Palvella Therapeutics (NASDAQ: PVLA) details QTORIN pipeline and cash position
Rhea-AI Filing Summary
Palvella Therapeutics is advancing its QTORIN platform for rare dermatologic and vascular malformation diseases. Lead candidate QTORIN 3.9% rapamycin anhydrous gel achieved highly statistically significant Phase 3 SELVA results in microcystic lymphatic malformations, supporting a rolling New Drug Application (NDA) submission planned for completion in 2H 2026 and potential U.S. approval and launch in 1H 2027. The program holds Breakthrough, Fast Track and Orphan designations and targets an estimated >30k diagnosed U.S. patients, with internal research indicating potential U.S. peak sales of >$1 billion at orphan-level pricing.
The same formulation is being developed for cutaneous venous malformations, where positive Phase 2 TOIVA data and Fast Track status underpin a planned Phase 3 initiation in Q4 2026, and for clinically significant angiokeratomas (Phase 2 initiated in April 2026). A second key program, QTORIN pitavastatin, is being advanced for DSAP with Phase 2 initiation expected in 2H 2026. Palvella reports an oversubscribed $230mm financing in Q1 2026 and $262 million in cash as of March 31, 2026, with 2026 cash expenses estimated at [~$90-95mm], which it states provides potential funding through multiple regulatory filings, an initial launch and several Phase 2 readouts.
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New Drug Application regulatory
rolling review regulatory
505(b)(2) submission regulatory
Orphan drug designation regulatory
Breakthrough Therapy Designation regulatory
vascular malformations medical
FAQ
What is Palvella Therapeutics' (PVLA) lead drug candidate and development status?
Which rare diseases is Palvella Therapeutics (PVLA) targeting with QTORIN rapamycin?
What additional QTORIN-based programs does Palvella Therapeutics (PVLA) describe?
What regulatory designations has QTORIN 3.9% rapamycin received according to Palvella (PVLA)?
What cash position and 2026 spending does Palvella Therapeutics (PVLA) report?
How large is the market opportunity for Palvella Therapeutics' (PVLA) microcystic LM program?
UNITED STATES
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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Item 8.01 Other Events.
On July 14, 2026, Palvella Therapeutics, Inc. (the “Company”) posted a corporate presentation to its website, which representatives of the Company will use in various meetings with investors from time to time. A copy of the presentation is filed herewith as Exhibit 99.1, and incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
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Corporate Presentation of Palvella Therapeutics, Inc., dated July 14, 2026* |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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PALVELLA THERAPEUTICS, INC. |
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July 14, 2026 |
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/s/ Matthew Korenberg |
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Matthew Korenberg |
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Chief Financial Officer |
First-in-disease therapies for patients with rare diseases Corporate Presentation July 2026
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 Company's expectations regarding the timing of completion of the New Drug Application ("NDA"), the planned regulatory framework for the Company's product candidates, the Company's ability and the ability of third-party manufacturers the Company engages to optimize and scale manufacturing, 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.
