Heart Arrest

Indivior is the maker of several treatments for opioid use disorder, as well as Opvee, which in May 2023 earned the first FDA approval for a nasal spray version of active ingredient nalmefene. A paper published this month in the journal Current Addiction Reports discusses the merits of intranasal medications that can reverse overdoses of high-potency synthetic opioids (HPSOs) such as fentanyl.Indivior funded the manuscript, which was based on the results of last summer’s Reversing Synthetic Opioid Overdose (RESPIRE) Expert Forum—also funded by the addiction-focused pharma—that brought together eight leaders representing emergency medicine, pharmacy, state health agencies, Indian Health Services, addiction research and forensic science.The company makes Opvee, an opioid overdose reversal medication that aligns with the expert panel’s recommendations.“Indivior is committed to partnering closely with healthcare providers, policymakers, and communities to ensure that advanced overdose reversal solutions reach those who need them most, especially as HPSOs drive unprecedented risks and challenges,” Christian Heidbreder, Ph.D., the company’s chief scientific officer, said in a statement.The paper’s publication came shortly before National Fentanyl Awareness Day, observed every year on April 29. Fentanyl and other synthetic opioids were involved in more than 90% of opioid overdose fatalities in the year preceding the July forum, according to the report. Indivior is the maker of several treatments for opioid use disorder, as well as Opvee, which in May 2023 earned the first FDA approval for a nasal spray version of active ingredient nalmefene.Naloxone is the current standard of care for treating opioid overdoses and is more widely available than nalmefene—helped along by its first over-the-counter FDA approval for Emergent BioSolutions’ 4 mg Narcan in early 2023. The new paper’s authors, however, suggest that nalmefene may be more effective in treating some overdoses, especially those involving HPSOs.The most crucial aspects of medications used to treat overdoses of synthetic opioids are rapid onset, long duration and high potency, according to the authors.Nalmefene outpaces naloxone on all three of those aspects: Data cited in the paper show that nalmefene has a higher opioid receptor affinity than naloxone. And, while naloxone reaches peak blood concentration in 30 minutes and has a circulating half-life of about two hours, nalmefene’s time to peak is 15 minutes and its half-life is longer than 11 hours, which may make it “particularly well-suited for reversing HPSO overdose,” they wrote.The experts also pointed to a model predicting that a single 4 mg dose of naloxone would reduce the likelihood of cardiac arrest following a fentanyl overdose from about 78% to 47%, while a single 3-mg dose of nalmefene would bring it down to 11.6%. Previous expert publications, including a September 2023 joint release (PDF) from the American College of Medical Toxicology and the American Academy of Clinical Toxicology, have suggested that more research is needed into the risks and benefits of nalmefene, as its longer duration of action could potentially lead to a longer period of the opioid withdrawal symptoms that are the primary adverse effect of all reversal meds.That longer duration may also create a “false sense of comfort that no further care is needed,” possibly leading patients to avoid seeking follow-up observation, the groups wrote at the time, concluding that nalmefene shouldn’t yet replace naloxone as the standard of care for opioid overdose reversal.Though the RESPIRE experts acknowledged the increased risk of precipitated withdrawal following overdose reversal with nalmefene, they wrote that such risks are “secondary to saving a life.”“With the ability to medically manage precipitated withdrawal, in concert with the uncertainty and unpredictability of HPSOs, overdose reversal strategies and agents that rapidly restore and sustain respiration should be aggressively implemented,” they wrote.The panel concluded by calling for greater research and real-world evidence collection around treatments for HPSO overdoses. And, to boost treatment with both naloxone and nalmefene, they “emphatically” recommended improvements to bystander education and training, greater access to reversal agents and a wide-scale destigmatization of addiction.“Only with investments in using new reversal medications, further controlled trials yielding strong evidence, adequately training bystanders and first responders, collecting outcome information, researching and developing new reversal agents, and improving access to opioid use disorder treatment and prevention will the opioid overdose epidemic be marshaled to avoid needless deaths,” they wrote.

