Hyperinsulinism

NIH findings may lead to insights on pregnancy complications, adult health BETHESDA, Md., May 2, 2025 /PRNewswire-HISPANIC PR WIRE/ -- What: The genes of male and female placentas have marked differences in how they are expressed, according to a study by researchers at the National Institutes of Health (NIH) and other institutions. These differences involve the presence or absence of tags on DNA known as methyl groups, which switch genes on or off without changing their structure. Understanding these DNA methylation patterns may inform future research on the higher risk for pregnancy complications involving male fetuses, such as stillbirth and prematurity, as well as later life health conditions that occur in adults who were born after a complicated pregnancy. Researchers analyzed male and female placental samples from a larger study for differences in their methylation patterns, and found differences in gene activity between male and female placentas that may play a role in birthweight and adult diseases. The study identified 2,497 previously unreported DNA sites that had different methylation patterns for males and females. Of these and more than 2,500 sites that had also been identified by previous studies, 66.9% of large increases in methylation occurred in DNA from male placentas and 33.1% from female placentas. Increases in methylation in male placentas was linked with greater neonatal size whereas those in females was linked with greater placental size. Some increases in methylation found in male placentas were located near the CCDC6 gene. Lower activation of CCDC6 has been linked with preterm birth in previous studies. Higher methylation near the FNDC5 gene was associated with lower expression of the gene in male placentas but not in female placentas. FNDC5 is involved with the manufacture of irisin, which protects the placenta from damage by reactive oxygen molecules and insulin resistance (cells' difficulty in using insulin to lower blood sugar.) Lower irisin levels have been associated with the pregnancy-related high blood pressure disorder, known as preeclampsia. Variations in the genes ATP5MG and FAM83A, expressed in female placentas, have been associated with asthma, hay fever, eczema (dry, itchy, inflamed skin) and higher risk for breast cancer later in life. Genetic factors influence the health differences between males and females, from before birth to later in life. Male fetuses grow faster than female fetuses and their pregnancies are more likely to be complicated by such conditions as preeclampsia (a hypertensive disorder of pregnancy), failure to grow at an adequate rate, and preterm birth. They also are more likely to die in the year after birth. Dysfunction of the placenta underlies many pregnancy complications and is thought to set the stage for male and female health differences that occur later in life. Variations in methylation patterns are thought to underlie many of these differences. The study was conducted by Fasil Tekola-Ayele, Ph.D., of the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and colleagues at other institutions. It appears in Nature Communications. Who: Fasil Tekola-Ayele, Ph.D., is available for comment on this study. Reference Tekola-Ayele F, et al. Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases. Nature Communications. DOI: 10.1038/s41467-025-58128-3 (2025) SOURCE Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health (NIH) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

VAMOS analysis highlights link between EVAF and reduced muscle quality Case series reports success with combination tesamorelin/GLP-1 receptor agonist therapy MONTREAL, May 02, 2025 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (“Theratechnologies” or the “Company”) (TSX: TH) (NASDAQ: THTX), a commercial-stage biopharmaceutical company, today announced two poster presentations at the 19th Annual American Conference for the Treatment of HIV (ACTHIV 2025), taking place May 1-3 in Chicago, Ill. Both presentations focus on issues surrounding excess visceral abdominal fat (EVAF), a common comorbidity in people with HIV (PWH). One poster presents a new analysis of data from the Visceral Adiposity Measurement and Observations Study (VAMOS), in which EVAF was associated with reduced muscle quality in aging PWH. VAMOS is the first trial designed to improve the understanding of the impact of EVAF on cardiovascular disease, steatotic liver disease, insulin resistance, and other metabolic parameters in PWH. The second presentation reports on a first-of-its-kind case series in which the combination of tesamorelin and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy was highly effective in reducing both EVAF and obesity in a real-world setting. “We are proud to continue our exploration into the complexities of excess visceral abdominal fat in people with HIV,” said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer of Theratechnologies. “As people with HIV live longer, analyses such as the data we are presenting at ACTHIV are critical to addressing this population’s evolving health needs. Our research adds to the growing understanding that body composition, most importantly EVAF, is a key factor in aging-related functional decline in HIV, and we are committed to investigating this complex relationship.” VAMOS Analysis Poster Title: Reduced Muscle Quality is Highly Prevalent in Aging People with HIV (PWH) and is Associated with Excess Visceral Abdominal Fat (EVAF) First Author: Zachary Henry, DO, AIDS Healthcare Foundation, Fort Lauderdale, Fla. In the latest analysis from the multicenter VAMOS study, researchers investigated how EVAF, compared to subcutaneous fat, is associated with muscle quality in PWH on modern anti-retroviral regimens, and explored potential drivers of this relationship. Among the 170 participants, EVAF prevalence was 58%. Muscle quality was found to be lower with increasing age of participants (r= -0.465; p<0.0001), but was not significantly correlated with body mass index (BMI) (r= -0.118; p=0.124). EVAF was associated with lower skeletal muscle quality, as demonstrated by lower muscle mean attenuation (r= -0.445; p<0.0001). The researchers concluded that increased levels of visceral fat – more so than subcutaneous fat or increasing BMI – strongly correlate with reduced skeletal muscle quality, which may amplify age-related functional declines. Tesamorelin/GLP-1 RA Case Series Poster Title: High Levels of Treatment Success Seen with Combined Use of Tesamorelin and GLP1-RAs in People with HIV First Author: Daniel Lee, MD, University of California San Diego Department of Medicine, San Diego, Calif. In the case series, investigators reported on the real-world use of tesamorelin for the treatment of EVAF in PWH, in combination with GLP-1 RAs, which are commonly used for diabetes and obesity management in the general population. Among the seven PWH evaluated in the case series, tesamorelin was initiated first in all cases to address EVAF, with a mean reduction in waist circumference of 1.3 inches. The principal reasons for adding a GLP-1-RA included improving BMI and diabetic control. Following at least six months of combination therapy, patients saw mean reductions in weight (-13 pounds), BMI (-2.2 kg/m2), and waist circumference (-3.4 inches), with six of the seven patients achieving their metabolic and body composition goals. Combination therapy is ongoing in most of the patients (6/7). This is the first known report of the dual use of these agents in PWH, highlighting their complementary but distinct mechanisms of action.​ “The combination of tesamorelin and GLP-1 medications represents a new frontier in metabolic care for people with HIV,” noted Dr. Marsolais. “By distinguishing between and targeting both excess visceral abdominal fat and generalized obesity, treatment strategies can be tailored to address the specific needs of people living with HIV.” Both posters can be found at www.theratech.com and www.acthiv.org following the conference. About Theratechnologies Theratechnologies (TSX: TH) (NASDAQ: THTX) is a specialty biopharmaceutical company focused on the commercialization of innovative therapies that have the potential to redefine standards of care. Further information about Theratechnologies is available on the Company's website at www.theratech.com, on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov. Follow Theratechnologies on LinkedIn and X. Forward-Looking Information This press release contains forward-looking statements and forward-looking information (collectively, the “Forward-Looking Statements”), within the meaning of applicable securities laws, that are based on our management’s beliefs and assumptions and on information currently available to our management. You can identify Forward-Looking Statements by terms such as "may", "will", "should", "could", “promising”, “would”, "outlook", "believe", "plan", "envisage", "anticipate", "expect" and "estimate", or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding the Company’s commitment to investigate the relationship between body composition and aging and the tailoring of treatment strategies for PWH. Forward-looking statements involve a number of assumptions, risks and uncertainties. Some of these assumptions include, but are not limited to, the duration of treatment and the responses to the administered drugs by PWH. Some of the risks include that PWH may not respond similarly when they take medicines and results may differ from what those were observed and reported through VAMOS and the tesamorelin/GLP-1 RA case series. The Company refers current and potential investors to the “Risk Factors” section of the Company’s Annual Information Form filed on Form 20-F dated February 26, 2025 available on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov under Theratechnologies’ public filings for the risks associated with the business of Theratechnologies. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-Looking Statements reflect current expectations regarding future events and speak only as of the date of this press release and represent the Company’s expectations as of that date. The Company undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law. Contacts: Media inquiries:Julie SchneidermanSenior Director, Communications & Corporate Affairscommunications@theratech.com514-336-7800 Investor Inquiries:Joanne ChoiSenior Director, Investor Relationsjchoi@theratech.com551-261-0401

