Palvella Therapeutics Completes Enrollment in Phase 2 TOIVA Trial of QTORIN Rapamycin for Cutaneous Venous Malformations

Phase 2 TOIVA trial successfully met recruitment target, enrolling 16 subjects at leading vascular anomaly centers; top-line data expected in mid-December 2025

Venous malformations are the most common type of vascular malformation, with skin involvement impacting an estimated approximately 50-80% of patients, which can result in bleeding, thrombosis, ulceration, disfigurement, and proliferation

QTORIN™ rapamycin has the potential to be the first approved therapy in the U.S. for more than an estimated 75,000 U.S. patients with cutaneous VMs

Nasdaq: PVLA) Palvella Therapeutics, Inc. (Palvella), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, today announced the successful completion of TOIVA, a Phase 2 trial of QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin) for the treatment of cutaneous venous malformations (cutaneous VMs). The Phase 2 trial enrolled 16 subjects at leading vascular anomaly centers, meeting the original recruitment target of approximately 15 subjects.

"Cutaneous venous malformations can have a severe impact on quality of life, leading to substantial morbidity and functional impairment of the skin, and yet there are currently no FDA-approved therapies to address this high unmet need," said Dr. Megha Tollefson, pediatric dermatologist at the Mayo Clinic in Rochester, Minnesota and Principal Investigator of TOIVA. "We are excited to see the results from TOIVA, and to better understand the potential benefit of QTORIN™ rapamycin for patients with cutaneous VMs."

Cutaneous VMs are a serious, rare genetic disease caused by mutations in genes that cause overactivation of the PI3K/mTOR signaling pathway, leading to dysfunctional veins within the skin. The Phase 2 TOIVA study is a single-arm, open-label, baseline-controlled clinical trial of QTORIN™ rapamycin, a novel, patented 3.9% rapamycin anhydrous gel which aims to harness the potential therapeutic benefits of rapamycin, an mTOR inhibitor, while minimizing systemic exposure of rapamycin and potential adverse reactions associated with systemic therapy. In the TOIVA trial, QTORIN™ rapamycin is administered topically once daily. Safety and tolerability will be assessed based on the incidence and severity of adverse events. The proof-of-concept study also 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 individual clinical manifestations which contribute to disease burden.

"An urgent need exists for an FDA-approved, targeted, localized therapy to treat cutaneous VMs," said Wes Kaupinen, Founder and Chief Executive Officer of Palvella. "The insights gained from this Phase 2 proof-of-concept study will be critical in guiding the design of future clinical trials and advancing Palvella's mission to bring the first FDA-approved therapy to the estimated more than 75,000 U.S. patients living with cutaneous VMs."

Top-line results from TOIVA are expected in mid-December 2025.

About Palvella Therapeutics
Founded and led by rare disease drug development 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 genetic skin diseases 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 genetic skin diseases, many of which are lifelong in nature. Palvella's lead product candidate, QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin), is currently being evaluated in the Phase 3 SELVA clinical trial in microcystic lymphatic malformations and the Phase 2 TOIVA clinical trial in cutaneous venous malformations. For more information, please visit www.palvellatx.com or follow Palvella on LinkedIn or X (formerly known as Twitter).

QTORIN™ rapamycin is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency for any indication.

Forward-Looking Statements
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Contact Information

Investors
Wesley H. Kaupinen
Founder and CEO, Palvella Therapeutics
wes.kaupinen@palvellatx.com

Media
Marcy Nanus
Managing Partner, Trilon Advisors LLC
mnanus@trilonadvisors.com