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VYN202 was generally well tolerated with no drug-related adverse eventsPharmacokinetic results demonstrated dose-dependent exposure of VYN202 in blood Pharmacodynamic activity observed on target engagement and inflammatory biomarkers Dosing has begun in the MAD portion of the trial with results expected in Q4 2024 BRIDGEWATER, N.J., Sept. 12, 2024 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need, today announced positive data from the single ascending dose (“SAD”) portion of its ongoing Phase 1a trial of VYN202. The Phase 1a trial is a two-part, double-blind, placebo-controlled dose-escalation study in healthy volunteers consisting of SAD and multiple ascending dose (“MAD”) components to evaluate the safety, tolerability, pharmacokinetics (“PK”) and pharmacodynamics of VYN202. Findings from the SAD portion of the Phase 1a trial to date are as follows: VYN202 Was Generally Well Tolerated Across All Dose Groups Single ascending doses of VYN202 across all cohorts were generally well tolerated up to and including the highest planned dose level. There were no serious adverse events, drug-related adverse events, or clinically significant abnormalities in clinical laboratory results or electrocardiogram findings. VYN202 Demonstrated Dose-Dependent PK VYN202 also met expected PK parameters, with plasma and urine drug concentrations of VYN202 increasing in a dose-dependent manner across all doses tested. VYN202 Demonstrated Pharmacodynamic Effects Participant blood samples were stimulated ex-vivo to assess the pharmacodynamic impact of single doses of VYN202 on key target-engagement and inflammatory biomarkers. Results demonstrated an increase in marker protein HEXIM1, indicative of target engagement of VYN202 with BET proteins1. Additionally, exploratory data from the SAD arm showed that single doses of VYN202 demonstrated biological activity and an inhibitory effect on select inflammatory biomarkers relevant to psoriasis and rheumatoid arthritis. Phase 1a MAD Portion of Trial Initiated The primary objectives of the MAD portion of the Phase 1a trial are to assess safety, tolerability, PK and pharmacodynamics of VYN202 over 14 days at different dose levels. Results are expected in Q4 2024. “These results from our SAD trial mark the first clinical data for our BD2-selective BET inhibitor, VYN202, and represent an important milestone for our Company and the development of our BET inhibitor platform,” said David Domzalski, President and Chief Executive Officer of VYNE. “We look forward to further assessing safety and PK as well as VYN202’s potential to impact several relevant biomarkers following multiple doses, which we expect to disclose next quarter. These data would inform the design of our planned studies in psoriasis and rheumatoid arthritis.” About VYN202 VYN202 is an innovative, oral small molecule BET inhibitor that has potential class-leading selectivity and potency for BD2 vs. BD1. By maximizing BD2 selectivity, VYNE believes VYN202 has the potential to be a more conveniently administered non-biologic treatment option for both acute control and chronic management of immuno-inflammatory indications, in which the damaging effects of unrestricted inflammatory signaling activity is common. VYN202 is structurally distinct from VYNE’s pan-BET inhibitor (VYN201) and covered by distinct Patent Cooperation Treaty and provisional composition of matter patent applications directed to new chemical entities and their uses. About BET InhibitorsBET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”). Recent research has identified a key role for these proteins in regulating activation of immune cells, including T and B cells, and subsequent inflammatory and fibrotic processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription, with additional potential in myeloproliferative neoplastic disorders. 1. Lin, Xiaoyu et al. “HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.” Molecular Cancer Therapeutics vol. 16,2 (2017): 388-396. doi:10.1158/1535-7163.MCT-16-0475. About VYNE Therapeutics Inc. VYNE is a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need. VYNE’s unique and proprietary BET inhibitors, which comprise its InhiBET™ platform, are designed to overcome limitations of early generation BET inhibitors by leveraging alternative routes of administration and enhanced selectivity. For more information about VYNE Therapeutics Inc. or its product candidates, visit www.vynetherapeutics.com. VYNE may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor VYNE’s website in addition to following its press releases, filings with the U.S. Securities and Exchange Commission (“SEC”), public conference calls, and webcasts. Cautionary Statement Regarding Forward-Looking StatementsThis release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements related to VYNE’s ability to successfully complete the Phase 1a SAD/MAD trial of VYN202 and to receive favorable results from such trial, as well as the timing of results from the MAD portion of the trial, the role of trial results in informing the design of