Dear Registry Participants (Current and Future),  This year is the 10th anniversary  of the PSC Partners Patient Registry, a perfect time for renewal, for the upgrade you can experience when you log into the Registry. What you will experience is   only the tip of the iceberg . The Registry is fulfilling a PSC Partners dream transformed into the tangible goal of facilitating and speeding up research towards PSC treatments and a cure.  This progress could only take place thanks to all of you participating in the Registry. With your enthusiasm to embark on this journey, you’ve helped open many new paths leading to patient-centered research, advocacy for our unmet needs, and empowerment of our 2,500 voices. Thanks to all 2,500 Registry participants, the Registry is thriving.  A New Registry Experience I will start with the tip of the iceberg, what you will experience when you enter your new space in the Registry and its website. (Please check out the Registry website  for the short video tutorials created to help you log in and navigate through the new features.) The platform has multi-language capabilities for our international participants or for those whose native language is not English. (The Registry platform supports English, Spanish, French, Italian, and German. The surveys are in English at this time but will be translated into these languages in the near future.)  You can now securely share your experience with your physicians and family members. You will be able to upload medical documents, MRIs, school forms, genetic reports, and more. You can track your symptoms and activities and share them with your physicians. The Registry has the capability to keep track of your adherence to medications and adverse events. You can create journal entries to describe the care you are receiving or the symptoms you are experiencing. The Registry website  is regularly updated with news on clinical trials, physicians treating Registry participants (Physician Map), the impact you are having on PSC research, and general news. To access your new Registry home, go to www.pscpartnersregistry.org  and select “Join Now” if you are NOT an existing participant. However, if you are an existing Registry participant, Select “Log In'' from our home page at pscpartnersregistry.org , enter your email address, and click on “Forgot your password?” in order to create a new password. (You must create a new password, even if you remember your previous password.) There are video and written tutorials  on the website to help you. Your Collective Impact Matters The above features are what you can  see. Below are a few of the PSC Partners initiatives that lie beneath the visible tip of the iceberg. They were each enabled by your participation in the Registry.   Your de-identified responses to Registry questions have helped shape the PSC Partners Strategic Research Plan . Over 800 people with PSC responded to Our Voices Survey  and expressed their priorities, which PSC Partners scientists and PSC thought leaders translated and transformed into a research plan. An in-person inaugural meeting brought together the PSC Partners International Collaborative Research Network ( ICRNetwork ) in 2023. Patients, clinicians, researchers, data analysts, and regulators (FDA representatives) formed working groups to discuss your research priorities and ways of implementing them with scientific rigor. Projects are already ongoing. WIND-PSC  was created in response to your research priorities and unmet needs. You let us know that your top research priority was to slow down disease progression.  Gaps were identified, one of which is the absence of dependable and solid PSC biomarkers, which are a requirement to determine whether a PSC drug is effective and can be approved. Over 10 medical centers and 2,000 people with PSC will be participating in this massive initiative. We will ask you for your participation.    Registry data informed us about the PSC symptoms that affect your quality of life, and, in response, a Symptom Assessment Program  (SAP) was created. Two experts interviewed some of you to listen to your description of your PSC symptoms. They are currently translating what they heard from you into validated tools that can be used in clinical trials to objectively measure changes in your symptoms. It is only through your participation and engagement that these tools can be developed and be used to determine the success of a new PSC drug.   Joining a rare disease registry is a powerful act that goes beyond simply providing data. It’s about building community, advocating for change, and actively participating in research. By adding your voices to the Registry, you are powerful partners in the quest for a cure. Patients are moving mountains, and the decision-makers are clearly hearing us. Please know that each email we send you is tied to our collective mission. Please do your very best to respond if you possibly can.  The Registry Team sending you these messages is comprised of three Moms whose children have PSC and two people with close connections to PSC. All of us together are passionately working towards treatments and a cure.  JOIN THE RACE! YOUR JOURNEY MATTERS. Together we are creating a world where a PSC diagnosis comes with a cure! Rachel Gomel  Director, PSC Partners Patient Registry The 3 Unstoppable PSC Moms who Believe in the PSC Community’s Unshakable Power! THE PSC PARTNERS REGISTRY TEAM Rachel Gomel , Director Sharon Nanz , Registry Curator Mary Vyas , Registry Strategist Susan O’Dell , Registry Analyst Brian Thorsen , Registry Webmaster We’re together in the fight, whatever it takes!

On February 4, 2026, the initial study details for Ipsen’s Phase 3 ELASCOPE clinical trial for elafibranor for treatment of PSC  were listed on ClinicalTrials.gov . Study enrollment is anticipated to start around April 2026 and key details of the study design are now available. “PSC Partners is thrilled to see Ipsen move forward with this global Phase III study,” said Ricky Safer, Founder and CEO of PSC Partners. “This is a key step forward in fulfilling our mission of finding a cure for PSC. We are grateful to Ipsen for their commitment to those affected by PSC and to all patients whose prior participation in research have made this milestone study possible.”   “Ipsen is honored to have launched a Phase III clinical study for people living with PSC,” added Jennifer Schranz, Senior Vice President, Global Head of Rare Diseases at Ipsen. “We are deeply committed to advancing potential treatments for rare liver diseases where there is a significant unmet need and few options for patients currently exist.”   Below is a summary of elafibranor and the pivotal global Phase III study: About Elafibranor: Elafibranor is a PPARα/δ agonist taken as an oral pill which can potentially treat PSC by decreasing bile acid synthesis and toxicity, increasing bile acid secretion, and decreasing inflammation. Together, these effects may lessen damage caused by cholestasis in PSC. The Phase 2 study  of elafibranor in PSC (the ELMWOOD trial) showed dose-dependent reductions in ALP and other markers of liver injury and fibrosis, as well as a favorable safety profile. Elafibranor is already approved by regulatory agencies for treatment of primary biliary cholangitis (PBC) as a second-line treatment when UDCA (Urso) is not effective for a patient. Study Details: The ELASCOPE trial anticipates enrolling 350 patients across approximately 200 sites globally. The study will be open to adults with large duct PSC and no history of liver transplant or decompensated cirrhosis (complications associated with advanced disease). Patients will be randomly assigned to receive elafibranor or a placebo.   Concurrent UDCA usage is allowed, along with most other stable ongoing treatments. Medications that are NOT concurrently allowed include, but are not limited to: norucholic acid, fibrates, seladelpar, and glitazones.   Study participation is expected to last up to five years to collect sufficient outcomes data (events associated with disease progression) to allow for effective comparison of the group receiving elafibranor to the placebo/control group.   For more information, including inclusion and exclusion criteria, please visit the study listing on ClinicalTrials.gov . PSC Partners is encouraged by the news of elafibranor advancing to Phase 3, the critical study phase to determine whether a drug will receive market approval by the FDA and other regulatory agencies. We will continue to share more information about this study as it becomes available.

Dear Registry Community, 2025 has been a banner year for the Patient Registry. Between important new surveys, Registry-led publications, external research support, and the launch of Spanish and French translations, the Registry is reaching ever greater heights. At the heart of the Registry’s success, making everything we do possible, is your active participation in the Registry. With 223 new participants in 2025, the Registry now represents over 2,770 people living with PSC from 55 countries. And with 2,083 surveys completed last year alone (more than double the previous year!), your voice is heard loud and clear. Your contributions to research are invaluable, and we will ensure that all the information you have shared will tangibly drive research forward. Looking ahead to 2026, we aim to further expand the Registry’s global reach and to bring the insights made possible by your data into new publications, which will be shared back with the community. You can also look forward to a new survey launching later this year to capture transplant and post-transplant experiences. On behalf of the Registry team, we wish you all good health and good care in 2026. May this year continue to bring us ever closer to a cure for PSC. - Brian Thorsen, Director, PSC Partners Patient Registry Meet our New Assistant Director Assistant Registry Director Fernanda Quevedo  joined the Patient Registry Team in early January, but she is not new to PSC research. Her work experience includes several years as the research program/project manager at the Resnek Family Center for PSC Research at Brigham and Women’s Hospital in Boston, Massachusetts, where she worked with Dr. Joshua Korzenik and his team. Now Available: Clinical Survey 2026 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? New Language Support: Spanish and French We are excited to announce that key parts of the Registry’s internal data platform, including most current surveys, are now available in Spanish and French . In addition, the public website also includes newly translated sections. With these translations, the Registry improves its global access and representation for those with PSC. Cholangiocarcinoma (CCA) Survey Results In Spring 2025, the Registry conducted the PSC and Cholangiocarcinoma (CCA) Patient Survey. This survey collected information on current practices of monitoring for CCA (also known as bile duct cancer), educational resources used by patients, and communication between patients and providers regarding CCA. Results from the survey were presented at AASLD’s The Liver Meeting 2025. 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. The Duct - the latest PSC news, updates and events The Viaduct - Patient Registry news For your privacy, any connection to the Registry will not be recorded in this signup form.

In Spring 2025, the Registry, in collaboration with PSC Support , conducted the PSC and Cholangiocarcinoma (CCA) Patient Survey. This multinational survey collected information on current practices of monitoring for CCA (also known as bile duct cancer), educational resources used by patients, and communication between patients and providers regarding CCA. Results from the survey  were presented at AASLD’s The Liver Meeting 2025 in Washington, DC. With 623 responses in just 7 weeks  between the Registry and PSC Support, it is clear this topic is of high importance to the community. Thank you to everyone who participated in this survey! Background: CCA Risk and Surveillance Guidelines People living with PSC are at a 400-fold higher risk for developing CCA than the general population: between 9% and 20% of people with PSC will develop CCA at some point in their lifetime. Even after liver transplant, CCA risk remains elevated, in part due to the chance of developing recurrent PSC. Unlike other liver cancers, CCA is not associated with the severity of liver fibrosis and disease and can happen at any time point after diagnosis. Therefore, ongoing CCA surveillance testing and early detection is an important part of patient care and may improve clinical outcomes. Early detection of CCA can lead to more treatment options, including potentially transplant, and a quicker connection to important support for cancer treatment. AASLD and EASL guidelines* recommend annual surveillance for CCA through MRCP (MRI of the liver, bile ducts, and pancreas) or ultrasound imaging. AASLD further specifies MRCP over ultrasound when possible. Doctors may also order blood tests for CA 19-9, a protein that can be elevated in the presence of CCA. The guidance does not make a recommendation for or against CA 19-9 testing, as the test has somewhat limited diagnostic power. More frequent follow-up imaging is recommended in cases of suspected (potential, but not confirmed), CCA. Through the International Collaborative Research Network, PSC Partners is supporting leading researchers who are working to develop and validate a new blood test for CCA. This test may allow for earlier, less invasive, and more accurate detection of CCA in PSC patients. Read more about the BIOMAP-PSC Project here . Patient-Provider Discussion of CCA Survey results showed that 50.8% of providers proactively discussed CCA risk with their patients. Proactive discussion from providers was strongly associated with patient knowledge on CCA. Overall, only 36% of respondents reported they had enough information on CCA. For patients in the United States, proactive discussion was also associated with adherence to the recommended use of annual MRCP. When CCA is proactively discussed without patient prompting, 56% of patients report adequate CCA knowledge . When healthcare providers have not proactively discussed CCA risk, 15% of PSC patients report adequate CCA knowledge . Healthcare providers in North America were more likely than providers in Europe to proactively discuss CCA. Hepatologists were more likely than gastroenterologists to proactively discuss CCA. Patient Perspectives As CCA is a serious topic but does not affect everyone, preferences on CCA discussion and management can vary greatly. Among survey respondents, 24% brought up significant fear or anxiety regarding CCA, and 5% of patients mentioned not wanting to discuss CCA until it becomes necessary. Here are a few standout quotes from de-identified survey responses: “It should not be underestimated how scary this sword hanging over the head of PSCers is.” “If I haven’t been diagnosed with it I don’t really need to discuss it with anyone. All it causes is anxiety.” “Getting CCA is a constant worry. I used to think it was an instant death sentence, but being a part of [PSC groups], I now realize that that is not necessarily true.” “It's a lingering risk, but it's helpful that my doctors have shown both a proactive approach to detection, and openness to discussing the real risk, but tempered by a calm approach to manage my expectations, and not excessively worry about something that hasn't happened yet.” It’s important to note you can shape the conversation around CCA . While only 68% of US patients reported annual MRCP (a key part of recommended management of CCA risk), you can discuss with your doctor whether it is appropriate for you to receive this imaging. PSC Partners is committed to building additional educational resources for CCA, along with other common issues associated with PSC. For more information about CCA, from education to support for patients and caregivers, please visit the Cholangiocarcinoma Foundation at cholangiocarcinoma.org . * Sources: AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma  (2022); EASL Clinical Practice Guidelines on sclerosing cholangitis  (2022)

In January, PSC Partners welcomed Assistant Registry Director Fernanda Quevedo as the newest member of the Registry team. She has extensive experience in research and research coordination and will be involved broadly in the work of the Registry. Fernanda holds a bachelor’s degree in neuroscience, with a minor in psychology, from the University of Texas at Austin. During her time there, she conducted research in pre-clinical studies of post-traumatic stress disorder (PTSD). More recently, she supported PTSD research as an adherence and supervision coordinator for research at a subsidiary of the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS). Prior to her time at MAPS, Fernanda spent five years working with Dr. Joshua Korzenik in the Crohn’s and Colitis Center and the Resnek Center for PSC at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Korzenik, the centers’ director, is a longtime friend and supporter of PSC Partners and frequently presents at the organization’s events. His involvement introduced Fernanda to the PSC Partners community.  “It was working with PSC Partners where … I was able to see what the community was doing and just how passionate people were about getting answers,” said Fernanda. “When I would meet with Ricky Safer [PSC Partners founder and CEO] and Rachel Gomel [Registry founder and advisor], I could really see how dedicated they were to not only finding answers for themselves, but also just finding better ways to support the PSC community.” As she looks forward, Fernanda hopes her efforts will help strengthen the work that’s already being done by PSC Partners, and she affirms that “we are relying on the community to express what the needs are.” She is focused on advancing high-quality research and expanding collaborative partnerships. Fernanda grew up in El Paso, Texas, and has returned to the general area, where she works remotely. Newly married, she and her husband Mat enjoy hiking with their pup. She has “many a hobby,” including baking, ceramics, and making wildlife ponds and aquariums.

