A new survey outside the Registry that focuses on understanding and improving the care of people living with PSC is now available. Every survey fills a different function, and this one, developed by two researchers at University of Miami, serves to build a comprehensive understan ding of PSC care, including quality of care and access to care. Please visit the survey website and complete the survey today!   Your input is incredibly valuable. Below is a message from the study investigators: Dear Registry Participants, Welcome to our survey! We're working to make healthcare better for people living with Primary Sclerosing Cholangitis (PSC), and your input is super important. We want to know about your experiences and thoughts to find ways to improve patient care. Your contribution means a lot to us. The survey includes simple and clear questions, and it should only take around 20-25 minutes. Your dedication to this research can really make a difference for people dealing with PSC, and we're excited about the positive impact we can make together. Best, Cynthia Levy, MD Adrielly Martins, FMD Shiff Center for Liver Diseases University of Miami If you have any questions or concerns regarding this survey, please contact Cynthia Levy or Adrielly Martins: (phone: 305-302-2474 or email: axm8717@med.miami.edu )

On February 19, 2025, Chemomab Therapeutics issued a press release announcing plans for a Phase 3 clinical trial for the treatment of PSC. The full press release is available on the Chemomab website.  The investigational drug being tested has been named nebokitug, previously studied in PSC in the SPRING Study as CM-101. PSC Partners is encouraged by the news that a potential drug for PSC is moving forward into the final stages of the drug approval process (Phase 3 clinical trial).  Some highlighted excerpts from the press release: The novel trial design does not require a liver biopsy. The trial is a randomized placebo-controlled (2:1 active to placebo ratio). Patients in the drug treatment arm will receive 20 mg/kg of nebokitug administered intravenously every three weeks. The primary endpoint* is the time-to-first clinical event[s] … associated with PSC disease progression, including more common clinical events such as acute cholangitis, strictures requiring intervention or portal hypertension as well as cholangiocarcinoma, transplant, or death. See the press release for the full list of specific events. Enrolled patients will remain in the trial until they experience one of the primary endpoint clinical events. On average, participants are expected to remain in the trial for about two years. Approximately 350 PSC patients will be enrolled in the trial, and the study population will be enriched** for patients with moderate and advanced disease. The FDA has agreed that a single Phase 3 trial, if successful, would be sufficient to proceed to regulatory review and potential drug approval. *Primary endpoint: The single most important outcome that researchers measure to determine whether a new treatment is effective. **Enriched: The investigators intend to enroll a higher number of participants matching these criteria than may be representative of the overall population of people with PSC. 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: 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.

A new survey on PSC and diet is available through the European Reference Network (ERN) and open to people living with PSC around the world. Diet and nutrition in PSC is a frequently discussed topic, and adding your voice will help to progress research in this important area! This survey was developed by Catarina Lindqvist (Karolinska Institutet, Sweden) and the ERN’s PSC Working Group. Because this anonymous survey is not connected to the Registry, it will ask some basic questions about your health. You can access the survey here. Below is a message from the study investigators: Dear individuals with PSC, We invite you to participate in an anonymous questionnaire that aims to further understand the dietary habits of individuals living with Primary Sclerosing Cholangitis (PSC). This research is designed to explore how individuals adapt their diets due to PSC, and if applicable, due to underlying Inflammatory Bowel Disease (IBD). Additionally, we seek to identify the primary sources of information individuals with PSC rely on for dietary advice. The questionnaire is divided into three sections: Background information Questions regarding PSC Questions regarding IBD (only applicable to individuals with coexisting IBD) Your participation in this questionnaire is crucial for advancing our understanding of how PSC and IBD influence dietary habits. The insights gained from this study will contribute to developing better support and resources for individuals managing these conditions. The link to the questionnaire:  https://ec.europa.eu/eusurvey/runner/a4aa42c5-0fe8-3d66-fc9c-e290ec541d4a The questionnaire is available in English, French, Spanish, Italian, German, Croatian, Hungarian, Czech, Polish and Swedish. Thank you for taking the time to share your experiences and contribute to this important research. Sincerely, Catarina Lindqvist, Karolinska Institutet, Sweden and the PSC Working Group We hope you will participate in this important survey. If you have any questions regarding this study, please contact the team using the Contact Form available in the right menu at the survey link.

