Cambridge Healthtech Institute’s Inaugural

New Small Molecule Drug Targets
( 新小分子标靶 )

RNA、免疫学与肿瘤学、微生物组

2020年6月2日~4日


Small molecule-based therapies have remained a mainstay of drug discovery and development activity, contributing to 75% of new drug approvals in the past five years, with the remaining modalities being comprised mostly of biologic-based therapies. Small molecules’ oral bioavailability and their ability to enter the cell is an advantage over biologics, especially because the number of intracellular disease targets being identified in the areas of immunology, oncology and the microbiome is increasing rapidly. Moreover, new approaches in biophysical and medicinal chemistry are enabling more effective discovery or design of small molecules that can modulate many of the newer intracellular targets of disease, which often are protein-protein interactions or large molecular complexes that are different from the traditional enzymatic targets of small molecules. The latest new type of intracellular target for which small molecule drug discovery is showing promise is RNA-based molecular complexes. Join fellow medicinal chemists and discovery scientists to stay abreast of, share knowledge, and discuss strategies for addressing some of the ‘hottest’ small molecule targets in the biomedical field.

Final Agenda

Recommended Short Course*

SC2: Immunology Basics: Focusing on Autoimmunity and Cancer

*Separate registration required.

6月2日 (二)

10:00 am Main Conference Registration Open

TARGETING RNA WITH SMALL MOLECULES

11:15 Chairperson’s Remarks

Pramod Pandey, PhD, Principal Scientist, Merck Research Labs Exploratory Science Center

11:25 FEATURED PRESENTATION: Drugging RNA with Small Molecules — A Drug Discovery Perspective

Jennifer Petter, PhD, Founder & CSO, Arrakis Therapeutics

RNA is upstream of all biology and thus presents a vast array of therapeutically attractive targets.  Most therapeutic agents that bind directly to RNA are either antibiotics blocking bacterial ribosome function or oligonucleotides with their attendant pharmaceutical limitations.  At Arrakis, we have identified druggable RNA sub-structures in mRNA and orally available small molecules that bind to those structures selectively and thereby modulate mRNA function.  In this talk I will describe recent results that support this larger mission.

11:55 Drugging RNA

Natalie Dales, PhD, Director, Global Discovery Chemistry, Novartis

12:25 pm Discovering Novel RNA-Binding Proteins for Small Molecule Drug Discovery

Pramod Pandey, PhD, Principal Scientist, Merck Research Labs Exploratory Science Center

A large fraction of the genome is transcribed into non-coding RNAs and many of these have been implicated in influencing diseases. We are studying these in the context of diseases, relating to barrier function/dysfunction. Towards that goal, we are developing chemical biology tools to study the RNA protein interactions and find novel targets for small molecule drug discovery.

12:55 Transition to Lunch

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break

TARGETING RNA WITH SMALL MOLECULES (CONT.)

2:00 Chairperson’s Remarks

Samie Jaffrey, MD, PhD, Greenberg-Starr Professor, Pharmacology, Weill Cornell Medicine

2:05 Detecting Interactions of Small Molecules with RNA Using Genetically Encoded Fluorescent RNAs

Samie Jaffrey, MD, PhD, Greenberg-Starr Professor, Pharmacology, Weill Cornell Medicine

Detecting and measuring small molecule binding to RNA in living cells has limited the development of therapeutic small molecule ligands of RNA. Here we show how small molecule target engagement on RNA can be imaged in real-time. In this approach, disease-relevant RNA sequences can be converted into fluorescent sensors for detecting small molecule binding, optimizing compounds, and for developing small molecule therapeutics.

2:35 Targeting Pre-mRNA Splicing with Small Molecules

Marla Weetall, PhD, Vice President, Pharmacology, PTC Therapeutics

Pre-mRNA splicing is emerging as a key control point in the expression of disease-modifying genes. Mutations causing alterations in splicing may result in diseases. Small molecules that affect pre-mRNA splicing have been identified and are being clinically developed. At PTC, we have developed a general approach to discover and develop drugs targeting splicing. Here we describe the application of this approach to spinal muscular atrophy, familial dysautonomia, and Huntington’s disease.

3:05 PANEL DISCUSSION: What Challenges Come with Targeting a New Modality

Moderator: Natalie Dales, PhD, Director, Global Discovery Chemistry, Novartis

RNA and its many different forms are a new target for small molecules. What challenges come with this new target? With so many new types of targets – mRNA, RNA-protein complexes, lncRNA, epitranscriptomics – what are the best practices moving forward?