Dear Registry Participant, Thank you for your participation in the PSC Partners Patient Registry. We are happy to bring the second issue of The VIADUCT to you! Email us at any time with your feedback, input or questions at  registrycoordinator@pscpartners.org . In this issue: From the Registry Director: Moving Research Forward Clinical Trials: Stay informed with Registry Resources | Fred Sabernick Shares His First-Hand Experience Boston: An Emerging Hub for PSC Research Home to the Resnek Family Center for PSC Research & the 2022 PSCP Conference The ROADMAP Initiative: A Map for PSC Patient Engagement Why We Ask You (Over and Over) How You're Feeling: The Value of Quality-of-Life Surveys Your Patient File: The Why & How of Uploading a Confirmation of PSC Diagnosis Registry Data Graphic: Age at PSC Diagnosis From the Registry Director Dear Registry Participants, So much has happened at PSC Partners and in our pandemic world since our first newsletter. We hope that COVID-19 hasn't touched you or your family and that you are managing during this very difficult period. During this time, PSC Partners and the Registry Team have been at work virtually, bringing to life your de-identified data in research studies, moving research forward by assisting drug developers, and forging new collaborations to expedite PSC research. Our hope is to make sure you feel engaged in the PSC activities PSC Partners is involved in. In this issue, we've included details on clinical trials with an interview with Fred Sabernik who shares his thoughts on his experience with clinical trials. You can read about the Patient Reported Outcome Measure (PROM) project, crucial for clinical trials and the drug approval process, and the ROADMAP Initiative (Research Opportunities And Development Meetings to Accelerate Progress). The Registry is integral to the patient- and stakeholder-engagement webinars that PSC Partners has been holding since June. We hope that you are already participating in the ROADMAP webinar series. These are interconnected webinars with recordings you can find on the PSC Partners website. Each topic is divided into two parts: the 100 and 200 series webinars. The 100 series webinars are directed at the patient community, and the 200 series webinars are designed for both patients and the medical community. The aim is to familiarize the patient community with the concepts and research projects that will move the whole PSC community, that is, PSC patients, researchers, clinicians, drug developers, and regulators, towards a collaborative international research network that requires the full engagement of patient representatives. This network will be launched at the PSC Partners Boston Conference next June. We want to emphasize that these webinars are meant to unify the PSC patient community with all stakeholders. This VIADUCT issue includes details on The Resnek Family Center for PSC Research at Brigham & Women's Hospital, Harvard University, in Boston, the location for the next PSC Partners Annual Conference. By being in the Registry and updating your health information, you are already part of the solution. I hope you can join the ROADMAP webinars so that together, we can create a world where a PSC diagnosis comes with a cure. Rachel Gomel, Registry Director Next webinar: August 11, 2021 at 6:00 pm Mountain Time; 8 pm Eastern Time; 10 am Sydney, Australia. Register here . Clinical Trials: Stay Informed with Registry Resources | Fred Sabernick Shares His First-Hand Experience The PSC Partners Registry keeps you informed about clinical trials and research studies, whether you are interested in joining one or are just keeping up with the latest advancements in PSC drug development research. The Registry, nearly 1900 participants strong and growing, is a valuable resource for researchers seeking PSC patients, and connecting patients and researchers is one of its important functions. Finding Clinical Trials As interest in PSC grows, so does the number of clinical trials. Researchers have been requesting help in recruiting PSC patients for trials or studies, and the Registry team contacts those participants who might be eligible by email. This in no way obligates a patient to participate, nor does it guarantee acceptance if one applies. Participants who are interested may then contact the research team directly for more information. Visit the CLINICAL TRIALS page on the Registry website to find:
 a listing of current clinical trials and studies
 a listing of pharmaceutical trial sponsors with whom PSC Partners has worked
 a link that is set up to search the clinicaltrials.gov for all interventional trials for PSC that are recruiting, not-yet recruiting, active but not recruiting, or enrolling by invitation. This site is sponsored by the NIH (National Institutes of Health).
 a link to an interactive map of trials (also from clinicaltrials.gov ) to explore trial and study opportunities by location. News releases and updates about clinical trials are posted in the NEWS section of the Registry site, found under the RESOURCES tab. If you are thinking of applying for a study or trial, be sure to educate yourself. The NIH page linked above contains detailed information that patients may want to read before joining a study (click on ABOUT STUDIES). Inclusion and Exclusion Criteria Every trial or study has inclusion and exclusion criteria for participation. One reason is uniformity of the test group – the fewer differences among participants, the more confident the researchers will be in the interpretation of trial results.
Another reason is safety. Growing children, elderly adults, and pregnant or lactating women are often excluded because the drug was not tested for safety in these populations in the earlier phase of drug development. In addition, comorbidities (other health conditions), organ dysfunction (in an organ other than the one for which the drug is being tested) and other medications that a patient takes may be cause for exclusion. Comorbidities and secondary organ dysfunction may put the patient at risk for adverse effects, or the patient may metabolize a trial drug differently, skewing trial results. The medications that a patient takes may influence the outcome or increase the risk of serious drug interactions. Post-transplant patients are often excluded from trials to prevent interactions with their life-sustaining anti-rejection medications. These exclusion criteria may seem daunting or frustrating, but there has been some new thinking about trial exclusions in recent years. Since many of the trial drugs that come to market are eventually prescribed to the very patients that were excluded from the trials, the FDA has issued guidance encouraging "enrollment practices that would lead to clinical trials that better reflect the population most likely to use the drug if the drug is approved." We may possibly see studies including more heterogeneous populations and new trial models that address the difficulties in conducting rare disease research. Fred Sabernick's First-Hand Experience with Clinical Trials  Why join trials? When asked why he joins trials, Fred said that the main reason he joins a trial is to see if a therapy that he has heard of may help him. He asks himself, "Can I get some improvement?" A close second, is a feeling of exerting some level of control over a disease that, to that point, had been uncontrolled." A third reason, he said, is "giving back, trying to improve the conditions that people are dealing with going forward. I have not yet said no to a clinical trial that's been offered to me." Was Fred concerned about worsening his condition rather than improving it as a result of the clinical trial?
  "It was during the [second] trial," said Fred. "My doctor and I discussed that at some length. I can't say enough about the team that treats me...they treat me with respect; they treat me as an individual; and they recognize the fact that their pat answer is often something I don't accept. Sometimes they have to go a little bit deeper to help me understand some things so that I can actually make an informed decision." What about other risks?
 Occasionally, clinical trials require invasive tests such as biopsies. Some patients elect not to accept the inconvenience and the risk that such tests carry. When asked about this, Fred said that he'd experienced only minor issues throughout his trial experiences. "Medicine is not exact, I get that," he said. "I don't expect [the trial doctors] to be perfect. I expect them to do their best and be prepared for the potentially negative outcomes and be prepared to help me through those. I'm prepared for anything." "I'm willing to accept a lot for a clinical trial ... I've never had any really negative experiences with them." Was Fred concerned about getting a placebo instead of the drug being tested? Many people are hesitant to join a trial because of the chance that they might get placed in the placebo control group and not get the trial drug. Fred suspects that he got a placebo in his first clinical trial, but he never learned whether he did or not. He says he looks at the issue pragmatically and reflects that placebos are "an essential part of the science...It's just part of the 'game.'" How was his communication with the research team?   The most recent trial in which Fred was enrolled was run by one of his own doctors, who suggested the trial to Fred. He found that the communication with the team was excellent, and they took his needs and convenience into account. "I discussed side effects and possible conditions pretty much on a weekly basis," he said, "They actually accommodated me [and switched my treatment locations] to a suburban site pretty close to my house." What would prevent Fred from joining a trial?
 Fred gave several reasons why he might not join a trial, "If I didn't think that it would have any benefit for me, then I don't know that I would join the trial," he said. "If I had [a less flexible job], that would certainly be a concern ... If the trial was not well-run ... I consider my time valuable." He said that video clinic visits and local lab draws make a trial more appealing. "Much of what is required to be done in clinic can be done virtually." Closing thoughts from Fred
: Choosing to join a trial is an individual decision. "Weigh the risks and benefits to you," said Fred. "But don't forget that you're also helping out your community, and that's not a responsibility to take lightly. We're not a huge patient population, and if we're going to get effective treatments or a cure, it's going to be through clinical trials." "You get what you give, and in this case, I am happy I am able to give, and I am willing to give." "Be informed. Learn the pros and cons and then make your decision. But don't be scared. Most of the trials that we [are offered] are past the safety testing stage." "I am pragmatically realistic about the trial itself. I don't expect miracles. I expect process. That's what a trial is all about. It's about process. If something is found that can help my condition... And if not, maybe it can help somebody else, and if it can't, well, then that's one thing we've ruled out." After a pause, Fred said, "Joining a trial is a conscious, balanced act of self-interest." But those of us who know and have worked with Fred at PSC Partners know that his definition of "self" includes all PSCers. Boston: An Emerging Hub for PSC Research In June 2022, PSC Partners will be holding its patient/caregiver conference in Boston, Massachusetts, a city that has gained special meaning for the PSC community with the recent establishment of the Resnek Family Center for PSC Research, a unique PSC-focused research center in the United States. The Resnek Center is part of Harvard's Brigham and Women's Hospital (BWH) and was established with a generous gift from Barbara and Frank Resnek, who have a family member with PSC. When the Resneks were searching for information about PSC treatments, they became discouraged by the limited treatment options available – until they talked to Dr. Joshua Korzenik and his research team at Harvard University. Dr. Korzenik, a member of the PSC Partners Scientific/Medical Advisory Committee, is the director of Harvard's Brigham and Women's Hospital Crohn's and Colitis Center and an assistant professor at Harvard Medical School. Dr. Korzenik is a thought leader in inflammatory bowel disease (IBD) research, and his leading-edge work gave the Resneks hope that his team could tackle PSC with the same innovative approach.BWH announced the launch of the Resnek Family Center in November 2019, with Dr. Korzenik at the helm as director. He continues as director of the Crohn's and Colitis Center as well - a natural pairing of research interests, since about three-quarters of PSC patients also have IBD. The Resnek Family Center's primary goal is to develop PSC therapies, and its vision includes establishing "a robust research pipeline" for those therapies. Current areas of investigation include genes, viruses, bacteria, metabolites, vascular causes, and environmental triggers. The Center's team of clinical investigators and scientists have expertise in gastroenterology, neuroscience, immunology, pathology, and translational medicine. Their goal is "to improve understanding and diagnosis of PSC, build an expansive collection of tissue samples to analyze the disease, and identify existing treatments that could work for PSC." Dr. Korzenik, principal investigator of an ongoing PSC dietary study, among many other PSC studies, is a Harvard alumnus, earning his bachelor's there before completing his medical degree from Albert Einstein College of Medicine in the Bronx, New York. His residency was at Beth Israel Deaconess Hospital, and he completed his fellowship in gastroenterology and clinical epidemiology at Yale University School of Medicine Hospital. He has authored or co-authored numerous scientific papers and has earned awards for his compassionate care as a clinician. Dr. Korzenik, along with Dr. Dan Pratt of Harvard Medical School and Massachusetts General Hospital (MGH), will be hosting the PSC Partners annual conference June 2-5, 2022, in Boston. Dr. Pratt is an assistant professor of medicine at Harvard and serves MGH as clinical director of liver transplantation and director of the Autoimmune and Cholestatic Liver Center. Speakers will include experts from both institutions. More details about the conference and related hotel arrangements will be released in the coming months. Watch for announcements on the PSC Partners main website and social media pages, as well as in mailings from the Registry and PSC Partners. If you haven't joined the PSC Partners mailing list, you can do so at www.pscpartners.org . One of Boston's more aspirational nicknames is "The Hub of the Universe" – or simply, "The Hub," a name coined by 19th-century poet and physician Oliver Wendall Holmes in a humorous article. When it comes to PSC research, however, the aspiration is quickly becoming a realization. Join us in "The Hub" next year! The ROADMAP Initiative: A Map for PSC Patient Engagement With the goal of expanding the patient role in research and drug development, PSC Partners has developed the ROADMAP initiative, a map towards more effective patient engagement. "ROADMAP" is an acronym for "Research Objectives and Development Meetings to Accelerate Progress," and the initiative aims to build a foundation of knowledge and collaboration in preparation for the next PSC Partners annual conference, June 2-5, 2022. ROADMAP meetings, which are online in webinar and discussion format, bring everyone – patients, researchers, clinicians, and drug developers – together at the same table. The ROADMAP initiative includes: Educating the patient community on research tools and developments Expanding the researcher base and strengthening multi-stakeholder communication Creating opportunities for researchers and clinicians to engage in meaningful discussions with an informed patient community PSC patients have much to offer researchers. They are the ones who can best describe their symptoms and quality of life; they know the endpoints and outcomes that would mean the most to them; they bring their trusted relationships with medical providers; and they bring a sense of urgency that only a patient truly understands. Each of the main topics has at least two webinars/discussions, including a "101" session that focuses on the PSC community and a "201" session that includes all stakeholder groups. The first two webinars addressed the topic of a PSC-specific "patient-reported outcome measure" (PROM) and its importance to PSC research. Another article in this newsletter explains PROMs more fully, and you can watch recordings of these two webinars at ROADMAP Initiative 101 and ROADMAP Initiative 201 (live discussion portions are not included for privacy reasons). Past ROADMAP webinars can be found here . It's an exciting time for the PSC community as the ROADMAP initiative maps out a promising new path for multi-stakeholder collaboration. The June 2022 conference, scheduled to be in person, will have an international collaborative component as it brings together the top international PSC researchers and clinicians. However, for this initiative to be successful, YOUR help is needed! By attending the ROADMAP meetings, you will learn about the latest in PSC research and you will have the opportunity to share your valuable experiences, which is so helpful to researchers. Visit the PSC Partners website at pscpartners.org to learn about the ROADMAP initiative and upcoming webinars, the next of which is August 11, 2021, at 6 p.m. Mountain Time. The topic is "The Research Landscape: Now and Into the Future - Five Concepts in PSC." We