planned studies in psoriasis and rheumatoid arthritis and the potential benefits of VYN202. All statements in this press release which are not historical facts are forward-looking statements. Any forward-looking statements are based on VYNE’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions that could cause actual results to differ materially and adversely from those set forth or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: VYNE’s ability to enroll patients in its clinical trials and successfully develop its product candidates; VYNE’s ability to complete and receive favorable results from clinical trials of its product candidates; 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. For a discussion of other risks and uncertainties, and other important factors, any of which could cause VYNE’s actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in VYNE’s Annual Report on Form 10-K for the year ended December 31, 2023 and VYNE’s other filings from time to time with the SEC. Although VYNE believes these forward-looking statements are reasonable, they speak only as of the date of this announcement and VYNE undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Given these risks and uncertainties, you should not rely upon forward-looking statements as predictions of future events. Investor Relations:John FrauncesLifeSci Advisors, LLC917-355-2395jfraunces@lifesciadvisors.com Tyler ZerondaVYNE Therapeutics Inc.908-458-9106Tyler.Zeronda@vynetx.com Media Relations: Mike BeyerSam Brown Inc.312-961-2502mikebeyer@sambrown.com

VYN202 has been designed to achieve class-leading potency and BD2-selectivity Trial will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202 in healthy volunteers; top-line data expected in 2H’24 BRIDGEWATER, N.J., June 13, 2024 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced that the first healthy volunteers have been dosed in the Phase 1a trial of VYN202. VYN202 is an oral small molecule BD2-selective bromodomain and extra-terminal domain (BET) inhibitor that is being developed for the treatment of immuno-inflammatory diseases. Top-line data are expected in the second half of 2024. “We are pleased to announce the initiation of the first-in-human clinical trial of VYN202, a highly selective and potent orally administered BET inhibitor. In preclinical testing, VYN202 achieved consistent improvements in disease severity across a variety of inflammatory and fibrotic models as well as reductions in pro-inflammatory and disease-related biomarkers,” said David Domzalski, President and CEO of VYNE. “We believe VYN202 has significant potential as a treatment option for a broad range of immune-mediated diseases, and we look forward to reporting top-line data from the Phase 1a trial in the second half of this year.” The Phase 1a trial is a first-in-human double-blind, placebo-controlled study in healthy volunteers and consists of single ascending dose (SAD) and multiple ascending dose (MAD) components. The trial is currently expected to enroll approximately 64 healthy adult subjects into five SAD and three MAD cohorts to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202. “Early generation BET inhibitors show similar affinity to both BD1 and BD2 bromodomains of BET proteins that has been implicated in both gastrointestinal and hematologic dose limiting toxicities,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “We believe VYN202’s high potency and selectivity towards the BD2 bromodomain of BET proteins may result in an improved benefit-risk pro treating immuno-inflammatory diseases. Following highly encouraging preclinical data, we are eager to evaluate the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202 to further inform our future clinical development plans.” About VYN202 VYN202 is an innovative, oral small molecule BD2-selective BET inhibitor that has been designed to achieve class-leading selectivity (BD2 vs. BD1), maximum potency versus BD2, and optimal oral bioavailability. By maximizing BD2 selectivity, VYNE believes VYN202 has the potential to be a more conveniently administered non-biologic treatment option for both acute control and chronic management of immuno-inflammatory indications, in which the damaging effects of unrestricted inflammatory signaling activity is common. VYN202 is structurally distinct from VYNE’s pan-BET inhibitor (VYN201) and covered by distinct PCT and provisional composition of matter patent applications directed to new chemical entities and their uses. About BET Inhibitors BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”), and recent research has identified a key role for these proteins in regulating B cell and T cell activation and subsequent inflammatory processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription with additional potential in myeloproliferative neoplastic disorders. About VYNE Therapeutics Inc. VYNE’s mission is to improve the lives of patients by developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions. The Company’s unique and proprietary bromodomain & extra-terminal (BET) domain inhibitors, which comprise its InhiBET™ platform, include a locally administered pan-BD BET inhibitor (VYN201) and an orally available BD2-selective BET inhibitor (VYN202) that were licensed from Tay Therapeutics Limited. For more information about VYNE Therapeutics Inc. or its product candidates, visit . VYNE may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor VYNE’s website in addition to following its press releases, filings with the U.S. Securities and Exchange Commission (“SEC”), public conference calls, and webcasts. Cautionary Statement Regarding Forward-Looking Statements This release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements related to the potential benefits of VYN202 as a therapy for a broad range of immune-mediated diseases and the expected timing for reporting top-line results from the Phase 1a trial in the second half of 2024. All statements in this press release which are not historical facts are forward-looking statements. Any forward-looking statements are based on VYNE’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions that could cause actual results to differ materially and adversely from those set forth or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: VYNE’s ability to enroll patients in its clinical trials and successfully develop its product candidates; VYNE’s ability to complete and receive favorable results from, clinical trials of its product candidates; 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. For a discussion of other risks and uncertainties, and other important factors, any of which could cause VYNE’s actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in VYNE’s Annual Report on Form 10-K for the year ended December 31, 2023 and VYNE’s other filings from time to time with the SEC. Although VYNE believes these forward-looking statements are reasonable, they speak only as of the date of this announcement and VYNE undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Given these risks and uncertainties, you should not rely upon forward-looking statements as predictions of future events. Investor Relations: John Fraunces LifeSci Advisors, LLC 917-355-2395 jfraunces@lifesciadvisors.com Tyler Zeronda VYNE Therapeutics Inc. 908-458-9106 Tyler.Zeronda@vynetx.com Media Relations: Mike Beyer Sam Brown Inc. 312-961-2502 mikebeyer@sambrown.com

Preclinical studies suggest VYN202 has the potential to be the most potent and selective BET inhibitor in development VYN202 has demonstrated a potent anti-inflammatory and anti-fibrotic effect in multiple validated preclinical models of autoimmune disease IND-enabling studies are ongoing in anticipation of an IND filing by year-end BRIDGEWATER, N.J., May 01, 2023 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced the selection of a development candidate for its oral BD2-selective bromodomain and extra-terminal (“BET”) inhibitor program, VYN202, for the treatment of immuno-inflammatory conditions. The lead candidate was selected by VYNE from a library of BD2-selective BET inhibitors that VYNE exclusively licensed from Tay Therapeutics following the receipt of a robust package of preclinical data, including encouraging results from well-validated animal models in various autoimmune disorders. VYNE also obtained rights to several other BD2-selective BET inhibitor compounds with attractive molecular profiles that the Company may develop, at its discretion, in the future. “After extensive testing of multiple compounds across several well-validated preclinical models, we are pleased to have selected a development candidate for VYN202, which is specifically designed to be delivered orally, for the treatment of immuno-inflammatory conditions,” said David Domzalski, President and Chief Executive Officer of VYNE. “We are encouraged by the potential class-leading data and profile demonstrated by VYN202 in preclinical studies to date, and we look forward to further progressing our IND-enabling program and advancing VYN202 into clinical development.” VYN202 targets BET proteins that play key roles in regulating gene transcription via epigenetic interaction (“reading”) with specific chemical motifs on H3 and H4 histone N-terminal tail domains that extend beyond a nucleosome unit. As epigenetic readers, BET proteins are super-enhancers of gene transcription that drive the hyperactive production of many pro-inflammatory proteins that characterize autoimmune and autoinflammatory diseases. Recent research has highlighted BET proteins as important contributors in regulating both B cell and T cell activity and, in preclinical models, BET inhibitors have demonstrated the potential to treat a range of immuno-inflammatory and fibrotic diseases.1,2 Early generation systemic BET inhibitors that inhibit both the BD1 and BD2 domains of BET proteins (pan-BD BET inhibitors) have historically been associated with gastrointestinal and hematological toxicities, such as thrombocytopenia (low platelet counts) in clinical trials.3 BD1 functionality has been associated with the regulation of genes responsible for maintaining homeostatic cellular processing, and that selectively inhibiting BD1 or BD1 and BD2 may contribute