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
What Makes Palvella Stand Apart Repeatably unlocking multi-billion dollar market opportunities in previously untreated orphan diseases First-in-Disease Focus Rare Diseases with Clear Disease Biology Leveraging Existing Human Proof-of-Concept and Safety Data Innovative QTORIN™ Platform: Durable IP Generation Veteran team executing rare disease model designed to reduce time and capital to FDA approval 1 2 3 4
What’s New at Palvella – Q3 2026 Leveraging QTORIN™ to expand into additional first-in-disease opportunities in orphan indications that are commercially underappreciated (see next slide) Deep rare disease pipeline with three QTORIN™ programs across six rare diseases anticipated by year end 2026 NDA submission underway with potential 1H 2027 FDA approval in microcystic LMs Completed Pre-NDA meeting with FDA, granted rolling review, first module of NDA submitted U.S. launch planning is accelerating for microcystic LMs (first indication) Multi-billion dollar uncontested TAM with estimated U.S. peak sales >$1 billion Sales force planned at ~40 reps, the upper end of prior ~20-40 rep range, to strengthen launch execution, field coverage, physician education, and patient access from day one 1H 2026 commercial talent recruited: Matt Pauls, Board Director (Savara, Soleno, Insmed), Jen McDonough, SVP Market Access (prev. Krystal Biotech); Kent Taylor, SVP Sales (prev. Arcutis) Well-capitalized after $230mm oversubscribed Q1 2026 financing
Palvella: Driving the Next Wave of Innovation in Under-appreciated Rare Skin Diseases and Vascular Malformations Estimated Diagnosed U.S. Prevalence1 30k+ Microcystic LMs 75k+ Cutaneous VMs 50k+ Clinically Significant Angiokeratomas 50k+ Disseminated Superficial Actinic Porokeratosis 1. Clarity Pharma, Trinity Life Sciences, MedaCorp, and ZS Associates. 2. MedaCorp market research. Market Research: % Physicians Who Would Consider QTORIN™ as First-line Therapy2 >80% across four indications None # of FDA-approved Therapies
Microcystic Lymphatic Malformations: Complete NDA Submission on Track for 2H 2026 with Anticipated U.S. Commercialization in 1H 2027 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. Microcystic Lymphatic Malformations 1 Positive Phase 3 SELVA data Completed pre-NDA meeting (June 2026) Rolling review granted by FDA Findings presented at ISSVA World Congress, May 2026 First module of rolling NDA submitted in Q2 2026; completed NDA submission on track for 2H 2026 Potential FDA approval and U.S. launch 1H 2027
Multiple High-Impact Pipeline Milestones in 2026: Density of Catalyst Creation Driven by QTORIN™ QTORIN™ 3.9% rapamycin anhydrous gel and QTORIN™ pitavastatin are 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. Clinically Significant Angiokeratomas 3 Fast Track Designated Phase 2 initiated April 2026, ahead of schedule Phase 2 data expected 2H 2027 Disseminated Superficial Actinic Porokeratosis 4 QTORIN™ pitavastatin formulation developed, IP filed Phase 2 initiation expected 2H 2026 Announcement expected 2H 2026 Potential pipeline-in-a-product QTORIN™ Third Program 5 DAVID OSBORNE, PhD Chief Innovation Officer QTORIN™ rapamycin fourth indication announcement expected 2H 2026 QTORIN™ Rapamycin Fourth Indication 6 Cutaneous Venous Malformations 2 Positive Phase 2 data P3 initiation expected Q4 2026 EOP2 meeting planned with FDA to discuss trial design
OUR LEAD PRODUCT CANDIDATE QTORIN™ 3.9% RAPAMYCIN ANHYDROUS GEL
HIGH DRUG LOADING CAPACITY High solubility → high concentrations → potential for rapid onset and large magnitude treatment effect 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 QTORIN™ product candidate eligible for composition IP on formulation QTORIN™: Reproducible Platform for Generating Novel, Topical Product Candidates in a Capital Efficient Manner QTORIN™ PLATFORM
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 11 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. Oral rapamycin is not a viable therapeutic option in skin diseases: Systemic toxicities & low biodistribution to the skin
Microcystic LMs Cutaneous VMs Clinically Significant Angiokeratomas Additional Potential Future Indications2 TODAY FUTURE Targeting announcement in 2026 and beyond = 5k 30k+ 75k+ 200k+ 50k+1 QTORIN™ Rapamycin: Fourth Indication Announcement in 2H 2026 1. Clarity Pharma research (July 2025), n=643 physicians surveyed. 2. Lapa et al., Journal of Cutaneous Medicine and Surgery, (2025). Pipeline-in-a-product strategy expands addressable U.S. patient pool by 10x beyond initial indication Estimated timeline for potential regulatory approval 2031+ 2032+ 2027 2029
QTORIN™ 3.9% RAPAMYCIN Microcystic Lymphatic Malformations FOR
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 hospitalizations Proliferative, 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).
