Palvella Therapeutics Announces First Patients Dosed in Phase 2 LOTU Trial of Fast Track-Designated QTORIN™ Rapamycin for Clinically Significant Angiokeratomas

Clinically significant angiokeratomas represent a rare, chronic and debilitating lymphatic malformation with no FDA-approved therapies and an estimated more than 50,000 diagnosed patients in the U.S.

Phase 2 single-arm, baseline-controlled trial expected to enroll up to 15 subjects at leading vascular anomaly centers and high-volume dermatology centers in the U.S.

Topline results from the Phase 2 trial are expected in the second half of 2027

WAYNE, Pa., May 04, 2026 (GLOBE NEWSWIRE) -- Palvella Therapeutics, Inc. (Palvella or “the Company”) (Nasdaq: PVLA), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare skin diseases and vascular malformations for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, today announced that the first patients have been dosed in LOTU, a multicenter Phase 2 clinical trial designed to evaluate the safety and efficacy of QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin) for the treatment of clinically significant angiokeratomas.

“Clinically significant angiokeratomas represent a chronic, debilitating condition characterized by hyperkeratotic vascular lesions that can bleed with minor trauma, are susceptible to infection, and significantly impair patients’ quality of life,” said Maria Buethe, MD, PhD, Division Chief of Dermatology at Rady Children’s Hospital of Orange County and Director of Pediatric Dermatology at the University of California, Irvine, and principal investigator of the LOTU study. “These lesions are especially burdensome when large or located in difficult to treat areas or when causing functional impairments. Current management relies on invasive, often destructive procedures, including laser therapy and electrocautery, which can be associated with pain, scarring, recurrence, and incomplete disease control. Angiokeratomas do not spontaneously regress and can increase in size, number, and severity over time, underscoring the need for a targeted therapeutic option.”

In 2025, the International Society for the Study of Vascular Anomalies (ISSVA) classified angiokeratomas as isolated lymphatic malformations, reflecting advances in the understanding of angiokeratomas as a lymphatic disease. This classification places angiokeratomas within the same ISSVA-recognized isolated lymphatic malformation category as microcystic lymphatic malformations, the lead indication for QTORIN™ rapamycin, strengthening the scientific rationale for extending QTORIN™ rapamycin into clinically significant angiokeratomas based on shared lymphatic disease biology. Emerging evidence implicating dysregulated mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) signaling pathways in lymphatic endothelial proliferation and abnormal vascular morphology further supports the mechanistic rationale for evaluating mTOR inhibition in angiokeratomas. Published case studies and real-world evidence suggest potential benefit from off-label mTOR inhibition; however, there are currently no FDA-approved therapies for angiokeratomas.

“We continue to see broad potential for QTORIN™ rapamycin across serious, rare diseases characterized by dysregulated mTOR signaling, significant patient burden, and no FDA-approved therapies,” said Wes Kaupinen, Founder and Chief Executive Officer of Palvella Therapeutics. “Clinically significant angiokeratomas represent a meaningful rare disease opportunity, with an estimated more than 50,000 diagnosed patients in the U.S. and no FDA-approved therapies. We are advancing this program in close collaboration with our scientific and medical collaborators, informed by significant unmet need, recent advances in the understanding of angiokeratomas as a lymphatic disease, and the central role of mTOR/VEGF signaling in lymphatic vascular biology. We look forward to reporting topline results from the Phase 2 study in the second half of 2027.”

The Phase 2 LOTU study is a single-arm, baseline-controlled clinical trial evaluating QTORIN™ rapamycin administered topically once daily for the treatment of clinically significant angiokeratomas. Safety and tolerability will be assessed based on the incidence and severity of adverse events. This proof-of-concept study includes multiple measures of efficacy, including change from baseline to Week 12 in clinician and patient global impression assessments, as well as assessments of specific clinical manifestations that contribute to disease burden. The Phase 2 LOTU study is expected to enroll up to 15 subjects, ages six and older, at leading vascular anomaly centers and high-volume dermatology centers in the U.S.

QTORIN™ rapamycin is a novel, patented 3.9% rapamycin anhydrous gel designed to harness the potential therapeutic benefits of rapamycin, an mTOR inhibitor, in affected skin, including dermal tissue where the vascular component of angiokeratomas resides, while minimizing systemic exposure and potential adverse reactions associated with systemic mTOR inhibition. QTORIN™ rapamycin was previously granted Fast Track Designation by FDA for the treatment of angiokeratomas, reflecting its potential to address an unmet medical need in a serious disease with no FDA-approved therapies.

About Palvella Therapeutics

Founded and led by rare disease biotech veterans, Palvella Therapeutics, Inc. (Nasdaq: PVLA) is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare skin diseases and vascular malformations for which there are no FDA-approved therapies. Palvella is developing a broad pipeline of product candidates based on its patented QTORIN™ platform, with an initial focus on serious, rare skin diseases and vascular malformations, many of which are lifelong in nature. Palvella’s lead product candidate, QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin), is currently being developed for the treatment of microcystic lymphatic malformations, cutaneous venous malformations, and clinically significant angiokeratomas. Palvella’s second product candidate, QTORIN™ pitavastatin, is currently being developed for the treatment of disseminated superficial actinic porokeratosis. For more information, please visit www.palvellatx.com or follow Palvella on LinkedIn or X (formerly known as Twitter).

QTORIN™ rapamycin and QTORIN™ pitavastatin are for investigational use only and neither has been approved by the FDA or by any other regulatory agency for any indication.