Orchestra BioMed’s Virtue® Sirolimus AngioInfusion Balloon™ (“Virtue SAB”) is the only non-coated drug-eluting balloon system under clinical investigation worldwide and has been awarded multiple FDA Breakthrough Device DesignationsThe Virtue Trial will be the first U.S. IDE head-to-head randomized evaluation of a sirolimus-eluting balloon versus a commercially available paclitaxel-coated balloon (AGENT™) for the treatment of coronary in-stent restenosis (“ISR”)Robust non-inferiority trial is designed to provide a clear pathway to regulatory approval as well as potentially showcase clinical advantages of Virtue SABWith the amended IDE approved by the FDA, Orchestra BioMed is currently targeting initiation of the Virtue Trial during the second half of 2025 NEW HOPE, Pa., April 29, 2025 (GLOBE NEWSWIRE) -- Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced that the U.S. Food and Drug Administration (“FDA”) has approved its Investigational Device Exemption (“IDE”) amendment to initiate an updated design of the Company’s planned Virtue SAB in the Treatment of Coronary ISR Trial (“Virtue Trial”). The IDE provides FDA regulatory clearance for Orchestra BioMed to initiate a U.S. pivotal clinical trial comparing its highly differentiated, next-generation Sirolimus-AngioInfusion Balloon, Virtue SAB to the Boston Scientific AGENT paclitaxel-coated balloon, currently the only drug-coated balloon (“DCB”) FDA-approved for a coronary indication. Data from the Virtue Trial will be used to support regulatory approval in the U.S. Virtue SAB and SirolimusEFR are investigational technologies owned by Orchestra BioMed, which also controls and is responsible for all regulatory filings, clinical operations, and drug and device supplies for the Virtue Trial. The Differentiation of Virtue SAB, An FDA Breakthrough Designated DeviceVirtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™, through a non-coated microporous AngioInfusion™ Balloon that protects the drug in transit to consistently deliver a large liquid dose, overcoming certain limitations of DCBs. SirolimusEFR™ enables tissue uptake and extended release of the required therapeutic levels of sirolimus (> 1ng/mg tissue concentration), the “gold-standard” drug for preventing arterial restenosis, through the critical healing period of approximately 30 days.​ Virtue SAB has been previously granted FDA Breakthrough Device Designation for the treatment of coronary ISR as well as for coronary small vessel disease and peripheral artery disease below-the-knee. In the multi-center SABRE pilot study, Virtue SAB demonstrated best-in-class clinical results for the treatment of coronary ISR, including 12-month target lesion failure of 2.8% and 6-month late lumen loss of 0.12mm. “Virtue SAB has the potential to be one of the most compelling technologies in interventional cardiology. It’s the only product in development that optimizes both the arterial tissue uptake and retention of sirolimus to achieve pharmacokinetics that match or even exceed those of proven ‘limus-eluting stents,” said Dean J. Kereiakes, M.D., FACC, MSCAI, Chairman of The Christ Hospital Heart & Vascular Institute, Medical Director of The Christ Hospital Research Institute, Professor of Clinical Medicine at The Ohio State University, Professor of Medicine at University of Cincinnati and Co-Principal Investigator on the Virtue Trial. Dr. Kereiakes continued: “Virtue SAB is designed to consistently deliver a large liquid dose of an extended-release formulation of sirolimus to overcome certain limitations of traditional DCBs, including lower doses due to surface area and coating integrity constraints, drug loss in transit leading to inconsistent dosing, and the risk of emboli from large coating particulates. As the coronary treatment landscape continues to shift toward more rapid adoption of DCBs, I’m excited about the potential of Virtue SAB to set a new standard of care.” “Drug-coated balloons are emerging as a new standard of care in the treatment of various coronary and peripheral indications, and I believe utilization of this class of technology will continue to grow and evolve over time as the science is expanding. In a field largely reliant on paclitaxel drug-coated balloons, Virtue SAB stands out as the only device with a completely different mechanism of action; namely to provide delivery of a large liquid dose of an extended-release formulation sirolimus," commented Allen Jeremias, MD, MSc, Associate Director of the Cardiac Catheterization Laboratory at St. Francis Hospital & Heart Center, and Co-Principal Investigator on the Virtue Trial. “Having had the opportunity to work with several DCBs, I anticipate continued momentum for this class, and am eager to see how Virtue SAB, particularly with its anti-restenotic, anti-inflammatory and cytostatic SirolimusEFR formulation, performs in a head-to-head trial against a paclitaxel-coated balloon.” Showcasing Distinctive and Sustainable Advantages of Virtue SAB Through a Head-to-Head Trial “We believe there is a multibillion-dollar U.S. market for coronary drug delivery balloons based on the significant unmet clinical need, market demand, and established reimbursement,” said David Hochman, Chairman and Chief Executive Officer of Orchestra BioMed. “We made a deliberate, strategic decision to pursue a head-to-head trial with the commercially available AGENT paclitaxel-coated balloon, underscoring our confidence in Virtue SAB as a fundamentally differentiated solution for the treatment of atherosclerosis. We believe this approach offers the most direct path to regulatory approval while also providing the best opportunity to demonstrate what we believe are