3:35 Sponsored Presentation (Opportunity Available)

4:05 Networking Refreshment Break and Transition to Keynote


PLENARY KEYNOTE SESSION

4:25 - 6:05 Driving Entrepreneurial Innovation to Accelerate Therapeutic Discoveries

The life sciences community has an unprecedented scientific arsenal to discovery, develop and implement treatments, cures and preventions that enhance human healthcare.

Moderator: Nadeem Sarwar, President, Eisai Center for Genetics Guided Dementia Discovery (G2D2), Eisai Inc.

Panelists: Anthony Philippakis, Chief Data Officer, Broad Institute; Venture Partner, GV

Barbara Sosnowski, Vice President and Global Head, Emerging Science & Innovation Leads, WWRDM, Pfizer

John Hallinan, Chief Business Officer, Massachusetts Biotechnology Council

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing

7:10 Close of Day

6月3日 (三)

7:30 am Registration Open and Morning Coffee

TARGETING AUTOIMMUNITY & INFLAMMATION

8:10 Chairperson’s Remarks

Dustin McMinn, PhD, Senior Director, Head of Chemistry, Kezar Life Sciences

8:15 An IL36 Antagonist for Probing Psoriasis

Chaohong Sun, PhD, Director & Research Fellow, Protein Sciences and Fragment Based Drug Discovery, AbbVie

8:45 Targeting Metabolic Pathway Regulators for Inflammation and Autoimmunity

Masha Poyurovsky, PhD, Vice President, Discovery Biology, Kadmon Corporation, LLC

The talk will provide an introductory overview of the metabolic pathways involved of immune cell function under the physiologic and pathologic conditions, providing specific examples of targeting metabolic pathways as means of regulating autoimmune inflammation. Primarily, we will present Kadmon’s programs targeting glucose transporters (GLUTs) and PAICS, an enzyme in the purine biosynthesis pathway, showing promise in in vitro and in vivo models of autoimmune disease.

9:15 Targeting the Mitochondria for Inflammation

Glenda Trujillo, PhD, Principal Scientist, CV and Fibrosis Drug Discovery Disease Sciences and Biology, R&D, Bristol-Myers Squibb

9:45 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

NEW MOLECULAR TARGETS FOR CANCER

11:00 Inhibitors of Sec61 as Novel Anti-Cancer Therapeutics

Dustin McMinn, PhD, Senior Director, Head of Chemistry, Kezar Life Sciences

Targeting and functionalization of most secreted and transmembrane proteins require co-translational translocation to the ER through the Sec61 translocon. Translocation is negotiated by interactions between Sec61 and signal sequences unique to each translating protein. Disruption of these interactions in specific or multi-signal sequence fashion presents an opportunity to modulate protein homeostasis toward therapeutic benefit. Development of signal and multi-signal sequence-selective Sec61 inhibitors as novel anti-cancer agents will be discussed.

11:30 Targeting Metabolic Susceptibilities in the Treatment of Hematologic Malignancies

Josh Murtie, PhD, Senior Director, Head of Cancer Biology, Agios

The treatment of hematologic malignancies has seen significant advances in the past decade, particularly in specific subgroups of patients. While many patients have benefited from these treatments, the prognosis for numerous others remains poor. Agios has focused on identifying metabolic vulnerabilities in a variety of cancers and has developed inhibitors of mutant IDH1 (AG-120; TIBSOVO) and DHODH (AG-636) with the goal of treating these malignancies.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

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

1:05 Session Break


PLENARY KEYNOTE SESSION

1:45 - 3:15

Lgr5 Stem Cell-Based Organoids in Human Disease

Hans Clevers, MD, CSO, Director of Research, Princess Máxima Center for Pediatric Oncology, University Medical Center Utrecht; Principal Investigator, Hubrecht Institute for Developmental Biology and Stem Cell Research

Systematically Drugging Ras

Stephen Fesik, PhD, Professor of Biochemistry, Pharmacology, and

Chemistry, Orrin H. Ingram II Chair in Cancer Research, Vanderbilt

University School of Medicine

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

SMALL MOLECULE IO TARGETS

4:00 Chairperson’s Remarks

Masha Poyurovsky, PhD, Vice President, Discovery Biology, Kadmon Corporation, LLC

4:05 Targeting the Adenosine Receptor for Immuno-Oncology

Olivier De Henau, MD, Medical Director, iTeos Therapeutics SA

4:35 IDO1 Inhibitors Discovered from DNA-Encoded Libraries

Bing Xia, PhD, NCE Encoded Library Technologies, RD Medical Science & Technology, GlaxoSmithKline

Indoleamine 2,3-dioxygenase-1 (IDO1) is induced and activated in response to viral and bacterial infection causing a dysfunctional immune response in clearing pathogens. IDO1 inhibitors (IDO1i) have the potential to restore immune function in indications such as cancer and infection. A structurally-unique IDO1i class was discovered through the affinity selection of a novel DNA-encoded library. After additional medicinal chemistry iterations, the compound series was elaborated into potential best-in-class preclinical molecules.

