ALTA-3263

Driven to make targeted medicines even more precise, Alterome Therapeutics pocketed a $132-million Series B to move a pair of oncogenic driver-targeting small molecules into the clinic within the next year.Led by Goldman Sachs Alternatives, Wednesday’s financing also saw participation from Canaan Partners, Driehaus Capital Management, Invus, Digitalis Ventures, Blue Owl Capital, as well as existing investors Orbimed, Nextech Invest, Vida Ventures, Boxer Capital, and Colt Ventures. The round adds to the $99 million Alterome raised in 2022 between a Series A and extension.The biotech takes its name from the biological alterome, which encompasses all the disease-driving alterations in genes – and largely remain undrugged. According to the company, while several medicines targeting oncogenic mutations have been approved, they can have off-target effects that limit their therapeutic window, diminishing their benefit for patients.Alterome is deploying its Kraken platform to design mutation- and isoform-selective small molecules that preferentially target cancer cells and avoid healthy cells. The goal of the structure-guided, machine learning approach is to improve the inhibitory power and safety profile of precision medicines.The Kraken provides atomic-level insights into molecular interactions to predict ligand and binding activity so Alterome’s team of medicinal chemists can discover selective, alteration-specific compounds. “The precision oncology field has arrived at a special moment with the exciting evolution of both drug discovery and precision medicine,” CEO Eric Murphy said. “A unique integration of structure-guided drug discovery with deep translational biology is facilitating the development of novel therapies that address previously inaccessible proteins.”Precision pipelineAlterome’s lead programme targets AKT1 E17K, a clinically validated oncogene that drives about 2% of all tumours, including breast, endometrial and prostate cancers. The oral small molecule, dubbed ALTA-2618, was designed to be a mutant-selective, covalent allosteric inhibitor of AKT1 E17K.The biotech’s second candidate, ALTA-3263, is directed against KRAS, a well-known regulator of cellular signalling that’s mutated in more than 20% of all cancers. However, according to Alterome, the first-generation of KRAS inhibitors had a narrow scope of mutational coverage leading to limited durability and poor tolerability. In contrast, Alterome’s compound is isoform-selective and targets 90% of KRAS mutations, including the most common, G12V and G12D.