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1 First-in-disease therapies for patients with rare genetic skin diseases Corporate Presentation September 2025
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2 Forward Looking Statements This presentation contains forward-looking statements of Palvella Therapeutics, Inc. (the Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. Forward- looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the Company’s future financial or business performance, conditions, plans, prospects, trends or strategies and other financial and business matters, the Company’s current and prospective product candidates and any additional indications or platform candidates, the Company's planned research and development activities, the Company's planned clinical trials, including timing of receipt of data from the same, the planned regulatory framework for the Company's product candidates, the strength of the Company's intellectual property portfolio, and projections of the Company’s future financial results and other metrics. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements. These forward-looking statements are based upon current estimates and assumptions of the Company and its management and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition, the ability of the company to grow and manage growth, maintain relationships with suppliers and retain its management and key employees; the success, cost and timing of the Company’s product development activities, studies and clinical trials; changes in applicable laws or regulations; the possibility that the Company may be adversely affected by other economic, business or competitive factors; the Company’s estimates of expenses and profitability; the evolution of the markets in which the Company competes; the ability of the Company to implement its strategic initiatives and continue to innovate its existing products; and the ability of the Company to defend its intellectual property. Nothing in this Presentation should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. The Company undertakes no duty to update these forward-looking statements. Industry and Market Data The Company may from time to time provide estimates, projections and other information concerning its industry, the general business environment, and the markets for certain conditions, including estimates regarding the potential size of those markets and the estimated incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties, and actual events, circumstances or numbers, including actual disease prevalence rates and market size, may differ materially from the information reflected in this presentation. Unless otherwise expressly stated, we obtained this industry, business information, market data, prevalence information and other data from reports, research surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data, and similar sources, in some cases applying our own assumptions and analysis that may, in the future, prove not to have been accurate. Trademarks This Presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this Presentation may be listed without the TM, SM © or ® symbols, but the Company will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights.
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3 PALVELLA (pɑlʋelːɑ, Finnish): TO SERVE Building an enduring rare disease biopharma company to address serious, rare genetic skin diseases
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4 Palvella: Leadership in Treating Serious, Rare Skin Diseases 597 Rare Skin Diseases Often chronic and debilitating; many have known genetic drivers Over 98% Have No Approved Therapies1 Lack of industry innovation and investment compared to other therapeutic areas (e.g., oncology, neurology, pulmonary) Selective in the indications we pursue: high unmet need, commercially attractive diseases Potential to develop the 1 ST & Only approved therapy 1. Licholai G., Rare Dermatology Orphan Disease Drug Development Opportunities & Challenges, Presented at Dermatology Summit, Jan 2019. “We have begun to see interest from investors and companies in developing treatments for a rare disease such as epidermolysis bullosa, but there are many other diseases within dermatology that remain unaddressed” John Doux, M.D., Barriers and Opportunities Across the Development Divide, The Society of Investigative Dermatology, 2015
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5 What’s New at Palvella – September 2025 U.S. launch planning is accelerating for microcystic LMs (first indication) • Hired Ashley Kline as Chief Commercial Officer (May 2025); previously led launch of Oxervate, first-in- disease topical therapy which surpassed $500 million in annual U.S. sales by year 5 • New insights from physician and payor market research indicate potential for strong uptake David Osborne, Ph.D. hired as Chief Innovation Officer (September 2025) • Co-Founder and former Chief Technical Officer of Arcutis Biotherapeutics (NASDAQ: ARQT) • Providing leadership across Palvella’s early-stage R&D pipeline, including maximizing the potential of the QTORIN platform, including second QTORIN product candidate Growing Commercial Opportunity for QTORIN Rapamycin • QTORIN rapamycin third clinical indication: targeting announcement in September 2025 • Researchers have identified > 25 mTOR-driven skin diseases, including vascular anomalies, genodermatoses, and non-vascular neoplasms (Fogel et al, Swarbrick et al, Lapa et al) • Anticipated pool of addressable QTORIN rapamycin patients to increase by > 10x with expansion into third indication and future additional indications
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6 Four High-Impact Milestones Between Now and End of Q1 2026 SEPTEMBER 2025 Q4 2025 ✓ Serious, rare, no FDA- approved therapies ✓ Commercially attractive QTORIN 3.9% rapamycin anhydrous gel Third Indication for QTORIN Rapamycin 1 Phase 2 Topline Data in Cutaneous VMs 3 ✓ Targeting ~15 subjects DECEMBER 2025 Q1 2026 New QTORIN Program 2 ✓ Serious, rare, no FDA- approved therapies ✓ Clear biology ✓ Commercially attractive ✓ Targeting <$10mm and <2.5 years to Phase 2 POC data QTORIN TM PLATFORM Phase 3 Topline Data in Microcystic LMs 4 EXCEEDED ENROLLMENT TARGET ✓ 51 subjects QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use.
