PRKAA2

Researchers have made a significant finding in determining the genetic background of dilated cardiomyopathy in Dobermanns. This research helps us understand the genetic risk factors related to fatal diseases of the heart muscle and the mechanisms underlying the disease, and offers new tools for their prevention. Researchers have made a significant finding in determining the genetic background of dilated cardiomyopathy in Dobermanns. This research helps us understand the genetic risk factors related to fatal diseases of the heart muscle and the mechanisms underlying the disease, and offers new tools for their prevention. Researchers from the University of Helsinki and the Folkhälsan Research Center, together with their international partners, have identified the genetic background of dilated cardiomyopathy, a disease that enlarges the heart muscle, in dogs and humans. Based on a dataset encompassing more than 500 Dobermanns, the disease was associated with two nearby genomic loci, where changes were identified in genes that affect the functioning, energy metabolism and structure of the heart muscle. The study revealed that these same risk genes cause heart muscle disease in human patients. A variety of factors can cause cardiomyopathy, but genetics play a significant role. Although dozens of genes underlying cardiomyopathy in humans have been identified, the hereditary nature and genetic background of the disease in dogs have remained unclear. "The situation with Dobermanns is serious in terms of both their health and breeding. The disease has been studied from various angles for decades without significant gene discoveries. Better diagnostic tools are needed, particularly in early diagnostics. Our new research might improve the situation," says Professor Hannes Lohi, the principal investigator in the project. The study has significant implications for veterinary medicine, providing a basis for developing a new genetic test for early diagnostics and breeding. Two novel risk genes identified in an extensive European cohort Various research data collected over decades on more than 500 Dobermanns from across Europe were combined for the research. The dogs in the study cohort were categorised into five different groups: With the help of genetic mapping, two adjacent gene loci in chromosome 5 were associated with dilated cardiomyopathy. Among the numerous genes in the loci, two, namely RNF207 and PRKAA2, demonstrated structural variation, which could have a detrimental effect on the functioning of the genes and cause heart failure. "The genetic mapping we conducted produced important observations. Until now, it has been unclear whether Dobermanns with differing symptoms have the same disease. The genes we identified are only associated with a dilated heart and affected cardiac function. Arrhythmia appears to be a genetically distinct disease. Our dataset was insufficient to identify genes causing arrhythmia only. We also observed that several genes affect cardiac function and identified a model of two genes that increase the disease risk," explains Professor Lohi. Gene discovery in dogs associated with cardiac muscle disorders in humans The significance of the gene discovery in dogs was investigated in human patients diagnosed with dilated cardiomyopathy using Dutch, English (UK Biobank) and Finnish (FinnGen) cohorts. Fifteen potentially harmful and predisposing variants in the same RNF207 and PRKAA2 genes, which had been identified in dogs, were discovered in humans. "The identical genetic background suggests that, to a degree, similar problems with the functioning of the heart muscle lead to dilated cardiomyopathy in both humans and dogs. A deeper understanding of the pathogenetic mechanisms is important, and Dobermanns represent a natural model organism for further research," Lohi states. A genetic test for breeding The DNA markers associated with the disease found in the study may be a step toward a genetic test, but it is important to confirm its clinical significance before such tests are offered. "We discovered how the variants of the two genes together increase the disease risk. However, a pilot is needed to combine genetic and health data to monitor how frequently individuals who belong to the at-risk group develop the disease for varying genetic reasons. Then, we can obtain a more accurate estimate of how the gene discoveries should be ideally interpreted and utilised. In any case, this is a hope-inspiring finding because, in the past, we lacked such tools," Lohi describes. The new gene discoveries enable new research hypotheses For the consistent synchronised pumping of the heart, the heart muscle cells must interact with each other. Unlike in skeletal muscles, in the cell membrane of the heart muscle are finger-like discs that conduct the undulation required for pumping. "Our study revealed that the RNF207 gene is expressed exactly in these discs. Earlier research has shown that RNF207 plays an important role in heart muscle contraction. The absence of these discs has also earlier been linked with cardiomyopathy. The other gene identified, PKAA2, serves as an energy sensor in the heart muscle, and its malfunction can reduce cardiac efficiency. Further research is required to understand the pathogenic mechanism, but we are in a good position to continue. A while ago, the disease was a total mystery, but now we have opened a view to its cellular-level secrets," Professor Lohi concludes. The research was funded by, among others, the Finnish Foundation for Cardiovascular Research, the Jane and Aatos Erkko Foundation, the Sigrid Jusélius Foundation, and many other funders from different countries. The study is part of Professor Hannes Lohi's canine gene research project, and the related article was published in the journal Genome Medicine.

