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1 First-in-disease therapies for patients with rare diseases Phase 3 SELVA Topline Data in Microcystic Lymphatic MalformationsFebruary 24, 2026
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2 Forward Looking StatementsThis 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 expected timing of the presentation of data from ongoing clinical trials, including the SELVA study, Palvella's marketing application plans, the potential clinical and safety benefits of QTORIN™ rapamycin and its potential to become a standard of care, the potential benefits of Palvella's designations for QTORIN™ rapamycin, including Breakthrough Therapy, Fast Track, and Orphan Drug, the potential for orphan drug exclusivity if approved, 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 Company’s plan to meet with regulatory authorities, 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 DataThe 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.TrademarksThis 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 Phase 3 SELVA Topline Data: Today’s Presenters Bohan WeiVP Corporate Development & New Product Planning Wes KaupinenFounder and CEOJeff Martini, PhDChief Scientific Officer Matt KorenbergChief Financial Officer Michael Kelly, MD, PhD•Pediatric hematologist-oncologist at Cleveland Clinic•Executive Director of Lymphangiomatosis & Gorham's Disease Alliance (LGDA)•Study investigator in Phase 3 SELVA study•Member of Palvella Medical and Scientific Advisory Board •Consultant to Palvella
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4 Opening RemarksWes KaupinenFounder and CEO QTORIN™ Rapamycin for Microcystic Lymphatic Malformations
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5 PALVELLA(pɑlʋelːɑ, Finnish): TO SERVE Building the leading rare disease biopharma company focused on developing and commercializing first-in-disease therapies for serious, rare skin diseases and vascular malformations
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6 mLM-IGA = Microcystic Lymphatic Malformation Investigator Global Assessment. Note: Data analyzed per statistical analysis plan; non-completer data imputed per statistical analysis plan for primary endpoint; endpoints tested according to pre-specified hierarchical testing procedure; statistical significance (p<0.05). : A Clear Path Forward for PatientsQTORIN™ Rapamycin at Week 24: Highly statistically significant across primary, key secondary, and all four secondary endpoints (all p<0.001) +2.13Mean improvement on mLM-IGA primary endpoint (p<0.001) 95%Participants aged ≥ 6 who completed the efficacy evaluation period: Palvella plans to advance quickly towards NDA filing, with potential approval in 1H:2027 86%“Much Improved” (+2) or “Very Much Improved” (+3) on mLM-IGAImproved on mLM-IGA
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7 Phase 3 SELVATopline ResultsDr. Jeff MartiniChief Scientific Officer QTORIN™ Rapamycin for Microcystic Lymphatic Malformations
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8 Microcystic Lymphatic Malformations:Serious, Debilitating, and Lifelong Genetics & Biology:Monogenic somatic PIK3CA mutations cause hyperactivated PI3K/mTOR Lymphorrhea: Persistent discharge of lymphatic fluid through skin layers Deep infections: Recurrent cellulitis and serious soft tissue infections, resulting in hospitalizationsProliferative, progressive disease with infiltrative lesions and no spontaneous regression No FDA-approved therapies > 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) and Gallagher et al, Orphanet Journal of Rare Diseases, (2022). Includes microcystic LM and mixed LM (patients with both microcystic and macrocystic disease).
