NEW YORK – Reveal Genomics, a two-year-old Spanish molecular diagnostics company headquartered in Barcelona, has launched its debut offering, HER2DX, a laboratory-based test for early-stage HER2-positive breast cancer patients that it claims can determine both the likelihood of recurrence as well as predict the likely response of patients to different anti-HER2 drugs.
The test consists of a 27-gene panel plus various clinical data inputs to produce scores related to recurrence likelihood and treatment outcome, and relies on proprietary algorithms developed by Reveal Genomics and its academic partners. A paper describing HER2DX and a validation study of its classifiers was published in the journal eBioMedicine in January.
CEO Patricia Villagrasa-Gonzalez said this week that the test is already available commercially in Spain, and the company intends to next launch its offering in Italy, as it expands to other European markets. The US market is also a priority for Reveal Genomics, she underscored, and the company is exploring partnerships to bring HER2DX to American patients, too.
"This year we are focused on Spain; we want to get the market share of private clinics," said Villagrasa-Gonzalez. "In parallel, we are exploring public healthcare systems," she said.
Villagrasa-Gonzalez described the Spanish healthcare system as "complex," as it is decentralized, meaning that the company has to interact with the individual health authorities of each of the country's 17 autonomous communities to secure reimbursement. "It's as if there were 17 ministries of health that manage their budget, unlike what happens in other countries where everything is centralized," she said.
One of Reveal Genomics' academic partners has been the University of Padova in Italy, a country on which the company has set its sights. Villagrasa-Gonzalez, a company cofounder who officially stepped into the chief executive role a year ago, said that Reveal Genomics is currently undertaking market access studies in Italy and France and is also interested in Germany and the UK as potential next steps. Once those studies are concluded, it will intensify its marketing efforts.
"This year, we also want to explore the US market to identify which should be our best operating model there," added Villagrasa-Gonzales. She noted that the company's test is currently offered via its central laboratory in Barcelona, but eventually the firm would like to decentralize and offer HER2DX as a kit that customers can run in their own facilities.
Reveal Genomics' test analyzes RNA isolated from formalin-fixed, paraffin-embedded breast cancer tissue samples, and turnaround time ranges from a week to 10 days. The test combines the expression signatures of its 27-gene panel with other clinical variables, and following analysis with its software, the test provides a patient-level risk score and a pathological complete response score to clinicians so they can make better informed decisions about treating their HER2-positive patients.
Villagrasa-Gonzalez said that about half a million patients are affected with HER2-positive disease per year, and, according to the US National Cancer Institute, about 14 percent of all breast cancer patients between 2014 and 2018 were HER2-positive. According to Villagrasa-Gonzalez, there is a pressing need for tools that can help to guide treatment decisions, as about a fifth of all HER2-positive patients still progress to incurable disease while receiving standard therapies, while the remainder are overtreated with expensive and often toxic therapies. She said that HER2DX therefore fills a gap in the treatment decision-making process.
Prior to launching HER2DX in Spain, the company, which currently has five employees, worked with some early-access partners, which resulted in the recent eBioMedicine study. The firm is also carrying out a study of the test's impact on the clinical decision-making process with partners at the Hospital Clinic Barcelona and would like to expand this study to other centers in Spain.
"We are talking to local governments from different regions in the country to collaborate," said Villagrasa-Gonzalez. She added that clinical data related to these studies will be presented at oncology meetings later this year.
Aleix Prat, another Reveal Genomics cofounder and its CSO, said that some preliminary data from the ongoing studies showed that in a third of cases, oncologists were changing their therapies based on the information obtained by HER2DX, while in the other two-thirds, the results helped to validate their treatment decisions.
"It gives more confidence about a therapy, which can be toxic, but knowing you need it reassures the patient and the physician that it was worth it," Prat said. Prat stressed that the study is still in process, and the firm and its partners have not yet formally published their findings.
Reveal Genomics' test is currently run in its central laboratory using NanoString Technologies' nCounter Analysis System, which relies on digital molecular barcoding technology to support multiplexed gene expression analysis.
