# Validation of the Genetically Malleable Oncopig Hepatocellular carcinoma (HCC) Model for Targeted Therapeutic Development

> **NIH NIH R44** · SUS CLINICALS, INC. · 2024 · $1,035,724

## Abstract

PROJECT ABSTRACT: The goal of this Phase II SBIR proposal is to further validate the genetically defined
Oncopig hepatocellular carcinoma (HCC) model—capable of modeling diverse HCC driver mutational profiles
through induced KRASG12D and TP53R167H expression and subsequent CRISPR editing—for preclinical
evaluation of locally delivered, personalized HCC therapies. HCC is an aggressive liver malignancy representing
the 7th most common cancer and the 4th most common cause of cancer death worldwide, illustrating the critical
need for improved HCC treatment options. Since HCC and other cancers are driven by the accumulation of
genetic driver mutations conferring selective growth advantages, personalized cancer models are required to
evaluate targeted therapeutics for this deadly disease. Furthermore, the use of transarterial delivery-based
approaches for HCC treatment combined with similarities in size and drug metabolism between pigs and humans
highlights the critical need and translational value of the genetically defined Oncopig HCC model for investigating
novel and re-purposed therapeutics targeting specific driver mutations. Importantly, there is broad interest in the
use of Oncopigs in preclinical trials (see Support Letters). This proposal will demonstrate differential efficacy of
transarterial targeted PI3K inhibitor delivery to Oncopig PTENKO (PI3K inhibitor responsive) and KEAP1KO (PI3K
inhibitor non-responsive) HCC tumors using a clinically relevant trial design. Use of liquid biopsies for minimally
invasive HCC driver mutation quantification (see Volition Support Letter) will facilitate translation of HCC
precision medicine approaches into clinical practice, currently lacking due to infrequency of routine HCC biopsy
collection for biological profiling. The genetically defined Oncopig HCC model will be validated for targeted
therapeutic testing by pursuing the following Specific Aims: (1) Characterize genetically defined Oncopig HCC
tumors over a clinically relevant 3-month diagnostic monitoring period. (2) Demonstrate delivery of targeted PI3K
inhibitor therapeutic doses to Oncopig HCC tumors via transarterial embolization. (3) Demonstrate efficacy of
transarterial targeted PI3K inhibitor delivery for Oncopig PTENKO HCC in a clinically relevant 3-month follow-up
timeframe. The ability to achieve quantifiable therapeutic PI3K inhibitor concentrations following transarterial
delivery in the genetically defined Oncopig HCC model will be demonstrated, in addition to a clinically relevant
difference in response (40% increase in complete response rate in PTENKO compared to KEAP1KO HCC) based
on clinically employed mRECIST guidelines. This work will validate the genetically defined Oncopig HCC
model for targeted therapeutic evaluation, enabling Sus Clinicals to provide personalized tumor
development and targeted therapeutic testing services using the Oncopig platform. Future work focused
on expanding Sus Clinicals commercialization of this techno...

## Key facts

- **NIH application ID:** 10931506
- **Project number:** 5R44CA285034-02
- **Recipient organization:** SUS CLINICALS, INC.
- **Principal Investigator:** LAWRENCE B. SCHOOK
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,035,724
- **Award type:** 5
- **Project period:** 2023-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931506

## Citation

> US National Institutes of Health, RePORTER application 10931506, Validation of the Genetically Malleable Oncopig Hepatocellular carcinoma (HCC) Model for Targeted Therapeutic Development (5R44CA285034-02). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10931506. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*