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9 QTORIN™: Targeted mTOR Inhibition with Dermal Target Engagement 3.9% concentration enabled through synergistic multi-excipient anhydrous solubilization system Elevated thermodynamic activity drives rapamycin vehicle release and skin bioavailability Deep dermal penetration & sustained dermal retention for prolonged inhibition of hyperactivated mTOR signaling Adherence-optimized vehicle designed for chronic dosing in pediatric and adult populations Single-phase gel maintaining dissolved rapamycin without crystallization or suspension QTORIN™ 3.9% Rapamycin Anhydrous Gel
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10 Upside Target Clinical ProfileSELVA OutcomeStatistically significant primary endpoint with mean mLM-IGA of ≥+1.5 at Week 24 Statistical significance on independent, blinded key secondary endpoint Safety profile: well-tolerated and similar to previous clinical trials Highly statistically significant with mean mLM-IGA of +2.13 at Week 24 (p<0.001) Highly statistically significant (p<0.001), including on all three clinical signs: vesicle appearance, height, leaking/bleeding Well-tolerated across both adult and pediatric patients, supporting chronic administration : QTORIN™ Rapamycin Exceeded Upside Case Profile Rollover into extension period in line with best-in-class drugs for rare diseases98% of Week 24 completers (43/44) rolled over to Extension period Note: Data analyzed per statistical analysis plan; non-completer data handled via multiple imputation per statistical analysis plan; endpoints tested sequentially according to pre-specified hierarchical testing; statistical significance (p<0.05). Week 24 completers included 43 participants ≥6 years old and 1 participant 3-5 years old.
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11 Phase 3 SELVA Trial DesignSingle-arm, baseline-controlled, QD dose Primary Endpoint: mLM-IGA (Investigator Global Assessment)Key Secondary Endpoint: Blinded mLM Multi-Component Static Scale (mLM-MCSS): independent, blinded review of randomized Baseline and Week 24 photos evaluating three key signs of disease: Vesicle Appearance, Height, Leaking/BleedingSecondary Endpoints: Live mLM-MCSS, Patient Global Impression of Change (PGI-C), Clinician and Patient Global Impression of Severity (CGI-S, PGI-S), and Incidence and Severity of Adverse Events Note: Of the 51 participants enrolled, 50 initiated treatment, including 49 aged ≥6 years (ITT population). During the 24-week efficacy evaluation period, six participants discontinued treatment: four participants discontinued for reasons unrelated to adverse events, one participant discontinued due to an adverse event not related to study drug, and one participant discontinued due to an adverse event possibly related to study drug. n=50 dosed (n=49 ITT population, n=1 in 3-5 year old cohort) Extension Period24+ weeksEfficacy Evaluation24 weeks BaselinePhoto Baseline (≥ 8 weeks)n=51 enrolled Live Clinician Assessment Supported by FDA Orphan Products Grant: Two tranches of non-dilutive funding received (most recent in Oct ‘25) n=43/44 completers rolled over to Extension periodEnd of TreatmentPhotoScreeningPhoto
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12 Phase 3 SELVA: Baseline CharacteristicsITT Population (n=49)1 Age, Mean [Range]19.4 [6-57]Sex M:F 24:25Prior Medical Interventions for mLM2 34 (69%)Laser 17 (35%)Sclerotherapy 14 (29%)Surgery 13 (27%)Topical Sirolimus [Rapamycin]13 (27%)Oral Sirolimus [Rapamycin]2 (4%) 1. 51 participants entered Baseline period; 50 dosed with QTORIN™ rapamycin (49 participants ≥6 years old = ITT population; 1 participant 3-5 years old included in safety database). 2. Percentages may not sum to 100% due to some patients having more than one intervention.
