Atavistik Bio has raised US$160m to develop new treatments for rare blood disorders and cancers using a drug design approach aimed at previously hard-to-target proteins.
Atavistik Bio develops oral medicines designed to bind to what are known as allosteric sites on proteins. Proteins are molecules in the body that control many biological processes.
Most small-molecule drugs attach to a protein’s active site, a pocket or groove where chemical reactions occur and which is relatively easy for drugs to bind to. By contrast, allosteric sites sit elsewhere on the protein but can still change how it behaves when targeted by a drug. These sites are often harder to identify. Atavistik says its in-house technology platform can locate them.
Targeting these allosteric sites could allow drugmakers to reach proteins that are otherwise difficult to target, or offer more precise ways of acting on known disease drivers.
The funding will support the development of its lead drug candidate, ATV-1601, which the company plans to move into human trials later this year for hereditary haemorrhagic telangiectasia (HHT). HHT is a genetic disorder that causes fragile, abnormal blood vessels to form.
In people with HHT, mutations can overactivate an enzyme called AKT1, which regulates the endothelial cells that line blood vessels. When this enzyme becomes overactive, abnormal blood vessels can form and rupture, leading to bleeding, chronic anaemia and, in severe cases, seizures or heart failure.
Current HHT treatments mainly manage symptoms and none are curative. By blocking AKT1 activity, Atavistik hopes to address the underlying cause of the disease.
Susan Pandya, chief medical officer at Atavistik, said the drug could “broadly address” the mutations responsible for the condition.
She added that ATV-1601’s ability to precisely target AKT1 while avoiding closely related variants of the same enzyme could make it more tolerable than the “pan-AKT inhibitors” other companies have invested in.
The drug previously showed what Pandya described as encouraging safety results in a phase 1 oncology study and is now moving towards an early-stage clinical trial in HHT.
Other companies, including Diagonal Therapeutics and Alnylam Pharmaceuticals, are also developing potential HHT treatments, although those medicines act on different targets. Unlike those therapies, Atavistik’s treatment is taken orally.
The company is also studying a JAK2 inhibitor in bone marrow cancers such as polycythaemia vera and myelofibrosis. These diseases cause the body to produce too many blood cells.
Certain JAK inhibitors are already approved for both conditions but are associated with blood-related side effects. chief executive officer Bryan Stuart said Atavistik believes its more selective approach could “achieve disease-modifying activity” while avoiding the issues “associated with broader JAK inhibition.”
The series B funding round was first announced in December and was later extended with a further US$40m investment from RA Capital Management.
Other investors include Nextech Invest, The Column Group, Lux Capital and Regeneron Ventures.
Atavistik previously raised US$100m through a series A round conducted between 2021 and 2023.