Phase 3 SELVA Trial Design Single-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/Bleeding Secondary 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 Period 24+ weeks Efficacy Evaluation 24 weeks Baseline Photo 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 period End of Treatment Photo Screening Photo
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 Patients QTORIN™ Rapamycin at Week 24: Highly statistically significant across primary, key secondary, and all four secondary endpoints (all p<0.001) +2.13 Mean improvement on mLM-IGA primary endpoint (p<0.001) 95% Participants aged ≥ 6 who completed the efficacy evaluation period: Potential to be first and only FDA-approved therapy for >30,000 diagnosed U.S. patients 86% “Much Improved” (+2) or “Very Much Improved” (+3) on mLM-IGA Improved on mLM-IGA
SELVA: Primary and Key Secondary Endpoints Achieved Mean Change at Week 24 (95% CI) p-value Primary Endpoint: Microcystic Lymphatic Malformation Investigator Global Assessment (mLM-IGA)* +2.13 (1.88, 2.38) p<0.001 Key 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) Highly statistically significant across primary, key secondary, and all four secondary endpoints (all p<0.001)
Phase 3 Results: Well-Tolerated and Favorable Safety Profile Rapamycin levels were below 2 ng/mL in systemic circulation on for all participants at all timepoints in the study Note: 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 Event 35 (70%) Severe (not related to study drug) 1 (2%) Serious (not related to study drug) 4 (8%) Any Treatment-Related1 Adverse Event 17 (34%) Severe 0 (0%) Serious 0 (0%) Treatment-Related1 AEs with ≥ 5% Incidence Application site acne 3 (6%) Application site discoloration 3 (6%) Application site pruritus 3 (6%) Possibly Treatment-Related AE Leading to Discontinuation 1 (2%)
Week 24 Baseline Phase 3 Results: Age 10, Male, mLM-IGA: +2 “Much Improved” Note: Selective photos. Thigh Thigh Prior Interventions: Multiple sclerotherapy procedures, antibiotics due to infection
Week 24 Baseline Phase 3 Results: Age 7, Female, mLM-IGA: +3 “Very Much Improved” Note: Selective photos. Elbow Elbow Prior Interventions: Laser therapy, compounded topical rapamycin (discontinued due to skin irritation)
Phase 3 SELVA and Phase 2 studies highly statistically significant and clinically meaningful; real-world studies from off-label rapamycin use as supportive evidence 1 Granted Breakthrough, Fast Track, and Orphan Designations, and FDA Orphan Drug Grant; intend to seek 6-month priority review 2 505(b)(2) submission: leveraging FDA’s prior findings for rapamycin to streamline review process 3 Seeking traditional approval (not accelerated) based on clinical endpoints; intent to seek broad label age 3 and above 4 Regulatory: NDA Submission On Track for 2H 2026 Breakthrough, Fast Track, and Orphan Designations granted Completed Pre-NDA Meeting with FDA Rolling Review Granted First NDA Module Submitted
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 Pending patents could extend U.S. IP into mid-2040s DAVID OSBORNE, PhD Chief Innovation Officer
QTORIN™ 3.9% RAPAMYCIN U.S. Commercial Launch Planning
Microcystic LMs: Multi-billion Dollar, Uncontested U.S. Market Opportunity with Commercial Build-Out Underway Large orphan market: Claims analysis presented at 2025 Society for Investigative Dermatology (SID) Meeting 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 population 2 Payor testing and orphan analogues validate expected orphan pricing corridor above $100k per patient per year 3 Concentrated prescriber base in vascular anomaly centers (VACs) & other clinics 4
QTORIN™ Rapamycin: >$1bn U.S. Peak Sales Potential in Microcystic LMs QTORIN™ Rapamycin Potential to Achieve >$1bn Peak Sales >30k diagnosed U.S. patients, with concentration in vascular anomaly centers Microcystic Lymphatic Malformations Annual ~$100k-$200k pricing range per patient Recent field checks, annual incidence estimates, published claims analysis Supported by Phase 3 SELVA data, payor testing, analogues QTORIN™ 3.9% rapamycin anhydrous gel 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 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 Additional Insights into Pediatric Population 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.
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
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 ~30-40 reps
QTORIN™ 3.9% RAPAMYCIN Cutaneous Venous Malformations FOR
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 and hyperproliferation of immature venous endothelial cells Dysfunctional venous architecture leads to bleeding, thrombosis, ulceration Lesions do not resolve spontaneously3 Skin involvement in ~50-80% of venous malformations patients2 Leads to physical & functional impairment, psychological distress, with no FDA-approved therapies > 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). 3. Fujino et al., Lymphatic Research and Biology, (2024).