hope you'll join in regardless of whether you plan to attend next June's conference in Boston. Your participation is valued, and all are welcome and encouraged to take part. Get on board - this train is going places! Why We Ask You (Over and Over) How You're Feeling: The Value of Quality-of-Life Surveys While blood and imaging tests play a big role in the study of a rare disease like PSC, researchers and clinicians are showing increased interest in the patient perspective of living with their disease. Such information about living with PSC can be obtained only from patients themselves. When a patient reports on their own health without any input from a doctor or other expert by a clinician or other expert, this information is referred to as a "Patient-Reported Outcome," or "PRO." When such information is collected in a systematic way through a survey that is rigorously tested and validated, the resulting tool is called a "PROM," or "Patient-Reported Outcome Measure." Why are PROMs important? In the research and clinical-trial setting, the inclusion of PROs, as measured by PROMs, can steer the direction of research priorities and help set clinical trial endpoints that matter to the patients. For example, with a robust PROM, decreased itching or improved energy levels may serve as clinical-trial endpoints. In fact, the U.S. Food and Drug Administration (FDA) now expects researchers and industry to incorporate PROMs into clinical trials and have published guidance documents to ensure these PRO tools are acceptable. These efforts aim to ensure patient-focused drug development. There is an urgent need for a validated, PSC-specific PROM, developed with PSC patient input that can be incorporated in all the phases of the PROM development. PSC Partners, along with experts in the field, is in the process of developing a PSC-specific PROM. The Registry collects patient-reported outcomes through surveys such as Our Voices Survey and the SF-36 Survey, the latter of which was developed by quality-of-life experts. SF-36 is a general survey that measures a patient's quality of life and is widely used across an array of health conditions. This survey takes approximately five minutes to complete. It is a validated quality-of-life survey and provides important information. Although it is not PSC-specific and therefore cannot be used to support clinical-trials, by taking the SF-36 Survey regularly, you will be contributing data to research and helping experts to develop a PSC-specific PROM. A participant can use the SF-36 Survey to document their own quality-of-life changes over time. The second quality-of-life survey that Registry participants are asked to complete is the Our Voices Survey, which was created last year in preparation for the PSC Partners October 2020 Patient-Focused Drug Development virtual meeting with the FDA. PSC patients and caregivers spoke about their PSC experience to FDA officials, researchers, clinicians, and drug-developers. Over 800 PSC patients completed the Our Voices Survey for the meeting, and many new registry participants have completed the survey since then. De-identified data informs PROM experts and researchers on what matters most to PSC patients. A quality-of-life survey has the most value when it is updated regularly to create a record of changes over time. Therefore, we will remind you to update the Registry surveys annually – or when significant changes occur in your health status. A small time investment keeps Registry files current and helps researchers develop trials and studies that accurately address the needs of the PSC community. PSC Partners hosted two webinars to address the topic of PSC-specific PROMs as part of the recently launched ROADMAP initiative. To watch recordings of these two webinars, please go to ROADMAP Initiative 101 and ROADMAP Initiative 201 . Visit the ROADMAP page at the PSC Partners website to learn about this initiative and upcoming webinars. Your Registry File: The Why & How of Uploading a Confirmation of PSC Diagnosis A very important piece of your Registry file is your confirmation of PSC diagnosis in the form of an uploaded medical document. This is a very easy process. Each of you who has access to such a record is asked to upload it to your registry file account. If you don't have one, please request one at your next doctor's visit and add it to your existing Registry file. Why is the confirmation needed? It is reviewed to verify with certainty that registry data represents patients with PSC. Researchers have requested that we do this. We do NOT share the document outside the Registry; it is for internal verification only. Please take a moment to log in to your registry account at PSCPartnersRegistry.org and see if you have provided this. If you have, it will be listed on your profile dashboard in the Medical Records section. What can serve as a confirmation of diagnosis? Any MRCP, ERCP, or doctor's report that has your name listed and states that you have or had PSC. The date does not matter; it can be an older document or a recent one. What format? The file can be -
 a screenshot of a document
 a photograph of a document
 a scan of a document
 a document downloaded from an online health portal To upload the document to the Registry, save your document image or file on your device. Log into the registry, click on the "Add Medical Records" in the attachment section of your profile dashboard, and upload your document file. While you are welcome to upload multiple documents and use the Registry as a safe place to store your test results, one confirmation document is all that is requested.If you need more help, please email the Registry team at registrycoordinator@pscpartners.org . Thank you for your help in ensuring the accuracy of the Patient Registry! Don't forget that Registry participants can log into the Registry, click on the VIEW DATA tab, and explore the de-identified data at any time. For example, above we show the reported age at PSC diagnosis. Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2021 PSC Partners Seeking a Cure

Welcome! In this issue: • From the Registry Director • Profile: Dr. Frank Anania of the FDA • Your Registry Data at Work • PSC Partners Poster Presentation: AASLD Liver Meeting, Nov. 2021 • Three Clinical Trials Currently Recruiting • Three Minutes with Frank Sasinowski • AASLD Patient Track Recap • Update on the ROADMAP Initiative From the Registry Director   Dear Registry Participant, The holidays are here and, once again, COVID-19 is affecting our lives in many different ways. Yet, the activity level hasn’t changed in the Registry. Day after day, we welcome new people to the Registry community. We celebrate each new participant and are grateful to each of you for understanding the importance of patient participation in research. We have passed the 2,000 mark! In this issue, we try to highlight the many new doors your de-identified data has opened. We also show how you’ve helped stimulate and speed up PSC research. We introduce to you one of the regulatory decision-makers, the FDA’s Dr. Frank Anania who assesses the safety and efficacy of new drugs for liver diseases including PSC. We hope that soon he will have plenty of PSC treatments to review! We provide you an example of how your data, featured during a large international hepatology poster session, serves as an effective tool for bringing PSC awareness of this community’s readiness to engage in research. We feature three clinical trials that are actively recruiting PSC patients and share a clip from one of our favorite speakers, Frank Sasinowski, from his keynote speech for the last ROADMAP webinar. We hope this short clip will inspire you to watch the recording of his whole presentation as well as those of previous ROADMAP webinars. By being in the Registry and updating your health information, you are already part of the solution. I hope you can join the ROADMAP webinars so that, together, we can create a world where a PSC diagnosis comes with a cure. Wishing you a Merry Christmas, happy holidays, and an uneventful 2022 filled with good news and hope, Rachel Gomel, Director, PSC Partners Patient Registry Profile: Dr. Frank Anania of the FDA Dr. Anania is one of the decision makers in PSC drug approval at the FDA. We invited Dr. Anania to tell us about himself and about the state of PSC drug development. It is our hope that  some of the treatments currently being studied in clinical trials will be successful. Dr. Anania wrote to the PSC Partners Patient Registry team in response to our interview request. He has been with the FDA for three years and currently serves as the deputy director of the newly created Division of Hepatology and Nutrition (DHN) under the leadership of Dr. Joseph Toerner, a regulatory expert on drug safety. Dr. Anania has been a clinician, professor, and biomedical researcher at Johns Hopkins, the University of Maryland, and, most recently, Emory University, where he conducted research on the mechanisms leading to hepatic fibrosis, specifically NASH. In his career as hepatologist, he writes that he treated many PSC patients and that he is “keenly aware” of the devastating nature of PSC, "a disease whose pathogenesis is little known." He recognizes the serious unmet needs of PSC patients. Dr. Anania writes that he is personally committed to the development of drugs for all chronic liver diseases, with a special attention to PSC, “in no small part due to [PSC’s] potentially devastating complications and because of the youthful population PSC often afflicts.” He stresses the importance of conducting basic research in finding effective treatments for PSC and recognizes the challenges presented by knowledge gaps in key areas such as the causes and mechanisms of PSC, genetic risk factors, the role of the gut microbiome, and more. Like PSC researchers and the PSC Partners team, Dr. Anania believes that discovering such information would improve clinical trial design and help identify optimal endpoints* in determining the effectiveness of a drug being trialed for PSC. PSC Partners, in collaboration with existing clinical registries, is actively in pursuit of solid endpoints. A natural history study project is in the active planning phase and will be the topic of the fourth phase of the ROADMAP webinar series. We thank Dr. Anania for connecting with the PSC Partners Patient Registry team. *A clinical endpoint is an outcome that represents direct clinical benefit, such as survival, decreased pain, or the absence of disease. A primary endpoint refers to the main result in a clinical trial that is measured at the end of a study to see if a given treatment worked. A surrogate endpoint is an indicator or sign used in place of another to tell if a treatment works. Surrogate endpoints include an improved symptom or lower biomarker levels. They may be used instead of stronger indicators, such as longer survival or improved quality of life, because the results of the trial can be measured sooner. Your Registry Data at Work You may be asking yourself what happens to your Registry data. You’ve completed surveys in the Registry; your responses have been reviewed; you’ve received acknowledgements for your valued participation; and, when you’re a possible match, you may have received our message letting you know that you may be a candidate for a clinical trial. However, that’s only what you see. What you don’t see is that your de-identified information travels far and in many directions. It is being used for studies or to search for candidates who could be a match for an upcoming clinical trial. Your accessibility and the large number of registry participants allow us to pursue new studies and help researchers with their PSC studies. 2000+ Registry participants empower PSC Partners to get involved at the earliest stages of PSC drug development. In the past few years, drug developers have expressed excitement about the large number of PSC patients who are committed to providing data to PSC research. You give these researchers a powerful message by joining the Registry. The pharmaceutical companies and researchers come to us, confident that we can help them. The FDA's requirement that drug developers involve patients throughout the drug-development process underscores the value of our community's input. Our recommendations are always welcomed and discussed with us, and many are implemented. In the process, we inform researchers of the challenges patients might face at each step of the trial. Our team goes over clinical trial protocols with a fine tooth-comb even though they have already received the scrutiny of regulators and clinical-trial experts. But, ultimately, the true patient experts are those affected by PSC, i.e. the potential clinical-trial participants who live with PSC day after day. Using our patient lens, we review the trial materials, ask questions, and suggest changes. We ask researchers questions like, “How will the patient feel about going to the hospital for injections eight times a month? Can some of the injections be given at the patient’s home?” The requested changes are implemented when possible. We call attention to ways patients can be protected: “Will a twelve-year-old feel emotionally drained with a two-hour interview for this study and in the absence of a parent?” We suggest that they split the interview. We recommend that the child’s parent be present to make sure the researcher is alerted if the interview becomes too emotionally draining for the child. We make suggestions on the language used to address patients: “In your communications with trial participants, could you avoid referring to PSC patients as ‘subjects,’ a dehumanizing term?” We point to ways of making the trial worthwhile to the patient: “It appears that the patients in the trial would be experiencing at least some PSC symptoms. It would mean sacrificing work and family time with a 25% chance of receiving a placebo and not even trying the drug. Would you consider adding an extension study to introduce the drug to patients who took the placebo for four months?” We make requests to ensure that patients are supported in every possible way: “If special care is required with a rare drug-induced event, will the patient’s physicians be informed and involved, and do you have any model of compensation for lost time resulting from an adverse event?” With the increase in clinical trials for PSC, we are involved in recruiting Registry participants to clinical trials and studies. One of the major obstacles drug developers face in deciding to study a rare disease such as PSC is the uncertainty of finding enough patients to fill their trial. The Registry reduces their reluctance. In response to the Registry team’s research requests, you have responded in large numbers: When asked to participate in a quality-of-life study attached to a clinical trial, 100 applications were submitted overnight. When your responses were sought in preparation for the PFDD meeting with the FDA, over 400 of you answered the call. You gave the same enthusiastic response to an invitation to participate in the Brigham and Women's Hospital nutrition study (DINER), which confirmed the PSC community’s enthusiasm to participate in research. A study on the impact of PSC on pregnancy became a community endeavor. Mothers with PSC who are in the Registry not only responded in large numbers but agreed to invite female family members to serve as controls for the study. The study was quickly populated, and the researchers rapidly gathered the data they needed. The stronger the response, the more we convince researchers that PSC, though rare, has a patient group that will be easy to locate. This is a critical time in PSC research. PSC Partners and international patient organizations, the FDA and international regulators, researchers, clinicians, and drug developers are working together to find biomarkers that can gauge the success or failure of a clinical trial conducted for PSC. As a Registry participant, your role is central to the success of these endeavors. Every step of the way, we must appear in large numbers to show that PSC patients have numerous and very serious unmet needs. The Registry Team is grateful for your responsiveness and for your commitment to find solutions for PSC. Together, we are creating a world where a PSC diagnosis comes with a cure. PSC Partners Presents Data at the 2021 AASLD Meeting Each year, the American Association for the Study of Liver Diseases (AASLD) holds The Liver Meeting, a conference that typically draws over 10,000 clinicians, researchers, drug developers, drug regulators, and patient representatives from around the world. During this year’s virtual meeting, PSC Partners Director of Research Strategy Ruth-Anne Pai, PhD, presented a poster that highlighted the findings of the October 2020 Patient-Focused Drug Development (PFDD) Forum on PSC. The Our Voices survey in the Registry served to guide the PFDD event with the FDA. The poster and poster abstract are available on the Impact page of the Registry website and conclude that: Findings from the Our Voices survey informed the development of the externally-led PFDD Forum for PSC and highlight the need for a more robust, validated Patient Reported Outcome Measure (PROM) for PSC. Overall, our results demonstrate the willingness of the PSC patient community to share experiences and guide the development of PROMs, which requires further perspective and expertise from the PSC research community. Your Registry data is important! It is analyzed and presented to PSC experts and researchers, who listen and learn from your patient experience and perspective. Your participation makes a difference! Three PSC Clinical Trials Currently Recruiting The COVID-19 pandemic has challenged