This past July, the American Liver Foundation (ALF) announced the opening of a new patient registry. You may be wondering how it compares to the PSC Partners Registry and whether you should join the ALF registry. Similarities of structure and function between the two include: a reliance on patient-reported data through registry surveys; a sharing of de-identified data with approved researchers; the ability for patients to add to or update their information through secure patient accounts; and communication with patients about research opportunities and research news. However, the purposes of the two registries and the patient groups included in each differ in important ways. The PSC Partners Patient Registry  is for those diagnosed with PSC, and the data collected supports research specifically focusing on PSC and the challenges facing those who live with PSC. The PSC Partners Registry includes patients from more than 50 countries around the world and of any age, including children. The only requirements to participate in the PSC Partners Registry are having a PSC diagnosis and having the ability to log onto the secure internet site to complete the surveys. Patients complete a core clinical survey that asks questions about their clinical history and PSC symptoms. Annual survey updates provide researchers with a record of disease progression or stability. Surveys that cover other areas of PSC research interest, such as health equity or topics related to current projects of PSC Partners, are available periodically. De-identified survey data is shared with PSC Partners-vetted research teams.  The PSC Partners Registry is a powerful tool for understanding the PSC experience in a detailed and focused way, and it supports PSC research by providing the patient perspective to researchers. The American Liver Foundation   Patient Registry  is for those diagnosed with any of more than 100 liver diseases. Adults 18 and over living in the U.S.  may join and participate. The ALF Registry’s stated purpose is “to provide researchers with a better understanding of liver diseases, the impact of treatments and resources for … liver disease, and how … liver disease affects [patients].” ALF may also provide educational resources to patients. A potential outcome and benefit of the ALF Registry’s broader study of liver diseases may be the discovery of commonalities among those diseases. This could lead to research into the cross-purposing of treatments between differing liver diseases. PSC patients are encouraged to join all registries for which they qualify. Each registry has its own purpose, and the more information that patients provide to researchers, the more quickly the researchers and drug developers may discover effective treatments for patients.

In November, a PSC Partners contingent, representing both the U.S. and Canada, attended the 8th PSC Forum and the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting  (TLM) in San Diego. The PSC Forum, held just prior to TLM, is a multi-stakeholder gathering of researchers, regulators, drug developers, and patients organized by UC Berkeley’s The Forum for Collaborative Research. The agenda included discussion of two current PSC Partners research projects: the WIND-PSC Study and the Acute Cholangitis Survey. The survey was developed by a PSC Forum working group co-chaired by PSC Partners and PSC Support U.K. and conducted, in part, through the PSC Partners Patient Registry. Registry Analyst Brian Thorsen presented an early analysis of the survey data (see slides here ). Following the PSC Forum, PSC Partners exhibited during TLM to extend awareness of its programs and research funding to the many research clinicians attending the meeting from around the world. Throughout the four-day event, meetings were held between PSC Partners and collaborators, potential collaborators, and industry partners. Two abstracts/posters that included your (de-identified) patient data were presented at TLM and have been added to the Registry website . To ensure your patient experience is represented in these and future analyses, please be sure to complete the surveys offered to you through the Registry!