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7 OUR LEAD PRODUCT CANDIDATE QTORIN 3.9% RAPAMYCIN ANHYDROUS GEL
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8 HIGH DRUG LOADING CAPACITY High solubility → high concentrations → potential for rapid onset and large magnitude treatment effect SAFETY AND TOLERABILITY Retaining active drug in the skin while minimizing systemic absorption DERMAL ENGAGEMENT Delivery to deeper layers of skin, often the site of disease pathophysiology IP Each QTORINTM product candidate eligible for composition IP on formulation QTORIN : Reproducible Platform for Generating Novel, Topical Product Candidates in a Capital Efficient Manner QTORIN TM PLATFORM
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9 Rapamycin Oral Rapamycin: Limitations Restrict Use in Skin Diseases Significant Barriers to Commercially Viable Topical Rapamycin Formulation Palvella’s QTORIN is designed to overcome these major obstacles Current Rapamycin Options Inadequate for Skin Diseases Strong immunosuppressive activity1 Poor biodistribution to and within the skin2 Systemic toxicities 1. Rapamune package insert. 2. Data on file; Kitayama et al., Journal of Derm. Science (2019). Poor solubility / low API concentration Chemically unstable Restricted skin penetration
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10 QTORIN 3.9% rapamycin anhydrous gel Our Breakthrough Innovation: QTORIN 3.9% Rapamycin Anhydrous Gel DERMAL ENGAGEMENT Rapamycin concentration in dermis exceeds IC90 for mTOR inhibition1 OPTIMIZED CONCENTRATION QTORIN synergistic solubility results in 3.9% concentration TOLERABILITY No traditional penetration enhancers; limited systemic absorption2 Intended for once daily at-home self-administration 10 QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use. 1. Data on file. 2.Clinical Study Report PALV-0609. API
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11 Micro LM Cutaneous VM Next Indication Additional Future Indications1 TODAY FUTURE INDICATIONS Targeting announcement in September 2025 Targeting announcement in 2026 and beyond = 5k 30k+ 75k+ 200k+50k+ Growing Commercial Opportunity for QTORIN Rapamycin: Pool of Addressable Patients Projected to Expand by >10x with Pipeline-in-a-Product Strategy Potential FDA approval timeline 2027 2029 2031+ 2032+ 1. Lapa et al., Journal of Cutaneous Medicine and Surgery, (2025).
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12 QTORIN 3.9% RAPAMYCIN Microcystic Lymphatic Malformations FOR
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13 Microcystic Lymphatic Malformations: Serious, Debilitating, and Lifelong Genetics & Pathophysiology: Monogenic somatic PIK3CA mutations cause hyperactivated PI3K/mTOR Lymphorrhea: Persistent discharge of lymphatic fluid through skin layers Deep infections: Cellulitis and other serious infections Natural history: Proliferation of infiltrative lesions with no spontaneous resolution Leads to serious impact to quality of life and hospitalizations, with no FDA-approved therapies Current options: surgeries, sclerotherapy (chemotherapy injections), laser therapy, off-label oral and topical mTOR inhibitors > 30k patients ESTIMATED DIAGNOSED IN THE U.S.1 Early onset: Present at birth and significant impact to adolescents 1. Incidence, prevalence, and care for patients with lymphatic malformations (LMs) in the U.S.: A claims-based analysis, Society of Investigative Dermatology, 2025. Primary prospective research conducted by Clarity Pharma and Sentero Pharma, claims analysis conducted by Trinity Life Sciences (June 2024). Includes microcystic LM and mixed LM (patients with both microcystic and macrocystic disease).
