University of KwaZulu-Natal

CAPE TOWN, South Africa, July 17, 2024 /PRNewswire/ -- Although South Africa has the largest number of people living with HIV worldwide, strides have been made in controlling the epidemic, especially in the reduction of HIV incidence, testing, and treatment. Equipped with MGI's advanced sequencing tools and technologies, researchers from the South African Medical Research Council (SAMRC) and University of KwaZulu-Natal (UKZN) are inching closer to finding the answer to the natural control of HIV infection, leading to improved health outcomes and quality of life amongst South Africans. Continue Reading The scientist from SAMRC is sequencing genomes on DNBSEQ-G400 High-throughput genetic sequencer With better understanding of HIV, awareness of the stigma and related inequalities has also been on a rise. Every year on Zero HIV Stigma Day (21 July), an observance in honor of Prudence Mabele, the first Black South African woman to publicly share her HIV status, the world is united to take actions against HIV stigma and challenge its impact. With initiatives such as this one by SAMRC and UKZN, more individuals and communities alike are being empowered to move beyond labels and redefine HIV narratives. The mystery of the HIV elite controller According to the latest survey by the Human Sciences Research Council, in 2022, there were approximately 7.8 million people afflicted with HIV in South Africa, the highest absolute number of people living with HIV globally. Yet despite having the largest genetic diversity in the world, African human genome sequences represent the lowest of all the human genomes that have been sequenced worldwide. There is a dire need to leverage genomics to back up and scale targeted intervention programs to put more people living with HIV on effective treatment. Of particular interest in the global investigations into HIV is "elite controllers" (ECs), a rare group of HIV‐1‐positive individuals whose immune systems can seemingly suppress the infection from developing without taking antiretrovirals (ARVs). For every 200 people living with HIV, around one may be an elite controller (0.5%). In South Africa, with its high rate of HIV infection, the prevalence of ECs also appears to be higher. By "unmasking" the secrets of ECs through research, clues can be revealed and new therapies potentially developed to benefit broader groups of people living with the disease. The promise of MGI's genomics technology In order to identify the polymorphism and mutations within individuals of African descent, and understand how they are associated with HIV disease progression, Dr. Veron Ramsuran, Associate Professor at UKZN, and Prof. Thumbi Ndung'u, Director for Basic & Translational Science at the Africa Health Research Institute, joined hands with SAMRC, MGI and local South African clinics in 2019 to take their 20+ years of work in EC research to the next level using whole genome sequencing (WGS). "The HIV Host Genome project was started at the same time as we launched SAMRC's African Genomics Centre in Cape Town with the support from MGI," said project co-investigator Rizwana Mia, also co-founder of the SAMRC Genomics Centre and Senior Program Manager in Precision Medicine at SAMRC. "The partnership saw MGI putting down a high-throughput sequencing workflow, and assisted us with the specialized scaled infrastructure design in our lab. This was at a time when there was no real infrastructure for large-scale next generation sequencing in Africa." "More importantly, by moving our laboratory workflow to scale, we are hoping to develop genomic research to address this quadruple burden of disease that South Africa faces," explained Mia. "Our project looks at a unique cohort of patients that have the ability to control the HIV virus to ascertain how disease progresses and the host-directed mechanisms for innate immune control. In addition, we included family sets to help us better understand the relationship between pediatric non-progressors and their parents who are also HIV positive, to uncover and genetic differences that may contribute to host immune control of HIV." As part of the project, MGI's highly efficient and advanced DNBSEQä sequencing technology, platforms, and workflow are playing an instrumental role. Relying on DNBSEQ's high accuracy, quick turnaround time and high cost-effectiveness, researchers are able to generate quality data for analyzing different HIV genotypes and identifying potential immunological mechanisms associated with ECs. Indeed, through collaborative efforts, the team has made significant progress in uncovering crucial genetic insights into the study of ECs. "We've identified new genes and polymorphism that are playing a role with HIV disease through new data generated from Whole Genome Sequencing," said Dr. Veron Ramsuran, principal investigator of the HIV Host Genome project. "Traditionally, there is a list of mutations or genes that are known to associate with HIV, yet they are largely based on studies on Caucasian populations. Our