Palvella Therapeutics (PVLA) Study Result summary

Executive summary / Executive summary of Phase II TOIVA study results

• QTORIN rapamycin achieved highly statistically significant improvements on multiple clinician- and patient-reported efficacy endpoints in cutaneous venous malformations at week 12, with a mean effect size of 1.5 on the cVM-IGA and a p-value <0.001.

• 73% of participants (11/15) showed at least a one-point improvement on the Overall CVM-IGA at week 12, and 67% were rated as much or very much improved.

• Statistically significant improvements were observed in lesion height, appearance, bleeding, and both dynamic and static severity scales, with rapid and consistent benefits.

• QTORIN rapamycin was generally well tolerated, with only mild to moderate application site reactions and no severe or unexpected adverse events; systemic rapamycin levels remained below quantifiable limits.

• Planning discussions with the FDA for Breakthrough Therapy Designation and Phase 3 pivotal study are underway.

Disease background / Disease overview / Additional context

• Cutaneous venous malformations are chronic, progressive, and debilitating, affecting over 75,000 U.S. patients, with symptoms including swelling, pain, bleeding, and functional limitations.

• The disease is genetically driven, most commonly by TEK or PIK3CA mutations, leading to mTOR hyperactivation and dysfunctional skin veins.

• Current management relies on procedural interventions like sclerotherapy and laser surgery, which do not address underlying disease biology and often result in recurrence.

• There are no FDA-approved therapies for cutaneous venous malformations, representing a significant unmet medical need for targeted, localized therapies.

• The therapeutic goal is to slow or halt biological progression and improve clinical signs.

Study design and patient population / Study design and methodology / Study design and background

• Phase II TOIVA was a single-arm, open-label, baseline-controlled study enrolling 16 patients aged six and older with cutaneous venous malformations, using once-daily topical QTORIN rapamycin gel for 12 weeks, with a 12-week extension.

• Each patient served as their own control, with efficacy and safety assessed at 12 and 24 weeks.

• 15 participants completed the efficacy evaluation at week 12; eligibility was confirmed by independent expert review.

• Efficacy was assessed using both clinician- and patient-reported outcomes, including global impression and specific clinical manifestations.

• Genetic testing was not required for enrollment, but participants included those with TEK, PIK3CA, and other mutations.