Cambridge Healthtech Institute’s Inaugural

New Small Molecule Drug Targets

RNA, Immunology & Oncology, and the Microbiome

June 2-4, 2020

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 - Detailed Agenda

*Separate registration required.

Tuesday, June 2


Molecules are crucial for delivering cellular information and genetic regulation, but until recently, the drug discovery world has emphasized protein drug targets. Our lack of knowledge in RNA biology prevented us from exploring possibilities of RNA drug targets, but with recent advances in technologies, such as sequencing, new therapeutic strategies are being explored. Join us as we discuss methods and tools to identify specific, potent, novel, small molecule binders of RNA.

10:00 am Main Conference Registration Open


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

Petter_JenniferJennifer 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

Pandey_PramodPramod 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


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

Jafferey_SamieSamie 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

Weetall_MarlaMarla 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

Dales_NatalieModerator: 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


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.

Sarwar_NadeemModerator: 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

Wednesday, June 3


Day 2 focuses on new disease targets in immunology and oncology which are being discovered at a rapid pace. Many are intracellular targets and therefore especially suited to modulation by small molecule-based drugs, as opposed to biologics, because small molecules can cross the cell membrane. Many of these new targets are also part of protein-protein interactions or large molecular complexes, which add to the challenges of new drug discovery.

7:30 am Registration Open and Morning Coffee


8:10 Chairperson’s Remarks

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

8:15 An IL36 Antagonist for Probing Psoriasis

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

IL-36 cytokines are pro-inflammatory members of the IL-1 superfamily that are upregulated in inflammatory disorders. Targeting IL-36 signaling has been an attractive approach for several dermatological diseases including psoriasis. In this talk, I will present our discovery of A-552, a novel first in class small molecule antagonist of the IL-36 signaling pathway. A-552 binds potently and selectively to human IL-36g and was capable of attenuating IL-36g induced responses in mouse and human disease models.

8:45 Targeting Metabolic Pathway Regulators for Inflammation and Autoimmunity

Poyurovsky_MashaMasha 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


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

McMinn_DustinDustin 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

Murtie_JoshJosh 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


1:45 - 3:15

Lgr5 Stem Cell-Based Organoids in Human Disease

Clevers_HansHans Clevers, MD, PhD, Principal Investigator of Hubrecht Institute and Princess Máxima Center, CSO of HUB Organoids Technology

Organoid technology opens a range of applications in fields such as physiology, study of disease, drug development and personalized medicine. Human organoids represent excellent disease models, be it infectious, hereditary or malignant  Eventually, cultured mini-organs may be used to replace transplant organs from donors. I will describe how we originally created ‘mini-guts’ via 3D culture systems of stem cells of the small intestine and colon, and then expanded the technology to virtually all human organs.

Systematically Drugging Ras

Fesik_StephenStephen Fesik, PhD, Professor of Biochemistry, Pharmacology, and Chemistry, Orrin H. Ingram II Chair in Cancer Research, Vanderbilt University School of Medicine

K-Ras is a small GTPase that is mutated in pancreatic (90%), colon (50%), and lung (30%) carcinomas. Downregulation of activated Ras reverses the transformed phenotype of cells and results in the dramatic regression of tumors in murine xenograft models. Thus, K-Ras inhibition represents an attractive therapeutic strategy for many cancers. In this presentation, I will discuss our efforts to directly target Ras at two sites and target SOS, a molecular partner of Ras, with activators and inhibitors. 

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


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

Xia_BingBing 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 - View Details

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

Thursday, June 4


Awareness of the impact of the human microbiome (microbe communities residing in our bodies) on our health has been steadily increasing over the past decade. The last day of the conference will explore strategies for either modulating the microbiome, sometimes specific targets, for controlling responsiveness to specific treatments, or to treat particular disease states.

8:00 am Registration Open and Morning Coffee


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

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

Over the last few years, there has been tremendous interest in the application of artificial intelligence and machine learning in drug discovery. Ultimately, the success of any predictive model comes down to three factors: data, representation, and algorithms. This presentation will provide an overview of these factors and how they are critical to the successful implementation and deployment of AI methods.

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


10:25 Chairperson’s Remarks

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

10:30 Engineering Microbes to Treat Metabolic and Immunological Diseases

Charbonneau_MarkMark Charbonneau, PhD, Head, Quantitative Biology, 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 engineered E. coli Nissle strains designed for the treatment of metabolic diseases.

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

Julia Kemis, PhD, Postdoctoral Fellow, Cheminformatics, Merck

Although the intestinal microbiome is a known modulator of drug pharmacokinetics and metabolism, we lack a comprehensive understanding of how drug metabolism varies among individual microbiomes. To address this challenge, we developed an informer set of compounds encompassing diverse drug-like chemical space that can be applied to functionally characterize microbiome samples. The informer set presents a novel strategy to compare and group microbiome samples of interest based on metabolic activity.

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

Abid_BilalBilal 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


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

Donabedian_DavidDavid 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