ALTA-2618

Allosteric, covalent inhibitor ALTA-2618 selectively and potently inhibits AKT1 E17K mediated cellular functions Strong anti-tumor activity against AKT1 E17K expressing PDX models and favorable pharmacokinetic properties demonstrated SAN DIEGO--(BUSINESS WIRE)-- Alterome Therapeutics, Inc., a biopharmaceutical company pioneering the development of next generation, small molecule targeted therapies for the treatment of cancer, today reported promising preclinical data from their lead pipeline candidate, ALTA-2618, a mutation-selective inhibitor for AKT1 E17K driven cancers. The data are being presented in a poster presentation on April 8th at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place in San Diego, CA on April 5-10, 2024. ALTA-2618 is an orally bioavailable, mutant-selective, and covalent allosteric inhibitor of AKT1 E17K. AKT1 E17K is a clinically validated oncogene that drives cancers, including breast, endometrial, and prostate cancers. This program is designed for patients with limited treatment options and is expected to begin clinical testing in the next year. “We’re excited to present data at AACR featuring Alterome’s lead program, ALTA-2618, the first AKT1 E17K-selective inhibitor. We believe this data provides validation of the strong dependence of certain cancers on this mutation and underscores the high impact a selective inhibitor could achieve with continuous target coverage,” said Eric Murphy, Ph.D., co-founder and CEO of Alterome Therapeutics. “This work was an important step forward in Alterome’s mission to discover precise therapies that generate preclinical tumor regressions with improved safety pro and supports the advancement of ALTA-2618 into first-in-human clinical trials in 2024.” Key Findings: ALTA-2618 is the first allosteric & mutant-selective drug for AKT1 E17K driven cancers. ALTA-2618 has favorable pharmacokinetic properties across multiple preclinical species. ALTA-2618 is well tolerated with daily oral dosing in tumor-bearing mice. The compound demonstrated significant anti-tumor effects in clinically-relevant PDX models driven by AKT1 E17K. No on-target toxicities (e.g., hyperglycemia) are observed with daily ALTA-2618 treatment. Poster Presentation Details: Title: Discovery of ALTA-2618, the first allosteric, mutant-selective targeted therapy for AKT1 E17K driven cancers Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 2 Date and Time: Monday, April 8 from 1:30 p.m. – 5:00 p.m. PT Abstract Number: LB173 / 19 Speaker/Lead Author: Tim Sen Wang, Ph.D., Alterome Therapeutics About Alterome Therapeutics, Inc. Alterome Therapeutics, Inc. is a precision oncology biotech developing alteration-specific therapeutics to address high-value and validated oncogenic drivers. The company is led by an expert team of precision oncology R&D leaders with a history of developing marketed oncology small molecule drugs. For more information, visit . Follow us on LinkedIn and Twitter.

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.