PSC Partners opened the Patient Registry for enrollment 10 years ago. However, the process of building a Registry began several years before its 2014 launch. Looking back to 2010, the concept of a patient-driven registry was in the realm of the impossible. The medical world questioned the value of any patient initiative, and the rare disease field remained unexplored. Hungry for treatments for our incurable disease, Registry Director and Founder, Rachel Gomel attended a crowded National Institutes of Health (NIH) meeting in Washington, D.C. There, we first heard the invigorating message that well-organized patient organizations could acquire the power to speed up research by creating their own patient-driven registries. These would be different from registries established by physicians and managed by medical centers. They would be organized by patients, run by patients, and the data would be provided by patients.  We couldn’t believe that patient-driven data could have a place in research. But it was the NIH, the Food and Drug Administration (FDA), clinicians, and researchers themselves who were showing us the way. PSC Partners was then a tiny team of passionate, eager patient and caregiver volunteers who believed that a cure for PSC could be within our reach if we brought awareness of our unmet needs to those positioned to help us stimulate research.  At that large workshop 14 years ago, many speakers shared their perspective on the huge hurdles that prevented rare disease research from moving forward. One story vividly persisted with us through the years and motivated us to keep pursuing the registry initiative. On the podium stood an elderly doctor who shared how she had zealously collected data from patients seriously impacted by a very rare disease. She described the devastating disease and the hours she had spent collecting each patient’s clinical information and recording their data into a registry. And yet, since her retirement, all the data she had painstakingly gathered was collecting dust on a shelf in her office.  No one was interested in the data, and no one wanted to maintain her registry. She burst into an impassioned plea, asking us - patient organizations - to take charge of our patients’ data, since patients would be the best and most responsible stewards of their data and would never allow this valuable information to die. We started our journey not knowing where the Registry would take us.  In 2012, the NIH selected PSC Partners for its pilot rare disease registry program. After two years of work with the NIH, the PSC Partners Patient Registry was launched in 2014. A steady stream of PSC community members came forward to share their medical information. Through the years, we’ve watched the transformation of the medical field and of the patient voice. It is no longer a surprise that the FDA, a U.S. institution that assesses and approves drugs, requires patient involvement in every step of research and drug development. Whereas blood tests, MRIs, and clinical tests were previously the primary objective measures of disease, now the patient voice describing how the patient feels and functions is becoming an equally important consideration. The 2020 “Our Voices Survey”, which so many of you completed and the results of which were shared in a meeting with the FDA, was a step towards highlighting the ways people with PSC feel and function in different phases of disease. If a new drug improves how a patient feels and functions, this improvement matters to the patient.  Researchers and the FDA are looking for ways to quantify how patients feel and function through standardized and disease-specific surveys that measure patient-reported outcomes (PRO). PSC Partners has hired two PRO experts to follow the lengthy scientific process in building a PSC-specific PRO for use in clinical trials. Some of you have participated in focus groups and interviews with these experts; your input is greatly appreciated. Accelerating Drug Development Hearing that the Registry now holds well over 2500 participants, drug developers consider our rare disease as a possible area to research. One memorable example of the impact of the Registry took place in Paris, at the 2018 International Liver Congress organized by the European Association for the Study of the Liver (EASL). A drug developer, curious about our modest patient booth that was surrounded by large, elaborate pharma booths, eagerly listened to our description of the Registry. A few hours later, he returned with his colleagues, who were excited to have discovered a rare disease in their field with easy access to patients. The Registry has pulled patients into the clinical trial space, which previously had been closed to us. Thanks in part to the Registry, PSC Partners has developed relationships with dozens of pharmaceutical and biotech companies. Based on data you provided, studies and posters have been presented in large international hepatology conferences. Pharmaceutical companies are coming to us earlier and earlier in the process of planning their clinical trials. What is your contribution to this process? Through the Registry, you have been telling us why you join clinical trials, what prevents you from joining, and how clinical trials could be improved to make them easy to join. We bring them your suggestions and concerns and ask them to make specific changes. Most have never met a PSC patient. We organize meetings so that those who develop the drugs and run the trials hear our stories and can ask questions. They tell us that meeting patients and understanding their unmet needs have added meaning and urgency to their daily work. And, very importantly, we help them recruit patients from the Registry so they can conduct their clinical trial. Researchers at the PSC Center of the University of California in San Francisco (UCSF) described the Registry data as “a gold mine” and are collaborating with us to publish your data. The publications represent an important milestone: they fill an important gap, as very few academic papers exist on the PSC patients’ voice. Through this collaboration, the patient voice is being translated into scientific, peer-reviewed literature, which we will continue to make available to you as soon as studies are published. Thanks to your participation in the Registry, there is more interest in PSC research, greater awareness of PSC and of patient needs, and better clinical trials. Thank you for responding to our requests. YOU are making an impact! Together, we are creating a world where a PSC diagnosis comes with a cure!

The 20th Anniversary PSC Partners Annual Conference took place in Phoenix, Arizona, on October 18-20, 2024. Throughout the conference weekend, more than 360 attendees were reminded of how far PSC Partners has come as an organization in the past 20 years and of the accelerating progress of PSC research. Evidence of that progress included the second gathering of the International Collaborative Research Network (ICRNetwork), which met prior to the general patient/caregiver conference. The ICRNetwork, launched in June 2022, is a group of key stakeholders, including researchers, clinicians, patients, and industry members, that was formed in response to PSC Partners’ focused efforts to forge a strategic research plan. Many of the ICRN members were speakers for the patient/caregiver sessions and presented up-to-date information on PSC management and research advances. One of the general sessions, “Industry Updates: Ongoing PSC Clinical Trials,” included reports by pharmaceutical representatives about several trials for which the Registry has assisted with trial design and/or recruitment, and in which some of you have participated. Presenters sharing updates about their PSC drug trials included Chemomab Therapeutics, Intercept Pharmaceuticals, Ipsen Biopharmaceuticals, Mirum Pharmaceuticals, and Pliant Therapeutics. You can find more information about their trials on the Clinical Trials page. Chemomab and Pliant gave similar presentations a few weeks later at “The Liver Meeting,” an annual global convening of hepatologists and other experts from around the world, sponsored by the American Association for the Study of Liver Diseases. Each presented late-breaking posters about their trial drug results. You can read the news releases and view the posters at the links below. Chemomab/SPRING trial: News Release Chemomab’s AASLD Poster Pliant/ INTEGRIS-PSC trial:  News Release Pliant's AASLD Poster The conference weekend was filled with enthusiasm as both PSC Partners and its Registry celebrated their respective anniversaries amid a growing sense of hope for the future of PSC research and much improved PSC treatments.

