QTORIN 3.9% (rapamycin topical) / Palvella Therapeutics, Ligand - LARVOL DELTA

Palvella Therapeutics Completes Rolling Submission of New Drug Application to FDA for QTORIN Rapamycin for the Treatment of Microcystic Lymphatic Malformations (The Manila Times) - "The NDA includes results from the Phase 3 SELVA trial, which met its primary endpoint, pre-specified key secondary endpoint, and all four secondary efficacy endpoints, with all six efficacy endpoints achieving statistical significance (all p Within 60 days, FDA will determine whether the application is complete and acceptable for filing and whether Priority Review will be granted....Accelerating U.S. launch readiness for a potential commercial launch of QTORIN rapamycin in the first half of 2027, if approved."

FDA filing • Launch US • Dermatology • Rare Diseases

Palvella Therapeutics Submits First Module of Rolling New Drug Application to FDA for QTORIN Rapamycin for the Treatment of Microcystic Lymphatic Malformations (GlobeNewswire) - "Palvella remains on track to submit the remaining modules and complete the NDA submission in the second half of 2026...As Palvella advances toward completion of the NDA submission, the Company is accelerating U.S. launch readiness for a potential standalone commercial launch of QTORIN rapamycin in the first half of 2027, if approved."

FDA event • FDA filing • Launch US • Dermatology • Rare Diseases

FDA Grants Rolling Review of Palvella’s QTORIN Rapamycin NDA for Microcystic Lymphatic Malformations (GlobeNewswire) - "Palvella remains on track to complete the NDA submission in the second half of 2026...Rolling review allows Palvella to submit completed sections of the QTORIN rapamycin NDA as they become available, enabling FDA review to proceed while the Company completes the remainder of the application."

FDA event • FDA filing • Dermatology • Rare Diseases

Palvella Therapeutics, Inc…announced completion of its pre-New Drug Application (NDA) meeting with FDA for QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin) in microcystic lymphatic malformations (microcystic LMs). (GlobeNewswire) - "Palvella remains on track to submit its NDA for QTORIN rapamycin in microcystic LMs in the second half of 2026. Palvella and FDA discussed the planned NDA evidence package, which is expected to include efficacy and safety data from Palvella’s Phase 3 SELVA study, including blinded independent review data and before-and-after photographs from all patients enrolled in the study, as well as supportive clinical data from the Phase 2 study that served as the basis for FDA’s Breakthrough Therapy designation for QTORIN™ rapamycin in microcystic LMs."

FDA event • FDA filing • Dermatology • Rare Diseases

Significant reductions in lesion bleeding with QTORIN™ 3.9% rapamycin in cutaneous venous malformations (SID 2026) - "Lesion bleeding, a clinically meaningful but heterogeneous cVM manifestation, can be prospectively evaluated and significantly improved with topical QTORIN™ 3.9% rapamycin. These findings support lesion bleeding as a patient-relevant endpoint and highlight the potential of localized mTOR inhibition to address high-impact cVM manifestations."

Cardiovascular

Cutaneous venous malformations have a significant negative impact on quality of life: Results from a phase 2 study (SID 2026) - " In the TOIVA Phase 2 open-label trial evaluating QTORIN™ 3.9% rapamycin topical gel, participants with clinically diagnosed cVM completed baseline semi-structured interviews prior to treatment... Baseline qualitative interviews elucidate the patient-experienced burden of moderate-to-severe cVM and underscore the value of patient-reported outcomes in clinical development. These data may inform endpoint selection, trial design, and patient-centric evaluation of therapeutic benefit."

HEOR • P2 data

A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 (Sirolimus) Topical Gel 3.9% in the Treatment of Angiokeratomas (LOTU) (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Palvella Therapeutics, Inc.

New P2 trial

SELVA: A Phase 3 Study Evaluating QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P3 | N=51 | Active, not recruiting | Sponsor: Palvella Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

TOIVA: A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 (Sirolimus) Topical Gel 3.9% in the Treatment of Cutaneous Venous Malformations (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Palvella Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Palvella Therapeutics Announces Issuance of European Patent Covering Anhydrous Compositions of Rapamycin (GlobeNewswire) - "European Patent No. 3565520...includes claims covering QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin), the Company’s lead product candidate from the QTORIN platform. The patent provides protection for anhydrous topical compositions and methods of use for QTORIN rapamycin, including for the treatment of microcystic lymphatic malformations, venous malformations, and other diseases associated with dysregulation of the mammalian target of rapamycin (mTOR) pathway....Patent protection extends into 2038."

