Engasertib

Atavistik Bio has raised an additional $40 million to build on a financing it closed just a few months ago, bringing the round's total to $160 million.The funds will fuel clinical development of ATV-1601, an oral allosteric AKT1-selective inhibitor for hereditary haemorrhagic telangiectasia (HHT), and also adcance a JAK2 V617F mutant-selective inhibitor for myeloproliferative neoplasms. While he declined to specify how the follow-on would extend the company's runway, CEO Bryan Stuart told FirstWord Atavistik is well capitalised to advance both programmes through clinical proof-of-concept.In December, Atavistik pocketed $120 million in a series B that was led by Nextech Invest and The Column Group and welcomed Regeneron Ventures as a new investor. The extension adds RA Capital Management to the syndicate.HHT is predominantly caused by loss-of-function mutations in ENG, ALK1 or SMAD4. ATV-1601 selectively targets hyperactive AKT1, a signaling protein that becomes overactive and contributes to underlying vascular abnormalities in the inherited bleeding disorder. Unlike broader pan-AKT inhibitors, which also block AKT2 and have been linked to side effects such as hyperglycaemia, ATV-1601 aims to spare AKT2 to make long-term treatment more feasible.The candidate was previously tested in a Phase I trial for solid AKT1 E17K–mutant tumours, though a "rapidly evolving treatment landscape and development paths" in HR-positive breast cancer have prompted the company to focus its testing of ATV-1601 on HHT, according to Chief Medical Officer Susan Pandya.Atavistik has said it plans to initiate its HHT trial in the first half of this year, joining other companies exploring therapies for the disease. The cohort includes Diagonal Therapeutics, which recently raised an oversubscribed $125-million series B to bankroll testing of its first-in-class clustering antibody, DIAG723, to correct impaired receptor signaling in HHT.Meanwhile, Vaderis Therapeutics is working on an oral AKT inhibitor called engasertib (VAD044) that has shown reductions in nosebleed frequency and duration in a 12-week proof-of-concept study recently published in NEJM."The companies developing drugs in the space are taking different approaches," Pandya noted. "We are excited about ATV-1601…because it has the potential to broadly address all of the loss-of-function mutations that cause HHT. This positions ATV-1601 as a potential all-comers therapy."