Camptothecin/Podophyllotoxin

Independent studies establish a differentiated mechanism for clinical-stage NEV-801 and reveal broader potential for Neovia’s proprietary oncology and ADC payload portfolio. NEWPORT BEACH, Calif. — September 2026 — Neovia Oncology LLC today announced the filing of a new patent application following independent confirmation that its clinical-stage oncology compound NEV-801 inhibits both human Topoisomerase I and Topoisomerase II through catalytic inhibition rather than the interfacial-poison mechanism associated with conventional topoisomerase-directed cancer drugs. The discovery materially changes the scientific and strategic understanding of NEV-801 and the broader Neovia compound portfolio. NEV-801 has completed Phase I clinical evaluation in patients with advanced malignancies, while related proprietary Neovia compounds are being developed and evaluated for potential applications including next-generation antibody-drug conjugate (ADC) payloads. For pharmaceutical and biotechnology companies developing new oncology therapeutics, the distinction may be particularly significant. Topoisomerase-directed agents have become important components of modern cancer therapy and ADC development. Neovia’s newly characterized mechanism introduces the possibility of approaching Topoisomerase I and II biology through a fundamentally different mechanism. A Different Approach to Topoisomerase Inhibition Most clinically established topoisomerase-directed cancer drugs act as interfacial poisons. Rather than simply inhibiting the enzyme, these agents stabilize normally transient enzyme-DNA cleavage complexes, creating persistent DNA strand breaks that contribute to tumor-cell killing but can also produce significant toxicity and mechanisms of resistance. Independent biochemical studies conducted by TopoGEN, Inc. , ( ) a specialist in DNA topoisomerase research and mechanistic drug characterization, demonstrated a different mechanism for NEV-801. NEV-801 inhibited the catalytic activity of both human Topoisomerase I and Topoisomerase II without stabilizing the DNA cleavage complexes characteristic of conventional topoisomerase poisons. The findings identify NEV-801 as a dual Topoisomerase I/II catalytic inhibitor and provide a new mechanistic explanation for observations made during the compound’s development and its higher efficacy with lower side effects (no SAEs) profile. “Dual catalytic Topoisomerase I/II inhibitors that are safe are highly consequential, if not revolutionary,” said Dr. Mark Muller, founder and CEO of TopoGEN, Inc. The distinction is potentially important because simultaneous catalytic inhibition of both enzymes offers a way to disrupt two complementary systems used by rapidly dividing cancer cells to manage DNA topology, without depending upon the DNA-damage mechanism associated with conventional topoisomerase poisons. Human Clinical Experience Already Established Unlike many newly discovered oncology mechanisms that begin with preclinical development, NEV-801 has already undergone first-in-human clinical evaluation. The Phase I study evaluated intravenous NEV-801 in patients with advanced malignancies for whom standard therapies were no longer effective or available. The clinical program therefore provides human exposure and safety experience for a molecule whose mechanism has now been more precisely characterized. This creates an unusual development sequence: the molecule reached human clinical testing before the full significance of its dual catalytic Topoisomerase I/II activity was understood. “The molecule has not changed. Our understanding of what it is has,” said Trevor G. Blake, Founder and CEO of Neovia Oncology . “We originally developed NEV-801 because of its activity across several cancer pathways and its ability to overcome mechanisms associated with multidrug resistance. Independent mechanistic work has now shown us something considerably more fundamental. We have a clinical-stage molecule capable of catalytically inhibiting both Topoisomerase I and Topoisomerase II without behaving like conventional topoisomerase poisons.” Implications Beyond NEV-801 The discovery has potential implications well beyond the clinical development of NEV-801. Neovia owns a broader proprietary family of related compounds. Several are being evaluated as potential ADC payload candidates, where potency, mechanism, therapeutic index and differentiation from existing payload classes are critical considerations. Topoisomerase-directed payloads have become an important component of the rapidly expanding ADC field. Neovia believes its compounds warrant investigation as a potentially differentiated approach because their underlying topoisomerase biology may differ materially from conventional poison-based payload mechanisms. The company is now extending its mechanistic work across additional members of the portfolio to determine whether the dual catalytic inhibition observed with NEV-801 is shared by related compounds and how those properties may translate into ADC payload applications. “This discovery caused us to look again at the entire portfolio,” Blake said. “NEV-801 gives us something particularly valuable: human clinical experience with the molecular family. Behind it are compounds that can now be investigated specifically for applications where high potency and mechanistic differentiation matter, including ADC payload development.” Potential Relevance to Drug Resistance Dual Topoisomerase inhibition may also be relevant to one of oncology’s persistent challenges: treatment resistance. Cancer cells can adapt to inhibition of a single biological pathway through compensatory mechanisms. Simultaneous inhibition of Topoisomerase I and II creates a different biological proposition by interfering with both major topoisomerase systems involved in managing DNA topology during replication and transcription. NEV-801 has previously demonstrated activity involving additional cancer-related pathways, including mechanisms associated with hypoxia and multidrug resistance. Neovia is now investigating how those observations relate to the newly established dual catalytic Topoisomerase mechanism and whether the combination contributes to the compound’s differentiated biological profile. Expanding the Neovia Platform The new patent application seeks additional intellectual-property protection arising from the mechanistic discovery and its potential therapeutic applications. Neovia is continuing development of NEV-801 while expanding characterization of related compounds for standalone oncology and ADC payload applications. The company believes the combination of a differentiated mechanism, existing human clinical experience, proprietary follow-on compounds and potential ADC applications creates opportunities for strategic collaboration, licensing and further development with pharmaceutical and biotechnology partners. “We are not announcing another variation of a known topoisomerase poison,” Blake said. “The independent studies indicate that we are dealing with a different mechanism. The next question is how broadly that distinction can be exploited across cancer therapeutics and ADCs. That is the work now underway.” About Neovia Oncology Neovia Oncology is a privately held USA clinical-stage oncology company developing differentiated cancer therapeutics designed to address treatment resistance and improve therapeutic options for patients with difficult-to-treat malignancies. The company’s lead clinical compound, NEV-801, has completed Phase I clinical evaluation in patients with advanced cancers. Neovia is also developing a proprietary portfolio of related oncology compounds, including candidates under evaluation for potential use as next-generation ADC payloads. Neovia is headquartered in Newport Beach, California. Clinical Trial: NCT02797795 Media and Business Development Contact Shashi@neoviaoncology.com 1 866 636 8423