2017 Archived Content
Fibrosis is an area of increasing research activity in the drug discovery industry, especially in the context of liver disease. A response to the injury of cells, fibrosis is at the nexus of several biologic processes such as inflammation, cell death and metabolic dysregulation in which our scientific knowledge has significantly increased in the past decade. Liver fibrosis, often occurring at the later stages of fatty liver disease and referred to as non-alcoholic steatohepatitis (NASH), is of special interest because the number of people with NASH has doubled in the past twenty years and no medical treatments exist though promising therapeutics are in late stage clinical trials. Join us at Cambridge Healthtech Institute’s Inaugural NASH and Fibrosis meeting to keep abreast of the rapid progress in new therapeutic candidates and share drug discovery strategies in this increasingly important medical field.
Final Agenda
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Tuesday, September 26
7:00 am Registration Open and Morning Coffee
8:00 Welcome Remarks
Anjani Shah, Ph.D., Conference Director, Cambridge Healthtech Institute
8:05 Chairperson’s Opening Remarks
Rebecca Taub, M.D., CMO & Executive Vice President, R&D, Madrigal Pharmaceuticals
8:10 KEYNOTE PRESENTATION: Overview of Non-Alcoholic Fatty Liver Disease -- Epidemiology, Diagnosis and Management
Kathleen Elizabeth Corey, M.D., Assistant Professor of Medicine, Massachusetts General Hospital
8:40 Updates on a Dual PPAR Agonist in Clinical Development for Treating NASH
Sophie Megnien, M.D., Chief Medical Officer, Genfit Corp.
9:10 Progress in the Development of FXR Agonists
Yat Sun Or, Ph.D., Senior Vice President, R&D and CSO, Enanta Pharmaceuticals, Inc.
FXR agonism is under investigation as a potential treatment for multiple metabolic and liver conditions, including NASH. A brief overview of FXR agonists in early clinical trials will be presented, as well as the preclinical data illustrating EDP-305 selectivity for FXR, its significant perturbation of FXR-dependent gene expression, and its striking effects on hepatocyte ballooning and liver fibrosis in multiple animal models.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 FXR Agonists in Phase II Development for NASH
Bryan Laffitte, Ph.D., Director, Discovery Pharmacology, Genomics Institute of the Novartis Research
10:55 Cenicriviroc, a Dual CCR2 and CCR5 Antagonist, for the Treatment of Liver Fibrosis in Adults with Nonalcoholic Steatohepatitis
Eric Lefebvre, M.D., Vice President, Head of Clinical Research and Development – NASH, Allergan
The CENTAUR Phase IIb study evaluated the oral chemokine receptor CCR2/5 antagonist cenicriviroc (CVC) in non-alcoholic steatohepatitis and liver fibrosis in adults at increased risk of progression to cirrhosis. CVC was well tolerated, with twice as many patients achieving ≥1-stage improvement in fibrosis and no steatohepatitis worsening vs. placebo after 1 year. Patients with higher disease activity and fibrosis stage showed greater numerical improvements in fibrosis.
11:25 Thyroid Hormone Receptor Targets
Rebecca Taub, M.D., CMO & Executive Vice President, R&D, Madrigal Pharmaceuticals
11:55 Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Poster Viewing
1:50 Chairperson’s Remarks
Bryan C. Fuchs, Ph.D., Assistant Professor of Surgery, Harvard Medical School
1:55 FEATURED PRESENTATION: Tools for Assessing Fibrosis and Monitoring Response to Treatment in Preclinical Models
Bryan C. Fuchs, Ph.D., Assistant Professor of Surgery, Harvard Medical School
There are a number of anti-fibrotic therapies entering clinical trials in NASH patients, but a major obstacle to their development is the lack of sensitive and noninvasive tools for assessing fibrosis. Here, we discuss our preclinical work to develop molecular imaging as a biomarker that could not only be used to select patients for clinical trials but also provide an early assessment of treatment efficacy.
2:25 Targeting Liver Fibrosis through Modulating the Wnt Pathway
Weilin Xie, Ph.D., Senior Principal Scientist, Biotherapeutics, Celgene
2:55 Late Breaking Presentation: Low-risk in-vivo Diagnosis of Pulmonary Fibrosis with Endobronchial Optical Imaging
Lida Hariri, M.D., Ph.D., Instructor, Pathology Department, Harvard Medical School
Idiopathic pulmonary fibrosis (IPF) is a fatal form of fibrotic interstitial lung disease (ILD). Diagnosis of IPF is essential to determine the most effective therapy for patients, but often requires surgical tissue resection, which has a high-risk profile. We aim to determine whether endobronchial optical imaging can serve as a low-risk method for in-vivo IPF diagnosis. We performed endobronchial optical imaging in ILD patients undergoing diagnostic wedge biopsy. Optical imaging was able to visualize diagnostic IPF features, and differentiate IPF from other ILDs. These findings support the potential of optical imaging as a minimally-invasive method for IPF diagnosis.
