Search Results

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

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

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

The repurposing of approved medications with potential new efficacy in rare diseases is challenging, as these medications are unlikely to be studied and be approved by the FDA for their potential new indication. In PSC, the use of oral vancomycin (OV), an approved and repurposed drug, remains an area of debate in both the clinical and patient communities. There is growing evidence of a clinical benefit with OV treatment for certain PSC patients, especially those with active IBD symptoms. However, there is no definitive study to determine the best approach for using OV in PSC, including which patients will most benefit from OV and what treatment time frame will be most effective. Although there are several randomized clinical trials (RCT) underway, it is unlikely that these will provide a timely answer or address many of the questions that remain about how to best use OV. Because of the lack of RCT data, access to OV remains a significant challenge for many patients. A recent publication in Digestive Diseases and Sciences (1) provides a rational scientific framework using an “adaptive treatment strategy” for OV in PSC patients. The article highlights an approach that considers current information, presents an algorithm for OV treatment while also acknowledging the risks and challenges. The treatment approach outlined is “adaptive” in two important ways. First, the treatment decisions are based on an individual patient's response. Second, the definitions of response to OV can be adapted and refined as new data become available. A similar approach was taken with the use of UDCA in PSC which led to an adaptive treatment algorithm that was incorporated into most of the clinical guidance and guidelines, despite the lack of a definitive RCT. There is still work that needs to be done to define treatment response for broad acceptance by the clinicians and payors. However, the authors propose a cogent starting point that can help support access to OV for patients who may benefit from it. We thank the authors for suggesting a practical approach to decision making in treating rare diseases with repurposed drugs such as OV for PSC. (1) Shah A, Tabibian J, Buness C, Holtman G. An “adaptive treatment strategy” for oral vancomycin in patients with the orphan disease primary sclerosing cholangitis. Digestive Disease and Sciences https://doi.org/10.1007/s10620-024-08497-4

The following is a message from Mirum Pharmaceuticals regarding their VISTAS study for volixibat, a possible new treatment for PSC-related pruritus (itch). They have recently expanded their inclusion criteria for this trial to include children with PSC ages 12 and older, and people who also have autoimmune hepatitis (AIH). If you are interested in participating, please contact the research team at this Mirum Pharmaceuticals link.   They will have answers to your questions. The Registry team can answer general questions or concerns but cannot answer specific questions or screen you for eligibility. Your participation is essential for the success of clinical trials for PSC. Thank you! Rachel Gomel, Director, PSC Partners Patient Registry, and the Registry Team Together, we are creating a world where a PSC diagnosis comes with a cure. registrycoordinator@pscpartners.org www.pscpartnersregistry.org Message from Mirum: LIVING WITH ITCH DUE TO PSC? You may be eligible for the VISTAS PSC Study if you: · Are 12 years of age or older · Have a confirmed diagnosis of Large Duct or Small Duct PSC · Are currently affected by itch caused by PSC · Have PSC with or without AIH Study participation will last 7~8 months with the option to continue in the long-term extension phase, where eligible participants will receive the investigational medication, volixibat for an indefinite amount of time. The study now includes a “decentralized” option in the US where all participants can enroll in the trial from the comfort of their home: all study activities will be performed at home by health professionals and supervised by a study physician using virtual visits. Participants who prefer to participate via the traditional hospital- or clinic-based approach may continue to do so. To learn more about the study please visit us at https://mirumclinicaltrials.com/pscstudy/