Thanks to your active participation in the Registry, significant progress has been made in PSC research. Four publications using Registry data were released in 2024  - two journal articles and two scientific posters. Topics include improving patient-centered clinical trial development, special considerations of pediatric PSC patients, and better understanding PSC-related fatigue and cholangitis. Click on each title to access the abstract and full article/poster (if available). Journal Article: Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials Using the Registry’s 2021-2023 “Our Voices” survey results, researchers looked at patient priorities in drug development and factors/barriers contributing to clinical trial participation. While 61% of patients with PSC reported interest in trial participation, only 26% have ever been asked. Conversations and education with/from hepatologists and gastroenterologists “are vital to closing the gap between trial interest and participation”. Journal Article: Caregiver-reported symptom burden and preferences for therapeutic goals in pediatric primary sclerosing cholangitis Also drawn from the “Our Voices” survey, this study summarizes responses from 51 pediatric PSC patients and caregivers. The responses reveal “a substantial patient/caregiver-reported symptom burden for children with PSC that impacts quality of life and limits access to clinical trials.” Conference Abstract/Poster: Understanding fatigue experiences through qualitative interviews with adults living with primary sclerosing cholangitis (PSC): An essential first step towards customizing a PSC-specific PROMIS® measure A series of in-depth interviews were conducted via recruitment from Registry participants. Analysis of presence, frequency, severity, and distress related to PSC symptoms led to fatigue emerging as a “prominent and distressing symptom.” These interviews inform development of a symptom assessment tool (survey) for use in clinical trials to measure the effectiveness of a treatment in improving patient-reported outcomes, including fatigue. Conference Abstract/Poster: Defining acute cholangitis as a clinical outcomes endpoint in adults with primary sclerosing cholangitis: Results of a multinational patient survey to develop a patient reported outcomes measure Using the “PSC Flare or Cholangitis Attack Patient Survey” , the Registry Team worked directly with an international team of researchers to characterize patient experiences with cholangitis attacks (acute cholangitis). This survey demonstrated a “broad dynamic range of the frequency and severity of symptoms”, and is a first step in developing a precise definition of acute cholangitis for use in clinical trials as a potential outcome of interest. Many thanks again to the Registry participants who have taken the surveys to make these publications possible! The “PSC Flare or Cholangitis Attack Patient Survey” is currently active in the Registry. Log in and complete this survey today! Data is always de-identified and your responses remain confidential while advancing PSC research.

A huge THANK YOU! to everyone who has kept the PSC Partners Patient Registry an active and constantly growing beacon of the patient voice in PSC research! Thanks to your time and effort, 179 new participants living with PSC  joined the Registry, and 416 surveys  were completed between the Registry’s re-launch in March and August 31. As part of the Registry’s 10th anniversary celebration, a drawing for three $100 gift cards was held for anyone who joined as a new participant, logged in and updated their profile information, and/or completed a survey by August 31. The winners of these gift cards have been randomly selected and contacted via email.  To maintain the confidentiality of Registry participants, the Registry will not be announcing their names. Congratulations to the winners, and thank you to each and every person who participated in the Registry to enter this drawing! Each actively engaged Registry participant and each completed survey provides a wealth of information to address pressing research questions and provide a better understanding of the impact of PSC on people living with the disease. There is always more to do – if you haven’t yet updated your profile information or taken the 2024 Clinical Survey, please log in and complete these tasks today! Stay tuned for two new surveys that will be launching in the coming weeks… Together, we are creating a world where a PSC diagnosis comes with a cure.

