Terremoto Biosciences has spelt out how the California biotech will use a $108 million series C round to continue its efforts to broaden the covalent drug alphabet.
Proceeds from the financing will be used to fund phase 1 studies of the company’s AKT1-selective inhibitor programs, according to an April 15 release. The lead candidate in this pipeline, dubbed TER-2013, is already in the clinic as a potential treatment for solid tumors with PIK3CA, AKT or PTEN mutations.
Next up is TER-4480, which Terremoto is hoping to take into a phase 1 study later this year for hereditary hemorrhagic telangiectasia (HHT), a rare, inherited bleeding disorder.
The South San Francisco- and San Diego-based biotech, which launched in 2022, is focused on harnessing covalent chemistry to develop small molecule medicines that are more specific, potent and overall superior for patients with a range of highly complex diseases, including cancer.
Covalent medicines have traditionally relied on binding to the amino acid cysteine, which is uncommon in proteins, thus limiting the number of potential drug targets. Instead, Terremoto is developing drugs that covalently bind to lysine, an amino acid that is present in nearly every protein of interest.
The company has picked AKT because it is a key regulatory protein involved in the progression of both cancer and HHT. Terremoto pointed to preclinical evidence that AKT1 is the “predominant disease driver,” while the structurally similar isoform AKT2 has a role in adverse effects like rash and dysregulation of glucose homeostasis.
“While there has been considerable advancement of other PI3K/AKT pathway inhibitors, the efficacy of these treatments has often been limited by toxicities—primarily due to PI3Kα or AKT2 inhibition,” the company explained in Wednesday’s release. “Using advanced medicinal chemistry capabilities, Terremoto has developed a novel class of AKT1-selective inhibitors to overcome these limitations, aiming to achieve deeper and more durable treatment response with an improved tolerability profile.”
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Terremoto co-founder and former CEO Peter Thompson, M.D., previously described lysine-targeted covalent chemistry as “a game of dynamic Tetris” due to the chemical and biological complexity of covalently binding to the amino acid in a selective, on-target way. Thompson was succeeded as CEO by Pfizer oncology vet Charles Baum, M.D., Ph.D., in 2024.
Today’s funding round saw new investors RA Capital Management, Deep Track Capital, Osage University Partners and BeOne Medicines join existing big-name backers OrbiMed, Third Rock Ventures, Novo Holdings and Cormorant Asset Management.
The latest raise follows a $75 million series A in 2022 and a $175 million series B in 2023.
