilly and Company between 2016 and 2021, a US-headquartered pharmaceutical company with approximately US$ 28 billion in sales in 2021. She held other digital and data sciences related roles of increasing responsibility over her 27 years of a successful career with Lilly, including a Global Brand Development Leader role between 2013-2016. Aarti holds a PhD in Applied Statistics from the University of California at Riverside, USA. She serves as a Board member at both NVIDIA Corporation and Northwestern Mutual, both since 2020. Yannis Skoufalos, former Global Product Supply Officer at Procter & Gamble between 2011 and 2019, a US-headquartered consumer goods company with approximately USD 81 billion in sales for the year ending in March 2023. He held other supply chain roles of increasing responsibility over his 35 years successful international career with Procter & Gamble and served under three different CEOs. He holds a Master of Science in Food Engineering and a Bachelor of Science in Chemical Engineering from the University of Leeds, UK. Yannis also currently serves on the Board of Directors of Hostess Brands, a public company in the US, and on the Board of Directors of Sustana, a recycled paper fiber company which is a privately held company of Blackstone. Remco Steenbergen, Chief Financial Officer of Deutsche Lufthansa AG since 2021, the largest airline group in Europe with approximately EUR 33 billion of sales in 2022. Before joining Lufthansa, he served as Group CFO at Barry Callebaut based in Switzerland from 2018 through 2020. Prior to that, he worked in multiple executive business and finance roles for Philips and KPMG. Remco also serves on the Board of Directors at Swiss International Air Lines since 2021. He holds a Post-Doctorate in Accountancy from the Erasmus University Rotterdam, Netherlands, and a Master in Business Administration from IMD Business School in Switzerland. Dr. Maria Varsellona, Chief Legal Officer and Company Secretary at Unilever since 2022, a UK-headquartered consumer goods company with approximately EUR 60 billion in sales. Between 2019 and 2022 she served as General Counsel and Company Secretary of the Switzerland-headquartered industrial company ABB. Prior, she served as Chief Legal Officer of Finland-headquartered telecom company Nokia, as well as President of Nokia Technologies. She has also served as General Counsel of Switzerland-headquartered Tetra Pak and held senior roles at General Electric’s Oil and Gas business. Maria holds a Juris Doctor degree from the University of Palermo, Italy. She served as a non-executive director on the board of Nordea Bank between 2016-2020 and on the board of ABB India between 2020 and 2022. A further member of the future Sandoz Board of directors with deep healthcare and US experience has been pre-selected with a view of being nominated for election at the Annual General Meeting of Shareholders in 2024. The Sandoz Board will consist of experienced and diverse business leaders with a track record of driving business and social impact in very competitive and complex environments. In total, 4 out of 10 members of the new Sandoz Board of Directors will be female, resulting in an above average 40% female-to-male ratio for this important governance body. “I am delighted to see our new board members join Sandoz. The composition of this new world class board and the capabilities of its leaders is in line with the Sandoz aspiration as a market leader in its industry. I am looking forward to working with the new board to help set the strategic direction for Sandoz and support its future development”, said Gilbert Ghostine, Chairman-designate of Sandoz. For more information on the Sandoz Board of Directors, please also see https://www.sandoz.com/people-culture/board-directors DisclaimerThis media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this media update, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this media update will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise. About NovartisNovartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 103,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world. Find out more at https://www.novartis.com About SandozSandoz, a Novartis division, is a global leader in generic pharmaceuticals and biosimilars. Our purpose is to pioneer access for patients by developing and commercializing novel, affordable approaches that address unmet medical needs. Our ambition is to be the world’s leading and most valued generics company. Our broad portfolio of high-quality medicines, covering major therapeutic areas, accounted for 2022 sales of USD 9.2 billion. # # # Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Richard Jarvis +41 79 584 2326 Julie Masow +1 862 579 8456 Anja von TreskowAnna Schäfers +41 79 392 9697+41 79 801 7267 Michael MeoMary Carmichael +1 862 274 5414+1 862 200 8344 SwitzerlandSatoshi Sugimoto +41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Samir Shah +41 61 324 7944 Sloan Simpson +1 862 345 4440 Nicole Zinsli-Somm +41 61 324 3809 Parag Mahanti +1 973 876 4912 Isabella Zinck +41 61 324 7188