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Rna Diagnostics Completes Phase I Trial for Breast Cancer Treatment Test, Aims for 2025 Launch


NEW YORK – After years of delays imposed by the COVID-19 pandemic, Rna Diagnostics said its recent Phase I study results support the use of its test to predict chemotherapy outcomes for breast cancer patients, and the firm plans to finish Phase II and publish results in 2025.

The Toronto-based firm's RNA Disruption Assay (RDA) is used to quantify ribosomal RNA fragmentation in tumor biopsies as a measurement of cell death resulting from preoperative therapy including neoadjuvant chemotherapy, and the results are used to determine whether a treatment is likely to result in pathological complete response and improved patient survival. The company is developing RDA as a laboratory-developed test (LDT).

In an interview, Rna Diagnostics CEO John Connolly said that Phase I results of the Breast Cancer Response Evaluation for Individualized Therapy (BREVITY) trial support the use of the assay to determine earlier in treatment which patients are likely to respond well to a chemotherapy regimen, helping clinicians to decide whether to escalate or de-escalate treatments. Based on the assay results, a doctor could decide to switch to different chemotherapy drugs, monoclonal antibodies, CDK4/6 inhibitors, or antibody-drug conjugates, or to proceed to surgery earlier.

The RDA test results are used to stratify patients into one of three groups that indicate whether the patient is showing non-response, partial response, or a good response to treatment that is likely to lead to pathologic complete response and event-free survival for more than five years. The company also plans to provide doctors details on where a patient's score falls on the continuum within those zones, Connolly said.

Researchers from Italy, France, Germany, Spain, Canada, and the United States recently published the Phase I BREVITY trial results in JNCI Cancer Spectrum, which was used to determine the cutoff points for stratifying patients by their treatment response during Phase II of the trial.

According to the authors, the RDA test's results were strongly associated with response to chemotherapy.

Patient tumor samples were analyzed by capillary electrophoresis using an Agilent 2100 Bioanalyzer, and an RNA disruption index value was calculated for each sample using a proprietary algorithm, the authors said. That index is expressed as a ratio between abnormal ribosomal RNA fragments and normal 28S and 18S ribosomal RNA bands.

Connolly said the Phase I results established a cutoff point with 93.3 percent negative predictive value for determining non-response to therapy. He said a non-response measurement will give physicians the most actionable information for decisions on patient treatment.

In the Phase I study, the testing process involved biopsies at two points during treatment for each of 80 patients with invasive breast cancer. Those patients were accrued from September 2020 through April 2022 with distribution across the four main breast cancer subtypes.

Seventy of those patients underwent subsequent treatments with two different drugs while 10 underwent multiple cycles with a single regimen. The first biopsies were conducted after the second cycle of chemotherapy, and the second biopsies were conducted either following the first round with the second drug or at day 55 of treatment with a single drug.

Connolly expects that recruitment for the 454-patient Phase II of the trial will finish by the end of this summer and the trial will end about six months later. If the trial goes as planned, the company will publish in 2025 the evidence it needs to bring its LDT to market. He expects the company will also commercialize the test in 2025 starting with a launch in the US followed by launches in Europe and Canada.

"We certainly have a lot of interest from doctors and breast cancer specialists in the US and Europe," he said. "And this seems to be very uniquely positioned because we're able to assess response with a high degree of certainty at an early time point during treatment, early enough that the doctors can change those regimens in response to the assessment of the tumor in response to that particular drug or drug combination."

COVID shutdown

Rna Diagnostics officials had previously said in 2018 that they expected to enroll more than 700 patients for the BREVITY trial in the following two years and make the RDA test available in 2020, but the COVID-19 pandemic changed those plans as the firm had to shut down the trial because cancer centers participating in the study prioritized the pandemic over clinical trials.

Rna Diagnostics plans to soon open CLIA-certified lab facilities in the US and in Central Europe but has not decided on the locations for those labs. Connolly said the firm also expects to achieve in June CLIA certification for the company's laboratory in Sudbury, Ontario, enabling it to perform the RDA test for the US market in the near term.

Rna Diagnostics has been funded so far by angel investors and venture capital investors, and the firm had announced in 2021 that it secured C$8 million (US$6.3 million) in Series A financing. Connolly said the company is in the process of a Series B financing round, through which it intends to raise about US$20 million to support the company through early commercialization in the US and Europe.

Connolly said Phase II of the BREVITY trial has completed about 75 percent of recruitment in seven countries. Most of the recruitment is occurring in Europe because of lower healthcare costs there, which is expected to lower the cost of running the clinical trials.

Maureen Trudeau, the principal investigator for the BREVITY trial and a breast cancer researcher at the University of Toronto, said the results from Phase I so far align with previous study results and indicate that the test is predictive of patient response to chemotherapy.

Trudeau, who is a clinical adviser for Rna Diagnostics, was the principal investigator on a study about a decade ago during which her team was trying to identify genetic markers that could be used to predict positive outcomes of chemotherapy regimens with epirubicin and docetaxel. Amadeo Parissenti, who is now the CSO for Rna Diagnostics, examined patient RNA and saw a predictive pattern of increased ribosomal RNA breakdown among patients who responded well to treatment.

"Amadeo said to me when we were doing our first study, 'I can tell you which patients are alive and which patients are dead,'" she said.

She added that Parissenti's accurate assessment of which patients did well or poorly sparked the idea of using RNA destruction to forecast outcomes for breast cancer patients. The technology also could be applied to other cancers such as lymphoma, said Trudeau, adding that lab-based studies have begun to examine those potential uses.

Connolly said Rna Diagnostics has focused its initial work on breast cancer because it is a major indication, it is easily accessed through needle biopsies, and oncologists need better ways to assess treatment response. His team thinks the test is applicable to all solid tumors that are treated with anti-cancer drugs, and he would like to develop tests for use in melanoma and rectal cancer.

Trudeau said the RDA test for breast cancer involves discomfort because it requires multiple biopsies, so the researchers need to show that the test can identify who is likely to do well with continued chemotherapy.

"There's a lot of potential in the future to use this test to further improve therapy for various classes of patients," Trudeau said.