AUBE00 / Roche, Chugai Pharmaceutical - LARVOL DELTA

Chemical optimization of N–Alkylated macrocyclic peptides enables oral bioavailability and KRAS–selective RAS inhibition (ACS-Fall 2026) - "Notably, AUBE00 exhibited absorption properties comparable to those of LUNA18, with 24–65% oral BA in animal models without the use of specialized formulations, while demonstrating a 10–14-fold preference for KRAS over other RAS isoforms. Together, these results demonstrate the feasibility of achieving oral BA and precise isoform selectivity in macrocyclic peptides and provide important guidance for the future optimization of drug-like peptides."

HRAS • KRAS • NRAS

AUBE00: A novel cyclic peptide pan-KRAS inhibitor targeting KRAS-activated cancers including KRAS-mutant cancers and wild-type colorectal cancer (AACR 2026) - "These include the FDA approval of G12C inhibitors such as sotorasib and adagrasib that target the OFF state of RAS, as well as the ongoing development of various non-G12C inhibitors and ON-state RAS inhibitor.Here we present AUBE00, a novel cyclic peptide that selectively binds to the OFF state of KRAS...Based on this biological insight, we compared efficacy of AUBE00 with RMC-6236, a pan-RAS(ON) inhibitor among models with various KRAS alterations...Furthermore, combination treatment with cetuximab and AUBE00 exhibited synergistic antiproliferative effects in vitro.In conclusion, our preclinical data establish AUBE00 as a promising therapeutic option for cancers harboring KRAS mutations as well as RAS wild-type colorectal cancer. AUBE00 is currently being evaluated in a Phase 1 dose escalation study to assess its safety, tolerability, and preliminary efficacy in patients with advanced solid tumors."

Colorectal Cancer • Oncology • Solid Tumor • KRAS • NF1

Chemical optimization of an orally bioavailable macrocyclic peptide KRAS inhibitors that achieve KRAS selectivity by recognizing a single amino acid difference (AACR 2026) - "Using this technology, we previously reported LUNA18 (Paluratide), a mid-sized cyclic peptide that binds reversibly to GDP-bound RAS isoforms (KRAS, NRAS, HRAS), inhibiting their signaling (J. In mouse xenograft models, oral administration of AUBE00 resulted in robust antitumor efficacy. A Phase 1 clinical trial in patients with advanced solid tumors is currently ongoing."

Oncology • Solid Tumor • HRAS • KRAS • NRAS

Study of AUBE00 in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Chugai Pharmaceutical | N=100 ➔ 130 | Trial completion date: Jun 2030 ➔ Dec 2029 | Trial primary completion date: Jun 2030 ➔ Dec 2029

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • KRAS

Study of AUBE00 in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Chugai Pharmaceutical

New P1 trial • Solid Tumor