Palvella Therapeutics, Inc. · NASDAQ:PVLA
Palvella Therapeutics — Technical Presentation (December 2025)
23 slides from Palvella Therapeutics's technical presentation, Dec 15, 2025
Slide 1: Phase 2 TOIVA Topline Data in Cutaneous Venous Malformations
1 First - in - disease therapies for patients with rare skin diseases Phase 2 TOIVA Topline Data in Cutaneous Venous Malformations December 15, 2025
Slide 2: Forward Looking Statements
2 Forward Looking Statements This presentation contains forward - looking statements of Palvella Therapeutics, Inc. (“the Company”) within the meaning of the P rivate Securities Litigation Reform Act of 1995. Forward - looking statements include all statements that are not historical facts, and in s
Slide 3: Phase 2 TOIVA Topline Data: Today's Presenters
3 Phase 2 TOIVA Topline Data : Today’s Presenters Michael Kelly , MD, PhD • Pediatric hematologist - oncologist at Cleveland Clinic • Study investigator in Phase 2 TOIVA study • Member of Palvella Medical and Scientific Advisory Board Bohan Wei VP Corporate Development & New Product Planning Wes Kau
Slide 4: Agenda
4 Agenda EXECUTIVE SUMMARY DISEASE OVERVIEW PHASE 2 TOIVA TOPLINE RESULTS SUMMARY Q&A Wes Kaupinen, Founder and CEO Michael Kelly, MD, PhD, Cleveland Clinic Jeff Martini, PhD, CSO Michael Kelly, MD, PhD, Cleveland Clinic Wes Kaupinen, Founder and CEO
Slide 5: Executive Summary: Phase 2 TOIVA Topline Results
5 • Achieved statistical significance on multiple pre - specified clinician - reported and patient - reported efficacy endpoints, including dynamic change endpoints and static severity endpoints • Overall Cutaneous Venous Malformations - Investigators’ Global Assessment (cVM - IGA): 7 - point clinic
Slide 6: Dr. Michael Kelly, Cleveland Clinic
6 Dr. Michael Kelly, Cleveland Clinic Pediatric hematologist - oncologist at Cleveland Clinic • One of the leading physician - scientists advancing modern, mutation - informed treatment paradigms in the vascular anomalies field • Involved in over 100 clinical trials for novel oncology and vascular a
Slide 7: Disease Overview
7 Disease Overview Dr. Michael Kelly, Cleveland Clinic QTORIN Rapamycin for Cutaneous Venous Malformations
Slide 8: Cutaneous Venous Malformations: High Unmet Medical Need
8 Cutaneous Venous Malformations: High Unmet Medical Need One of the most significant unmet medical needs in vascular malformations field Most common vascular malformation, affecting estimated > 75k patients in the U.S. 1 Chronic, lifelong disease course 1. Gallagher et al, Orphanet Journal of Rare
Slide 9: Cutaneous Venous Malformations: Relentless Cycle of Microthromboses and Functional Loss
9 Cutaneous Venous Malformations : Relentless Cycle of Microthromboses and Functional Loss Abnormal Vessels Bleeding Chronic Micro - thromboses Height (elevation/ engorgement) Phleboliths (painful calcium deposits) TEK/PIK3CA/Other VM Mutations mTOR Hyperactivation Endothelial Dysfunction Therapeuti
Slide 10: Constitutively Active Signaling Not Addressed by Non-specific, Episodic Treatments
10 Constitutively Active Biological Signaling is Not Addressed by Non - specific, Episodic Treatments Sclerotherapy Laser Surgery ⮽ Does not address underlying causal biology of disease ⮽ Highly invasive and traumatic ⮽ Any improvement likely to be limited and short - term Disease will reliably recu
Slide 11: Phase 2 TOIVA Topline Results
11 Phase 2 TOIVA Topline Results Dr. Jeff Martini, Chief Scientific Officer Dr. Michael Kelly, Cleveland Clinic QTORIN Rapamycin for Cutaneous Venous Malformations
Slide 12: Progress Towards the Potential First Targeted Therapy for Cutaneous Disease
