Mestag Therapeutics Enlists Leading Cancer Biology & Immunology Advisors to Support Clinical Development of its Lead Oncology Program

Mestag Therapeutics recently announced the appointments of additional distinguished, world-leading advisors to guide the development of its lead program M300, a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor.

The new appointments expand Mestag’s advisors and comprise a unique group of investigators with extensive experience in the development of novel cancer therapies and specific expertise in the field of TLS biology in cancer. TLSs are aggregates of immune cells which provide a site of entry and education for immune cells in the tumor. The presence of TLS in tumors has recently become recognized as strongly predictive of improved patient outcomes and better response to therapy.

Susan Hill, PhD, Chief Executive Officer of Mestag Therapeutics, said “Mestag’s M300 program opens up a new paradigm for the treatment of solid tumors. Advances in understanding TLS biology in cancer, and the associated benefit to patient outcomes, have enabled us to design a first-in-class program with the potential to benefit large numbers of patients with cancer. We are honored to work with such an eminent group of experts in this field to drive the program urgently into the clinic.”

The newly appointed M300 advisors comprise Prof. Gabriele Bergers, group leader at the Flanders Institute for Biotechnology (VIB) Center for Cancer Biology and Professor of Oncology at the University of Leuven in Leuven, Belgium; Prof. Julie R. Brahmer, Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology; Prof. Jeffrey L. Browning, Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology; Prof. Wolf H. Fridman, Professor Emeritus of Immunology at Université Paris-Cité, France; Prof. Catherine Sautès-Fridman, Professor Emeritus at Université Paris-Cité; Prof. Elizabeth M. Jaffee, Professor of Oncology and Deputy Director at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; and Prof. Ignacio Melero, Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra.

Ignacio Melero, MD, PhD, advisor to Mestag and Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra, said, “I look forward to collaborating with Mestag and to be a part of their world-class advisory team. I believe there is potential to develop transformative therapies for patients battling cancer. Mestag’s novel approach leverages known immunobiology, which for the first time, is being translationally harnessed to stimulate an anti-cancer immune environment within cancer tissue. Recent evidence supports the beneficial role of tertiary lymphoid structures in cancer, and the ability of a therapy to safely increase their presence could result in an efficacious intervention in patients with solid tumors.”

Gabriele Bergers, PhD, is a Professor of Oncology at the University of Leuven and a group leader at the Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology in Leuven since 2016. Before her move to the VIB, she was a Professor in the Department of Neurological Surgery and a PI in the Brain Tumor Research Center (BTRC) at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), for 20 years. She has made seminal discoveries about perivascular tumor niches regarding the vasculature and the immune cell compartment in regulating neovascularization, inflammation, and TLS formation in cancer and in revealing and understanding intrinsic and evasive resistance mechanisms of tumors to antiangiogenic immunotherapies. Dr. Bergers has received awards, including the Sidney Kimmel, the Sandler Opportunity, UCSF Breakthrough Biomedical Research, and the Judah Folkman. She has acted as an external advisory board member for a number of universities and pharmaceutical companies. Dr. Bergers was the Co-director of the Tumor Microenvironment Brain Tumor Center at UCSF and an advisor to the Max-Planck-Institute for Biomedicine in Muenster, Germany. She was a scientific co-founder of Oncurious.

Julie R. Brahmer, MD, is the Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-Leader of Cancer Immunology, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology. She also directs the Kimmel Cancer Center on the Johns Hopkins Bayview campus and is co-principal investigator on Johns Hopkins’ National Clinical Trials Network (NCTN) cooperative group grant. Dr. Brahmer is an active clinical leader in the treatment of lung cancer and mesothelioma. Dr. Brahmer’s research and clinical practice focuses on the development of new therapies for the treatment of lung cancer and mesothelioma. She is a member of the American Society of Clinical Oncology, serves on the board of directors of the Society of Immunotherapy for Cancer, and is the Chair of the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee. She is also on the medical advisory board of several lung cancer patient advocacy groups including LUNGevity, the Lung Cancer Research Fund, and Lung Cancer Research Foundation of America.