Cutaneous Venous Malformations: Near-term Phase 3 Pivotal Study Planned No FDA-approved therapies Fast Track Designation Granted Pipeline-in-a-product: sNDA planned > 75k patients ESTIMATED DIAGNOSED IN THE U.S. POSITIVE PHASE 2 DATA ANNOUNCED DEC 2025 Most common vascular malformation with significant treater overlap with microcystic lymphatic malformations New 24-week data presented at ISSVA World Congress May 2026 by Dr. Jim Treat (CHOP) Recent publication highlights off-label sirolimus as the most utilized medical therapy for VMs (Coulie et al, July 2026) Clinical development plan: On track for Phase 3 trial initiation in Q4 2026 Planning for EOP2 meeting with FDA to discuss Phase 3 trial design Breakthrough Therapy resubmission planned, incorporating TOIVA patient interviews and new 24-week data, following FDA’s recent decision (July 2026) to not grant the designation at this time
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 outcomes persist in cutaneous disease Limaye et al (2009, 2015) Teng et al (2025) QTORIN™ RAPAMYCIN On Target, In Tissue Phase 2 TOIVA Data (2025) Plausible mechanism 3.9% concentration Dermal penetration Extensive CMC package 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.
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), other clinician- and patient-reported outcomes Statistics: Intent-to-Treat (ITT) population, based on available data at each time point and analyzed per statistical analysis plan Key Entry Criteria: Enriched for patients with cutaneous disease and confirmed by third party eligibility consult team; genetics not required Enrollment: 16 participants enrolled and dosed Sites: Note: Statistical significance (p<0.05) is nominal as there was no adjustment for multiplicity amongst efficacy endpoints. Data analyzed per statistical analysis plan; ITT analyzed with no imputation of values for missing data. Single arm, QTORIN™ rapamycin treatment (QD) Efficacy Evaluation Period 12 weeks Screening / Baseline Visit Exit Interview with participant Entry Interview with participant Treatment Extension Period 12 weeks
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: +1.5 (p<0.001) Median effect size at week 12: +2.0 73% of participants (11/15 participants) demonstrated at least a 1-point improvement on the Overall cVM-IGA at Week 12 67% of participants (10/15 participants) were rated as either “Much Improved” (+2) or “Very Much Improved” (+3) on the Overall cVM-IGA at Week 12 Overall cVM-IGA at Week 12 (n=15) Internal threshold to progress to Phase 3: ~30% Note: Statistical significance (p<0.05) is nominal as there was no adjustment for multiplicity amongst efficacy endpoints. Data analyzed per statistical analysis plan; ITT analyzed with no imputation of values for missing data. 1. Genetic testing was not required as part of the protocol; Palvella is continuing efforts to collect genetic data on trial participants.
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: Meaningful Improvement in Patient QoL Participant Qualitative Interview: “I’ve definitely noticed some improvements…it’s definitely had a positive effect…It’s more comfortable to wear a bra now…I’ve had less pain in that specific area” Note: Selective photos.
Day 28 Day 56 Day 84 Day 168 (n=14) p-value 0.001 0.001 <0.001 <0.001 cVM Clinical Signs: Height/Engorgement and Appearance Results Through 24 Weeks New 24-week data on two of the key clinical signs measured in the TOIVA trial: height/engorgement and appearance Data on bleeding, another key clinical sign in cutaneous venous malformations, were recently presented at the 83rd Annual Meeting of the Society for Investigative Dermatology Day 28 Day 56 Day 84 Day 168 (n=14) p-value 0.027 0.001 <0.001 <0.001 Note: Mean change and p-values collected on observed data only. cVM-MCSS (cutaneous VM multi-component static scale) Height and Appearance are rated on 5-point scales ranging from 1 to 5; negative values indicate improvements from Day 1
Phase 2 Results: Safety and Tolerability QTORIN™ 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 severe events) Majority of AEs were mild No SAEs related to study drug No unexpected AEs Rapamycin levels were below the lower limit of quantification (2 ng/mL) in systemic circulation on a standard lab assay for all participants at all timepoints in the study Significantly below 5 ng/mL which is the lower boundary where rapamycin begins to exert immunosuppressive effects
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.