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14 QTORIN Rapamycin for Micro LMs: On Target, In Tissue rapamycin Target: mTOR Tissue: Dermis • Monogenic somatic mutations leads to overactivated PI3K/mTOR signaling • QTORIN delivers pharmacologically active levels of rapamycin to diseased tissue QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use.
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15 QTORIN Rapamycin: Phase 2 Study in Microcystic LMs n=12; QD dose James Treat, MD Joyce Teng, MD, PhD Alison Small, MDMilton Waner, MDSteve Kempers, MD Single arm, QTORIN rapamycin treatment (QD) (12 weeks)Baseline (4 weeks) Study Objectives: Safety and efficacy Results • Clinically & statistically significant on pre-specified global and individual endpoints • Patient exit interviews and photographs align with clinical data
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16 -3 -2 -1 0 1 2 3 * * * * ** Statistically significant across key clinician- assessed individual signs of microcystic LM at week 12 • Height (p<0.0001) • Leaking (p<0.005) • Bleeding (p<0.05) • Erythema (p<0.005) • Hyperkeratosis (p<0.005) Phase 2: Clinically Meaningful, Statistically Significant Improvements Mean CGI-C: + 2.42 (p<0.0001) Clinician Global Impression of Change Patient Global Impression of Change Week 4 Week 8 Week 12 Week 4 Week 8 Week 12 Very Much Improved Much Improved Minimal Improvement No Change Minimally Worse Much Worse Very Much Worse n=12; QD dose * = p-value <0.0001 → 100% of participants were either “Much Improved” or “Very Much Improved” on CGI-C after 12 weeks of treatment → Palvella was subsequently granted FDA Breakthrough Therapy Designation based on this data
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17 Week 12 Phase 2 Results: Visible Improvement Baseline Patient CGI-C: Very Much Improved (+3). QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use. Underarm Underarm
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18 Week 12 Baseline Phase 2 Results: Visible Improvement Wrist Wrist Patient CGI-C: Very Much Improved (+3). QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use.
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19 Phase 2 Results: Safety and Tolerability TREATMENT-AFFECTED DRUG-RELATED AES RELATED ANY GRADE EVENTS (%, N=12) Application site pain 3 (25) Application site pruritus 3 (25) Application site discharge, Application site erythema, Application site paraesthesia, Nodule, Eczema, Skin exfoliation, Diarrhea, Headache 1 (8.3) each • QTORIN rapamycin had favorable safety profile and was well-tolerated • All TreatmentRelated Adverse Events were moderate or mild (no severe events) • No discontinuations due to AEs • No unexpected AEs Low blood levels of rapamycin detected: 0.12 ng/mL (mean) Significantly below 5 ng/mL which is the lower boundary where rapamycin begins to exert immunosuppressive effects
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20 Phase 3 SELVA Enrollment: Exceeded Target of 40 Patients Single-arm, baseline-controlled, 24-week efficacy evaluation, QD dose, age 3+(1) *Denotes sites that also participated in Phase 2 trial. 1. Patients ages 3-5 will be excluded from primary endpoint. Enrollment closed in June 2025 with n=51 patients; top-line readout anticipated Q1 2026 Joyce Teng, MD, PhD Principal Investigator * * * Primary Efficacy • mLM-IGA (Investigator Global Assessment), a 7-point clinician change scale Key Secondary • Blinded mLM Multi-Component Static Scale (mLM-MCSS) Data anticipated Q1 2026
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21 Phase 3 Study Design Mimics Phase 2 Study Phase 3 trial design based on statistical significance with n=12 in Phase 2 Phase 2 Size n=12 Key Efficacy Endpoints CGI -C, a 7-point clinician change scale 1 (p<0.0001) Study duration 12 weeks Baseline Controlled ✓ QD Dosing ✓ Moderate to severe study population ✓ Phase 3 n=40 (for NDA safety database) mLM-IGA, a 7-point clinician change scale (primary)2 24 weeks ✓ ✓ ✓ > 99% powered Phase 3 primary endpoint (mLM-IGA) mimics Phase 2 CGI-C endpoint • 7-point change scale • Single item question related to lesion severity (not composite) Key improvements • Protocol requirement to reference pre-treatment photo to aid assessment • Descriptions added to each point on the scale 1. CGI-C is a 7-point change scale ranging from –3 (very much worse) to +3 (very much improved). 2. mLM-IGA is 7-point change scale ranging from –3 (very much worse) to +3 (very much improved) that uses baseline photos as a required component for live clinician assessment of lesion change.
