VYNE Therapeutics (VYNE) - 2025 Q2 - Quarterly Results

Phase 2b Trial Results for Repibresib Gel in Nonsegmental Vitiligo and Company Strategy This section details the Phase 2b trial outcomes for Repibresib gel in nonsegmental vitiligo, including efficacy, safety, and the company's strategic decision to seek a partner for its continued development Executive Summary of Trial Results and Company Actions The Phase 2b trial for Repibresib gel in nonsegmental vitiligo did not meet its primary (F-VASI50) or key secondary (F-VASI75) endpoints, leading VYNE to terminate the extension phase and seek an external partner - Trial did not meet primary endpoint (F-VASI50) or key secondary endpoint (F-VASI75)[1][2][4] - Repibresib 3% showed nominally statistically significant effects in percent change from baseline in F-VASI (-43.6% vs. Vehicle: -25.6%) and T-VASI (-28.3% vs. Vehicle: -16.2%)[2][4] - Company believes results were impacted by unusually high vehicle effect and higher-than-expected dropout rate in active arms (Repibresib 3%: 36.6%; Vehicle: 10.6%)[2][4] - VYNE will terminate the extension phase of the trial and seek an external partner for Repibresib[2][4] - The company remains confident in its InhiBET BET inhibitor platform[4] Phase 2b Trial Design and Methodology The Phase 2b trial was a randomized, double-blind, vehicle-controlled, multi-center study evaluating Repibresib gel at 1%, 2%, and 3% concentrations in 177 subjects with nonsegmental vitiligo - Trial design: Randomized, double-blind, vehicle-controlled, multi-center[3] - Subjects: 177 subjects (mITT population) with nonsegmental vitiligo[3] - Dosing: Repibresib gel at 1%, 2%, and 3% concentrations, once daily (QD)[3] - Primary endpoint: Proportion of subjects achieving F-VASI50 at Week 24 versus vehicle[3][5] - Key secondary endpoints: Proportion of subjects achieving F-VASI75 at Week 24, percent change from baseline in F-VASI score at week 24[3][5][6] - Exploratory endpoint: Percent change from baseline in T-VASI score at week 24[3][7] Detailed Efficacy Results This section details the specific numerical outcomes for the trial's efficacy endpoints, showing that while primary and key secondary endpoints were not met, the 3% Repibresib dose significantly improved percent change from baseline for F-VASI and T-VASI Primary Endpoint: Proportion of Subjects Achieving F-VASI50 at Week 24 | Endpoint at Week 24 | Repibresib 3% | Repibresib 2% | Repibresib 1% | Vehicle | | :------------------ | :------------ | :------------ | :------------ | :------ | | Proportion of Subjects Achieving F-VASI50 | 19.5% | 16.3% | 17.4% | 23.4% | | P-Value | 0.1245 | 0.6497 | 0.9718 | | Key Secondary Endpoint: Proportion of Subjects Achieving F-VASI75 at Week 24 | Endpoint at Week 24 | Repibresib 3% | Repibresib 2% | Repibresib 1% | Vehicle | | :------------------ | :------------ | :------------ | :------------ | :------ | | Proportion of Subjects Achieving F-VASI75 | 9.8% | 7.0% | 10.9% | 6.4% | | P-Value | 0.1468 | 0.4096 | 0.2946 | | Key Secondary Endpoint: Percent Change from Baseline in F-VASI at Week 24 | Endpoint at Week 24 | Repibresib 3% | Repibresib 2% | Repibresib 1% | Vehicle | | :------------------ | :------------ | :------------ | :------------ | :------ | | Mean Percent Change from Baseline in F-VASI, % (SD) | -43.6 (5.7) | -25.7 (5.7) | -30.2 (5.2) | -25.6 (4.9) | | P-Value | 0.0020 | 0.9892 | 0.4002 | | Exploratory Endpoint: Percent Change from Baseline in T-VASI at Week 24 | Endpoint at Week 24 | Repibresib 3% | Repibresib 2% | Repibresib 1% | Vehicle | | :------------------ | :------------ | :------------ | :------------ | :------ | | Mean Percent Change from Baseline in T-VASI, % (SD) | -28.3 (6.1) | -15.2 (6.1) | -16.4 (5.2) | -16.2 (4.9) | | P-Value | 0.0436 | 0.8757 | 0.9670 | | Safety and Tolerability Profile Repibresib gel exhibited a higher rate of mostly mild, cutaneous treatment-emergent adverse events compared to vehicle, with application site pain being the most common, and no increased risk of thrombocytopenia or GI-related serious adverse events - Higher rate of treatment emergent adverse events (TEAE) for Repibresib gel compared to vehicle[8] - Most common TEAEs (>5%) were cutaneous, with application site pain being the most frequent (Repibresib 3%: 14.0%; Vehicle: 3.8%)[8] - 8 subjects receiving Repibresib gel discontinued due to an AE, compared to none in the vehicle group[8] - Majority of skin-related TEAEs were mild (76.0%) and resolved during the study, with no clear dose-dependent increase in frequency[8] - One non-drug-related serious adverse event (cholelithiasis without obstruction) occurred