REVEAL GENOMICS® HER2DX® Genomic Test to Undergo First Prospective Trial as Part of the DEFINITIVE Project, Funded by the European Commission

REVEAL GENOMICS, S.L., a pioneering biotechnology start-up based in Barcelona that is poised to transform precision oncology with its biomarker innovations, has announced the start of the DEFINITIVE study, led by FRCB-IDIBAPS, representing the first prospective trial for HER2DX^®.

This landmark study will be pivotal in bolstering the clinical validations already acquired for HER2DX^®. The study seeks to secure the prospective validation for endorsement by clinical guidelines and ensure recognition and reimbursement across Europe. As a collaborating partner in this study, REVEAL GENOMICS^® is committed to generating robust evidence designed to influence and evolve standard clinical practices.

Dr. Tomás Pascual, medical oncologist, researcher at Hospital Clínic/FRCB-IDIBAPS, SOLTI executive board member, and Principal Investigator in the DEFINITIVE clinical trial, expressed his optimism about the trial's potential impact, "This trial represents a significant opportunity to enhance patients' quality of life without compromising the efficacy of the treatment. It employs a non-invasive diagnostic tool, HER2DX^®, to achieve this goal. We are immensely grateful to all our partners and the multidisciplinary team participating in this trial. Their collaboration has been instrumental in developing this project and will be crucial to its successful delivery."

Dr. Patricia Villagrasa, CEO and co-founder of REVEAL GENOMICS^®, stresses that "at REVEAL GENOMICS, we believe in pushing the boundaries of precision medicine. The start of the DEFINITIVE study for HER2DX^® is a crucial step in our journey to reshape how oncology treatments are approached and administered globally."

HER2DX^®: seeking to change the paradigm in HER2+ breast cancer

Recent progress in treating HER2-positive breast cancer has significantly shifted the emphasis from post-surgery therapies to treatments administered prior to surgery. This shift offers multiple benefits, which include reducing tumor stages for less invasive surgeries, evaluating tumor response to systemic treatments, and tailoring adjuvant treatments based on the pathological responses observed during surgery.

Moreover, coupled with significant progress in early-stage HER2+ breast cancer treatment through chemotherapy with multiple drugs and targeted therapies, it also means a more optimistic outlook for patients. However, unmet needs and unanswered questions persist.

Firstly, some patients still face recurrence, despite current treatments. Secondly, most patients could be cured using less aggressive treatments. Moreover, the acute and long-term side effects from anti-HER2 agents and chemotherapy underscore the need for tools that offer deeper insights into tumor behavior, treatment responses, and risk of recurrence.

The DEFINITIVE trial seeks to assess the clinical efficacy of HER2DX^® by comparing the outcomes of patients who undergo the genomic test with those who do not. This study will crucially ascertain the real-world applicability of HER2DX^® in clinical settings.

HER2DX^® is a genomic test for personalized HER2+ breast cancer treatments, able to predict survival outcomes and the likelihood that patients will respond to treatment.

A thorough evaluation of the test's implementation strategies, its cost-saving benefits, and its introduction in various European contexts is integral to the DEFINITIVE study's role in broadening access to HER2DX^® by all patients.

The DEFINITIVE study: making results accessible

The kickoff meeting for the DEFINITIVE project was held at FRCB-IDIBAPS headquarters on January 11 and 12. More than 30 people from all participating entities from 9 different countries met to lay the foundations of the project and initiate each of the actions proposed in a coordinated manner.

"The start of the DEFINITIVE trial is fundamental for the prospective validation of HER2DX^® clinical utility. Moreover, it addresses crucial areas, including an extensive health technological assessment and patients' perspectives, incorporating their views during all the phases of the project", says Dr. Olga Martínez Sáez, medical oncologist and researcher at Hospital Clínic/FRCB-IDIBAPS, and Co-Principal Investigator in the DEFINITIVE clinical trial.

The DEFINITIVE study is a 5-year pragmatic, randomized clinical trial that seeks to demonstrate that HER2DX^® can improve quality of life and reduce not only toxicities but also direct and indirect costs, while maintaining efficacy endpoints and survival outcomes. The trial will incorporate the test into clinical practice for patients with HER2+ early-stage breast cancer, thereby allowing personalized therapeutic decisions.

