By George Vratsanos, M.D., and Luke Devey, M.D., Ph.D., Janssen Immunology
There are many critical decisions to make in early-stage drug development, which must be informed by deep insights into the biology of disease. With the rapid advances of medical science, it is important to acknowledge that the entirety of the expertise to guide those decisions cannot be found within one company, a realization that is both humbling and energizing. For this reason, deep and enduring collaborative relationships between academia and industry can be mutually invaluable: both parties bring complementary resources and expertise to a shared mission of seeing new scientific advances translated into novel therapeutics.
Last year, Janssen Biotech and the University of Oxford established the Cartography collaboration to understand similarities and differences in the pathogenic pathways driving different immune-mediated inflammatory diseases, by creating a cellular map of expressed genes and proteins. Our objective is to better understand disease at the molecular, cellular, and pathway levels that will enable the identification of novel actionable therapeutic targets. Furthermore, in the Cartography collaboration, Janssen and Oxford are employing the latest technologies to dissect which types of patients – biologically – will respond best to a targeted therapy, an approach often referred to as precision medicine. In this piece, we describe how we are working closely with collaborators at the University of Oxford, leveraging the latest technologies to build a systematic knowledge base to support decision-making in drug discovery and development.
What Has The Collaboration Accomplished So Far?
The Janssen-Oxford Cartography collaboration is a unique model of co-creation in drug development where industry and academic colleagues work alongside each other to design rigorous and creative experiments. Janssen teams are paired with Oxford’s physicians and scientists to create a consortium that contributes to a unique body of data that we call an “atlas” of disease. There are many challenges in delivering this work, from recruiting patients to development of novel analytical approaches, both in the lab and computationally.
So far, the team has laid the foundation for accelerating our understanding of human disease pathophysiology at the cellular and molecular levels, offering the potential for discovering new drug targets, establishing new biomarker signatures, and creating possibilities for identifying new uses, or indications, for Janssen therapeutics in development or on the market.
Our scope is wide: in phase one, initiated in 2021, Cartography spanned the full range of immune-mediated inflammatory diseases. This ground-breaking model has proven so successful that our strategic Cartography collaboration with Oxford has been expanded in a second phase to encompass additional disorders across four therapeutic areas: infectious disease, vaccines, oncology, and neuroscience. These areas will utilize the infrastructure established in the original project to address knowledge gaps in an efficient multifaceted approach. Cartography collaboration projects will allow us to understand cellular tissue-based networks across multiple diseases and organs and relate them to those in the blood. Those single-cell data sets will be complemented by additional multiomic data such as serum proteomics and bulk RNA and DNA sequences, creating a cross organ atlas that can be referenced to additional multilayer analysis. The project establishes a unique research ecosystem in which to collaborate across disciplines between Janssen and Oxford scientists.
As data are integrated into the cellular map, our vision is to build an in silico resource to validate therapeutic targets early and to discover biomarkers and mechanistic strata of the patient population. The data that are generated are comprehensive and complex. Computational biologists from Janssen and Oxford can then seek to gain novel insights from the data set and address questions across target pathways, diseases, and specific patient populations, allowing for expedient decision-making about medicines in our R&D pipeline. As the atlas continues to grow in diseases from several therapeutic areas, this potentially allows us to compare the relevance of key mechanisms across diverse diseases.
Novel Single-Cell Technology Uncovering Pathogenic Pathways
Advances in next-generation sequencing, minimally invasive biopsy techniques, and computational biology have enabled scientists to build deep profiles of individual cells. The detailed cellular map of genes and proteins that Janssen and Oxford scientists are creating through their collaboration uses a new technique called Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq).1
CITE-Seq is capable of measuring cell surface proteins along with single-cell RNA sequencing to uncover the pathogenic pathways active in cells. Then, a novel computational approach integrates cellular proteomics and transcriptomics into an efficient, single-cell readout. CITE-Seq provides a detailed view into disease states, enabling insight into pathological processes within single cells and even abnormalities in how those cells interact with each other. Oxford has an outstanding track record of using this pioneering technique, and the Janssen collaboration represents a scale-up to enable insights across diseases to support pharma decision-making.
