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.

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

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

Help researchers worldwide unlock the mysteries of primary sclerosing cholangitis (PSC). Complete your profile and join the PSC Partners Patient Registry to contribute your voice and experiences to our collective knowledge of PSC! You are an important piece of the PSC puzzle! Join the PSC Partners Registry to take action and drive PSC research forward. JOIN NOW LOG IN The Registry is a platform to amplify your voice in PSC research. The PSC Partners Patient Registry is a digital platform where basic data on people living with PSC is collected and stored. Data is primarily collected through online surveys completed by the participant living with PSC, or a qualified caregiver. Join the Registry to... Complete surveys that confidentially capture your experiences and address key questions in PSC research; Document and track your medical history with PSC, including treatments, symptoms, and healthcare providers; Elect to receive information about participating in research and clinical trials . You will be notified if you qualify for a study and can choose to contact the study team. The PSC Partners Patient Registry is open to everyone with PSC, wherever you are in the world. Parents and caregivers can join on behalf of their children. Any information you share is de-identified before sharing with researchers. No patient-identifying data ever leaves the Registry. LEARN MORE Latest News from the Registry The VIADUCT - Issue 8 Issue 8 - Spring 2025 In this issue: From the Registry Director • Cholangiocarcinoma (CCA) Survey • WIND-PSC Enrolling Patients •... Chemomab Announces Results from Open Label Extension of SPRING Trial for Nebokitug (CM-101) in PSC Today, March 27, 2025, Chemomab Therapeutics issued a press release announcing results from the Open Label Extension (OLE) section of the... External Survey on PSC and Quality of Healthcare A new survey outside the Registry that focuses on understanding and improving the care of people living with PSC is now available. Every... What is the PSC Partners Patient Registry? What can I expect after I join? Learn More Join the Registry to add your information to our collective voice. Join Now Interactive map of healthcare providers provided by PSC Partners Patient Registry participants. Find PSC Specialists Data is power Thanks to people like you, the experience of living with PSC can be understood like never before. The more health information we collect through this patient registry, the closer we can get to helping our research community find treatments that work. Check out this video to learn more. "Where well-implemented registries and active patient organizations exist, the likelihood for developing a treatment for the disease in question is increased." (Eurordis-NORD-CORD) For questions, email registrycoordinator@pscpartners.org Visit PSC Partners website: pscpartners.org Join the Registry today! We're together in the fight, whatever it takes. With appreciation to Espen Bunæs for design support

Help researchers worldwide unlock the mysteries of primary sclerosing cholangitis (PSC). Complete your profile and join PSC Partners Seeking a Cure in advancing PSC research towards a cure. Your participation is important. Welcome to the PSC Partners Patient Registry! If you or a loved one has the rare liver disease primary sclerosing cholangitis (PSC), you are in the right place! This site was developed and is supported by PSC Partners Seeking a Cure, a nonprofit organization dedicated to providing education and support to PSC patients, families, and caregivers. Another vital mission of PSC Partners is to support researchers in their quest to find causes, treatments, and cures for this rare disease. The PSC Partners Patient Registry was initiated in 2014 in response to the difficulty of locating PSC patients and collecting PSC data to conduct research on our rare disease. Our aim with the Registry has been to add the patient’s voice to every facet of PSC research and to facilitate and speed up PSC research towards a cure. All those diagnosed with PSC are encouraged to participate. Parents can join the Registry to enroll their child. A spouse can participate on behalf of their partner. All data in the Patient Registry is de-identified. When a researcher requests information, no identifying information (name, date of birth, address, or phone number) ever leaves the Registry. Researchers, approved by the PSC Partners Patient Registry Team, request de-identified registry data for their research, for patient recruitment in clinical trials, and for developing clinical study protocols. Participants of the PSC Partners Patient Registry represent an important voice of the PSC community: They engage in research by completing surveys and joining clinical trials. They help us advocate by expressing their unmet needs. When new treatments arrive, the Registry can help track the effectiveness of the new drug and can speed up drug approval. If you or your child appears to be a match for a study or a clinical trial, the registry coordinator will contact you. It would be your choice to connect with the researcher(s) to let them know if you are interested. To join, we request that you enter your General Information, give consent, complete the Clinical Survey, and that you provide a proof of diagnosis which could be a recent or old MRCP or ERCP result, or a doctor’s report that states you have PSC. You can learn more about the specifics of the registry by clicking on the various links on this site. We hope you will be inspired to join the PSC Partners Patient Registry. Your voice is crucial for this small and dispersed PSC community! You can help researchers worldwide by taking around 30 minutes of your time to complete your profile - or your child’s or loved one’s profile. Join the hundreds of men, women, and children who are helping to advance PSC research towards treatments and a cure! We are together in this fight, whatever it takes! Join us! The registry coordinator is available to respond to any questions you may have. Please don't hesitate to reach out by email at registrycoordinator@pscpartners.org . Mary Vyas, Registry Director Rachel Gomel, Senior Registry Advisor Brian Thorsen, Assistant Registry Director Sharon Nanz, Registry Coordinator Susan O'Dell, Registry Analyst Chris Bowlus, MD, Registry Scientific Advisor , Chief of Gastroenterology, UC Davis All rights reserved © PSC Partners Seeking a Cure

< Back 2020 Diet in PSC Survey (DOCK) - Active Now The relationship between nutrition and PSC is complex and little is known about it. Diet may have an impact on PSC and/or Ulcerative Colitis (UC), but this has not been well established. Researchers led by by PI investigator Joshua Korzenik, MD at Brigham and Women’s Hospital would like to learn more about the relationship between diet, PSC and UC. Registry participants will be notified if they are eligible for this study which consists of two online surveys.