5:05 Find Your Table, Meet Your Moderator

5:10 Roundtable Breakout Discussions

TABLE: Targeting Cellular Metabolism: Not Just for Treating Cancer Anymore

Moderator: Masha Poyurovsky, PhD, Vice President, Discovery Biology, Kadmon Corporation, LLC

TABLE: Microbiome-Based Drug Development

Moderator: Caroline Kurtz, PhD, Head, Portfolio Strategy & Product Development, Synlogic

TABLE: What Happens When You Get Off-Target Effects When You Target RNA?

Moderator to be Announced

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

6月4日 (四)

8:00 am Registration Open and Morning Coffee


PLENARY KEYNOTE SESSION

8:30 - 9:40 Applications of Artificial Intelligence in Drug Discovery – Separating Hype from Utility

Patrick Walters, PhD, Senior Vice President, Computation, Relay Therapeutics

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

CHARACTERIZING THE MICROBIOME

10:25 Chairperson’s Remarks

Christopher Weidenmaier, PhD, Principal Scientist, Biology, Finch Therapeutics

10:30 Engineering Microbes to Treat Metabolic and Immunological Diseases

Caroline Kurtz, PhD, Head, Portfolio Strategy & Product Development, Synlogic

There is a growing appreciation of how the complex interactions occurring between the host and the gut microbiome play a role in human health and disease. At Synlogic, we engineer pathways into bacteria to enable secretion or consumption of known metabolites to modulate disease processes.  This presentation will review the design and translational development of specific, engineered E. coli Nissle strains for treatment of metabolic diseases, immunological diseases and cancer. The targets our microbes are engineered against will also be presented.

11:00 Drugs and Bugs: Microbiome Metabolism of Small Molecules

Julia Kemis, PhD, Postdoctoral Fellow, Cheminformatics, Merck

11:30 It Takes Guts to Rev Up CARs: Using the Gut Microbiome to Modulate Response to CAR T Cells

Bilal Abid, MD, Assistant Professor of Medicine, Medical College of Wisconsin

The gut microbiome has been shown, in pre-clinical and clinical settings, to homogenize and improve responses to immunotherapy, by enhancing innate and adaptive anti-cancer immune responses. Based on shared immunological and microbiological mechanisms, we are examining the potential of the gut microbiome in enhancing responses to CAR T-cells and as biomarkers of response and survival. Chimeric Antigen Receptor (CAR) T cells are autologous T cells re-directed towards a tumor-specific antigen and are FDA-approved for patients with refractory B-cell ALL and DLBCL.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

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

1:05 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

TARGETING THE MICROBIOME

2:00 Chairperson’s Remarks

Julia Kemis, PhD, Postdoctoral Fellow, Cheminformatics, Merck

2:05 Inflammatory Bowel Disease and the Microbiome

Christopher Weidenmaier, PhD, Principal Scientist, Biology, Finch Therapeutics

Inflammatory bowel diseases like ulcerative colitis and Crohn’s disease are characterized by altered mucosal immune responses and a dysbiotic microbiome. Finch uses machine learning models on clinical and microbiome intervention data to identify clinically relevant bacterial strains. This human-first discovery platform allows to identify and isolate strains with the ability to therapeutically modulate disease pathophysiology. Building consortia from such strains enables Finch to develop therapeutic candidates while minimizing translational risk.

2:35 Therapeutic Applications Based on the Gut-Brain Axis: Small Molecule Based Approaches to Treat CNS Diseases

David Donabedian, CEO, Axial Biotherapeutics

Axial Biotherapeutics is taking a revolutionary approach to treating CNS diseases by focusing on developing gut retentive, small molecules and delivering them to the gut and not the brain.

3:05 Presentation to be Announced

3:35 Close of Conference

* 活动内容有可能不事先告知作更动及调整。

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6月2日~4日

加速标靶发现

扩大化合物与Druggable空间

新小分子标靶

新适应症与模态

癌症免疫疗法进步

疾病模型

肿瘤治疗领域临床前研究策略的模式与工具

药物代谢与安全性测试的进步

癌症免疫疗法生物标记

临床与转译生物标记

新药发现与开发的AI

6月3日~4日

新药发现的技术


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