HIV research is adding to the general pool of knowledge pertaining to individuals of African descent, which will thereby inform new treatment and new vaccine opportunities." "What's important is also understanding how drugs interact with the individual," added Ramsuran. "We've found in the past that certain polymorphism is associated with drug metabolism in genes. Building on this understanding of drugs in combination with the genetics of the individual, we can develop prediction tools to inform clinicians on drug type or dosage depending on the presence of the polymorphism to facilitate a more rapid metabolism of the drug." The key to understanding South African human genomes Through infrastructure and technical support from MGI, SAMRC has been refining the science of genomics for personalized medicine, besides HIV, to benefit Africa's diverse gene pool. Notably, the establishment of the SAMRC Genomics Centre in 2019, the first high-throughput genome sequencing facility in the continent, has enhanced South Africa's ability to sequence, analyze and store human genomes, unlocking a new level of cutting-edge research. The cooperation has also seen SAMRC sequencing the very first plant species for the African BioGenome Project in 2023 using MGI's DNBSEQ-G400* versatile benchtop sequencer and single-tube long fragment read (stLFR) technology. By empowering applications of their platforms in agrigenomics, MGI has also been contributing to the improvement of biodiversity protection, food security and environmental health across Africa. Encouragingly, investigations into Africa's diseases will continue beyond this point. The HIV Host Genome project has lain the groundwork for the ambitious National 110K Human Genome Project. This large-scale population study will involve 110,000 participants from the South African population, aiming to understand more about of their genomic diversity, address various health challenges, and pave the way for personalized medicine in the country. Furthermore, the data collected will be incorporated into a national population database, enhancing research outcomes and deepening disease understanding for Africa. Given South Africa's diverse population, limited human genomics data and significant healthcare burden from diseases such as HIV, understanding pathogenesis and inherent mutations is important for implementing targeted treatments and public health programs. With its lower sequencing cost, high quality data, and efficient all-in-one workflows, MGI will continue to drive progress in studying rare HIV phenotypes, which holds great promise in advancing the development of targeted interventions and cures– not only for HIV – but many other diseases. "Looking at the genetic variation and its impact on HIV is a gamechanger, because it will shed light on some of the best immune responses that can be generated against the HIV virus," stated Prof. Thumbi Ndung'u, principal investigator of several of the project's cohort studies. "And actually, this knowledge will be widely applicable and could have an impact on other diseases - infectious and non-infectious – as well as their drug interventions. It will make sure that Africans, just like everybody else, are at the center of drug and vaccine development." In June this year, MGI introduced its HIV-1 genotyping and drug resistance detection package on its portable low throughput DNBSEQ-E25, and mid-low throughput DNBSEQ-G99 sequencers. This package unitizes deep sequencing to detect low-frequency mutation associated with drug resistance. When combined with MGI's automated sample preparation systems and HIV-Genome Pro software, users benefit from a streamlined tool capable of rapid and accurate detection of HIV-1, drug resistance analysis, genome assembly, mutation detection, and evolutionary tracing. The process is highly efficient with DNBSEQ-E25 to process up to 16 samples from RNA to report in 28.5 hours, while DNBSEQ-G99 can handle up to 120 samples in just 24 hours. For more details on this groundbreaking HIV research project, check out this in-depth video created in collaboration with Nature Research Custom Media. Photo - Logo -

Results from the EXPEDITE study of Remodulin® induction prior to Orenitram® therapy to be presented at ATS Baseline patient data from the TETON studies of Tyvaso® Inhalation Solution in patients with idiopathic pulmonary fibrosis to be presented at ATS ATS presentation examines geographical barriers as a social determinant of health for PAH patients; demonstrates UT’s commitment to reducing barriers to PAH care Data on United Therapeutics’ xenotransplantation and ex-vivo lung perfusion efforts to be presented at ISHLT At ATS, United Therapeutics is hosting a sponsored symposium on PH-ILD and is sponsoring the ATS 2023 Women’s Forum SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that recent research across its development portfolio will be presented at the International Society for Heart and Lung Transplantation (ISHLT) 43rd Annual Meeting and Scientific Sessions in Denver, Colorado