Avotres
From Breakthrough Scientific Discovery to Effective Clinical Applications

Avotres Inc. is a clinical stage biotechnology company developing transformational immunotherapies for autoimmune diseases (AID), cancers, transplantation rejection and precision detective assays.

Breakthrough Science

● The Avotres Platform stems from the discovery of a novel nonclassical MHC Class Ib molecule Qa-1/ HLA-E restricted regulatory pathway, referred as Q/E CD8+ Treg pathway, a “Master Regulator” of self-nonself discrimination in the periphery to maintain self-tolerance.

● Q/E CD8+ Treg pathway functions by selective down-regulation of pathogenic self-reactive T cells via a specific recognition of a common target structure, a complex of Q/E-Hsp60sp (in general) and HLA-E/Hsp60sp (in humans), serving as a Biomarker, preferentially expressed on the surface of all self-reactive T cells by the T cell receptor (TCR) on the Q/E CD8+ Treg cells. Such specific recognition locks down the unique, antigen-independent specificity of Q/E CD8+ Treg pathway and initiate a selective down-regulation of self-reactive T cell pool, leading to self-tolerance.

● This “Master Regulator” pathway is defective in the majority (approx. 90%) of patients with AID across over 20 distinct auto-immune diseases that had been tested by us on the clinical diagnosed AID patients so far.

● Correction/Restoration of this pathway, by our first Avotres drug AVT001, enables antigen-independent therapeutic solutions without impairing normal ongoing anti-infection and anti-tumor immunity.

Pioneering Pathogenic Antigen-independent Cell-based Vaccine

Our current pipeline consists of assets with the potential to diagnose, prevent, treat and even “cure” as disease modifying therapies:

● AVT001 – A clinical stage autologous dendritic cell-based vaccine for AID and transplant rejection

● AVT-Dx001 - A potency molecular/cellular assay to assess the functional status of the “Master Regulator” pathway, a potential tool for early diagnosis of AID which could also precisely guide clinical treatments.

● The unique specificity of the regulation by the Q/E CD8+ Treg pathway presents a rarely seen therapeutic advantage to target a wide spectrum of autoimmune diseases and other immunologically relevant conditions without the necessity to identify the disease specific pathogenic antigens, which is an extremely challengeable task currently.

Lead Asset, AVT001, Showcases Strong “Evidence Chain” From Research to Drug Development

● Clinical proof of concept demonstrating safety/tolerability and efficacy in a new onset Type 1 Diabetes (T1D) Phase I/II clinical trial with statistically significant reduction in C-peptide decline vs. placebo.

● Biological proof of concept with AVT-Dx001 successfully identifying the pathway defect and predicting response of AVT001

● Initial FDA feedback supporting entering a phase IIb proof of concept study (PoC) for multiple sclerosis (MS)

● Supporting preclinical evidence from human ex vivo studies in nearly 300 patients with >20 distinct autoimmune diseases and 3 mouse models **(NOD¹, EAE² and ATT³)

Avotres has made a breakthrough scientific discovery on how the immune system achieves self/nonself discrimination and is transforming it into effective clinical applications in autoimmune diseases, cancers, and transplantation rejection!

Avotres’ Mission

*Koshland ED ‘s famous statement more than 3 decades’ ago: “Of all the mysteries of modern science, the mechanism of self/nonself discrimination in the immune system ranks at or near the top.”

● To explore and answer this central conundrum in basic and clinical immunology:

• ◾ How does the immune system continuously achieve peripheral self-nonself discrimination after normal thymic negative selection is completed?


• ◾ What is/are the exact cellular/molecular mechanism/s of peripheral self-nonself discrimination by which the immune system controls autoimmunity to maintain self- tolerance?

● To transform the ground-breaking scientific discovery into effective clinical applications, in four medical arears: autoimmune diseases, cancers, transplantation rejection and a precision detective system.

Currently, “Avotres” is trying a completely new approach based on an original and innovative scientific conceptual framework to explore the science of self-nonself discrimination and open a new path on its clinical applications. By pioneering an innovative clinical approach based on a novel conceptual framework in the context of understanding self-tolerance achieved by a mechanism of peripheral self-nonself discrimination mediated by the Q/E CD8+ Treg pathway, “Avotres” is determined to make a difference that has long been needed in the field of immunotherapy.

● *Koshland DE, Jr. 1990 Science 248(4961):1273
● **NOD - non-obese diabetic, EAE - Experimental Autoimmune Encephalomyelitis, ATT – Adult transplantation tolerance