( 繊維症の標的化 )
The incidence of fibrosis, a normal part of wound healing, but also, under persistent inflammation or injury, a disease process that contributes to organ damage, has been steadily increasing over the past decade. This could be partly due to the percentage of elderly and thus chronic disease and inflammation rising in the population. Activity in the drug development arena for fibrosis has also grown. Much of the progress has been spurred by the fields of autoimmunity and inflammation which are revealing common mechanisms for fibrosis across the organs where fibrosis is most frequently observed: lung, liver, heart, kidney and skin. The approval of two drugs for a form of lung fibrosis, idiopathic fibrosis (IPF), has also accelerated progress in the field. However it is likely that multiple therapeutic approaches for treating fibrosis will be necessary because of the many contributors to the condition. For this reason, CHI’s Inaugural Targeting Fibrosis conference aims to convene the leading fibrosis researchers from academics and industry working across organ types, as well as immunology and inflammation investigators to share progress and shape future directions in this burgeoning field of new drug discovery.
RECOMMENDED PREMIUM PACKAGE:
Choose 2 Short Courses and 2 Conferences/Training Seminars
September 16 Pre-Conference Short Course: SC1: Immunology Basics: Focusing on Autoimmunity and Cancer
September 17-18 Conference: Targeting NASH
September 18 Dinner Short Course: SC9: Targeted Protein Degradation Using PROTACs, Molecular Glues and More
September 18-19 Conference: Targeting Fibrosis
Day 1 | Day 2
11:20 am Conference Registration Open
PLENARY KEYNOTE PROGRAM
Click here for full abstracts.
12:20 pm Event Chairperson’s Opening Remarks
An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute
12:30 Plenary Keynote Introduction
Anjan Chakrabarti, Vice President, Discovery Chemistry, Syngene International Ltd
12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells
David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University
1:20 PROTACs: Past, Present, and Future
Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University
2:00 Close of Plenary Keynote Program
2:00 Dessert Break in the Exhibit Hall with Poster Viewing
2:45 Organizer's Welcome Remarks
2:50 Chairperson’s Opening Remarks
Carolyn Cuff, PhD, Senior Director, Translational Immunology, Immunology Discovery, AbbVie Bioresearch Center
2:55 FEATURED PRESENTATION: An Overview of Fibrosis and the Hope of Pharmacologic Treatments
Bryan Fuchs, PhD, Senior Director, Research TA Head for GI & Liver Disease, Ferring Research Institute
Chronic fibroproliferative diseases are a significant health concern accounting for nearly 45% of all deaths in the developed world. A considerable amount of effort over the last decade has better defined the common and tissue-specific pathways and mechanisms that drive fibrogenesis and have led to a few approved therapies. This presentation will cover clinical successes and failures and highlight drug development challenges including the lack of translatable animal models and non-invasive biomarkers.
3:25 Targeting Integrins for Fibrotic Diseases
Liangsu Wang, PhD, Vice President, Head of Biology, Morphic Therapeutic
Integrins lie at the heart of many biological processes and are involved in the pathophysiology of a variety of human diseases. This talk will discuss the roles of integrins in fibrotic diseases, highlight some key data on pharmacological effects of Morphic small molecule inhibitors against selected integrin targets, and share our insights of molecular modes of action of different inhibitors and the implications of integrin conformations in disease microenvironment.
3:55 Late Breaking Presentation
4:25 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Targeting Integrins for Fibrosis
Ji Zhang, PhD, Scientist, Cardiorenal Metabolic & Ophthalmologic Drug Discovery, Merck Research Labs
Fibrosis is an evolutionarily conserved mechanism developed by an organism to survive chronic injury. Excessive fibrosis, however, leads to disruption of organ function and is a common feature of many chronic diseases. We are developing new medicines for multiple indications and this presentation will describe some of our efforts to target integrins for fibrosis.
5:30 IDL-2965: A Selective, Highly Potent, Clinical-Stage, Oral Integrin Antagonist for Treatment of Chronic Fibrosis
Karl Kossen, PhD, Senior Vice President, Translational Science, Indalo Therapeutics
IDL-2965 is an oral small-molecule integrin antagonist that potently inhibits αvβ1, αvβ3, and αvβ6. These integrins play central roles in TGF-β activation and the ability of stiff extracellular matrix to promote fibro-blast activation and survival. Once-daily, oral, therapeutic dosing reduces fibrosis in multiple animal models across organ systems with minimal effective doses ranging from 0.4 to 3 mg/kg. 28-day GLP safety studies suggest a large therapeutic index. IDL-2965 entered clinical studies in April 2019.
6:00 Established and Emerging Integrin Targets and Treatments for Fibrosis
Scott Turner, PhD, Vice President, Translational Sciences, Pliant Therapeutics
Fibrosis is a common pathway for progression of many debilitating diseases associated with loss of organ function. Integrins play a key role in regulating TGF-β activation and cell-matrix interactions, and thus represent attractive antifibrotic targets. We evaluated small molecule integrin inhibitors with different selectivity profiles in lung, liver and kidney models of injury and fibrosis, in tissue slices from patients with lung and liver fibrosis, as well as assessed non-invasive in vivo biomarkers of target engagement.
6:30 Dinner Short Course Registration
Click here for details on short courses offered.
9:30 Close of Day
Day 1 | Day 2
7:00 am Registration Open
7:30 Interactive Breakfast Breakout Discussion Groups - View All Breakouts
Grab a cup of coffee and 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.
