Terremoto Advances TER-2013 With FDA Fast Track Designation

Terremoto Biosciences has received U.S. Food and Drug Administration (FDA) Fast Track Designation for TER-2013, its lead AKT1-selective small-molecule inhibitor, in patients with locally advanced, unresectable, or metastatic hormone receptor-positive (HR+), HER2-negative breast cancer harboring AKT, PI3K, or PTEN alterations.

The designation applies to patients whose disease has progressed following at least one endocrine-based therapy and a CDK4/6 inhibitor.

Fast Track status expedites the development and review of therapies for serious conditions with significant unmet medical need. The designation enables more frequent FDA interactions and may support eligibility for accelerated approval or priority review if regulatory requirements are met.

Selective AKT1 Targeting to Address Resistance

Alterations in the PI3K/AKT/PTEN signaling pathway are among the most common drivers of endocrine resistance and disease progression in HR+/HER2- breast cancer. While pan-AKT inhibitors such as capivasertib and ipatasertib have demonstrated clinical activity, their broader inhibition of multiple AKT isoforms has been associated with toxicities including hyperglycemia, rash, and diarrhea.

TER-2013 takes a differentiated approach by selectively targeting AKT1, the isoform most closely linked to tumor growth in cancers with pathway alterations. Preclinical studies showed potent and sustained AKT1 inhibition while sparing AKT2, AKT3, and other off-target proteins. The therapy also demonstrated durable antitumor activity across xenograft models harboring PIK3CA, AKT1, or PTEN alterations while avoiding AKT2-related hyperglycemia and other off-target toxicities observed with earlier pan-AKT inhibitors.

If confirmed clinically, selective AKT1 inhibition could improve tolerability while maintaining antitumor activity, potentially addressing a key limitation of earlier AKT-targeted therapies.

Phase 1 Progresses Toward Expansion

TER-2013 is under evaluation in a first-in-human Phase 1 trial (NCT07109726) enrolling patients with advanced solid tumors harboring AKT, PI3K, or PTEN pathway alterations.

The dose-escalation phase has been completed, and Terremoto is finalizing dose selection for proof-of-concept expansion cohorts. Expansion cohorts will evaluate clinical activity in molecularly defined patient populations, including breast cancer and other tumors driven by PI3K/AKT/PTEN pathway alterations.

The company has not disclosed timelines for initial clinical readouts, but enrollment into expansion cohorts is expected following dose confirmation.

Leadership Highlights Clinical Need

Charles Baum, MD, PhD, Chief Executive Officer of Terremoto Biosciences, said the FDA’s decision underscores the ongoing need for more effective treatment options for patients whose disease progresses despite current standards of care.

James Christensen, PhD, President and Head of Research and Development, noted that TER-2013 was developed to overcome limitations associated with earlier pan-AKT inhibitors. He highlighted the molecule’s ability to maintain strong inhibition of the disease-driving AKT1 isoform while reducing off-target activity that may contribute to treatment-related toxicities.

Next Steps in Development

With Fast Track Designation secured, Terremoto plans to advance Phase 1 development, finalize dose selection, and initiate expansion cohorts. The company also intends to explore additional tumor types characterized by AKT, PI3K, or PTEN alterations, potentially broadening the therapeutic reach of TER-2013 as clinical data mature.

While Fast Track status does not guarantee approval, it provides a clearer regulatory pathway as clinical development advances.

Reference

Terremoto Biosciences Granted FDA Fast Track Designation for TER-2013, an AKT1-Selective Small Molecule Inhibitor for Breast Cancer | Terremoto