NASH and Fibrosis

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. Thus NASH drug development is a growing area of activity in the pharmaceutical industry. Despite the challenge of measuring NASH, there are a few NASH drug candidates in late-stage clinical trials and many more in Phase I and early Phase II trials. Liver fibrosis is similar to the fibrotic disease process in other organs, where scientific understanding and advances are also rapidly occurring. CHI's NASH and Fibrosis 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.

Final Agenda

Wednesday, September 26

7:00 am Registration Open and Morning Coffee

NASH Drug Candidates

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

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

Nash Drug Candidates and Targets

10:25 Galectin 3 Inhibitor for NASH Cirrhosis

Peter Traber, MD, CEO, Galectin Therapeutics

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 Targeting the MetA2P Pathway for NASH

Thomas E. Hughes, PhD, President and CSO, Zafgen

11:55 Sponsored Presentation (Opportunity Available)

12:25 pm Session Break

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing

Emerging Targets for Liver Fibrosis

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?

Laurent Fischer, PhD, Therapeutic Area Head, Fibrosis, Allergan

2:25 A Bispecific Antibody Mimetic of FGF21 for Metabolic Diseases and NASH

James A. Ernst, PhD, Senior Scientist, Department of Protein Science, Genentech, Inc.

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 Sponsored Presentation (Opportunity Available)

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.

MCHR1 antagonism is a new target approach for the treatment of NASH and CSTI-100 appears to be the furthest advanced compound in the industry. Emerging evidence from studies with CSTI-100 and the literature suggest this approach may have advantages over current clinical approaches. In addition, Jim Harwood has been a consultant to this program for about 10 years, and he recommended we apply to present at this prestigious forum.

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 available on the conference website.

6:05 Welcome Reception in the Exhibit Hall

7:10 Close of Day

Thursday, September 27

7:30 am Registration Open and Morning Coffee

Tools and Targets for Fibrosis

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 School

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, Associate Director, Translational Medicine Group, Takeda

9:05 Sponsored Presentation (Opportunity Available)

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, PLIANT Therapeutics

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 Presentation to be Announced

11:20 Luncheon Presentation (Sponsorship Opportunity Available) or 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