distinctive and sustainable advantages of our proprietary technology.” Mr. Hochman continued, “The superior safety and efficacy of sirolimus over paclitaxel was made clear by the performance of drug-eluting stents. Published meta-analysis involving 76 trials show ‘limus-eluting stents have significantly better clinical performance than paclitaxel-eluting stents in terms of target lesion revascularization and major adverse cardiac events.1 We believe this is due to their ability to maintain sufficient drug tissue concentration through the critical healing period of approximately 30 days, because stents that failed to do this did not perform well clinically.2,3,4 Virtue SAB is the only drug delivery balloon that has demonstrated comparable drug tissue levels to clinically successful drug-eluting stents in large published preclinical studies, without the need to leave a permanent metal implant in the artery. Our pilot clinical results with Virtue SAB also highlight the potential for optimal clinical outcomes with robust sirolimus delivery. We’re excited to showcase the full potential of Virtue SAB in this landmark trial and are proud of our team and grateful to our clinical collaborators for their work in achieving this important milestone.” The Virtue Trial is a prospective, multi-center, randomized trial comparing clinical outcomes of Virtue SAB to AGENT Paclitaxel DCB in the treatment of coronary ISR, a difficult-to-treat and serious complication of coronary stenting. The primary endpoint is a non-inferiority comparison of Target Lesion Failure (TLF) defined as a composite of cardiac death, nonfatal target vessel myocardial infarction and ischemia-driven target lesion revascularization at 12 months. The trial will randomize 740 patients across up to 75 centers in the U.S. With the amended IDE approved by the FDA, Orchestra BioMed is currently targeting initiation of the Virtue Trial during the second half of 2025, bringing the Company one step closer to delivering a next-generation solution for atherosclerotic disease. About Coronary In-Stent Restenosis (ISR)Coronary ISR is a serious complication of coronary stenting, which can increase the risk of life-threatening heart problems. It is characterized by a re-narrowing of a coronary artery segment that was previously treated with a stent. According to the National Cardiovascular Data Registry, coronary ISR occurs in up to 10% of stented patients during the first year and continues at a rate of up to 3% per year thereafter, resulting in an estimated over 325,000 coronary ISR lesions annually worldwide that may require treatment. If left untreated, coronary ISR may lead to stable angina, unstable angina, acute coronary syndrome, acute myocardial infarction, or death. About Virtue SABVirtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™ through a non-coated microporous AngioInfusion™ Balloon that protects the drug in transit to consistently deliver a large liquid dose overcoming certain limitations of drug-coated balloons. SirolimusEFR delivered by Virtue SAB has been shown in published preclinical series involving hundreds of arterial deliveries to achieve sustained tissue levels well above the known required therapeutic tissue concentration for inhibiting restenosis (1 ng/mg tissue) for the entire critical healing period of approximately 30 days. Virtue SAB demonstrated positive three-year clinical data in coronary ISR in the SABRE study, a multi-center prospective, independent core lab-adjudicated clinical study of 50 patients conducted in Europe. Virtue SAB has been granted Breakthrough Device Designation by the FDA for specific indications relating to coronary ISR, coronary small vessel disease and peripheral artery disease below-the-knee. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is atrioventricular interval modulation (AVIM) therapy for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing the Virtue® Sirolimus AngioInfusion™ Balloon (SAB) for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The company has received four Breakthrough Device Designations from the U.S. FDA across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn. References to Websites and Social Media Platforms References to information included on, or accessible through, websites and social media platforms do not constitute incorporation by reference of the information contained at or available through such websites or social media platforms, and you should not consider such information to be part of this press release. Forward-Looking StatementsCertain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to the timing of the initiation and of the Virtue Trial, the number of patients to be enrolled in the Virtue Trial, and the potential safety and efficacy of the Company’s product candidates, including the ability of Virtue SAB to overcome certain limitations of DCBs. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s product candidates; the timing of, and the Company’s ability to achieve, expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s annual report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 31, 2025, as updated by any risk factors disclosed under the heading “Item 1A. Risk Factors” in the Company’s subsequently filed quarterly reports on Form 10-Q. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Investor ContactJeremy FefferLifeSci AdvisorsJfeffer@lifesciadvisors.com Media ContactKelsey Kirk-EllisOrchestra BioMedkkirkellis@orchestrabiomed.com References 1Xinlin Zhang, et. al. PLOS ONE 2014 May 20;9(5):e97934. 2https://slideplayer.com/slide/5787004. 3 Tada, et. Al., Am Heart J. 2013 Jan;165(1):80-6. 4Leon M LBT III, Session 3014 ACC 2011.

