Beyond Cancer Reports Updated Survival and Safety Data from Phase 1 UNO Trial Presented at AACR 2026

Beyond Cancer's UNO Trial Shows Durable Survival in Heavily Pretreated Patients

Beyond Cancer, Ltd. announced updated follow-up data from its Phase 1 UNO trial (NCT05351502) at the American Association for Cancer Research (AACR) Annual Meeting 2026. The trial evaluated intratumoral ultra-high concentration nitric oxide (UNO) in ten heavily pretreated patients with unresectable cutaneous or subcutaneous lesions, including breast cancer, squamous cell carcinoma, and melanoma. As of February 2, 2026, six of ten patients remained alive between 22 to 40 months following a single UNO injection, with median overall survival not yet reached. Two patients with triple-negative breast cancer showed no evidence of disease. The treatment demonstrated a generally favorable safety and tolerability profile, with most adverse events being Grade 1 or 2. Additionally, the company received a U.S. patent allowance for its proprietary gas delivery technology for UNO.

• The Phase 1 UNO trial demonstrated notable durability of survival in a challenging, heavily pretreated patient population. Six of ten patients, who had received a median of four prior systemic therapies, remained alive between 22 to 40 months after a single intratumoral UNO injection. Median overall survival had not been reached at the last follow-up, and two triple-negative breast cancer patients continued to show no evidence of disease, suggesting significant therapeutic potential in a salvage-stage setting with limited treatment alternatives.
• UNO therapy exhibited a generally favorable safety and tolerability profile in the Phase 1 study. Most treatment-related adverse events were predominantly Grade 1 or Grade 2, indicating a manageable side effect profile. A single treatment-related serious adverse event (hypoxia) occurred at the 25,000 ppm dose but was not considered dose-limiting and resolved fully, supporting the potential for UNO to be further developed with a favorable toxicity profile.
• Beyond Cancer significantly strengthened its intellectual property portfolio with the U.S. Patent and Trademark Office issuing a Notice of Allowance for a patent application titled, “System and Method for Delivery of Gas to a Tissue.” This patent allowance covers the company's proprietary gas delivery technology for UNO, providing a robust foundation for the continued development and potential commercialization of its ultra-high concentration nitric oxide platform for solid tumors.

Addressing Unmet Needs in Heavily Pre-treated Solid Tumors

Current treatment approaches for solid tumors face multiple interconnected challenges that limit therapeutic efficacy and patient outcomes. These limitations span from fundamental drug selectivity issues to complex resistance mechanisms that emerge during treatment. The challenges are particularly pronounced in heavily pre-treated patients where conventional therapies have reached their efficacy plateau.

• Poor drug selectivity - Conventional anticancer drugs display relatively poor selectivity for neoplastic cells, particularly in solid tumors, leading to significant off-target effects and toxicity

• Hypoxic tumor microenvironment - Hypoxic environments prevalent in solid tumors create challenging conditions for treatment effectiveness and require specialized drug design approaches

• Intratumor heterogeneity - Contributes to treatment failure by initiating phenotypic diversity that enables drug resistance to emerge and introduces tumor sampling bias in therapeutic targeting

• Cancer stem cell populations - Stem-like cells identified within solid tumors drive drug resistance, metastasis, and local relapse, representing a persistent reservoir of treatment-resistant disease

• Robust resistance mechanisms - Expression or development of drug resistance decreases efficacy through multiple pathways including increased glutathione transferases, enhanced DNA repair, and metabolic plasticity

• EGFR inhibitor resistance - Tyrosine-kinase inhibitors like gefitinib and erlotinib show limited clinical efficacy due to resistance development, caused in more than 50% of cases by emergence of secondary T790M point-mutation in EGFR's ATP-binding cleft

• Immunosuppressive environment - Immune evasion and the immunosuppressive tumor microenvironment pose significant challenges for immunotherapy approaches in solid tumors

• Efficacy plateau of conventional therapy - Traditional chemotherapeutic regimens have reached an efficacy plateau against most solid tumors while maintaining significant toxicity profiles

Updated Safety and Survival Data for UNO in Solid Tumors

Recent published data demonstrates that nitric oxide exhibits variable safety profiles across different therapeutic applications and delivery methods. The tolerability depends significantly on the specific indication, dosing regimen, patient population, and route of administration. Clinical experience spans from well-established uses in neonatal care to emerging applications in oncology and antimicrobial therapy.

