Vaderis Therapeutics has emerged from stealth with a clinical-phase treatment for a genetic blood vessel disorder that it licensed from Almac Discovery.
The drug candidate, VAD044, is a once-daily, orally administered, allosteric AKT inhibitor that Vaderis has taken into clinical development as a treatment for hereditary hemorrhagic telangiectasia, a condition in which malformations of blood vessels lead to outcomes including strokes and digestive tract bleeding.
Evidence that the PI3K/AKT/mTOR pathway is frequently mutated in cancers has led multiple research groups to develop AKT inhibitors. However, Almac found relatively few groups were working on allosteric inhibitors, which induce a conformational change to inhibit activation of the pathway.
Seeing allosteric inhibitors as a way to improve selectivity for AKT, and circumvent feedback mechanisms that are commonly observed following treatment with ATP competitive inhibitors, Almac Discovery got to work, as Alan Lamont, the company’s vice president of business development and licensing, explained.
“When we first entered the AKT field, the vast majority of the AKT inhibitors in development were ATP competitive, thus we saw an opportunity to develop a best in class, subtype selective, allosteric AKT inhibitor for use in specific cancer indications. Once we had developed such an inhibitor, we were able to profile the compound in therapeutic indications beyond oncology where AKT played an important role, and this subsequently led to the collaboration with Vaderis,” said Lamont.
Vaderis struck a licensing deal with Almac Discovery and raised around CHF18m ($18.4m) from Medicxi in 2020, leading to its recent emergence from stealth and initiation of a proof-of-concept clinical trial of VAD044.
The progress of VAD044 is built on the early work Almac Discovery did to identify and advance the drug candidate. Armed with the capabilities to initiate new discovery projects and take them up to candidate drug status, the biotech presented Vaderis with a molecule that was already in late-stage preclinical development.
“We used a combination of high-throughput screening and knowledge-based design, based on published scaffolds, to identify VAD044. Structural biology was also used to understand and optimize binding modes, and enhance selectivity. To complement the internal capabilities and expertise that Almac Discovery has, we also utilize an extensive network of partners (e.g. CROs; academic collaborators; scientific, medical, and regulatory consultants) to advance novel assets,” said Lamont.