BARCELONA, Spain - TelAve -- ARJUNA Therapeutics, a pre-clinical-stage biotechnology company developing a first-in-class mitochondrial redox targeting platform for treatment-resistant cancers, today announced a strategic research collaboration with Pangaea Oncology and the Dr Rosell Oncology Institute (Barcelona, Spain) to evaluate Ag5 in patient-derived tumour material from patients with third-line non-small cell lung cancer (NSCLC) who have progressed following treatment with osimertinib (Tagrisso®) or KRAS inhibitor therapy.

The collaboration will utilise Pangaea Oncology's unique access to patient-derived tumour material from one of the world's la rgest and most deeply characterised cohorts of advanced NSCLC patients, combined with the world-class translational oncology expertise of the Dr Rosell Oncology Institute. The programme will evaluate the sensitivity of post-osimertinib and post-KRASi patient-derived tumour specimens to Ag5, validate ARJUNA's predictive biomarker panel in a clinical patient population, and generate the translational evidence package required to support ARJUNA's planned Phase 1 clinical trial.

"Third-line NSCLC represents one of the most urgent and commercially significant opportunities in oncology," said Dr. Ross Breckenridge FRCP PhD, CEO of ARJUNA Therapeutics. "When patients progress after Tagrisso or a KRAS inhibitor, there is effectively nothing left on the shelf. Ag5 is specifically designed for this patient population – its mechanism of action directly targets the convergent mitochondrial vulnerability that emerges when tumours develop resistance to targeted therapies. This collaboration with one of the world's leading NSCLC centres gives us the highest-quality translational data to take into our IND filing, and is a big step towards the clinic for Ag5."

Dr. Rafael Rosell, President and Founder of Pangaea, adds: "Cancer patients who progress after osimertinib and a KRAS inhibitor face extremely limited clinical options. ARJUNA's approach, targeting a convergent mitochondrial vulnerability in these resistant tumours, is both innovative and highly promising. This collaboration enables us to validate this mechanism in a real clinical setting and accelerate the introduction of new therapeutic options into oncology practice."

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About the Clinical Opportunity

NSCLC accounts for approximately 85% of lung cancer cases - comprising 236,000 annual US diagnoses and 537,700 cases across the seven major markets (Delve Insight, 2025). The overall NSCLC therapeutics market was valued at $33.9 billion in 2024 and is projected to reach $66 billion by 2032 (Fortune Business Insights, 2024); the osimertinib (Tagrisso®) market alone is forecast to grow from $6.67 billion in 2024 to $14.17 billion by 2033 (Business Research Insights, 2024). Despite advances with first- and second-line targeted therapies, the vast majority of patients ultimately develop resistance. Those who have exhausted both osimertinib and a KRAS G12C inhibitor face median overall survival of approximately 8–10 months on salvage chemotherapy, with no approved targeted option. In China - where lung cancer is the leading malignancy with over 1.06 million new cases annually (National Cancer Center of China, 2022) and EGFR mutation rates reach 40% in adenocarcinoma - the post-osimertinib resistance setting represents a patient population of exceptional scale and unmet need. ARJUNA estimates peak annual sales potential of $2.15 billion for Ag5 in the third-line NSCLC indication.

About Ag5

Ag5 is ARJUNA's lead Therapeutic Molecular Cluster (TMC) - an entirely novel class of small molecule medicine comprised of metal atoms, developed through a quantum chemistry process. Ag5 is the first molecule simultaneously to inhibit both the thioredoxin (TRX) and glutathione (GSH) mitochondrial antioxidant systems, triggering rapid, irreversible cancer cell death via a catalytic mechanism that is selective for cells generating high levels of mitochondrial reactive oxygen species (ROS) - a hallmark of drug-resistant and metastatic tumour cells. Ag5 crosses the blood-brain barrier and has demonstrated single-agent efficacy in multiple preclinical models of cancer. A clinically available antidote (N-acetylcysteine) exists.

ARJUNA is targeting an Investigational New Drug (IND) application in 2027, with a Phase 1 "Rescue" Trial in post-TKI NSCLC with glioblastoma multiforme to follow.

ABOUT PANGAEA ONCOLOGY

Pangaea Oncology, led by Dr. Rafael Rosell and Javier Rivela and founded in Barcelona in 2006, is a medical services company focused on precision oncology, with the goal of improving survival and quality of life for cancer patients.

The company operates across two main areas: (i) its healthcare division, which brings together the efforts of several affiliated organizations (Dr. Rosell Oncology Institute, International Breast Cancer Center, Pectus Respiratory Health, and IOB Institute of Oncology in Barcelona), treating more than 9,000 new cases per year and averaging 82,000 total visits annually. (ii) Its diagnostics and R&D services division, serving both its own patients and the pharmaceutical industry, through which the company provides molecular and in vitro diagnostic services (biomarker discovery) and other clinical and preclinical services to leading international companies.

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Pangaea has a strong technological component, centered on proprietary and innovative molecular diagnostic techniques, with particular emphasis on its liquid biopsy, early detection, and in vitro technology programs. The integration of these areas forms the foundation of Pangaea's future growth strategy.

ABOUT DR. ROSELL ONCOLOGY INSTITUTE (IOR)

The Dr. Rosell Oncology Institute is a multidisciplinary oncology team composed of leading oncologists (and pulmonologists), highly specialized across different types of cancer and led by Dr. Rafael Rosell, a globally recognized authority in lung cancer and advanced research. With more than 600 scientific publications, he has been referred to as "the European leader in lung cancer" by The Lancet and also serves as Principal Investigator and Scientific Advisor to ARJUNA Therapeutics.

In clinical practice, the team handles more than 25,000 patient visits annually across Barcelona's leading and most renowned hospitals, where it also collaborates with specialized oncological surgery units. In addition, the Institute includes a dedicated clinical trials unit, offering patients access to some of the most innovative international clinical trials, in which the team plays both leading and active recruitment roles.

About ARJUNA Therapeutics

ARJUNA Therapeutics is a pre-clinical stage biotechnology company developing Therapeutic Molecular Clusters (TMCs) - a first-in-class platform of sub-nanometre metal medicines - for the treatment of drug-resistant and metastatic cancers. ARJUNA's lead asset, Ag5, targets the fundamental mitochondrial vulnerability shared by all aggressive cancers, with a mutation-agnostic mechanism that is active across multiple tumour types and resistant to acquired drug resistance. For more information, visit www.arjunatherapeutics.com.

Media/Investor Contact:
Konstantina Georgieva
ARJUNA Therapeutics
info@arjunatherapeutics.com

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Forward-Looking Statements

This press release contains forward-looking statements within the meaning of applicable securities laws. Such statements involve known and unknown risks and uncertainties. Actual results may differ materially from those anticipated. ARJUNA Therapeutics undertakes no obligation to update forward-looking statements.

Note: Tagrisso® is a registered trademark of AstraZeneca. Sotorasib (Lumakras®) is a registered trademark of Amgen. Adagrasib (Krazati®) is a registered trademark of Bristol Myers Squibb / Mirati Therapeutics. Trademarks are used for identification purposes only.