Patent Supporting Gout and Autosomal Dominant Polycystic Kidney Disease ProgramsCALGARY, Alberta, April 28, 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 receipt of notification that the patent “Xanthine Oxidase Inhibitor Formulations” will be granted by the European Patent Office. The patent covers compositions and methods of formulating using XORTX’s proprietary formulations of xanthine oxidase inhibitors (“XOI”) for the treatment of health consequences of chronically high uric acid, gout, renal, cardiovascular and other diseases where aberrant purine metabolism has been implicated in disease progression. Dr. Allen Davidoff, CEO of XORTX stated, “This patent covers compositions of formulations key to XORTX’s platform technology and this issuance strengthens our intellectual property portfolio in the European Union (“EU”). Importantly, this European patent broadens protection of our first-in-class program for gout as well as supporting our autosomal dominant polycystic kidney disease (“ADPKD”) program. This patent focuses on the health consequences that arise from uric acid crystal formation due to hyperuricemia in conditions including gout, kidney stone formation, cardiovascular disease and covers novel therapeutic solutions developed specifically to address these problems. The granting of this patent provides additional breadth of patent to XORTX for commercialization and partnering opportunities throughout Europe. Including this newly granted patent, XORTX now has five granted patents in the United States (“US”) and/or EU covering compositions and uses of uric acid lowering agents to treat gout, the health consequences of hyperuricemia, and progressive kidney disease.” About Hyperuricemia, Gout and Health Consequences It is estimated that 14% of the adult population has hyperuricemia – i.e. serum uric acid levels greater than the normal range. Approximately 3% of the US population suffer from gout as a result of their hyperuricemia, though not all individuals who have hyperuricemia develop gout. The factors that contribute to hyperuricemia include genetic factors(1), dietary factors and lifestyle choices. Nucleotides are normally broken down in the blood by the xanthine oxidase (“XO”) enzyme through the purine metabolic pathway. This results in the formation of uric acid. However, if an individual experiences chronically high blood uric acid concentrations (hyperuricemia), they often experience health consequences including gout, kidney stones, diabetes, cardiovascular disease, and renal failure. Evidence that unique health consequences may arise from hyperuricemia, independent of the health consequences of gout, suggest that aberrant purine metabolism, hyperuricemia, merits an increased therapeutic focus. Lowering blood levels of uric acid in gout patients is strongly correlated with improved health outcomes. Recent groundbreaking studies by Wang et al. suggests linkage of genetic factors to the overexpression of XO(1). Recently, emerging discoveries link genetic factors to specific populations and show that higher XO expression is associated with a variety of conditions including hyperuricemia(2), general sepsis, organ failure and sepsis associated with acute respiratory distress syndrome (ARDS)(3,4), kidney dysfunction(3,4), diabetes(5), polycystic kidney disease(1,5) and kidney failure(6,7). From a mechanistic standpoint, these studies advocate for a precision medicine approach in which genetic risk variants would guide treatment decisions(1). Addressable Gout Market Opportunity In North America, approximately 3.5 million people suffer from gout due to elevated uric acid levels in blood. The therapeutic options to lower uric acid levels include three major classes of drugs: 1) oral uricosurics that are used to decrease the reabsorption of uric acid by the kidney; 2) intravenous uricase enzymes that are used to metabolize uric acid in the blood for excretion; and 3) oral XOIs that are used to inhibit the production of uric acid by the purine metabolic pathway. XOIs are the preferred first-line treatment for gout. Allopurinol is the most commonly prescribed XOI, with approximately 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 allopurinol intolerant patients. While Febuxostat achieved peak sales of approximately US$450 million1, it now carries a Black Box warning due to its associated risk of sudden cardiovascular death and its use has declined significantly. This decline in Febuxostat use has created an opportunity for a novel XOI to address the underlying unmet medical need which the XRx-026 program aims to fill. References: Korsmo HW, Emerging roles of xanthine oxidoreductase in chronic kidney disease, Antioxidants, June 2024Major TJ, et all, Evaluation of the diet wide contribution to serum urate levels: Met-analysis of population based cohorts, BMJ, 363, k3952, 2018Gao, Li et al., Xanthine oxidoreductase gene polymorphism are associated with high risk of sepsis and organ failure, Respir. Res, 24, 177_2023Liu H, et al., Genetic variants in XDH are associated with prognosis off gastric cancer in a Chines population, 663, 196, 2013Wang et al., Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR,” The authors identified an expression quantitative trait loci (QTL) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (XO), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in diabetic kidney disease in male mice. They concluded that certain types of alleles of a gene that controls the expression of xanthine oxidase can be over expressed in CKD, diabetic kidney disease and polycystic kidney disease.Kudo M et al., Functional Characterization of Genetic Polymorphisms Identified in the Promotor Region of the Xanthine Oxidase Gene, Drug Metab. Pharmacokinet., 25, 599, 2010Boban M, et al., Circulating purine compound, uric acid, and xanthine oxidase/dehydrogenate relationship in essential hypertension and end stage renal disease., Ren. Fail., 36, 613, 2014 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.