Atavistik Bio Secures FDA IND Clearance and Fast Track Designation for ATV-1601 in Hereditary Hemorrhagic Telangiectasia
核心洞察
The FDA cleared the Harmony-HHT Phase 1/2 IND, allowing Atavistik Bio (搜索) to advance ATV-1601 directly into a randomized, placebo-controlled study in moderate to severe HHT.
ATV-1601, an oral selective allosteric AKT1 (搜索) inhibitor, received Fast Track Designation and has disease-modifying potential across all HHT driver mutations (ENG, ALK1, SMAD4).
HHT affects over 80,000 people in the U.S. and 1.6 million globally as the second most prevalent inherited bleeding disorder, with no currently approved therapies.
Atavistik Bio (搜索) announced that the U.S. Food and Drug Administration (搜索) has cleared its investigational new drug application for ATV-1601, an oral selective allosteric AKT1 (搜索) inhibitor, and granted Fast Track Designation for the treatment of Hereditary Hemorrhagic Telangiectasia (搜索). The clearance enables the Cambridge, Massachusetts-based biotechnology company to launch the Harmony-HHT Phase 1/2 trial, which will evaluate ATV-1601 in individuals with moderate to severe HHT.
The FDA's clearance of the Harmony-HHT study design allows Atavistik Bio (搜索) to leverage existing clinical data with ATV-1601 and proceed directly into a randomized study, an approach that creates the opportunity to accelerate development timelines while rapidly generating clinical proof-of-concept data.
"We recognize the significant burden HHT places on individuals and families, as recurrent bleeding, chronic anemia, and progressive complications can affect daily life and well-being," said Susan Pandya, M.D., Chief Medical Officer at Atavistik Bio (搜索). "Treatment options are largely limited to supportive care and invasive interventions. ATV-1601 has the potential to provide a disease-modifying approach for people living with HHT."
A Disease with High Unmet Need
HHT is the second most prevalent inherited bleeding disorder, affecting more than 80,000 people in the United States and approximately 1.6 million people globally. Despite this substantial patient population, no approved therapies are currently available for the condition.
The disease is caused by loss-of-function mutations in the ENG, ALK1, or SMAD4 genes, which encode proteins that regulate the growth and branching of endothelial cells into blood vessels. When these proteins are impaired, the AKT1 (搜索) pathway becomes hyperactivated, resulting in malformed blood vessels known as arteriovenous malformations. These AVMs can rupture or cause abnormal blood flow, leading to chronic bleeding, anemia, organ damage, and in some cases, life-threatening complications.
Mechanism and Preclinical Evidence
ATV-1601 is an investigational oral allosteric inhibitor that selectively targets AKT1 (搜索), a key driver of the vasculopathy underlying HHT. By selectively inhibiting AKT1, the compound has the potential to provide a disease-modifying approach that addresses all HHT-driver mutations — ENG, ALK1, and SMAD4 — with a well-tolerated profile.
In preclinical HHT models harboring ENG, ALK1, and SMAD4 mutations, ATV-1601 significantly reduced AVM formation, supporting its potential as a novel therapy applicable for all people living with HHT.
Harmony-HHT Trial Design
The Harmony-HHT study (NCT07601425) is a Phase 1/2 proof-of-concept trial designed to evaluate the safety and efficacy of ATV-1601. Part 1 is a randomized, double-blind, multicenter, placebo-controlled study evaluating three oral dosing regimens of ATV-1601 over a 16-week treatment period. Eligible participants who complete Part 1 may enroll in an open-label extension (Part 2) to receive ATV-1601.
Atavistik Bio (搜索) is a clinical-stage biotechnology company developing novel allosteric therapeutics with an internal pipeline focused on rare hematology. Beyond ATV-1601, the company is advancing a JAK2V617F mutant-selective inhibitor program for myeloproliferative neoplasms. The company is backed by top-tier investors including The Column Group, Nextech Invest, Lux Capital, Regeneron Ventures, and RA Capital Management.