Terremoto Biosciences has closed a Series C financing round worth $108m, which will allow the company to usher its range of AKT-1 selective inhibitors through early clinical development across multiple rare disease and cancer indications.
The California-based biotech secured this funding from several new and existing investors, including industry giants like Novo Holdings, OrbiMed and Third Rock Ventures, as well as RA Capital Management, Cormorant Asset Management and BeOne Medicines.
With this cash in hand, Terremoto will now advance its AKT-1-selective inhibitors through Phase I, with a specific focus on oncological indications like hormone receptor (HR)-positive breast cancer, as well as rare bleeding disorder, hereditary haemorrhagic telangiectasia (HHT).
The jewel in Terremoto’s oncology crown and its most developed asset is its selective ATK1 blocker, TER-2031, which the company is currently evaluating in a first-in-human Phase I trial (NCT07109726). This study is exploring the drug’s safety and efficacy in solid tumours harbouring PIK3CA, AKT, or PTEN mutations – incorporating patients with indications like breast, ovarian, squamous head and neck and endometrial cancer, as per ClinicalTrials.gov.
Alongside its efforts in oncology, Terremoto hopes to take TER-4480, another ATK1 inhibitor, to the clinic in HHT later in 2026. Regulators are yet to approve any therapies for this inherited bleeding disorder, which impacts around 1.4 million people worldwide, as per Cure HHT. This makes it the second most common bleeding disorder in the US after Von Willebrand disease.
Making AKTs more tolerable
In November 2023, AstraZeneca notched a milestone by becoming the first company to secure approval for an AKT inhibitor, Truqap (capivasertib), which is now available to patients with HR-positive, HER2-negative advanced breast cancer.
While the non-selective AKT1, 2 and 3 blocker has demonstrated its potential in multiple solid tumour indications and has become one of AstraZeneca’s flagship oncology products, it can cause significant side effects. Upon treatment, some patients experience glucose dysregulation, as well as increased susceptibility to infections and liver toxicity.
According to Terremoto, side effects associated with AKT inhibitors are generally linked to AKT2. This led the company to theorise that an AKT1-selective therapy could overcome the toxicity hurdles associated with this drug class – offering a more tolerable therapy for patients.
Terremoto is not the only biotech attempting to harness a next-generation AKT approach, as Atavistik Bio recently dosed its first subject in a Phase I trial on its selective allosteric AKT1 E17K blocker, ATV-1601, in adults with solid tumours.
According to GlobalData’s Pharmaceutical Intelligence Center, there are 37 ongoing clinical trials evaluating AKT inhibitors in Phase I-III.
GlobalData is the parent company of Pharmaceutical Technology.
