# Advancing a Candidate Human Polyclonal Anti-Thymocyte Globulin Product Produced in Transchromosomal Bovine for Transplant Induction/Acute Rejection and T1D Therapy

> **NIH NIH R44** · SAB BIOTHERAPEUTICS, INC. · 2020 · $418,106

## Abstract

Currently available anti-thymocyte globulin (ATG) products are polyclonal animal antibodies (ATGAM – equine
polyclonal ATG, Thymoglobulin – rabbit polyclonal ATG) and have found broad use as immune tolerizing agents,
particularly for induction therapy in a majority of tissue transplants, for acute transplant rejection, and as
treatment for graft vs. host disease following bone marrow transplants. Early clinical trials also suggest ATG may
have a role in immunomodulation to treat the underlying autoimmunity of type 1 diabetes (T1D). However,
animal-derived ATG products can result in serum sickness 5-15 days after administration as the recipient's
immune system reacts to these xenobiotic immunoglobulins, rendering any subsequent redosing particularly
problematic. An agent that could combine the beneficial effects of the current animal ATG products but avoid the
xenobiotic responses would bring significant advantages to each of these therapeutic areas. This proposal seeks
to produce potent fully human ATG polyclonal antibodies by immunizing transchromosomal bovines (TcBs) with
human thymocytes in combination with a strong adjuvant and immune stimulator. TcB-derived fully human
polyclonal ATG antibodies (SAB-142) will have potent activity and would eliminate the risk of anaphylaxis and
serum sickness associated with xenobiotic IgG products. Success of this proposal will result in an IND filing that
will facilitate a Phase 2 clinical trial to evaluate safety, tolerability, and efficacy.
Previous studies have demonstrated that TcBs can produce large amounts of human polyclonal antibodies with
extremely high titers and neutralizing activity against various antigens, including viruses, proteins, bacteria, and
whole cell antigens following multiple immunizations. A phase I clinical trial has shown that the human antibody
products produced by TcBs are safe and well-tolerated in healthy subjects (ClinicalTrials.gov NCT02508584). In
this proposal, SAB Biotherapeutics, Inc. (SAB) and Sanford Research intend to expand our earlier proof-ofconcept
studies to produce a human ATG polyclonal antibody product (SAB-142) using SAB’s innovative human
antibody production platform technology (diversitAb™) and evaluate the antibodies in pre-clinical studies. There
are two phases in this project: Phase 1 – (1) Evaluate and compare SAB-142 with ATGAM and Thymoglobulin
for direct cytotoxicity toward conventional T cells, (2) Examine SAB-142 affinity toward red blood cells (RBCs),
and evaluate the effects of RBC adsorption on SAB-142 binding to peripheral blood mononuclear cells, and (3)
Evaluate and compare SAB-142 with ATGAM and Thymoglobulin for binding affinity to multiple subsets of
PBMCs. Phase 2 – (1) Production of two naïve TcBs for SAB-142 production, (2) Immunization and plasma
collection from TcBs for SAB-142 production, (3) Purification of a pre-clinical lot and a clinical lot (cGMP) of SAB-
142 for use in Aims 4 and 5, (4) Develop and qualify a target-specific po...

## Key facts

- **NIH application ID:** 10007757
- **Project number:** 5R44AI142905-03
- **Recipient organization:** SAB BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Alexei Yurievitch Savinov
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,106
- **Award type:** 5
- **Project period:** 2019-01-09 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007757

## Citation

> US National Institutes of Health, RePORTER application 10007757, Advancing a Candidate Human Polyclonal Anti-Thymocyte Globulin Product Produced in Transchromosomal Bovine for Transplant Induction/Acute Rejection and T1D Therapy (5R44AI142905-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10007757. Licensed CC0.

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