Summit Clinical Research

Here are 5 key takeaways from the presentation on Efimosfermin alfa (BOS-580) presented by Dr. Mazen Noureddin, MD, MHSc at the American Association for the Study of Liver Diseases (AASLD) TLM24. 1. Statistically Significant Improvements in MASH Resolution and Fibrosis Reduction ? Efimosfermin achieved remarkable results in a 24-week Phase 2 study: ? MASH resolution without worsening of fibrosis: 68% vs. 29% in placebo (p=0.002). ? Fibrosis improvement (≥1 stage) without worsening of NASH: 45% vs. 21% in placebo (p=0.038). ? Combined endpoint of fibrosis improvement and MASH resolution: 39% vs. 18% in placebo (p=0.066). ? These outcomes highlight Efimosfermin’s efficacy in improving histological features of MASH after just six doses. 2. Significant Reductions in Liver Fat ? Efimosfermin demonstrated robust reductions in liver fat as measured by MRI-PDFF: ? ≥30% relative fat reduction: 79% vs. 20% in placebo (p<0.001). ? ≥50% relative fat reduction: 50% vs. 7% in placebo (p<0.001). ? Liver fat normalization (<5%): 32% vs. 3% in placebo (p=0.004). ? These improvements underscore its potential to resolve key metabolic dysfunctions associated with MASH. 3. Metabolic and Glycemic Improvements ? In patients with Type 2 Diabetes: ? Efimosfermin reduced HbA1c by 0.7% at Week 24 (statistically significant and clinically meaningful). ? HbA1c reductions became significant as early as Week 12 and continued through the trial. ? Additional improvements in metabolic markers align Efimosfermin’s benefits with the needs of high-risk populations. 4. Favorable Safety Profile ? Efimosfermin was well-tolerated, with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate: ? Common TEAEs: nausea (30%), diarrhea (21%), and vomiting (14%). ? Low rates of injection site reactions (<5%) and no significant appetite changes or weight gain. ? Serious adverse events (2%) were rare and unrelated to the drug in most cases. ? Importantly, the drug had a low discontinuation rate due to side effects (5%). 5. Validation of Histological and Non-Invasive Markers ? Efimosfermin reduced Enhanced Liver Fibrosis (ELF) scores by -0.7 at Week 24 compared to placebo (-0.2, p=0.005). ? While VCTE showed a -1.9 kPa reduction, it was not statistically significant due to a high placebo response. ? These results, alongside MRI-PDFF reductions and histological improvements, strongly validate Efimosfermin’s dual impact on liver health. Efimosfermin alfa (BOS-580) demonstrated statistically significant and clinically meaningful improvements in histological, metabolic, and non-invasive markers of MASH. Its once-monthly dosing, favorable safety profile, and strong efficacy make it a promising candidate for further development as a treatment for MASH-related fibrosis. EASL | The Home of Hepatology, Global NASH Council, Boston Pharmaceuticals, Matthew Bryant, Naim Alkhouri, MD, FAASLD, Houston Research Institute In collaboration with CHATGPT4o

Late breaker update: “Once-monthly Efimosfermin Alfa (BOS-580) in Metabolic Dysfunction-associated Steatohepatitis with F2/F3 Fibrosis: Results from a 24 Week, Randomized, Double-blind, Placebo-controlled, Phase 2 Trial” with Mazen Noureddin, MD, MHSc at American Association for the Study of Liver Diseases (AASLD). Efimosfermin alfa (BOS-580): Long-acting, Once-monthly FGF21 Analogue with Extended Half-life and Balanced Pharmacological Activity. Efimosfermin Once-monthly Achieved Statistically Significant MASH Resolution and Fibrosis Improvement after only 6 doses. MASH Resolution: Without Worsening of Fibrosis at Week 24. 29% vs 68% Fibrosis Improvement ≥1 Stage Without Worsening of MASH? at Week 24 21% vs. 45%. Statistically Significant HFF Response Rates Measured by MRI-PDFF. Liver Fat Normalization (≤5%): 3% vs. 32% Treatment Emergent Adverse Events (TEAE) * Most TEAs were mild to moderate; one grade 3 drug-related TEAE * Low rates (<5%) of changes in appetite (either increase or decrease) and no reported weight gain * Low rates (<5%) of any injection site reactions Take Aways: * Once-monthly efimosfermin achieved statistically significant improvement compared to placebo after 24 weeks treatment: - Fibrosis improvement ≥1 stage without worsening of MASH - MASH resolution without worsening of fibrosis * Improvement in fibrosis biomarkers and significant reductions in non-invasive markers of liver injury and liver fat * Statistically significant and clinically meaningful improvement in HbA1c in participants with T2D * In this study, efimosfermin was generally well-tolerated and gastrointestinal events were the most frequently reported TEAEs, which were predominantly mild to moderate * Overall, there was a low rate of discontinuations due to adverse events * These promising Phase 2 data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis Global NASH Council, EASL the home of Hepatology, Boston Pharmaceuticals, Matthew Bryant