researchers and posed problems in conducting clinical trials and studies. Despite the pandemic, PSC research continues and in fact, exciting studies with innovative patient-friendly protocols are currently underway. Below are three trials that are currently recruiting. VISTAS: a pruritus drug trial Relentless itching (pruritus) is one of the most troublesome symptoms that some liver patients experience. Mirum Pharmaceuticals, a California company focusing its efforts on the unmet needs of the rare liver disease community, has already received FDA approval for their new drug Livmarli, which treats severe itch in pediatric patients with Alagille syndrome, another rare liver disorder. Mirum is hoping to have the same success in the PSC community for the investigational drug volixibat. Over 20 U.S. center sites are enrolling adult PSC patients with pruritus in Mirum’s “VISTAS” study to determine the efficacy and safety of the drug. The trial is a 32-week, double-blind*, placebo-controlled study. Patients will have the potential option to continue with an open-label extension study in which they continue taking volixibat for up to two years. Mirum is actively recruiting for its clinical trial. If you suffer from pruritus, you may be a candidate for this Phase 2 trial. You can find more information about the Mirum VISTAS study here and here . Mayo Clinic: oral vancomycin trial Oral vancomycin normalizes liver enzymes and improves symptoms in some PSC patients. However, it is not FDA-approved for PSC, and small studies have had mixed results. Mayo Clinic has embarked on a larger Phase 2 trial to test the safety and efficacy of oral vancomycin for PSC. All three Mayo locations - Minnesota, Arizona, and Florida - as well as Arizona State University, are participating in the study. More information about the Mayo vancomycin study is available here . SPRING: an anti-fibrotic drug trial As PSC advances, progressive liver fibrosis leads to cirrhosis. Investigators at Chemomab Therapeutics, a clinical-stage biotech company headquartered in Tel Aviv, Israel, is looking for a treatment to improve fibrosis. On December 2, 2021, the company announced that it will soon expand recruitment for its Phase 2 SPRING trial of its interventional drug CM-101 into the U.S. CM-101 is a first-in-class neutralizing monoclonal antibody † that targets CCL24, a protein found to be overexpressed in fibrotic cells. Preclinical trials have suggested that CCL24 plays an important role in promoting liver fibrosis and inflammation. By targeting and neutralizing this protein, it is hoped that CM-101 will slow fibrosis progression. The SPRING study of CM-101 for use in PSC is already underway in Israel and Europe, and the U.S. FDA has just cleared the drug for trials in the U.S. Chemomab plans to enroll patients at numerous U.S. sites in the near future. The trial is a double-blind, placebo-controlled, 15-week study designed to evaluate the safety and efficacy of CM-101 in patients with PSC. Read more about the Chemomab SPRING study here . These studies have something in common: they need patients to enroll! If you are interested in participating in any of these studies, please click on the links above. Please check the Patient Registry clinical trials page for updates on PSC trials and how to locate trials near you. * A double-blind study is one in which neither the participants nor the researchers know who is receiving a particular treatment. † A neutralizing monoclonal antibody is a type of protein that is made in the laboratory and can bind to certain targets in the body, neutralizing their effect. Three-Minutes with Frank Sasinowski: The Effectiveness of the Patient Voice Frank Sasinowski was the keynote speaker for the most recent PSC Partners ROADMAP webinar. He spoke passionately about the power of the patient voice. Frank Sasinowski combines extensive FDA experience with a compassionate perspective of the patient. Take three minutes to experience his compelling testimonials of the impact of the patient voice in drug approval for rare diseases. Frank concludes this video clip with this statement: "I just want to emphasize, whenever you think you are not important, YOU ARE!" The full video of this ROADMAP meeting is available on demand here . Patients and Advocates Welcomed to the AASLD Liver Meeting The American Association for the Study of Liver Diseases (AASLD) had a robust patient program track at its annual Liver Meeting in November, illustrating the trend towards placing higher value on patient experience. Founded in 1950, the AASLD is the leading organization of scientists and health care professionals studying and treating liver disease, and its annual conference typically attracts over 10,000 attendees. For most of its history, the AASLD has been strictly a professional organization, but in recent years it has enhanced opportunities for patient engagement. This year’s virtual Liver Meeting was the second time that a dedicated patient track was included in the conference programming. Patients were also able to attend most of the professional and scientific sessions if they wished. (PSC Partners has hosted an exhibitor's booth for years. Pictured here from pre-COVID meetings.) The patient programming included both a range of patient-centric topics and curated disease-centric sessions that distilled key information and takeaways from the scientific sessions, posters, and abstracts. The patient track included 18 sessions; those of particular relevance to the PSC community were: How Physician-Patient Partnerships Can Improve Liver Disease Care & Research  •  Making an Impact Where You Are: Patient Voices as a Vehicle for Change  •  Grit, Grace, Gratitude & Resilience: What You Wish Your Doctors Knew About You  •  COVID-19  •  Nutrition 101 for Patients with Chronic Liver Diseases  •  Cirrhosis: Improving Quality through Patient Empowerment  •  Pediatrics and Rare Diseases  •  Autoimmune Liver Disease  •  Community Conversations with the American Liver Foundation, Global Liver Alliance, and others  •  Practice Guidelines Debrief for Patients  •  Patient Debrief: Topline Clinical Research – What this Means for Patients Of special note is that new AASLD clinical practice guidelines for PSC are nearing completion. Dr. Christopher Bowlus, the Registry’s scientific advisor, gave a preliminary report on the work of the AASLD PSC guideline committee. The new guidelines, soon to be formally adopted, will give updated recommendations for clinicians treating patients with PSC. The guidelines encompass testing and/or treatment for PSC, associated IBD, recurrent PSC after transplant, cancer surveillance, and intrahepatic cholangiocarcinoma, as well as transplant criteria. The existing guidelines were published in 2010. The enhanced patient engagement opportunities offered by the AASLD highlight the importance of patient participation. (Though The Liver Meeting was in November, many of the sessions remain online through February 16, 2022, and registration remains open. Patients, caregivers, and advocates can register on the AASLD site for a fee.) Update on the ROADMAP Initiative By now you may be aware of the PSC Partners ROADMAP initiative, a unique webinar series. Designed to expand the patient role in research and drug development, the meetings have afforded an exciting level of increased patient engagement with the professional PSC community. PSC clinicians, researchers, drug developers, and regulatory agencies are all invited to the webinar meetings and attend alongside the patient community. ROADMAP is an acronym for Research Objectives and Development Meetings to Accelerate Progress , and the webinar series kicked off in April with an introductory meeting that painted the big picture of how patient engagement and collaboration could look in PSC research. Since then, six more meetings have been held: two focused on patient symptoms, three on research and the first of two on drug development. The sessions are numbered, and those designated as “101” sessions focus mainly on the PSC community, while those numbered “201” or “301” include all stakeholder groups. The Drug Development 201 meeting, “Our Pursuit of a Cure for PSC: Patient-Focused Drug Development,” will be held on January 11, 2022. Subsequent meetings will focus on natural history studies as a valuable research tool. Each meeting begins with one or more keynote speakers, followed by small group breakout rooms facilitated by one or more PSC experts. Patients have the rare opportunity to ask questions, suggest research topics, and otherwise engage with PSC thought leaders. To enhance understanding and provide additional context, written educational materials and short videos, as well as recordings of the webinar presentations, can be found on the  PSC Partners ROADMAP page. Register here for the January ROADMAP meeting. Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2021 PSC Partners Seeking a Cure

In this issue: •  From the Registry Director • Mini-PFDDs • Patient Registry Video Tour • Help Us Grow & Diversify the Registry! • PSC Partners WIND Natural History Project • ROADMAP Wrap-up • PSC Research: Collaborative Efforts From the Registry Director Dear Registry Participants, Excitement is mounting as we approach the 18th PSC Partners Annual Conference, which is being planned in collaboration with Brigham and Women's and Massachusetts General hospitals (Harvard University). We invite all 2000 of you, Registry participants, to join us. The main conference  will take place June 2nd-5th, and pre-conference events will start on May 2nd. We can promise you an educational and fun community virtual event! Thanks to our sponsors, there is no required conference fee. Conference registration opens soon, and it only takes a couple of minutes to register. Registration for the pre-conference events  is open now. Hope to meet you in one of the virtual community rooms! The Registry Team's aim with this VIADUCT issue is to update you on your most recent impact on PSC research. Your survey responses were at work during the "mini-PFDDs," which were an offshoot of the Patient-Focused Drug Development Meeting (PFDD). These mini meetings were held for pharmaceutical companies conducting clinical trials for PSC and were a demonstration of the power of your voice. We would like you to intimately know your Registry. We therefore prepared a Registry tour on video to help you navigate the treasures that are accessible to you as Registry participants. Who can best report the lived patient experience but the patients themselves? The FDA and European EMA have mandated the integration of the voice of the patient in the drug trial and approval process. We've described PSC Partners' WIND project, which hopefully will fill an important gap. We are actively seeking ways of reaching communities that are underrepresented in the Registry. You may be able to help the Registry Team increase diversity in the Registry. We provide you with actionable suggestions. You may have missed some of the webinars in the ROADMAP series paving the way to the 2022 conference. There is great value in watching the recorded videos to find out how these webinars forged relationships among scientists and patients, and how they served to engage scientists in patient projects. Finally, find out why creating duplicate Registry accounts creates difficulties in curation and why we ask you to avoid starting new accounts if you can't remember your Registry password and/or ID. We are always there to help. Together, we are creating a world where a PSC diagnosis comes with a cure. On behalf of the Registry Team, Rachel Gomel, Director, PSC Partners Patient Registry Your Registry Participation & "Mini-PFDDs" Your participation in the Registry quietly produces impact that may not be readily visible to all. Recently, one important example was the "mini-PFDD" events which PSC Partners has been holding for pharmaceutical companies conducting clinical trials for PSC. In 2020, you were asked to complete the "Our Voices Survey," and PSC Partners used your responses to structure the Making Our Voices Heard meeting with the FDA (Patient-Focused Drug Development meeting). Registry participants and PSC community members, 850 in all, offered most valuable information on the impact of PSC on their lives. They also shared what they most wanted improved in their PSC journey. The PSC Partners planning team, working under the FDA's guidance, very quickly understood the magnitude of this event and its potential. The event was clearly impactful: 1,216 viewers, including pharmaceutical companies, patients, caregivers, and regulators, watched and/or participated in the webinar. FDA representatives who were in the audience wanted us to know that the heart-wrenching PSC stories had moved them to tears throughout the event. Yet it was still too early to know about the specific and unexpected outcomes the PFDD meeting would bring and keeps bringing. The PFDD was six-hours long and comprehensive. To accommodate targeted audiences, the PSC Partners team created short "mini-PFDD" meetings for pharmaceutical companies conducting clinical trials for PSC. We selected sections from the PFDD recording that would be pertinent to each clinical trial and to the audience that was being targeted. Most often, these audiences had not yet met a single PSC patient. So far, PSC Partners has held three mini-PFDD meetings. With Mirum Pharmaceuticals currently conducting a Phase 2 clinical trial for pruritus (itching), patient testimonials describing their bewildering pruritus experience were selected from the PFDD meeting video, and in-person (via Zoom) patient panelists shared with Mirum staff the devastating impact of pruritus on their lives. Later, in November 2021, PSC Partners presented extensive patient feedback from Our Voices Survey at the Mirum Principal Investigator Meeting which took place during the American Association for the Study of Liver Diseases meeting (AASLD). For Pliant Therapeutics, which is conducting a Phase 2 clinical trial with their anti-fibrotic drug , PSC Partners presented different PFDD video clips from the PFDD meeting that focused on the pain and fear patients felt as their disease progressed, and a new panel of patients generously shared their very personal and painful stories with the Pliant staff. The mini-PFDDs provided researchers, staff, and coordinators, most of whom have studied the disease but haven't met real patients, an opportunity to ask the patient panelists questions. Among the multitude of positive comments we have received, the one that meant most to us was, "There wasn't a dry eye in the audience," a statement that provided evidence that PSC had left the textbooks and test tubes, and had come to life for these researchers as the cruel, life-shattering, and devastating disease it can be for so many. The mini-PFDDs have been adding the patient voice to clinical trials. Understanding the patient journey adds flesh and blood to drug development. One researcher said, "After meeting PSC patients, I go to work with a mission. Meeting the patients has added passion to my work." Through Registry newsletters, we hope to convey the impact your participation has on PSC research. When we ask you to complete surveys or let you know that you may be a match for a clinical trial, your responsiveness changes the PSC research landscape, even if it is not immediately visible to you. For a rare disease such as PSC, no matter how rare, a responsive and engaged community is like a magnet to researchers who trust that they will find a large pool of patients to study. Together we are stronger! We are grateful for every one of you. The PSC Voice of the Patient Report Documents the PSC PFDD meeting This recently completed report summarizes input shared by patients living with PSC and their caregivers during the 2020 PFDD and serves as a resource for all those interested in conducting PSC research and clinical trials. The link to the report will be available on the FDA website. This comprehensive document includes an 8-page executive summary, a 54-page meeting report, and 100 appendix pages containing full transcripts of testimony as well as audience comments. Check it out here . PSC Partners is sincerely grateful to all who opened their hearts and courageously shared their very personal, and often painful stories of living with PSC. Patient Registry Video Tour: How to Find Data, Trials, and More in the Registry Website Did you know that Registry participants can view de-identified collective survey data on the Registry website? Or find information about clinical trials? Or access a variety of other resources? This short video illustrates how to navigate the Registry site so that you can access its many features. Most are viewable by all participants, but collective survey results are only available for the surveys that you have completed – a good incentive to complete them all! Join the tour! UPDATE (Jan 2024): This video is out of date. Stay tuned for new information on how to navigate the Registry data, which will be available in the Instructional Videos page! Help us grow and diversify the Registry! PSC Partners launched the Patient Registry eight years ago, and the attention given it by biotech and pharmaceutical companies have fully confirmed its validity and importance. The Registry, with more than 2,000 participants, has earned credibility as stewards of the patient voice. However, your medical team may not have heard about the Registry. You can play an important role in serving as ambassador and spreading the information to your medical team and to others with PSC you may know. Other than increasing numbers, an important Registry goal is to increase participation among underrepresented populations. Our