3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced
4:05 FAP and FGF21: Complementary Targets for the Treatment of NASH
Travis W. Bainbridge, MS, Senior Scientific Researcher, Department of Protein Chemistry, Genentech, Inc.
Fibroblast activation protein (FAP) is a membrane-bound protease expressed at sites of tissue remodeling, inflammation and fibrosis. FGF21 is a hepatoprotective hormone we identified as an FAP substrate. Cleavage by FAP inactivates FGF21, while FAP inhibition increases endogenous levels of active FGF21, making FAP an attractive target for liver disease. Additionally, a FAP-specific activity assay for monitoring the pharmacodynamics of FAP inhibitors will be described.
4:35 CANCELLED: Targeting Ammonia with OCR-002 Reduces the Progression of Non-Alcoholic Fatty Liver Disease
Rajiv Jalan, M.D., Ph.D., Professor of Hepatology, University College London
NAFLD is characterized by reduced activity of key urea cycle enzymes resulting in hyperammonemia. Pathophysiological concentrations of ammonia produce activation of stellate cells, which can be reversed by administration of the ammonia-lowering drug, OCR-002. Treatment of a rodent model of NAFLD (high-fat high-cholesterol diet) with OCR-002 prevented progression of fibrosis, providing proof of concept for an ammonia lowering therapy in NAFLD that can be readily translated.
5:05 Interactive Breakout Discussion Groups
Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are below. Please click here for full details on all breakouts.
Non-Invasive Assessment of Liver Fibrosis
Moderator: Bryan C. Fuchs, Ph.D., Assistant Professor of Surgery, Harvard Medical School
- Serum tests: will omic analyses hold the key?
- Which imaging technologies have the most promise?
- Are tools that assess dynamic changes needed for early assessment of anti-fibrotics?
Animal Models for Fibrosis
Moderator: Weilin Xie, Ph.D., Senior Principal Scientist, Biotherapeutics, Celgene
- Who has used what?
- Pros and cons of different models
- What looks promising
NASH Drug Development Challenges
Moderator: Eric Lefebvre, M.D., Vice President, Head of Clinical Research and Development – NASH, Allergan
- Translational tools
- Role of biomarkers
- FDA guidance
- Defining target population
6:05 Welcome Reception in the Exhibit Hall (Sponsorship Opportunity Available)
7:10 Close of Day
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Wednesday, September 27
7:30 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
H. James Harwood Jr., Ph.D., Founder and CEO, Delphi BioMedical Consultants, LLC
8:05 Roles of LPA and S1P in Lung Fibrosis
Rachel Knipe, M.D., Instructor of Medicine, Harvard Medical School and Assistant Physician, Laboratory of Andrew Tager, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital
8:35 Epigenetic Targets for Cardiorenal Fibrosis
Timothy A. McKinsey, Ph.D., Director, Consortium for Fibrosis Research & Translation, Department of Medicine, University of Colorado – Anschutz Medical Campus
Despite the well-accepted roles for fibrosis in the pathogenesis of heart failure and chronic kidney disease, there are no FDA-approved therapies to combat excessive extracellular matrix deposition in cardiac or renal tissue. I will discuss our recent findings suggesting that specific epigenetic regulatory proteins serve crucial pro-fibrotic functions, and the potential for small molecule inhibitors of these factors for the treatment of cardiorenal fibrosis.
9:05 Report-back from Breakout Discussion Moderators
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:20 Moving from Lung Fibrosis to Liver Fibrosis
Ying Luo, Ph.D., CEO, GNI Group
A new compound targeting liver fibrosis has shown excellent efficacy in liver fibrosis and kidney fibrosis animal models. It also showed significantly improved safety profile over pirfenidone in Phase I studies. Currently, it is in a 240 patient Phase II studies for HBV-associated liver fibrosis in China.
10:50 The Development of PAT-1251, a Small Molecule LOXL2 Inhibitor to Treat Fibrosis
John Hutchinson, Ph.D., President and CSO, PharmAkea
LOXL2 catalyzes oxidation of ε-amines of lysine residues within collagen, generating reactive aldehydes that condense to form collagen cross-linkages. Dysregulation of this process can lead to fibrosis. PAT-1251 was identified as a potent irreversible inhibitor of LOXL2 that is highly selective over LOX and other AOs. PAT-1251 significantly reduced fibrosis in mouse lung bleomycin models and has completed healthy volunteer Phase I trials.
11:20 Enjoy Lunch on Your Own
12:35 pm Plenary Keynote Program
(click here for details)
2:00 Refreshment Break in the Exhibit Hall with Poster Viewing
2:45 Close of Conference
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