A beautiful tribute to Dr. Stephen Harrison by Maru/Mary Rinella at American Association for the Study of Liver Diseases (AASLD). “Thank you very much…for giving me the honor of being able to say a few words about Stephen, who is a friend to many of us in this room. Stephen's academic accomplishments really stand for themselves. He really did more than most people could aspire in his medical career, and he had a very truncated life, unfortunately. As you all know, he was a natural leader. Early in his career, he applied this to serve his country in a distinguished career in the military. He did two tours in Iraq and reached the rank of colonel and, despite all this, still accomplished what he did. For those who didn't know him, you certainly knew of him and it's certainly fitting to remember him in the late breaker session. I actually don't remember a late breaker session where he wasn't presenting. And everyone who was fortunate enough to know him actually felt like they were his friends, and I really think that they were. He really had a legendary work ethic, which I'm sure you all know. He had boundless amounts of energy, and he would famously say, among many hilarious adages that if the birds were chirping, that he should be working. So passionately, he focused on providing really the best care for his patients, and he always kept that front of mind. I think that really fueled his drive to bring the first drug to market, and he was extremely excited and proud about this. And he finally achieved that on March 14th, only six weeks before he died. So Stephen really had equal measure of kindness and optimism and actually many of you know that he really extended a hand to help anyone who might need it or benefit from it, which is that generosity that we don't always see. And among many skills, I think most relevant to those of you in this room, he would distill the learnings from each study, no matter how big or small, and what the outcome was, to sort of inform the design and conduct of future trials. So, he really was a true visionary. He brought together across industry and academics to advance the field, and most importantly, to improve the life of his patients. So, I'd like to really thank him for his exceptional leadership. His energy and contagious optimism. And I really believe that the field and all of us who knew him are really less without him. So, thank you.” American Association for the Study of Liver Diseases (AASLD), Global NASH Council, EASL the home of Hepatology, 89bio, Boehringer Ingelheim, Novo Nordisk, Eli Lilly and Company, Madrigal Pharmaceuticals, Medscape Education, Pinnacle Clinical Research, Summit Clinical Research, Arizona Liver Health, Houston Liver Institute, Regeneron, Boston Scientific

Dr. Naim Alkhouri delivered an insightful presentation on Treatment of MetALD: Challenges and Opportunities, shedding light on the growing complexity of metabolic dysfunction- and alcohol-associated liver disease (MetALD). Key takeaways included: *The rise of the Steatologist, a specialist in hepatology, addiction medicine, and obesity medicine, enhanced with tools like prescription digital therapeutics for lifestyle and mental health support. *Evidence that MetALD is associated with higher rates of fibrosis and metabolic-associated liver outcomes (MALOs) compared to MASLD, as shown in Swedish cohort studies and U.S. transplant data. *Promising efficacy of resmetirom in MetALD patients, as seen in the MAESTRO-NASH trial, highlighting its potential in treatment strategies. Dr. Alkhouri emphasized the urgent need for trial designs to address MetALD specifically and for inclusion of MetALD patients in broader MASH research. This important work continues to drive innovation in liver health care and research. #LiverHealth #MetALD #MASLD #ClinicalResearch #AASLD Naim Alkhouri, MD, FAASLD, Anita Kohli, Richard Manch, Yessica Sachdeva, Tessa Janovsky Rida Nadeem, MD, MSPH Michelle Jones Kelly Black Nick Engelke, American Association for the Study of Liver Diseases (AASLD), Fatty Liver Alliance, Mazen Noureddin, MD, MHSc, Angie Coste Novo Nordisk Boehringer Ingelheim Madrigal Pharmaceuticals Fortrea Ipsen, Akero Therapeutics, Echosens, Gilead Sciences, AbbVie, Eli Lilly and Company, Boston Pharmaceuticals, 89bio, GSK, Summit Clinical Research