current data would be strengthened by increasing the number of participants of color and ethnicity. Also, though PSC is more common in men, more women than men have joined the Registry. An accurate representation of the PSC patient community is important for trials and studies. YOU can help increase the number of Registry participants by bringing the Registry to your providers' attention so that they can invite their other PSC patients to join. Also, if you are comfortable with others knowing that you are a Registry participant, take opportunities to encourage other PSC patients to join. You can do this individually or on social media in any PSC groups to which you belong (including PSC Partners groups). What are key points worthy of sharing? The Registry is our community's best tool for advancing PSC research. All the patient information is stored in a secure environment that protects privacy. The Registry is HIPAA* and FISMA** compliant (U.S. government standards). All personal data is de-identified before it is shared with researchers. No information that could identify you and your family members leaves the Registry. Registry participants who meet general clinical-trial criteria are contacted by the Registry. The participants can then decide whether they would like to connect with the clinical trial team. Participants can access and update their own information. After completing a survey, participants can see the combined, de-identified data for all survey respondents. Those who participate are making a difference! If you need more information or have questions about advocating for the Registry, please contact registrycoordinator@pscpartners.org . We are working on ways to reach a wider PSC community. Your help is one important way to increase diversity in the Registry. You can find more information in our Registry brochure. * The acronym for Health Insurance Portability and Accountability Act (1996) which was created for the protection of identifiable health information. HIPAA requires the protection and confidential handling of protected health information. ** An acronym for Federal Information Security Management Act is legislation meant to ensure the security of data in the federal government. Annual reviews are conducted to assess the security controls in information systems. WIND: a New PSC Partners Initiative PSC Partners is planning the launch of a major new initiative named "PSC Partners WIND." What is PSC Partners WIND? WIND, or Worldwide Integration of Natural History Databases, is a PSC Partners-led and sponsored initiative that will make valuable patient data available to researchers. This will give them a better understanding of the lived PSC experience. The WIND database will serve as a central location where PSC natural history data is securely shared with PSC Partners and with the broader PSC research community. Medical centers from around the world will be invited to contribute clinician-reported natural history data. Why is the natural history of a disease important? Natural history refers to the usual course of a disease over time. When natural history is captured, patients are followed over time as their PSC progresses. With a patient's consent, important data, such as treatments, complications, and more, can be stored securely in a natural history registry. Natural history studies are crucial to PSC research and will one day enable us to get the right treatment to the right PSC patients at the right time. The main differences between a natural history registry (or database) and a patient registry are the types of data, and how the data is captured. The PSC Partners Patient Registry is a patient-reported registry. A natural history registry includes systematic and regular collection of past or current data from medical records, imaging data, hospitalization records, and lab test results. The systematic capture of these health data over time is key to enabling the completion of natural history studies. For more on the basics of natural history studies, please consider watching (or rewatching) the recording of the ROADMAP Natural History 101 . What are the main objectives of WIND? WIND aims to contribute to development of biomarkers which may be used to demonstrate effectiveness of an investigational drug for PSC; provide external control group data for late-stage clinical trials in lieu of placebo groups; and collect various measures of quality of life simultaneously with physician-reported clinical data. Who is involved in WIND? How can I join? To support drug development, PSC Partners is working with great urgency to establish formal partnerships with academic researchers and institutions, and we will keep PSC Partners Registry participants and the community updated on which sites are ready to enroll patients into the WIND cohort. Enrollment is targeted to start in 2023. Stay tuned! Where can I learn more? If you missed the March 23, 2022, ROADMAP 201 Natural History webinar that featured the introduction of WIND, you can watch the recording .  Also, attend the Annual PSC Partners Conference that will be held virtually June 2-5, 2022, to learn more about the WIND initiative. Visit the WIND page of the PSC Partners website for more details. ROADMAP Wraps Up, Forges New Connections The PSC Partners ROADMAP webinar series wrapped up in March with the announcement of the PSC Partners WIND project. Ten times over twelve months, the PSC patient/caregiver community and medical/research/industry stakeholders came together to learn, exchange ideas, and raise questions that will spark new research studies in the coming years. Launched in April 2021, the ROADMAP initiative's primary goal was to accelerate progress to find therapies and a cure for PSC by: Educating the patient community on the research landscape Broadening the researcher base and strengthening multi-stakeholder communication Creating opportunities for researchers and clinicians to engage in meaningful discussions with an informed patient community In support of that goal, the webinars aimed to build a foundation of knowledge and collaboration leading up to the June 2022 PSC Partners Annual Conference, where next steps will be discussed. Open to patients, researchers, clinicians, and drug developers, the ROADMAP webinars included both educational segments and small-group discussions. The patient community learned about research developments; the PSC researcher base was expanded; and multi-stakeholder communication was strengthened. Four broad areas of learning and discussion were covered: symptoms and patient-reported outcome measures; research; drug development; and natural history studies, in particular the new WIND project. You can find a brief video explaining the ROADMAP initiative on the ROADMAP page of the PSC Partners website, in addition to all ROADMAP webinar recordings and accompanying educational materials. These resources are recommended as context for the upcoming PSC Partners June conference. PSC Research: Collaborative Efforts Collaboration is key for successfully advancing rare disease research. Research partnerships are efficient and effective because they pool expert resources, increase patient reach, and eliminate research duplication. Several exciting, dedicated collaboratives are part of the global PSC research landscape. The International PSC study group (IPSCSG) Founded in Oslo, Norway, in 2010, the IPSCSG membership represents more than 20 countries throughout Europe and North America, as well as Israel, Australia, and Japan. Members come from both basic research and clinical research, and a key aim is to coordinate PSC research projects. Aligning important PSC research topics efficiently among IPSCSG researchers eliminates redundancy and, ideally, enables enrollment of larger patient cohorts into trials and studies. The group currently has several studies underway. The IPSCSG established Common Data Elements (CDEs)* for PSC that are now included in their joint patient databases for patient data. The PSC Partners Patient Registry uses a subset of these CDEs in our Clinical Survey for consistency. In 2016, the PSC Partners annual conference, which was co-hosted by Yale University, was held back-to-back with the first U.S. meeting of the IPSCSG. Several members of the group gave presentations to conference attendees, who also had opportunities to meet informally with IPSCSG members. Joint plenary session with the IPSCSG - June 26, 2016, Yale University The PSC Forum The PSC Forum is part of The Forum for Collaborative Research (The Forum), a public/private partnership that brings together groups of U.S. and European stakeholders interested in specific diseases. These stakeholders include the FDA, EMA (European Medicines Agency), patients/patient advocates, researchers, and industry (pharmaceutical and biotech). Founded in 1997, The Forum was instrumental in finding effective treatments for Hepatitis C and HIV. In 2016, The Forum was approached by PSC Partners and asked to consider the establishment of a PSC-specific group. The steering committee turned its attention to PSC and launched the PSC Forum in 2017. In the PSC Forum working groups and larger meetings, stakeholders wrestle with the issues impeding research and drug development for PSC. Working groups address areas such as PSC research endpoints, clinical trial inclusion/exclusion criteria, and patient databases. Dr. Veronica Miller, director of The Forum and an expert in regulatory science, has become an important partner of PSC Partners, assisting with various projects, including planning and moderating of the 2020 Patient-Led Drug Development forum with the Food and Drug Administration. The Forum is based in Washington, D.C., and is under the auspices of the University of California Berkeley School of Public Health, where Dr. Miller is an adjunct professor. PSC Partners is a sponsor of the PSC Forum. Ricky Safer, CEO of PSC Partners, Rachel Gomel, Director of the PSC Partners Patient Registry, and Martine Walmsley, Chair of Trustees, PSC Support, are the patient representatives serving on the PSC Forum steering committee. The Consortium for Autoimmune Liver Diseases (CALiD) CALiD has a growing membership of researchers and patient advocates throughout North America and Israel. Its members have an interest or expertise in autoimmune liver diseases, including PSC, primary biliary cholangitis (PBC), and autoimmune hepatitis (AIH). Dr. Chris Bowlus of the University of California Davis School of Medicine founded CALiD in 2016. Dr. Bowlus is also co-chair of the PSC Partners Scientific and Medical Advisory Committee and medical advisor for the Patient Registry. CALiD's main mission is to create a coordinated and standardized natural history database combining the efforts of individual institutions. One of CALiD's collaborative projects has been an analysis of over 2,200 PSC patients to compare the proportion of Black patients with PSC at each CALiD center with the Black population in each center's metropolitan area. The purpose was to identify whether PSC is rare in Black populations and to highlight the problem of minority underrepresentation in many prior PSC research studies, most of which are based on white patients of Northern European descent. Results of the 2018 study can be found here . PSC Partners has attended CALiD meetings since the collaborative's inception and has witnessed its significant growth through the years. The growing collaboration among researchers brings hope that that new PSC treatments and an eventual cure are on the horizon. You can read more about each of these groups at the links below. International PSC Study Group The PSC Forum at The Forum for Collaborative Research CALiD *Common Data Elements (CDEs) help provide consistency in the way data is collected, formatted, and described. Complications Caused by Duplicate Registry Accounts Keeping up with one's online accounts is a challenge in today's internet era. It's easy to lose account access due to lost passwords and obsolete email addresses. Perhaps you've even forgotten your Registry password. You might be tempted to create a second Registry account if you have forgotten your login information, but please think twice before doing so. Duplicate accounts skew the research data, as each account is counted as a separate patient, and the curator has to search for duplicates. The Registry team can help get you back into your original account. If you forgot your login info but still have the same email address, please use the retrieval tool on the login page. If you still have trouble, you can email us at registrycoordinator@pscpartners.org and we will help you. If you have changed your email address since you joined the Registry, please log in and update it or email the new address to registrycoordinator@pscpartners.org . It will be updated for you. Your email address needs to be up to date to use the retrieval tool on the login page. Also, your current email address is vital so that the Registry team can reach you with information about your personal account, request health updates, and send you research opportunities when you may qualify. If you already have two accounts, we are manually merging them, preserving all your survey data. Merging files is detailed, time-consuming work, so please help out by maintaining only one account. Thank you! Clinical Trials are Recruiting! Don't forget to check the Registry Clinical Trials page for updates on active clinical trials! The 2022 Annual PSC Partners Conference is Almost Here! The PSC Partners Annual Conference will meet virtually this year, June 2-5, 2022, in collaboration with Dr. Josh Korzenik, Brigham and Women's Hospital, and Dr. Dan Pratt, Massachusetts General Hospital. We are excited to see you in attendance as we bring our community together for important conversations, exciting research updates, and renewed connection via our interactive, virtual platform. Registration opens May 1.   #PSCPConference2022 Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2022 PSC Partners Seeking a Cure

Issue 5 - October 2022 Welcome! In this issue:  • From the Registry Director • The Clinical Trial Landscape in PSC • Current International PSC Research • The ChiLDRen Study • Gilead's PRIMUS Trial Terminated •  Patient-friendly Clinical Trial Design • Highlights of the 2022 International Liver Congress • Meet PSCP's Ruth-Anne Pai, PhD •  Clinical Trials Are Recruiting From the Registry Director Dear Registry Participants, Whether you are a person living with PSC, or the relative, friend, or caregiver of one, you probably never stop searching to understand how research into PSC treatments is progressing.  In this newsletter, you will find a review of PSC Partners’ recent webinar about current trials; highlights of the annual conference session on the international PSC research landscape; information about a current, exciting study for children and young adults; an invitation to submit ideas and concerns about trials that we can take to those conducting clinical trials; and more. You can also explore trial information at your convenience on the Registry website. The Registry team maintains a list of currently enrolling PSC clinical trials and studies on the “Clinical Trials” webpage and provides links to detailed information about them. On the same page, you can find links to more general information, such as a map of trial locations and an explanation of clinical trial “phases.” A demonstration of how to find the trial page and navigate the map resource is included in a short Registry video tour that can be found here (time stamp 3:40). An important function of the Registry is to assist in connecting PSC patients with clinical trials or studies for which they may be eligible. Based on your answers to the patient surveys, you may receive occasional emails with information about a clinical trial that is recruiting PSC patients. PSC Partners encourages all patients to learn as much as possible when making decisions about joining a study or trial. That is why we created a new Registry feature, the “Publications Related to Clinical Trials in PSC” page , located in the Resources section of the website. Here we suggest ways of evaluating studies, articles, and information related to ongoing clinical trials. Regardless of whether you are interested in or eligible for a trial, staying abreast of PSC research progress will keep you informed about new treatments and discoveries. Your engagement and your input about study design and methods is valued. “Together, we are creating a world where a PSC diagnosis comes with a cure!” On behalf of the Registry team, Rachel Gomel, Director, PSC Partners Patient Registry The Clinical Trial Landscape in PSC - Overview of a PSC Partners Webinar One of the recent PSC Partners post-conference webinars brought together the current clinical trial perspectives in PSC. Numerous clinical trial updates were presented at the September 21 event , “The Clinical Trial Landscape in PSC: Current and New Opportunities for Patients.” A panel of experts discussed ongoing PSC studies and clinical trials. The goal of this webinar was to familiarize the PSC community with what clinical trial participation entails, with the different types of clinical trials that are being conducted, and on ways we can advance towards new treatments and the much anticipated cure. Trials/studies presented were: Brigham and Women’s Hospital (DINER nutrition study) Chemomab Therapeutics (SPRING study of novel antifibrotic, anti-inflammatory, biologic drug CM-101) CymaBay Therapeutics (study of Seladelpar for impact on PSC disease progression) Escient Pharmaceuticals (trial of drug EP547 for pruritus) Gilead Sciences (PRIMIS study of Cilofexor for fibrosis) - This trial was terminated after the webinar; see details below. HighTide Therapeutics (study of HTD180 drug, also known as berberine ursodeoxycholate, with anticipated anti-inflammatory, anti-cholestatic, and antifibrotic properties) Mayo Clinic (oral vancomycin trial) Mirum Pharmaceuticals (VISTAS trial of volixibat for pruritus) Pliant Therapeutics (INTEGRIS-PSC trial of the antifibrotic drug PLN-74809) You are invited to watch the recorded presentations and learn about these ongoing or recently completed trials. Current International PSC Research: Updates from the 2022 PSC Partners Conference An update on international PSC research activity was one of the most popular sessions at the June 2022 PSC Partners conference. Conference co-host Dr. Joshua Korzenik  moderated the presentation, titled “International PSC Research: Updates Across Spectrum – From IBD & Fibrosis to Genetics & Environment.” This informative conference session is online and includes the following three presentations and a question-and-answer segment. “Fibrosis and Fibrotic Mechanisms in Primary Sclerosing Cholangitis,” presented by Richard Green, MD, of Northwestern University Feinberg School of Medicine (time stamp: 3:19 ) “The Norwegian PSC Research Center…an Update from Oslo and Bergen,” presented by Tom Hemming Karlsen, MD, PhD, Norwegian PSC Research Center (time stamp: 20:19 ) “PSC and IBD. A Close Relationship. Siblings or Distant Cousins? What We Can Learn from It,” presented by Joshua R. Korzenik, MD, Brigham and Women’s Hospital (time stamp: 38:57 ) The Q&A portion was moderated by Joel Pekow, MD, of University of Chicago Medicine. Kirsten Muri Boberg, MD, PhD, of the Norwegian PSC Research Center, joined Drs. Green and Korzenik to answer questions submitted by conference participants (time stamp: 58:03 ). You are encouraged to check out what’s new in PSC research and find out the ways in which it is gaining momentum towards developing better treatments for people living with PSC. The ChiLDReN Study: an Opportunity for Children and Young Adults with PSC The Childhood Liver Disease Research Network (ChiLDReN) is a collaborative team of medical professionals, patient support organizations, and the National Institutes of Health (NIH). With clinical sites and research laboratories in the U.S., Canada, and the United Kingdom, ChiLDReN sponsors a number of natural history studies focused on rare cholestatic liver diseases, including a new study on PSC in the pediatric and young adult PSC population. “Primary Sclerosing Cholangitis in Children,” is an observational, 10-year prospective natural history study funded by the NIH.