NEO-811 / Neomorph - LARVOL DELTA

Development of NEO-811, a molecular glue degrader of ARNT (HIF-1β) with potent single agent activity in ccRCC (AACR 2026) - P1 | "Thus, the HIF-2⍺ antagonist belzutifan has demonstrated beneficial clinical activity in ccRCC, gaining clinical approvals for use in patients with ccRCC as well as for VHL disease associated tumors, pheochromocytomas and paragangliomas. Additionally, PDX studies indicate that ARNT degradation can provide superior anti-tumor activity when compared to clinical HIF-2 antagonists and VEGFR tyrosine kinase inhibitors (TKIs).NEO-811 is currently in clinical development in the USA and Canada in a FIH Phase 1/2 study (Clinicaltrials.gov NCT07300241). This study will evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of NEO-811 administered as a single agent in adult subjects with locally advanced or metastatic non-resectable ccRCC."

Clear Cell Renal Cell Carcinoma • Oncology • ARNT • CRBN • GSPT1 • HIF1A • IKZF1 • SALL4

Preclinical characterization of NEO-811, a novel molecular glue degrader of ARNT for the treatment of clear cell renal cell carcinoma (AACR 2026) - "Critically, NEO-811 retained activity in HIF-2α inhibitor-resistant cells that harbored previously described mutations. In conclusion, our findings highlight the potential of ARNT degradation as a promising therapeutic modality for the treatment of VHL-deficient ccRCC."

Preclinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CRBN • EPAS1 • HIF1A • VHL

Discovery and optimization of NEO-811, a first-in-class molecular glue degrader of ARNT, utilizing structure-based drug design (AACR 2026) - "A cryo-EM structure confirmed direct ARNT recruitment to CRBN and revealed opportunities to enhance the depth of degradation and selectivity against neosubstrates. A medicinal chemistry campaign incorporating structure-based drug design enabled the development of NEO-811, a potent and selective degrader of ARNT entering clinical trials for treatment of ccRCC."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CRBN • EPAS1 • IL17RB • VHL

Targeting HIF pathway with a novel and potent ARNT molecular glue degrader for the treatment of renal cell carcinoma (AACR 2026) - "Importantly, NEO-811 still retained activity in 786-O xenografts that expressed a HIF-2α mutant (i.e., G323E) that conferred resistance to inhibitors. These data provide preclinical evidence and scientific rationale to further investigate NEO-811, a potent and selective ARNT molecular glue degrader, clinically in patients with ccRCC VHL deficient tumors."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ARNT • CRBN • EPAS1 • HIF1A • NDRG1 • VHL

Neomorph Announces First Patient Dosed in Phase 1/2 Trial Evaluating NEO-811 For the Treatment of Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma (GlobeNewswire) - "The Phase 1/2 NEO-811-101 trial is a first-in-human, open-label study consisting of a single agent dose-escalation phase followed by dose expansion cohorts. The study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of NEO-811 in patients with locally advanced or metastatic non-resectable ccRCC."

First-in-human • Trial status • Clear Cell Renal Cell Carcinoma • Von Hippel-Lindau Syndrome