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22 Regulatory: NDA Submission Planned for H2 2026 Breakthrough, Fast Track, and Orphan Designations granted Anticipating expedited regulatory pathway: i. Breakthrough Therapy, Fast Track, and Orphan Drug Designations ii. Planned 505(b)(2) pathway iii. Potential for six-month priority review iv. Potential for rolling NDA submission v. Real-world evidence supporting rapamycin in microcystic LMs Phase 3 SELVA Study: FDA Orphan Products Grants Awardee • Single arm, baseline-controlled Phase 3 SELVA study was named one of seven awardees of an FDA orphan products grant (out of 51 applicants) • Based on scientific and technical merit • Up to $2.6 million in non-dilutive funding FDA Overview: • Center: Center for Drug Evaluation Research (CDER) • Division: Dermatology and Dentistry o Leadership: Dr. Jill Lindstrom remains in Director role • NDA Review: Due to planned 505(b)(2) pathway, division leadership expected to be responsible for NDA decision Breakthrough Therapy Designation Fast T rack Designation Orphan Drug Designation “Single-arm trials may be an important option in rare diseases with well-understood pathophysiology and a well-defined disease course" - FDA’s May 2014 Draft Guidance: Expedited Programs for Serious Conditions – Drugs and Biologics
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23 QTORIN 3.9% RAPAMYCIN U.S. Commercial Launch Planning
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24 Microcystic LMs: Pre-Commercial Work Validates Attractive Multibillion-Dollar Uncontested U.S. Market Dynamics ASHLEY KLINE Chief Commercial Officer Joined May 2025 Recently elucidated genetics enable development of first targeted therapy to address causal mTOR pathway with minimal side effects Large orphan market: Claims analyses verified > 30k estimated diagnosed U.S. patients, with >1,500 incident patients annually 1 Positioned to be first and only FDA-approved therapy; market research indicates strong intent to prescribe, including in pediatric population2 Orphan analogues and recent payor testing validate expected orphan pricing corridor3 Concentrated prescriber base in vascular anomaly centers (VACs) & other clinics 4
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25 QTORIN Rapamycin Physician Market Research: Potential to be First Line, Standard of Care Therapy for Microcystic LMs Product X: Topical 3.9% rapamycin gel, including results from Phase 2 study of QTORIN rapamycin Core Intent to Prescribe Insights 98% of physicians Percent of my microcystic LM patients I would prescribe Product X: 75% of patients New: Additional Insights into Pediatric Population New: Physician Segmentation Insights VAC* Physicians (n=21) Non-VAC Physicians (n=31) 73% of patients 77% of patients *Vascular Anomaly Centers 17 of 52 physicians stated they would prescribe to 100% of patients “[Product X] would be an excellent safe option that I would readily prescribe” Would consider Product X as a first-line therapy 96% of physicians See advantages to targeted, localized delivery of Product X for pediatric patients compared to oral mTOR or PI3K inhibitor “Most parents would not like a young child treated with a systemic drug with so many potential long-term and serious side effects” Source: Medacorp Research, 2024. n=52 microcystic LM treaters.