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13 SELVA: Primary and Key Secondary Endpoints Achieved Mean Change at Week 24 (95% CI)p-valuePrimary Endpoint: Microcystic Lymphatic Malformation Investigator Global Assessment (mLM-IGA)*+2.13 (1.88, 2.38)p<0.001Key Secondary Endpoint: Blinded Microcystic Lymphatic Malformation Multi-Component Static Scale**-3.36 (-4.34, -2.38)p<0.001 Note: Data analyzed per statistical analysis plan; non-completer data imputed per statistical analysis plan for primary endpoint; endpoints tested according to pre-specified hierarchical testing procedure; statistical significance (p<0.05). *Dynamic change scales (7-point scales ranging from "Very Much Worse" (-3) to "Very Much Improved" (+3); positive values indicate improvements from baseline)**mLM-MCSS (Sum of three static severity scales: Height, Leaking/Bleeding, Vesicle Appearance: Each scale rated "Clear or Almost Clear" (1) to "Very Severe" (5); total score 3-15. Test baseline to Week 24 change; negative values indicate improvements from baseline)
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14 SELVA: All Additional Secondary Endpoints AchievedMean Change at Week 24 (95% CI)p-value Patient Global Impression of Change*+1.9 (1.66, 2.16)p<0.001Live mLM-MCSS**-4.6 (-5.20, -3.92)p<0.001Clinician Global Impression of Severity***-1.7 (-1.91, -1.39)p<0.001Patient Global Impression of Severity***-1.0 (-1.26, -0.74)p<0.001 Note: Data analyzed per statistical analysis plan; non-completer data imputed per statistical analysis plan for primary endpoint; endpoints tested according to pre-specified hierarchical testing procedure; statistical significance (p<0.05). *Dynamic change scales (7-point scales ranging from "Very Much Worse" (-3) to "Very Much Improved" (+3); positive values indicate improvements from baseline)**mLM-MCSS (Sum of three static severity scales: Height, Leaking/Bleeding, Vesicle Appearance: Each scale rated "Clear or Almost Clear" (1) to "Very Severe" (5); total score 3-15. Test baseline to Week 24 change; negative values indicate improvements from baseline) ***Static severity scales (5-point scales ranging from 1 to 5; negative values indicate improvements from baseline)
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15 Phase 3 Results: Well-Tolerated and Favorable Safety Profile Rapamycin levels were below 2 ng/mL2 in systemic circulation on for all participants at all timepoints in the studyNote: n=50 participants in efficacy evaluation evaluated for safety. 1. Denotes related or possibly related. 2. Validated assay of lower limit of quantification (100 pg/mL). Number of Participants (%)Any Treatment-Emergent Adverse Event35 (70%)Severe (not related to study drug)1 (2%)Serious (not related to study drug) 4 (8%)Any Treatment-Related1 Adverse Event17 (34%)Severe 0 (0%)Serious 0 (0%)Treatment-Related1 AEs with ≥ 5% IncidenceApplication site acne3 (6%)Application site discoloration3 (6%)Application site pruritus3 (6%)Possibly Treatment-Related AE Leading to Discontinuation1 (2%)
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16 KOL PerspectiveDr. Michael KellyCleveland Clinic QTORIN™ Rapamycin for Microcystic Lymphatic Malformations
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17 Phase 3 Results: Age 10, Female Note: Selective photos. Back
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18 Week 24Baseline Phase 3 Results: Age 10, Female, mLM-IGA: +2 “Much Improved” Note: Selective photos. Back Back
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19 Phase 3 Results: Age 10, Male Note: Selective photos. Back
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20 Week 24BaselinePhase 3 Results: Age 10, Male, mLM-IGA: +2 “Much Improved” Note: Selective photos. Thigh Thigh
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21 Week 24Baseline Phase 3 Results: Age 14, Female, mLM-IGA: +3 “Very Much Improved” Note: Selective photos. Neck Neck
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22 Week 24BaselinePhase 3 Results: Age 7, Female, mLM-IGA: +3 “Very Much Improved” Note: Selective photos. Elbow Elbow
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23 QTORIN™ Rapamycin Has the Potential to be First-Line and Standard of Care in Microcystic Lymphatic Malformations Targets underlying pathobiology 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. Large magnitude treatment effect in two prospective trials Favorable safety profile allowing for chronic therapy QTORIN™ 3.9% Rapamycin
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24 SummaryWes KaupinenFounder and CEO QTORIN™ Rapamycin for Microcystic Lymphatic Malformations
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25 Palvella: Leading the Way in Addressing Rare Skin Diseases and Vascular Malformations Planned NDA submission in 2H:2026Potential first FDA-approved therapy in mLM; U.S. launch prep accelerating Pipeline-in-a-product: Broad potential to address mTOR-driven diseasesPlatform: QTORIN™ pitavastatin and new QTORIN™ program (2H:2026) 1 2 4 5 $1-$3 billion U.S. peak sales potential (mLM + cVM) 3
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26 Striving to be first for rare disease patients Thank You