# Treg-depleting immunotherapy

> **NIH NIH R44** · SONOVAL LLC · 2020 · $250,548

## Abstract

Abstract
Sonoval is expanding its successful biologic drug platform technology to develop second generation versions of
the cancer therapeutic Ontak, with the potential to advance the field of regulatory T cells (Tregs)-depleting
immunotherapy through a mechanism previously unique to Ontak alone. Sonova;’s therapeutics will target Tregs
for treatment of major solid tumors, which afflict >50,000 Americans per year, by transiently and potently
depleting these CD25+ cells while being non-toxic to other cell types. Tregs contribute to cancer progression by
suppressing anti-tumor immune responses Thus far, one of the lead second generation candidates has
demonstrated 3-5-fold anti-tumor effect as monotherapy compared to no treatment, and in novel application,
enhances check-point inhibitor (CPI) activity by up to 5-fold in murine models of solid tumors.
For over a decade, Ontak was approved for treatment of cutaneous T-cell lymphoma, making it the first antibody
fusion protein of non-monoclonal origin approved for use by the FDA. Ontak was also found to be effective in
the treatment of several solid tumors by transient Treg depletion in the tumor microenvironment. Despite its
clinical success Ontak suffered from two critical drawbacks: a 25% rate of vascular leak syndrome (VLS), and
significant manufacturing inconsistencies that included variable levels of protein aggregates (up to 40%) and
detergent contamination. These issues led to the drug being taken off the market in 2011.
Sonoval’s second generation versions of Ontak, SON-211 and SON-301, both show reduced VLS and are
potential lead drugs for development. Further, Sonoval holds IP on a novel production method that solves prior
manufacturing problems and enables product to be made with 0% aggregation and no detergent. In preliminary
experiments, compared to Ontak, SON-211 shows an improved safety profile; a lower dose response; and
equipotent anti-tumor efficacy in 3 murine tumor models (melanoma, colon carcinoma, renal cell cancer). in these
same models, SON-211 monotherapy is significantly potentiated by the addition of CPI, paving the path to novel
sequential combination treatment regimens. Further, SON-211 has been show to deplete CD39+ activated Treg
in the tumor microenvironment by 72%, and to increase levels of effector T cells in tumors, while not depleting
resting Tregs in spleen. The purpose of this Fast Track project is to finalize lead compound identification (Phase
I), and to meet safety, efficacy and manufacturing milestones (Phase II) needed to progress to IND approval.
Phase I’s single Aim will be to evaluate SON-211 and SON-301 based on their levels of superiority to Ontak in
safety (VLS testing), anti-tumor efficacy with and without CPI, and production efficiency of fermentation, at 5-liter
scale. Phase II Aims include: 1) Determine optimal dosing regimen as anti-cancer monotherapy and as dual
sequential immunotherapy with CPI; 2) Optimize production/purification; 3) Conduct pr...

## Key facts

- **NIH application ID:** 10154865
- **Project number:** 1R44CA254764-01A1
- **Recipient organization:** SONOVAL LLC
- **Principal Investigator:** WILLIAM Ramses BISHAI
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $250,548
- **Award type:** 1
- **Project period:** 2020-09-07 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154865

## Citation

> US National Institutes of Health, RePORTER application 10154865, Treg-depleting immunotherapy (1R44CA254764-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10154865. Licensed CC0.

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