Cambridge Healthtech Institute’s 2nd Annual

Targeting Fibrosis

Developing Medical Therapies for Fibrotic Diseases

September 17 - 18, 2020 ALL TIMES EDT

CHI’s 2nd Annual Targeting Fibrosis conference will follow the model of last year’s successful launch by covering a mix of drug discovery successes and development challenges in the field of fibrosis. Presentations will focus on new molecular entities being targeted by small molecules, biologics, or newer modalities that show potential for reducing organ fibrosis. Most of the compounds with clinical success are in the lung, so much of the conference will focus on that organ. However, fibrosis of the kidney, skin, and other organs may also be covered to assess common scarring mechanisms and molecular pathways. Liver fibrosis will mostly be covered in the preceding NASH conference at this Discovery on Target event. We hope you can join us to share progress and discuss future directions in the field of fibrosis, an area whose disease burden is steadily increasing as the population of elderly, and thus, chronic disease and inflammation, rises.

Thursday, September 17

PLENARY KEYNOTE PROGRAM

12:20 pm

PLENARY KEYNOTE: Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.

12:45 pm LIVE Q&A:

Plenary Keynote Discussion

Panel Moderator:
Stewart Fisher, PhD, CSO, C4 Therapeutics, Inc.
Panelist:
William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics
12:55 pm LIVE PANEL AND Q&A:

Plenary Keynote Discussion: De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Panelists:
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Stephen A. Hitchcock, PhD, Head, Research, Takeda Pharmaceuticals, Inc.
1:35 pm Lunch Break - View Our Virtual Exhibit Hall

DRUG DEVELOPMENT CHALLENGES

2:05 pm KEYNOTE PRESENTATION:

From Genes to Mechanisms to Medicines: The Arc of Discovery for Fibrotic Diseases

Anna Greka, MD, PhD, Associate Professor of Medicine, BWH/Harvard Medical School/Broad Institute
2:25 pm

Humanized IPF Mouse Models

Cory M. Hogaboam, PhD, Professor, Medicine, Cedars-Sinai Medical Center

Initiated by the intravenous injection of cells from IPF lung biopsy or explants into SCID mouse strains, IPF cells promote persistent, non-resolving, lung remodeling in SCID mice, unlike cells from normal lung samples. Potential advantages and pitfalls of human-specific targeting approaches in a humanized SCID model of pulmonary fibrosis will also be addressed. 

2:45 pm

Translational Trends in Fibrosis Drug Discovery

Carolyn Cuff, PhD, Lead, Translational Immunology & Discovery R&D, AbbVie
3:05 pm Session Break
3:25 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Vanessa M. Morales-Tirado, PhD, Principal Research Scientist I, Translational Immunology, Abbvie Bioresearch Center
Panelists:
Anna Greka, MD, PhD, Associate Professor of Medicine, BWH/Harvard Medical School/Broad Institute
Cory M. Hogaboam, PhD, Professor, Medicine, Cedars-Sinai Medical Center
Carolyn Cuff, PhD, Lead, Translational Immunology & Discovery R&D, AbbVie
3:45 pm Happy Hour - View Our Virtual Exhibit Hall
4:15 pm Close of Day

Friday, September 18

CLINICAL CANDIDATES

10:00 am

Translational Pharmacology of TD139, an Inhaled Small-Molecule Galectin-3 Inhibitor for the Treatment of IPF

Rob Slack, PhD, Director of Pharmacology, Galecto, Inc.

Galectin-3 is a ß-galactoside-binding lectin highly expressed in fibrotic tissue of diverse etiologies and has been shown to play a key role in organ fibrosis. Galecto, Inc. has developed a number of high-affinity and selective galectin-3 inhibitors currently undergoing clinical investigation in fibrotic diseases of the lung and liver. This talk will focus on the translational pharmacology of these galectin-3 inhibitors and their potential as anti-fibrotic therapies.

