Non-alcoholic Steatohepatitis (NASH) is a disease of the liver that starts with an accumulation of fat and proceeds to inflammation and scarring of the liver. The scarring begins as fibrosis, but can worsen to cirrhosis and eventual liver failure. The
global incidence of NASH is rapidly rising and no medical treatments exist. Advances in the scientific understanding of the fibrotic disease process in other organs are also rapidly occurring. This conference convenes discovery scientists in academics,
biotech and pharma who work in the area of fibrosis, inflammation or liver disease to share insights, tools and stay abreast of this emerging and rapidly progressing field.
Day 1 | Day 2 | Download Brochure
RECOMMENDED ALL ACCESS PACKAGE:
Choose 2 Short Courses
or 1 Symposium and 2 Conferences/Training Seminars
Wednesday, September 26
7:00 am Registration Open and Morning Coffee
8:00 Welcome Remarks
Anjani Shah, PhD, Conference Director, Cambridge Healthtech Institute
8:05 Chairperson’s Opening Remarks
Bryan C. Fuchs, PhD, Assistant Professor of Surgery, Harvard Medical School
8:10 KEYNOTE PRESENTATION: NASH Basic Science Overview and Medical Landscape
Brent Tetri, MD, Director, Division of Gastroenterology and Hepatology; Professor of Internal Medicine, Saint Louis University School of Medicine
NASH is histologic phenotype that represents the consequences of stress on multiple metabolic, inflammatory and fibrogenic pathways. It can thus be expected that patients develop NASH due to environmental, metabolic, genetic and epigenetic reasons that
vary among individuals. This talk will provide a high-level overview of the pathways thought to be mechanistically important in both the pathogenesis of NASH and the resulting fibrosis and how these pathways might be targeted with pharmacotherapy.
9:10 Thyroid Hormone Receptor Agonists for Treating NASH
Rebecca Taub, MD, CMO
& Executive Vice President, Research & Development, Madrigal Pharmaceuticals
I will present topline public data from our latest clinical study on MGL-3196, a β-selective thyroid hormone receptor (THR) agonist. MGL-3196 is an orally administered, small-molecule, liver-directed compound that is currently in Phase II development
for NASH. The data show highly significant reduction of liver fat and biomarkers of inflammation and fibrosis at 12 weeks in a 36 week serial liver biopsy study.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Therapeutic Approaches to Cirrhotic versus Pre-cirrhotic NASH
Peter Traber, MD, Partner, Alacrita Consulting; Adjunct Professor of Medicine, University of Pennsylvania School of Medicine
NASH is a chronic, slowly progressive inflammatory and fibrotic disease of the liver which progresses in some individuals to cirrhosis with its attendant complications, including death and liver transplant. In this presentation, the differences in
the pathophysiology and impact on patients between pre-cirrhotic and cirrhotic NASH will be reviewed. Additionally, acceptable and potential regulatory endpoints for clinical trials will be reviewed and put in the context of current ongoing development
programs. The publicly disclosed information on established clinical trial programs in cirrhotic NASH will be reviewed and compared, and thoughts about future clinical development for NASH cirrhosis will be discussed.
10:55 ACC Inhibitor for NASH
Jamie Bates, PhD, Senior Research Scientist, I Fibrosis, Gilead
ACC1 and 2 catalyze the rate-limiting step of de novo lipogenesis (DNL) and inhibit mitochondrial fatty acid oxidation, respectively. GS-0976, a liver-directed acetyl-CoA carboxylase (ACC) inhibitor is currently in
Phase II for NASH. We demonstrate that DNL inhibition suppresses the activation of hepatic stellate cells (HSCs) in vitro and reduces liver fibrosis in two rodent models. These data demonstrate that, in addition
to decreasing lipotoxicity in hepatocytes, ACC inhibition directly inhibits HSC activation.
11:25 LXR Inverse Agonists for the Treatment of NASH
Claus Kremoser, PhD, CEO, Phenex
Nuclear Receptor targeted drugs such as FXR, TRbeta or PPAR agonists have emerged as effective approaches to combat NASH but they all come with limitations. LXR is known as a functional counterplayer of FXR and as such, inhibiting LXR function
by inverse agonist ligands should yield similar effects than activating FXR. Animal data show that beyond strong anti-steatotic properties, LXR inverse agonists demonstrate novel, unprecendeted antidiabetic effects.
11:55 How HepQuant Tests May Aid Drug Development
Steve Helmke, CSO, HepQuant, LLC
Hepquant tests are minimally invasive, blood-based and use cholates as probes to measure the effects of disease on liver function and physiology. The main output, Disease Severity Index (DSI), is a liver score from 0 to 50 that is reproducible and can quantify disease severity and track changes over time.
12:25 pm Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Poster Viewing
1:50 Chairperson’s Remarks
H. James Harwood Jr., PhD, Founder and CEO, Delphi BioMedical Consultants, LLC
1:55 Is Combination Therapy the Future of NASH Treatment?
