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

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

PALV-04: CODY: A Study Evaluating The Safety And Efficacy Of QTORIN 3.9% Sirolimus Topical Gel For The Prevention Of Basal Cell Carcinomas (BCCs) In Patients With Gorlin Syndrome (clinicaltrials.gov) - P2 | N=73 | Completed | Sponsor: Palvella Therapeutics, Inc. | Recruiting ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Study Evaluating the Safety and Efficacy of PTX-022 (QTORIN Sirolimus) in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P2 | N=12 | Completed | Sponsor: Palvella Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

SELVA: A Phase 3 Study Evaluating QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Palvella Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Jul 2026

Enrollment open • Trial completion date

SELVA: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Evaluating Safety and Efficacy of QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Palvella Therapeutics, Inc. | Initiation date: Apr 2024 ➔ Jul 2024

Trial initiation date

SELVA: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Evaluating Safety and Efficacy of QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Palvella Therapeutics, Inc.

New P3 trial

Palvella Therapeutics Announces U.S. FDA Breakthrough Therapy Designation Granted to QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN™ rapamycin) for the Treatment of Microcystic Lymphatic Malformations (GlobeNewswire) - "Palvella Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to QTORIN rapamycin™ for the treatment of Microcystic Lymphatic Malformations (Microcystic LMs)....The Breakthrough Therapy Designation for QTORIN rapamycin is based on positive Phase 2 results from a multi-center, open-label trial of once-daily QTORIN rapamycin in Microcystic LMs."

Breakthrough therapy designation • Oncology • Skin Cancer

Palvella Therapeutics Announces Planned Pivotal Phase 3 Study Design of QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Microcystic Lymphatic Malformations and Topline Results from Phase 2b CODY Study in Gorlin Syndrome (GlobeNewswire) - "Palvella Therapeutics, Inc...today announced the planned pivotal Phase 3 study design of QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin), a topical mTOR inhibitor and the lead product candidate from the QTORIN™ platform, in Microcystic Lymphatic Malformations (Microcystic LMs)....The Phase 3 SELVA pivotal study will be a 24-week, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of QTORIN rapamycin in patients with Microcystic LMs....The primary and key secondary endpoints will be clinician-reported outcomes."

New P3 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Palvella Therapeutics Announces Planned Pivotal Phase 3 Study Design of QTORIN 3.9% Rapamycin Anhydrous Gel (QTORIN rapamycin) for the Treatment of Microcystic Lymphatic Malformations and Topline Results from Phase 2b CODY Study in Gorlin Syndrome (GlobeNewswire) - P2b | N=60 | CODY (NCT04893486) | Sponsor: Palvella Therapeutics, Inc. | "The company also announced topline results from the Phase 2b CODY study that evaluated QTORIN rapamycin in individuals with Basal Cell Carcinomas (BCCs) in Gorlin Syndrome (GS)....QTORIN rapamycin was generally well-tolerated with the most common adverse events being application site pain and pruritus. No participants experienced drug related serious adverse events (SAE), and no unexpected adverse events occurred....In the Intent to Treat population (n=73), while QTORIN rapamycin demonstrated numerical improvement compared to placebo on the primary endpoint of prevention of new BCCs based on the cumulative number of new biopsy-confirmed BCCs on the face through Week 24, the results were not statistically significant."

P2b data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Phase 2 study of the safety and efficacy of QTORIN rapamycin in the treatment ofmicrocystic lymphatic malformations (ISID 2023) - "QTORIN 3.9%rapamycin anhydrous gel was granted FDA Fast Track Designation for treatment ofMicrocystic LM... 12-weeks oftargeted, topical treatment with QTORIN rapamycin resulted in significant clinicalbenefit for patients with cutaneous manifestation of microcystic LM. Based on thestatistically significant and clinically meaningful results, a Ph.3 placebo-controlledstudy is currently being planned."

Clinical • Late-breaking abstract • P2 data • Dermatology • Pediatrics

A Study Evaluating the Safety and Pharmacokinetics of QTORIN Rapamycin 3.9% Anhydrous Gel in the Treatment of Adults With Pachyonychia Congenita (clinicaltrials.gov) - P3 | N=45 | Recruiting | Sponsor: Palvella Therapeutics, Inc.

New P3 trial

A Prospective Phase II Clinical Trial of CD26/Dipeptidyl Peptidase (DPP)-IV Inhibition for Prevention of Acute Graft Versus Host Disease (aGVHD) Following Myeloablative Allogeneic Peripheral Blood Stem Cell (PBSC) Transplantation. (TCT-ASTCT-CIBMTR 2020) - P2; " Patients received thiotepa (15 mg/kg) and cyclophosphamide (120 mg/kg), followed by G-CSF mobilized PBSC from matched related (6/6 HLA match) or unrelated (10/10 HLA match) donors. Sitagliptin (600 mg q12 hours) was given on days -1 to day +14, together with tacrolimus and sirolimus through day +100, then tapering until day +180... CD26/DPP-IV inhibition with sitagliptin is well-tolerated and significantly reduced the rate of aGVHD by day +100 in patients undergoing myeloablative allogeneic PBSCT transplantation."

Clinical • P2 data • Acute Kidney Injury • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Cytomegalovirus Infection • Graft versus Host Disease • Immune Modulation • Infectious Disease • Inflammation • Mucositis • Myelodysplastic Syndrome • Nephrology • Oncology • Septic Shock • Transplantation • CAV1

Study Evaluating the Safety and Efficacy of PTX-022 (QTORIN Sirolimus) in the Treatment of Microcystic Lymphatic Malformations (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Palvella Therapeutics, Inc. | Trial completion date: Jul 2022 ➔ Dec 2022 | Trial primary completion date: Apr 2022 ➔ Nov 2022

Trial completion date • Trial primary completion date

PALV-04: CODY: A Study Evaluating The Safety And Efficacy Of QTORIN 3.9% Sirolimus Topical Gel For The Prevention Of Basal Cell Carcinomas (BCCs) In Patients With Gorlin Syndrome (clinicaltrials.gov) - P2b | N=60 | Recruiting | Sponsor: Palvella Therapeutics, Inc. | Trial completion date: Sep 2022 ➔ Mar 2023 | Trial primary completion date: Aug 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Novel preclinical patient-derived lung cancer models reveal inhibition of HER3 and MTOR signaling as therapeutic strategies for NRG1 fusion-positive cancers. (PubMed, J Thorac Oncol) - "We identify the MTOR pathway as a candidate vulnerability in NRG1 fusion-positive lung adenocarcinoma that may warrant further pre-clinical evaluation, with the eventual goal of finding additional therapeutic options for patients in whom ERBB-directed therapy fails. Moreover, our results uncover heterogeneity in downstream oncogenic signaling among NRG1-rearranged cancers, possibly histology-dependent, the therapeutic significance of which requires additional investigation."

Journal • Preclinical • Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EIF4EBP1 • ERBB3 • NRG1 • SLC3A2