* Study investigators are seeking 700 young PSC patients at nine North American sites. Those aged 2 – 25 at time of screening with a diagnosis of either large-duct PSC or small-duct-only PSC may be eligible if they meet the other specific criteria. Those currently taking ursodeoxycholic acid or oral vancomycin for treatment of their PSC may remain on it. The purpose of the ChiLDReN study is to collect medical and other data to learn more about PSC, how it progresses, and identify factors that may cause the disease to progress more quickly; and to ask questions about how PSC symptoms affect a child's life to learn more about its impact on their daily functioning. Also, participants who are seen at one of the clinical sites will be asked to contribute information, DNA, and other specimens. The information and specimens will be available to investigators to carry out approved research aimed at learning more about the possible causes and long-term effects of PSC. Detailed information about the study and participating sites can be found at clinicaltrials.gov , including site locations, the site’s contact person, and their contact information (scroll down to “Locations”). Please contact them directly for specific study information. Given the rarity of PSC in young people, it is imperative that investigators work together across treatment centers in order to have study cohorts that are large enough to draw statistically sound conclusions. PSC Partners is extremely grateful to the investigators working on this study for their collaborative approach to gathering this important data, and to the NIH for funding the study. *through the National Institute of Diabetes and Digestive and Kidney Diseases program (NIDDK) Gilead's PRIMUS trial is terminated early On September 27, 2022, Gilead Sciences announced the early termination of the PRIMUS study, its phase 3 study of the investigational drug Cilofexor. Although there were no reported safety issues, the trial evidence to date did not show that the drug was effective for PSC. The decision to stop the trial was based on the results reached after the first 160 participants had completed Week 96 of the trial. The primary endpoint was improvement of fibrosis measured with a biopsy. Investigators saw no benefit to continuing the trial. You can read the Gilead statement here . This is certainly disappointing news. However, a “failed” trial is not a failure if lessons are learned that prove helpful going forward. Especially when a disease mechanism is unclear, such as in PSC, an unsuccessful trial can provide clarity regarding the disease process. Other times, the trial design may prove faulty even though carefully planned; such mistakes are informative to future trials and may even provide new information about the disease itself. PSC Partners continues its collaboration with Gilead and hopes that they will persist in seeking a treatment for PSC. If you took part in the PRIMUS study, you are deeply appreciated. The research process is lengthy, difficult, and sometimes disappointing; however, without study participants, it would go nowhere. Patients willing to participate in clinical trials are key to the ultimate goal of treatments and a cure for PSC. For more information, please contact Gilead Public Affairs at public_affairs@gilead.com . How can clinical trials become more patient friendly? Your input is needed! PSC Partners frequently communicates with PSC researchers and drug developers about patient-friendly trial design. Too often, the burden of travel, invasive testing, too-stringent inclusion/exclusion criteria, and more, limit the number of patients willing to enroll in a trial, which naturally slows the pace of research. Have you ever participated in a clinical trial? Wanted to but didn’t meet the inclusion criteria? Met the criteria but found the requirements too burdensome or the potential risk too high? We want to hear from you! Some of you may have participated in a trial and had a positive and rewarding experience. We would love to hear from you, too. It would help to know what the trial team did right. Your comments about both positive and negative trial experiences as well as concerns or limitations that may keep you from enrolling in a clinical trial are valued. You can contribute to the patient voice in shaping patient-friendly trials. You can share your thoughts by email at registrycoordinator@pscpartners.org OR, if you prefer to be anonymous, you can fill out this two-question Google Survey . If you email, Sharon or Rachel will be responding to you. Some points you may want to address:                         Considerations about inclusion and exclusion criteria, which are meant to ensure trial safety and uniformity in testing Thoughts on the trial drug Thoughts about frequency and type of testing Logistics such as travel frequency and time spent at the trial site Comments on health impact incurred by the trial Communication quality regarding consent documents, your role in the trial, and/or availability of the trial team to answer questions Compensation for expenses incurred or payment for your time Access to study results Fears, concerns, and/or positive experiences The chart below shows the percentage of Registry Clinical Survey respondents who were currently participating in a clinical trial related to PSC at the time they completed the survey (blue bar) or who had previously participated in a PSC clinical trial or donated a biospecimen for PSC research (red bars). The green bars signify the percentages of respondents who indicated that they are willing to be contacted in the future about PSC trials and biospecimen donation for PSC research. Receiving information about trials and studies does not obligate participants to enroll or donate.  The relatively low figures for current or past participation raise some questions: Are too many patients not a match for clinical trials? Are researchers unable to reach those who could be a match? Are clinical trials not easily accessible to people with PSC? No matter what the reasons are, these figures show that people with PSC are very willing to participate in research. Thank you for taking a few minutes to email us at registrycoordinator@pscpartners.org OR respond to the anonymous Google survey with your comments. The PSC community has been sharing thoughts and concerns through surveys and discussions. PSC Partners brings your de-identified input to the attention of researchers and trial developers when reviewing trial protocols, with the intent of helping them design trials that are as patient friendly as possible. Highlights of the 2022 International Liver Congress PSC Partners Board Member Jesse Kirkpatrick, PhD, has chosen to pursue a career focused on PSC, following a family member's PSC diagnosis. Now a Harvard medical student and postdoctoral researcher at the Massachusetts Institute of Technology, Dr. Kirkpatrick is conducting PSC research with the goal of answering key unsolved questions in PSC. He recently attended the 2022 International Liver CongressTM (ILC), which was hosted in London by the European Association for the Study of the Liver (EASL), and shared a few of the highlights with the Registry team. Dr. Kirkpatrick described the recently updated EASL Clinical Practice Guidelines* on sclerosing cholangitis as “one of the most relevant” topics discussed. The EASL PSC guidelines  were published in the Journal of Hepatology in September 2022 and a brief summary, i ncluding EASL's strong recommendations, can be found here . Dr. Kirkpatrick also noted that the conference included a symposium on bile acids featuring three cholestatic liver disease experts. He particularly highlighted Dr. Binita Kamath’s talk about the work being conducted around ileal bile acid transporter (IBAT) disruption. IBATs are molecules involved in the reabsorption of bile acids from the intestine, and novel drugs targeting IBATs show promise for treating the itch associated with liver disease. “It sounds like relief is coming for PSC patients with pruritus,” he said. A poster about a multinational pruritus study in which PSC Partners participated was presented at the ILC by Dr. Kris Kowdley of Washington State University. PSC Partners CEO Ricky Safer, Registry Director Rachel Gomel, and Medical Liaison Joanne Hatchett are among the co-authors. You can find a link to the poster abstract on the Registry’s new “Publications Related to Clinical Trials” page , which is accessible to both Registry participants and other patients with PSC interested in joining clinical trials. Look under the Mirum trial heading for the link to the 2022 Kowdley article in the Journal of Hepatology . The 6th Biennial Meeting of the International PSC Study Group (IPSCSG) also took place at the 2022 ILC. The IPSCSG’s aim is to coordinate PSC research projects between leading institutions worldwide. Jesse Kirkpatrick is a member of the IPSCSG, as is Ruth-Anne Pai of PSC Partners. Dr. Kirkpatrick is an integral part of PSC Partners’ efforts to expand its global reach through the International Collaborative Research Network initiative and informational webinars featuring international research and advocacy partners. *The American Association for the Study of Liver Diseases (AASLD) has also recently published a PSC Guidance, which can be found here . PLEASE NOTE: While meetings such as the recent EASL ILC are for scientists, professional organizations are increasingly becoming more accessible for patients. If you are interested in following EASL and accessing its scientific publications and online resources, EASL has announced a new patient membership option at a cost of €25 (Euros, about $24 US). Visit their membership page for more information. If you are interested in attending scientific meetings, the AASLD is hosting The Liver Meeting® in Washington, DC, November 4-8, 2022, and registration for patients/caregivers is available for both in-person and virtual attendance at a very reduced rate of $50. Most of the content is aimed at researchers and clinicians, but there is a patient/caregiver track as well. The sessions cover all things liver-related; cholestatic liver disease is a small part of the agenda. Register here . Meet Director of Research Strategy Ruth-Anne Pai, PhD When doctoral candidate Ruth-Anne Pai was matched with PSC Partners as a scientific advisor through the Chan Zuckerberg Initiative’s Rare As One (RAO) project, little did she know that she had found her next professional home. After advising the organization for a few months, Ruth-Anne discovered that PSC Partners was planning to hire a director of research strategy.  “The role aligned so well with what I hoped to do after my PhD [studies] and I was thrilled when offered the opportunity to position my scientific training to support the PSC community,” Ruth-Anne said. She joined the PSC Partners staff in April 2021. A native of eastern Pennsylvania, Ruth-Anne earned a BA in Biological Sciences at Cornell University and a PhD in Immunology from the University of Pennsylvania. Her doctoral dissertation included identification of two new treatments for an idiopathic form of Castleman disease – another rare disease with liver involvement. Her mentor at UPenn, Dr. David Fajgenbaum – himself a Castleman patient – was the keynote speaker at the 2022 PSC Partners annual conference. “I’ve had the amazing honor of working with Ruth-Anne Langan Pai over the years on Castleman’s Disease,” he said in his conference address , “and I’m just so thrilled that she is the research director for PSC Partners doing such important work.” Ruth-Anne’s focus at PSC Partners is on several new initiatives. She has a leadership role in crafting a Strategic Research Plan and launching the International Collaborative Research Network ( ICRNetwork ); and she is integrally involved developing the Worldwide Integration of Natural History Databases ( WIND ) project and a new PSC-specific patient-reported outcome measure (PROM). “Having Ruth-Anne Pai among us has been a game changer!” said Registry Director Rachel Gomel. “She has led the PSC Partners leadership team to embark in patient-driven research and has helped us bring the patient voice to the forefront." Ruth-Anne’s dedication to research was inspired by her ninth-grade biology teacher, who instilled in her “a love for scientific exploration through science fair.” Ruth-Anne developed a specific interest in immunology at Cornell, where she decided to focus on human disease. As a new PhD student at UPenn, Ruth-Anne was offered a lab rotation opportunity working with Dr. Fajgenbaum on Castleman disease research. “Dr. David Fajgenbaum taught me to always remember the needs of the patient community I serve and to work with urgency and purpose every day,” she said. When asked what insights into PSC her background in immunology provides, she replied, “There are many parallels between the work and skills I gained during my PhD [studies], and the research landscape in PSC, from the challenges of studying a heterogeneous rare disease to the importance of utilizing a multiomic approach to study early disease mechanisms.” “At PSC Partners, my ultimate goal is to provide all of the support I possibly can to accelerate the discovery and development of treatments and a cure for PSC,” said Ruth-Anne. “While one aspect of this is to develop key research projects and collaborations, I aim to support the PSC community in any way that leads to improved quality of life and outcomes.” Ruth-Anne Pai presented a poster illustrating PSC Partners' Roadmap Initiative at the CZI Rare As One meeting in June 2022.  As a researcher, Ruth-Anne understands the significance of the PSC Partners Registry. “Participation from the patient and caregiver community is so critical in that it enables the completion of clinical studies and is an incredible resource for PSC researchers,” she said. “We are so grateful to current and future participants in the Registry, who are active and crucial contributors to our quest for a cure for PSC.” Ruth-Anne presently lives near Seattle, Washington, with her husband, where they enjoy trail-hiking and traveling to visit family. Don't forget to check the Registry Clinical Trials page for updates on active clinical trials! Click image or  here to visit the Registry list of PSC ongoing clinical trials. “Together, we are creating a world where a PSC diagnosis comes with a cure!” Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2022 PSC Partners Seeking a Cure

