adiponectin

PETACH TIKVA, Israel--( BUSINESS WIRE )-- Can-Fite BioPharma Ltd . (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, today reported new data on Namodenoson’s anti-obesity mechanism of action. New data demonstrate that treatment of fat cells (3T3-L1 adipocytes) with Namodenoson leads to modulation of proteins that increase adiponectin level. Adiponectin is a regulator of fat production in the cells, resulting in the inhibition of fat levels. Furthermore, Namodenoson reduced body weight in an experimental animal model of obesity induced by a high fat diet. In a Phase IIa NASH study, in patients treated with Namodenoson, a 2.1% weight loss was observed after 3 months of treatment ( Safadi at Al ) and a significant decrease in serum adiponectin levels was found. “These new preclinical data, together with the excellent safety profile of Namodenoson in humans demonstrated to date, serve as robust support for its potential development as an anti-obesity drug,” said Pnina Fishman, Ph.D., CSO & Executive Chairman of Can-Fite BioPharma. The global obesity treatment market is lucrative due to the awareness of a link between chronic diseases and obesity. The World Health Organization reports that obesity has nearly tripled since 1975 and at least 2.8 million people are dying as a results of obesity each year. According to Goldman Sachs Research , the anti-obesity medications market is estimated reached $6 billion on an annualized basis in 2023 and is expected to grow to $100 billion by 2030. About Can-Fite BioPharma Ltd. Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF) is an advanced clinical stage drug development Company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer, liver, and inflammatory disease. The Company's lead drug candidate, Piclidenoson recently reported topline results in a Phase III trial for psoriasis and is expected to commence a pivotal Phase III. Can-Fite's cancer and liver drug, Namodenoson, is being evaluated in a Phase IIb trial for the treatment of steatotic liver disease (SLD), a Phase III pivotal trial for hepatocellular carcinoma (HCC), and the Company is planning a Phase IIa study in pancreatic cancer. Namodenoson has been granted Orphan Drug Designation in the U.S. and Europe and Fast Track Designation as a second line treatment for HCC by the U.S. Food and Drug Administration. Namodenoson has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. CF602, the Company's third drug candidate, has shown efficacy in the treatment of erectile dysfunction. These drugs have an excellent safety profile with experience in over 1,600 patients in clinical studies to date. For more information please visit: www.canfite.com . Forward-Looking Statements This press release may contain forward-looking statements, about Can-Fite’s expectations, beliefs or intentions regarding, among other things, its product development efforts, business, financial condition, results of operations, strategies or prospects. All statements in this communication, other than those relating to historical facts, are “forward looking statements”. 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Important factors that could cause actual results, performance or achievements to differ materially from those anticipated in these forward-looking statements include, among other things, our history of losses and needs for additional capital to fund our operations and our inability to obtain additional capital on acceptable terms, or at all; uncertainties of cash flows and inability to meet working capital needs; the initiation, timing, progress and results of our preclinical studies, clinical trials and other product candidate development efforts; our ability to advance our product candidates into clinical trials or to successfully complete our preclinical studies or clinical trials; our receipt of regulatory approvals for our product candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of our product candidates; our ability to establish and maintain strategic partnerships and other corporate collaborations; the implementation of our business model and strategic plans for our business and product candidates; the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and our ability to operate our business without infringing the intellectual property rights of others; competitive companies, technologies and our industry; risks related to the COVID-19 pandemic and the Russian invasion of Ukraine; risks related to not satisfying the continued listing requirements of NYSE American; and statements as to the impact of the political and security situation in Israel on our business. More information on these risks, uncertainties and other factors is included from time to time in the “Risk Factors” section of Can-Fite’s Annual Report on Form 20-F filed with the SEC on March 30, 2023 and other public reports filed with the SEC and in its periodic filings with the TASE. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Can-Fite undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws.