• Inhaled nitric oxide in respiratory applications shows generally acceptable tolerability but requires careful monitoring, with abrupt discontinuation causing significant hemodynamic complications in 25.8% of patients with acute hypoxemic respiratory failure, including cardiovascular collapse from acute right ventricular afterload increases

• Pediatric populations demonstrate good tolerability across multiple studies, with no clinically important side effects observed in 37 neonates treated with sildenafil (working through NO pathway) for persistent pulmonary hypertension, and well-tolerated responses in antimicrobial applications using inhaled NO at 150-250 ppm for 4 weeks

• Cardiovascular applications reveal dose-dependent effects, with nitroglycerin causing venodilation at lower doses and arteriodilation at higher doses, while immediate-release sodium nitrite produces manageable asymptomatic blood pressure drops of 10/6 mmHg in diabetic patients

• Recreational nitrous oxide abuse presents significant neurological risks, causing myeloneuropathy through vitamin B12 metabolism disruption, with 87.5% of abuse patients showing T2 hyperintensity on MRI and severe motor deficits from axonal dysfunction

• Novel delivery systems show promising safety profiles, with S-nitrosothiol-loaded nanoparticles for lymphatic delivery demonstrating low-to-negligible systemic NO accumulation and no apparent inflammation, while NO-releasing nanoparticles face challenges with toxicity and clinical application despite encouraging antimicrobial results

• Systemic administration challenges include the short half-life of NO (1-5 seconds), uncontrolled blood circulation release, and potential for extensive side effects from NO donors affecting both local tumor microenvironments and causing systemic hypotension from iNOS overexpression

Nitric Oxide's Diverse Therapeutic Applications Beyond Cancer

Nitric oxide-based therapies are being investigated across multiple therapeutic areas beyond oncology, with particularly active research in cardiovascular, metabolic, and rare disease applications. However, specific clinical trial intervention model details are limited in the available literature.

Ultra-High Nitric Oxide: A New Frontier in Localized Cancer Therapy

The recent announcement from Beyond Cancer, Ltd. regarding updated follow-up data from its Phase 1 UNO trial marks a potentially significant development in the treatment landscape for localized, refractory solid tumors. In a small cohort of ten heavily pretreated patients with unresectable cutaneous or subcutaneous lesions, including breast cancer, squamous cell carcinoma, and melanoma, the intratumoral administration of ultra-high concentration nitric oxide (UNO) demonstrated remarkable durability. Six of these patients remained alive between 22 to 40 months following a single injection, with the median overall survival not yet reached. Notably, two patients with triple-negative breast cancer, a subtype known for its aggressive nature and lack of targeted therapies, achieved no evidence of disease.

This early data is particularly compelling given the high unmet need in this patient population, who often have exhausted conventional treatment options. The favorable safety and tolerability profile, with most adverse events being Grade 1 or 2, further strengthens the potential of UNO. The underlying scientific premise leverages the complex biology of nitric oxide (NO). While NO has a dual role in cancer, with some studies linking lower or chronic NO exposure to tumor progression and metastasis, research also consistently shows that high concentrations of NO can induce potent cytotoxicity and apoptosis in tumor cells. The key differentiator for UNO appears to be its ability to deliver ultra-high concentrations directly into the tumor, potentially tipping the balance towards anti-tumorigenic effects and remodeling the tumor microenvironment to enhance therapeutic outcomes.

Strategically, these results suggest several implications:

• UNO could emerge as a vital localized therapy for patients with refractory solid tumors, offering a new option where current treatments fall short.

• The company's recently granted U.S. patent for its proprietary gas delivery technology provides a strong intellectual property foundation, protecting its unique approach and offering a competitive edge.

• The broad activity observed across different tumor types hints at UNO's potential as a platform technology, though future development will likely focus on specific indications with the highest unmet need.

However, it is crucial to acknowledge the inherent risks associated with early-phase data. The small sample size and heterogeneous nature of the patient population mean that these promising results require validation in larger, controlled studies. The complex and sometimes contradictory role of NO in cancer also necessitates careful consideration of the therapeutic window and potential for off-target effects. Furthermore, the practicalities of consistently delivering ultra-high concentrations of gas intratumorally will need to be addressed as the therapy progresses through development. Despite these considerations, the long-term survival and complete responses observed in such a challenging patient group position UNO as a novel and exciting candidate that warrants close attention from the oncology community.