Patent • Dermatology • Rare Diseases

Phase 3 SELVA study evaluating QTORIN rapamycin 3.9% anhydrous gel (QTORIN rapamycin) for microcystic lymphatic malformations (microcystic LMs) remains on track, with topline results anticipated in March 2026; pending positive results, an NDA submission is planned for the second half of 2026 (The Manila Times) - "Following positive Phase 2 results for QTORIN rapamycin for the treatment of cutaneous venous malformations announced in December 2025, requested a Preliminary Breakthrough Therapy Designation Advice meeting with the U.S. Food and Drug Administration, anticipated in the first quarter of 2026"

FDA event • FDA filing • P3 data: top line • Rare Diseases

Palvella Therapeutics Granted FDA Fast Track Designation for QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Angiokeratomas (The Manila Times) - "Palvella plans to meet with the FDA in the first half of 2026 to discuss the proposed design of a Phase 2 study of approximately 10-20 patients, with study initiation expected in the second half of 2026."

Fast track • New P2 trial • Dermatology

Palvella Therapeutics Granted Sixth U.S. Patent Covering 0.1–20% Anhydrous Compositions of Rapamycin and Other mTOR Inhibitors (GlobeNewswire) - "Palvella Therapeutics, Inc...announced that the United States Patent and Trademark Office (USPTO) issued patent No. 12,329,748 for claims related to the Company's lead product candidate QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin). The patent provides broad protection for the proprietary anhydrous topical composition and methods of use for QTORIN rapamycin...The newly granted U.S. patent encompasses a wide range of composition and method-of-use claims for QTORIN rapamycin and other mTOR inhibitors—including temsirolimus and everolimus—formulated in anhydrous compositions."

Patent • Dermatology

Palvella Therapeutics Completes Enrollment in Phase 3 SELVA Trial of QTORIN Rapamycin for Microcystic Lymphatic Malformations, Exceeding Enrollment Target by Over 25% (GlobeNewswire) - "The Phase 3 trial enrolled 51 subjects, exceeding the original target of 40 subjects by over 25%....Top-line results from SELVA are expected in the first quarter of 2026, with a New Drug Application submission planned for the second half of 2026."

FDA filing • P3 data: top line • Trial status • Dermatology

Palvella Therapeutics Granted Additional U.S. Patent for QTORIN Rapamycin for the Treatment of Microcystic Lymphatic Malformations (GlobeNewswire) - "Palvella Therapeutics, Inc...today announced that the United States Patent and Trademark Office (USPTO) issued patent No. 12,268,673 for claims related to the Company's lead product candidate QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin). The newly granted U.S. patent is part of Palvella’s expanding intellectual property portfolio directed to novel therapies targeting microcystic lymphatic malformations (microcystic LMs) and other rare skin diseases....The granted patent 'Anhydrous Compositions of mTOR Inhibitors and Methods of Use' broadens protection for QTORIN™ rapamycin and the conditions related to its use in clinical indications, including microcystic LMs....Fifth issued patent in the U.S. for QTORIN rapamycin with anticipated patent life extending into 2038."

Patent • Dermatology

Palvella Therapeutics Announces QTORIN Rapamycin 3.9% Anhydrous Gel for the Treatment of Microcystic Lymphatic Malformations Featured in Oral Presentation by Amy Paller, M.S., M.D., Chair of Dermatology at Northwestern University’s Feinberg School of Medicine, at the 15th World Congress of Pediatric Dermatology (GlobeNewswire) - P3 | N=40 | SELVA (NCT06239480) | Sponsor: Palvella Therapeutics, Inc. | "Microcystic LMs are congenital mosaic lesions that gradually increase in size with risk of complications and are best managed aggressively during childhood; Microcystic LMs are proliferative with no spontaneous regression...100% of participants were either 'Very Much Improved' (41.7%) or “Much Improved” (58.3%) as rated by the Clinician Global Impression of Change (CGI-C), a 7-point change scale conducted by live clinician assessment; 83% of participants were either 'Very Much Improved' (25%) or 'Much Improved' (58.3%) as rated by the Patient Global Impression of Change, a 7-point change scale reported by patients; QTORIN rapamycin was generally well-tolerated; all treatment related adverse events were moderate or mild and there were no discontinuations due to adverse events....SELVA is currently enrolling patients at 13 centers in the United States...."

