• Study provides insight into cellular immunity mounted against peptides of SARS-CoV-2 generated from non-canonical translations of the genome

• Novel epitopes discovered by Sabeti Lab, Broad Institute of MIT and Harvard; T cell memory response in individuals identified and elucidated by Repertoire’s DECODE™ platform

CAMBRIDGE, Mass. – June 2, 2021 – Repertoire Immune Medicines, a clinical-stage biotech company decoding the immune synapse to create novel immune therapies for cancer, immune disorders, infectious disease and other serious diseases, today announced the publication of new research that provides novel insights into how SARS-CoV-2 infected cells interact with the immune system. These findings, published online in the peer-reviewed journal Cell, provide new understanding into viral antigen presentation – from canonical open reading frames (ORFs) and internal out-of-frame ORFs – and how they may help epitope selection of peptides for immune monitoring and vaccine development for SARS-CoV-2 and other disease areas.

The manuscript, Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs, highlights findings from the first examination of SARS-CoV-2 antigen presentation on infected human cell lines using a method called immunopeptidomics. The approach revealed the presentation of several unexpected peptides derived from non-canonical reading frames of the SARS-CoV-2 genome, which were subsequently shown to be relevant in disease using a transgenic mouse model and human COVID patients. Together, these assays uncovered high T cell reactivity to novel peptides, with one peptide generating greater responses in COVID-19 patients than some of the most immunodominant T cell epitopes described in previous scientific literature.

The study was conducted by researchers at the Sabeti Lab, Broad Institute of MIT and Harvard, and headed by Pardis Sabeti, M.D., D.Phil. The biological significance of these discoveries in infected individuals were demonstrated using Repertoire’s proprietary DECODE™ platform. Through DECODE, researchers discovered the T cells that recognize epitopes in convalescent patients.

“We were pleased to collaborate on this exciting project, which exposes a surprising and uncharacterized source for T cell epitopes from SARS-CoV-2 genome,” said Shira Weingarten-Gabbay, Ph.D., Broad Institute. “The insights from this work increase our understanding of the interaction between SARS-CoV-2 and the immune system, and could potentially extend to additional pathogens as well.”

“The findings from this research provide important insights into the nature and dynamics of viral protein expression and presentation in COVID-19,” said Daniel Pregibon, Ph.D., Head of Platform Discovery and Technology, Repertoire. “We are delighted that we were able to use Repertoire’s technology to demonstrate the relevance of the novel epitopes discovered by the Sabeti Lab’s immunopeptidomics approach, and we look forward to furthering the science in this area to better design next-generation vaccines for COVID-19 and beyond.”

About Repertoire Immune Medicines

Repertoire Immune Medicines is a fully integrated immune medicines company dedicated to creating treatments for serious diseases based on the power of the human T cell repertoire to eliminate cancer cells, target pathogens and regulate immune function. Repertoire’s strategy lies in understanding the immune synapse – the interaction between specific T cells and the corresponding antigen presenting cells that dictate T cell activity. The company’s proprietary DECODE™ technology platform, developed by Repertoire scientists, provides a unique understanding of the full repertoire of interactions between T cell receptors (TCRs) and their antigen targets. The ability to decode these interactions represents one of the greatest opportunities for innovation in medical science.

Repertoire’s team of more than 120 operates from sites in Cambridge, Massachusetts, and Zurich, Switzerland, using its DECODE technology to rationally design treatments for cancers, autoimmune disorders and infectious diseases. The company’s first product in the clinic, for metastatic solid tumors, is a novel multiclonal T cell therapy consisting of naïve, rare T cells derived from the peripheral blood, activated against a curated set of antigens, and armed with a proprietary cytokine payload. In the field of autoimmunity, Repertoire has discovered novel immune targets from patients with type 1 diabetes and other autoimmune diseases, providing the foundation for novel therapeutic candidates. The company is also using its DECODE platform to discover infectious disease antigens and responding T cell clones, providing the opportunity to develop targeted medicines for infectious diseases. To date, the company has raised more than $350 million from leading healthcare investors.

To learn more about Repertoire Immune Medicines, please visit our website: www.repertoire.com and follow us on LinkedIn and Twitter.