New research combined both physiological and archaeological evidence to argue that not only did prehistoric women engage in the practice of hunting, but their female anatomy and biology would have made them intrinsically better suited for it. When Cara Ocobock was a young child, she often wondered at the images in movies, books, comics and cartoons portraying prehistoric men and women as such: "man the hunter" with spear in hand, accompanied by "woman the gatherer" with a baby strapped to her back and a basket of crop seeds in hand. "This was what everyone was used to seeing," Ocobock said. "This was the assumption that we've all just had in our minds and that was carried through in our museums of natural history." Many years later, Ocobock, an assistant professor in the Department of Anthropology and director of the Human Energetics Laboratory at the University of Notre Dame, found herself as a human biologist studying physiology and prehistoric evidence and discovering that many of these conceptions about early women and men weren't quite accurate. The accepted reconstruction of human evolution assumed males were biologically superior, but that interpretation wasn't telling the whole story. Relying on both physiological and archaeological evidence, Ocobock and her research partner, Sarah Lacy, an anthropologist with expertise in biological archaeology at the University of Delaware, recently published two studies simultaneously in the journal American Anthropologist. Their joint research, coming from these two angles, found that not only did prehistoric women engage in the practice of hunting, but their female anatomy and biology would have made them intrinsically better suited for it. Of her and her co-author's dual-pronged research, which was the cover story for the November issue of Scientific American, Ocobock said, "Rather than viewing it as a way of erasing or rewriting history, our studies are trying to correct the history that erased women from it." Female physiology and estrogen, the 'unsung hero of life' In their physiological study, the two researchers explained that prehistoric females were quite capable of performing the arduous physical task of hunting prey and were likely able to hunt successfully over prolonged periods of time. From a metabolic standpoint, Ocobock explained, the female body is better suited for endurance activity, "which would have been critical in early hunting because they would have had to run the animals down into exhaustion before actually going in for the kill." Two huge contributors to that enhanced metabolism are hormones -- in this case, estrogen and adiponectin, which are typically present in higher quantities in female bodies than in male. These two hormones play a critical role in enabling the female body to modulate glucose and fat, a function that is key in athletic performance. Estrogen, in particular, helps regulate fat metabolism by encouraging the body to use its stored fat for energy before using up its carbohydrate stores. "Since fat contains more calories than carbs do, it's a longer, slower burn," Ocobock explained, "which means that the same sustained energy can keep you going longer and can delay fatigue." Estrogen also protects the body's cells from damage during heat exposure due to extreme physical activity. "Estrogen is really the unsung hero of life, in my mind," Ocobock said. "It is so important for cardiovascular and metabolic health, brain development and injury recovery." Adiponectin also amplifies fat metabolism while sparing carbohydrate and/or protein metabolism, allowing the body to stay the course during extended periods, especially over great distances. In this way, adiponectin is able to protect the muscles from breaking down and keeps them in better condition for sustained exercise, Ocobock explained. The female body structure itself is another element Ocobock and Lacy found to be of advantage in terms of endurance and effectiveness for prehistoric hunters. "With the typically wider hip structure of the female, they are able to rotate their hips, lengthening their steps," Ocobock detailed. "The longer steps you can take, the 'cheaper' they are metabolically, and the farther you can get, faster. "When you look at human physiology this way, you can think of women as the marathon runners versus men as the powerlifters." Archaeology tells more of the story of 'woman the hunter' Several archaeological findings indicate prehistoric women not only shared in the resulting injuries of the dangerous business of close-contact hunting, but that it was an activity held in high esteem and valued by them. "We have constructed Neandertal hunting as an up-close-and-personal style of hunting," Ocobock said, "meaning that hunters would often have to get up underneath their prey in order to kill them. As such, we find that both males and females have the same resulting injuries when we look at their fossil records." Ocobock described those traumatic injuries as being similar to those received by modern-day rodeo clowns -- injuries