P3 data • P3 data: top line • Dermatology

Palvella Therapeutics to Expand Phase 3 SELVA Clinical Trial of QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Microcystic Lymphatic Malformations to Include the Younger Pediatric Population, Children 3 to 5 Years Old (GlobeNewswire) - "Company remains on track to report top line results from SELVA, a Phase 3 single-arm, baseline-controlled trial evaluating QTORIN rapamycin for the treatment of microcystic LMs, in Q1 2026...Palvella Therapeutics, Inc...today announced that it will expand SELVA, the Company's Phase 3 clinical trial of QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin) for the treatment of microcystic lymphatic malformations (microcystic LMs), to include patients ages 3 to 5 years old. Previously, trial participants were required to be at least 6 years old. This decision follows communication with the U.S. Food and Drug Administration (FDA) in which the agency deemed the Company's proposed expansion acceptable."

Clinical protocol • P3 data: top line • Dermatology

Palvella Therapeutics Announces Publication of Results from Phase 2 Clinical Trial of QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Microcystic Lymphatic Malformations in the Journal of Vascular Anomalies (GlobeNewswire) - P2 | N=12 | NCT05050149 | Sponsor: Palvella Therapeutics, Inc. | "'The Phase 2 results highlight QTORIN rapamycin’s potential to be the first targeted therapy for children and adults living with microcystic lymphatic malformations, a serious, rare genetic disease'...the publication presents results demonstrating nominal statistical significance across several of the efficacy endpoints assessing the change from pre-treatment baseline to end of treatment (Week 12) with once daily QTORIN rapamycin (n=12), including clinician and patient global impression assessments as well as assessments of individual clinical manifestations that are important disease burdens for individuals living with microcystic LMs. QTORIN rapamycin was generally well-tolerated with no participants experiencing drug related serious adverse events."

P2 data • Dermatology

Palvella Therapeutics Announces First Patients Dosed in Phase 2 TOIVA Clinical Trial of QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Cutaneous Venous Malformations (GlobeNewswire) - "Palvella Therapeutics, Inc...announced the first patients have recently been dosed in TOIVA, 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 cutaneous venous malformations."

Trial status • Dermatology

TOIVA: A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 (Sirolimus) Topical Gel 3.9% in the Treatment of Cutaneous Venous Malformations (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Palvella Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

TOIVA: A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 (Sirolimus) Topical Gel 3.9% in the Treatment of Cutaneous Venous Malformations (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Palvella Therapeutics, Inc.

New P2 trial

Palvella Therapeutics Awarded Up to $2.6 million Grant from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development to Support Phase 3 Single-Arm, Baseline-Controlled Trial in Microcystic Lymphatic Malformations (GlobeNewswire) - "Palvella Therapeutics, Inc...today announced the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development has awarded the company a grant of up to $2.6 million to support the ongoing Phase 3 SELVA trial of QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin) for the treatment of microcystic lymphatic malformations (microcystic LMs)."

Financing • Dermatology

Phase 2/3 Study Evaluating the Safety and Efficacy of PTX-022 in Treatment of Adults With Pachyonychia Congenita (clinicaltrials.gov) - P2/3 | N=73 | Completed | Sponsor: Palvella Therapeutics, Inc. | Unknown status ➔ Completed

Trial completion

VAPAUS: A Multicenter, Phase 3 Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Pachyonychia Congenita (clinicaltrials.gov) - P3 | N=87 | Completed | Sponsor: Palvella Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

VALO-2: Study Evaluating the Safety and Efficacy of PTX022 in the Treatment of Adults With Pachyonychia Congenita (clinicaltrials.gov) - P3 | N=36 | Completed | Sponsor: Palvella Therapeutics, Inc. | Active, not recruiting ➔ Completed | Phase classification: P3b ➔ P3

Phase classification • Trial completion