RPTR-168

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Repertoire® Immune Medicines announced today that Torben Straight Nissen has been appointed as interim Chief Executive Officer, succeeding John Cox, who will continue with the company in an advisory role. With more than two decades of leadership experience, Straight Nissen joins the company as it shifts its resources and operations to focus primarily on unlocking the potential of Repertoire’s DECODE™ Platform to develop transformative immune medicines against novel immune targets in cancer, autoimmune disorders, and infectious disease. “ I want to thank John for his leadership and vision for harnessing the potential of the immune repertoire to develop new medicines,” said Doug Cole, M.D., Chairman, Repertoire and Managing Partner, Flagship Pioneering. “ As the first CEO of Repertoire, John established the company to deliver novel immune medicines to patients, and we will continue to build upon this bold ambition.” Cole continued, “ We welcome Torben as the next CEO of Repertoire. His significant experience leading and shaping platform-based biotech companies makes him well-positioned to drive Repertoire forward toward unlocking the potential of its DECODE platform.” “ Repertoire has applied its proprietary DECODE platform to develop an unprecedented and unique understanding of the immune synapse. I am energized by the opportunity to leverage Repertoire’s powerful platform to develop novel and highly selective immune-based medicines for the treatment of cancer, autoimmune disorders, and infectious disease,” said Straight Nissen. “ I look forward to working with Repertoire’s impressive team to provide new and important therapies for patients with these diseases.” “ The mission of Repertoire is to discover the immune codes that drive cellular immunity and to use those codes to create new immune medicines,” said Cox. “ Our recent discoveries of novel epitopes and T cell receptors in cancer and autoimmune diseases demonstrate the promise of the platform that we built. I am grateful to each member of the Repertoire team for making these advancements possible, and to the leadership team that built this company. I look forward to seeing Repertoire continue its mission to create a new class of immune medicines under Torben’s leadership.” About Torben Straight Nissen Torben Straight Nissen is a senior partner at Flagship Pioneering, contributing to Flagship’s strategic and operational objectives, including the origination of new Flagship Labs companies. He is an experienced biotech entrepreneur and has been a member of Flagship’s ecosystem since first joining as President of Rubius Therapeutics in 2016. Prior to joining Flagship, Straight Nissen was at Pfizer where he led Strategic Portfolio Management for the company’s worldwide R&D organization and oversaw a portfolio spanning from discovery to Phase 2 across all major therapeutic areas. He has held leadership positions in multiple biotech companies, including Ascendis Pharma and Maxygen. Straight Nissen currently serves on the board of Axcella Health and is the founding CEO of FL84. He is also a co-author or co-inventor of over 100 publications and published patents. Company Update In October, the company stopped Phase 1 clinical studies of its autologous multi-targeted T cell therapeutic candidates, RPTR-147 and RPTR-168 in human papillomavirus (HPV) positive tumors. This followed an assessment of recent data which showed that while stable disease was observed in a small group of patients, this effect was limited and does not support advancing these programs. The company plans to apply the translational insights from these studies to inform its ongoing development of novel treatments for solid tumors. These changes reposition the company as a pre-clinical organization with reduced operational needs, and as a result, the company reduced its staff earlier this month. Going forward, Repertoire will focus on unlocking the potential of its proprietary DECODE platform to develop transformative medicines against novel immune targets in cancer, autoimmune disorders and infectious disease. About the DECODE™ Platform The DECODE platform is a powerful discovery engine that characterizes essential elements of the immune synapse. In particular, the platform identifies T cell receptor-antigen pairs in the context of other important features of the immune synapse, such as T cell function and how antigens are presented by molecules on antigen-presenting cells, known as major human leukocyte antigen, or HLA, molecules. Repertoire intends to utilize these insights into key drivers that govern immune function to design and develop novel immune product candidates. About Repertoire® Immune Medicines Repertoire Immune Medicines is a biotechnology company dedicated to creating treatments for diseases based on the power of the human T cell repertoire to eliminate cancer cells, target pathogens and regulate immune function in autoimmune disease. Our proprietary DECODE TM platform is designed to provide a comprehensive understanding of the full repertoire of interactions between T cell receptors and their antigen targets that take place when diseased cells are present. This complex and intricate biological process is known as the immune synapse. We believe the ability to decode these interactions represents one of the greatest opportunities for innovation in medical science. Utilizing our DECODE platform, our goal is to identify the specific T cell-antigen pairs that provide immune surveillance in cancer, generate memory responses to pathogens, and those that cause tissue damage in autoimmune disease. Repertoire was founded in 2019 by Flagship Pioneering. Its team operates from sites in Cambridge, Massachusetts and Zurich, Switzerland and uses its DECODE technology to rationally design treatments for cancers, autoimmune disorders and infectious diseases. To learn more about Repertoire, please visit our website: www.repertoire.com and follow us on LinkedIn and Twitter .

Repertoire Immune Medicines announced today that Science Advances published preclinical research demonstrating the company’s cell-tethering technology can deliver the potent cytokine interleukin-12 (IL-12) to solid tumors without eliciting the severe systemic toxicities typically associated with the use of this cytokine. The research, conducted in mouse models, found that the use of cell-tethered IL-12 elevated anti-tumor activity in the immunosuppressive tumor microenvironment (TME). “A tumor has multiple mechanisms that help it avoid recognition and elimination by the immune system. These defense mechanisms remain a major challenge for cellular immunotherapies to achieve a durable clinical response,” said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. “In this preclinical research, Repertoire’s cell-tethering technology delivered dose-controlled amounts of IL-12 onto the surface of tumor-targeted T cells. These IL-12-tethered T cells were associated with pronounced repolarization of the tumor microenvironment, ultimately resulting in enhanced T cell response, which has the potential to improve the efficacy of the cellular immunotherapies.” Tumors have immunosuppressive microenvironments that can limit the efficacy of cellular immunotherapies used in cancer treatment. Immune-stimulating cytokines such as IL-12 have been shown to counter the immunosuppressive conditions within the tumor. However, the dose of IL-12 required to achieve these beneficial effects has been associated with severe systemic toxicities. In the publication, “Cell-surface tethered IL-12 repolarizes the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy,” Repertoire’s tethering technology achieved direct and localized delivery of IL-12 to tumors without systemic toxicities. The use of tethered IL-12 was also associated with repolarization of myeloid-derived suppressor cells into activated inflammatory monocytes that support anti-tumor activity in the TME. Repertoire is currently investigating the use of cell-tethered IL-12 in an ongoing Phase 1 study of its investigational candidate RPTR-168 for human papillomavirus-positive tumors.