Palvella and Ligand Expand Strategic Partnership

Rare Daily Staff

Palvella Therapeutics said it has expanded its strategic partnership with Ligand Pharmaceuticals to accelerate phase 3 development of Qtorin rapamycin for the treatment of microcystic lymphatic malformations.

Under the terms of the amended agreement, Palvella received an upfront payment of $5 million from Ligand. In return, Ligand’s existing tiered royalty on worldwide commercial sales of Qtorin rapamycin increased to 8.0 to 9.8 percent. Additionally, Palvella granted Ligand an option to acquire a single-digit royalty on each novel topical product candidate generated from its Qtorin platform, which can be exercised at a future date.

Microcystic lymphatic malformations (microcystic LMs) are rare, chronically debilitating genetic disease caused by dysregulation of the PI3K/mTOR pathway. The disease is characterized by localized masses of malformed lymphatic vessels that protrude through the skin barrier and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis. The natural history of microcystic LMs is progressive, with symptoms generally worsening during life, including increases in the number and size of cysts that lead to complications and lifetime morbidity. There are currently no FDA-approved treatments for the estimated more than 30,000 patients with microcystic LMs in the United States.

Qtorin rapamycin is a novel, 3.9 percent rapamycin anhydrous gel currently under development by Palvella for the treatment of microcystic LMs and other serious, functionally debilitating skin diseases driven by the overactivation of the mammalian target of rapamycin (mTOR) pathway. There are currently no FDA-approved treatments for patients with microcystic LMs in the United States.

Palvella previously announced positive phase 2 results from a multi-center, open-label trial of once-daily Qtorin rapamycin in microcystic LMs. In the phase 2 study, 100 percent of participants were either “much improved” or “very much improved” as rated by the Clinician Global Impression of Change after 12 weeks of once-daily Qtorin rapamycin treatment. The U.S. Food and Drug Administration granted Breakthrough Therapy designation to Qtorin rapamycin for the treatment of microcystic lymphatic malformations in November 2023. Based on the positive phase 2 results and a productive end-of-phase 2 meeting with FDA, Palvella plans to conduct a pivotal phase 3 study in approximately 50 adult and pediatric patients. In addition to Breakthrough Therapy designation, the FDA previously granted Fast Track designation and Orphan Drug designation to Qtorin rapamycin for the treatment of microcystic LMs.

“With an estimated more than 30,000 diagnosed patients in the U.S. suffering from microcystic lymphatic malformations, we see a very significant and attractive commercial opportunity for Qtorin rapamycin as the first potential FDA-approved therapy for this lifelong disease which causes significant patient morbidity from a very young age,” said Wes Kaupinen, founder and CEO of Palvella.

Photo: Wes Kaupinen, founder and CEO of Palvella