NEW YORK — Ignite Proteomics, a recently established subsidiary of healthcare firm IMAC Holdings, is the latest entity looking to commercialize the reverse-phase protein array (RPPA) technology developed by George Mason University researchers Emanuel Petricoin and Lance Liotta.
The Golden, Colorado-based company, which launched last month, is targeting its RPPA-based testing to biopharma firms to aid in target discovery as well as to clinicians and for clinical trial work to help guide therapy in cancer patients, said Faith Zaslavsky, CEO of Ignite and IMAC.
In RPPA assays, samples such as tissues or cell lysates are printed on slides in arrays and then probed with antibodies to proteins of interest, allowing researchers to measure the expression of dozens to hundreds of proteins of interest in a sample. The approach is highly sensitive and capable of working with small samples, such as tumor biopsies prepared using laser-capture microdissection.
In oncology, RPPA has commonly been used to assess the presence and activation of various cancer-linked proteins and cancer-linked protein signaling pathways, often with the aim of identifying potential therapeutic targets. In 2006, Petricoin and Liotta founded a company, Theranostics Health, that aimed to apply RPPA technology to guide cancer treatment and drug development.
In 2013, Theranostics launched a test for guiding therapy in breast cancer called TheraLink that measured the protein markers HER2, EGFR, and HER3 as well as proteins across the JAK-STAT, MAP kinase, and mTOR pathways.
In 2015, Theranostics launched an expanded version of TheraLink that included a total of 24 protein targets. The test did not see significant uptake, however, and in 2016 Avant Diagnostics acquired Theranostics' CLIA laboratory and the TheraLink assay.
In 2020, drug company OncBioMune Pharmaceutical acquired Avanta and changed its name to Theralink Technologies, which, in 2023, became a subsidiary of IMAC via a stock-for-stock reverse merger. Zaslavsky, who was formerly president of oncology for Myriad Genetics, joined Theralink as president and chief operating officer in 2022 and became CEO in 2023. She was appointed CEO of IMAC in May 2024.
Ignite offers what it calls the Ignite Proteomics RPPA assay, which measures a total of 32 proteins, including the proteins that comprised the former TheraLink assay. Much of the data on the assay has been generated in breast cancer, which remains the company's primary focus, but it is also working to demonstrate the assay's utility in other cancers including brain, pancreatic, ovarian, and endometrial, Zaslavsky said.
Last month, researchers including Ignite scientists and Petricoin published a case report in NPJ Precision Oncology in which they used to test to select trastuzumab deruxtecan (AstraZeneca and Daiichi Sankyo’s Enhertu) treatment for a triple-negative breast cancer patient who had previously received several other lines of therapy. The patient was HER2 negative by traditional immunohistochemistry. Additionally, the authors noted, next-generation sequencing identified no alterations in HER2, HER3, or EGFR that "would have otherwise predicted the patient as a potential responder to" trastuzumab deruxtecan. RPPA analysis, however, showed moderate HER2 expression and activation (as measured by protein phosphorylation level). Following trastuzumab deruxtecan treatment based on the RPPA analysis, the patient had a complete response.
The case report follows several studies suggesting that RPPA-based tests could aid in therapy selection for breast cancer patients. Last year, Petricoin and his GMU colleagues identified an RPPA-based protein phosphorylation signature that distinguished between triple-negative breast cancer (TNBC) patients likely to respond to anti-HER2 therapies and those likely to respond to immune checkpoint therapy.
Prior to that, Petricoin and his collaborators found that some TNBC patients with elevated phosphorylation levels of EGFR and HER2 responded to Puma Biotechnology's anti-HER2 tyrosine kinase inhibitor Nerlynx (neratinib) despite being HER2 negative based on standard pathology.
Nonetheless, the RPPA test has, across all its incarnations, struggled to gain commercial traction. Zaslavsky said that for part of 2023, Theralink Technologies had shut down its lab operations due to a lack of funds.
Petricoin, who is a consultant and chair of the science advisory board at Ignite, suggested that the recent case study could help drive interest in the Ignite assay as it provides an example of a patient "being treated prospectively based upon the [assay results] … and the patient did extraordinarily well."
"We need to validate this in much larger study sets," he added. "We need to understand, was this an N of one, did we just get lucky? Or is this generalizable?"
He said he and his colleagues are working to test the assay in more metastatic breast cancer patients as well as to test it retrospectively in biobanks containing samples from metastatic breast cancer patients treated with trastuzumab deruxtecan.
Virginia-based Inova Health System, where the patient in the case report was treated, is also ramping up its use of the Ignite assay. According to Thomas Conrads, director of women's health research at Inova Fairfax Hospital and a coauthor on the case report, the hospital has been investigating the feasibility of including the Ignite data as part of its molecular tumor board program. He said that over the last 16 months the hospital has run the Ignite assay on around 200 patients.
Last year, Conrads and his Inova colleagues presented an abstract at the American Society of Clinical Oncology annual meeting detailing early results from this work with the Ignite assay. Of a group of 117 patients with metastatic solid tumors, they were able to collect RPPA and NGS data from 64, while in the case of 48 patients, data was not collected due to inadequate specimens or patient death. The abstract did not specify what became of samples from the remaining five patients. The median time from patient consent to RPPA testing to return of results was 47.4 days, and in 59 percent of patients, the RPPA data provided additional treatment options.
Conrads said that the NPJ Precision Oncology report "represents the first of what [Inova plans to release] out of our experience with the return of protein-level data using RPPA testing," and noted that the researchers continue to closely monitor the outcomes of patients whose therapy has been guided by the Ignite data. He said that while the Ignite assay was "designed and credentialed within the context of" breast cancer, the hospital has been using it across a range of cancer types.
Conrads added that Inova is now trying to increase the throughput of its RPPA testing processes to use it in an upcoming basket trial where therapeutics will be selected based on proteomic and phosphoproteomic measurements made by the Ignite assay.
Zaslavsky said that Ignite currently has 2,500 test orders booked across its biopharma, clinical trials, and clinical businesses. She said the company, which has around 20 employees, is planning a funding round in the near future but did not specify how much it aims to raise.