AVTX-006 is a dual mTOR inhibitor (a class of drugs that inhibit the mammalian target of rapamycin) in development for the treatment of lymphatic malformations.

Targeting mTOR in Lymphatic Malformations

Complex lymphatic malformations are rare, noncancerous masses thought to be caused by the abnormal development of the lymphatic system and are usually present at birth or by 2 years of age. Regardless of size, lymphatic malformations may cause functional impairment of nearby structures or organs and disfigurement of affected areas.

Complex lymphatic malformations often have activating variants along the PI3K/AKT/mTOR pathway, leading to local proliferation of lymphatic endothelial cells and perturbation of lymph flow. Currently, the main therapeutic options for treating lymphatic malformations are percutaneous drainage, surgery, sclerotherapy, laser therapy, radiofrequency ablation, and medical therapy.

Proliferation of Lymphatic Endothelial Cells

A clinical proof-of-concept using the mTORC1 inhibitor, sirolimus, has demonstrated clinical utility in lymphatic malformations. AVTX-006 has the potential to improve upon both the safety and efficacy of single mTOR inhibition (sirolimus) in lymphatic malformations.

Attributes of AVTX-006

  • Orphan Drug Designation and Rare Pediatric Disease Designation; eligible for Priority Review Voucher upon approval
  • High-potency, dual mTORC1/2 inhibitor maximizing impact of mTOR blockade with potential for improved efficacy and tolerability relative to sirolimus
  • Active in vitro against a broad panel of tumor cell lines, including models resistant to rapalogs
  • Generally well tolerated in a phase 1 study, with significantly lower doses than the maximum tolerated dose likely required for treatment