Star Seyedkazemi, PharmD, Associate Vice President, Clinical Development, Liver Therapeutic Area, Allergan
2:25 A Bispecific Antibody Mimetic of FGF21 for Metabolic Diseases and NASH
James A. Ernst, PhD, Senior Scientist, Department of Protein Science,
Activation of the FGF21 pathway has been shown to improve several features of metabolic disease in animals. Here we describe a novel bispecific antibody that mimics the function and metabolic effects of FGF21. Treatment with this antibody
improves glycemic and lipid profiles in mouse disease models and reduces body weight in mice and non-human primates. These effects mimic the activity of FGF21 on both mice and non-human primates, suggesting that antibody-mediated activation
of FGF21 pathway would be an effective treatment for type 2 diabetes.
2:55 Late Breaking Presentation
3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced
4:05 Targeting Liver Fibrosis through Modulating the Wnt Pathway
Weilin Xie, PhD, Senior Principal Scientist, Biotherapeutics, Celgene
4:35 CSTI-100, a Melanin-Concentrating Hormone Receptor 1 (MCHR1) Antagonist, for the Treatment of NASH
Pete Guzzo, PhD, Founder and CEO, ConSynance Therapeutics, Inc.
CSTI-100 is a selective MCHR1 antagonist that has successfully completed Phase 1 clinical studies in overweight subjects. In preclinical models of NASH, CSTI-100 demonstrated the following positive effects:
Reductions in key liver inflammatory, fibrosis and injury biomarkers; Reductions in liver triglycerides, non-esterified fatty acids and cholesterol; Improvements in liver histology; Fat-selective weight loss due to reduction
in food intake; Improvements in glucose tolerance and insulin sensitivity.
5:05 Interactive Breakout Discussion Groups - View Details
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.
Non-Invasive Assessment of Liver Fibrosis
Moderator: Bryan C. Fuchs, PhD, 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?
NASH Drug Development Challenges
Moderator: Rebecca Taub, MD, CMO & Executive Vice President, Research & Development, Madrigal Pharmaceuticals
- Role of biomarkers
- FDA guidance
- Defining target population
- Animal models
Cirrhosis and NASH
Moderator: Peter Traber, MD, Partner, Alacrita Consulting; Adjunct Professor of Medicine, University of Pennsylvania School of Medicine
- Challenges in treating cirrhosis and NASH
- Common and unique targets between cirrhosis and NASH
- Designing clinical trials for NASH cirrhosis
6:05 Welcome Reception in the Exhibit Hall with Poster Viewing
7:10 Close of Day
Day 1 | Day 2 | Download Brochure
Thursday, September 27
7:30 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Rebecca Taub, MD, CMO & Executive Vice President, Research & Development, Madrigal Pharmaceuticals
8:05 FEATURED PRESENTATION: Animal Models for NASH
Bryan C. Fuchs, PhD, Assistant Professor of Surgery, Harvard Medical
Generating robust fibrosis in the setting of a metabolic syndrome that resembles human clinical NASH remains a challenge for preclinical animal models. Despite these limitations, a plethora of animal models have been utilized in the NASH
drug development landscape. Here, we will summarize the most commonly used models and discuss their relevance to the human disease and how they might be better utilized to enhance translation into the clinic.
8:35 NASH and Fibrosis Serum Biomakers
Saurabh Gupta, PhD, Director, Translational Medicine and Early Clinical, Takeda Pharmaceuticals International Co.
Clinical Diagnosis of NASH and evaluation of anti-fibrotic activity in clinical trials heavily relies on the histological readouts based on liver biopsy, a highly invasive, variable and a non-representative technique. We will summarize soluble biomarkers which have shown most promising results in terms of fibrosis and NASH staging, and measuring the anti-fibrotic activity in clinical trials.
9:05 Breakout Discussions Report-Back
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:20 Targeting Integrins for the Treatment of Fibrosis
Scott M. Turner, PhD, Vice President, Translational Sciences,
Integrin receptors regulate multiple processes involved in inflammation, cell adhesion and fibrosis. αv integrins are of interest as antifibrotic targets due to their role in cell-specific TGFβ activation and promotion of fibrosis.
Selective targeting of specific integrins with small molecule inhibitors can interrupt the pro-fibrotic TGFβ pathway, without the risks associated with systemic TGFβ inhibition. We have developed oral small molecule integrin
inhibitors with demonstrated antifibrotic activity in primary human tissue slices and preclinical models of fibrosis.
10:50 Featured Presentation: Development of a Novel Targeted HSP47 siRNA Lipid Nanoparticle for the Treatment of Hepatic Fibrosis
Edgar D. Charles, MD, Clinical Development Lead, Liver Fibrosis, Bristol -Myers Squibb
11:20 Enjoy Lunch on Your Own
11:50 Conference Registration Open
12:20 pm Plenary Keynote Program
2:00 Refreshment Break in the Exhibit Hall with Poster Viewing
2:45 Close of Conference
Day 1 | Day 2 | Download Brochure