Atavistik Bio has raised an additional $40 million as the startup prepares for clinical testing of a drug in development for treating a rare and potentially life-threatening bleeding disorder.
The new cash announced Thursday brings in new investor RA Capital Management. It’s an extension of a $120 million Series B round the startup raised late last year.
Cambridge, Massachusetts-based Atavistik is developing a treatment for hereditary hemorrhagic telangiectasia (HHT), a disease in which genetic mutations lead to abnormal blood vessels susceptible to rupture. Frequent nosebleeds are a common sign of HHT but the disorder can also lead to gastrointestinal bleeding and ruptures of artery and vein connections in organs. There are no FDA-approved therapies for HHT.
Atavistik’s drug candidate, ATV-1601, is small molecule inhibitor of AKT1, a protein that plays a role in signaling pathways that regulate the growth and proliferation of cells. While AKT inhibitors have been developed for cancer, such drugs come with a range of side effect risks from also hitting AKT2. Atavistik’s molecule is designed to selectively inhibit AKT1, which the company says is the primary driver of the abnormal cell growth behind HHT. Atavistik initially tested ATV-1601 in cancer, where Phase 1 results showed a favorable safety profile. The company is now focusing on developing this molecule for HHT.
ATV-1601 comes from an Atavistik platform technology that discovers molecules that can bind to allosteric sites, places on a protein other than active sites, the pockets that are conventional locations to bind a drug. The platform screens proteins against metabolites, then uses artificial intelligence and machine learning techniques to understand the interactions. That understanding guides the design of small molecule drugs. The Atavistik technology came from the lab of Jared Rutter, a professor of biochemistry at the University of Utah.
Shifting ATV-1601’s development from cancer to HHT brings Atavistik into a small group of companies vying to become the first to bring patients a treatment for the bleeding disorder. Alnylam Pharmaceuticals is in mid-stage clinical development with ALN-6400, an RNA interference therapy that targets plasminogen, a liver protein that drives the breakdown of fibrin mesh that stabilizes blood clots. Tectonic Therapeutic in in Phase 1 testing with TX2100, an antibody designed to block the APJ receptor. This receptor mediates signaling by the peptide hormone apelin, which promotes the formation of new blood vessels. Tectonic first disclosed this drug’s mechanism of action during an investor event last week.
HHT has also drawn interest from other startups. Diagonal Therapeutics aims to treat the rare disease by fixing the signaling problems that lead to abnormal blood vessel formation. Lead program DIAG723 is a clustering antibody designed to address dysregulated ALK1 signaling in endothelial cells. In January, Diagonal closed a $125 million Series B round to advance this program into the clinic in the first half of this year.
In addition to supporting the HHT program, Atavistik said its new capital will also finance continued preclinical development of a drug for myeloproliferative neoplasms (MPNs), a group of rare and life-threatening blood cancers. The company says the JAK2 V617F mutation is the most common driver mutation in patients living with MPNs. While JAK inhibitors are already available, Atavistik says they inhibit mutated and non-mutated forms of the protein. The startup’s drug candidate is designed to selectively address the JAK2 V617F mutation.
Atavistik launched in 2021 backed by a $60 million Series A round of financing led by The Column Group. That firm and Nextech Invest led the $120 million Series B round that was announced in late December. Other investors in Atavistik include Lux Capital and Regeneron Ventures.
“This additional funding further strengthens our ability to accelerate the development of best-in-class therapies designed to deliver superior efficacy, improved tolerability profiles, and potentially transformative outcomes for patients,” Atavistik CEO Bryan Stuart said in a prepared statement.
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