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26 Highly Concentrated Patient Population: ~400 Established High Volume Centers for Treating Vascular Malformations Comprise ~50% of Market Source: Palvella and ZS Associates claims analysis (2025). 1. Cohen-Cutler et al., The Journal of Pediatrics, (2023). CLAIMS ANALYSIS SUPPORTS THREE SEGMENTS ~50% Tier One – High Volume Centers: Vascular Anomaly Centers (VACs) and Other Clinics • Already established Centers of Excellence for mLM • ~96% of VACs today prescribe oral mTOR inhibitors1: familiarity with class & mechanism of drug ~20% Tier Two Targets ~30% All Other Providers Highly Concentrated Patients: ~50% of market at ~400 centers Secondary Targets at Launch Long-tail Targets Omni-channel approach Inside sales can provide a high ROI Apply additional learnings from Oxervate and other orphan launches All three market segments to be covered by orphan sales force of ~20-40 reps
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27 Payor Research (Q2 2025): High Unmet Need Rare Disease with Low Likelihood of Step-edits Safety & Tolerability of Product X Clinical Efficacy of Product X L H L H Budget Impact of Disease (mLM) L H “ We are very hands off here, we leave it to the specialists to decide what is best. – National MCO I would not implement a compounded sirolimus [rapamycin] step-through because sirolimus [rapamycin] is already less safe and compounding introduces additional safety concerns. – National MCO “ Key: Current With Product X Source: Blinded Payor Research Spring 2025, n=11 U.S. payors including National & Regional MCO Pharmacy Directors and National PBMs. ClearView Health Partners research (Q2 2025). The likelihood of an off-label rapamycin step-through is low due to limited KOL support and lack of robust data n = 11 U.S. payors
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28 1. Medscape Medical News interview with Mandy Fahey, Insmed Director of Corporate Communications (2018). 2. Assumes one course of 8-week therapy for both eyes. 3. Horizon Therapeutics Management guidance and Wall Street research. Price dependent on weight-based dosing. 4. Insmed corporate presentation (2025). 5. Sacchetti et al., Clin Opth (2014). 6. Stan et al., Clin Endocrinol (Oxf) (2024), Horizon Therapeutics investor presentation (2023). ~$135k1 Rare Disease Medications Refractory non- tuberculous mycobacterial (NTM) lung infections Thyroid eye disease ~12K-17K prevalent U.S. patients4 ~65K-100K prevalent U.S. patients6 ~$200k-350k3 Indication Market Size U.S. Annual List Price at Launch QTORIN Rapamycin Pricing: Prior First-in-Disease Launches and Recent Topical Orphan Launches Support Potential Orphan Drug Pricing Neurotrophic keratitis ~50K prevalent U.S. patients5 ~$190k2
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29 Strong Medical Affairs Presence in 2026 and Beyond • Educating on underlying genetic pathology of disease and relevance of a targeted therapeutic approach • Informing on importance of early therapeutic intervention to prevent progression, especially during early childhood and puberty • High touch engagement with investigators and future potential prescribers, including both dermatologists and hematologists • Many derms and hematologists are already working together as part of coordinated care teams in VACs Planned Attendance at Key Medical Congresses: Recruiting underway for U.S. medical affairs team to focus on driving disease state awareness and other market shaping activities
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30 QTORIN 3.9% RAPAMYCIN Cutaneous Venous Malformations FOR
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31 Cutaneous Venous Malformations: Serious, High Unmet Need Genetics & Pathophysiology: Monogenic TIE2 or PIK3CA over- activating mutations; part of the PI3K/mTOR pathway Dysregulated growth of malformed veins impacting the skin Dysfunctional venous architecture leads to bleeding, thrombosis, ulceration Hyperproliferation of immature venous endothelial cells Skin involvement in ~50-80% of venous malformations patients2 Leads to physical & functional impairment, psychological distress, with no FDA-approved therapies Current options: laser treatment, sclerotherapy, off-label systemic pharmacotherapies limited by toxicities > 75k patients ESTIMATED DIAGNOSED IN THE U.S.1 1. Primary prospective research conducted by Clarity Pharma. 2. Rikihisa et al., Journal of Vascular Surgery, (2019); Boon et al., Arch Dermatol, (2004); Mazoyer et al., Arch Dermatol, (2008).