to unwanted dose limiting toxicities.1,4 VYN202 is designed to be significantly more selective in inhibiting BD2 than BD1 with the objective of limiting the potential of similar safety concerns associated with earlier pan-BD BET inhibitors. VYNE has initiated IND-enabling studies for VYN202 and intends to submit an IND by year-end. Under VYNE’s license agreement with Tay, VYNE has exclusive worldwide rights to the compounds in its InhiBET™ platform, including VYN202, for all human disease applications. Gilan et al, Science., 2020 April 24; 368(6489): 387Kawahito et al, Pulm. Pharma. & Therp., 2021; 70:102057Sun et al, Front. Pharmacol., 2021; 11:621093Faivre et al, Nature, 2020; 578:306 About VYNE Therapeutics Inc. VYNE’s mission is to improve the lives of patients by developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions. The Company’s unique and proprietary bromodomain & extra-terminal (BET) domain inhibitors, which comprise its InhiBET™ platform, includes a locally administered pan-BET inhibitor (VYN201) and an orally available BD2-selective BET inhibitor (VYN202) that were licensed from Tay Therapeutics Limited. For more information about VYNE Therapeutics Inc. or its product candidates, visit www.vynetherapeutics.com. VYNE may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor VYNE’s website in addition to following its press releases, filings with the U.S. Securities and Exchange Commission, public conference calls, and webcasts. Cautionary Statement Regarding Forward-Looking Statements This release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding VYNE’s plans and development timelines for VYN202, including the submission of an IND by year end, VYNE’s InhiBET™ platform, and other statements regarding the future expectations, plans and prospects of VYNE. All statements in this press release which are not historical facts are forward-looking statements. Any forward-looking statements are based on VYNE’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions that could cause actual results to differ materially and adversely from those set forth or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: VYNE’s ability to successfully develop its product candidates; the timing of commencement of future non-clinical studies and clinical trials; VYNE’s ability to enroll patients and successfully progress, complete, and receive favorable results in, clinical trials for its product candidates; VYNE’s intentions and its ability to obtain additional funding, either through equity or debt financing transactions or collaboration arrangements; disruptions related to COVID-19 or another pandemic, epidemic or outbreak of a contagious disease, on the ability of VYNE’s suppliers to manufacture and provide materials for VYNE’s product candidates, initiating and retaining patients in clinical trials, operating results, liquidity and financial condition; developments and projections relating to competitors and the pharmaceuticals industry, including competing drugs and therapies; the timing or likelihood of regulatory filings and approvals or clearances for product candidates; VYNE’s ability to comply with various regulations applicable to its business, including Nasdaq continued listing rules; VYNE’s ability to create intellectual property and the scope of protection it is able to establish and maintain for intellectual property rights covering its product candidates, including the projected terms of patent protection; risks that any of VYNE’s patents may be held to be narrowed, invalid or unenforceable or one or more of VYNE’s patent applications may not be granted and potential competitors may also seek to design around VYNE’s granted patents or patent applications; the timing, costs or results of litigation, including litigation to protect its intellectual property; VYNE’s ability to successfully challenge intellectual property claimed by others; estimates of VYNE’s expenses, capital requirements, its needs for additional financing and its ability to obtain additional capital on acceptable terms or at all; VYNE’s ability to attract and retain key scientific or management personnel; and VYNE’s expectations regarding licensing, business transactions and strategic operations. For a discussion of other risks and uncertainties, and other important factors, any of which could cause VYNE’s actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in VYNE’s Annual Report on Form 10-K for the year ended December 31, 2022, as well as discussions of potential risks, uncertainties, and other important factors in VYNE’s subsequent filings with the U.S. Securities and Exchange Commission. Although VYNE believes these forward-looking statements are reasonable, they speak only as of the date of this announcement and VYNE undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Given these risks and uncertainties, you should not rely upon forward-looking statements as predictions of future events. Investor Relations: John FrauncesLifeSci Advisors, LLC917-355-2395jfraunces@lifesciadvisors.com Tyler ZerondaVYNE Therapeutics Inc.908-458-9106Tyler.Zeronda@vynetx.com