on April 19-22, 2023, and at the American Thoracic Society (ATS) International Conference in Washington, D.C. on May 19-24, 2023. At ATS, United Therapeutics will host an educational symposium on pulmonary hypertension associated with interstitial lung disease (PH-ILD) and is sponsoring the ATS 2023 Women’s Forum. “Our posters and presentations at ISHLT 2023 will provide additional insight into outcomes associated with our ex-vivo lung perfusion program and initial detail into recent xenotransplant work in human preclinical models using our UHeart™ xenoheart,” noted Gil Golden, M.D., Ph.D., Chief Medical Officer at United Therapeutics. “In addition, we’re excited to present an overview of the phase 4 ARTISAN study that seeks to investigate a novel targeted treatment approach, aimed at the reduction of pathologically high mean pulmonary artery pressures through early and rapid parenteral treprostinil up-titration, potentially leading to improved right ventricular structure and function in patients with pulmonary arterial hypertension.” “Following top line data last year, we’re looking forward to presenting additional data from the EXPEDITE study that demonstrated a short induction period with Remodulin could lead to more rapidly achieving an efficacious dose of Orenitram, as well as baseline data from the TETON studies of nebulized Tyvaso in patients with idiopathic pulmonary fibrosis,” said Andrew Nelsen, PharmD, Vice President, Global Medical Affairs at United Therapeutics. “We are also looking forward to presenting data from ongoing research into the often-overlooked geographic differences in access to care among PAH patients in the U.S.” ISHLT posters and presentations include: Poster Session 2. Cardiology, Thursday, April 20, 4:15 - 5:15 PM MT: THU-144 851 – ARTISAN: A Novel Study of Mean Pulmonary Artery Pressure-Targeted Approach with Early and Rapid Treprostinil Therapy to Reverse Right Ventricular Remodeling in Pulmonary Arterial Hypertension. Presented by Raymond Benza, The Ohio State University. Poster Session 3. Pulmonology, Friday, April 21, 5:00 - 6:00 PM MT: FRI-217 1233 – Utilization and Outcomes with Single Lung Transplantation Following Ex Vivo Lung Perfusion Using a Centralized Lung Evaluation System at a Dedicated Facility. Presented by Jorge Mallea, Mayo Clinic Florida. Poster Session 3. Pulmonology, Friday, April 21, 5:00 - 6:00 PM MT: FRI-218 1234 – Comparison of Lung Utilization from NRP-DCD vs Non-NRP DCD Using EVLP. Presented by Sean Francois, Vanderbilt University Medical Center. Session 93. A MIDSUMMER NIGHT'S DREAM: From Mitochondria to Xenotransplantation: Novel Research Coming to You!, Saturday, April 22, 11:45 - 11:55 AM MT: 203 – Two 10-Gene Modified Xenoheart Transplants into Brain Dead Decedents. Presented by Nader Moazami, NYU Langone Health. Plenary 3. General Session III, Saturday, April 22, 9:50 - 10:15 AM MT: Xenotransplantation: The Future is Now. Presented by Robert Montgomery, NYU Langone Transplant Institute. ATS posters and presentations include: Mini Symposium, Monday May 22, 3:51 - 4:03 AM ET: B97 – Remodulin Induction Facilitates Rapid Achievement of Therapeutic Doses of Oral Treprostinil: Results from the EXPEDITE Study. Presented by John Kingrey, Integris Baptist Medical Center. Rapid abstract poster discussion session, Sunday, May 21, 9:00 - 11:00 AM ET: A22/304 – Understanding Differences in Geographic Access to Care Among Patients Treated for Pulmonary Arterial Hypertension in the United States. Presented by Natalie West, United Therapeutics. Thematic poster session, Sunday, May 21, 11:30 - 1:15 PM ET: A59/P766 – Preliminary Baseline Data from the TETON Phase 3 Clinical Trials of Inhaled Treprostinil in the Treatment of Idiopathic Pulmonary Fibrosis. Presented by Steven Nathan, INOVA Fairfax Hospital. Thematic poster session, Monday, May 22, 11:30 - 1:15 PM ET: B57/P161 – Win Ratio Analysis of the FREEDOM-EV Trial - A Hierarchical Approach to Multiple Clinical Endpoints. Presented by James White, University of Rochester Medical Center. Thematic poster session, Monday, May 22, 11:30 - 1:15 PM ET: B57/P168 – Assessing the Correlation Between Actigraphy Data and Clinical Measures: Insights From The ADAPT Registry. Presented by James Gagermeier, Loyola University Medical Center. Thematic poster session, Monday, May 22, 11:30 - 1:15 PM ET: B57/P175 – Correlation of WHO Functional Class and Patient-Reported Outcome Measures in Adults with Pulmonary Arterial Hypertension. Presented by Karim El-Kersh, University of Nebraska Medical Center. Thematic poster session, Monday, May 22, 11:30 - 1:15 PM ET: B59/P209 – Study Design of the Decentralized EVOLVE Study Evaluating Real-world Use of Next Generation Infusion Pumps to Deliver Parenteral Treprostinil in Patients with Pulmonary Arterial Hypertension. Presented by Margo Sketch, United Therapeutics. Thematic poster session, Monday, May 22, 11:30 - 1:15 PM ET: B59/P215 – Dose-response Analyses of Treprostinil Inhalation Powder in PAH and Its Effect on 6MWD. Presented by Karim El-Kersh, University