# Process Development and Preclinical Advancement of a Novel Nanoparticle Formulation for Immune Activation

> **NIH NIH R44** · SAROS THERAPEUTICS INC · 2023 · $1,196,731

## Abstract

Summary
Despite the success of immune checkpoint inhibitors for some types of cancer, the overall response rate remains
suboptimal. The majority of solid tumors exclude T-cells (termed “cold”), thus presenting a key limiting factor for
cancer immunotherapy. Activation of the cGAS-STING pathway has been demonstrated to induce anti-tumor
immune responses with impressive efficacy in preclinical studies. However, clinical stage STING agonists, based
on cyclic dinucleotides (CDNs), suffer from major limitations, including: 1) Administration via intratumoral
injection. STING agonists administered intratumorally are cleared rapidly, and intratumoral injection reduces their
utility against metastatic cancer. 2) Conventional STING agonists do not readily cross the cell membrane, failing
to maximize activation of STING located within the cytosol. 3) Cell penetration of conventional STING agonists
is not biased to the dendritic cells and macrophages which is the cell type needed to drive an anti-tumor immune
response. 4) Conventional STING agonists do not work across the human population due to variations in STING
haplotypes. Indeed, in recent phase I clinical trials, STING agonists given intratumorally exhibited only marginal
efficacy. Hence, a potent platform for systemic delivery of STING agonists is urgently needed to improve patient
outcomes. Saros Therapeutics is developing a novel nanotechnology (referred to as SNP) that addresses each
of these limitations by: 1) Incorporating manganese along with CDA, a CDN-based STING agonist, in the nano-
formulation. We have shown that Mn augments the activation of STING by CDA, lowering the dose necessary
to achieve a significant biologic (Type I IFN expression) and therapeutic (tumor growth/survival) benefit. 2)
Incorporating the Mn-CDA complex in a nanoparticle protects the CDA from degradation, extending half-life and
facilitating uptake by myeloid cells (DC, macrophages) that drives a Type I IFN response by the immune cells in
the TME. The combination of Mn+CDA incorporated into a nanoparticle formulation also improves the safety
profile of this therapy and allows administration by IV, ensuring systemic exposure and improved responses in
settings of multiple tumors and metastasis. Based on our compelling data, we will examine the potency of SNP
preparations in human patient biopsy samples. We will assess pharmacokinetic and tissue retention
characteristics of SNP in both mice and non-human primates and benchmark against other STING agonists. We
will develop microfluidic methods for large scale production of SNP in anticipation of transfer to a contract
development and manufacturing organization (CDMO). Results from these studies will accelerate the
development of our novel nanotechnology with the aim of quickly bringing immunotherapy’s benefits to more
patients with cancer.

## Key facts

- **NIH application ID:** 10758714
- **Project number:** 1R44CA281497-01A1
- **Recipient organization:** SAROS THERAPEUTICS INC
- **Principal Investigator:** Richard Johnson
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,196,731
- **Award type:** 1
- **Project period:** 2023-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758714

## Citation

> US National Institutes of Health, RePORTER application 10758714, Process Development and Preclinical Advancement of a Novel Nanoparticle Formulation for Immune Activation (1R44CA281497-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10758714. Licensed CC0.

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