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.
Final Agenda
Wednesday, September 18
11:20 am Conference Registration Open (America Foyer)
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 (America Ballroom)
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 NEW: Cell Therapy for Liver Fibrosis Using Reprogrammed Hepatic Stellate Cells Locked into a Quiescent-like State
Michael Choi, MD, Assistant Professor, Medicine, Harvard Medical School
Hepatic stellate cell (HSC), once activated, plays a central role in promoting progressive liver fibrosis. We identified a key driver to reprogram activated HSC back toward quiescence to generate what we designate as induced quiescent hepatic stellate
cell (iqHSC). iqHSCs had morphologic, transcriptional, and functional phenotype similar to that of truly quiescent HSCs. Finally, performing cell therapy with iqHSCs locked into a quiescent-like state in mouse models of liver injury attenuated hepatic
inflammation and fibrosis. Cell therapy using iqHSCs could be a template for treating multiple human liver diseases that lead to fibrosis.
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 NEW: Role of Integrin-alpha V in Fibrosis and Inflammation
Kevin Hart, PhD, Principal Scientist, Inflammation, Pfizer
Since some integrins can serve as master regulators of fibrosis, we investigated if integrin-alpha V is critical during polarized inflammatory responses during tissue damage disease models. While data confirmed a role for integrin-alpha V in type 17-associated
fibrosis, integrin-alpha V was not critical to the development of type 2-driven fibrosis. However, our studies reveal a novel mechanism through which fibroblasts, via integrin-alpha V expression, are capable of regulating immune polarization.
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 (America Foyer)
Click here for details on short courses offered.
9:30 Close of Day
Thursday, September 19
7:00 am Registration Open (America Foyer)
Essex Ballroom
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
- Senolytics
- 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 (America Ballroom)
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 Breakout Discussion Report-Back
Moderator: Carolyn Cuff, PhD, Senior Director, Translational Immunology, Immunology Discovery, AbbVie Bioresearch Center
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 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.
3:40 Close of Conference
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