to the head and chest where they were kicked by the animal, or to the limbs where they were bitten or received a fracture. "We find these patterns and rates of wear and tear equally in both women and men," she said. "So they were both participating in ambush-style hunting of large game animals." Second, Ocobock said, there is evidence of early female hunters in the Holocene period in Peru where females were buried with hunting weapons. "You don't often get buried with something unless it was important to you or was something that you used frequently in your life. "Furthermore, we have no reason to believe that prehistoric women abandoned their hunting while pregnant, breastfeeding or carrying children," Ocobock added, "nor do we see in the deep past any indication that a strict sexual division of labor existed." The bottom line, Ocobock noted, was that "hunting belonged to everyone, not just to males," especially in prehistoric societies where survival was an all-hands-on-deck activity. "There weren't enough people living in groups to be specialized in different tasks. Everyone had to be a generalist to survive." Fighting bias "This revelation is especially important in the current political moment of our society where sex and gender are in a spotlight," Ocobock said. "And I want people to be able to change these ideas of female physical inferiority that have been around for so long." When talking about reconstructing the past in order to better understand it -- and to conduct "good science" -- Ocobock said scientists have to be extremely careful about how modern-day bias can seep into one's interpretations of the past. She cautioned that researchers have to be aware of their own biases and make sure they are asking the proper questions so the questions don't lead them down the road of looking for what it is they want to see. "We have to change the biases we bring to the table, or at least to give pause before we assign those biases. And in a broader sense, you cannot outrightly assume somebody's abilities based on whatever sex or gender you have assigned by looking at them," Ocobock concluded.

The phase II study led by Dr. Kenneth Cusi evaluating lanifibranor in patients with T2D and MASLD was selected as late breaker.Two additional scientific abstracts from the NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH have been selected for presentation. The two abstracts show: the correlation between the increase of adiponectin under lanifibranor and the improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis.the improvement of liver histology and markers of cardiometabolic health in patients with NASH treated with lanifibranor, independent of PNPLA3 genotype. Daix (France), Long Island City (New York, United States), November 6, 2023 – Inventiva (Euronext Paris and Nasdaq: IVA) (the “Company”), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of nonalcoholic steatohepatitis (NASH) and other diseases with significant unmet medical needs, today announced that the phase II trial led by Dr. Cusi in patients with type two diabetes (T2D) has been accepted as late breaker, at the upcoming The Liver Meeting® 2023 hosted by the American Association for the Study of Liver Diseases on November 10-14, 2023 in Boston. In addition two other scientific abstracts have been selected for poster presentation. The late breaker abstract “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” presents results from a study sponsored by Dr. Cusi at the University of Florida, that evaluates the effect of lanifibranor on insulin resistance in the liver, muscle and adipose tissue, as well as its effect on intrahepatic triglyceride (IHTG) content in patients with T2D and Metabolic dysfunction associated steatotic liver disease (MASLD)1. The second abstract evaluates the correlation between adiponectin response with lanifibranor and the improvement of histological and serum markers of NASH severity, both in terms of disease activity and fibrosis. The change in adiponectin levels at end of treatment (categorized as unchanged, moderate or high increase) correlated positively to histological endpoints of NASH resolution and no worsening of fibrosis, improvement of fibrosis and no worsening of NASH, and NASH resolution and fibrosis improvement. The degree of adiponectin level increase correlated also with improvement of the NASH-CRN and SAF-Activity scores as well as with improvement of the individual components: steatosis, inflammation and ballooning. Lanifibranor-associated adiponectin increase also correlated with the improvement in histological fibrosis stage, pro-C3 levels and MACK-3 score. These data further support that adiponectin is a biomarker for the efficacy of lanifibranor treatment across the disease spectrum of NASH, from cardiometabolic health – as previously shown – to hepatic health. As a reminder, a 3.82 and 4.50 fold increase in adiponectin level were respectively reported in the 800mg arm and 1200mg arm during Inventiva’s NATIVE Phase IIb clinical trial. The third abstract evaluates the