in the Repibresib 1% cohort[8] - No increased risk of thrombocytopenia or GI-related serious adverse events was observed[8] Financial Update As of June 30, 2025, VYNE Therapeutics expects to report unaudited cash, cash equivalents, and investments of approximately $39.6 million, subject to finalization of financial results Unaudited Cash Position (as of June 30, 2025) | Metric | Amount | | :-------------------------------- | :------------- | | Cash, cash equivalents and investments | ~$39.6 million | - The cash estimate is preliminary and subject to change pending the actual results of, and completion of, the Company's condensed consolidated financial statements for the quarter ended June 30, 2025[14] Product Candidate Information This section provides an overview of Repibresib, a pan-bromodomain BET inhibitor, and VYN202, an oral small molecule BET inhibitor, highlighting their design and therapeutic potential About Repibresib Repibresib is a pan-bromodomain BET inhibitor designed for local administration as a "soft" drug, aiming for low systemic exposure to treat inflammatory conditions and showing preclinical efficacy - Repibresib is a pan-bromodomain BET inhibitor[9] - Designed for local administration as a "soft" drug to address inflammatory cell signaling pathways[9] - Provides low systemic exposure[9] - Produced consistent reductions in pro-inflammatory and disease-related biomarkers and improvements in disease severity in preclinical models[9] About VYN202 VYN202 is an innovative, oral small molecule BET inhibitor with potential class-leading selectivity for BD2 versus BD1, aiming to be a differentiated, non-biologic treatment for immuno-inflammatory conditions - VYN202 is an innovative, oral small molecule BET inhibitor[10] - Potential for class-leading selectivity and potency for BD2 vs. BD1[10] - Aims to be a differentiated, conveniently administered, non-biologic treatment for immuno-inflammatory indications[10] Corporate Information and Disclosures This section provides details about VYNE Therapeutics Inc., investor relations contacts, and a cautionary statement regarding forward-looking statements and associated risks About VYNE Therapeutics Inc. VYNE Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions using its InhiBET™ platform - Clinical-stage biopharmaceutical company[12] - Focuses on developing differentiated therapies for chronic inflammatory and immune-mediated conditions with high unmet need[12] - Utilizes the InhiBET™ platform, comprising unique and proprietary BET inhibitors[12] - InhiBET™ inhibitors are designed to overcome limitations of early generation BET inhibitors via alternative administration routes and enhanced selectivity[12] Investor Relations Contact Investor relations inquiries can be directed to specified contacts at LifeSci Advisors, LLC or VYNE Therapeutics Inc., with VYNE also using its website for Regulation FD disclosures Investor Relations Contacts | Name | Affiliation | Phone | Email | | :----------- | :------------------ | :---------- | :---------------------- | | John Fraunces | LifeSci Advisors, LLC | 917-355-2395 | jfraunces@lifesciadvisors.com | | Tyler Zeronda | VYNE Therapeutics Inc. | 908-458-9106 | Tyler.Zeronda@VYNEtx.com | - VYNE uses its website (www.vynetherapeutics.com) to comply with disclosure obligations under Regulation FD[13] Cautionary Statement Regarding Forward-Looking Statements This section highlights that the release contains forward-looking statements subject to risks, uncertainties, and assumptions that could cause actual results to differ materially, advising investors to review SEC filings for risk factors - The release contains forward-looking statements regarding clinical development, future expectations, plans, and prospects[14] - These statements are subject to risks, uncertainties, and assumptions that could cause actual results to differ materially[14] - Risks include VYNE's ability to successfully develop its product candidates; the timing of commencement of future preclinical studies and clinical trials; VYNE's ability to complete and receive favorable results from clinical trials of its product candidates; VYNE's ability to find a partner for repibresib; VYNE's ability to obtain additional funding, either through equity or debt financing transactions or collaboration arrangements; and VYNE's ability to comply with various regulations applicable to its business[14] - The preliminary cash estimate for June 30, 2025, is unaudited and subject to change[14] - Investors should not rely on forward-looking statements as predictions and should review SEC filings for risk factors[14]