● XORTX will focus on key steps to advance a NDA filing for Gout indication ● CALGARY, Alberta, April 30, 2025 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANU), a late stage clinical pharmaceutical company focused on developing innovative therapies to treat gout and progressive kidney disease, is pleased to announce it has received responses from the US Food and Drug Administration (the “FDA”) and clarified key steps for a new drug application (“NDA”) for the Company’s novel proprietary formulation of oxypurinol for the treatment of gout. The Type B meeting conducted by the FDA, included review of chemistry, manufacturing, pharmacology, toxicology and clinical evidence to support the Company’s XRx-026 program for the treatment of gout. Responses from the FDA substantially confirmed and clarified the remaining key steps necessary prior to filing a NDA to gain marketing approval for XORLO™ in the US using the FDA 505(b)2 development pathway. With this FDA guidance, XORTX will now advance the following key steps to support the NDA application and its submission for the XRx-026 program for gout. i) Finalize meeting minutes with the FDA regarding the agency and XORTX’s responses; ii) Prepare and file an Investigative New Drug (“IND”) application for the XRx-026 program;iii) Characterize pharmacokinetics of the commercial tablet formulation of XORLO™ in absence and in the presence of food;iv) Manufacture, validate commercial supplies of drug accompanied by stability data in parallel with the NDA preparation; and v) Prepare and file a NDA for marketing approval of XORLO™.Dr. Allen Davidoff, CEO of XORTX commented, “The clarity gained during this review of supporting data with the FDA will permit the further advancement of the XRx-026 program and will facilitate the timely completion of key steps necessary for filing the NDA. The Company believes that the gout NDA may be filed in the H1 2026. We continue to prioritize our XRx-026 program and advance this much needed therapeutic option for individuals with gout.” The Company will provide further updates following final communications with the FDA once meeting minutes are finalized and available. About Hyperuricemia and Gout In the US it is estimated that approximately 44 million individuals have circulating uric acid above the normal range(1). The prevalence of gout was 3.9% or 9.2 million individuals. Mean serum urate levels were 6.0 mg/dL among men and 4.8 mg/dL among women, with hyperuricemia prevalences of 20.2% and 20.0%, respectively. The prevalence of ULT use among patients with gout was 33% during 2007 to 2014 and remained stable over time (P for trend >0.05)(1). Gout is an inflammatory arthritis that is triggered by the crystallization of monosodium urate inside the joints and is preceded by hyperuricemia. Gout flares lead to substantial morbidity by causing severe pain, reduced quality of life(2), decreased physical function(2,3), increased healthcare costs(4), and lost economic productivity(5). Furthermore, gout is strongly associated with the metabolic syndrome(5), and may contribute to myocardial infarction(6,7), type 2 diabetes mellitus(8), chronic kidney disease(9), and premature mortality(6,10,11). About the XRx-026 Program and XORLOTM The XRx-026 program is developing XORLO™, a proprietary formulation of oxypurinol to treat individuals suffering from gout. At present, oral xanthine oxidase inhibitors (“XOIs”) are the preferred therapeutic option used to inhibit the production of uric acid and decrease chronically high uric acid in the circulation. Allopurinol is the most commonly prescribed XOI, with approximately 3.3 million prescriptions written per year in North America, however 3 to 5% of patients cannot tolerate Allopurinol. An alternative XOI, Febuxostat, was launched in the US in 2009 with the hope of treating individuals with gout, however while Febuxostat achieved peak sales greater than US$450 million1 after its launch, a Black Box warning due to its associated risk of sudden cardiovascular death resulted in a decline in its use. XORLO™ can address this unmet medical need and accelerating advancement of the XRx-026 program through an NDA filing is now a priority for XORTX. About Type B Meetings with the FDA Type B meetings for each potential application (e.g., investigational new drug application (IND), NDA, biologics license application (BLA)) or combination of closely related products developed by the same sponsor or applicant (e.g., same active ingredient but different dosage forms being developed concurrently). Typically, it may be appropriate to conduct more than one of some of the Type B meetings for concurrent development of a product for unrelated claims. References: (1) Chen-Xu M_Prevalence of Gout and Hyperuricemia in the US_ArthritisRheumatol_71-6_991-999_2019_nihms-1002533(2) Singh JA. Quality of life and quality of care for patients with gout. Curr Rheumatol Rep. 2009 4;11(2):154–60. [PubMed: 19296889] (3) Burke BT, Köttgen A, Law A, Windham BG, Segev D, Baer AN, et al. Physical Function, Hyperuricemia, and Gout in Older Adults. Arthritis Care Res. 2015 12;67(12):1730–8. (4) Rai SK, Burns LC, De Vera MA, Haji A, Giustini D, Choi HK. The economic burden of gout: A systematic review. Semin Arthritis Rheum. 2015 8;45(1):75–80. [PubMed: 25912932] (5) Choi HK, Ford ES. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med. 2007 5;120(5):442–7. [PubMed: 17466656] (6) Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007 8 21;116(8):894–900. [PubMed: 17698728] (7) Liu S-C, Xia L, Zhang J, Lu X-H, Hu D-K, Zhang H-T, et al. Gout and Risk of Myocardial Infarction: A Systematic Review and Meta-Analysis of Cohort Studies. Pizzi C, editor. PLOS ONE. 2015 7 31;10(7):e0134088. [PubMed: 26230580] (8) Choi HK, De Vera MA, Krishnan E. Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology. 2008 8 13;47(10):1567–70. [PubMed: 18710901] (9) Roughley MJ, Belcher J, Mallen CD, Roddy E. Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies. Arthritis Res Ther. 2015 12;17(1). (10) Kuo C-F, See L-C, Luo S-F, Ko Y-S, Lin Y-S, Hwang J-S, et al. Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology. 2010 1;49(1):141–6. [PubMed: 19933595] (11) Fisher MC, Rai SK, Lu N, Zhang Y, Choi HK. The unclosing premature mortality gap in gout: a general population-based study. Ann Rheum Dis. 2017 7;76(7):1289–94. [PubMed: 28122760]About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with three clinically advanced products in development: 1) our lead program XRx-026 program for the treatment of gout; 2) XRx-008 program for ADPKD; and 3) XRx-101 for acute kidney and other acute organ injury associated with respiratory virus infections. In addition, the Company is developing XRx-225, a pre-clinical stage program for Type 2 diabetic nephropathy. XORTX is working to advance products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications that improve the quality of life and health of individuals with gout and other important diseases. Additional information on XORTX is available at www.xortx.com. For more information, please contact: Allen Davidoff, CEONick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727nick@alpineequityadv.com or +1 617 901 0785 Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein. Forward Looking Statements This press release contains express or implied forward-looking statements pursuant to applicable securities laws. These forward-looking statements include, but are not limited to, the Company's beliefs, plans, goals, objectives, expectations, assumptions, estimates, intentions, future performance, other statements that are not historical facts and statements identified by words such as "expects", "anticipates", "intends", "plans", "believes", "seeks", "estimates" or words of similar meaning. These forward-looking statements and their implications are based on the current expectations of the management of XORTX only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Such risks, uncertainties, and other factors include, but are not limited to, our ability to obtain additional financing; the accuracy of our estimates regarding expenses, future revenues and capital requirements; the success and timing of our preclinical studies and clinical trials; the performance of third-party manufacturers and contract research organizations; our plans to develop and commercialize our product candidates; our plans to advance research in other kidney disease applications; and, our ability to obtain and maintain intellectual property protection for our product candidates. Except as otherwise required by applicable law and stock exchange rules, XORTX undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting XORTX is contained under the heading “Risk Factors” in XORTX’s Annual Report on Form 20-F filed with the SEC, which is available on the SEC's website, www.sec.gov (including any documents forming a part thereof or incorporated by reference therein), as well as in our reports, public disclosure documents and other filings with the securities commissions and other regulatory bodies in Canada, which are available on www.sedarplus.ca. ___________________ 1 Source: Takeda Pharmaceutical Company 2018 Annual Report.