impact of the PNPLA3 variant I148M, which is strongly associated with risk for and the progression of NASH, on the histological and cardiometabolic response to lanifibranor. In a retrospective analysis of Inventiva’s NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH, histological and circulating marker responses were evaluated by PNPLA3 genotype subgroup. The response to lanifibranor treatment on the histological endpoints was similar across the three PNPLA3 genotype (II/IM/MM) despite a higher activity score measured at baseline in patients with MM genotype.In addition, the improvement of cardiometabolic health markers (glycemic control, insulin, HOMA-IR, HsCRP, CAP and adiponectin) following treatment with lanifibranor was similar in the three PNPLA3 genotypes. These results demonstrate that the efficacy of lanifibranor on both liver histology and markers of cardiometabolic health appears to be independent of PNPLA3 status. The details of the presentation are as follows: Abstracts: Abstract title: “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” Poster number: 5035-C Presentation type: Late breaker poster presentation Authors: Diana Barb, Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Fernando Bril, Philippe Huot-Marchand, Lucile Dzen, Jean-Louis Junien, Pierre Broqua, Andrea Ortiz Rocha, Romina Lomonaco, Michael P Cooreman, Ken Cusi Date: November 12, 2023 – 1:00pm - 2:00pm (EST) Abstract title: “Lanifibranor-associated adiponectin increase correlates with improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis” Poster number: 2458-C Presentation type: Poster presentation Authors: Michael P. Cooreman, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Sven Francque Date: November 11, 2023 – 8:30am - 5:00pm (EST) Abstract title: “Lanifibranor improves liver histology and markers of cardiometabolic health in patients with NASH independent of PNPLA3 genotype: a retrospective analysis of the native study” Poster number: 2457-C Presentation type: Poster presentation Authors: Louis Griffel, Sven Francque, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Michael P. Cooreman Date: November 11, 2023 – 8:30am - 5:00pm (EST) Inventiva will also be present with a booth: we are inviting you to visit us from Saturday November 11 through Monday November 13, 2023, during exhibition hall opening hours at booth #D3027 located in the exhibition hall of the conference center. About lanifibranor Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (PPAR) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of NASH. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and pre-clinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of NASH. About Inventiva Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with NASH (also known as metabolic dysfunction-associated steatohepatitis (MASH)), mucopolysaccharidoses (“MPS”) and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline. Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with NASH, a common and progressive chronic liver disease for which there are currently no approved therapies. Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting an oncology development candidate for its Hippo signaling pathway program. The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly-owned research and development facility. Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com Contacts Inventiva Pascaline Clerc EVP, Strategy and Corporate Affairs media@inventivapharma.com +1 240 620 9175 Brunswick Group Tristan Roquet Montegon / Aude Lepreux / Matthieu Benoist Media relations inventiva@brunswickgroup.com +33 1 53 96 83 83 Westwicke, an ICR Company Patricia L. Bank Investor relations patti.bank@westwicke.com +1 415 513-1284 Important Notice This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. 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Given these risks and uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements. Please refer to the Universal Registration Document for the year ended December 31, 2022 filed with the Autorité des Marchés Financiers on March 30, 2023, the Annual Report on Form 20-F for the year ended December 31, 2022 filed with the Securities and Exchange Commission on March 30, 2023 and the Company’s half-year report for the period ended June 30, 2023 for other risks and uncertainties affecting Inventiva, including those described from time to time under the caption “Risk Factors”. Other risks and uncertainties of which Inventiva is not currently aware may also affect its forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. All information in this press release is as of the date of the release. Except as required by law, Inventiva has no intention and is under no obligation to update or review the forward-looking statements referred to above. Consequently, Inventiva accepts no liability for any consequences arising from the use of any of the above statement. 1 Inventiva-PR-Cusi-Lani-Topline-Results-EN-06132023.pdf (inventivapharma.com) Attachment Inventiva - PR - AASLD Abstracts 2023 - EN - 11062023