Jeffrey L. Browning, PhD, is a Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology. He has a PhD in biochemistry from the University of Wisconsin. As a research scientist in the immunobiology discovery group at Biogen from 1984 to 2012, he centered on the tumor necrosis factor (TNF) family of regulatory molecules, including the discovery of the lymphotoxin, B-cell activating factor (BAFF) and TNF-like weak inducer of apoptosis (TWEAK) systems, and translation of modulators of the lymphotoxin pathway to the clinic in indications ranging from autoimmune disease and inflammatory bowel disease to oncology. He joined Boston University School of Medicine in 2013, with a current focus on altered vascular and stromal states in the perivascular compartment in the skin of systemic sclerosis and lupus patients and the impact on the pathology. Early in his career, he undertook postdoctoral work in the biophysics department of the University of Basel, Switzerland, using nuclear magnetic resonance to study membrane structure; and in the neurobiology department at the University of California, San Francisco researching the neuromuscular junction.

Wolf H. Fridman, MD, is Professor Emeritus of Immunology at Université Paris-Cité. He is an expert in analysis of the tumor microenvironment, demonstrating that context, including functionality, location and density of the immune infiltrate in colorectal tumors, is the major prognostic factor for human cancers. He is involved in developing bioinformatic tools to quantify tumor microenvironment cells used to predict prognosis and immunotherapeutic responses in renal cell and colorectal cancers and sarcomas. His immune classification of soft tissue sarcoma tumors helped demonstrate that TLS and B cell signatures predict favorable clinical outcomes and therapeutic responses to anti-PD-1 therapy better than T cells, findings recently extended to other cancers treated with immune checkpoint blockers. These showed plasma cells generated inside TLS produce anti-tumor antibodies associated with a patient’s response to immunotherapy, opening the way for novel immune-based tools for efficient prognosis and therapy.

Catherine Sautès-Fridman, PhD, is Professor Emeritus at Université Paris-Cité. She is the former Director of the Cancer, Immunology and Immunopathology department and Director of the Immunotherapy and Cancer team at Centre de Recherche des Cordeliers. Her research focuses on the heterogeneity of the immune and inflammatory components of the tumor microenvironment to identify new prognostic and theranostic markers. She carried out work in several fields: histocompatibility antigens, demonstration of the association of human leukocyte antigens (HLAs) with beta2-microglobulin and description of the 3rd histocompatibility locus in mice, H-2L and HLA-C in man, receptors for immunoglobulin G antibodies (biological activity and 3D structure), immuno-oncology (role of interleukin-17, TIME profiles of patients at risk of disease progression in localized kidney cancers, role of Tertiary Lymphoid Structures). She is the former President of the French Society of Immunology and European Federation of Immunological Societies. She founded the EFIS-EJI Ita Askonas Award to acknowledge female group leaders in immunology, and she founded the first European Congress of Immunology. She is Editor-in-Chief of La Revue Immunité et Cancer.

Elizabeth M. Jaffee, MD, is an internationally recognized expert in cancer immunology and pancreatic cancer. She is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-Director of the Skip Viragh Pancreatic Cancer Center, and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focus is on developing novel immunotherapies for the treatment and prevention of pancreatic cancer. Prof. Jaffee is a past President of AACR and has served on several committees at the National Cancer Institute. She is Chief Medical Advisor to the Lustgarten Foundation for Pancreatic Cancer Research, and the Inaugural Director of the Convergence Institute for Integrating Technologies and Computational Sciences at Johns Hopkins. She is Chair of President Biden’s Cancer Panel.

Ignacio Melero, MD, PhD, is Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra. He leads a group working in translational tumor immunotherapy with an emphasis on cell therapy, cytokine gene therapy, and immune-stimulatory monoclonal antibodies. Earlier in his career, Dr. Melero contributed to seminal discoveries in the function of Natural Killer cells, and T-cell co-stimulation via CD137 (4-1BB). Dr. Melero has been awarded the BIAL Prize of Medicine, the Conde de Cartagena Award from the Royal Academy of Medicine, Doctor Durantez LAIR Foundation Award and a CRI research award. He has served on advisory boards of Bristol Myers-Squibb, Roche-Genentech, AstraZeneca, Merck Serono and Boehringer Ingelheim, and holds research grants by Pfizer, Bristol Myers Squibb, and Alligator.

M300 is a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor. TLSs are aggregates of immune cells that form in tumor tissue as part of our bodies’ natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLSs. TLSs in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy.

Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients. We are progressing a pipeline of sophisticated first-in-class antibodies designed to improve the lives of patients with cancer and inflammatory disease. Together with our collaboration partner Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies.

Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Women’s Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation – JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures. Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies. For more information, visit  www.mestagtherapeutics.com.