of Nebraska Medical Center. Thematic poster session, Tuesday, May 23, 11:30 - 1:15 PM ET: C36/P898 – The PAH Patient Perspective: Factors Influencing Treatment Initiation with Inhaled Prostacyclin Therapy. Presented by Karim El-Kersh, University of Nebraska Medical Center. Poster discussion session, Wednesday, May 24, 8:00 - 10:00 AM ET: D28/501 – A Novel Approach to Clinical Change Endpoints: A Win Ratio Analysis of the INCREASE Trial. Presented by Steven Nathan, INOVA Fairfax Hospital. Poster discussion session, Wednesday, May 24, 8:00 - 10:00 AM ET: D28/505 – The Safety and Efficacy of Inhaled Treprostinil in Patients with PH-ILD on Supplemental Oxygen: A Post-hoc Analysis of the INCREASE Study. Presented by Sandeep Sahay, Houston Methodist Hospital. Sponsored events at ATS include: PH-ILD Reimagined: 2023 Updates in Disease State, Treatment, and Device Options, Sunday, May 21, 5:30 PM ET, featuring Jamie Rutland, West Coast Lung, Rutland Medical Group; Steven Nathan, INOVA Fairfax Hospital; and Colleen McEvoy, Washington University Physicians. The symposium will be held at the Renaissance Hotel Washington, DC Downtown, Potomac Ballroom, Salon 1-3. The ATS 2023 Women’s Forum, Monday, May 27, 11:45 AM - 1:15 PM ET, featuring Refiloe, University of KwaZulu Natal, and Mina Gaga, Imperial College and the Royal Brompton Hospital. About Orenitram® (treprostinil) Extended-Release Tablets Indication Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%). Important Safety Information for Orenitram Contraindications Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure. Warnings and Precautions Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms. The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum. Adverse Reactions In the 12-week, placebo-controlled, monotherapy study, and an event-driven, placebo-controlled, combination therapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw, pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain. Drug Interactions Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients. Specific Populations Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies with Orenitram in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production. Safety and effectiveness of Orenitram in pediatric patients have not been established. Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. Caution should be used when selecting a dose for geriatric patients. There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients. Please see Full Prescribing Information and Patient Information at or call 1-877-UNITHER (1-877-864-8437). About Remodulin® (treprostinil) Injection Indication Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition. Important Safety Information for Remodulin Warnings and Precautions Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration. Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms. Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function. Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Remodulin may produce symptomatic hypotension. Remodulin inhibits platelet aggregation and increases the risk of bleeding. Adverse Reactions In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were sometimes severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27% vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%), jaw pain (13% vs. 5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%). Drug Interactions Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Specific Populations In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in patients with severe hepatic insufficiency. Safety and effectiveness of Remodulin in pediatric patients have not been established. It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients. There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production. Please see accompanying Full Prescribing Information for Remodulin. For additional information, visit or call Customer Service at 1-877-UNITHER (1-877-864-8437). About TYVASO® (treprostinil) Inhalation Solution and TYVASO DPI® (treprostinil) Inhalation Powder INDICATION TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are prostacyclin mimetics indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration. Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic arterial pressure, either product may produce symptomatic hypotension. Both products inhibit platelet aggregation and increase the risk of bleeding. Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness. Like other inhaled prostaglandins, TYVASO and TYVASO DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO and TYVASO DPI. DRUG INTERACTIONS/SPECIFIC POPULATIONS The concomitant use of either product with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. Safety and effectiveness in pediatric patients have not been established. Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH‑ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety pro in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. ADVERSE REACTIONS Pulmonary Arterial Hypertension (WHO Group 1) In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the 3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea (5.9%). Pulmonary Hypertension Associated with ILD (WHO Group 3) In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH. Please see Full Prescribing Information for TYVASO or TYVASO DPI, Instructions for Use manuals for TD-100 and TD-300 TYVASO® Inhalation System and TYVASO DPI™ Inhalation Powder, and additional information at or call 1‑877‑UNITHER (1-877-864-8437). United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun, we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/PBC. Forward-looking Statements Statements included in this press release that are not historical in nature are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements relating to upcoming medical conference posters and presentations, our ARTISAN and TETON clinical studies, our ability to create value and sustain our success in the long-term, as well as our efforts to develop technologies that either delay the need for transplantable organs or expand the supply of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of April 18, 2023, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. REMODULIN, ORENITRAM, and TYVASO are registered trademarks of United Therapeutics Corporation. UHEART is a trademark of United Therapeutics Corporation. View source version on businesswire.com: Contacts Dewey Steadman at (202) 919-4097 Email: ir@unither.com Source: United Therapeutics Corporation View this news release online at:

An international team of researchers has mapped out the values and benefits of elephants to help overcome conservation challenges and conflict. New research examining the services and benefits of elephants has revealed many values are often overlooked when deciding how they should be protected. The collaboration between universities in England and South Africa, including the University of Portsmouth, found conservation strategies often have a narrow focus and tend to prioritise certain values of nature, such as economic or ecological, over moral ones. When looking specifically at elephants, the study found financial benefits including ecotourism, trophy hunting and as a source of ivory or labour, often conflicts with the animal's ecological, cultural and spiritual contributions. The authors argue not fully understanding or considering the value systems of all stakeholders involved in conservation, including local people, leads to social inequality, conflict and unsustainable strategies. Study co-author Antoinette van de Water, from the University of KwaZulu-Natal in South Africa, said: "We chose to look at elephants as the case study because their conservation can be especially challenging and contentious. "We're not saying economic contributions aren't important, but there's a lot of different values at play and they all need to be considered in conservation strategies if they are going to succeed." The study also highlights conservation decision makers tend to take a single worldview when considering the value of nature. Co-author Dr Lucy Bates, from the University of Portsmouth, explained: "Whether it's economic, ecological, or social, a blanket approach to values can impact the success of a conservation strategy. "Consider something like the ivory trade for example. International trade in ivory is illegal, but many southern African countries want to restart the trade leading to contention across the African continent. If you focus less on the potential economic value of ivory, and turn to other ways elephants can support communities, it can be a game-changer. "On a smaller scale, you can also apply this framework to defining protected areas and what land could be made available to elephants. By listening to those living in these areas, you can get a clear understanding of how decisions will affect human life as well, and work out ways to resolve any issues." The paper, published in Ecosystems Services, says nature's non-material benefits include recreation, inspiration, mental health, and social cohesion. But it points out broader moral values, such as human rights, environmental justice, rights of nature and intergenerational legacy, also have a big part to play in the success of conservation. The study recommends incorporating moral values related to biodiversity conservation into the valuation framework to create a positive loop between benefits to humans and to nature. The researchers believe that this approach will help policymakers and managers have a better understanding of what elephants mean to people, why elephants are important in themselves, and what values and interests are at stake. It can also be applied to other species and ecosystems. "What is really needed is a change of thinking," added Antoinette van de Water. "Conservation policies are often based on price tags. Our pluralist valuation system provides solutions that are not based on economic gains or political status for the few, but instead on long-term common good and the goals and aspirations of societies."