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32 Epidermis Dermis Subcutaneous / Internal VM Cutaneous VM Bleeding, thrombosis, ulceration, disfigurement, and proliferation can significantly impact patient QoL QTORIN Rapamycin Targets Cutaneous Venous Malformations: On Target, In Tissue Current unmet need for targeted, localized therapy for Cutaneous Venous Malformations
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33 “A sustained benefit of sirolimus was observed in 84% of TIE2-mutated and 83% of the PIK3CA-mutated patients. ” Data Supporting Rapamycin Use in TIE2 and PIK3CA Mutations 1. Data on file. TIE2 VENOUS MALFORMATION MODEL Preclinical Evidence Boscolo 2015 ORAL RAPAMYCIN VASE Clinical Study Seront 2023 25+ published papers support rapamycin’s clinical benefit in Venous Malformations1 “Efficacy of rapamycin in this model and in patients in our clinical pilot study suggests rapamycin as the first molecular therapy for VMs.” “Rapamycin is establishing itself as the gold standard for venous malformations… Topical agents…could abolish the need for systemic treatments that have wider toxicity” ORAL RAPAMYCIN LIMITATIONS Need for Topicals Seront 2019 Rapamycin and the treatment of venous malformations VASCULAR BIOLOGY: EDITED BY M. LUISA IRUELA ARISPE Seront, Emmanuela,b; Van Damme, An b,c,; Boon, Laurence M.d,e; Vikkula, Miikkabde
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34 Phase 2 TOIVA Study in cVMs: Full Enrollment Anticipated Sept ‘25 Single-arm, baseline-controlled, QD dose, age 6+, 12 weeks, n=~15 No Statistical Hierarchy of Endpoints Safety o Safety and tolerability Efficacy o Cutaneous venous malformation – investigators’ global assessment (7- point clinician change scale) o Cutaneous venous malformation - multicomponent static scale o Other clinician and patient-reported outcomes Topline data anticipated December 2025 Megha Tollefson, MD Principal Investigator 11 total sites open and enrolling, with 3 opened in July / August ‘25 (recently opened in July / August)
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35 Would you consider Product X over oral mTOR and PI3K inhibitors? Would you consider this as a first-line therapy for cutaneous VM patients? 90% 86% Survey of 50 high-volume dermatologists and hematologists with an average of 10.6 cutaneous VM patients seen per month % Yes Current options: laser treatment, off- label systemic pharmacotherapies limited by toxicities Product X: topical 3.9% rapamycin gel Market Research in Cutaneous VMs (Sept 2024): Strongly Indicates QTORIN Rapamycin’s Potential as First Line Therapy ” “Essentially all patients with VMs would be considered for Product X” “This product would be life changing for current patients with limited treatment options” Source: Medacorp.
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36 QTORIN PLATFORM Additional Rare Skin Diseases FOR
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37 Key Value Drivers from Pipeline Programs in Second Half of 2025 Additional mTOR-driven indication for QTORIN Rapamycin (Sept ‘25) New QTORIN Program (Q4:25) QTORIN QTORIN PLATFORM QTORIN 3.9% rapamycin anhydrous gel is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use. QTORIN rapamycin next indication • Serious, rare, no FDA-approved therapies • mTOR drives disease pathology • Commercially attractive New QTORIN program • Serious, rare, no FDA-approved therapies • Clear biology • Commercially attractive • Targeting <$10mm and <2.5 years to Phase 2 POC data QTORIN 3.9% rapamycin anhydrous gel
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38 Finance & IP
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39 Well-Capitalized Through Multiple Inflection Points with Funding from Leading Healthcare-Dedicated Investors Dec. 2024 FinancingStrong Cash Position Innovative operating model prioritizing capital efficiency Oversubscribed $78.9mm Financing co-led by ~2 years Runway into 2H 2027 $70.4 million Cash at 6/30/2025 $9.3 million R&D + G&A expenses in Q2 2025 ~$55 million Projected cash at year end
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40 Strong Barriers Through Multi-Layered Exclusivity Strategy Granted U.S. Patents Trade Secrets Regulatory Orphan drug designation and 7-year data exclusivity from anticipated FDA approval Multiple trade secrets related to proprietary formulation processes and manufacturing know-how 6 issued U.S. patents with claims through at least 2038 Including protection against 0.1% to 20% anhydrous gel compositions of rapamycin and other mTOR inhibitors IP portfolio, trade secrets, and regulatory exclusivities through at least 2038
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41 What Sets Palvella Apart: Building The Leader in Rare Genetic Skin Diseases Late-stage rare disease pipeline and QTORIN platform QTORIN rapamycin in two ongoing studies: Phase 3 (microcystic lymphatic malformations) and Phase 2 (cutaneous venous malformations), with additional QTORIN product candidates planned QTORIN rapamycin: potential to be first approved therapy and standard of care in U.S. for microcystic LMs and cutaneous VMs Both are serious, rare mTOR-driven genetic diseases currently with no FDA-approved therapies Phase 3 designed for success & expedited regulatory pathway Highly statistically significant Phase 2 results in microcystic LMs contributed to Breakthrough Therapy Designation, single arm baseline-controlled Phase 3 study, and FDA Orphan Product Grant Striving to be first for rare disease patients U.S. commercial opportunity: multi-billion dollar TAM in mLMs and beyond Insights from recent physician and payor market research indicate potential for strong uptake
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42 Striving to be first for rare disease patients Thank You
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43 A 34-year, 28-subject study confirmed no spontaneous regression No Spontaneous Regression Well-Established in Microcystic LMs * Consistent with well-established history of PI3K Related Overgrowth Spectrum, which includes microcystic LM **Kato M et al., Plast Reconstr Surg Glob Open. 2017 Sep 25;5(9):e1501.
