AKT1 E17K

AKT1 E17K mutation is a clinically validated oncogene that impacts greater than 40,000 cancer patients per year in the United States, with the highest prevalence in breast, endometrial, and prostate cancersAs a selective allosteric AKT1 E17K inhibitor, ATV-1601 has the potential to provide enhanced target inhibition, superior efficacy and improved tolerability compared to pan-AKT inhibitorsAtavistik Bio anticipates initiating a first-in-human study with ATV-1601 in patients with AKT1 E17K mutant tumors in early 2025Preclinical data on ATV-1601 to be presented at the EORTC-NCI-AACR Symposium on October 23, 2024The company continues to leverage the AMPS™ platform to bring forward additional high-value precision oncology programs CAMBRIDGE, Mass., Oct. 15, 2024 (GLOBE NEWSWIRE) -- Atavistik Bio, a biotechnology company discovering the next generation of precision allosteric therapeutics inspired by the body’s natural regulators, today announced its precision oncology development candidate ATV-1601, an orally bioavailable selective allosteric small molecule inhibitor for AKT1 E17K-driven cancers. ATV-1601 was developed leveraging the company’s AMPS™ technology, which is seamlessly integrated with its AI-enabled drug discovery engine to rapidly advance programs from discovery into development. “ATV-1601’s nomination as our first oncology development candidate is a major milestone for the company, validating the capabilities of our proprietary platform to rapidly discover and advance novel precision allosteric therapeutics for targets that have historically been hard to drug. We anticipate significant progress in our portfolio in the upcoming year for high value oncology targets that address the unmet needs of large patient populations,” said Bryan Stuart, Chief Executive Officer, Atavistik Bio. “We are working to quickly advance ATV-1601 to the clinic and to achieve early clinical proof of concept for this program. We believe our precision allosteric small molecule offers several advantages to target the difficult-to-drug AKT1 E17K mutation, with the potential to improve the lives of many cancer patients.” AKT1 E17K mutation is a clinically validated oncogene that impacts greater than 40,000 cancer patients per year in the United States, with the highest prevalence in breast, endometrial, and prostate cancers. In addition, early evidence indicates that the AKT1 E17K mutation appears to be an emerging mechanism of resistance to PI3Kα-targeted cancer therapies. A selective allosteric AKT1 E17K inhibitor has the potential to be a transformative therapy against the validated AKT1 E17K oncogenic driver as well as resistance mutations emerging from PI3Kα-targeted therapies. The only approved AKT-targeted therapy is a pan-AKT inhibitor that blocks all three isoforms of AKT (AKT1, AKT2, and AKT3). Pan-AKT inhibitors offer limited efficacy for patients with AKT1 E17K-driven mutant tumors due to insufficient inhibition of the AKT1 E17K mutation. Additionally, pan-AKT inhibitors can cause significant adverse events, such as AKT2-driven hyperglycemia, rash, and diarrhea, which leads to treatment discontinuation or dose-reductions in a considerable subset of patients. ATV-1601, a selective allosteric AKT1 E17K inhibitor, has the potential to provide enhanced target inhibition, superior efficacy and improved tolerability compared to pan-AKT inhibitors for AKT1 E17K-driven cancers. Atavistik Bio anticipates initiating a first-in-human study with ATV-1601 in patients with AKT1 E17K-mutant tumors in early 2025. “Behind ATV-1601, we have a robust pipeline of precision oncology programs derived from our AMPS platform, said Marion Dorsch, Ph.D., President and Chief Scientific Officer, Atavistik Bio. “We look forward to advancing our internal pipeline with urgency while also broadening the reach of our platform through partnerships to discover important new allosteric therapeutics across other diseases.” Atavistik Bio EORTC-NCI-AACR Symposium Data Presentation Details Date:Wed., October 23, 2024Time:12.00 – 19.00 CETPoster Session:New DrugsPoster Title:ATV-1601 is a Potent and Selective Allosteric Inhibitor of AKT1 E17K and Shows Profound and Durable Regressions in AKT1 E17K-Driven Patient-Derived Xenograft ModelsPoster #:PB128 About Atavistik Bio Atavistik Bio is a biotechnology company accelerating the discovery and development of transformative precision allosteric therapeutics to address serious unmet patient needs, with a focus on oncology. Atavistik Bio is led by an experienced team of drug hunters with a proven track record of developing marketed small molecule therapies and supported by top-tier investors, including The Column Group, Nextech Invest, and Lux Capital. To learn more, visit us at atavistikbio.com and follow us on LinkedIn. Media Contact: Liz MeloneMelone Communications, LLCliz@melonecomm.com

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.