The study brings together a group of international experts in breast cancer from leading hospitals, as well as experts in medical statistics, comprehensive cancer networks, and clinical trials; regulatory experts; Health Technology Assessment (HTA) experts; innovative Small and Medium Enterprises (SMEs) related to technology; policymakers; patient associations; living labs; and medical societies.

The DEFINITIVE study will be a collaborative effort involving 18 esteemed entities from across the healthcare and research spectrum. This includes leading hospitals, research groups, universities, and cancer care organizations. Participants include the following:

1. Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (SPAIN)
2. Hospital Clínic de Barcelona (SPAIN)
3. SOLTI Breast Cancer Research Group (SPAIN)
4. UNICANCER (FRANCE)
5. Westdeutsche Studiengruppe GmbH (GERMANY)
6. Austrian Breast & Colorectal Cancer Study Group (AUSTRIA)
7. Università degli Studi di Padova (ITALY)
8. Istituto Oncologico Veneto IRCCS (ITALY)
9. Istituto Europeo di Oncologia (ITALY)
10. University College Cork - National University of Ireland (IRELAND)
11. The Sheba Fund for Health Services and Research (ISRAEL)
12. ERASMUS University Rotterdam (NETHERLANDS)
13. Center for Medical Data Science, Medical University of Vienna (AUSTRIA)
14. Institut Català d'Oncologia (SPAIN)
15. Europa Donna - European Breast Cancer Coalition (ITALY)
16. Société Internationale d'Oncologie Gériatrique (SWITZERLAND)
17. Sharing Progress in Cancer Care (SPCC) (SWITZERLAND)
18. Reveal Genomics S.L. (SPAIN)

Each of these organizations contributes their unique expertise and resources, thereby making this a truly comprehensive and multidisciplinary effort in advancing cancer research.
The DEFINITIVE study will include patients with newly diagnosed stage II-IIIA HER2+ breast cancer to be treated based on the HER2DX^® test results or without them (i.e. following local clinical guidelines). The inclusion and exclusion criteria will be broad in order to ensure that the trial's results can be applied to the wider population receiving treatment in real-world settings, thereby allowing the participation of a diverse range of patients, including the elderly and fragile.

The trial will be conducted across 44 sites in a total of 7 European and associated countries, analyzing the data of around 300 patients.

In addition to the clinical and logistical aspects of the study, we will take a comprehensive approach in order to ensure broad access to the test within society. This approach encompasses various initiatives:

• Health Technology Assessment (HTA) Strategies: to evaluate the test's effectiveness and value in a healthcare setting.
• Patient-Oriented Events: to inform and engage patients directly, thereby enhancing their understanding and acceptance of the test.
• Continuing Education for Healthcare Professionals: to keep medical practitioners abreast of the latest developments and applications of the test.
• Communication and Dissemination Efforts: targeting the general public, these actions are designed to raise awareness and knowledge about the test and its potential benefits.

About HER2DX^®?
HER2DX^® is the world's first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS^®? since January 2022, the HER2DX^® is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX^® is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX^® predicts:

• Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
• pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
• ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low, and HER2+ breast cancer.

About HER2+ breast cancer
HER2+ breast cancer accounts for 20% of all diagnosed breast tumors. This represents more than 390,000 new cases diagnosed worldwide every year, meaning that, on average, 3 women are diagnosed with HER2+ breast cancer every 4 minutes. HER2+ breast cancer is clinically and biologically heterogeneous, and standard clinical-pathological assessment has proven insufficient in capturing this heterogeneity. Understanding this biological heterogeneity is key to identifying the prognosis of each patient and the benefit from systemic therapies that target HER2.

About REVEAL GENOMICS^®?
REVEAL GENOMICS, S.L. is a biotechnology start-up seeking to change the way biomarkers are used in oncology. It is focused on developing innovative diagnostic tools to define the best therapeutic options for patients with cancer. The company uses pioneering techniques, sophisticated computer applications, and machine learning to reveal new cancer research data.

REVEAL GENOMICS, S.L. is a spin-off company of Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS,) the University of Barcelona (U.B.), and the Vall d'Hebron Institute of Oncology (VHIO).

REVEAL GENOMICS^® and HER2DX^®?are registered trademarks of REVEAL GENOMICS, S.L.

Web: www.reveal-genomics.com. Twitter: @revealgenomics