?? #SummitClinicalResearch is honored to celebrate the legacy of our co-founder Dr. Stephen Harrison, who was posthumously awarded the inaugural #Echosens Liver Health Legacy Award at AASLD: The Liver Meeting 2024. ?? Dr. Harrison was recognized for his groundbreaking contributions to liver disease diagnostics and treatments, which have forever changed patient care and advanced the field of hepatology. His award, presented by Summit’s CSO Dr. Mazen Noureddin, was graciously accepted in his honor by Summit’s CEO Gail Hinkson and Dr. Rashmee Patil, Pinnacle Clinical Research’s CEO, during an inspiring event hosted by Echosens. This prestigious award was part of the Echosens Liver Health Super Shaper Awards, honoring transformative leaders in liver health, including: ???? Dr. Catherine Williamson: Advancing liver disease research in pregnancy. ???? Dr. J?rn M. Schattenberg: A leader in hepatology and mentor to future specialists. Dr. Harrison’s legacy continues to impact lives worldwide, and we are proud to see his dedication to liver health celebrated on this global stage. #LiverHealthMatters #ClinicalResearch #Legacy #AASLD2024

Mazen Noureddin, MD, MHSc shares insights about Rezdiffra at the American Association for the Study of Liver Diseases (AASLD) theater, sponsored by Madrigal Pharmaceuticals. “Patients with NASH with moderate to advanced liver fibrosis* require prompt identification and therapeutic management due to risk of disease progression”. Predictor of Risk: Patients with fibrosis stage F2 or F3 are at a higher risk of developing major liver events. Unpredictable Rate of Progression: Rates of fibrosis progression are unpredictable and vary from patient to patient depending on comorbid conditions, genetic profile, environmental factors, and disease severity. Increasing in Prevalence: NASH with fibrosis stage F2 or F3 is increasing in prevalence, yet many patients remain undiagnosed and unmanaged. “MASH is the second most common cause of transplant in women”. “Patients at high risk for NASH with fibrosis often have common comorbidities.” “AASLD, AGA, and AACE guidances all recommend sequential risk assessment with NITs to identify adult patients with NASH with moderate to advanced liver fibrosis.” Rezdiffra: “Please do not use in cirrhotic patients”. Rezdiffra is a partial agonist of THR-B,* which is the major form of THR in the liver * Stimulation of THR-B in the liver reduces intrahepatic triglycerides ? Actions of thyroid hormone outside the liver (including the heart and bones) are largely mediated through THR-a The efficacy and safety of Rediffra were evaluated in Trial 1 (MAESTRO-NASH; N=888). MAESTRO-NASH is an ongoing Phase 3, randomized, double-blind, placebo-controlled trial. Week 52 dual primary endpoints: 1. NASH Resolution: resolution of steatohepatitis and no worsening of liver fibrosis. 2. Fibrosis Improvement: ≥1-stage improvement in fibrosis without worsening of steatohepatitis. Madrigal Patient Support (MPS) has a dedicated team that can help provide timely assistance and support. American Association for the Study of Liver Diseases (AASLD)

???We’re thrilled to share the winners of?the inaugural Echosens Liver Health Super Shaper Award, first revealed yesterday at AASLD: The Liver Meeting 2024! These exceptional physicians have made transformative contributions to liver health and improved lives worldwide. This award honors their dedication, innovation, and impact on the field: ? ???Dr. Stephen Harrison: Remembered?with the Echosens Liver Health Legacy Award for his pioneering contributions.? ? ?????Dr. Catherine Williamson: Advancing liver disease research in pregnancy. ? ?????Dr. J?rn Schattenberg: A leader in hepatology and mentor to future specialists. ? Each of these honorees has left a lasting mark on liver health. Join us in celebrating their remarkable achievements and commitment to this critical field.? #LiverHealthMatters? https://lnkd.in/ef7r3vDK ??

?? Congratulations to Project Manager Mario D'Gyves on his 3rd #workanniversary with #SummitClinicalResearch! ??

???????????? ???????????????? ???????????????? ???? ?????????? ????????! We’re excited that Mazen Noureddin, MD, MHSc, Summit’s Chief Scientific Officer, will be sharing his deep expertise on MASLD/MASH advancements at #AASLD2024, including non-invasive diagnostics and new therapies, during the following sessions: ?????????????? ????????????, ?????????????? ??????????: ?? ???????????? ?????????????????? November 16, 2024 9:45 AM - 10:45 AM ?????????????????? (????????????????????) – ?? ?????????????????? ???????????? ?????? ???????????????? November 18, 2024 10:00 AM - 10:45 AM For more details, visit Dr. Noureddin’s AASLD Speaker Page: https://lnkd.in/ev3AtdTe ??????’?? ???????? ???????? ?????????????????????? ???? ???????????? ???????? ?? ???????????? ???? ?????????? ????????????????! #LiverResearch #ClinicalTrials #SummitClinicalResearch