FDA Grants Fast Track Designation to TER-2013 for Advanced Breast Cancer

The FDA has granted fast track designation to the investigational, orally bioavailable small-molecule inhibitor TER-2013 for the treatment of specific cohorts of patients with advanced breast cancer.¹ The designation applies to patients with locally advanced, unresectable or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2–) breast cancer harboring 1 or more AKT, PI3K, or PTEN alterations, whose disease has progressed following at least 1 endocrine-based therapy and a CDK4/6 inhibitor.¹

The FDA's fast track program is designed to facilitate the development and expedite the review of therapeutics intended to treat serious conditions and fill unmet medical needs. This designation provides Terremoto Biosciences, the sponsor, with opportunities for more frequent regulatory interactions regarding the clinical development plan, trial designs, and data requirements necessary to support a potential marketing application. Additionally, programs with fast track status may qualify for priority review and accelerated approval if prespecified clinical criteria are met.

“The designation reinforces the significant unmet need for effective treatment options for patients with advanced breast cancer,” said Charles Baum, MD, PhD, CEO of Terremoto Biosciences, in a news release. “We are committed to advancing highly selective therapies designed to expand treatment options for patients with difficult to treat cancers.”

Therapeutic Rationale and Mechanism of Action

The PI3K/AKT/PTEN cell-signaling pathway is frequently dysregulated in breast cancer, serving as a primary mechanism of resistance to standard endocrine therapies and CDK4/6 inhibitors.² While pan-AKT inhibitors have historically demonstrated clinical efficacy in managing pathway-mutated tumors, their utility has been significantly restricted by class-wide toxicities. Classic adverse events associated with pan-AKT inhibition include severe hyperglycemia, skin rash, and gastrointestinal distress, such as diarrhea.¹

Hyperglycemia is primarily driven by the inhibition of the AKT2 isoform, which mediates systemic insulin signaling and glucose homeostasis.³ TER-2013 was engineered to selectively target the AKT1 isoform while sparing AKT2 and AKT3 proteins. In preclinical evaluations, this isoform-specific selectivity allowed for sustained inhibition of tumor cell growth without inducing the metabolic disruption or off-target toxicities typically seen with broader pan-AKT approaches. Preclinical xenograft models harboring PIK3CA, AKT1, or PTEN alterations demonstrated robust and durable anti-tumor responses when exposed to the therapeutic.

Current Clinical Development

The therapeutic is currently undergoing evaluation in a first-in-human, open-label phase 1 clinical trial (NCT07109726).³ The study is enrolling patients with advanced solid tumors characterized by documented AKT, PI3K, or PTEN pathway alterations. Investigators have successfully completed the dose-escalation phase of the trial, which focused on establishing initial safety, tolerability, and pharmacokinetic profiles.

Efforts are currently focused on identifying and selecting the optimal dose for proof-of-concept expansion cohorts.¹ These upcoming expansion arms will evaluate the efficacy and safety of TER-2013 in specific molecularly defined patient populations, including the HR+/HER2– breast cancer cohort highlighted by the FDA designation. Terremoto Biosciences has indicated plans to explore additional expansion opportunities in other solid tumor types utilizing this AKT1-selective strategy.

REFERENCES

1. Terremoto Biosciences granted FDA Fast Track Designation for TER-2013, an AKT1-selective small molecule inhibitor for breast cancer. Press release. Terremoto Biosciences. June 3, 2026. Accessed June 3, 2026. https://www.businesswire.com/news/home/20260603010020/en/

2. Razavi P, Chang MT, Xu G, et al. The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 2018;34(3):427-438.e6. doi:10.1016/j.ccell.2018.08.008

3. A Phase 1/​2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/​PI3K/​PTEN Pathway Alterations. ClinicalTrials.gov. Updated May 22, 2026. Accessed June 3, 2026. https://clinicaltrials.gov/study/NCT07109726