On November 15, 2018 Neovia Oncology reported that Substantial limitations in the response rates for cancer immunotherapy and increasing drug-resistance in cancer patients in general have led to a search for rational drug combination therapy (Press release, Neovia Oncology, NOV 15, 2018, View Source [SID1234531343]). It has been reported that Topoismerase types I (Topo I) and II (Topo II), already well recognized as important targets for inhibiting cellular DNA replication, are highly expressed in many cancers and also ‘cross-talk’ with Epidermal Growth Factor Receptor, which is the target of several recently approved cancer drugs. Moreover Topo I inhibitors have recently been shown to augment T-cell mediated antitumor immune response and enhance the efficacy of immunotherapy. Currently approved Topo inhibitor drugs, however, are single agents and known to be highly toxic even at low doses.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Neovia’s NEV-801 investigational product is the result of structure-based drug design to create a covalently conjugating camptothecin and podophyllotoxin derivative multi-inhibitor (simultaneously inhibiting topo I and II) with potent anti-cancer efficacy through a synergistic immune response but with minimal toxicity. For example, when used as a single agent in preclinical studies of Chronic Myelogenous Leukemia models, NEV-801 causes tumor sizes to diminish, with 38% of tumors disappearing completely and a 98% tumor growth inhibition rate compared to 0% and 33%, respectively, for leading marketed drug Imatinib (Gleevec). Weight loss was effectively overcome within a week of continued administration. Additionally in an ovarian cancer model NEV-801 was shown to be synergistic with immune checkpoint inhibitors PD-1 and CTLA-4.
Neovia is currently studying NEV-801 in a Phase 1 dose-escalation, dose-confirmation trial, in which anti-tumor effects are also being evaluated to determine the tumor types to be targeted in Phase 2. Through cohort 3 (80 mg), NEV-801 has been well tolerated with no reported serious adverse events. Importantly, NEV-801 can also be used as an oral anticancer drug, which is strongly recommended for cancer therapy of patients, since PK data analysis demonstrates that it can pass the Caco-2 cell membrane with a high permeability of 9.2. This also explains the lower GI-related toxicity.
Neovia has a strong patent portfolio with protection into 2035, with plans to file for Orphan Drug designation that will extend exclusivity for 7 years in the US and 10 years in Europe after approvals.