Health equity is the state in which everyone has a fair and just opportunity to attain their highest level of health*. The mission of PSC Partners is to drive research to identify treatments and a cure for PSC while providing education and support for those impacted by this rare disease. Why are we surveying our community about health equity topics? PSC can affect anyone. We need a better understanding of who is impacted by PSC and the barriers that can impede your care. PSC Partners’ goal is to facilitate ways to reduce these barriers. PSC Partners needs your help. Please complete this brief survey. Your participation will make a difference in the care of people living with PSC, as well as provide vital information in the search for treatments and a cure. This survey can be completed by a PSC patient or a caregiver on behalf of the PSC patient. In this survey, the PSC patient is referred to as the “participant.” Please be sure that this survey is completed JUST ONCE for each participant. Are you... A PSC Partners Patient Registry participant? Please complete the Health Equity in PSC Survey through the Registry. Click REGISTRY PARTICIPANT LOGIN to get started now. Log in to your registry account, complete the Health Equity in PSC Survey, and also update your Clinical Survey. This option saves you time: the Health Equity in PSC Survey in the Registry has fewer questions because you won't be asked to provide information that has already been collected in the Registry. --OR-- Not yet a PSC Partners Patient Registry participant? If you are not a participant in the Patient Registry, you are invited to join today and complete the Health Equity in PSC Survey through the Registry. Benefits of doing so include: Provides a more complete picture of your PSC diagnosis and experience because your response to this health equity survey within the Registry will be one among other surveys. You can update your information over time. You will receive information about opportunities to participate in research, clinical trials, medical advances and other news from the Registry Continues to strengthen the power of the Registry by demonstrating Registry engagement of the PSC community. Click on JOIN REGISTRY NOW to set up your account, complete the NEW Clinical Survey and the Health Equity in PSC Survey. --OR-- Not interested in PSC Partners Patient Registry participation at this time? You can complete the Health Equity in PSC Survey without being a Patient Registry participant. With this option, your responses will fulfill a single-use purpose as no identifying information (such as name, phone number, address, date of birth) is collected. Registry team will not be able to contact you directly to give you future survey results or to let you know about opportunities to participate in research. Click on SINGLE-USE SURVEY button above to leave the Patient Registry site and complete the Health Equity in PSC Survey outside the Registry. Each of these three options will support the purposes of this survey! For questions or clarification, please email registrycoordinator@pscpartners.org. Thank you! *Centers for Disease Control and Prevention https://www.cdc.gov/healthequity/whatis/index.html

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!

Joanne Hatchett, PSC Partners Medical Science Liaison, sat down for a Zoom interview with Dr. Gideon Hirschfield. Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at the Toronto Centre for Liver Disease, Toronto General Hospital and Professor of Medicine in the Division of Gastroenterology at the University of Toronto. He also serves on the PSC Partners Scientific Medical Advisory Committee. The discussion focused on the Our Voices survey, clinical trials, and the value of the patient-led PSC Partners Patient Registry. Enjoy, and thank you Dr. Hirschfield! "The more people that speak, the better!" Why taking surveys through the patient registry is important: Linking messages with the clinical records helps researchers! Enables patients to possibly be the catalyst for a good idea! The Our Voices Survey and the PFDD ... "is a well-timed, important initiative!" "Each piece of the puzzle keeps people excited." To find the survey, please JOIN NOW or LOGIN to your registry account at www.pscpartnersregistry.org. Navigate to the PROFILE tab and you'll see the Our Voices survey listed. While you are there, please take or update your Clinical Survey! All rights reserved © PSC Partners Seeking a Cure

The clinical trials resources page has been updated on 1/27/21 to reflect two clinical trials currently recruiting. PLN 74809: Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC). Pliant Therapeutics's PLN 74809 is an antifibrotic drug. It is in Phase 2a trial for PSC. The clinical trial is taking place in 22 centers throughout the U.S. The drug received Orphan Drug Designation for PSC. For more details on the trial, please see the clinicaltrials.gov listing and the Pliant Therapeutics site. Volixibat: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (VISTAS). The purpose of this clinical research study, sponsored by Mirum Pharmaceuticals, is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus* associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC. For more details on the trial, please see the clinicaltrials.gov listing, the Mirum Pharmaceuticals site, and the businesswire article. *Localized or generalized itching, a prevalent and distressing symptom of cholestasis.

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, including 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