According to Prat, Reveal Genomics' use of the nCounter platform could lay the ground for eventual expansion into selling HER2DX kits to labs that have the instrument.
"It's highly reproducible and can be decentralized eventually," said Prat. "It opens up opportunities for standardization, automation, and whoever has that machine can use it down the road if we have a kit." He did not provide any timeline around such a strategy, though, and the company has yet to detail pricing for the test.
In a recent eBioMedicine paper, the authors presented the HER2DX algorithm, which incorporates tumor size, nodal staging, and gene expression signatures related to immune infiltration, tumor cell proliferation, luminal differentiation, and the expression of the HER2 amplicon into a pathological response score.
The authors said they used 432 HER2-positive tumors to train their prognostic risk model, and 260 cases from a separate cohort were used to verify the accuracy of the developed risk score. Additionally, the authors used 116 cases treated with neoadjuvant, anti-HER2-based chemotherapy to train a model of pathological complete response, and then used two other cohorts numbering 158 cases to validate the model's accuracy. To further validate the test, they analyzed five other cohorts, representing about 1,000 patients with early-stage HER2 positive breast cancer.
The authors claimed their data support the use of HER2DX to produce two different clinical endpoints: long-term survival and likelihood of achieving a pathological complete response with therapy. Both scores, they noted, could be used in tandem to guide therapy for cancer patients.
"The evidence suggests that HER2DX risk score might be able to identify a substantial proportion of patients with early-stage, HER2-positive breast cancer who do not need additional therapies, such as pertuzumab, trastuzumab, emtansine, or neratinib, because of their favorable survival outcomes with chemotherapy and trastuzumab, plus endocrine therapy if hormone receptor-positive," the authors wrote.
The authors added that additional studies are needed to support the use of both HER2DX scores to "help de-escalate systemic and/or loco-regional treatments, such as the duration of trastuzumab or the amount of chemotherapy."
"In my opinion, it's a nice paper, but we need more of such studies," said Javier Cortés, a clinical investigator in the breast cancer research program at Vall d'Hebron Institute of Oncology in Barcelona, who is a coauthor on the new paper and also an early adopter of HER2DX. Cortés is not affiliated with Reveal Genomics and did not play any role in test development.
Cortés noted that he has used platforms like Oncotype Dx and Agendia's MammaPrint in the past to predict the likelihood of breast cancer recurrence in estrogen receptor-positive, HER2-negative patients, but HER2DX fills a gap for HER2-positive patients.
"In general, in cancer, not all patients are the same, not all tumors are the same, and trying to optimize who will need more and less treatment is a matter of need," said Cortés. "We have worked with [tests for] estrogen receptor-positive patients for many years to try and de-escalate treatment," said Cortés. "This is why, in my opinion, HERDX might play a similar role to escalate or de-escalate treatment."
While he called for additional studies of HER2DX, Cortés said that he is already using the test to guide treatment in his clinic, as "there are some patients who might benefit today from this tool."
Financing plans and future tests
Reveal Genomics was founded in September 2020 to commercialize genomic tests to guide cancer treatment with the goal of having a test on the market within three years, an objective the firm has now easily met. At the time of its launch, the company had raised about €500,000 in seed funding.
Villagrasa-Gonzalez said this week that the firm has had a business angel investor on board since February. "Our idea is to look for further funding, public and private, that will help us further develop new indications of HER2DX and a second product of our pipeline," she commented. "I continuously talk with potential investors and partners to help Reveal Genomics move forward."
The company is also preparing for a Series A round in 2023 to support international expansion.
Much of the work underlying its diagnostics foray was accomplished within the Hospital Clinic Barcelona, as well as with partners at the University of North Carolina School of Medicine, who had previously helped to develop the PAM50 signature, later licensed to and commercialized by NanoString as Prosigna, which is now marketed and sold by Veracyte through a licensing deal reached in late 2019.