THE CURATIVE IMMUNE SYSTEM
EXTRAORDINARILY COMPLEX. WONDERFULLY POWERFUL.
THE IMMUNE SYSTEM IS
THE MOST SUCCESSFUL MEDICINE
The power of the immune system to cure disease has been apparent for over one hundred years; within our bodies, it continuously deploys more medicines than all of the world pharmaceutical companies in combination. Disease arises when our immune system is weakened, evaded or co-opted. For the first time in human history, the codes that dictate immune recognition of healthy and diseased tissues, that demarcate immune cell phylogeny, and that determine immune responses are within our grasp.

Repertoire Immune Medicines has been established with the goals of decoding the immune system on a cell-by-cell basis and deploying this information to empower the next generation of rationally and uniquely designed Immune Medicines that go well beyond current advancements in CAR-T therapy and immune checkpoint inhibitors, which have been, thus far, powerful demonstrations of the potential of the immune system to cure patients with otherwise no therapeutic options. To reestablish dominance and to augment our body’s Immune Security Lexicon, Repertoire Immune Medicines empowers our immune systems to combat infection and malignancy while avoiding damage to healthy tissues or autoimmunity. 
T CELLS: UNDERSTANDING
CURATIVE POTENTIAL 
At the center of the immune system is a legion of T cells working to safeguard our health by detecting and acting on danger signals – be those invader pathogens, incipient tumors, or other threats arising either outside or within our bodies. This “Immune Security System” Lexicon comprises some 20 million different, specific groups of T cells. Each group – or clonotype – is defined by its own unique T cell receptor (TCR) sequence, and each TCR sequence in turn recognizes a limited set of corresponding target antigens.

Evolved over millions of years, the extraordinary diversity intrinsic to this system shields our bodies against the vast majority of attacks and quickly neutralizes them, with the probability of any one attack breaching the system being exceptionally low. In other words, T cells are far more effective in preventing and curing disease than any man-made medicine has ever been.

At Repertoire Immune Medicines, we believe that decoding the universe of TCR - antigen codes that drive health and disease represents one of the greatest opportunities for innovation in medical science. We are working at full tilt towards this goal and are on the brink of discoveries that will bring the power of our immune system to bear upon the lives of the countless patients we intend to serve.
THE IMMUNE SYNAPSE AND ALL
THAT IT CONTROLS
When a specific antigen code and the corresponding TCR code permit productive binding of the T cell to the unhealthy cell, the T cell is activated and kills the unhealthy cell. This interface, allowing recognition, binding and activation, is known as the “immune synapse.” It is the basis for how a T cell can selectively attack unhealthy, antigen code-bearing cells while sparing the body’s own healthy cells. The immune synapse depends on a number of molecules for its function, among which the antigen - TCR pair is key in that it serves as a selective and exclusive set of instructions, or codes, to activate or not activate. Repertoire Immune Medicines’ focus is on decoding specific TCR - antigen codes and their binding relationships to build a new view of the immune response.
THE INFLUENCE OF THE LOCAL
T-CELL ENVIRONMENT
The immune system conquers disease using a multi-pronged approach in e.g., eliminating tumors. The cancer-immunity cycle starts by (1) cancer cells releasing “antigens” that allows the immune system to recognize them. (2) Specialized immune cells take them to T cells located in lymph nodes (3) T cells then become primed/activated by these foreign antigens. (4) Activated T cells then move to the tumor and (5) T cells reach the cancer cell and “infiltrate” the tumor in order to attack it. (6) The T cells are able to recognize foreign cancer cells based on the antigens they released earlier. (7) T cells destroy cancer cells by activating a series of steps that lead to cell death.

The ability of the immune system to eliminate tumors and provide durable clinical responses is limited by negative feedback mechanisms developed by the tumors. Immunotherapies aim to reactivate all the steps in the tumor-immunity cycle and re-establish effector T cell activity. Therapies relying on synergy between potent T cell responses and modulators of tumor microenvironment (TME) may provide the most benefit.