- Data add to the growing body of clinical and scientific evidence demonstrating the therapeutic potential of Aramchol, a stearoyl CoA desaturase (SCD 1) down regulator, for the treatment of NASH and Fibrosis - A Phase 3 program is currently ongoing with a higher daily Aramchol dose [11-October-2021] TEL AVIV, Israel, October 11, 2021 /PRNewswire/ -- Galmed Pharmaceuticals (Nasdaq: GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company for liver, metabolic and inflammatory diseases announced today that the one-year results of the global Phase 2b randomized placebo-controlled ARREST Trial of Aramchol in patients with NASH have been published in Nature Medicine ( ). The ARREST Phase 2b study randomized 247 patients with NASH confirmed by liver biopsy. Patients were randomized 2:2:1 to receive Aramchol 400mg, 600mg or placebo once daily. The manuscript describes the complete data analyses including reduction in liver fat by imaging, improvements in liver histology and liver enzymes as well as the very good safety pro Aramchol. Aramchol is the most advanced down regulator of SCD 1 in clinical development. Aramchol, by targeting this single receptor, an important metabolic master switch, induces cascade of events that leads to two main changes: in hepatocytes, Aramchol elevates the fatty acids oxidation (or in other words – fat burn) and influences AMPK, which results also in reducing glycemic parameters; and in hepatic stellate cells, Aramchol down regulates collagen production (i.e. fibrosis). Data from the ARREST Phase 2b study published in this paper demonstrate how the mechanism of action of Aramchol translates into clinical performance. This published study, in addition to mechanistic studies demonstrated and published thus far, provided the rationale for the continued development of Aramchol for patients with NASH and fibrosis and a potential to further improved efficacy using higher drug exposure (>50% higher). The ARMOR study - a Phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of Aramchol 300mg twice daily in subjects with NASH with an open-label part to evaluate the safety, PK and treatment response kinetics of Aramchol is currently ongoing (NCT04104321). Prof. Vlad Ratziu, Professor of Hepatology, Sorbonne Université, the paper's lead author and the ARMOR study co-principal investigator commented "The publication of the detailed results of the ARREST trial in a prestigious general medical journal such as Nature Medicine speaks to the interest of the scientific community towards this molecule with an innovative mode of action and its potential for treating fibrotic NASH. We look forward to seeing the impact of an optimized Aramchol exposure in NASH patients from the Phase 3 ARMOR trial" "The publication of these data in Nature Medicine speaks to the strong interest from the clinical community in this unmet need area. We are grateful to all the patients and clinical sites that participated in the study around the world", said Allen Baharaff, President and Chief Executive Officer of Galmed. "Coupled with new recent publications elucidating Aramchol's MoA and particularly its direct effect on fibrosis, these results underscore the significant potential of Aramchol as a therapeutic option for patients diagnosed with NASH and Fibrosis. We are committed to evaluating the safety and efficacy of Aramchol in patients diagnosed with NASH and Fibrosis in our ongoing ARMOR Phase 3 study." About Aramchol and Non-alcoholic Steatohepatitis (NASH) Aramchol (arachidyl amido cholanoic acid) is a novel fatty acid bile acid conjugate, liver targeted SCD1 modulator, developed as an oral therapy for the treatment of nonalcoholic steatohepatitis ("NASH") and fibrosis. Aramchol's ability to modulate hepatic lipid metabolism was discovered and validated in animal models, demonstrating downregulation of the three key pathologies of NASH: steatosis, inflammation and fibrosis. The effect of Aramchol on fibrosis is mediated by downregulation of steatosis and directly on human collagen producing cells. Aramchol has been granted Fast Track Designation status by the FDA for the treatment of NASH. NASH is an emerging world crisis impacting an estimated 3% to 5% of the U.S. population and an estimated 2% to 4% globally. It is the fastest growing cause of liver cancer and liver transplant in the U.S. due to the rise in obesity. NASH is the progressive form of non-alcoholic fatty liver disease that can lead to cardiovascular disease, cirrhosis and liver-related mortality. There are currently no approved therapies for NASH. Galmed Pharmaceuticals Ltd. Galmed Pharmaceuticals Ltd. is a clinical stage drug development biopharmaceutical company for liver, metabolic and inflammatory diseases. Our lead compound, Aramchol™, a backbone drug candidate for the treatment of NASH and fibrosis is currently in a Phase 3 registrational study. We are also collaborating with the Hebrew University in the development of Amilo-5MER, a 5 amino acid synthetic peptide. Forward-Looking Statements: This press release may include forward-looking statements. Forward-looking statements may include, but are not limited to, statements relating to Galmed's objectives, plans and strategies, as well as statements, other than historical facts, that address activities, events or developments that Galmed intends, expects, projects, believes or anticipates will or may occur in the future. These statements are often characterized by terminology such as "believes," "hopes," "may," "anticipates," "should," "intends," "plans," "will," "expects," "estimates," "projects," "positioned," "strategy" and similar expressions and are based on assumptions and assessments made in light of management's experience and perception of historical trends, current conditions, expected future developments and other factors believed to be appropriate. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Many factors could cause Galmed's actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to, the following: the timing and cost of Galmed's pivotal Phase 3 ARMOR trial, or the ARMOR Study or any other pre-clinical or clinical trials; completion and receiving favorable results of the ARMOR Study for Aramchol or any other pre-clinical or clinical trial; the impact of the COVID-19 pandemic; regulatory action with respect to Aramchol or any other product candidate by the FDA or the EMA; the commercial launch and future sales of Aramchol or any other future products or product candidates; Galmed's ability to comply with all applicable post-market regulatory requirements for Aramchol or any other product candidate in the countries in which it seeks to market the product; Galmed's ability to achieve favorable pricing for Aramchol or any other product candidate; Galmed's expectations regarding the commercial market for NASH patients or any other indication; third-party payor reimbursement for Aramchol or any other product candidate; Galmed's estimates regarding anticipated capital requirements and Galmed's needs for additional financing; market adoption of Aramchol or any other product candidate by physicians and patients; the timing, cost or other aspects of the commercial launch of Aramchol or any other product candidate; the development and approval of the use of Aramchol or any other product candidate for additional indications or in combination therapy; and Galmed's expectations regarding licensing, acquisitions and strategic operations. More detailed information about the risks and uncertainties affecting Galmed is contained under the heading "Risk Factors" included in Galmed's most recent Annual Report on Form 20-F filed with the SEC on March 18, 2021, and in other filings that Galmed has made and may make with the SEC in the future. The forward-looking statements contained in this press release are made as of the date of this press release and reflect Galmed's current views with respect to future events, and Galmed does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Company Codes: NASDAQ-SMALL:GLMD

Sept. 30, 2021 06:30 UTC LYON, France--(BUSINESS WIRE)-- Regulatory News: POXEL SA (Euronext – POXEL – FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders, today announced its participation at upcoming investor conferences in October 2021. HealthTech Innovation Days Conference – France Biotech - Paris, France (virtual) Date: October 4-5 Thomas Kuhn, CEO of Poxel, and Anne Renevot, CFO, will be available for one-on-one virtual meetings. H.C. Wainwright 5th Annual NASH Conference (virtual) Date: October 12 Members of the Poxel management team will present Poxel’s two NASH clinical-stage candidates, PXL770 and PXL065, and will be available for one-on-one virtual meetings. PXL770 is a first-in-class, oral direct adenosine monophosphate-activated protein kinase (AMPK) activator. PXL065 is a novel, oral, proprietary deuterium-stabilized R-stereoisomer of pioglitazone. About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders. Poxel has clinical and earlier-stage programs from its adenosine monophosphate-activated protein kinase (AMPK) activator and deuterated thiazolidinedione (D-TZD) platforms targeting chronic and rare metabolic diseases. For the treatment of NASH, PXL065 (deuterium-stabilized R-pioglitazone) is in a streamlined Phase 2 trial (DESTINY-1). PXL770, a first-in-class direct AMPK activator, has successfully completed a Phase 2a proof-of-concept trial for the treatment of NASH, which met its objectives. For the rare inherited metabolic disorder, X-linked adrenoleukodystrophy (ALD), the company intends to initiate Phase 2a proof of concept studies with PXL065 and PXL770 in patients with adrenomyeloneuropathy (AMN). TWYMEEG® (Imeglimin), Poxel’s first-in-class lead product that targets mitochondrial dysfunction, has been approved and launched for the treatment of type 2 diabetes in Japan. Poxel expects to receive sales-based payments and royalties from Sumitomo Dainippon Pharma. Poxel has a strategic partnership with Sumitomo Dainippon Pharma for Imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast Asian countries. The Company intends to generate further growth through strategic partnerships and pipeline development. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. View source version on businesswire.com: Contacts Poxel SA Catherine David Investor Relations & Communication Manager catherine.david@poxelpharma.com +33 7 64 57 61 78 Aurélie Bozza Investor Relations & Communication Director aurelie.bozza@poxelpharma.com +33 6 99 81 08 36 Elizabeth Woo Senior Vice President, Investor Relations & Communication elizabeth.woo@poxelpharma.com Investor relations / Media - EU/US Trophic Communications Stephanie May or Valeria Fisher poxel@trophic.eu +49 171 185 56 82 or +49 175 804 1816 Investor relations / Media - France NewCap Emmanuel Huynh or Arthur Rouillé poxel@newcap.eu +33 1 44 71 94 94 Source: POXEL SA View this news release online at: