The Registry team is thrilled to announce that the Registry is now available in Spanish and French languages. Surveys, informed consent forms, and all other features are available in Spanish and French .  This includes much of the general information on the Registry available at pscpartnersregistry.org . ACCESSING THE TRANSLATIONS From pscpartnersregistry.org , you can access translations by selecting the flag icon at the top of the webpage or within the page menu (on mobile). The Spanish and French versions can also be accessed by clicking on the globe icon at the top right of the Registry login page  and Participant Dashboard. EXPANDING OUR GLOBAL REACH With Spanish and French resources, the Registry aims to expand global access and gain better representation for those living with PSC. These two languages were prioritized to support our American and Canadian community. Additional languages will be added in the future. Translations of surveys and the informed consent form were produced by Language Scientific Inc., a medical and technical translation company whose focus encompasses healthcare, research, pharmaceutical, and related sectors. Registry Senior Advisor Rachel Gomel and other multilingual members of the PSC Partners community reviewed the translations carefully, and all content has been approved by North Star Review Board. Thank you - gracias  - merci  - for your participation as the Registry grows in new and exciting ways!

The new Clinical Survey 2026 was just released and is available in your Registry account. Have you ever wondered why the Registry updates this survey every year and why we request that you update it annually? What’s new?  In the Clinical Survey 2026, you will find changes and additions to the Symptoms section. These updates include questions developed by the PSC Partners’ Symptom Assessment Project  (SAP) team and asked in the recent Symptom Assessment Survey (now closed). The goal of the SAP initiative is to create a validated patient-reported outcome measure that can be used to measure endpoints in clinical trials. Including the same questions in the Clinical Survey supports that goal. Additionally, some questions have been reworded to bring them into alignment with surveys now being used in the international WIND-PSC project . In this way, more corresponding data points can be collected, accelerating PSC research. All participants who have not filled out a Clinical Survey in the last six months  are invited to log in and fill out the 2026 version now . If you completed the Clinical Survey 2025 more recently, it is preferable that you wait until a little later this year to complete the new version. Prior responses will be pre-filled where appropriate to help you move through the survey more quickly. No change in your health?  It is just as important to take the survey yearly if you have had no change in symptoms as it is to report health changes. Both are vital information to researchers working hard to map out how PSC progresses – or doesn’t – and under what circumstances. For example, perhaps medication you are taking or a diet you are following is helping you. That is key information. You’ve had a transplant? It’s important to update the survey annually so that we know that you have had a transplant (a significant outcome) and whether or not you have had a recurrence of PSC since then. Your survey responses and general profile information determine some of the emails we send you. When the Registry team sends out emails recruiting for clinical trials, we filter for basic eligibility based on your latest survey responses and demographic information, such as your age or where you live. You will receive more appropriate emails about trial opportunities if your survey and your profile information are up to date. Accurate survey data is key to advancing PSC research – please take the Clinical Survey 2026!

On September 8, 2025, Mirum Pharmaceuticals Inc. issued a press release announcing enrollment completion for the Phase 2b VISTAS study. This clinical trial is studying volixibat versus placebo to treat pruritus (itch) associated with PSC. Volixibat works by reducing bile acids in the blood, which may decrease the frequency and severity of pruritus. The VISTAS study targeted an enrollment of 200 adult and pediatric (12 years and older) participants living with PSC. Earlier blinded interim results showed a sufficient improvement in pruritus and no safety concerns, allowing the study to continue and complete enrollment. An initial summary of final results of the trial are expected in the 2nd quarter of 2026. There are currently no approved treatments for pruritus or other PSC related symptoms. If successful, this study may support the FDA approval of the first drug to treat this debilitating PSC symptom. PSC Partners is deeply grateful for every person living with PSC who chooses to participate in clinical trials, including this study. Your participation enables development of safe and effective treatments for PSC for all. We will continue to update the community as more information becomes available regarding this study. Read the full press release from Mirum on their website.

In 2024, the Registry team sat down with the leadership at North Star Review Board, which serves as the independent review board (IRB) for the Registry.  Dr. Stephen Rosenfeld, chair and executive director, and Patricia Seymour, director, had wonderful insights into the history and practices of IRBs, including what their roles look like and how they work with the Registry. Their work includes reviewing study protocols and progress, which for the Registry includes reviewing the consent processes, Registry policies, and any new studies/surveys launched on the Registry platform. IRBs help ensure that the well-being of participants in any studies are protected. In the Registry, this includes making sure that patient privacy and confidentiality is respected throughout all Registry operations. If you have any questions or concerns as a Registry participant (or prospective participant), you can contact the North Star Review Board at info@northstarreviewboard.org . Access a written transcript here. About North Star Review Board “North Star Review Board is a nonprofit Research Ethics Review Board (RERB) founded in 2021 by experienced IRB professionals who wanted to provide a new model of IRB review.    Our staff and board members bring decades of experience in board review and operations. We want to assure compliance AND build trust in research as a public good and at a reasonable cost.   While the scope of IRB review is defined by regulation, advances in science and technology raise important issues of trust, rights, and welfare on which regulations are silent. These issues include the implications of research with Big Data, Artificial Intelligence and Machine Learning for science and healthcare delivery, the proper use of genetic data, and the obligation to make research opportunities accessible to all.  Our commitment to offer services to other non-profit organizations and independent investigators ensures that research that is not currently well funded has a chance to be conducted. We believe that researchers in the social sciences, education and in the rare disease space, to name a few, deserve quality regulatory and ethical review without spending nearly their entire research budget on IRB review. For these and other areas, as an RERB, we acknowledge unanswered ethical questions in ways that promote discussion and give voice to the perspectives of research participants. We want to assure compliance AND build trust in research as a public good.” Dr. Stephen Rosenfeld, Chair and Executive Director, North Star Review Board Learn more at learningirb.org .

Living with PSC, Leading with Hope You might notice this issue of The Viaduct  has a new look, in more ways than one! As your new Registry director, it is my honor to serve you in fulfilling the Registry’s mission to facilitate, expedite, and advance patient-centered research towards treatments and a cure for PSC. When I was diagnosed with PSC, I felt the same as many of you did: hopeless, uncertain, fearful. As I pored over medical websites, papers, and personal stories, two things became clear. First, there is wide variability in people’s experiences living with PSC. What may be true for one person doesn't hold for another. Second, there is a lot we don’t yet know about PSC. Eventually, I discovered the Registry, and it was immediately clear that this would be a key part to solving the PSC puzzle. Each of us is affected by PSC in our own way. Your unique experience is a treasure trove of knowledge, and the Registry strives to make your voice heard clearly and fully. And yet, it is only through our unified voice that we can drive research forward. Everyone must add their piece of the puzzle to identify the underlying patterns and shine light on this complex disease. Today, working with the incredible Registry team, reviewing the vast wealth of data you have helped contribute to, and connecting with the vibrant community, I am not just hopeful. I am certain that together, we will create a world where a PSC diagnosis comes with a cure. - Brian Thorsen, Director, PSC Partners Patient Registry Now Available: Symptom Assessment Survey Developed by the PSC Partners Symptom Assessment Project, the Symptom Assessment Survey  measures three major symptoms of PSC: fatigue, brain fog, and liver pain . If you are an adult with PSC and have experienced ANY or ALL  of these symptoms in the past seven days , whether your symptoms were mild or severe, please log into the Registry and take this important survey. Cholangiocarcinoma (CCA) Surveillance and Education In May 2025, Stephen Rossi, chief scientific officer at PSC Partners, presented initial results from the PSC and Cholangiocarcinoma (CCA) Patient Survey  at a Precision BTC Network meeting focused on biomarker development for CCA diagnosis and management. With 624 survey responses in just seven weeks, it is abundantly clear that this topic is of high importance to the community. Many thanks to all respondents, both from the Registry and from PSC Support (UK), who co-developed this survey. Improving Access to Care De-identified results from the Registry’s Health Equity in PSC Survey  were presented in May 2025 at the annual Digestive Disease Week conference held in San Diego, California. The survey is currently active for Registry participants to complete. More responses are needed to better understand the wide range of backgrounds and experiences of people living with PSC. Potential Treatments for PSC In May 2025, major news came from the EASL Congress on two potential treatments for PSC. Read more  or listen to a breakdown of the research in our new PSC Breaking News  podcast. Enrollment Complete for VISTAS Phase 2b Study On September 8, 2025, Mirum Pharmaceuticals announced the completion of enrollment for the VISTAS study  of volixibat versus placebo to treat pruritus (itch) associated with PSC. PSC Partners is deeply grateful for every person living with PSC who chooses to participate in clinical trials, including this study. Your participation enables development of safe and effective treatments for PSC for all. Meet the North Star Review Board In 2024, the Registry Team sat down with the leadership at North Star Review Board, who serves as the independent review board (IRB) for the Registry. Learn more about their work and role in protecting participant rights and ensuring your safety and privacy. Learning from Registry Data: PSC Symptoms This chart was created using the most recent Clinical Survey responses from 2,222 Registry participants. There is significant overlap: on average, Registry participants have experienced 5.5 out of the 11 listed symptoms. PSC often comes with a major symptom burden. Researchers are working to develop a more nuanced understanding of these symptoms and how to effectively measure changes over time. The Symptom Assessment Survey helps build this in-depth profile of key PSC symptoms. Stay Connected with PSC Partners Sign up to receive the information that matters most to you— from research and volunteer openings to our three e-newsletters:  The Beacon - new, scientific research newsletter providing a comprehensive look at how patient-driven research and donor contributions make an impact. Read the inaugural edition . The Duct - the latest PSC news, updates and events The Viaduct - Patient Registry news

In May 2025, the annual Digestive Disease Week (DDW) conference was held in San Diego,  California. This conference brings together clinicians, researchers, and industry leaders from across gastroenterology, hepatology, and other related fields of medicine. De-identified results from the Registry’s Health Equity in PSC Survey  were presented in a poster session at the DDW conference. Led by Dr. Kidist Yimam (California Pacific Medical Center) and co-authored by members of the Registry team and PSC Partners’ Health Equity Committee, the poster highlighted socioeconomic and demographic factors of people living with PSC, and how these factors can impact the quality of healthcare patients receive. Results from the Survey Some highlights from the poster include: Women were more likely to report a delay in PSC diagnosis. Household income was associated with satisfaction with healthcare received. About 20% of respondents live more than 100 miles from the nearest transplant center. Only 11% of respondents have ever participated in a clinical trial. Click here to read the full poster. Your Voice is Needed At the time this poster was presented, 541 Registry participants had completed the Health Equity Survey. While this is an excellent start, every additional response matters — a particularly high response rate is needed to identify patterns in the wide experiences of this community. The survey is still available in the Registry  for you to complete today. As always, no identifying information ever leaves the Registry. Your responses are kept confidential and only de-identified data is shared with researchers. Thank you to all Registry participants who have added their voice to this survey! In addition to supporting the search for a cure for PSC, you are accelerating research to improve PSC care for all.

The Precision BTC Network, a European-focused international coalition to improve care of biliary tract cancer (also referred to as CCA or BTC), held a meeting in Mallorca in May 2025 focused on biomarker development for CCA diagnosis and management. At the meeting, Stephen Rossi, chief scientific officer at PSC Partners, presented preliminary results from the PSC and Cholangiocarcinoma (CCA) Patient Survey , which was available in the Registry from March 26 to May 16, 2025. With 624 responses  in just seven weeks, it is abundantly clear that this topic is of high importance to the community. Many thanks to all survey respondents, both through the Registry and through PSC Support (UK), who co-developed this survey with PSC Partners. Your voice is moving mountains! The survey revealed large variability in current practices of monitoring for CCA in patients with PSC, who are at significantly higher risk for developing CCA than the general population. While differences in regional guidelines between North America and Europe lead to differences in care, the survey highlighted both  the importance of discussing CCA proactively with one’s doctor and a strong desire from the community for improved education regarding CCA. Thanks in part to community input, PSC Partners' International Collaborative Research Network has funded a study to advance early detection methods for CCA . The ultimate goal of this project is to bring new tools into the hands of doctors and patients. Understanding current practices in CCA surveillance is important to understand how prospective new tools can be integrated into patient care. Results from the survey will be made publicly available later this year.

Dear PSC Registry Community, It is time for me to leave my position of Director of the PSC Partners Patient Registry. As founder of the Registry, I’ve lived through the realization of what sixteen years ago had seemed like an unreachable dream. Even before its inception, we knew how potentially valuable this Registry could be as a repository of data on our rare and complicated disease with patients thinly spread out throughout the world. Through the years, I witnessed how the Registry gradually became a magnet attracting drug developers and researchers. I cherished the lasting relationships I formed by the simple act of answering questions about the Registry to those living with PSC and to researchers wanting to get closer to our community. It was a gift to see the spark in the eyes of drug developers who said they felt “a new sense of purpose in their work” and “fresh excitement each day as they worked on their drug” after hearing PSCers telling the story of their PSC journey. We’ve had countless rewards. You’ve made patient-partnered research a reality! I leave the Registry in great hands. Brian Thorsen, who has been working with me as Associate Director, has seamlessly taken my place. As a person living with PSC, Brian is as passionate as I am about finding solutions to resolve PSC. His expertise as a statistician educated at the University of California, Berkeley, serves the Registry well, especially now that the Registry is partnering in research, initiating research, and powerfully representing the patient voice. The change in leadership doesn’t change anything with the Registry protocol. You will always maintain the right to withdraw from the Registry, and once in the Registry, you don’t need to go through the consent process again. If you have any questions, don’t hesitate to contact Brian ( brian@pscpartners.org ). For those of you who have become my friends, you know where to find me. I will always be there for you ( rachel@pscpartners.org ).  With love and gratitude, Rachel Gomel

The Registry team is excited to announce that a new Symptom Assessment Survey is now available in the Registry. Developed by the PSC Partners Symptom Assessment Project, this survey measures three major symptoms of PSC: fatigue, brain fog, and liver pain .   If you are an adult with PSC* and have experienced ANY or ALL  of these symptoms in the past seven days **, whether your symptoms were mild or severe, please log into the Registry and take this survey. * Including post-transplant with recurrent PSC. ** If you have NOT had any of these symptoms in the past seven days, please wait to take the survey. You can take it later on if you are experiencing these symptoms. ABOUT THE SURVEY Registry participants helped create this new assessment tool. Work began in 2022 with the input of focus group volunteers, recruited through the Registry. Years of detailed interviews with many people living with PSC shaped these tools into the questionnaires you can now view in the Registry. By completing this survey, you provide an important piece of evidence to show these questionnaires are effective tools. This supports the goal of using them in clinical trials, so researchers can show that a treatment improves these symptoms. Your voice directly supports development of new treatments for PSC. Read more about the survey and the research team in a recent VIADUCT newsletter . Thank you in advance for your participation! If you have not logged into the Registry since it moved to an updated platform in March 2024, you will need to reset your password using the “Forgot your password?” feature on the login page.

In May 2025, the European Association for Study of the Liver (EASL) hosted its annual congress in Amsterdam, Netherlands. Late-breaking oral presentations on potential treatments for PSC featured results from two clinical trials: Dr. Falk Pharma: Norucholic acid for the treatment of primary sclerosing cholangitis: 96-week analysis of a pivotal phase 3 trial , presented by Michael Trauner Ipsen Pharmaceuticals: Elafibranor for primary sclerosing cholangitis: the ELMWOOD phase II randomised controlled trial , presented by Cynthia Levy PSC Partners is encouraged by the positive results from both studies, which offer hope to the community. No treatments have yet been approved for PSC, and the success of these two studies offers potential pathways to a treatment. Norucholic Acid (NCA): Results from European Phase 3 Study in PSC On May 7, 2025, Dr. Falk Pharma announced results from their phase 3 study of norucholic acid (also known as norursodeoxycholic acid, or norUDCA). The NCA Phase III trial was a 96 week study of 301 PSC patients, 205 patients receiving 1500 mg daily of NCA and 96 receiving a placebo. 78% of patients were concurrently taking UDCA (Ursodeoxycholic acid, or Urso/Ursodiol). The combined primary endpoint* was reduction of alkaline phosphatase (ALP) levels** to less than 1.5x the upper limit of normal (ULN), along with no worsening of fibrosis stage. All patients in the study began with ALP levels greater than this threshold. The following key results were achieved in the study at week 96: A higher rate of patients taking NCA achieved the primary endpoint (15.1%) versus placebo (4.1%). Among those not concurrently taking UDCA, a larger difference was seen: 20.3% on NCA and UDCA vs 0% on placebo and not taking UDCA. A higher rate of patients receiving NCA had improvement in fibrosis versus placebo, and a lower rate had worsening of fibrosis versus placebo. Other liver enzyme markers had sustained improvement for patients on NCA but not on placebo. NCA demonstrated a favorable safety and tolerability profile, with similar rates of adverse events versus placebo. As this study was conducted solely in European countries, approval as a treatment for PSC would only be considered in Europe based on this study alone. A separate path would have to be pursued for approval in the United States by the FDA. Learn more:   About NCA:  NCA is a derivative of UDCA, an approved treatment for PBC that is sometimes prescribed for off-label use in treatment of PSC. Trial details from ClinicalTrials.gov Written abstract from EASL (LBO-001) Press release from Dr. Falk Pharma *Primary endpoint: The most important outcome(s) that researchers measure to determine whether a new treatment is effective. In the case of a combined primary endpoint, both measures need to be achieved. **ALP is a biomarker collected through blood samples for measuring and predicting disease progression in PSC. Elafibranor: Results from International Phase 2 Study in PSC On May 10, 2025, Ipsen Pharmaceuticals will present results from their Phase II ELMWOOD study. The ELMWOOD study was a 12 week study of 68 patients who were randomly assigned to receive 80 mg or 120 mg of elafibranor or a placebo. The primary endpoint of this study was safety and tolerability of elafibranor. The following key results were achieved in the study: Elafibranor showed “significant dose-dependent reductions in alkaline phosphatase (ALP)” versus placebo after 12 weeks, with greater reduction in the 120 mg treatment group: -171.1 U/L in 120 mg, -103.2 U/L in 80 mg, and +32 U/L in placebo. Enhanced Liver Fibrosis (ELF) scores, another marker for disease progression, also stabilized in the elafibranor group compared with placebo. Patients in the 120 mg elafibranor treatment group also experienced improvements in pruritus (PSC-related itch) versus placebo. Elafibranor demonstrated a favorable safety and tolerability profile, with comparable rates of adverse events to placebo. Learn more: About Elafibranor:  Elafibranor was approved by the FDA in 2019 as a Breakthrough Therapy Designation as a second-line treatment for primary biliary cholangitis (PBC), when UDCA did not succeed as a first-line treatment. Trial details from ClinicalTrials.gov Written abstract from EASL (OS-089) Press release from Ipsen Pharmaceuticals PSC Partners will continue to update the community as more information becomes available regarding this study. Please check back for updates, including on the Registry’s Ongoing Clinical Trials page.