Translational Tools for Studying Fibrosis
Moderator: Vanessa M. Morales-Tirado, PhD, Senior Scientist III, Translational Immunology, Immunology Discovery, AbbVie Bioresearch Center
- Advanced physiological models in fibrosis (animal models for safety and efficacy)
- Current and novel biomarkers in discovery
- New in vitro/ex vivo assays (3D cellular and organotypic models)
Promising New Fibrosis Targets
Moderator: Victor J. Thannickal, MD, Professor & Director, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham
- Cross-over Immuno-Oncology targets
- Inflammation/Immune system targets
Establishing Proof of Concept in Fibrosis
Moderator: Karl Kossen, PhD, Senior Vice President, Translational Science, Indalo Therapeutics
- Biomarkers and imaging techniques
- Enabling preclinical studies: opportunities and limitations
- Notable clinical programs
8:30 Transition to Sessions
8:40 Chairperson’s Remarks
Cory M. Hogaboam, PhD, Professor, Department of Medicine, Cedars-Sinai Medical Center
8:45 FEATURED PRESENTATION: Cell Senescence and Senolytic Strategies in IPF
Cory M. Hogaboam, PhD, Professor, Department of Medicine, Cedars-Sinai Medical Center
Cellular senescence is a state of permanent growth arrest combined with stereotyped phenotypic changes and it has an important role in maintaining physiological homeostasis. While cellular senescence may be a protective mechanism in modulating proliferative capacity, the accumulation of senescent fibroblasts and epithelial cells is now recognized as a key pathogenic mechanism in idiopathic fibrosis (IPF), a form of lung fibrosis. This presentation will cover therapeutic interventions that target and reduce the burden of senescent cells, which are promising for modulating the progression of IPF and other age-related lung disease.
9:15 Utility and Futility: Cell Co-Cultures and Ex Vivo Tissue Slices as Fibrosis Models
Glenda Trujillo, PhD, Principal Scientist, CV and Fibrosis Drug Discovery Disease Sciences and Biology, R&D, Bristol-Myers Squibb
This presentation will discuss the pros and cons of using ex-vivo precision-cut tissues and cell co-cultures for anti-fibrotic compound testing and fibrosis biomarker identification.
9:45 Developing Translational Tools for the Development of Anti-Fibrotic Therapies
Melanie Ruzek, PhD, Principal Scientist, Translational Immunology, AbbVie
Assessment of anti-fibrotic drug activities and/or fibrosis endpoints within target tissues can be difficult due to accessibility or limited frequency of collections. Thus, novel methodologies are needed for non-invasive or peripheral biomarkers that will reflect tissue fibrosis and local anti-fibrotic drug activities. Case studies of some of these approaches will be discussed.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced
10:55 Targeting ROS-Generating NADPH Oxidases in Aging and Fibrosis
Victor J. Thannickal, MD, Professor & Director, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham
Fibrosis may be viewed as a physiological, evolutionarily-conserved response to tissue injury, even at the cost of a loss in organ structure/function. This “trade-off” may result in progressive/pathological fibrosis when certain genes associated with tissue repair manifest antagonistically pleiotropic effects with aging. In this seminar, we provide evidence for the reactive oxygen species (ROS)-generating enzyme, NADPH oxidase 4 (Nox4), in age-related lung fibrosis and pre-clinical studies to support its therapeutic targeting.
11:25 CXCR4: A Novel i-body for the Treatment of Fibrosis
Mick Foley, PhD, CSO, AdAlta Limited
AdAlta has used its unique human single domain protein platform to identify a novel i-body, AD-214, that specifically antagonizes the GPCR CXCR4 and shows both anti-inflammatory and anti-fibrotic in several animal models of fibrosis.
11:55 Enjoy Lunch on Your Own
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Remarks
Brian J. Murphy, PhD, Senior Principal Scientist, CV and Fibrosis Drug Discovery Disease Sciences and Biology, R&D, Bristol-Myers Squibb
2:10 Late Breaking Presentation
2:40 Lysyl Oxidase and Lysyl Oxidase-Like Inhibitors for the Direct Treatment of Fibrosis
Jonathan Foot, PhD, Senior Research Scientist, Drug Discovery, Pharmaxis Ltd.
The lysyl oxidase (LOX/LOXL1-4) family are proteins involved in the cross-linking of elastin and collagen fibrils in the extracellular matrix. Up-regulation of one or more of the LOX family can lead to aberrant cross-linking, excessive local collagen deposition and propagation of pro-fibrotic signaling. This can lead to tissue scarring, fibrosis and ultimately organ failure. We will present strategies to directly target lysyl oxidases using small molecule inhibitors, and their effectiveness in treating fibrosis.
3:10 Discovery and Development of NTZ as an Anti-Fibrotic Agent in NASH
Suneil Hosmane, PhD, Executive Vice President, Strategic Development, Genfit
Nitazoxanide, or NTZ, is an approved anti-parasitic agent that has shown promising activity against fibrosis in preclinical disease models. We are currently evaluating NTZ in an investigator-initiated Phase 2 proof-of-concept clinical trial for the treatment of NASH-induced significant or severe fibrosis.
3:40 Targeting ROCK in Fibrotic Disease
Masha Poyurovsky, PhD, Vice President, Discovery Biology, Kadmon Corporation, LLC
Rho-associated coiled-coil kinase (ROCK) is central to the control of cell movement and shape. This presentation will cover the role of ROCK in the regulation of the bio-mechanical and biochemical signaling pathways in fibrotic disease. We discuss re-sults of Kadmon’s ROCK inhibitor discovery program which integrated lessons from earlier ROCK inhibitors, SBDD and medicinal chemistry. Our compounds are currently progressing toward early stage clinical development and Phase II clinical trials for IPF.
4:10 Close of Conference
Please click here to return to the agenda for Targeting NASH