CITE-Seq technology is also being deployed in the context of a novel early phase clinical trial to understand the precise mechanism of action of new therapeutics in the Arthritis Therapy Acceleration Programme (A-TAP).
A-TAP: Collaborating On The Translation Of Novel Biology In The Clinic
Funded by the Kennedy Trust for Rheumatology Research, A-TAP brings together the Universities of Birmingham and Oxford, seven National Health Service (NHS) partners in the United Kingdom, and industry to jointly develop treatments for immune-mediated inflammatory diseases based on the underlying causes of inflammatory disease.
A-TAP represents the first time in which Janssen Immunology is collaborating with an academic partner on an early phase clinical trial to determine how one pathway may work across several diseases. In one clinical trial, driven by Bayesian cell-based outcomes, we are examining the biology of a programmed cell death receptor-1 (PD-1) agonist monoclonal antibody across three indications — rheumatoid arthritis (RA), ulcerative colitis (UC), and Sjögren’s syndrome (SS). In this setting, it is possible to take samples for CITE-Seq analysis before and after novel therapeutics to understand in detail how the medicine has modified disease biology in the target tissue. By performing these studies across diseases together, it will be possible to unify and analyze these data much more effectively than it would be if it were a disparate set of smaller individual collaborations.
Toward Mutually Beneficial Outcomes And Shared Goals
To be successful in unlocking the molecular drivers of immune-mediated inflammatory diseases, academia and industry must work together to find solutions. Our academic collaborators have a broad clinical footprint: their access to patients enables us to look across a wide variety of different diseases and break down not just the bench to bedside silo but also the bedside to bedside, inter-specialty silos. They also have a strong track record in pioneering new laboratory techniques and novel computational approaches, enabling us to better analyze molecular drivers of disease for individuals. We also benefit from having access to some of the foremost experts in their fields of immunology who bring invaluable scientific insights and ideas to our collaborations.
As industry collaborators, we offer our partners insight into the process of drug development and how novel scientific insights can support pharma decision-making. The collaborations also open the potential for a stream of published research. And together we will design and conduct studies and analyze and interpret data that we hope will break new ground in bringing new medicines to patients.
Our innovative Cartography and A-TAP collaboration models have demonstrated the mutually beneficial value of partnerships and meaningful outcomes in our shared goal of expediting the development of molecularly targeted immune therapies. Ultimately, we aim to enable clinicians to treat the right patients with the right medications at the right doses that will lead to remission or potentially lead to cures.
- Stoeckius, M., Hafemeister, C., Stephenson, W. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat Methods 14, 865–868 (2017). https://doi.org/10.1038/nmeth.4380.
About The Authors:
George Vratsanos, M.D., is vice president, translational science and medicine (TSM) for the Immunology Therapeutic Area at Janssen Research & Development, LLC. Prior to joining Janssen, Vratsanos served as executive global program head of the Immunology and Dermatology franchises at Novartis. Before that, he led Roche’s clinical development in autoimmune diseases as the translational medicine leader. A rheumatologist by training, Vratsanos earned his M.D. from New York University and completed a postdoctoral fellowship in rheumatology/immunology at Yale University. He holds a B.S. and an M.S. in biomedical engineering from Columbia University. Follow him on LinkedIn.
Luke Devey, M.D, Ph.D., is vice president and head of translational sciences for the Immunology Therapeutic Area at Janssen Research & Development, LLC. In May 2020, he was conferred the title of Visiting Professor of Immunology by the University of Oxford. Previously, Devey served as executive director, head of early discovery biology at Celgene. Prior to Celgene, he spent five years at GSK as senior director, translational medicine. Devey received his Bachelor of Medicine and Bachelor of Surgery (BMBCh) in medicine and his MA in physiological sciences at the University of Oxford, his Ph.D. in medicine from the University of Birmingham and his MRCSEd from the Royal College of Surgeons of Edinburgh. Follow him on LinkedIn.