Issue 6 - June 2023 In this issue: From the Registry Director • New CZI Grant Awarded to PSC Partners • Patient Focus Groups Provide Feedback • Oral Vancomycin & Insurance Coverage • European Clinicians Survey Results • Call to Action: What is the Registry Not Asking? • Highlights: Clinical Trials & Studies From the Registry Director Dear Registry Participants, PSC Partners and the PSC Partners Patient Registry are moving at rapid speed through involvement in large international projects; increased patient engagement in producing new patient data through the Registry; and in growing clinical trial participation. Nothing happens in a vacuum. Your involvement, your participation is creating a snowball effect that transcends geographic boundaries. In this issue of the VIADUCT, we bring to you the news of a large grant received by PSC Partners in collaboration with a Toronto multicenter research team that is studying PSC at the cellular level. You will find a report on a survey implemented in the Registry regarding insurance coverage of oral vancomycin. We’ve also reviewed the thought-provoking results from a European study and expand on the impact of the Registry on the PSC research community. You will find an overview of several clinical trials for PSC that are currently enrolling. We need your help as the Registry team plans for a future Clinical Survey update. You’ll find a link to an anonymous Google survey where you can provide your suggestions. What questions aren’t being asked in the Registry surveys that you think should be asked? We cannot emphasize enough the value and the importance of your participation. We wish we were together in person, openly expressing our yearning for a cure. As you quietly complete surveys and participate in trials, we hear your voice loud and clear. Never hesitate to ask us your questions. We’re together in our relentless search for a cure. On behalf of the Registry team, Rachel Gomel, Director, PSC Partners Patient Registry New CZI grant awarded to PSC Partners for Collaborative Research Project In December 2022, PSC Partners was selected for new four-year funding by the Chan Zuckerberg Initiative (CZI) for a unique patient-partnered study to be conducted by PSC Partners and a Toronto multi-center research team. The grant will support a research initiative aimed at advancing understanding of the fundamental biology underlying pediatric PSC and PSC-IBD. This CZI award is truly unique for PSC Partners, as this is the first time that the organization has applied for funding for a scientific proposal as partners with an academic research team.The project is led by two principal investigators (PIs). PSC Partners Canada President and Registry team member, Mary Vyas, will serve as the patient organization PI, and Sonya MacParland, PhD, senior scientist, Ajmera Transplant Centre in Toronto (part of the Canada-wide University Health Network), will be the Canadian research team’s coordinating PI. Members of the team leading this innovative research project include, (L to R), Mary Vyas, President at PSC Partners Canada, Drs. Sonya MacParland, Senior Scientist at UHN's Ajmera Transplant Centre, Amanda Ricciuto staff gastroenterologist at SickKids, and Gary Bader, affiliate scientist at the Princess Margaret Cancer Centre. (Photo: UHN) The project, “Understanding the Cellular Ecosystem of Primary Sclerosing Cholangitis,” will focus on clarifying the cellular mechanisms of pediatric PSC-IBD and identifying potential cellular targets for effective therapies. Up to two million dollars will be awarded for this initiative. This includes a budget for PSC Partners to provide patient-focused input at every step of the project, support participant recruitment, and to oversee knowledge translation to the patient community. Most of the funding will pay for advanced and expensive technology to execute this single-cell research study. The research funds will go to the collaborating Toronto institutions: University of Toronto, The Hospital for Sick Children, University Health Network, Toronto Centre for Liver Disease, Ajmera Transplant Centre, and Mt. Sinai Hospital. Your participation and the large number of participants in the Registry attracted attention to PSC, despite it being such a rare disease, and, in doing so, played a vital role in the granting of this competitive CZI award. When Dr. MacParland first learned of the PSC Partners Patient Registry about five years ago, she became excited about the research possibilities. Having access to the de-identified data of over 2,000 patients supported her decision to focus her research efforts on PSC and led to an exciting relationship between PSC Partners and her team of researchers.  For several years, PSC Partners Canada President Mary Vyas, Registry Director Rachel Gomel, and PSC Partners volunteer Katie Bingham, PhD, have been serving as integrated patient collaborators ¹ on a large-scale PSC study led by Dr. MacParland that compares PSC liver tissue to healthy liver tissue. Click on the video to view a 3-minute interview from 2021 with Dr. Sonya MacParland, whose work focuses on translating the immune biology of the liver into clinical applications - and how the PSC Partners Patient Registry helps advance that goal. “Beyond incorporating the patient perspective in research design, our partners ensure that our work is grounded in the patient experience,” said Dr. MacParland.² The relationship existing between the research team and PSC Partners laid the foundation for the application for the most recent Patient-Partners Collaboration CZI grant by providing evidence of our ability to work well as a collaborative team.³ The award is a major milestone for the PSC patient community. To date, PSC Partners has pursued its mission to drive research to identify treatments and a cure for PSC through the WIND-PSC and PROM initiatives and through awarding seed grants to promising researchers. This is the first time that PSC Partners is a grant recipient for a project in which the patient organization plays a formal collaborative role in a scientific project. PSC Partners' new role of being a grantee, besides being a grantor, represents a momentous change in PSC research. ¹An integrated patient collaborator is the title given by the Canadian Institutes of Health Research. ²As quoted in a UHN press release about the grant award. ³Further details about the CZI “Patient-Partnered Collaborations for Single-Cell Analysis of Rare Inflammatory Pediatric Disease” grant can be found  here . Patient Focus Groups Provide Feedback for WIND-PSC Initiative Last fall, as part of the planning for the WIND-PSC initiative , PSC Partners recruited volunteers to participate in focus groups to discuss existing patient symptom surveys. The volunteers all belong to the Patient Registry and have personal experience with common PSC symptoms, including fatigue, sleep disturbance, cognitive dysfunction (brain fog), itch, abdominal or liver pain, and depression or anxiety. PSC Partners staff members, Medical Liaison Joanne Hatchett, and Research Program manager Sarah Curup Callif, organized the recruitment effort and were encouraged by the number of people who showed interest in participating. “It really reaffirmed that our community is so excited. They want to make a difference. They want to be involved,” Joanne said. Participants represent the U.S. and Canada and were assigned to one of two focus groups. Prior to meeting, each person received copies of various existing symptom surveys to review and compare. Such survey instruments, called Patient Reported Outcome Measures (PROMs), will be used in the WIND-PSC registry to capture participants’ symptoms over time. In November, each focus group met separately via Zoom with qualitative  research expert Donna Evon, PhD, of the University of North Carolina, to begin the process of selecting patient symptom surveys to be included in the WIND-PSC study. The focus groups reviewed, discussed, and compared the various PROMs to determine which they thought best capture and reflect PSC symptoms. They also reflected on the process of administering PROMS and similar surveys. Both Joanne and Sarah were extremely pleased with the quality of the input received. “The people who were there were amazing,” said Joanne. “They were so attentive to the details of what they were looking at, how they felt, and how they expressed their thoughts.” “It helps us move forward with confidence,” said Sarah. The participants’ input will form the basis for a larger, future community and Registry survey that will be submitted for publication and will help make decisions about which existing PROMs to use in the WIND-PSC initiative. “Their impact made a difference, whether it was filling out an interest form, attending a focus group, or even just being aware,” said Sarah, "It really helps us to move forward…it seems like within the PSC community, people are so eager to help and to participate. We are thankful. We just can’t thank them enough!” WIND-PSC  is one of two multi-year projects being developed by PSC Partners International Collaborative Research Network ( ICRNetwork ). The other is the development of an improved PSC-specific PROM that will better inform clinical trial research, a need confirmed by the focus group members. Dr. Evon and Director of the Center for Health Measurement at Duke University Bryce Reeve, PhD, are collaborating with PSC Partners and the ICRNetwork on the PROM project. The WIND-PSC and PROM initiatives are concurrently moving forward. Oral Vancomycin and Insurance Coverage: Data Results From Recent PSC Partners Survey In late February, the Registry launched a short-term survey, “Oral Vancomycin and Insurance,” in which respondents were asked to share their experiences with oral vancomycin and insurance coverage. Emails were sent to all Registry participants who had indicated on their Clinical Survey that they are or were taking vancomycin for PSC, and the survey was promoted on the PSC Partners social media pages. The de-identified data was aggregated and is available for you to view in the Resources/News section of the Registry website .  The purpose of this short-term, focused survey was to provide data to PSC community members who were meeting with lawmakers and others on Rare Disease Day, February 28. This is the reason it was only available for a short period of time. Many thanks to Registry Strategist Mary Vyas for implementing the survey and for the quick turnaround of the data analysis! By launching this survey through the Registry, data integrity, informed consent, and patient privacy in an IRB-approved environment were maintained. Collecting data in the way that the Registry does, with IRB oversight, increases the scientific merit of the data, especially with respect to the ability to publish in a peer-reviewed journal. The PSC Partners Registry team is very grateful to the many community members who have joined the Registry and who respond to calls for participation. Your participation is even more valuable when your Registry account is complete and up to date. If you take oral vancomycin for PSC and did not receive an email invitation to complete the survey, perhaps your Clinical Survey or your email address needs to be updated. Please return regularly to your Registry account and add or update anything that is missing. Check your profile information for accuracy, upload a document confirming your PSC diagnosis if you have not already, and update your Clinical Survey and the SF-36 (quality of life measure) yearly or when you have changes in medical status. Please email registrycoordinator@pscpartners.org if you have any questions, are unable to access your account, or would like help uploading a document. Please do not create a duplicate account – we are happy to help you access and update your original account. European Clinician Survey: PSC Treatment Varies Among Providers Results of a survey published in late 2022 show that there is “substantial variation” among European clinicians in the treatment of PSC and “considerable discrepancies” between practice guidelines and clinical management. PSC researchers from the European Research Network Rare-Liver group (ERN RARE-LIVER) surveyed European hepatologists affiliated with the ERN and/or the International PSC Study Group (IPSCSG) to find out about differences in PSC management and whether clinicians adhered to the clinical practice guidelines set forth by the European Association for the Study of the Liver (EASL). In the full-text research publication , “Survey uncovering variations in the management of primary sclerosing cholangitis across Europe,” the authors state, “There is a scarcity of data that consistently support the use of medical therapy to prevent disease progression and prolong transplant-free survival in PSC.” The researchers believe that identifying the differences in PSC management is essential for optimizing treatment and, therefore, they conducted the survey to “uncover differences in real-life clinical practices.” The study report gives the following summary highlights, as quoted below: Substantial variations in the treatment and monitoring of patients with PSC was seen across Europe. Considerable discrepancies between practice and published guidelines in the management of patients with PSC existed. Despite no robust evidence or clear recommendations, most [European] physicians [surveyed] treated all their patients with UDCA [ursodiol]. Regular screening for cholangiocarcinoma was performed by 90% of physicians. A variety of screening methods were used. In PSC without IBD detected at diagnosis of the bile duct disease, most physicians would repeat colonoscopy on a regular basis. The report also provides details and graphics of their findings. In the table below, a few of the study findings are compared to aggregate PSC Partners Patient Registry data. European Study Report Registry Data UDCA (Ursodiol) 82% of physicians who responded prescribe UDCA either routinely (50%) or selectively (32%) to their PSC patients. 80.6% of survey respondents have taken UDCA at some point.  Oral Vancomycin 16% of physicians who responded treat selected PSC patients with oral vancomycin. 18.5% of survey respondents have taken oral vancomycin for PSC at some point. Colonoscopy 34% of physicians who responded ordered a colonoscopy every 5 years for patients with PSC but no IBD at diagnosis, and another 34% repeated the test within 3-5 years. 27% of physicians only referred patients for repeat colonoscopy if they developed symptoms of IBD. 93% of survey respondents have had one or more colonoscopies, and 68.4% are expecting to have one annually or biannually. Authors of the study conjecture that PSC management may be even more disparate than the study findings, since all respondents belong to the ERN-RARE and/or the IPSCSG and thus are likely to be somewhat more aligned in their clinical practices. They concluded that their results “confirm that existing data and recommendations for clinicians are inadequate for uniform patient management” and proposed that “established international networks and research associations should work to coordinate guideline recommendations in order to generate a better basis for developing clinical trials and to improve the daily management of patients with PSC.” EASL and AASLD practice recommendations In 2022, the U.S. and the European professional hepatology associations each published updated recommendations for the diagnosis and management of PSC. You may wish to review these informative documents. Click on images below to read the EASL guidelines and AASLD guidance. Call to action for all patients and caregivers: What is the Registry not asking? Periodically, the Patient Registry’s main Clinical Survey is updated to include new questions posed by PSC research. Questions that can provide additional insight into the PSC experience are added, and prior survey responses are carried over to maintain continuity. This is the time for you, patients and caregivers, to provide input as new versions of the survey are developed. What is the Registry currently not asking? This Google survey  prompts you to consider areas of possible concern and offers a way to share your ideas on the Registry survey. Your perspective about how PSC impacts you is invaluable and unique. If you would like to provide suggestions, they will be considered very seriously. TO REMIND YOURSELF OF THE QUESTIONS IN THE CURRENT CLINICAL SURVEY: Login  to your Registry account,* go to your PROFILE dashboard, and either: Update the Clinical Survey, if you haven't updated in the past year (click on “Update survey”). OR, if you've already updated your information within the last year, click on "Download Results" next to the survey name to view questions and your responses. While plans for an update to the Clinical Survey are still in the early stages, your input is needed now. The Google survey can be completed here . Thank you in advance for sharing your thoughts and for engaging in shaping PSC research! * Do you need help accessing your account? Just reply to this email ( registrycoordinator@pscpartners.org ) and we will help you. Please do not create a new account!  Highlights: Clinical Trials and Studies An important function of the Registry is to assist in connecting PSC patients with clinical trials or studies for which they may be eligible or simply interested in following, and the Registry team strives to do so through emails, publications, and a dedicated web page. Many PSC trials and studies are underway. Some are highlighted below, and you are encouraged to visit the Registry’s clinical trial  page  often to learn about others.  The ELMWOOD Study - enrolling patients now:  The Elmwood study, sponsored by Ipsen Pharmaceutical, is an interventional study of the drug Elafibranor, a drug originally tested for use in steatohepatitis (NASH) and cardiometabolic conditions. It is now being tested for safety and efficacy in PSC. Study centers are located in the U.S., Canada, and Spain. For full information, including contact information, click  here .  