Her2 is expressed in ~25% of breast cancers and correlates with highly aggressive disease. Her2-targeted therapies are highly efficacious against Her2-positive cancer, yet no clinical imaging agents can assess Her2 status in vivo. EvoRx Technologies has developed a method to discover cyclic peptides that have antibody-like affinities and selectivities, high stability in serum, and rapid systemic clearance. In our Phase I contract, we showed that EVO- 004 has rapid, high levels of tumor uptake with minimal background in mouse models, developed an efficient, automated radiochemical synthesis, and obtained preliminary PET/CT images in mice showing specific tumor uptake as well as rapid clearance and low liver uptake. In Phase II, we aim to complete pre-clinical experiments, enabling first-in-human PET/CT imaging studies with EVO-004. We will use mouse model imaging studies of primary and metastatic cancer models to establish the sensitivity and limit of detection for Her2-positive disease, optimize EVO-004 radiochemical synthesis for clinical production, perform GMP validation studies, and establish dosimetry in rodent and primate models to determine tracer toxicity and establish the maximum safe dose for patient trials. Lastly, we will obtain an IND to deploy our PET tracer in patients with Her2-positive inflammatory breast cancer to demonstrate safety and concordance with biopsy-proven Her2-positive disease.

Public Health Relevance

Molecular imaging can improve clinical choices for breast cancer treatment. We propose to develop more accurate and non-invasive imaging molecules to identify patients who would benefit from targeted cancer therapies. This technology will reduce the need for invasive biopsies and unnecessary surgeries and provide physicians with a powerful tool to personalize breast cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44CA206771-03
Application #
9270534
Study Section
Special Emphasis Panel (ZRG1-SBIB-T (10)B)
Program Officer
Zhao, Ming
Project Start
2016-05-06
Project End
2018-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
3
Fiscal Year
2017
Total Cost
$1,144,342
Indirect Cost
Name
Evorx Technologies, Inc.
Department
Type
Domestic for-Profits
DUNS #
078283114
City
Pasadena
State
CA
Country
United States
Zip Code
91106
Pisaneschi, Federica; Kelderhouse, Lindsay E; Hardy, Amanda et al. (2017) Automated, Resin-Based Method to Enhance the Specific Activity of Fluorine-18 Clicked PET Radiotracers. Bioconjug Chem 28:583-589