12 Venous Malformations: Progress Towards the Potential First Targeted Therapy for Unaddressed Cutaneous Disease Known Genetics / Clear Biology Real - world Evidence Real - world evidence supports rapamycin’s off - label use in primarily internal manifestations of VMs… …however, poor patient outcome
Slide 13: Phase 2 TOIVA Study in cVMs
13 Phase 2 TOIVA Study in cVMs : 24 - Week Study Single - arm, baseline - controlled, QD dose, age 6+ Safety and Tolerability Efficacy (no pre - specified primary endpoint): cVM - IGA (7 - point clinician change scale), cutaneous VM multi - component static scale (cVM - MCSS), o ther clinician - and
Slide 14: Statistically Significant Improvements on Dynamic Change Scales
14 Statistically Significant Improvements on Dynamic Change Scales Participants (n=15) at Week 12 Mean Change / p - value Note: 7 - point scales ranging from - 3 to +3; positive values indicate improvements from baseline +1.5 (p < 0.001) Overall Cutaneous Venous Malformations Investigator Global Ass
Slide 15: Overall cVM-IGA: 73% of Participants Demonstrated Improvement at Week 12
15 Overall cVM - IGA: 73% of Participants Demonstrated Improvement at Week 12 Single - arm, baseline - controlled, QD dose, age 6+ • Overall cVM - IGA: 7 - point clinician - assessed dynamic change scale ranging from “Very Much Worse” ( - 3) to “Very Much Improved” (+3) • Mean effect size at week 12
Slide 16: Overall cVM-IGA: Rapid, Time Dependent Response Observed
16 Overall cVM - IGA: Rapid, Time Dependent Response Observed % of Participants with At Least a 2 - point Improvement on Overall cVM - IGA 31% 50% 67% 0% 25% 50% 75% 100% Week 0 Week 4 Week 8 Week 12 Percentage of Participants Single - arm, baseline - controlled, QD dose, age 6+ Note: Statistical si
Slide 17: Statistically Significant Improvements on Key Static Severity Scales
17 Statistically Significant Improvements on Key Static Severity Scales Participants (n=15) at Week 12 Mean Change / p - value Note: 5 - point scales ranging from 1 to 5; negative values indicate improvements from baseline - 1.0 (p < 0.001) Overall Clinician Global Impression of Severity (CGI - S) -
Slide 18: Phase 2 Results: Visible Improvement (CHOP Participant)
18 Site: CHOP Investigator: Dr. Denise Adams Participant Age: 17 Mutation: TEK cVM - IGA at Week 12: Very Much Improved (+3) Week 12 Baseline Phase 2 Results: Visible Improvement Participant Qualitative Interview: “I’ve definitely noticed some improvements…it’s definitely had a positive effect…It’s
Slide 19: Phase 2 Results: Visible Improvement (Cleveland Clinic Participant)
19 Site: Cleveland Clinic Investigator: Dr. Michael Kelly Participant Age: 13 Mutation: PIK3CA cVM - IGA at Week 12: Much Improved (+2) Week 12 Phase 2 Results: Visible Improvement Note: Selective photos. Week 12 Baseline Participant Qualitative Interview: “It’s slowed down bleeding and the color ha
Slide 20: Phase 2 Results: Safety and Tolerability
20 Phase 2 Results: Safety and Tolerability • QTORI N rapamycin was generally well - tolerated , similar to previous clinical trials • Most common Treatment - Emergent Adverse Events were application site reactions (erythema, 25%) • All Treatment - Related Adverse Events were moderate or mild (no se
Slide 21: Summary
21 Summary Wes Kaupinen Chief Executive Officer QTORIN Rapamycin for Cutaneous Venous Malformations
Slide 22: QTORIN Rapamycin Has the Potential to Be the First FDA-Approved Therapy for Cutaneous Venous Malformations
22 QTORIN Rapamycin has the Potential to Be the First FDA - Approved Therapy for Cutaneous Venous Malformations Achieved statistical significance on multiple pre - specified clinician - reported and patient - reported efficacy endpoints, including 73% of participants (11/15 participants) demonstrate
Slide 23: Thank You
23 Striving to be first for rare disease patients Thank You
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