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44 QTORIN Rapamycin: “Pipeline-in-a-Product” to Address Broad Range of mTOR-Driven Skin Diseases Larger, controlled studies are needed to define optimal concentrations, formulations, and dosing schedules. “ “ > 25 mTOR-driven skin diseases Vascular anomalies, genodermatoses, non-vascular neoplasms, and others Need for safe and effective FDA-approved therapy for these indications 2015 2021 2025
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45 Microcystic LMs: Multiple Studies Indicate > 30k Diagnosed U.S. Patients *Includes microcystic LM and mixed LM (patients with both microcystic and macrocystic manifestations). 1. Claims analysis conducted by Trinity Life Sciences (June 2024). 1. Physician Survey published 2022 2. Claims Analysis conducted 20241 3. Claims Analysis conducted 2025 Multiple analyses support > 30K diagnosed U.S. prevalence* Estimated U.S. incidence* ~1,500 annually or more
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46 Regulatory: Real-world Evidence to Support NDA Submission Sirolimus in the Treatment of Microcystic Lymphatic Malformations: A Systematic Review Joyce M.C. Teng, MD, PHD,1 Adrienne Hammill, MD, PHD,2 Jeff Martini, PHD,3 and James Treat, MD4 LYMPHATIC RESEARCH AND BIOLOGY ©Mary Ann Liebert, Inc. DOI: 10.1089/lrb.2021.0103 French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations Nicolas Leboulanger1,2*, Annouk Bisdorff3, Olivia Boccara4, Anne Dompmartin5, Laurent Guibaud6, Christine Labreze7, Jacques Lagier8, Bénédicte Lebrun-Vignes9, Denis Herbreteau10, Aline Joly11, Julie Malloizel-Delaunay12, Arnaud Martel8, Stéphane Munck13, Frédérique Saint-Aubin14 and Annabel Maruani15,16 Leboulanger et al. Orphanet Journal of Rare Diseases (2023) 18:10 https://doi.org/10.1186/s13023-022-02608-y “Micro LMs represent therapeutically challenging congenital vascular lesions. There is no universally accepted gold standard of care and there are no FDA approved therapies…this review examines clinical data over the last 10 years on the role of sirolimus [rapamycin]…a total of 16 studies were identified…clinically meaningful, long-term improvement (up to 3 years) was noted…however, developing a commercial topical sirolimus formulation faces important challenges.” “Sirolimus [rapamycin] is the disease-modifying treatment of choice. It should be started early in life (early childhood) to prevent the increase in volume of the LM.”
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47 Multiple Studies Indicate At Least Half of Venous Malformation Cases Have Cutaneous Involvement ~80% of 1,517 cases ~47% of 2,075 cases ~65% of 118 cases Percentage of venous malformation cases with cutaneous involvement
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48 Palvella Capitalization Detail 1. Includes 0.2 million of BVF Partners converted preferred shares. 2. Based on closing price of $50.13 as of 8/25/25. Does not include dilutive impact from 2.7 million options outstanding with a weighted average exercise price of $13.56. Basic Shares Outstanding1 Assuming Conversion of Pre- Funded Warrants Adjusted Shares Outstanding Market Capitalization2 NUMBER OF SHARES (MILLIONS) 11.3 2.5 13.7 ~$690mm