A new survey is available in the Registry: the PSC Flare or Cholangitis Attack Patient Survey . Why take a survey about PSC flares/cholangitis? Though those who live with PSC may know what a cholangitis attack feels like, surprisingly, the medical world has not agreed on a definition. That is why researchers need information from adult PSC patients about their experience with PSC flares/cholangitis. We request that patients, not caregivers, take this survey. If you have ever experienced a PSC flare or cholangitis attack, whether your symptoms were mild or severe, please log in today to complete this survey! Note: If you have never experienced a flare, or if you have previously completed this survey via Google Forms (see below), you don’t have to take this survey. If in the first few questions you respond that you took the survey before, or that you’ve never had a flare/cholangitis attack, the survey will stop there. If you are a Registry participant, by taking a couple of minutes to let us know that you have taken the survey already, we will know not to send you reminder emails to complete the survey. If you’re not sure whether you previously took this survey, here is what the start of the survey looks like in Google Forms. If you are not a Patient Registry participant, you are encouraged to join today  and take this survey in the Registry after completing your account setup. If you do not wish to at this time, you can instead complete the PSC Flare or Cholangitis Attack Patient Survey  through Google Forms. No identifying information (such as name, phone number, address, date of birth) is collected. Click on the SINGLE USE SURVEY button above to leave the Patient Registry site and complete the PSC Flare or Cholangitis Attack Patient Survey   outside the Registry . About the Survey The survey will capture your symptoms before, during, and after your most recent PSC flare/cholangitis attack. This information will help characterize the prevalence and frequency of symptoms and the impact of these episodes on people living with PSC.  The survey will also include questions about the treatment and care you received, if sought, during your most recent PSC flare/cholangitis attack. Understanding your symptoms through your first-hand experience and from treatments you received during these episodes will help inform clinical trial design and is an important first step in establishing a better standard of care for those living with PSC. To access the survey, log into the Registry here  and find it on the Dashboard or in the Surveys tab on the left menu. Again,   patients should complete the survey for themselves. Caregivers should not complete it on behalf of their patient. This survey has been developed by PSC Partners  (based in the U.S.) and PSC Support  (based in the U.K.) as part of their work with the PSC Forum Acute Cholangitis Working Group. Thank you for your participation, which is critical in advancing PSC research.  Rachel Gomel, Patient Registry Director Together, we are creating a world where a PSC diagnosis comes with a cure!

Three Recent Announcements from: Pliant, NGM, and Chemomab PSC Partners is encouraged by the initial positive data from the CM-101 Phase 2 SPRING Trial which brings hope to our community that an effective treatment may be on the horizon. Of great importance to our community was the news that there were very few side-effects and no safety issues observed in PSC patients treated with CM-101. The decreases in measures of liver injury and fibrosis, as well as the improvement in itch, suggest a potential for improving liver health and symptoms, hopefully slowing the progression of this life-threatening disease. According to Chemomab Therapeutics, their plan is to discuss the SPRING trial results with the FDA later this year. The goal is to conduct a larger clinical trial that could possibly lead to an approved therapy for people with PSC. Given there are no approved therapies for PSC, it is important to study drugs with unique mechanisms such as CM-101 which targets both inflammation and fibrosis differently than other investigational drugs. We now have announcements from three companies with investigational PSC drugs that may move forward into larger studies with longer treatment.  PSC Partners has been actively engaged with all three companies, supporting these future studies and communicating updates with the PSC patient community. Our team is carefully reviewing the results from these new studies and will continue to share information through our regular channels.  News releases from the sponsors: Bexotegrast  (Pliant Therapeutics) Aldafermin  (NGM Bio) CM-101  (Chemomab) Ricky Safer, MA CEO and Founder, PSC Partners Seeking a Cure Stephen Rossi, PharmD CSO, PSC Partners Seeking a Cure Rachel Gomel, MA Registry Director, PSC Partners Seeking a Cure

On July 15, 2024, Pliant Therapeutics announced positive results from their Phase 2a INTEGRIS-PSC trial for bexotegrast in treatment of PSC. In this randomized controlled study of bexotegrast, the 320 mg arm showed the following key findings (as stated by the sponsor): The 320 mg cohort demonstrated improvement in liver stiffness by transient elastography at Week 24 compared to placebo Statistically significant improvement observed in alkaline phosphatase (ALP) levels over 24 weeks compared to increased levels on placebo Continued improvement in hepatocyte function and bile flow by contrast MRI imaging was observed from Week 12 to Week 24 FDA guidance provided clarity on next steps of PSC development program Bexotegrast at 320 mg was well tolerated up to 40 weeks of treatment with no treatment-related severe or serious adverse events The 320 mg cohort demonstrated improvement in liver stiffness by transient elastography at Week 24 compared to placebo Statistically significant improvement observed in alkaline phosphatase (ALP) levels over 24 weeks compared to increased levels on placebo Continued improvement in hepatocyte function and bile flow by contrast MRI imaging was observed from Week 12 to Week 24 FDA guidance provided clarity on next steps of PSC development program Read the full press release on Pliant’s website . This news comes as a follow-up to the preliminary results at 12 weeks from the same INTEGRIS-PSC trial . This marks the completion of the Phase 2a trial; the Registry will continue to provide updates as more information becomes available. Thank you to everyone who has participated in this trial and all clinical trials! More information about all PSC clinical trials can be found on the PSC Partners Patient Registry website .