Terremoto Bio’s AKT1 inhibitor receives FDA Fast Track status for breast cancer

Edited by Robert McTiernan··2 min read

South San Francisco-based Terremoto Biosciences unveiled the receipt of US FDA Fast Track Designation for TER-2013, an orally bioavailable, AKT1-selective small molecule inhibitor. The award is related to the molecule’s potentail as a treatment for locally advanced, unresectable or metastatic hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer harboring one or more AKT/PI3K/PTEN alterations following progression on at least one endocrine-based therapy and a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for advanced disease.

Fast Track Designation enables more frequent interactions with the FDA on development plans, trial design, and data requirements, and makes TER-2013 eligible for rolling review, Priority Review, and Accelerated Approval if relevant criteria are met. No prior expedited designations for TER-2013 have been disclosed.

TER-2013 is currently being evaluated in a Phase I clinical trial (NCT07109726) in patients with solid tumors harboring AKT/PI3K/PTEN pathway alterations. According to the company, the dose-escalation portion of this first-in-human study has been completed and selection of an optimal dose for proof-of-concept expansion cohorts is ongoing. No clinical efficacy, safety, or pharmacokinetic data with numeric readouts have been publicly disclosed; the evidentiary basis for the designation therefore rests on preclinical findings and the established unmet need in the target population. In preclinical xenograft models harboring PIK3CA, AKT1, or PTEN genetic alterations, TER-2013 demonstrated potent and sustained AKT1 inhibition while sparing AKT2, AKT3, and other off-target proteins at efficacious doses, and produced durable anti-tumor activity without AKT2-dependent hyperglycemia, rash, or diarrhea — toxicities associated with pan-AKT inhibition.

The company closed a USD 108 million Series C financing round in April 2026, with TER-2013 identified as the lead asset.

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Research context

The designated population — patients with HR+/HER2- advanced breast cancer who have progressed on both endocrine therapy and a CDK4/6 inhibitor — represents a setting where PI3K/AKT pathway activation is a documented resistance mechanism and where approved options with durable, well-tolerated activity remain limited. The only approved AKT inhibitor in this space is capivasertib (AstraZeneca/Daiichi Sankyo, marketed as Truqap), a pan-AKT inhibitor that received US FDA approval in November 2023 in combination with fulvestrant for HR+/HER2- locally advanced or metastatic breast cancer with AKT1/PIK3CA/PTEN alterations. Ipatasertib (Roche/Genentech), another pan-AKT inhibitor, has been evaluated in Phase III trials in breast cancer but has not received approval in this indication.

Both capivasertib and ipatasertib inhibit all three AKT isoforms. Inhibition of AKT2 is associated with hyperglycemia, which has constrained dosing in clinical practice. TER-2013 is designed to inhibit only AKT1 — the isoform most directly implicated in driving tumor growth in PIK3CA-mutant and PTEN-altered breast cancer — while sparing AKT2 and AKT3, with the goal of preserving anti-tumor activity and reducing metabolic toxicity. Whether this selectivity translates into a clinically differentiated tolerability or efficacy profile will depend on data from the ongoing expansion cohorts, which have not yet been reported publicly.

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