T cell responses become selective through the TCR - antigen interaction. Cytokines and other immune modulators can stimulate the immune function of the tumor microenvironment and provide support to the T cell to stay vivid.
THE REPERTOIRE LEXICON
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ANCHOR Technology
A reversibly cross-linked nanogel of immunomodulators that are tethered to cells and where the nanogel slowly degrades and releases the immunomodulator for autocrine stimulation.
Antigen
A substance which induces an immune response in the body.
BRIDGE Technology
A fusion protein of a targeting ligand towards a receptor on an immune cell that is linked to an immunomodulator, whereby the fusion protein can be tethered to the surface of immune cells for paracrine and autocrine stimulation.
CLOUD Technology
A lipid-based nanoformulation of encapsulated small molecule immunomodulators that is then tethered to specific immune cells and released from the immune cell to induce paracrine stimulation.
Clonotype
A T (or B) cell with a unique nucleotide sequence for its surface expressed receptor that arises during the gene rearrangement process for that receptor.
Clonotype ID
A procedure that detects and quantifies T cells that are specific for a given antigen within a biological sample.
Curative Immune System
The power of the immune system to cure disease; within our bodies, it continuously deploys more therapies than all of the world pharmaceutical companies in combination.
Designer Immune Medicines
A therapy that targets multiple antigens in the context of patient-specific HLA alleles, that enlist optimized T cell clonotypes, and that is armed with immunomodulators to overcome tolerizing mechanisms within an inhospitable environment, thereby empowering capabilities to eliminate an acute insult and to provide functional memory that augments the Immune Security Status.
Epitope
Also known as an antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.
HLA
Human leukocyte antigen
Immune Code
The unique combination of peptide sequence, HLA allele and TCR sequence that dictate the antigen-specific recognition and response of a T cell clonotype.
Immune Medicine
A substance or component derived from, that enlists, or is elicited by the immune system to protect the body from possibly harm and mediated via specific recognition and response to an antigen.
Immune Monitoring
A set of procedures that characterizes the composition and functional state of a population of clonotypes over time and/or as a response to a treatment.
Immune Security System:
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Immune Synapse
The interface between an antigen-presenting cell or target cell and a lymphocyte such as a T, B or Natural Killer (NK) cell.
Immunomodulator
A natural or synthetic agent that activates, enhances, suppresses or restores immune function.
Immunophenotyping
A set of procedures that characterize a range of innate and adaptive immune cell phenotypes and functions, including cell surface markers and/or soluble mediators (e.g., cytokines and chemokines), that shape the outcome of the immune response. Immune Security Status: the ability of the immune cells to combat infection and malignancy while avoiding damage to healthy tissues or autoimmunity.
MCR
A chimeric receptor comprised of the extracelluar domains of a pMHC and the intracellular portions of a TCR.
MEDi
Mammalian epitope display.
Multiantigen therapy
An Immune Medicine that targets a series of antigens.
Multiclonal design
Generation of multiple clonotypes that target single or multiple antigens through recognition of specific epitopes to impart desired functions.
PRIME™ T cells
Repertoire Immune Medicine’s proprietary Prime Repertoire Immune Encoded T cells, which are a multi-antigen-targeted natural T cells for use in adoptive cell transfer. PRIME T cells are natural, multiclonal CD8 and CD4 cells featuring an optimized phenotype and high antigen-specific reactivity to multiple tumor antigens. PRIME T cells can be combined with tethered immunomodulators to make designer immunotherapies that target multiple antigens and provide T cell support and tumor microenvironment remodeling to enhance immune function.
Peptide
A short sequence of amino acids PRIME™.
Repertoire
The sum of the unique receptors carried by T cells and B cells that compose a patient’s adaptive immune system.
STREAM™ manufacturing
The Repertoire Immune Medicine’s manufacturing platform that expands a T cell product from a patient to PRIMETM T-cell product. The STREAM biomanufacturing platform uses a proprietary dendritic cell priming technology to naturally expand a patients own tumor reactive T cells in an HLA independent manner. High process yields and the ability to freeze the resulting drug product enable repeat dosing for continued immune therapy, while automation and Single Use technologies support rapid, on-demand manufacturing. To enable the rapid deployment of novel immune coded therapies to patients, the STREAM platform features a modular production system that accelerates new products into the clinic.
Single cell sequencing
Sequence information from individual cells with optimized next-generation sequencing (NGS) technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment.
T cells:
Repertoire Immune Medicines’ proprietary Primed Repertoire Immune Encoded T cells, which are a multi-antigen-targeted natural T cells for use in adoptive cell transfer.
TCR
T cell receptor.
Target Tissue
The site in the body at which an Immune Medicine exerts its action. TCR: T cell receptor
Tethered Immune Modulator
A cytokine or small molecule immunomodulator that is associated with the cell either on the surface or within.
Tetramers
Macromolecules comprised of 4 identical pMHC molecules and further bound to a unique molecular identifier (UMI).
pMHC
A major histocompatibility complex (MHC) molecule loaded with a peptide.