QTORIN™ 3.9% RAPAMYCIN Clinically Significant Angiokeratomas FOR
> 50k patients ESTIMATED DIAGNOSED IN THE U.S.1 Clinically Significant Angiokeratomas: Superficial Lymphatic Malformations Persistent and extensive: Lesions can be large and increase in size, number, and extent over time Chronically debilitating lymphatic-derived skin lesions associated with bleeding, pain, and functional impairment Recurrent bleeding: Friction can cause fragile lesions to frequently bleed Disease Biology: Increased VEGF and mTOR signaling, leading to vessel dilation and hyperkeratosis Natural history: No tendency for spontaneous regression Wang et al., Journal of Cutaneous Pathology, (2014); Trindade et al., Am J Dermopathol, (2014); Prindaville et al., Pediatric Dermatology, (2017); Singh et al, Indian Journal of Dermatology, (2023); Caraffa et al, International Journal of Infection, (2025); Molla, Clinical, Cosmetic and Investigative Dermatology, (2024). Ivy H, Julian CA. Angiokeratoma Circumscriptum. Treasure Island (FL): StatPearls Publishing; 2025 Jan; Lapa et al., Journal of Cutaneous Medicine and Surgery, (2025). 1. Clarity Pharma research (July 2025), n=643 physicians surveyed. Palvella’s focus to include Fordyce, Solitary, Mibelli, and Circumscriptum subtypes No FDA-approved therapies Pipeline-in-a-product: sNDA planned Phase 2 trial initiated April 2026 ahead of schedule
QTORIN™ PITAVASTATIN Disseminated Superficial Actinic Porokeratosis FOR
> 50k patients ESTIMATED DIAGNOSED IN THE U.S.1 Disseminated Superficial Actinic Porokeratosis (DSAP): Chronic, Pre-Cancerous, and Progressive Persistent and extensive: Clonal proliferation of abnormal keratinocytes leads to increased number and size of lesions Risk of malignant transformation: Premalignant disease with transformation to non-melanoma skin cancers2 Genetics & Disease Biology: Autosomal dominant (primary) or de novo germline mutation leads to accumulation of toxic intermediates Natural history: Spontaneous regression is extremely rare2 No FDA-approved therapies Phase 2 trial initiation expected 2H 2026 1. Clarity Pharma research (April 2025), n=277 physicians surveyed. 2. Williams, Grant M., et al. “Porokeratosis.” StatPearls Publishing, 2024. Significant impact to quality of life: clinical signs include skin disfigurement, burning, and persistent itch
Unmet Need for First FDA-approved Topical Mevalonate Pathway Inhibitor for DSAP Proof-of-concept study, demonstrating a plausible mechanistic approach Significant need for an FDA-approved topical mevalonate pathway inhibitor Recently published systematic review in Clinical and Experimental Dermatology (Martini et al, 2026) included 24 case studies of off-label use of topical statin therapy in porokeratosis… …however, today poor patient outcomes persist due to lack of access and known variability in unapproved formulations which can limit safety, efficacy, and quality Oral statins are not a viable therapeutic option in DSAP: High first pass metabolism and/or sub-therapeutic biodistribution to the skin
Clear Biology: Targeting the Causal Mevalonate Pathway Target: Mevalonate Pathway Tissue: Epidermis & Dermis Site of pathogenesis-directed therapy An on-target, in-tissue approach could result in significant clinical improvement *HMGCR = 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Image sources: Milani D, Warbasse E, Chen WS. Porokeratosis. PathologyOutlines.com website. *
Using QTORIN™, we considered and tested a wide range of mevalonate pathway inhibitors QTORIN™ Pitavastatin: On Target, In Tissue QTORIN™ PITAVASTATIN Molecule Potency Optimal Skin PK Stability Pitavastatin Mev. Inhibitor 2 Mev. Inhibitor 3 Mev. Inhibitor 4 Mev. Inhibitor 5 Mev. Inhibitor 6 Mev. Inhibitor 7 Did not meet some or all pre-defined target product attributes Pitavastatin is an FDA-approved next-generation oral statin for patients with primary hyperlipidemia and mixed dyslipidemia Superior inhibition of the mevalonate pathway compared to all molecules evaluated Key characteristics: Payload: > 2% concentration achieved Dermal penetration: in vitro penetration test confirms > IC90 Low systemic absorption Encouraging preliminary drug stability IP: Filed formulation & method of use IP and licensed Yale IP
Platform QTORIN™
QTORIN™: New Product Development Engine VALIDATION OF QTORIN™ PLATFORM Two positive clinical study readouts (Phase 3 SELVA trial and Phase 2 TOIVA trial results) PLANNING TO PURSUE PLATFORM DESIGNATION We expect to apply for FDA’s Platform Technology Designation Program following QTORIN™ rapamycin’s targeted approval in 2027 SCALING OF PIPELINE WITH NEW QTORIN™ PROGRAMS Rapidly advancing and testing multiple molecules through QTORIN™ platform in capital- and time-efficient manner We plan to announce one new QTORIN™ program and one new QTORIN™ rapamycin indication later this year DAVID OSBORNE, PhD Chief Innovation Officer
Finance
Well-Capitalized with High-Quality Investor Participation in $230mm Oversubscribed Feb. 2026 Financing Following Positive SELVA Data Potential to Fund Through: QTORIN™ + 505(b)(2) + rare disease focus offers potential for attractive ROI NDA filing, FDA approval, and, if approved, U.S. launch for QTORIN™ rapamycin in microcystic LMs NDA filing for QTORIN™ rapamycin in cutaneous VMs Multiple Phase 2 data readouts from pipeline programs $262 million 3/31/26 cash 2026 cash expenses: [~$90-95mm] 2026 GAAP expenses: [~$105-110mm]
What Sets Palvella Apart: Building The Leader in Rare Skin Diseases and Vascular Malformations Positive Phase 3 data in microcystic lymphatic malformations, focused on NDA rolling submission and potential U.S. commercial launch QTORIN™ rapamycin: potential to be first approved therapy and SOC in U.S. for microcystic LMs, cutaneous VMs, and angiokeratomas U.S. commercial opportunity: multi-billion dollar TAM in mLMs, with potential to expand addressable pool of patients by 10x Striving to be first for rare disease patients Deep pipeline of rare disease therapies: six diseases anticipated by year end 2026
Striving to be first for rare disease patients Thank You
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.
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.”
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
* * * * * * 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
Upside Target Clinical Profile SELVA Outcome Statistically 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 diseases 98% 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.
Phase 3 SELVA: Baseline Characteristics ITT Population (n=49)1 Age, Mean [Range] 19.4 [6-57] Sex M:F 24:25 Prior 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.
SELVA: All Additional Secondary Endpoints Achieved Mean Change at Week 24 (95% CI) p-value Patient Global Impression of Change* +1.9 (1.66, 2.16) p<0.001 Live mLM-MCSS** -4.6 (-5.20, -3.92) p<0.001 Clinician Global Impression of Severity*** -1.7 (-1.91, -1.39) p<0.001 Patient 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)
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
Commercial Opportunity for Clinically Significant Angiokeratomas Anticipate drug pricing similar to QTORIN™ rapamycin for Microcystic LMs and Cutaneous VMs based on disease severity and lack of FDA-approved therapies Pricing >50k clinically significant angiokeratomas in the U.S. based on nationally representative, blinded, real-world observational study conducted July 2025 (n=643 physicians)1 Estimated Diagnosed U.S. Prevalence 96% would incorporate Product X (topical 3.9% rapamycin gel) into their practice 85% believe there is unmet need for a novel treatment across all subtypes “A topical application that was basically asymptomatic in terms of its application…would be ideal for these intractable cases” Market Research2 (n=50 physicians) Clarity Pharma research (July 2025), n=643 physicians surveyed. 2. Medacorp Survey (September 2025), n=50 physicians surveyed.
Attractive U.S. Commercial Opportunity for DSAP anticipated based on disease severity and lack of FDA-approved therapies Orphan Pricing diagnosed DSAP patients in the U.S. based on two sources (Clarity Pharma, n=277 physicians; Zagoras et al, 2023) and confirmed by KOL calls >50k Market research (n=55 physicians)1: of physicians would incorporate Product X (topical mevalonate pathway inhibitor) into their practice of physicians would consider Product X as a first line therapy for DSAP patients 100% 96% 1. MedaCorp Survey (August 2025), n=55 physicians surveyed.