Today, March 27, 2025, Chemomab Therapeutics issued a press release announcing results from the Open Label Extension (OLE) section of the SPRING trial, which offered SPRING participants the opportunity to receive nebokitug (CM-101) for an additional 33 weeks (up to 48 weeks of exposure to nebokitug).  PSC Partners is encouraged by the positive nebokitug OLE data shared in the press release. Key takeaways from the press release that are important to patients: More than 90% of the eligible study patients elected to join the OLE. The OLE data offers a very favorable safety and tolerability profile of nebokitug in PSC.  The OLE data provides evidence of stabilization of liver function tests and fibroscan and the reduction of serum bile acid levels. Reductions in markers of liver fibrosis (ELF and PRO-C3 tests) are a positive signal that nebokitug may have an impact on clinical outcomes, particularly for those with more advanced disease (fibrosis stages 2 and 3). The design of the previously announced Phase 3 study includes time to first clinical outcome as a primary endpoint* and will enhance for those with advanced disease.  Overall, between these favorable OLE results and the previously announced enrollment criteria for the planned Phase 3 Study ( see notice here ) a wider range of patients will be included in this study, and patients with more advanced disease will be a key priority. The full press release is available on the Chemomab website. PSC drug development has been challenging. PSC Partners encourages patients to remain engaged and respond to requests to make our voices heard and our priorities known.  To ensure that new therapies complete their full course of clinical development, please engage in the numerous opportunities PSC Partners offers for you to share your experience and perspective. We will continue to open new doors to bring patient perspectives to the foreground. With your help, we will support enrollment into these studies to prevent delays in completing research that can lead to the approval of effective drugs.    To stay directly informed about study opportunities and to advance PSC research, please join the Patient Registry . *Primary endpoint: The single most important outcome that researchers measure to determine whether a new treatment is effective. A Phase 3 trial is the final phase of clinical trials before the Food and Drug Administration (FDA) conducts a review to determine whether to approve the drug for market. An overview of the phases of clinical trials can be found here  (source FDA). PSC Partners will continue to update the community as more information becomes available regarding this study. Please check back for updates, including on the Registry’s Ongoing Clinical Trials page. For more information regarding CM-101: Previous news article: Phase 3 Trial Announcement from Chemomab for Nebokitug (CM-101) in PSC Previous news article: Chemomab Announces CM-101 Phase 2 SPRING Trial Results More results from the open-label extension of the SPRING trial are expected in the first quarter of 2025. Two scientific publications related to CM-101 are available in the Related Publications page  of the Registry’s Clinical Trials section.

Quotes from interviews of patients living with PSC describing their fatigue, presented as a poster at AASLD's The Liver Meeting 2024 . Patient-reported outcomes (PROs) are used as clinical trial endpoints* for some diseases, but the Food and Drug Administration (FDA) has not yet approved any PRO assessment tools for establishing the effectiveness of a new PSC treatment. While some PRO tools exist for PSC, they do not meet the FDA’s standards. PSC Partners is leading the Symptom Assessment Project (SAP), an initiative whose goal is to develop FDA-approved PRO tools for three common PSC symptoms that impact quality of life – fatigue, brain fog (cognitive impairment), and pain around the liver. Lead investigators for the project are Donna Evon, Ph.D., Duke University, and Bryce Reeve, Ph.D., University of North Carolina – Chapel Hill. They are working to create three separate validated questionnaires about the above symptoms. The multi-stage validation process ensures that the assessment tool accurately captures the intended information and is fit for its intended purpose. “The Symptom Assessment Project is important to the PSC community,” says Dr. Evon, “because [the questionnaires] will capture experiences that can be shared with healthcare providers who may be able to help, and, ultimately, these measures will be used to evaluate the benefits of new treatments for PSC.” Work on this tool began in 2022 with the input of focus group volunteers, who all belong to the Patient Registry and have personal experience with common PSC symptoms. Group participants helped to identify and rank the symptoms that most affected their quality of life, and they reviewed the PRO tools that were currently being used for PSC. The Symptom Assessment Project is nearly finished developing the three questionnaires (fatigue, brain fog, and pain around the liver). These tools will become available in a Registry survey later this year. Obtaining real-world data from a large group of people living with PSC (including those in the Registry) is a key step in development of these tools to support their ultimate use in a clinical trial setting. Drs. Evon and Reeve published an article in the March 2025 edition of Current Opinions in Gastroenterology  that gives an overview of FDA guidance regarding PRO tools; reviews existing PRO tools; highlights how the new SAP questionnaires will adhere to FDA guidance; and encourages collaborations among academic, industry, and patient advocacy organizations in the design of these new tools. The article abstract is available here . *Endpoint: a measurable outcome used to determine the effect of a treatment in a clinical trial.