10:20 am

Anti-Fibrotic Activity of PLN-74809, a Clinical Stage Dual avb6/avb1 Integrin Inhibitor

Scott Turner, PhD, Vice President, Translational Sciences, Pliant Therapeutics

PLN-74809 is an avb6/avb1 dual integrin inhibitor which blocks the activation of latent TGF-b1 and 3 by epithelial cells and fibroblasts. TGF-b is a well-established pro-fibrotic cytokine, however previous attempts to broadly inhibit TGF-b with antibodies or kinase inhibitors have produced unacceptable side effects, preventing their use in the treatment of fibrosis. By targeting the activation of TGF-b with a selective inhibitor of avb6 and avb1 we are able to reduce the activity of TGF-b in the areas where there is upregulation of these integrin targets. We have shown by PET imaging, immunohistochemistry and protein quantification, that avb6 and avb1 are upregulated in the fibrotic regions of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). Furthermore, we have demonstrated in animal models and human precision cut tissue slices that treatment with PLN-74809 can significantly reduce fibrosis. In Phase 1 clinical trials we have demonstrated proof of mechanism in alveolar macrophages isolated from healthy volunteers dosed with PLN74809. PLN-74809 is currently being studied in two Phase 2 clinical trials, INTEGRIS-IPF and INTEGRIS-PSC.

10:40 am

Inhibition of Dimeric Calpains Results in Reduction of Lung and Liver Fibrosis

Maria E. Fuentes, PhD, Executive Vice President, Research, Blade Therapeutics

Calpains are non-lysosomal, calcium-activated cysteine proteases that play multiple roles in a wide range of cell types. A subgroup of this calpain family, dimeric calpains (CAPN1, 2 and 9), have been shown to play a role in fibrotic disease models. Blade Therapeutics has developed selective calpain inhibitors that are active at inhibiting collagen production in in vitro systems and they reduce lung and liver fibrosis in vivo.

11:00 am Session Break
11:20 am LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Kevin Hart, PhD, Principal Scientist, Inflammation, Pfizer Inc.
Panelists:
Rob Slack, PhD, Director of Pharmacology, Galecto, Inc.
Scott Turner, PhD, Vice President, Translational Sciences, Pliant Therapeutics
Maria E. Fuentes, PhD, Executive Vice President, Research, Blade Therapeutics
11:40 am Refresh Break - View Our Virtual Exhibit Hall
1:25 pm Brown Bag Lunch and Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Grab your own lunch 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. Discussion topics and moderators will be listed on the website.


BREAKOUT: New Fibrosis Targets & Establishing Proof of Concept

Katerina Leftheris, PhD, VP & Head, Chemistry, Pliant Therapeutics
  • Renal fibrosis targets
  • Inflammation/Immune targets
  • Current and novel biomarkers
  • Imaging techniques in discovery

NEW TARGETS

2:00 pm

Caveolin, a New IPF Target

Brian Windsor, PhD, CEO, Lung Therapeutics

Caveolin-1 (Cav-1) regulates numerous cell signaling pathways related to fibrotic processes. As the loss of cell membrane Cav-1 protein is observed in many fibrotic diseases, it has remained elusive as a target for fibrosis. We have developed LTI-03, a peptide derived from the Cav-1 scaffolding domain, which has demonstrated efficacy in a variety of preclinical fibrosis models via multiple routes of administration. Our data indicates that LTI-03 attenuates profibrotic mechanisms and protects lung epithelial cells critical for surfactant production and lung homeostasis.

2:20 pm

Cell-Specific Roles of Integrin Alpha V in Inflammation and Fibrosis

Kevin Hart, PhD, Principal Scientist, Inflammation, Pfizer Inc.

Integrin-alpha V serves as a master driver of fibroproliferative diseases in multiple organs. We investigated roles for integrin-alpha V interactions on fibroblasts and cholangiocytes, and defined novel roles for cell-specific expression of ITGAV in the regulation of inflammatory responses and in driving microenvironmental fibrogenesis.

2:40 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Cory M. Hogaboam, PhD, Professor, Medicine, Cedars-Sinai Medical Center
Panelists:
Brian Windsor, PhD, CEO, Lung Therapeutics
Kevin Hart, PhD, Principal Scientist, Inflammation, Pfizer Inc.
Atul Tiwari, Phd, Deputy Research Director, Discovery, Syngene International Ltd
3:00 pm Close of Conference

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