The PACIFIC study - enrolling patients now:   There is an increased interest in researching PSC pruritus (itching), as it is frequently mentioned by patients as one of the most difficult PSC symptoms. The PACIFIC study, sponsored by Escient Pharmaceuticals, is focusing on pruritus and is a phase 2 interventional trial of the drug EP547 for use in PSC. The Escient  website  states that EP547 has a “novel, targeted mechanism of action” and “blocks the activation of itch neurons by all bile acids and bilirubin.” Seven U.S. study locations are located in California, Mississippi, New York, and Texas, and are open to patients with PSC, ages 18 to 80, who have moderate to severe pruritus. Additional information and qualifying criteria can be found  here . The SPRING study - enrolling patients now:  Sponsored by Chemomab Therapeutics, the phase 2a  SPRING study  is an interventional trial that is currently recruiting for 45 study centers in the U.S., U.K., Israel, Germany, and Spain. The Chemomab  website  states, “Chemomab has established strong pre-clinical evidence that demonstrates the potent anti-cholestatic and anti-fibrotic effects of CM-101 in PSC.” CM-101 is a monoclonal antibody delivered by intravenous infusion every three weeks.The web page above includes a video link that explains CM-101’s mechanism of action in PSC. The VISTAS study - enrolling patients now:   Sponsored by Mirum Pharmaceuticals, the VISTAS study is testing their drug volixibat for pruritus. The pediatric version of the drug, Livmarli, was recently  approved  by the FDA for Alagille Syndrome, a rare pediatric bile duct disease. Over 50 trial sites have opened throughout the US, in Canada, Germany, UK, and Israel. All patients are given the opportunity to take the drug. You can find out more about the trial  here . The ItCH-PSC study - enrolling patients now:   The ItCH-PSC study is a basic research study with an aim of understanding more about the frequency, severity, and persistence of itching in patients with PSC. The principal investigator is Dr. Chris Bowlus of UC Davis in Sacramento, and six study centers¹ are participating throughout the U.S. Participants will need to travel to the study center up to three times. Inclusion criteria shared by the researchers state that the study is open to all adult patients with PSC (18 years of age and older) who have not had a liver transplant and who do not have concomitant liver diseases other than IBD and autoimmune hepatitis. There is no experimental drug intervention involved; participants will have blood draws and fill out questionnaires. If you are interested in learning more, please fill out the ItCH-PSC interest form . ¹ItCH-PSC participating study sites are located in the U.S. at UC Davis, Sacramento, University of Colorado, Aurora; Henry Ford University, Michigan, Indiana University, Indianapolis; University of Miami, Massachusetts General Hospital, Boston. If you live near or can travel to one of these sites and are interested in learning more about becoming involved with this study, please complete above interest form. How do you know if you meet the criteria for a trial? Most interventional studies (clinical trials) are listed at ClinicalTrials.gov . Interventional studies are testing a drug, device, procedure, or activity, and both the inclusion and exclusion criteria are posted on the site. For the studies listed above, most have complete details listed on the ClinicalTrials site. Links are embedded above. Every trial or study has inclusion and exclusion criteria for participation. Though patients are sometimes frustrated if they don’t meet the criteria, there are important reasons for these, including the need for uniformity in the test group and, especially, safety. Certain medical conditions might put a patient at greater risk. If you don’t qualify for an interventional trial, you can still help further research by joining other types of studies and by participating fully in the Patient Registry. A strong, “A+” Registry profile has every survey completed; the Clinical Survey and SF-36 Quality-of-Life Survey updated within the last year; an attached medical record confirming that you have PSC, your healthcare provider added to your record, and, of course, complete and accurate contact information. Are you receiving Registry emails about trials? Is your Registry profile information correct? If you received this newsletter via email, congratulations – your email address is up to date! If you accessed this through the Registry website or social media, please check the email address listed on your Registry profile to ensure that it is correct. Whenever the Registry team sends out emails about trial opportunities, about 5-10% of them are returned to us because the email address is no longer valid. Depending upon your answers to the patient surveys in the PSC Partners Patient Registry, you may receive occasional emails with information about clinical trials that are recruiting PSC patients. Have you filled out each survey and kept them up to date? Receiving an email does not obligate you to participate or to contact the researchers. It is for your information. Whether or not you are able or choose to participate personally, you are urged to visit the Registry’s Clinical Trials  page  frequently to learn about the many ongoing research efforts geared towards better treatments for PSC. The research process is lengthy, difficult, and sometimes disappointing; however, without study participants, it would go nowhere. Patients willing to participate in research studies are key to the ultimate goal of treatments and a cure for PSC. On behalf of the PSC community, we thank you for having participated or for planning to participate. Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2023 PSC Partners Seeking a Cure

Issue 7 - Winter 2025 In this issue: From the Registry Director • A New Era • Your Data in Publication - 2024 • Clinical Trial News • Registry Data Presented at TLM • Your Powerful Impact • PSC Partners Registry and Other Registries From the Registry Director Dear Registry Participants, This has been an incredibly fruitful year for the Registry. Between a move to the new and improved Registry platform, several publications making use of Registry data, and the launch of two new surveys, the Registry is more active than ever before! With so much coming out from the Registry, the VIADUCT will be published more frequently next year. I look forward to the Registry continuing this growth in 2025. Be on the lookout for a new 2025 Clinical Survey launching on January 2. If you haven't yet logged into the new platform, or completed the 2024 survey, you've got a few days to get to it before the next survey launches! To best capture changes over time, it’s recommended to wait at least 6 months since completing your last annual survey. You will receive a reminder when it’s the ideal time to take the 2025 Clinical Survey. Thank you for your continued support and engagement with the Registry. By logging in, completing any available surveys, and updating your information when needed, you directly support PSC research and center the patient voice in the path towards a cure for PSC. Kind regards, Rachel Gomel and the Registry Team A New Era for the PSC Partners Registry Community 2024 has been a big year for the PSC Partners Patient Registry, which celebrated the 10th anniversary of its initial opening and the March launch of an upgraded data platform. Click the "READ MORE" button below to learn about the upgraded Registry site. Driving Research: Your Data in Publication - 2024 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. Topics include improving patient-centered clinical trial development, special considerations of pediatric PSC patients, and better understanding PSC-related fatigue and cholangitis. Clinical Trial News Announced at PSC Partners Annual Conference The 20th Anniversary PSC Partners Annual Conference took place in Phoenix, Arizona, on October 18-20, 2024. The "Industry Updates: Ongoing PSC Clinical Trials" general session featured reports by pharmaceutical representatives about several trials. A few weeks later, more late-breaking news came from The Liver Meeting , held in San Diego, California by the American Association for the Study of Liver Diseases (AASLD). Registry Data Presented at PSC Forum and AASLD's The Liver Meeting In November, a PSC Partners contingent, representing both the U.S. and Canada, attended the 8th PSC Forum and the AASLD's The Liver Meeting  (TLM). Two current PSC Partners research projects were discussed at the PSC Forum, and two posters that included your (de-identified) patient data were presented at TLM. Your Powerful Impact 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. From a 2012 pilot program with the NIH to a “gold mine” for PSC research and accelerating drug development, the Registry has grown far beyond what was once thought possible for patient-led research initiatives. PSC Partners Registry and Other Registries: An Example of Different Types of Registries This past July, the American Liver Foundation (ALF) announced the opening of a new patient registry. While similar in function and structure, the ALF has different goals and eligibility requirements compared to the PSC Partners Patient Registry. PSC patients are encouraged to join all registries for which they qualify! Learn more about the new ALF registry and how the two registries differ. Snapshot of Registry Data This word cloud was generated from responses to the "PSC Flare or Cholangitis Attack Patient Survey", currently active in the Registry. If you haven't yet, add your response today! Established in collaboration with the Office of Rare Diseases Research ( ORDR ), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) © 2024 PSC Partners Seeking a Cure

Issue 8 - Spring 2025 In this issue: From the Registry Director • Cholangiocarcinoma (CCA) Survey • WIND-PSC Enrolling Patients • Clinical Trial News • External Studies and Surveys • Symptom Assessment Project • Registry Superstars • Learning from Registry Data From the Registry Director Rachel Gomel (left) and Mary P Vyas (right) Dear Registry Community, Sixteen years have gone by since the PSC Partners Patient Registry was just a lofty idea, a dream I believed could turn into reality. The time has now come for me to pass on the baton to teammate   Mary P Vyas , serving as Registry Strategist to date and involved in numerous PSC Partners initiatives. A Berkeley, M.I.T., and Stanford University graduate and President of PSC Partners Canada, she brings her creativity and action-minded spirit to leading the team as Registry Director. I will continue as Senior Registry Advisor. The Registry is in great hands. We continue to be very excited about the Registry’s move to our new and much-improved home. The new platform holds state-of-the-art features to support research and Registry participants, maintains tight security, and is managed by the PSC Partners Registry team of super experts (each with a connection to PSC) who guard your precious information and turn it into research.   Now that we’ve settled, the Registry Team hopes to receive those of you who haven’t yet made the move to the new Matrix platform. It is an easy task: on the Registry website pscpartnersregistry.org , take the simple steps to log in,* complete the updated 2025 Clinical Survey, and explore the Registry’s new features.   It is crucial that you make this move, that you complete the new surveys and enter your voice into research. We hope to show you the highlights and impact  of your participation. With your enthusiastic participation, PSC research can only flourish.    Together, we are creating a world where a PSC diagnosis comes with a cure! Rachel Gomel, Senior Advisor, PSC Partners Patient Registry *The site supports Chrome, Edge, and Safari browsers. Please note that the first time that you log into the upgraded site, you will have to reset your password using the “Forgot your password?” link on the login page. You will be asked to review and complete a general profile information form. Take the PSC and Cholangiocarcinoma (CCA) Survey A new survey is available in the Registry, focusing on screening and surveillance for bile duct cancer  (cholangiocarcinoma, or CCA) in people living with PSC. Anyone with a PSC diagnosis, including post-transplant, can and are urged to take the survey through the Registry. Log in and complete this survey today! Responses are requested by April 14th. Trailblazing WIND-PSC Study is Enrolling Patients and Adding Study Sites The 5-year prospective study, led by PSC Partners, collects data from enrolled patients to act as a "synthetic placebo" group for a clinical trial. This opens up new pathways to approving treatments for PSC and can reduce the enormous costs associated with clinical trials. Investigational Drug for PSC Advances to Phase 3 Trial Few investigational PSC drugs have, to date, moved forward to a Phase III clinical trial. For a drug to do so, it must first meet initial trial goals surrounding safety, efficacy, and identification of side effects. Chemomab Therapeutics, an Israeli clinical stage biotechnology company, has announced plans to move forward with a Phase III clinical trial of nebokitug (CM-101). The planned Phase III trial will assess changes in the “time-to-first-event” to typical PSC clinical events, such as cholangitis attacks, strictures requiring intervention, portal hypertension, etc.. and will not require liver biopsies. Trial participants will stay on nebokitug until they experience such a clinical event endpoint. PSC Partners issued a statement with more information about the announcement, including the Chemomab press release. Trials and External Surveys in Need of Participants Are you interested in helping to advance PSC research by participating in a trial or completing a survey? Two prospective drug trials are in need of additional U.S. patients. The research team is led by Dr. Josh Korzenik, director of the Crohn's and Colitis Center and director of the Resnek Family Center for Primary Sclerosing Cholangitis Research at Brigham and Women's Hospital. Additionally, two surveys are available for those living with PSC. These surveys are not hosted in the Registry, but are also offered through secure and confidential platforms. Read more about the surveys and – if you haven’t yet – complete them today! Open globally:   PSC and Quality of Healthcare Survey   (University of Miami) For Europeans:   PSC and Diet Survey   (European Reference Network) The Symptom Assessment Project: Building New Endpoints for Clinical Trials Quotes from interviews of patients living with PSC describing their fatigue, presented as a poster at AASLD's The Liver Meeting 2024 . Three common PSC symptoms – fatigue, brain fog, and liver pain – lack research-quality assessment tools. The PSC Partners-led Symptom Assessment Project aims to fill that gap. Registry Superstars The Registry team would like to spotlight and thank those Registry participants who have been especially active in the Registry. Because identifying information NEVER leaves the Registry, we can’t share their names here, so we will email them individually to thank them for their loyal participation in the Registry.  19 Registry Superstars have completed 10 or more surveys  as of December 2024. 180 Rising Stars have completed 5 or more surveys . With 4 currently active surveys in the Registry (not counting the Healthcare Provider Map Submission Form), a new participant can become a Rising Star as soon as two consecutive years of Clinical Surveys have been completed! Active users demonstrate they recognize that patients CAN accelerate the trajectory of PSC research. There IS hope for better treatments and a cure for PSC, and every active Registry member plays a powerful role. We encourage YOU to become one of our stars this year as, together, we are creating a world where a PSC diagnosis comes with a cure! Learning from Registry Data: Relatives with PSC People living with PSC often ask, “What is the chance that my child develops PSC?”  Studies have shown that PSC does have a genetic component, but developing PSC is not likely even if a family member has PSC. To better understand the family link in PSC, the Registry team analyzed Clinical Surveys from 2,182  Registry participants. Here’s what we found: 1.74% (38) of participants reported a parent or child with PSC. 4.48% (96) reported a blood relative with PSC (including immediate or extended family). This does not mean that there is a 1.74% chance that a child of someone with PSC develops PSC: because this analysis does not account for the number of children in a family, the true chances are likely lower.  For comparison, 11.6% of Registry participants reported a parent or child with IBD, and 16.6% reported a blood relative with IBD. Thank you to everyone who has completed a Clinical Survey to make these types of analyses possible! If you know a relative or acquaintance living with PSC who is not yet in the Registry, we encourage you to ask them to join today. An EASY action to safeguard your account! If this newsletter reached your inbox, the Registry has your correct email. To be sure that we can always  reach you: 1) Log into your Registry account* and confirm all of your contact info in the General Information section.** Consider adding an optional email address, which is used in case your primary email address is no longer valid. 2) If your contact information changes, let us know! Please do not make a second account! If you have trouble accessing your account, the Registry team can help. Thank you for helping the Registry team keep you connected and up to date. *If you have an older account and haven’t logged in during 2024 or 2025, you will need to reset your password , as the Registry moved to an upgraded platform in early 2024. The Registry supports Chrome, Edge, and Safari browsers. **You can edit all demographic info except your email address . To update an email, please contact us at registrycoordinator@pscpartners.org , and the Registry team will change it.