Atavistik Bio has achieved a significant milestone by dosing the first patient in its Phase 1 clinical trial of ATV-1601, a first-in-class selective allosteric inhibitor targeting AKT1 E17K-mutant solid tumors. This development marks the company's transition to clinical-stage operations and represents a potential breakthrough in precision oncology for a validated oncogenic driver affecting more than 40,000 cancer patients annually in the United States.
Novel Mechanism Addresses Current Treatment Limitations
ATV-1601 leverages a reversible allosteric mechanism of action to selectively inhibit AKT1 E17K, distinguishing it from existing pan-AKT inhibitors that block all three AKT isoforms (AKT1, AKT2, and AKT3). The AKT1 E17K mutation shows highest prevalence in breast, endometrial, and prostate cancers, and emerging evidence indicates it may serve as a resistance mechanism to PI3Kα-targeted cancer therapies.
Current pan-AKT inhibitors face significant limitations in treating AKT1 E17K-driven tumors due to insufficient inhibition of the specific mutation and AKT2-driven tolerability issues that lead to treatment discontinuation or dose reductions in a considerable subset of patients. In preclinical studies, ATV-1601 demonstrated enhanced target inhibition, superior efficacy, and improved tolerability compared to pan-AKT inhibitors.
"Dosing the initial patient in our first-in-human study of ATV-1601 represents a significant milestone as we transition to a clinical stage biotechnology company and an important step forward in our efforts to develop innovative treatments for patients," said Bryan Stuart, Chief Executive Officer at Atavistik Bio. "As a selective allosteric AKT1 E17K inhibitor, ATV-1601 has generated a highly differentiated preclinical profile, which we believe has the potential to address significant unmet need for patients."
Phase 1 Study Design and Objectives
The first-in-human, open-label Phase 1a/1b study (NCT07038369) will evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of ATV-1601 in two treatment approaches. The study includes monotherapy evaluation in participants with advanced or metastatic AKT1 E17K-mutant solid tumors, and combination therapy with fulvestrant in participants with AKT1 E17K-mutant hormone receptor-positive/HER2-negative breast cancer.
The Phase 1 study incorporates both dose escalation and expansion phases for ATV-1601 monotherapy, as well as escalation and expansion phases for the combination with fulvestrant. This comprehensive design aims to establish optimal dosing while gathering preliminary efficacy data across different patient populations.
Technology Platform and Development Strategy
ATV-1601 was developed using Atavistik Bio's proprietary AMPS™ technology, which is integrated with an AI-enabled drug discovery engine designed to rapidly advance programs from discovery into development. The company is advancing a pipeline of precision allosteric oncology candidates, all discovered in-house, targeting a broad range of target classes.
The selective allosteric approach represents a potential paradigm shift in AKT-targeted therapy, offering the possibility of greater efficacy and tolerability specifically for AKT1 E17K-driven cancers. As the only approved AKT-targeted therapy currently available is a pan-AKT inhibitor, ATV-1601's selective mechanism could provide a transformative treatment option for patients with this specific mutation.
Stuart emphasized the company's commitment to rapid progression toward proof-of-concept data, stating, "We look forward to evaluating ATV-1601 in the clinic and moving rapidly toward early proof-of-concept data for this program."
